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Researchers exploring ways to mitigate aging’s impact on diabetes
LOS ANGELES – When Derek LeRoith, MD, PhD, was a medical student, he remembers professors telling him that human tissue response to aging diminishes over time, and that individuals can develop insulin resistance purely from aging.
“Whether that was right or wrong I don’t know, but certainly it seems to be one of the major issues that leads to the increase in diabetes, with all of its associated aspects such as dyslipidemia and hypertension,” he said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease.
According to Dr. LeRoith, professor of medicine and director of research in the division of endocrinology at Icahn School of Medicine at Mount Sinai, New York, studies have demonstrated that the elderly have worse glucose tolerance, compared with younger adults. One such analysis found that the insulin secretion index and disposition index are lower in the elderly, compared with their younger patients (Diabetes 2003;52[7]:1738-48). “But it’s not just the insulin resistance per se,” he said. “It’s also a defect of the beta cell. .”
Another major issue for aging patients is the impact of diabetes on cognitive decline and the formation of Alzheimer’s disease. “There’s a suggestion that the brain has insulin resistance and that this may also affect cognitive decline and Alzheimer’s,” Dr. LeRoith said. “But there are other aspects: insulin insufficiency, hyperglycemia, and, of course ... hypoglycemia. There is a debate as to what the major causes are. Is it amyloid beta accumulation, or is it vascular damage?”
In collaboration with Israeli researchers, Dr. LeRoith and his associates have been evaluating patients that belong to the Maccabi Health System in Tel Aviv, which has a diabetes registry with complete hemoglobin A1c measurements since 1998. One study of 897 registry participants found a strong association between worse diabetes control and worse cognition (Am J Geriatr Psych 2014;22:1055-9). Specifically, an interaction of duration of type 2 diabetes with HbA1c was associated with executive functioning (P = .006), semantic categorization (P = .019), attention/working memory (P = .011), and overall cognition (P = .006), such that the associations between duration of type 2 diabetes and cognitive impairment increased as HbA1c levels increased – but not for episodic memory (P = .984).
In a separate analysis of patients from the same registry, Dr. LeRoith and his colleagues evaluated the relationships of long-term trajectories of glycemic control with cognitive performance in cognitively normal elderly with type 2 diabetes (PLoS ONE 9[6]:e97384 doi: 10.1371/journal.pone.0097384). They found that subjects with stable HbA1c over time had the lowest HbA1c at study entry and performed best on cognitive measures, “suggesting that the trajectile of HbA1c over 10 or 12 years can really influence the cognitive ability in these patients,” he said.
Another, unrelated study found that insulin in combination with other diabetes medication is associated with less Alzheimer’s neuropathology (Neurology 2008;71:750-7), while an Alzheimer’s mouse model from Dr. LeRoith and his colleagues demonstrated that high dietary advanced glycation end products are associated with poorer spatial learning and accelerated amyloid beta deposition (Aging Cell 2016;15:309-16). “From that study we conclude that high dietary advance glycation end (AGE) products may be neurotoxic and that a diet low in AGEs may decrease dementia risk, particularly in diabetic elderly who are at increased risk and have higher levels of AGEs,” he said.
Potential ways to mitigate some of aging’s effects on the course of diabetes include caloric restriction, exercise, and taking metformin, Dr. LeRoith said. “There is a correlation between fitness and cognitive function, so the implication for clinical practice in individuals with diabetes is to encourage them to engage in physical activity on most days of the week,” he said. “It’s also known that depression makes the diabetes worse and depression makes cognitive function worse. It’s been suggested that if you have patients who are depressed, you should treat them with antidepressants if necessary, because this may help with their cognitive function.”
Meanwhile, an ongoing trial first announced in 2016 known as Targeting Aging with Metformin (TAME) is exploring the effects of metformin in helping to delay the aging process (Cell Metab 2016;23[6]:1060-5). Early support exists that metformin may delay cognitive decline and Alzheimer’s, even in non–type 2 diabetes. “An intended consequence of this effort is to create a paradigm for evaluation of pharmacologic approaches to delay aging,” the researchers wrote in an article describing the project, which is funded by the National Institute on Aging. “The randomized, controlled clinical trial we have proposed, if successful, could profoundly change the approach to aging and its diseases and affect health care delivery and costs.”
Dr. LeRoith reported having no financial disclosures.
LOS ANGELES – When Derek LeRoith, MD, PhD, was a medical student, he remembers professors telling him that human tissue response to aging diminishes over time, and that individuals can develop insulin resistance purely from aging.
“Whether that was right or wrong I don’t know, but certainly it seems to be one of the major issues that leads to the increase in diabetes, with all of its associated aspects such as dyslipidemia and hypertension,” he said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease.
According to Dr. LeRoith, professor of medicine and director of research in the division of endocrinology at Icahn School of Medicine at Mount Sinai, New York, studies have demonstrated that the elderly have worse glucose tolerance, compared with younger adults. One such analysis found that the insulin secretion index and disposition index are lower in the elderly, compared with their younger patients (Diabetes 2003;52[7]:1738-48). “But it’s not just the insulin resistance per se,” he said. “It’s also a defect of the beta cell. .”
Another major issue for aging patients is the impact of diabetes on cognitive decline and the formation of Alzheimer’s disease. “There’s a suggestion that the brain has insulin resistance and that this may also affect cognitive decline and Alzheimer’s,” Dr. LeRoith said. “But there are other aspects: insulin insufficiency, hyperglycemia, and, of course ... hypoglycemia. There is a debate as to what the major causes are. Is it amyloid beta accumulation, or is it vascular damage?”
In collaboration with Israeli researchers, Dr. LeRoith and his associates have been evaluating patients that belong to the Maccabi Health System in Tel Aviv, which has a diabetes registry with complete hemoglobin A1c measurements since 1998. One study of 897 registry participants found a strong association between worse diabetes control and worse cognition (Am J Geriatr Psych 2014;22:1055-9). Specifically, an interaction of duration of type 2 diabetes with HbA1c was associated with executive functioning (P = .006), semantic categorization (P = .019), attention/working memory (P = .011), and overall cognition (P = .006), such that the associations between duration of type 2 diabetes and cognitive impairment increased as HbA1c levels increased – but not for episodic memory (P = .984).
In a separate analysis of patients from the same registry, Dr. LeRoith and his colleagues evaluated the relationships of long-term trajectories of glycemic control with cognitive performance in cognitively normal elderly with type 2 diabetes (PLoS ONE 9[6]:e97384 doi: 10.1371/journal.pone.0097384). They found that subjects with stable HbA1c over time had the lowest HbA1c at study entry and performed best on cognitive measures, “suggesting that the trajectile of HbA1c over 10 or 12 years can really influence the cognitive ability in these patients,” he said.
Another, unrelated study found that insulin in combination with other diabetes medication is associated with less Alzheimer’s neuropathology (Neurology 2008;71:750-7), while an Alzheimer’s mouse model from Dr. LeRoith and his colleagues demonstrated that high dietary advanced glycation end products are associated with poorer spatial learning and accelerated amyloid beta deposition (Aging Cell 2016;15:309-16). “From that study we conclude that high dietary advance glycation end (AGE) products may be neurotoxic and that a diet low in AGEs may decrease dementia risk, particularly in diabetic elderly who are at increased risk and have higher levels of AGEs,” he said.
Potential ways to mitigate some of aging’s effects on the course of diabetes include caloric restriction, exercise, and taking metformin, Dr. LeRoith said. “There is a correlation between fitness and cognitive function, so the implication for clinical practice in individuals with diabetes is to encourage them to engage in physical activity on most days of the week,” he said. “It’s also known that depression makes the diabetes worse and depression makes cognitive function worse. It’s been suggested that if you have patients who are depressed, you should treat them with antidepressants if necessary, because this may help with their cognitive function.”
Meanwhile, an ongoing trial first announced in 2016 known as Targeting Aging with Metformin (TAME) is exploring the effects of metformin in helping to delay the aging process (Cell Metab 2016;23[6]:1060-5). Early support exists that metformin may delay cognitive decline and Alzheimer’s, even in non–type 2 diabetes. “An intended consequence of this effort is to create a paradigm for evaluation of pharmacologic approaches to delay aging,” the researchers wrote in an article describing the project, which is funded by the National Institute on Aging. “The randomized, controlled clinical trial we have proposed, if successful, could profoundly change the approach to aging and its diseases and affect health care delivery and costs.”
Dr. LeRoith reported having no financial disclosures.
LOS ANGELES – When Derek LeRoith, MD, PhD, was a medical student, he remembers professors telling him that human tissue response to aging diminishes over time, and that individuals can develop insulin resistance purely from aging.
“Whether that was right or wrong I don’t know, but certainly it seems to be one of the major issues that leads to the increase in diabetes, with all of its associated aspects such as dyslipidemia and hypertension,” he said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease.
According to Dr. LeRoith, professor of medicine and director of research in the division of endocrinology at Icahn School of Medicine at Mount Sinai, New York, studies have demonstrated that the elderly have worse glucose tolerance, compared with younger adults. One such analysis found that the insulin secretion index and disposition index are lower in the elderly, compared with their younger patients (Diabetes 2003;52[7]:1738-48). “But it’s not just the insulin resistance per se,” he said. “It’s also a defect of the beta cell. .”
Another major issue for aging patients is the impact of diabetes on cognitive decline and the formation of Alzheimer’s disease. “There’s a suggestion that the brain has insulin resistance and that this may also affect cognitive decline and Alzheimer’s,” Dr. LeRoith said. “But there are other aspects: insulin insufficiency, hyperglycemia, and, of course ... hypoglycemia. There is a debate as to what the major causes are. Is it amyloid beta accumulation, or is it vascular damage?”
In collaboration with Israeli researchers, Dr. LeRoith and his associates have been evaluating patients that belong to the Maccabi Health System in Tel Aviv, which has a diabetes registry with complete hemoglobin A1c measurements since 1998. One study of 897 registry participants found a strong association between worse diabetes control and worse cognition (Am J Geriatr Psych 2014;22:1055-9). Specifically, an interaction of duration of type 2 diabetes with HbA1c was associated with executive functioning (P = .006), semantic categorization (P = .019), attention/working memory (P = .011), and overall cognition (P = .006), such that the associations between duration of type 2 diabetes and cognitive impairment increased as HbA1c levels increased – but not for episodic memory (P = .984).
In a separate analysis of patients from the same registry, Dr. LeRoith and his colleagues evaluated the relationships of long-term trajectories of glycemic control with cognitive performance in cognitively normal elderly with type 2 diabetes (PLoS ONE 9[6]:e97384 doi: 10.1371/journal.pone.0097384). They found that subjects with stable HbA1c over time had the lowest HbA1c at study entry and performed best on cognitive measures, “suggesting that the trajectile of HbA1c over 10 or 12 years can really influence the cognitive ability in these patients,” he said.
Another, unrelated study found that insulin in combination with other diabetes medication is associated with less Alzheimer’s neuropathology (Neurology 2008;71:750-7), while an Alzheimer’s mouse model from Dr. LeRoith and his colleagues demonstrated that high dietary advanced glycation end products are associated with poorer spatial learning and accelerated amyloid beta deposition (Aging Cell 2016;15:309-16). “From that study we conclude that high dietary advance glycation end (AGE) products may be neurotoxic and that a diet low in AGEs may decrease dementia risk, particularly in diabetic elderly who are at increased risk and have higher levels of AGEs,” he said.
Potential ways to mitigate some of aging’s effects on the course of diabetes include caloric restriction, exercise, and taking metformin, Dr. LeRoith said. “There is a correlation between fitness and cognitive function, so the implication for clinical practice in individuals with diabetes is to encourage them to engage in physical activity on most days of the week,” he said. “It’s also known that depression makes the diabetes worse and depression makes cognitive function worse. It’s been suggested that if you have patients who are depressed, you should treat them with antidepressants if necessary, because this may help with their cognitive function.”
Meanwhile, an ongoing trial first announced in 2016 known as Targeting Aging with Metformin (TAME) is exploring the effects of metformin in helping to delay the aging process (Cell Metab 2016;23[6]:1060-5). Early support exists that metformin may delay cognitive decline and Alzheimer’s, even in non–type 2 diabetes. “An intended consequence of this effort is to create a paradigm for evaluation of pharmacologic approaches to delay aging,” the researchers wrote in an article describing the project, which is funded by the National Institute on Aging. “The randomized, controlled clinical trial we have proposed, if successful, could profoundly change the approach to aging and its diseases and affect health care delivery and costs.”
Dr. LeRoith reported having no financial disclosures.
EXPERT ANALYSIS FROM WCIRDC 2018
Nuedexta mainly prescribed for dementia, Parkinson’s
Only 15% of patients prescribed dextromethorphan hydrobromide plus quinidine sulfate had pseudobulbar affect due to multiple sclerosis or amyotrophic lateral sclerosis, the condition for which this drug is labeled, according to an analysis of two national commercial insurance claims databases published online Jan. 7 in JAMA Internal Medicine.
Conversely, 57% of patients prescribed dextromethorphan-quinidine (Nuedexta) had a diagnosis of Parkinson’s disease or dementia. Furthermore, according to Medicare Part D data, prescriptions for dextromethorphan-quinidine rose 15-fold during a recent 6-year period, with a concurrent 50-fold rise in reimbursement. “In response to findings such as ours, further attention should be paid to educating prescribers about the actual benefits and risks of this costly drug combination,” Michael Fralick, MD, and his associates at Brigham and Women’s Hospital and Harvard Medical School, Boston, wrote in their paper.
The Food and Drug Administration approved Nuedexta in 2010 for the treatment of pseudobulbar affect after it produced modest improvements in laughing or crying episodes in a 12-week, placebo-controlled trial of patients with multiple sclerosis (MS) or amyotrophic lateral sclerosis (ALS). The initial FDA label noted: “Nuedexta has not been shown to be safe or effective in other types of emotional lability that can commonly occur, for example, in Alzheimer’s disease and other dementias.” Then, in 2015, patients with Alzheimer’s disease showed modest improvements in agitation scores when they received dextromethorphan-quinidine in a 10-week, placebo-controlled, industry-designed and sponsored trial. Although the dextromethorphan-quinidine arm also had higher rates of falls, urinary tract infections, and serious adverse events, the prescribing information was updated in 2015 to remove the statement about patients with dementia.
To assess real-world prescribing patterns for dextromethorphan-quinidine, Dr. Fralick and his associates analyzed data from 12,858 patients who filled a prescription for this medication between 2010 and 2017 and were recorded in the Optum Clinformatics Data Mart or Truven Health MarketScan databases. Only 8.4% of patients had a diagnosis of MS and only 6.8% had ALS, while 57% had dementia and/or Parkinson’s disease and 28% had an unknown diagnosis. The number of patients prescribed dextromethorphan-quinidine rose from nearly 3,300 in 2011 to more than 50,000 in 2016, while spending on this medication by the Centers for Medicare & Medicaid Services increased from $3.9 million to $200.4 million during the same time period.
Current treatments for behavioral symptoms of dementia “are largely ineffective, and thus clinicians may want to prescribe dextromethorphan-quinidine to see if it helps their patients,” the researchers wrote. “Yet the absence of data showing efficacy, coupled with the demonstrated risks of falls and possible cardiac effects, calls this strategy into question.
“Further studies should be required to evaluate the safety and effectiveness of this medication as it is currently being used,” the authors suggested.
Study funders included the Laura and John Arnold Foundation, the Harvard Program in Therapeutic Science, the Engelberg Foundation, and the University of Toronto Clinician Scientist Training Program. One author disclosed grants from the Food and Drug Administration Office of Generic Drugs and Division of Health Communication unrelated to the study topic.
SOURCE: Fralick M et al. JAMA Inter Med. 2019 Jan 7. doi: 10.1001/jamainternmed.2018.6112
Only 15% of patients prescribed dextromethorphan hydrobromide plus quinidine sulfate had pseudobulbar affect due to multiple sclerosis or amyotrophic lateral sclerosis, the condition for which this drug is labeled, according to an analysis of two national commercial insurance claims databases published online Jan. 7 in JAMA Internal Medicine.
Conversely, 57% of patients prescribed dextromethorphan-quinidine (Nuedexta) had a diagnosis of Parkinson’s disease or dementia. Furthermore, according to Medicare Part D data, prescriptions for dextromethorphan-quinidine rose 15-fold during a recent 6-year period, with a concurrent 50-fold rise in reimbursement. “In response to findings such as ours, further attention should be paid to educating prescribers about the actual benefits and risks of this costly drug combination,” Michael Fralick, MD, and his associates at Brigham and Women’s Hospital and Harvard Medical School, Boston, wrote in their paper.
The Food and Drug Administration approved Nuedexta in 2010 for the treatment of pseudobulbar affect after it produced modest improvements in laughing or crying episodes in a 12-week, placebo-controlled trial of patients with multiple sclerosis (MS) or amyotrophic lateral sclerosis (ALS). The initial FDA label noted: “Nuedexta has not been shown to be safe or effective in other types of emotional lability that can commonly occur, for example, in Alzheimer’s disease and other dementias.” Then, in 2015, patients with Alzheimer’s disease showed modest improvements in agitation scores when they received dextromethorphan-quinidine in a 10-week, placebo-controlled, industry-designed and sponsored trial. Although the dextromethorphan-quinidine arm also had higher rates of falls, urinary tract infections, and serious adverse events, the prescribing information was updated in 2015 to remove the statement about patients with dementia.
To assess real-world prescribing patterns for dextromethorphan-quinidine, Dr. Fralick and his associates analyzed data from 12,858 patients who filled a prescription for this medication between 2010 and 2017 and were recorded in the Optum Clinformatics Data Mart or Truven Health MarketScan databases. Only 8.4% of patients had a diagnosis of MS and only 6.8% had ALS, while 57% had dementia and/or Parkinson’s disease and 28% had an unknown diagnosis. The number of patients prescribed dextromethorphan-quinidine rose from nearly 3,300 in 2011 to more than 50,000 in 2016, while spending on this medication by the Centers for Medicare & Medicaid Services increased from $3.9 million to $200.4 million during the same time period.
Current treatments for behavioral symptoms of dementia “are largely ineffective, and thus clinicians may want to prescribe dextromethorphan-quinidine to see if it helps their patients,” the researchers wrote. “Yet the absence of data showing efficacy, coupled with the demonstrated risks of falls and possible cardiac effects, calls this strategy into question.
“Further studies should be required to evaluate the safety and effectiveness of this medication as it is currently being used,” the authors suggested.
Study funders included the Laura and John Arnold Foundation, the Harvard Program in Therapeutic Science, the Engelberg Foundation, and the University of Toronto Clinician Scientist Training Program. One author disclosed grants from the Food and Drug Administration Office of Generic Drugs and Division of Health Communication unrelated to the study topic.
SOURCE: Fralick M et al. JAMA Inter Med. 2019 Jan 7. doi: 10.1001/jamainternmed.2018.6112
Only 15% of patients prescribed dextromethorphan hydrobromide plus quinidine sulfate had pseudobulbar affect due to multiple sclerosis or amyotrophic lateral sclerosis, the condition for which this drug is labeled, according to an analysis of two national commercial insurance claims databases published online Jan. 7 in JAMA Internal Medicine.
Conversely, 57% of patients prescribed dextromethorphan-quinidine (Nuedexta) had a diagnosis of Parkinson’s disease or dementia. Furthermore, according to Medicare Part D data, prescriptions for dextromethorphan-quinidine rose 15-fold during a recent 6-year period, with a concurrent 50-fold rise in reimbursement. “In response to findings such as ours, further attention should be paid to educating prescribers about the actual benefits and risks of this costly drug combination,” Michael Fralick, MD, and his associates at Brigham and Women’s Hospital and Harvard Medical School, Boston, wrote in their paper.
The Food and Drug Administration approved Nuedexta in 2010 for the treatment of pseudobulbar affect after it produced modest improvements in laughing or crying episodes in a 12-week, placebo-controlled trial of patients with multiple sclerosis (MS) or amyotrophic lateral sclerosis (ALS). The initial FDA label noted: “Nuedexta has not been shown to be safe or effective in other types of emotional lability that can commonly occur, for example, in Alzheimer’s disease and other dementias.” Then, in 2015, patients with Alzheimer’s disease showed modest improvements in agitation scores when they received dextromethorphan-quinidine in a 10-week, placebo-controlled, industry-designed and sponsored trial. Although the dextromethorphan-quinidine arm also had higher rates of falls, urinary tract infections, and serious adverse events, the prescribing information was updated in 2015 to remove the statement about patients with dementia.
To assess real-world prescribing patterns for dextromethorphan-quinidine, Dr. Fralick and his associates analyzed data from 12,858 patients who filled a prescription for this medication between 2010 and 2017 and were recorded in the Optum Clinformatics Data Mart or Truven Health MarketScan databases. Only 8.4% of patients had a diagnosis of MS and only 6.8% had ALS, while 57% had dementia and/or Parkinson’s disease and 28% had an unknown diagnosis. The number of patients prescribed dextromethorphan-quinidine rose from nearly 3,300 in 2011 to more than 50,000 in 2016, while spending on this medication by the Centers for Medicare & Medicaid Services increased from $3.9 million to $200.4 million during the same time period.
Current treatments for behavioral symptoms of dementia “are largely ineffective, and thus clinicians may want to prescribe dextromethorphan-quinidine to see if it helps their patients,” the researchers wrote. “Yet the absence of data showing efficacy, coupled with the demonstrated risks of falls and possible cardiac effects, calls this strategy into question.
“Further studies should be required to evaluate the safety and effectiveness of this medication as it is currently being used,” the authors suggested.
Study funders included the Laura and John Arnold Foundation, the Harvard Program in Therapeutic Science, the Engelberg Foundation, and the University of Toronto Clinician Scientist Training Program. One author disclosed grants from the Food and Drug Administration Office of Generic Drugs and Division of Health Communication unrelated to the study topic.
SOURCE: Fralick M et al. JAMA Inter Med. 2019 Jan 7. doi: 10.1001/jamainternmed.2018.6112
FROM JAMA INTERNAL MEDICINE
Key clinical point:
Major finding: Only 8.4% of patients had a diagnosis of multiple sclerosis and only 6.8% had amyotrophic lateral sclerosis, while 57% had dementia and/or Parkinson’s disease and 28% had an unknown diagnosis.
Study details: Population-based cohort study of 12,858 patients prescribed dextromethorphan-quinidine between 2010 and 2017.
Disclosures: Study funders included the Laura and John Arnold Foundation, the Harvard Program in Therapeutic Science, the Engelberg Foundation, and the University of Toronto Clinician Scientist Training Program. One author disclosed grants from the Food and Drug Administration Office of Generic Drugs and Division of Health Communication unrelated to the study topic.
Source: Fralick M et al. JAMA Intern Med. 2019 Jan 7. doi: 10.1001/jamainternmed.2018.6112.
Does rituximab delay disability progression in patients with secondary progressive MS?
, according to a retrospective analysis published online Jan. 7 in JAMA Neurology.
The results suggest that “B-cell depletion by rituximab may be therapeutically beneficial in these patients,” said study author Yvonne Naegelin, MD, of the department of neurology at University Hospital Basel, Switzerland, and her colleagues. “A prospective randomized clinical trial with a better level of evidence is needed to confirm the efficacy of rituximab in such patients.”
Research indicates that B cells play a role in the pathogenesis of relapsing-remitting and secondary progressive MS, and rituximab, a monoclonal CD20 antibody, may deplete B cells in the peripheral immune system and CNS. “Owing to the limited treatment options for secondary progressive MS and the extrapolation of results in relapsing-remitting MS and primary progressive MS, rituximab was used off-label for the treatment of secondary progressive MS,” the authors said. They compared disability progression in patients who were treated with rituximab at MS centers in Switzerland with disability of control patients with secondary progressive MS who did not receive rituximab. The control patients were part of an observational cohort study at MS centers in Switzerland and the Netherlands. Data for the present analysis were collected between 2004 and 2017.
The investigators matched rituximab-treated and control patients 1:1 using propensity scores. Matching variables were sex, age, EDSS score, and disease duration at baseline. Rituximab-treated patients had a mean age of 49.7 years, mean disease duration of 18.2 years, and mean EDSS score of 5.9; 59% were women. Controls had a mean age of 51.3 years, mean disease duration of 19.4 years, and mean EDSS score of 5.7; 61% were women.
A covariate-adjusted analysis of the matched set found that rituximab-treated patients had a significantly lower EDSS score during a mean follow-up of 3.5 years (mean difference, –0.52). In addition, time to confirmed disability progression was delayed in the rituximab-treated group (hazard ratio, 0.49). “Approximately 75% of untreated and 50% of treated individuals in our cohorts developed clinically significant confirmed progression for the 10-year period,” Dr. Naegelin and her colleagues reported. Complications, mainly related to infections, occurred in five cases during treatment. The researchers did not identify major safety concerns, however.
Dr. Naegelin had no conflict of interest disclosures. Several coauthors disclosed research support and compensation from pharmaceutical companies.
SOURCE: Naegelin Y et al. JAMA Neurol. 2019 Jan 7. doi: 10.1001/jamaneurol.2018.4239.
, according to a retrospective analysis published online Jan. 7 in JAMA Neurology.
The results suggest that “B-cell depletion by rituximab may be therapeutically beneficial in these patients,” said study author Yvonne Naegelin, MD, of the department of neurology at University Hospital Basel, Switzerland, and her colleagues. “A prospective randomized clinical trial with a better level of evidence is needed to confirm the efficacy of rituximab in such patients.”
Research indicates that B cells play a role in the pathogenesis of relapsing-remitting and secondary progressive MS, and rituximab, a monoclonal CD20 antibody, may deplete B cells in the peripheral immune system and CNS. “Owing to the limited treatment options for secondary progressive MS and the extrapolation of results in relapsing-remitting MS and primary progressive MS, rituximab was used off-label for the treatment of secondary progressive MS,” the authors said. They compared disability progression in patients who were treated with rituximab at MS centers in Switzerland with disability of control patients with secondary progressive MS who did not receive rituximab. The control patients were part of an observational cohort study at MS centers in Switzerland and the Netherlands. Data for the present analysis were collected between 2004 and 2017.
The investigators matched rituximab-treated and control patients 1:1 using propensity scores. Matching variables were sex, age, EDSS score, and disease duration at baseline. Rituximab-treated patients had a mean age of 49.7 years, mean disease duration of 18.2 years, and mean EDSS score of 5.9; 59% were women. Controls had a mean age of 51.3 years, mean disease duration of 19.4 years, and mean EDSS score of 5.7; 61% were women.
A covariate-adjusted analysis of the matched set found that rituximab-treated patients had a significantly lower EDSS score during a mean follow-up of 3.5 years (mean difference, –0.52). In addition, time to confirmed disability progression was delayed in the rituximab-treated group (hazard ratio, 0.49). “Approximately 75% of untreated and 50% of treated individuals in our cohorts developed clinically significant confirmed progression for the 10-year period,” Dr. Naegelin and her colleagues reported. Complications, mainly related to infections, occurred in five cases during treatment. The researchers did not identify major safety concerns, however.
Dr. Naegelin had no conflict of interest disclosures. Several coauthors disclosed research support and compensation from pharmaceutical companies.
SOURCE: Naegelin Y et al. JAMA Neurol. 2019 Jan 7. doi: 10.1001/jamaneurol.2018.4239.
, according to a retrospective analysis published online Jan. 7 in JAMA Neurology.
The results suggest that “B-cell depletion by rituximab may be therapeutically beneficial in these patients,” said study author Yvonne Naegelin, MD, of the department of neurology at University Hospital Basel, Switzerland, and her colleagues. “A prospective randomized clinical trial with a better level of evidence is needed to confirm the efficacy of rituximab in such patients.”
Research indicates that B cells play a role in the pathogenesis of relapsing-remitting and secondary progressive MS, and rituximab, a monoclonal CD20 antibody, may deplete B cells in the peripheral immune system and CNS. “Owing to the limited treatment options for secondary progressive MS and the extrapolation of results in relapsing-remitting MS and primary progressive MS, rituximab was used off-label for the treatment of secondary progressive MS,” the authors said. They compared disability progression in patients who were treated with rituximab at MS centers in Switzerland with disability of control patients with secondary progressive MS who did not receive rituximab. The control patients were part of an observational cohort study at MS centers in Switzerland and the Netherlands. Data for the present analysis were collected between 2004 and 2017.
The investigators matched rituximab-treated and control patients 1:1 using propensity scores. Matching variables were sex, age, EDSS score, and disease duration at baseline. Rituximab-treated patients had a mean age of 49.7 years, mean disease duration of 18.2 years, and mean EDSS score of 5.9; 59% were women. Controls had a mean age of 51.3 years, mean disease duration of 19.4 years, and mean EDSS score of 5.7; 61% were women.
A covariate-adjusted analysis of the matched set found that rituximab-treated patients had a significantly lower EDSS score during a mean follow-up of 3.5 years (mean difference, –0.52). In addition, time to confirmed disability progression was delayed in the rituximab-treated group (hazard ratio, 0.49). “Approximately 75% of untreated and 50% of treated individuals in our cohorts developed clinically significant confirmed progression for the 10-year period,” Dr. Naegelin and her colleagues reported. Complications, mainly related to infections, occurred in five cases during treatment. The researchers did not identify major safety concerns, however.
Dr. Naegelin had no conflict of interest disclosures. Several coauthors disclosed research support and compensation from pharmaceutical companies.
SOURCE: Naegelin Y et al. JAMA Neurol. 2019 Jan 7. doi: 10.1001/jamaneurol.2018.4239.
FROM JAMA NEUROLOGY
Key clinical point: Among patients with secondary progressive MS, those treated with rituximab may accrue less disability.
Major finding: Rituximab-treated patients, compared with controls, had a significantly lower EDSS score during a mean follow-up of 3.5 years (mean difference, –0.52).
Study details: A retrospective study of 88 propensity score–matched patients with secondary progressive MS.
Disclosures: Dr. Naegelin had no disclosures. Several coauthors disclosed research support and compensation from pharmaceutical companies.
Source: Naegelin Y et al. JAMA Neurol. 2019 Jan 7. doi: 10.1001/jamaneurol.2018.4239.
Synthetic opioids drive spike in U.S. fatal drug overdoses
New federal statistics suggest that the opioid epidemic in the United States is evolving as physicians crack down on the use of prescription painkillers: Fatal drug overdose deaths rose by 12% from 2016 to 2017, boosted by a wave of fatalities linked to illicit synthetic opioids like fentanyl that are now linked to an estimated 60% of opioid-related deaths.
“Overall, the overdose epidemic continues to worsen, and it has grown increasingly complex by coinvolvement of prescription and illicit drugs,” Lawrence Scholl, PhD, MPH, and his associates at the Centers for Disease Control & Prevention wrote in the Morbidity and Mortality Weekly Report.
The new statistics provide more evidence that 2017 marked “a sharp increase in what has characterized as the third wave of the opioid epidemic,” said drug and health policy researcher Stephen Crystal, PhD, of Rutgers University, New Brunswick, N.J., in an interview. He was referring to a wave that experts believe started in 2013 amid a spike in U.S. overdose deaths from fentanyl and other synthetic opioids.
The new report analyzes fatal drug overdose data from 2013 to 2017. According to the findings, the total number of those overdoses rose to 70,237 in 2017, up from 63,632 in 2016. The highest drug overdose death rates in 2017 were in West Virginia, followed by Ohio, Pennsylvania, and the District of Columbia.
Some statistics did not change much from 2016 to 2017: About two-thirds of the drug overdose deaths were linked to opioids in both years, and the death rate of cases linked to prescription drugs and heroin remained steady. (Death rates in the report were age adjusted.)
However, the percentage of fatal overdose cases linked to synthetic opioids grew 45% from 2016 to 2017. Overall, 60% of opioid-related fatal overdoses in 2017 involved synthetic opioids.
The report identifies increases in several areas from 2016 to 2017. Opioid-related drug overdose deaths among black people rose by 25%, and an analysis of data from 34 states and the District of Columbia found the highest increases in death rates in North Carolina (29%), Ohio (19%), and Maine (19%).
In regard to deaths linked to synthetic opioids specifically, the highest death rates in 2017 were in West Virginia (37 per 100,000), Ohio (32 per 100,000), and New Hampshire (30 per 100,000).
“Part of what we’re seeing in these increased numbers are individuals who have pain, can’t get prescribed opioids, and turn to street drugs,” Dr. Crystal said, adding that “abruptly cutting patients off is not good, and leaving patients with a lot of untreated pain is not good. If people are going to be discontinued [from opioids] or have their doses reduced, the taper needs to be done very slowly and carefully.”
Synthetic opioids were not the only drugs that are driving up fatal overdoses, as the death rates of cases linked to cocaine and psychostimulants (such as methamphetamine) jumped by more than a third in 2017.
“The most important thing these numbers are telling me is that it’s becoming more and more attractive to drug dealers to put fentanyl in the heroin, cocaine, and other drugs they sell,” Dr. Crystal said. “When that happens, dependence on street drugs becomes much more deadly. It’s almost impossible to get the dose right. Every time you shoot up, you’re taking a chance that you’ll overdose.”
The report had limitations, including the fact that details about drug use were missing from 12% (2016) and 15% (2017) of death certificates in fatal overdose cases. By state, the percentages of those death certificates that included drug information ranged from as little as 55% to 99%.
There’s some possible positive news: The report points to preliminary data from 2018 suggesting that the number of annual drug overdose deaths may be leveling off – although it says more analysis is needed to confirm the trend.
Dr. Crystal, however, is not celebrating. “I don’t see this as a good news story, really,” he said, adding that there’s “a little too much of people patting themselves on the back” because they’re proud of cutbacks in opioid prescriptions.
“This doesn’t have to do with the huge number of people who got started with opioids years ago” and are now at risk of using street drugs, he said. “We haven’t engaged that population at the rate we need to. And flattening out at 70,000 drug overdoses a year is not a good news story.”
Dr. Crystal reported no relevant disclosures.
SOURCE: Scholl L et al. MMWR. 2019 Jan 4;67(5152):1419-27.
New federal statistics suggest that the opioid epidemic in the United States is evolving as physicians crack down on the use of prescription painkillers: Fatal drug overdose deaths rose by 12% from 2016 to 2017, boosted by a wave of fatalities linked to illicit synthetic opioids like fentanyl that are now linked to an estimated 60% of opioid-related deaths.
“Overall, the overdose epidemic continues to worsen, and it has grown increasingly complex by coinvolvement of prescription and illicit drugs,” Lawrence Scholl, PhD, MPH, and his associates at the Centers for Disease Control & Prevention wrote in the Morbidity and Mortality Weekly Report.
The new statistics provide more evidence that 2017 marked “a sharp increase in what has characterized as the third wave of the opioid epidemic,” said drug and health policy researcher Stephen Crystal, PhD, of Rutgers University, New Brunswick, N.J., in an interview. He was referring to a wave that experts believe started in 2013 amid a spike in U.S. overdose deaths from fentanyl and other synthetic opioids.
The new report analyzes fatal drug overdose data from 2013 to 2017. According to the findings, the total number of those overdoses rose to 70,237 in 2017, up from 63,632 in 2016. The highest drug overdose death rates in 2017 were in West Virginia, followed by Ohio, Pennsylvania, and the District of Columbia.
Some statistics did not change much from 2016 to 2017: About two-thirds of the drug overdose deaths were linked to opioids in both years, and the death rate of cases linked to prescription drugs and heroin remained steady. (Death rates in the report were age adjusted.)
However, the percentage of fatal overdose cases linked to synthetic opioids grew 45% from 2016 to 2017. Overall, 60% of opioid-related fatal overdoses in 2017 involved synthetic opioids.
The report identifies increases in several areas from 2016 to 2017. Opioid-related drug overdose deaths among black people rose by 25%, and an analysis of data from 34 states and the District of Columbia found the highest increases in death rates in North Carolina (29%), Ohio (19%), and Maine (19%).
In regard to deaths linked to synthetic opioids specifically, the highest death rates in 2017 were in West Virginia (37 per 100,000), Ohio (32 per 100,000), and New Hampshire (30 per 100,000).
“Part of what we’re seeing in these increased numbers are individuals who have pain, can’t get prescribed opioids, and turn to street drugs,” Dr. Crystal said, adding that “abruptly cutting patients off is not good, and leaving patients with a lot of untreated pain is not good. If people are going to be discontinued [from opioids] or have their doses reduced, the taper needs to be done very slowly and carefully.”
Synthetic opioids were not the only drugs that are driving up fatal overdoses, as the death rates of cases linked to cocaine and psychostimulants (such as methamphetamine) jumped by more than a third in 2017.
“The most important thing these numbers are telling me is that it’s becoming more and more attractive to drug dealers to put fentanyl in the heroin, cocaine, and other drugs they sell,” Dr. Crystal said. “When that happens, dependence on street drugs becomes much more deadly. It’s almost impossible to get the dose right. Every time you shoot up, you’re taking a chance that you’ll overdose.”
The report had limitations, including the fact that details about drug use were missing from 12% (2016) and 15% (2017) of death certificates in fatal overdose cases. By state, the percentages of those death certificates that included drug information ranged from as little as 55% to 99%.
There’s some possible positive news: The report points to preliminary data from 2018 suggesting that the number of annual drug overdose deaths may be leveling off – although it says more analysis is needed to confirm the trend.
Dr. Crystal, however, is not celebrating. “I don’t see this as a good news story, really,” he said, adding that there’s “a little too much of people patting themselves on the back” because they’re proud of cutbacks in opioid prescriptions.
“This doesn’t have to do with the huge number of people who got started with opioids years ago” and are now at risk of using street drugs, he said. “We haven’t engaged that population at the rate we need to. And flattening out at 70,000 drug overdoses a year is not a good news story.”
Dr. Crystal reported no relevant disclosures.
SOURCE: Scholl L et al. MMWR. 2019 Jan 4;67(5152):1419-27.
New federal statistics suggest that the opioid epidemic in the United States is evolving as physicians crack down on the use of prescription painkillers: Fatal drug overdose deaths rose by 12% from 2016 to 2017, boosted by a wave of fatalities linked to illicit synthetic opioids like fentanyl that are now linked to an estimated 60% of opioid-related deaths.
“Overall, the overdose epidemic continues to worsen, and it has grown increasingly complex by coinvolvement of prescription and illicit drugs,” Lawrence Scholl, PhD, MPH, and his associates at the Centers for Disease Control & Prevention wrote in the Morbidity and Mortality Weekly Report.
The new statistics provide more evidence that 2017 marked “a sharp increase in what has characterized as the third wave of the opioid epidemic,” said drug and health policy researcher Stephen Crystal, PhD, of Rutgers University, New Brunswick, N.J., in an interview. He was referring to a wave that experts believe started in 2013 amid a spike in U.S. overdose deaths from fentanyl and other synthetic opioids.
The new report analyzes fatal drug overdose data from 2013 to 2017. According to the findings, the total number of those overdoses rose to 70,237 in 2017, up from 63,632 in 2016. The highest drug overdose death rates in 2017 were in West Virginia, followed by Ohio, Pennsylvania, and the District of Columbia.
Some statistics did not change much from 2016 to 2017: About two-thirds of the drug overdose deaths were linked to opioids in both years, and the death rate of cases linked to prescription drugs and heroin remained steady. (Death rates in the report were age adjusted.)
However, the percentage of fatal overdose cases linked to synthetic opioids grew 45% from 2016 to 2017. Overall, 60% of opioid-related fatal overdoses in 2017 involved synthetic opioids.
The report identifies increases in several areas from 2016 to 2017. Opioid-related drug overdose deaths among black people rose by 25%, and an analysis of data from 34 states and the District of Columbia found the highest increases in death rates in North Carolina (29%), Ohio (19%), and Maine (19%).
In regard to deaths linked to synthetic opioids specifically, the highest death rates in 2017 were in West Virginia (37 per 100,000), Ohio (32 per 100,000), and New Hampshire (30 per 100,000).
“Part of what we’re seeing in these increased numbers are individuals who have pain, can’t get prescribed opioids, and turn to street drugs,” Dr. Crystal said, adding that “abruptly cutting patients off is not good, and leaving patients with a lot of untreated pain is not good. If people are going to be discontinued [from opioids] or have their doses reduced, the taper needs to be done very slowly and carefully.”
Synthetic opioids were not the only drugs that are driving up fatal overdoses, as the death rates of cases linked to cocaine and psychostimulants (such as methamphetamine) jumped by more than a third in 2017.
“The most important thing these numbers are telling me is that it’s becoming more and more attractive to drug dealers to put fentanyl in the heroin, cocaine, and other drugs they sell,” Dr. Crystal said. “When that happens, dependence on street drugs becomes much more deadly. It’s almost impossible to get the dose right. Every time you shoot up, you’re taking a chance that you’ll overdose.”
The report had limitations, including the fact that details about drug use were missing from 12% (2016) and 15% (2017) of death certificates in fatal overdose cases. By state, the percentages of those death certificates that included drug information ranged from as little as 55% to 99%.
There’s some possible positive news: The report points to preliminary data from 2018 suggesting that the number of annual drug overdose deaths may be leveling off – although it says more analysis is needed to confirm the trend.
Dr. Crystal, however, is not celebrating. “I don’t see this as a good news story, really,” he said, adding that there’s “a little too much of people patting themselves on the back” because they’re proud of cutbacks in opioid prescriptions.
“This doesn’t have to do with the huge number of people who got started with opioids years ago” and are now at risk of using street drugs, he said. “We haven’t engaged that population at the rate we need to. And flattening out at 70,000 drug overdoses a year is not a good news story.”
Dr. Crystal reported no relevant disclosures.
SOURCE: Scholl L et al. MMWR. 2019 Jan 4;67(5152):1419-27.
FROM MMWR
Prenatal valproate exposure raises ADHD risk
Children exposed to valproate in utero were 48% more likely to be diagnosed with ADHD when compared with unexposed children in a population-based cohort study of more than 900,000 children in Denmark.
Antiepileptic drug exposure is associated with an increased risk of various congenital malformations, but its role in the development of ADHD in children has not been well documented, first author Jakob Christensen, MD, PhD, DrMedSci, of Aarhus (Denmark) University Hospital, and his colleagues wrote in their paper, published online Jan. 4 in JAMA Network Open.
The researchers identified 913,302 singleton births in Denmark from 1997 through 2011, with children followed through 2015.
Overall, children who were prenatally exposed to valproate had a 48% increased risk of ADHD. Antiepileptic drug exposure was defined as 30 days before the estimated day of conception to the day of birth, and included valproate, clobazam, and other antiepileptic drugs. The average age of the children at the study’s end was 10 years, and approximately half were male.
A total of 580 children were exposed to valproate in utero; of these, 8.4% were later diagnosed with ADHD, compared with 3.2% of 912,722 children who were not exposed to valproate. In addition, the absolute 15-year risk of ADHD was 11% in valproate-exposed children vs. 4.6% in unexposed children. No significant associations appeared between ADHD and other antiepileptic drugs.
The study findings were limited by several factors, including the contraindication of valproate for use in pregnancy, which may mean that the women taking valproate had more severe disease, the researchers noted.
“Due to the observational nature of this study, we cannot rule out that the observed risk increase for ADHD is at least in part explained by the mother’s health condition that triggered the prescription of valproate during pregnancy,” they said. Other limitations included a lack of data on the exact amounts of valproate taken during pregnancy and the potential impact of nonepilepsy medications, they noted.
However, the results were strengthened by the large size and population-based cohort, and support warnings by professional medical organizations against valproate use in pregnancy, the researchers said. “As randomized clinical trials of valproate use during pregnancy are neither feasible nor ethical, our study provides clinical information on the risk of ADHD associated with valproate use during pregnancy,” they concluded.
The study was supported by grants to various authors from the Danish Epilepsy Association Central Denmark Region, the Aarhus University Research Foundation, the Lundbeck Foundation, the National Institutes of Health, the Novo Nordisk Foundation, and the European Commission.
SOURCE: Christensen J et al. JAMA Network Open. 2019;2(1):e186606. doi: 10.1001/jamanetworkopen.2018.6606.
The data from the current study differ from a recent meta-analysis of five studies that did not find a statistically significant increase in ADHD risk in children associated with prenatal valproate exposure, Kimford J. Meador, MD, wrote in an accompanying editorial (JAMA Network Open. 2019;2[1]:e186603. doi: 10.1001/jamanetworkopen.2018.6603).
“The discrepancy between the present study and the prior meta-analysis might be due to the meta-analysis using different analytical approaches and examining studies with smaller sample sizes, higher attrition rates, shorter follow-ups, and cohort differences,” Dr. Meador said. “Nevertheless, the findings by Christensen et al. are consistent with multiple studies demonstrating adverse neurodevelopmental effects associated with fetal valproate exposure.”
Given the potential risks associated with valproate exposure not only for behavior problems such as ADHD but also for congenital malformations and other cognitive and behavioral issues in children, women of childbearing age who are using valproate or considering a prescription should be counseled for informed consent, Dr. Meador said.
Dr. Meador advocated additional research on the impact of antiepileptic drugs during pregnancy and risk assessment strategies, including “a national reporting system for congenital malformations, routine preclinical testing of all new antiseizure medications for neurodevelopmental effects, monitoring of antiseizure medication prescription practices for women of childbearing age to determine whether emerging knowledge is being appropriately applied, and improved funding of basic and clinical research to fully delineate risks and underlying mechanisms of anatomical and behavioral teratogenesis from antiseizure medications.”
Dr. Meador is affiliated with the department of neurology and neurological sciences at Stanford (Calif.) University. He disclosed research support from the National Institutes of Health and Sunovion, and travel support from UCB. The Epilepsy Study Consortium pays Stanford University for his research consultant time related to Eisai, GW Pharmaceuticals, NeuroPace, Novartis, Supernus, Upsher-Smith Laboratories, UCB, and Vivus.
The data from the current study differ from a recent meta-analysis of five studies that did not find a statistically significant increase in ADHD risk in children associated with prenatal valproate exposure, Kimford J. Meador, MD, wrote in an accompanying editorial (JAMA Network Open. 2019;2[1]:e186603. doi: 10.1001/jamanetworkopen.2018.6603).
“The discrepancy between the present study and the prior meta-analysis might be due to the meta-analysis using different analytical approaches and examining studies with smaller sample sizes, higher attrition rates, shorter follow-ups, and cohort differences,” Dr. Meador said. “Nevertheless, the findings by Christensen et al. are consistent with multiple studies demonstrating adverse neurodevelopmental effects associated with fetal valproate exposure.”
Given the potential risks associated with valproate exposure not only for behavior problems such as ADHD but also for congenital malformations and other cognitive and behavioral issues in children, women of childbearing age who are using valproate or considering a prescription should be counseled for informed consent, Dr. Meador said.
Dr. Meador advocated additional research on the impact of antiepileptic drugs during pregnancy and risk assessment strategies, including “a national reporting system for congenital malformations, routine preclinical testing of all new antiseizure medications for neurodevelopmental effects, monitoring of antiseizure medication prescription practices for women of childbearing age to determine whether emerging knowledge is being appropriately applied, and improved funding of basic and clinical research to fully delineate risks and underlying mechanisms of anatomical and behavioral teratogenesis from antiseizure medications.”
Dr. Meador is affiliated with the department of neurology and neurological sciences at Stanford (Calif.) University. He disclosed research support from the National Institutes of Health and Sunovion, and travel support from UCB. The Epilepsy Study Consortium pays Stanford University for his research consultant time related to Eisai, GW Pharmaceuticals, NeuroPace, Novartis, Supernus, Upsher-Smith Laboratories, UCB, and Vivus.
The data from the current study differ from a recent meta-analysis of five studies that did not find a statistically significant increase in ADHD risk in children associated with prenatal valproate exposure, Kimford J. Meador, MD, wrote in an accompanying editorial (JAMA Network Open. 2019;2[1]:e186603. doi: 10.1001/jamanetworkopen.2018.6603).
“The discrepancy between the present study and the prior meta-analysis might be due to the meta-analysis using different analytical approaches and examining studies with smaller sample sizes, higher attrition rates, shorter follow-ups, and cohort differences,” Dr. Meador said. “Nevertheless, the findings by Christensen et al. are consistent with multiple studies demonstrating adverse neurodevelopmental effects associated with fetal valproate exposure.”
Given the potential risks associated with valproate exposure not only for behavior problems such as ADHD but also for congenital malformations and other cognitive and behavioral issues in children, women of childbearing age who are using valproate or considering a prescription should be counseled for informed consent, Dr. Meador said.
Dr. Meador advocated additional research on the impact of antiepileptic drugs during pregnancy and risk assessment strategies, including “a national reporting system for congenital malformations, routine preclinical testing of all new antiseizure medications for neurodevelopmental effects, monitoring of antiseizure medication prescription practices for women of childbearing age to determine whether emerging knowledge is being appropriately applied, and improved funding of basic and clinical research to fully delineate risks and underlying mechanisms of anatomical and behavioral teratogenesis from antiseizure medications.”
Dr. Meador is affiliated with the department of neurology and neurological sciences at Stanford (Calif.) University. He disclosed research support from the National Institutes of Health and Sunovion, and travel support from UCB. The Epilepsy Study Consortium pays Stanford University for his research consultant time related to Eisai, GW Pharmaceuticals, NeuroPace, Novartis, Supernus, Upsher-Smith Laboratories, UCB, and Vivus.
Children exposed to valproate in utero were 48% more likely to be diagnosed with ADHD when compared with unexposed children in a population-based cohort study of more than 900,000 children in Denmark.
Antiepileptic drug exposure is associated with an increased risk of various congenital malformations, but its role in the development of ADHD in children has not been well documented, first author Jakob Christensen, MD, PhD, DrMedSci, of Aarhus (Denmark) University Hospital, and his colleagues wrote in their paper, published online Jan. 4 in JAMA Network Open.
The researchers identified 913,302 singleton births in Denmark from 1997 through 2011, with children followed through 2015.
Overall, children who were prenatally exposed to valproate had a 48% increased risk of ADHD. Antiepileptic drug exposure was defined as 30 days before the estimated day of conception to the day of birth, and included valproate, clobazam, and other antiepileptic drugs. The average age of the children at the study’s end was 10 years, and approximately half were male.
A total of 580 children were exposed to valproate in utero; of these, 8.4% were later diagnosed with ADHD, compared with 3.2% of 912,722 children who were not exposed to valproate. In addition, the absolute 15-year risk of ADHD was 11% in valproate-exposed children vs. 4.6% in unexposed children. No significant associations appeared between ADHD and other antiepileptic drugs.
The study findings were limited by several factors, including the contraindication of valproate for use in pregnancy, which may mean that the women taking valproate had more severe disease, the researchers noted.
“Due to the observational nature of this study, we cannot rule out that the observed risk increase for ADHD is at least in part explained by the mother’s health condition that triggered the prescription of valproate during pregnancy,” they said. Other limitations included a lack of data on the exact amounts of valproate taken during pregnancy and the potential impact of nonepilepsy medications, they noted.
However, the results were strengthened by the large size and population-based cohort, and support warnings by professional medical organizations against valproate use in pregnancy, the researchers said. “As randomized clinical trials of valproate use during pregnancy are neither feasible nor ethical, our study provides clinical information on the risk of ADHD associated with valproate use during pregnancy,” they concluded.
The study was supported by grants to various authors from the Danish Epilepsy Association Central Denmark Region, the Aarhus University Research Foundation, the Lundbeck Foundation, the National Institutes of Health, the Novo Nordisk Foundation, and the European Commission.
SOURCE: Christensen J et al. JAMA Network Open. 2019;2(1):e186606. doi: 10.1001/jamanetworkopen.2018.6606.
Children exposed to valproate in utero were 48% more likely to be diagnosed with ADHD when compared with unexposed children in a population-based cohort study of more than 900,000 children in Denmark.
Antiepileptic drug exposure is associated with an increased risk of various congenital malformations, but its role in the development of ADHD in children has not been well documented, first author Jakob Christensen, MD, PhD, DrMedSci, of Aarhus (Denmark) University Hospital, and his colleagues wrote in their paper, published online Jan. 4 in JAMA Network Open.
The researchers identified 913,302 singleton births in Denmark from 1997 through 2011, with children followed through 2015.
Overall, children who were prenatally exposed to valproate had a 48% increased risk of ADHD. Antiepileptic drug exposure was defined as 30 days before the estimated day of conception to the day of birth, and included valproate, clobazam, and other antiepileptic drugs. The average age of the children at the study’s end was 10 years, and approximately half were male.
A total of 580 children were exposed to valproate in utero; of these, 8.4% were later diagnosed with ADHD, compared with 3.2% of 912,722 children who were not exposed to valproate. In addition, the absolute 15-year risk of ADHD was 11% in valproate-exposed children vs. 4.6% in unexposed children. No significant associations appeared between ADHD and other antiepileptic drugs.
The study findings were limited by several factors, including the contraindication of valproate for use in pregnancy, which may mean that the women taking valproate had more severe disease, the researchers noted.
“Due to the observational nature of this study, we cannot rule out that the observed risk increase for ADHD is at least in part explained by the mother’s health condition that triggered the prescription of valproate during pregnancy,” they said. Other limitations included a lack of data on the exact amounts of valproate taken during pregnancy and the potential impact of nonepilepsy medications, they noted.
However, the results were strengthened by the large size and population-based cohort, and support warnings by professional medical organizations against valproate use in pregnancy, the researchers said. “As randomized clinical trials of valproate use during pregnancy are neither feasible nor ethical, our study provides clinical information on the risk of ADHD associated with valproate use during pregnancy,” they concluded.
The study was supported by grants to various authors from the Danish Epilepsy Association Central Denmark Region, the Aarhus University Research Foundation, the Lundbeck Foundation, the National Institutes of Health, the Novo Nordisk Foundation, and the European Commission.
SOURCE: Christensen J et al. JAMA Network Open. 2019;2(1):e186606. doi: 10.1001/jamanetworkopen.2018.6606.
FROM JAMA NETWORK OPEN
Key clinical point:
Major finding: The children whose mothers used valproate between 90 days before conception and birth had a 48% increased risk of ADHD compared with children whose mothers did not use valproate.
Study details: The data come from a population-based cohort study of 913,302 children in Denmark.
Disclosures: The study was supported by grants to various authors from the Danish Epilepsy Association Central Denmark Region, the Aarhus University Research Foundation, the Lundbeck Foundation, the National Institutes of Health, the Novo Nordisk Foundation, and the European Commission.
Source: SOURCE: Christensen J et al. JAMA Network Open. 2019;2(1):e186606. doi: 10.1001/jamanetworkopen.2018.6606.
Cerebral small vessel disease progression linked to MCI in hypertensive patients
Patients with hypertension who show substantial progression of cerebral small vessel disease over time have sixfold higher odds of developing mild cognitive impairment than do those without signs of progression on brain MRI, new research has found.
The results, published online Jan. 4 in Hypertension, come from a longitudinal, population-based study of 976 patients with hypertension but with no history of dementia or clinical stroke. Participants underwent a vascular risk assessment, brain MRI, cognitive evaluation, and blood sampling at baseline, and 345 patients were also retested after a mean of nearly 4 years.
Researchers saw significant sixfold higher odds of developing incident mild cognitive impairment (MCI) among individuals who showed marked progression of periventricular white matter hyperintensities – an imaging hallmark of cerebral small vessel disease – compared with individuals who did not show any progression (odds ratio = 6.184; 95% confidence interval, 1.506-25.370; P = .011).
Patients with greater progression of periventricular white matter hyperintensities also showed significantly greater decreases in global cognition scores – both in total DRS-2 Z-score and executive function Z-score – when compared against individuals without white matter hyperintensity progression.
“As MCI is one of the most important risk factors in the development of dementia, future research should investigate the mechanisms by which PVH [periventricular white matter hyperintensities] trigger cognitive impairment and the clinical utility of its assessment,” wrote Joan Jiménez-Balado of Vall d’Hebron Research Institute, Barcelona, and his associates.
However, deep white matter hyperintensity progression – as opposed to periventricular – was not linked to cognitive changes, except in the case of bilateral occipital deep white matter hyperintensity changes, which were linked to a significant worsening in the attention Z-score.
The authors noted that the different impacts of periventricular versus deep white matter hyperintensities may relate to a number of factors. The first was that deep white matter hyperintensities disrupt cortico-cortical connections but periventricular ones are more likely to affect long cortico-subcortical association fibers, which “would be an important variable to determine the impaired networks involved in cognition.”
They also suggested that periventricular and deep white matter hyperintensities may affect different neuromodulator systems; the periventricular white matter could be closer to ascending cholinergic bundles that may play a role in vascular cognitive impairment.
Periventricular white matter hyperintensities may also accelerate the deposition of amyloid because of their association with venous collagenosis, which is linked to ischemia and disruptions of the interstitial fluid circulation.
“On the other hand, [deep white matter hyperintensity] may be more related to hypoperfusion, as deep areas are particularly vulnerable to low [blood pressure],” the authors wrote, while stressing that the pathophysiology of white matter hyperintensities is not fully understood, so further research is needed.
Overall, the 345 patients with follow-up data had a median age of 65 years at baseline and mean blood pressure of 143/78.2 mm Hg at baseline and 146.5/75 mm Hg at follow-up. White matter hyperintensity changes occurred periventricularly in 22% and in deep white matter in 48%. The researchers saw new infarcts in 6.1% of patients, and 5.5% had incident cerebral microbleeds. While incident cerebral microbleeds were significantly associated with declines in the attention Z-score, they did not affect other cognitive functions, and incidental infarcts were also not associated with cognitive changes.
Baseline blood pressure and average blood pressure during follow-up were not associated with changes in cardiac small vessel disease lesions. However, diastolic – but not systolic – blood pressure at baseline and follow-up was positively correlated with total, attention, and executive function DRS-2 Z-scores at follow-up.
Three-quarters of patients showed cognitive changes associated with normal aging both at baseline and follow-up, 9.1% had stable MCI, and 9.1% of patients had incident MCI. However, 6.6% of subjects reverted back to normal aging after having MCI at baseline.
The authors noted that they did not examine markers of neurodegeneration, such as tau or amyloid-beta, which could also be linked to hypertension and cerebral small vessel disease lesions.
The study was supported by Instituto de Salud Carlos III, AGAUR (Agency for Management of University and Research Grants), the Secretary of Universities and Research of the Department of Economy and Knowledge, and the European Regional Development Fund. The authors said they have no conflicts of interest.
SOURCE: Jiménez-Balado J et al. Hypertension. 2019 Jan 4. doi: 10.1161/HYPERTENSIONAHA.118.12090
Patients with hypertension who show substantial progression of cerebral small vessel disease over time have sixfold higher odds of developing mild cognitive impairment than do those without signs of progression on brain MRI, new research has found.
The results, published online Jan. 4 in Hypertension, come from a longitudinal, population-based study of 976 patients with hypertension but with no history of dementia or clinical stroke. Participants underwent a vascular risk assessment, brain MRI, cognitive evaluation, and blood sampling at baseline, and 345 patients were also retested after a mean of nearly 4 years.
Researchers saw significant sixfold higher odds of developing incident mild cognitive impairment (MCI) among individuals who showed marked progression of periventricular white matter hyperintensities – an imaging hallmark of cerebral small vessel disease – compared with individuals who did not show any progression (odds ratio = 6.184; 95% confidence interval, 1.506-25.370; P = .011).
Patients with greater progression of periventricular white matter hyperintensities also showed significantly greater decreases in global cognition scores – both in total DRS-2 Z-score and executive function Z-score – when compared against individuals without white matter hyperintensity progression.
“As MCI is one of the most important risk factors in the development of dementia, future research should investigate the mechanisms by which PVH [periventricular white matter hyperintensities] trigger cognitive impairment and the clinical utility of its assessment,” wrote Joan Jiménez-Balado of Vall d’Hebron Research Institute, Barcelona, and his associates.
However, deep white matter hyperintensity progression – as opposed to periventricular – was not linked to cognitive changes, except in the case of bilateral occipital deep white matter hyperintensity changes, which were linked to a significant worsening in the attention Z-score.
The authors noted that the different impacts of periventricular versus deep white matter hyperintensities may relate to a number of factors. The first was that deep white matter hyperintensities disrupt cortico-cortical connections but periventricular ones are more likely to affect long cortico-subcortical association fibers, which “would be an important variable to determine the impaired networks involved in cognition.”
They also suggested that periventricular and deep white matter hyperintensities may affect different neuromodulator systems; the periventricular white matter could be closer to ascending cholinergic bundles that may play a role in vascular cognitive impairment.
Periventricular white matter hyperintensities may also accelerate the deposition of amyloid because of their association with venous collagenosis, which is linked to ischemia and disruptions of the interstitial fluid circulation.
“On the other hand, [deep white matter hyperintensity] may be more related to hypoperfusion, as deep areas are particularly vulnerable to low [blood pressure],” the authors wrote, while stressing that the pathophysiology of white matter hyperintensities is not fully understood, so further research is needed.
Overall, the 345 patients with follow-up data had a median age of 65 years at baseline and mean blood pressure of 143/78.2 mm Hg at baseline and 146.5/75 mm Hg at follow-up. White matter hyperintensity changes occurred periventricularly in 22% and in deep white matter in 48%. The researchers saw new infarcts in 6.1% of patients, and 5.5% had incident cerebral microbleeds. While incident cerebral microbleeds were significantly associated with declines in the attention Z-score, they did not affect other cognitive functions, and incidental infarcts were also not associated with cognitive changes.
Baseline blood pressure and average blood pressure during follow-up were not associated with changes in cardiac small vessel disease lesions. However, diastolic – but not systolic – blood pressure at baseline and follow-up was positively correlated with total, attention, and executive function DRS-2 Z-scores at follow-up.
Three-quarters of patients showed cognitive changes associated with normal aging both at baseline and follow-up, 9.1% had stable MCI, and 9.1% of patients had incident MCI. However, 6.6% of subjects reverted back to normal aging after having MCI at baseline.
The authors noted that they did not examine markers of neurodegeneration, such as tau or amyloid-beta, which could also be linked to hypertension and cerebral small vessel disease lesions.
The study was supported by Instituto de Salud Carlos III, AGAUR (Agency for Management of University and Research Grants), the Secretary of Universities and Research of the Department of Economy and Knowledge, and the European Regional Development Fund. The authors said they have no conflicts of interest.
SOURCE: Jiménez-Balado J et al. Hypertension. 2019 Jan 4. doi: 10.1161/HYPERTENSIONAHA.118.12090
Patients with hypertension who show substantial progression of cerebral small vessel disease over time have sixfold higher odds of developing mild cognitive impairment than do those without signs of progression on brain MRI, new research has found.
The results, published online Jan. 4 in Hypertension, come from a longitudinal, population-based study of 976 patients with hypertension but with no history of dementia or clinical stroke. Participants underwent a vascular risk assessment, brain MRI, cognitive evaluation, and blood sampling at baseline, and 345 patients were also retested after a mean of nearly 4 years.
Researchers saw significant sixfold higher odds of developing incident mild cognitive impairment (MCI) among individuals who showed marked progression of periventricular white matter hyperintensities – an imaging hallmark of cerebral small vessel disease – compared with individuals who did not show any progression (odds ratio = 6.184; 95% confidence interval, 1.506-25.370; P = .011).
Patients with greater progression of periventricular white matter hyperintensities also showed significantly greater decreases in global cognition scores – both in total DRS-2 Z-score and executive function Z-score – when compared against individuals without white matter hyperintensity progression.
“As MCI is one of the most important risk factors in the development of dementia, future research should investigate the mechanisms by which PVH [periventricular white matter hyperintensities] trigger cognitive impairment and the clinical utility of its assessment,” wrote Joan Jiménez-Balado of Vall d’Hebron Research Institute, Barcelona, and his associates.
However, deep white matter hyperintensity progression – as opposed to periventricular – was not linked to cognitive changes, except in the case of bilateral occipital deep white matter hyperintensity changes, which were linked to a significant worsening in the attention Z-score.
The authors noted that the different impacts of periventricular versus deep white matter hyperintensities may relate to a number of factors. The first was that deep white matter hyperintensities disrupt cortico-cortical connections but periventricular ones are more likely to affect long cortico-subcortical association fibers, which “would be an important variable to determine the impaired networks involved in cognition.”
They also suggested that periventricular and deep white matter hyperintensities may affect different neuromodulator systems; the periventricular white matter could be closer to ascending cholinergic bundles that may play a role in vascular cognitive impairment.
Periventricular white matter hyperintensities may also accelerate the deposition of amyloid because of their association with venous collagenosis, which is linked to ischemia and disruptions of the interstitial fluid circulation.
“On the other hand, [deep white matter hyperintensity] may be more related to hypoperfusion, as deep areas are particularly vulnerable to low [blood pressure],” the authors wrote, while stressing that the pathophysiology of white matter hyperintensities is not fully understood, so further research is needed.
Overall, the 345 patients with follow-up data had a median age of 65 years at baseline and mean blood pressure of 143/78.2 mm Hg at baseline and 146.5/75 mm Hg at follow-up. White matter hyperintensity changes occurred periventricularly in 22% and in deep white matter in 48%. The researchers saw new infarcts in 6.1% of patients, and 5.5% had incident cerebral microbleeds. While incident cerebral microbleeds were significantly associated with declines in the attention Z-score, they did not affect other cognitive functions, and incidental infarcts were also not associated with cognitive changes.
Baseline blood pressure and average blood pressure during follow-up were not associated with changes in cardiac small vessel disease lesions. However, diastolic – but not systolic – blood pressure at baseline and follow-up was positively correlated with total, attention, and executive function DRS-2 Z-scores at follow-up.
Three-quarters of patients showed cognitive changes associated with normal aging both at baseline and follow-up, 9.1% had stable MCI, and 9.1% of patients had incident MCI. However, 6.6% of subjects reverted back to normal aging after having MCI at baseline.
The authors noted that they did not examine markers of neurodegeneration, such as tau or amyloid-beta, which could also be linked to hypertension and cerebral small vessel disease lesions.
The study was supported by Instituto de Salud Carlos III, AGAUR (Agency for Management of University and Research Grants), the Secretary of Universities and Research of the Department of Economy and Knowledge, and the European Regional Development Fund. The authors said they have no conflicts of interest.
SOURCE: Jiménez-Balado J et al. Hypertension. 2019 Jan 4. doi: 10.1161/HYPERTENSIONAHA.118.12090
FROM HYPERTENSION
Key clinical point: Cerebral small vessel disease changes are associated with the development of mild cognitive impairment in hypertensive patients.
Major finding: Periventricular white matter hyperintensities in patients with hypertension were associated with sixfold higher odds of mild cognitive impairment.
Study details: A longitudinal, population-based study of 345 patients with hypertension.
Disclosures: The study was supported by Instituto de Salud Carlos III, AGAUR (Agency for Management of University and Research Grants), the Secretary of Universities and Research of the Department of Economy and Knowledge, and the European Regional Development Fund. The authors said they have no conflicts of interest.
Source: Jiménez-Balado J et al. Hypertension. 2019 Jan 4. doi: 10.1161/HYPERTENSIONAHA.118.12090.
How can I improve opioid safety at my hospital?
Quality improvement is essential
Case
A 67-year-old opioid-naive male with a history of obstructive sleep apnea and chronic kidney disease became unresponsive 2 days after hip replacement. Physical exam revealed a respiratory rate of 6 breaths/minute and oxygen saturation of 82%. He had received 6 doses of 6-mg IV morphine within the past 7 hours. How can I improve opioid safety at my hospital?
Background
Opioids are the most commonly prescribed class of medication in the hospital and the second–most common class causing adverse drug events (ADEs), the most serious being respiratory depression and death.1
Opioid ADEs and side effects can cause prolonged length of stay and patient suffering. These vary from potentially life-threatening events such as serotonin syndrome and adrenal insufficiency to more manageable problems still requiring intervention such as constipation, urinary retention, cognitive impairment, nausea, and vomiting. Treatment of side effects can lead to complications, including side effects from antiemetics and urinary tract infections from catheters.
A 4-year review found 700 deaths in the United States attributed to patient-controlled analgesia (PCA) use.2 Another study revealed that one out of every 200 patients has postoperative respiratory depression attributable to opioids.3
It is estimated that 2 million patients a year become chronic opioid users. Inpatient opioid prescribing contributes to this problem;4 for instance, 5.9% of patients after minor surgery and 6.5% after major surgery become chronic opioid users if discharged with an opioid.5 Calcaterra et al. found 25% of opioid-naive medical patients received an opioid at discharge from a medical service.6 Those patients had an odds ratio of 4.90 for becoming a chronic opioid user that year.6
Most hospitals have incomplete or outdated policies and procedures for safe opioid prescribing and administration.7 The Joint Commission on Accreditation of Healthcare Organizations has specific pain standards for pain assessment, pain management, and safe opioid prescribing for hospitals. Additions and revisions were developed to go into effect Jan. 1, 2018. (Table 1)8
Quality improvement
Quality improvement (QI) is an effective way to improve opioid safety. The Society of Hospital Medicine has developed a QI guide, “Reducing adverse drug events related to opioids” or “RADEO,” to increase safety and decrease serious ADEs attributable to opioids.7
The steps in the RADEO program are as follows:
1. Assemble your team
It is critical to identify and include stakeholders from multiple disciplines on your project team. This team will be essential to develop a practical project, identify barriers, create solutions, and gain buy-in from medical staff and administrative leadership.
Front-line staff will have invaluable insight and need to be team members. The majority of interventions are performed by nurses; therefore, nursing leadership and input is essential. Representatives from pharmacy, information technology, and the quality department will be extremely valuable team members to guide you through the correct approach to a successful QI project.
A project champion can keep a high profile for the project and build and lead the team.
Identify an “executive sponsor” such as your CEO, CMO, or CNO. This leader will focus the team on issues critical to your organization, such as accreditation from governmental agencies, and help you obtain dedicated time and resources. Aligning with hospital goals will make your project a priority.
Coordinate with existing opioid initiative teams in the hospital to integrate efforts. This will keep the work of different departments aligned and allow you to learn from pitfalls and barriers the other groups experienced.
Patients/families contribute a unique and valuable perspective. Consider including a member of your hospital’s patient and family advisory council on your team.
2. Perform a needs assessment
Determine the current state of your hospital including: opioid prescribers; opioids prescribed; areas with increased ADEs or naloxone use; formulary restrictions, policies, or guidelines for monitoring, prescribing, and administering opioids; order sets; safety alerts; provider education; or patient education.
Your risk management or quality department may be able to a share root cause analysis of ADEs related to opioids. Joint Commission and CMS recommendations as well as other regulatory requirements may shape your QI interventions.8
Most importantly, review all of the concerns and priorities of your diverse team, which will identify areas of most pressing need and provide insight regarding needs you have not considered.
3. Develop SMART aims
Frame your QI project into a series of well-defined, clear SMART aims.9
Specific: Who will carry out the intervention? Who is your target population? What will be improved? In what way will it be improved?
Measurable: What will be measured? How it will be measured? Does it measure the outcome that needs to be improved?
Attainable/achievable: Ensure you have the resources and time to achieve the aim.
Relevant: Ensure each aim moves your team toward the project vision.
Timely: The aim should be achieved within a realistic time frame, long enough to meet goals but not so long that interest is lost.
An example of a poor aim is “Clinicians will improve knowledge of opioids.”
An example of a SMART aim is “75% of inpatient opioid prescribers including MDs, NPs, and PAs will complete and pass the opioid safety training module by July 1, 2018.”
4. Choose metrics
Outcome metrics measure if the intervention has improved patient safety, for example, measuring a decrease in opioid related ADEs. Structure metrics are the physical and organizational properties of the health care delivery setting, for example, the presence of EMR opioid safety. Processes are communication and practice patterns, for example, adherence to policy by examining nursing documentation of pain assessments.
5. Development and implementation 7,10
Use PDSA for development and implementation of the QI intervention.
Plan: Determine the intervention group such as a specific unit, number of units, and if there will be a control group. Determine who will collect the data, if baseline data will be collected, and who will analyze the data. Your information technology department will be essential to determine if the data can be collected via the EMR and how. Input from your multidisciplinary team is critical to anticipate unintended consequences, such as limiting opioid prescribing at discharge inadvertently increasing emergency department visits for pain control.
Do: Start as a small pilot study to make it as easy as possible to implement the project and begin data collection. A small-scale intervention will be more manageable and allow rapid responses to unanticipated problems.
Study: Analyze the data early to determine if the intervention is improving opioid safety and if alterations are needed. At this stage both process metrics (are processes being followed?) and outcome metrics (is the process leading to a desired outcome?) are important.
Act: Based on data analysis, refine the intervention as necessary. You may have to repeat cycles of PDSA to develop the final intervention. Then implement the final intervention to the entire hospital.
The Joint Commission recommendations for opioid QI
The Joint Commission recommends7 the following to reduce opioid-related respiratory depression:
- Effective processes which include processes such as tracking and analyzing ADEs related to opioids.
- Safe technology which includes using technology such as the EMR to monitor opioid prescribing of greater than 90 morphine milligram equivalents.
- Effective tools which include valid and reliable tools to improve opioid safety, such as the Pasero Opioid Induced Sedation Scale (POSS).
- Opioid education and training which includes provider and patient education such as patient discharge education.
Education
Develop educational interventions to ensure medical and hospital staff are aware of new processes, with an emphasis on “why.”7 If possible, use web-based programs that provide CME. Improve education interventions by using multiple live, interactive, and multimedia exposures.
Principles for successful interventions
- Keep it simple for the end user. This makes it more likely that the intervention is performed. Minimize complex tasks such as calculations and if possible design automated processes.
- Build your process into current work flow. If possible simplify or streamline work flow. A project that competes with staff’s other tasks and competing priorities is doomed to fail. It is critical to have input from those performing the intervention to develop a user-friendly and less disruptive intervention.
- Design reliability into the process. Make your intervention the default action. Build prompts into the work flow. Standardize the intervention into the work flow. And, consider having the intervention at scheduled intervals.7
Opioid safety QI interventions
Interventions for improving opioid safety and reducing opioid -elated ADEs may be generalized into areas including risk screening and assessment, pain treatment, opioid administration, pain assessment, post opioid administration monitoring, and patient and provider education (Table 2).7
Back to the case
The patient received naloxone. His respiratory rate and oxygen saturation returned to normal. His dose of morphine was reduced and his interval increased. A multimodal approach was implemented including low-dose scheduled acetaminophen. There were no further ADEs while maintaining good pain control.
A multidisciplinary opioid task force was created and performed a hospital-wide review of opioid ADEs. Opportunities for improvement were identified and new procedures implemented. The Pasero opioid sedation scale (POSS) was added to the nursing work flow to monitor patients who received an opioid for sedation. An algorithm was developed for opioid-naive patients including guidance for opioid selection, dosing, and frequency. Multiple pain control modalities were added to pain control order sets. Annual training was developed for opioid prescribers, pharmacists, and nurses regarding safe and responsible use of opioids.
And, lastly, in-hospital and discharge patient education was developed for patients and families to be well-informed of opioid risk and benefit including how to identify and respond to ADEs.
Bottom line
Quality improvement is an effective method to improve patient safety and reduce serious adverse events related to opioids in the hospital setting.
Dr. Holmes-Maybank, is codirector, Fundamentals of Patient Care Year 1 and Internship 101, and chair, Clinical Competency Examination Committee, division of hospital medicine, Medical University of South Carolina. Dr. Frederickson is medical director, Hospital Medicine and Palliative Care at CHI Health, Omaha, Neb., and assistant professor at Creighton University School of Medicine, Omaha.
References
1. Davies EC et al. Adverse drug reactions in hospital inpatients: a prospective analysis of 3695 patient-episodes. PLoS One. 2009;4(2):e4439. doi: 10.1371/journal.pone.0004439. Epub 2009 Feb 11.
2. Association for the Advancement of Medical Instrumentation. Infusing patients safely: Priority issues from the AAMI/FDA Infusion Device Summit. 2010;1-39.
3. Dahan Aet al. Incidence, reversal, and prevention of opioid-induced respiratory depression. Anesthesiology. 2010;112:226-238. doi: 10.1097/ALN.0b013e3181c38c25.
4. Estimate about opioid users.
5. Brummett CM et al. New persistent opioid use after minor and major surgical procedures in U.S. adults. JAMA Surg. 2017;152(6):e170504. doi: 10.1001/jamasurg.2017.0504.
6. Calcaterra SL et al. Opioid prescribing at hospital discharge contributes to chronic opioid use. J Gen Intern Med. 2016;31(5):478-85. doi: 10.1007/s11606-015-3539-4.
7. Frederickson TW et al. Reducing adverse drug events related to opioids implementation guide. Philadelphia: Society of Hospital Medicine, 2015.
8. Joint Commission enhances pain assessment and management requirements for accredited hospitals. The Joint Commission Perspectives. 2017;37(7):2-4.
9. Minnesota Department of Health. SMART objectives.
10. Agency for Healthcare Research and Quality. Health Literacy Universal Precautions Toolkit, 2nd Edition.
Plan-Do-Study-Act (PDSA) Directions and Examples.
Recommended reading
Dowell D et al. CDC guideline for prescribing opioids for chronic pain – United States, 2016. Recommendations and Reports. 2016 Mar 18;65(1):1-49.
Frederickson TW et al. Using the 2018 guidelines from the Joint Commission to kickstart your hospital’s program to reduce opioid-induced ventilatory impairment. Anesthesia Patient Safety Foundation Newsletter. 2018;33(1):1-32.
Herzig SJ et al. Safe opioid prescribing for acute noncancer pain in hospitalized adults: a systematic review of existing guidelines. J Hosp Med. 2018 Apr;13(4):256-62. doi: 10.12788/jhm.2979.
Herzig SJ et al. Improving the safety of opioid use for acute noncancer pain in hospitalized adults: a consensus statement from the society of hospital medicine. J Hosp Med. 2018 Apr;13(4):263-71. doi: 10.12788/jhm.2980.
Joint Commission enhances pain assessment and management requirements for accredited hospitals. The Joint Commission Perspectives. 2017;37(7):2-4.
Key points
- Quality improvement is required by the Joint Commission and is an effective method to improve opioid safety in the hospital setting.
- It is critical to the success of a QI project to develop a multidisciplinary team.
- Input from frontline users of the intervention is essential to produce an effective intervention.
- Executive sponsorship and aligning the goals of your QI project with those of your institution will prioritize your project and increase resource availability.
Quiz
1. Based on a needs assessment at your hospital you assemble a multidisciplinary team to improve education for patients discharged on opioids. You recognize the importance of multidisciplinary input to develop a successful intervention for discharge education. Essential team members include all EXCEPT the following:
a. Executive sponsor
b. Patient representative
c. Nursing
d. Medical student representative ---- CORRECT
Explanation: The assembly of a multidisciplinary team is critical to the success of a QI intervention. An executive sponsor may assist you in aligning your goals with that of the hospital and provide resources for its development and implementation. Patient input would help determine how to best deliver the education. Lastly, the individuals carrying out the intervention are essential to develop an intervention that will easy for the end user and increase the likelihood of being used, in this case nursing.
2. You performed a review of naloxone use at your hospital and find that it is greater than similar hospitals. Prior to starting the QI project, you review SHM’s “Reducing adverse events related to opioids implementation guide” and learn that keys to success for QI implementation include:
a. A team of primarily hospitalists
b. Implementing the intervention hospital wide
c. Information technology input for data collection ---- CORRECT
d. No team – it is more effective to work alone
Explanation: Successful implementation of a QI project involves a multidisciplinary team. It is critical to involve information technology early in the development of the project to determine how and if the data can be collected from the EMR. It is best to pilot the intervention on one or two units to make alterations as needed rapidly and perfect the final intervention prior to rolling it out to the entire hospital.
3. You have assembled a multidisciplinary team to respond to the newly revised JCAHO pain standards. An example of a requirement from the new and revised JCAHO standards for pain assessment and management includes:
a. Programs for physician wellness
b. No opioids for chronic pain
c. No more than 5 days of opioids for acute pain
d. Nonpharmacologic pain management options ---- CORRECT
Explanation: JCAHO released new and revised requirements for pain assessment and management including offering nonpharmacologic pain management options. (See Table 1)
4. Your multidisciplinary QI team decides to develop a project to reduce respiratory depression in patients receiving opioids by monitoring for sedation with the Pasero Opioid Induced Sedation Scale. Principles for successful QI interventions include:
a. Complex tasks
b. Make the intervention a default action ---- CORRECT
c. Avoid EMR prompts
d. Competing with other hospital priorities
Explanation: Principles for successful QI interventions include keeping tasks simple, ensuring the intervention does not compete with other priorities, making the intervention the default action, installing prompts in the EMR, and standardizing the intervention into the work flow.
Quality improvement is essential
Quality improvement is essential
Case
A 67-year-old opioid-naive male with a history of obstructive sleep apnea and chronic kidney disease became unresponsive 2 days after hip replacement. Physical exam revealed a respiratory rate of 6 breaths/minute and oxygen saturation of 82%. He had received 6 doses of 6-mg IV morphine within the past 7 hours. How can I improve opioid safety at my hospital?
Background
Opioids are the most commonly prescribed class of medication in the hospital and the second–most common class causing adverse drug events (ADEs), the most serious being respiratory depression and death.1
Opioid ADEs and side effects can cause prolonged length of stay and patient suffering. These vary from potentially life-threatening events such as serotonin syndrome and adrenal insufficiency to more manageable problems still requiring intervention such as constipation, urinary retention, cognitive impairment, nausea, and vomiting. Treatment of side effects can lead to complications, including side effects from antiemetics and urinary tract infections from catheters.
A 4-year review found 700 deaths in the United States attributed to patient-controlled analgesia (PCA) use.2 Another study revealed that one out of every 200 patients has postoperative respiratory depression attributable to opioids.3
It is estimated that 2 million patients a year become chronic opioid users. Inpatient opioid prescribing contributes to this problem;4 for instance, 5.9% of patients after minor surgery and 6.5% after major surgery become chronic opioid users if discharged with an opioid.5 Calcaterra et al. found 25% of opioid-naive medical patients received an opioid at discharge from a medical service.6 Those patients had an odds ratio of 4.90 for becoming a chronic opioid user that year.6
Most hospitals have incomplete or outdated policies and procedures for safe opioid prescribing and administration.7 The Joint Commission on Accreditation of Healthcare Organizations has specific pain standards for pain assessment, pain management, and safe opioid prescribing for hospitals. Additions and revisions were developed to go into effect Jan. 1, 2018. (Table 1)8
Quality improvement
Quality improvement (QI) is an effective way to improve opioid safety. The Society of Hospital Medicine has developed a QI guide, “Reducing adverse drug events related to opioids” or “RADEO,” to increase safety and decrease serious ADEs attributable to opioids.7
The steps in the RADEO program are as follows:
1. Assemble your team
It is critical to identify and include stakeholders from multiple disciplines on your project team. This team will be essential to develop a practical project, identify barriers, create solutions, and gain buy-in from medical staff and administrative leadership.
Front-line staff will have invaluable insight and need to be team members. The majority of interventions are performed by nurses; therefore, nursing leadership and input is essential. Representatives from pharmacy, information technology, and the quality department will be extremely valuable team members to guide you through the correct approach to a successful QI project.
A project champion can keep a high profile for the project and build and lead the team.
Identify an “executive sponsor” such as your CEO, CMO, or CNO. This leader will focus the team on issues critical to your organization, such as accreditation from governmental agencies, and help you obtain dedicated time and resources. Aligning with hospital goals will make your project a priority.
Coordinate with existing opioid initiative teams in the hospital to integrate efforts. This will keep the work of different departments aligned and allow you to learn from pitfalls and barriers the other groups experienced.
Patients/families contribute a unique and valuable perspective. Consider including a member of your hospital’s patient and family advisory council on your team.
2. Perform a needs assessment
Determine the current state of your hospital including: opioid prescribers; opioids prescribed; areas with increased ADEs or naloxone use; formulary restrictions, policies, or guidelines for monitoring, prescribing, and administering opioids; order sets; safety alerts; provider education; or patient education.
Your risk management or quality department may be able to a share root cause analysis of ADEs related to opioids. Joint Commission and CMS recommendations as well as other regulatory requirements may shape your QI interventions.8
Most importantly, review all of the concerns and priorities of your diverse team, which will identify areas of most pressing need and provide insight regarding needs you have not considered.
3. Develop SMART aims
Frame your QI project into a series of well-defined, clear SMART aims.9
Specific: Who will carry out the intervention? Who is your target population? What will be improved? In what way will it be improved?
Measurable: What will be measured? How it will be measured? Does it measure the outcome that needs to be improved?
Attainable/achievable: Ensure you have the resources and time to achieve the aim.
Relevant: Ensure each aim moves your team toward the project vision.
Timely: The aim should be achieved within a realistic time frame, long enough to meet goals but not so long that interest is lost.
An example of a poor aim is “Clinicians will improve knowledge of opioids.”
An example of a SMART aim is “75% of inpatient opioid prescribers including MDs, NPs, and PAs will complete and pass the opioid safety training module by July 1, 2018.”
4. Choose metrics
Outcome metrics measure if the intervention has improved patient safety, for example, measuring a decrease in opioid related ADEs. Structure metrics are the physical and organizational properties of the health care delivery setting, for example, the presence of EMR opioid safety. Processes are communication and practice patterns, for example, adherence to policy by examining nursing documentation of pain assessments.
5. Development and implementation 7,10
Use PDSA for development and implementation of the QI intervention.
Plan: Determine the intervention group such as a specific unit, number of units, and if there will be a control group. Determine who will collect the data, if baseline data will be collected, and who will analyze the data. Your information technology department will be essential to determine if the data can be collected via the EMR and how. Input from your multidisciplinary team is critical to anticipate unintended consequences, such as limiting opioid prescribing at discharge inadvertently increasing emergency department visits for pain control.
Do: Start as a small pilot study to make it as easy as possible to implement the project and begin data collection. A small-scale intervention will be more manageable and allow rapid responses to unanticipated problems.
Study: Analyze the data early to determine if the intervention is improving opioid safety and if alterations are needed. At this stage both process metrics (are processes being followed?) and outcome metrics (is the process leading to a desired outcome?) are important.
Act: Based on data analysis, refine the intervention as necessary. You may have to repeat cycles of PDSA to develop the final intervention. Then implement the final intervention to the entire hospital.
The Joint Commission recommendations for opioid QI
The Joint Commission recommends7 the following to reduce opioid-related respiratory depression:
- Effective processes which include processes such as tracking and analyzing ADEs related to opioids.
- Safe technology which includes using technology such as the EMR to monitor opioid prescribing of greater than 90 morphine milligram equivalents.
- Effective tools which include valid and reliable tools to improve opioid safety, such as the Pasero Opioid Induced Sedation Scale (POSS).
- Opioid education and training which includes provider and patient education such as patient discharge education.
Education
Develop educational interventions to ensure medical and hospital staff are aware of new processes, with an emphasis on “why.”7 If possible, use web-based programs that provide CME. Improve education interventions by using multiple live, interactive, and multimedia exposures.
Principles for successful interventions
- Keep it simple for the end user. This makes it more likely that the intervention is performed. Minimize complex tasks such as calculations and if possible design automated processes.
- Build your process into current work flow. If possible simplify or streamline work flow. A project that competes with staff’s other tasks and competing priorities is doomed to fail. It is critical to have input from those performing the intervention to develop a user-friendly and less disruptive intervention.
- Design reliability into the process. Make your intervention the default action. Build prompts into the work flow. Standardize the intervention into the work flow. And, consider having the intervention at scheduled intervals.7
Opioid safety QI interventions
Interventions for improving opioid safety and reducing opioid -elated ADEs may be generalized into areas including risk screening and assessment, pain treatment, opioid administration, pain assessment, post opioid administration monitoring, and patient and provider education (Table 2).7
Back to the case
The patient received naloxone. His respiratory rate and oxygen saturation returned to normal. His dose of morphine was reduced and his interval increased. A multimodal approach was implemented including low-dose scheduled acetaminophen. There were no further ADEs while maintaining good pain control.
A multidisciplinary opioid task force was created and performed a hospital-wide review of opioid ADEs. Opportunities for improvement were identified and new procedures implemented. The Pasero opioid sedation scale (POSS) was added to the nursing work flow to monitor patients who received an opioid for sedation. An algorithm was developed for opioid-naive patients including guidance for opioid selection, dosing, and frequency. Multiple pain control modalities were added to pain control order sets. Annual training was developed for opioid prescribers, pharmacists, and nurses regarding safe and responsible use of opioids.
And, lastly, in-hospital and discharge patient education was developed for patients and families to be well-informed of opioid risk and benefit including how to identify and respond to ADEs.
Bottom line
Quality improvement is an effective method to improve patient safety and reduce serious adverse events related to opioids in the hospital setting.
Dr. Holmes-Maybank, is codirector, Fundamentals of Patient Care Year 1 and Internship 101, and chair, Clinical Competency Examination Committee, division of hospital medicine, Medical University of South Carolina. Dr. Frederickson is medical director, Hospital Medicine and Palliative Care at CHI Health, Omaha, Neb., and assistant professor at Creighton University School of Medicine, Omaha.
References
1. Davies EC et al. Adverse drug reactions in hospital inpatients: a prospective analysis of 3695 patient-episodes. PLoS One. 2009;4(2):e4439. doi: 10.1371/journal.pone.0004439. Epub 2009 Feb 11.
2. Association for the Advancement of Medical Instrumentation. Infusing patients safely: Priority issues from the AAMI/FDA Infusion Device Summit. 2010;1-39.
3. Dahan Aet al. Incidence, reversal, and prevention of opioid-induced respiratory depression. Anesthesiology. 2010;112:226-238. doi: 10.1097/ALN.0b013e3181c38c25.
4. Estimate about opioid users.
5. Brummett CM et al. New persistent opioid use after minor and major surgical procedures in U.S. adults. JAMA Surg. 2017;152(6):e170504. doi: 10.1001/jamasurg.2017.0504.
6. Calcaterra SL et al. Opioid prescribing at hospital discharge contributes to chronic opioid use. J Gen Intern Med. 2016;31(5):478-85. doi: 10.1007/s11606-015-3539-4.
7. Frederickson TW et al. Reducing adverse drug events related to opioids implementation guide. Philadelphia: Society of Hospital Medicine, 2015.
8. Joint Commission enhances pain assessment and management requirements for accredited hospitals. The Joint Commission Perspectives. 2017;37(7):2-4.
9. Minnesota Department of Health. SMART objectives.
10. Agency for Healthcare Research and Quality. Health Literacy Universal Precautions Toolkit, 2nd Edition.
Plan-Do-Study-Act (PDSA) Directions and Examples.
Recommended reading
Dowell D et al. CDC guideline for prescribing opioids for chronic pain – United States, 2016. Recommendations and Reports. 2016 Mar 18;65(1):1-49.
Frederickson TW et al. Using the 2018 guidelines from the Joint Commission to kickstart your hospital’s program to reduce opioid-induced ventilatory impairment. Anesthesia Patient Safety Foundation Newsletter. 2018;33(1):1-32.
Herzig SJ et al. Safe opioid prescribing for acute noncancer pain in hospitalized adults: a systematic review of existing guidelines. J Hosp Med. 2018 Apr;13(4):256-62. doi: 10.12788/jhm.2979.
Herzig SJ et al. Improving the safety of opioid use for acute noncancer pain in hospitalized adults: a consensus statement from the society of hospital medicine. J Hosp Med. 2018 Apr;13(4):263-71. doi: 10.12788/jhm.2980.
Joint Commission enhances pain assessment and management requirements for accredited hospitals. The Joint Commission Perspectives. 2017;37(7):2-4.
Key points
- Quality improvement is required by the Joint Commission and is an effective method to improve opioid safety in the hospital setting.
- It is critical to the success of a QI project to develop a multidisciplinary team.
- Input from frontline users of the intervention is essential to produce an effective intervention.
- Executive sponsorship and aligning the goals of your QI project with those of your institution will prioritize your project and increase resource availability.
Quiz
1. Based on a needs assessment at your hospital you assemble a multidisciplinary team to improve education for patients discharged on opioids. You recognize the importance of multidisciplinary input to develop a successful intervention for discharge education. Essential team members include all EXCEPT the following:
a. Executive sponsor
b. Patient representative
c. Nursing
d. Medical student representative ---- CORRECT
Explanation: The assembly of a multidisciplinary team is critical to the success of a QI intervention. An executive sponsor may assist you in aligning your goals with that of the hospital and provide resources for its development and implementation. Patient input would help determine how to best deliver the education. Lastly, the individuals carrying out the intervention are essential to develop an intervention that will easy for the end user and increase the likelihood of being used, in this case nursing.
2. You performed a review of naloxone use at your hospital and find that it is greater than similar hospitals. Prior to starting the QI project, you review SHM’s “Reducing adverse events related to opioids implementation guide” and learn that keys to success for QI implementation include:
a. A team of primarily hospitalists
b. Implementing the intervention hospital wide
c. Information technology input for data collection ---- CORRECT
d. No team – it is more effective to work alone
Explanation: Successful implementation of a QI project involves a multidisciplinary team. It is critical to involve information technology early in the development of the project to determine how and if the data can be collected from the EMR. It is best to pilot the intervention on one or two units to make alterations as needed rapidly and perfect the final intervention prior to rolling it out to the entire hospital.
3. You have assembled a multidisciplinary team to respond to the newly revised JCAHO pain standards. An example of a requirement from the new and revised JCAHO standards for pain assessment and management includes:
a. Programs for physician wellness
b. No opioids for chronic pain
c. No more than 5 days of opioids for acute pain
d. Nonpharmacologic pain management options ---- CORRECT
Explanation: JCAHO released new and revised requirements for pain assessment and management including offering nonpharmacologic pain management options. (See Table 1)
4. Your multidisciplinary QI team decides to develop a project to reduce respiratory depression in patients receiving opioids by monitoring for sedation with the Pasero Opioid Induced Sedation Scale. Principles for successful QI interventions include:
a. Complex tasks
b. Make the intervention a default action ---- CORRECT
c. Avoid EMR prompts
d. Competing with other hospital priorities
Explanation: Principles for successful QI interventions include keeping tasks simple, ensuring the intervention does not compete with other priorities, making the intervention the default action, installing prompts in the EMR, and standardizing the intervention into the work flow.
Case
A 67-year-old opioid-naive male with a history of obstructive sleep apnea and chronic kidney disease became unresponsive 2 days after hip replacement. Physical exam revealed a respiratory rate of 6 breaths/minute and oxygen saturation of 82%. He had received 6 doses of 6-mg IV morphine within the past 7 hours. How can I improve opioid safety at my hospital?
Background
Opioids are the most commonly prescribed class of medication in the hospital and the second–most common class causing adverse drug events (ADEs), the most serious being respiratory depression and death.1
Opioid ADEs and side effects can cause prolonged length of stay and patient suffering. These vary from potentially life-threatening events such as serotonin syndrome and adrenal insufficiency to more manageable problems still requiring intervention such as constipation, urinary retention, cognitive impairment, nausea, and vomiting. Treatment of side effects can lead to complications, including side effects from antiemetics and urinary tract infections from catheters.
A 4-year review found 700 deaths in the United States attributed to patient-controlled analgesia (PCA) use.2 Another study revealed that one out of every 200 patients has postoperative respiratory depression attributable to opioids.3
It is estimated that 2 million patients a year become chronic opioid users. Inpatient opioid prescribing contributes to this problem;4 for instance, 5.9% of patients after minor surgery and 6.5% after major surgery become chronic opioid users if discharged with an opioid.5 Calcaterra et al. found 25% of opioid-naive medical patients received an opioid at discharge from a medical service.6 Those patients had an odds ratio of 4.90 for becoming a chronic opioid user that year.6
Most hospitals have incomplete or outdated policies and procedures for safe opioid prescribing and administration.7 The Joint Commission on Accreditation of Healthcare Organizations has specific pain standards for pain assessment, pain management, and safe opioid prescribing for hospitals. Additions and revisions were developed to go into effect Jan. 1, 2018. (Table 1)8
Quality improvement
Quality improvement (QI) is an effective way to improve opioid safety. The Society of Hospital Medicine has developed a QI guide, “Reducing adverse drug events related to opioids” or “RADEO,” to increase safety and decrease serious ADEs attributable to opioids.7
The steps in the RADEO program are as follows:
1. Assemble your team
It is critical to identify and include stakeholders from multiple disciplines on your project team. This team will be essential to develop a practical project, identify barriers, create solutions, and gain buy-in from medical staff and administrative leadership.
Front-line staff will have invaluable insight and need to be team members. The majority of interventions are performed by nurses; therefore, nursing leadership and input is essential. Representatives from pharmacy, information technology, and the quality department will be extremely valuable team members to guide you through the correct approach to a successful QI project.
A project champion can keep a high profile for the project and build and lead the team.
Identify an “executive sponsor” such as your CEO, CMO, or CNO. This leader will focus the team on issues critical to your organization, such as accreditation from governmental agencies, and help you obtain dedicated time and resources. Aligning with hospital goals will make your project a priority.
Coordinate with existing opioid initiative teams in the hospital to integrate efforts. This will keep the work of different departments aligned and allow you to learn from pitfalls and barriers the other groups experienced.
Patients/families contribute a unique and valuable perspective. Consider including a member of your hospital’s patient and family advisory council on your team.
2. Perform a needs assessment
Determine the current state of your hospital including: opioid prescribers; opioids prescribed; areas with increased ADEs or naloxone use; formulary restrictions, policies, or guidelines for monitoring, prescribing, and administering opioids; order sets; safety alerts; provider education; or patient education.
Your risk management or quality department may be able to a share root cause analysis of ADEs related to opioids. Joint Commission and CMS recommendations as well as other regulatory requirements may shape your QI interventions.8
Most importantly, review all of the concerns and priorities of your diverse team, which will identify areas of most pressing need and provide insight regarding needs you have not considered.
3. Develop SMART aims
Frame your QI project into a series of well-defined, clear SMART aims.9
Specific: Who will carry out the intervention? Who is your target population? What will be improved? In what way will it be improved?
Measurable: What will be measured? How it will be measured? Does it measure the outcome that needs to be improved?
Attainable/achievable: Ensure you have the resources and time to achieve the aim.
Relevant: Ensure each aim moves your team toward the project vision.
Timely: The aim should be achieved within a realistic time frame, long enough to meet goals but not so long that interest is lost.
An example of a poor aim is “Clinicians will improve knowledge of opioids.”
An example of a SMART aim is “75% of inpatient opioid prescribers including MDs, NPs, and PAs will complete and pass the opioid safety training module by July 1, 2018.”
4. Choose metrics
Outcome metrics measure if the intervention has improved patient safety, for example, measuring a decrease in opioid related ADEs. Structure metrics are the physical and organizational properties of the health care delivery setting, for example, the presence of EMR opioid safety. Processes are communication and practice patterns, for example, adherence to policy by examining nursing documentation of pain assessments.
5. Development and implementation 7,10
Use PDSA for development and implementation of the QI intervention.
Plan: Determine the intervention group such as a specific unit, number of units, and if there will be a control group. Determine who will collect the data, if baseline data will be collected, and who will analyze the data. Your information technology department will be essential to determine if the data can be collected via the EMR and how. Input from your multidisciplinary team is critical to anticipate unintended consequences, such as limiting opioid prescribing at discharge inadvertently increasing emergency department visits for pain control.
Do: Start as a small pilot study to make it as easy as possible to implement the project and begin data collection. A small-scale intervention will be more manageable and allow rapid responses to unanticipated problems.
Study: Analyze the data early to determine if the intervention is improving opioid safety and if alterations are needed. At this stage both process metrics (are processes being followed?) and outcome metrics (is the process leading to a desired outcome?) are important.
Act: Based on data analysis, refine the intervention as necessary. You may have to repeat cycles of PDSA to develop the final intervention. Then implement the final intervention to the entire hospital.
The Joint Commission recommendations for opioid QI
The Joint Commission recommends7 the following to reduce opioid-related respiratory depression:
- Effective processes which include processes such as tracking and analyzing ADEs related to opioids.
- Safe technology which includes using technology such as the EMR to monitor opioid prescribing of greater than 90 morphine milligram equivalents.
- Effective tools which include valid and reliable tools to improve opioid safety, such as the Pasero Opioid Induced Sedation Scale (POSS).
- Opioid education and training which includes provider and patient education such as patient discharge education.
Education
Develop educational interventions to ensure medical and hospital staff are aware of new processes, with an emphasis on “why.”7 If possible, use web-based programs that provide CME. Improve education interventions by using multiple live, interactive, and multimedia exposures.
Principles for successful interventions
- Keep it simple for the end user. This makes it more likely that the intervention is performed. Minimize complex tasks such as calculations and if possible design automated processes.
- Build your process into current work flow. If possible simplify or streamline work flow. A project that competes with staff’s other tasks and competing priorities is doomed to fail. It is critical to have input from those performing the intervention to develop a user-friendly and less disruptive intervention.
- Design reliability into the process. Make your intervention the default action. Build prompts into the work flow. Standardize the intervention into the work flow. And, consider having the intervention at scheduled intervals.7
Opioid safety QI interventions
Interventions for improving opioid safety and reducing opioid -elated ADEs may be generalized into areas including risk screening and assessment, pain treatment, opioid administration, pain assessment, post opioid administration monitoring, and patient and provider education (Table 2).7
Back to the case
The patient received naloxone. His respiratory rate and oxygen saturation returned to normal. His dose of morphine was reduced and his interval increased. A multimodal approach was implemented including low-dose scheduled acetaminophen. There were no further ADEs while maintaining good pain control.
A multidisciplinary opioid task force was created and performed a hospital-wide review of opioid ADEs. Opportunities for improvement were identified and new procedures implemented. The Pasero opioid sedation scale (POSS) was added to the nursing work flow to monitor patients who received an opioid for sedation. An algorithm was developed for opioid-naive patients including guidance for opioid selection, dosing, and frequency. Multiple pain control modalities were added to pain control order sets. Annual training was developed for opioid prescribers, pharmacists, and nurses regarding safe and responsible use of opioids.
And, lastly, in-hospital and discharge patient education was developed for patients and families to be well-informed of opioid risk and benefit including how to identify and respond to ADEs.
Bottom line
Quality improvement is an effective method to improve patient safety and reduce serious adverse events related to opioids in the hospital setting.
Dr. Holmes-Maybank, is codirector, Fundamentals of Patient Care Year 1 and Internship 101, and chair, Clinical Competency Examination Committee, division of hospital medicine, Medical University of South Carolina. Dr. Frederickson is medical director, Hospital Medicine and Palliative Care at CHI Health, Omaha, Neb., and assistant professor at Creighton University School of Medicine, Omaha.
References
1. Davies EC et al. Adverse drug reactions in hospital inpatients: a prospective analysis of 3695 patient-episodes. PLoS One. 2009;4(2):e4439. doi: 10.1371/journal.pone.0004439. Epub 2009 Feb 11.
2. Association for the Advancement of Medical Instrumentation. Infusing patients safely: Priority issues from the AAMI/FDA Infusion Device Summit. 2010;1-39.
3. Dahan Aet al. Incidence, reversal, and prevention of opioid-induced respiratory depression. Anesthesiology. 2010;112:226-238. doi: 10.1097/ALN.0b013e3181c38c25.
4. Estimate about opioid users.
5. Brummett CM et al. New persistent opioid use after minor and major surgical procedures in U.S. adults. JAMA Surg. 2017;152(6):e170504. doi: 10.1001/jamasurg.2017.0504.
6. Calcaterra SL et al. Opioid prescribing at hospital discharge contributes to chronic opioid use. J Gen Intern Med. 2016;31(5):478-85. doi: 10.1007/s11606-015-3539-4.
7. Frederickson TW et al. Reducing adverse drug events related to opioids implementation guide. Philadelphia: Society of Hospital Medicine, 2015.
8. Joint Commission enhances pain assessment and management requirements for accredited hospitals. The Joint Commission Perspectives. 2017;37(7):2-4.
9. Minnesota Department of Health. SMART objectives.
10. Agency for Healthcare Research and Quality. Health Literacy Universal Precautions Toolkit, 2nd Edition.
Plan-Do-Study-Act (PDSA) Directions and Examples.
Recommended reading
Dowell D et al. CDC guideline for prescribing opioids for chronic pain – United States, 2016. Recommendations and Reports. 2016 Mar 18;65(1):1-49.
Frederickson TW et al. Using the 2018 guidelines from the Joint Commission to kickstart your hospital’s program to reduce opioid-induced ventilatory impairment. Anesthesia Patient Safety Foundation Newsletter. 2018;33(1):1-32.
Herzig SJ et al. Safe opioid prescribing for acute noncancer pain in hospitalized adults: a systematic review of existing guidelines. J Hosp Med. 2018 Apr;13(4):256-62. doi: 10.12788/jhm.2979.
Herzig SJ et al. Improving the safety of opioid use for acute noncancer pain in hospitalized adults: a consensus statement from the society of hospital medicine. J Hosp Med. 2018 Apr;13(4):263-71. doi: 10.12788/jhm.2980.
Joint Commission enhances pain assessment and management requirements for accredited hospitals. The Joint Commission Perspectives. 2017;37(7):2-4.
Key points
- Quality improvement is required by the Joint Commission and is an effective method to improve opioid safety in the hospital setting.
- It is critical to the success of a QI project to develop a multidisciplinary team.
- Input from frontline users of the intervention is essential to produce an effective intervention.
- Executive sponsorship and aligning the goals of your QI project with those of your institution will prioritize your project and increase resource availability.
Quiz
1. Based on a needs assessment at your hospital you assemble a multidisciplinary team to improve education for patients discharged on opioids. You recognize the importance of multidisciplinary input to develop a successful intervention for discharge education. Essential team members include all EXCEPT the following:
a. Executive sponsor
b. Patient representative
c. Nursing
d. Medical student representative ---- CORRECT
Explanation: The assembly of a multidisciplinary team is critical to the success of a QI intervention. An executive sponsor may assist you in aligning your goals with that of the hospital and provide resources for its development and implementation. Patient input would help determine how to best deliver the education. Lastly, the individuals carrying out the intervention are essential to develop an intervention that will easy for the end user and increase the likelihood of being used, in this case nursing.
2. You performed a review of naloxone use at your hospital and find that it is greater than similar hospitals. Prior to starting the QI project, you review SHM’s “Reducing adverse events related to opioids implementation guide” and learn that keys to success for QI implementation include:
a. A team of primarily hospitalists
b. Implementing the intervention hospital wide
c. Information technology input for data collection ---- CORRECT
d. No team – it is more effective to work alone
Explanation: Successful implementation of a QI project involves a multidisciplinary team. It is critical to involve information technology early in the development of the project to determine how and if the data can be collected from the EMR. It is best to pilot the intervention on one or two units to make alterations as needed rapidly and perfect the final intervention prior to rolling it out to the entire hospital.
3. You have assembled a multidisciplinary team to respond to the newly revised JCAHO pain standards. An example of a requirement from the new and revised JCAHO standards for pain assessment and management includes:
a. Programs for physician wellness
b. No opioids for chronic pain
c. No more than 5 days of opioids for acute pain
d. Nonpharmacologic pain management options ---- CORRECT
Explanation: JCAHO released new and revised requirements for pain assessment and management including offering nonpharmacologic pain management options. (See Table 1)
4. Your multidisciplinary QI team decides to develop a project to reduce respiratory depression in patients receiving opioids by monitoring for sedation with the Pasero Opioid Induced Sedation Scale. Principles for successful QI interventions include:
a. Complex tasks
b. Make the intervention a default action ---- CORRECT
c. Avoid EMR prompts
d. Competing with other hospital priorities
Explanation: Principles for successful QI interventions include keeping tasks simple, ensuring the intervention does not compete with other priorities, making the intervention the default action, installing prompts in the EMR, and standardizing the intervention into the work flow.
Acute-onset quadriplegia with hyperreflexia
A 79-year-old man presented with sudden-onset bilateral weakness in the lower and upper extremities that had started 6 hours earlier. He reported no vision disturbances or urinary incontinence. He was afebrile, with a blood pressure of 148/94 mm Hg, heart rate 98 bpm, and oxygen saturation of 95% on room air.
Physical examination revealed quadriplegia with hyperreflexia, sustained ankle clonus, and bilateral Babinski reflex, as well as spontaneous adductor and extensor spasms of the lower extremities.
Funduscopy was negative for optic neuritis. Results of a complete blood cell count and renal and liver function testing were within normal limits.
The patient was admitted to the intensive care unit. Methylprednisolone 1 g was given intravenously once daily for 5 days, with plasma exchange every other day for 5 sessions. A workup for neoplastic, autoimmune, and infectious disease was negative, as was testing for serum aquaporin-4 antibody (ie, neuromyelitis optica immunoglobulin G antibody).
Over the course of 7 days, the patient’s motor strength improved, and he was able to walk without assistance. Steroid therapy was tapered, and he was prescribed rituximab to prevent recurrence.
LONGITUDINALLY EXTENSIVE TRANSVERSE MYELITIS
A subtype of transverse myelitis, LETM is defined by partial or complete spinal cord dysfunction due to a lesion extending 3 or more vertebrae as confirmed on MRI. The clinical presentation can include paraparesis, sensory disturbances, and gait, bladder, bowel, or sexual dysfunction.1 Identifying the cause requires an extensive workup, as the differential diagnosis includes a wide range of conditions2:
- Autoimmune disorders such as Behçet disease, systemic lupus erythematosus, and Sjögren syndrome
- Infectious disorders such as syphilis, tuberculosis, and viral and parasitic infections
- Demyelinating disorders such as multiple sclerosis and neuromyelitis optica
- Neoplastic conditions such as intramedullary metastasis and lymphoma
- Paraneoplastic syndromes.
In our patient, the evaluation did not identify a specific underlying condition, and testing for serum aquaporin-4 antibody was negative. Therefore, the LETM was ruled an isolated idiopathic episode.
Idiopathic seronegative LETM has been associated with fewer recurrences than seropositive LETM.3 Management consists of high-dose intravenous steroids and plasma exchange. Rituximab can be used to prevent recurrence.4
- Trebst C, Raab P, Voss EV, et al. Longitudinal extensive transverse myelitis—it’s not all neuromyelitis optica. Nat Rev Neurol 2011; 7(12):688–698. doi:10.1038/nrneurol.2011.176
- Kim SM, Kim SJ, Lee HJ, Kuroda H, Palace J, Fujihara K. Differential diagnosis of neuromyelitis optica spectrum disorders. Ther Adv Neurol Disord 2017; 10(7):265–289. doi:10.1177/1756285617709723
- Kitley J, Leite MI, Küker W, et al. Longitudinally extensive transverse myelitis with and without aquaporin 4 antibodies. JAMA Neurol 2013; 70(11):1375–1381. doi:10.1001/jamaneurol.2013.3890
- Tobin WO, Weinshenker BG, Lucchinetti CF. Longitudinally extensive transverse myelitis. Curr Opin Neurol 2014; 27(3):279–289. doi:10.1097/WCO.0000000000000093
A 79-year-old man presented with sudden-onset bilateral weakness in the lower and upper extremities that had started 6 hours earlier. He reported no vision disturbances or urinary incontinence. He was afebrile, with a blood pressure of 148/94 mm Hg, heart rate 98 bpm, and oxygen saturation of 95% on room air.
Physical examination revealed quadriplegia with hyperreflexia, sustained ankle clonus, and bilateral Babinski reflex, as well as spontaneous adductor and extensor spasms of the lower extremities.
Funduscopy was negative for optic neuritis. Results of a complete blood cell count and renal and liver function testing were within normal limits.
The patient was admitted to the intensive care unit. Methylprednisolone 1 g was given intravenously once daily for 5 days, with plasma exchange every other day for 5 sessions. A workup for neoplastic, autoimmune, and infectious disease was negative, as was testing for serum aquaporin-4 antibody (ie, neuromyelitis optica immunoglobulin G antibody).
Over the course of 7 days, the patient’s motor strength improved, and he was able to walk without assistance. Steroid therapy was tapered, and he was prescribed rituximab to prevent recurrence.
LONGITUDINALLY EXTENSIVE TRANSVERSE MYELITIS
A subtype of transverse myelitis, LETM is defined by partial or complete spinal cord dysfunction due to a lesion extending 3 or more vertebrae as confirmed on MRI. The clinical presentation can include paraparesis, sensory disturbances, and gait, bladder, bowel, or sexual dysfunction.1 Identifying the cause requires an extensive workup, as the differential diagnosis includes a wide range of conditions2:
- Autoimmune disorders such as Behçet disease, systemic lupus erythematosus, and Sjögren syndrome
- Infectious disorders such as syphilis, tuberculosis, and viral and parasitic infections
- Demyelinating disorders such as multiple sclerosis and neuromyelitis optica
- Neoplastic conditions such as intramedullary metastasis and lymphoma
- Paraneoplastic syndromes.
In our patient, the evaluation did not identify a specific underlying condition, and testing for serum aquaporin-4 antibody was negative. Therefore, the LETM was ruled an isolated idiopathic episode.
Idiopathic seronegative LETM has been associated with fewer recurrences than seropositive LETM.3 Management consists of high-dose intravenous steroids and plasma exchange. Rituximab can be used to prevent recurrence.4
A 79-year-old man presented with sudden-onset bilateral weakness in the lower and upper extremities that had started 6 hours earlier. He reported no vision disturbances or urinary incontinence. He was afebrile, with a blood pressure of 148/94 mm Hg, heart rate 98 bpm, and oxygen saturation of 95% on room air.
Physical examination revealed quadriplegia with hyperreflexia, sustained ankle clonus, and bilateral Babinski reflex, as well as spontaneous adductor and extensor spasms of the lower extremities.
Funduscopy was negative for optic neuritis. Results of a complete blood cell count and renal and liver function testing were within normal limits.
The patient was admitted to the intensive care unit. Methylprednisolone 1 g was given intravenously once daily for 5 days, with plasma exchange every other day for 5 sessions. A workup for neoplastic, autoimmune, and infectious disease was negative, as was testing for serum aquaporin-4 antibody (ie, neuromyelitis optica immunoglobulin G antibody).
Over the course of 7 days, the patient’s motor strength improved, and he was able to walk without assistance. Steroid therapy was tapered, and he was prescribed rituximab to prevent recurrence.
LONGITUDINALLY EXTENSIVE TRANSVERSE MYELITIS
A subtype of transverse myelitis, LETM is defined by partial or complete spinal cord dysfunction due to a lesion extending 3 or more vertebrae as confirmed on MRI. The clinical presentation can include paraparesis, sensory disturbances, and gait, bladder, bowel, or sexual dysfunction.1 Identifying the cause requires an extensive workup, as the differential diagnosis includes a wide range of conditions2:
- Autoimmune disorders such as Behçet disease, systemic lupus erythematosus, and Sjögren syndrome
- Infectious disorders such as syphilis, tuberculosis, and viral and parasitic infections
- Demyelinating disorders such as multiple sclerosis and neuromyelitis optica
- Neoplastic conditions such as intramedullary metastasis and lymphoma
- Paraneoplastic syndromes.
In our patient, the evaluation did not identify a specific underlying condition, and testing for serum aquaporin-4 antibody was negative. Therefore, the LETM was ruled an isolated idiopathic episode.
Idiopathic seronegative LETM has been associated with fewer recurrences than seropositive LETM.3 Management consists of high-dose intravenous steroids and plasma exchange. Rituximab can be used to prevent recurrence.4
- Trebst C, Raab P, Voss EV, et al. Longitudinal extensive transverse myelitis—it’s not all neuromyelitis optica. Nat Rev Neurol 2011; 7(12):688–698. doi:10.1038/nrneurol.2011.176
- Kim SM, Kim SJ, Lee HJ, Kuroda H, Palace J, Fujihara K. Differential diagnosis of neuromyelitis optica spectrum disorders. Ther Adv Neurol Disord 2017; 10(7):265–289. doi:10.1177/1756285617709723
- Kitley J, Leite MI, Küker W, et al. Longitudinally extensive transverse myelitis with and without aquaporin 4 antibodies. JAMA Neurol 2013; 70(11):1375–1381. doi:10.1001/jamaneurol.2013.3890
- Tobin WO, Weinshenker BG, Lucchinetti CF. Longitudinally extensive transverse myelitis. Curr Opin Neurol 2014; 27(3):279–289. doi:10.1097/WCO.0000000000000093
- Trebst C, Raab P, Voss EV, et al. Longitudinal extensive transverse myelitis—it’s not all neuromyelitis optica. Nat Rev Neurol 2011; 7(12):688–698. doi:10.1038/nrneurol.2011.176
- Kim SM, Kim SJ, Lee HJ, Kuroda H, Palace J, Fujihara K. Differential diagnosis of neuromyelitis optica spectrum disorders. Ther Adv Neurol Disord 2017; 10(7):265–289. doi:10.1177/1756285617709723
- Kitley J, Leite MI, Küker W, et al. Longitudinally extensive transverse myelitis with and without aquaporin 4 antibodies. JAMA Neurol 2013; 70(11):1375–1381. doi:10.1001/jamaneurol.2013.3890
- Tobin WO, Weinshenker BG, Lucchinetti CF. Longitudinally extensive transverse myelitis. Curr Opin Neurol 2014; 27(3):279–289. doi:10.1097/WCO.0000000000000093
Can lifestyle modifications delay or prevent Alzheimer’s disease?
Clinicians have devoted strenuous efforts to secondary prevention of Alzheimer’s disease (AD) by diagnosing and treating patients as early as possible. Unfortunately, there is no cure for AD, and the field has witnessed recurrent failures of several pharmacotherapy candidates with either symptomatic or disease-modifying properties.1 An estimated one-third of AD cases can be attributed to modifiable risk factors.2 Thus, implementing primary prevention measures by addressing modifiable risk factors thought to contribute to the disease, with the goal of reducing the risk of developing AD, or at least delaying its onset, is a crucial public health strategy.
Cardiovascular risk factors, such as hypertension, hyperlipidemia, diabetes, hyperhomocysteinemia, obesity, and smoking, have emerged as substantive risk factors for AD.3 Optimal management of these major risk factors, especially in mid-life, may be a preventive approach against AD. Although detailing the evidence on the impact of managing cardiovascular risk factors to delay or prevent AD is beyond the scope of this article, it is becoming clear that “what is good for the heart is good for the brain.”
Additional modifiable risk factors are related to lifestyle habits, such as physical exercise, mental and social activity, meditation/spiritual activity, and diet. This article reviews the importance of pursuing a healthy lifestyle in delaying AD, with the corresponding levels of evidence that support each specific lifestyle modification. The levels of evidence are defined in Table 1.4
Physical exercise
Twenty-one percent of AD cases in the United States are attributable to physical inactivity.5 In addition to its beneficial effect on metabolic syndrome, in animal and human research, regular exercise has been shown to have direct neuroprotective effects. High levels of physical activity increase hippocampal neurogenesis and neuroplasticity, increase vascular circulation in the brain regions implicated in AD, and modulate inflammatory mediators as well as brain growth factors such as brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1).6
The definition of regular physical exercise varies across the literature, but usually implies aerobic exercise—an ongoing activity sufficient to increase the heart rate and the need for oxygen, sustained for 20 to 30 minutes per session.7 Modalities include household activities and leisure-time activities. In a large prospective cohort study, Scarmeas et al8 categorized leisure-time activities into 3 types:
- light (walking, dancing, calisthenics, golfing, bowling, gardening, horseback riding)
- moderate (bicycling, swimming, hiking, playing tennis)
- vigorous (aerobic dancing, jogging, playing handball).
These types of physical exercise were weighed by the frequency of participation per week. Compared with being physically inactive, low levels of weekly physical activity (0.1 hours of vigorous, 0.8 hours of moderate, or 1.3 hours of light exercise) were associated with a 29% to 41% lower risk of developing AD, while higher weekly physical activity (1.3 hours of vigorous, 2.3 hours of moderate, or 3.8 hours of light exercise) were associated with a 37% to 50% lower risk (level III).8
In another 20-year cohort study, engaging in leisure-time physical activity at least twice a week in mid-life was significantly associated with a reduced risk of AD, after adjusting for age, sex, education, follow-up time, locomotor disorders, apolipoprotein E (ApoE) genotype, vascular disorders, smoking, and alcohol intake (level III).9 Moreover, a systematic review of 29 randomized controlled trials (RCTs) showed that aerobic exercise training, such as brisk walking, jogging, and biking, was associated with improvements in attention, processing speed, executive function, and memory among healthy older adults and those with mild cognitive impairment (MCI; level IA).10
Continue to: From a pathophysiological standpoint...
From a pathophysiological standpoint, higher levels of physical exercise in cognitively intact older adults have been associated with reduced brain amyloid beta deposits, especially in ApoE4 carriers.11 This inverse relationship also has been demonstrated in patients who are presymptomatic who carry 1 of the 3 known autosomal dominant mutations for the familial forms of AD.12
Overall, physicians should recommend that patients—especially those with cardiovascular risk factors that increase their risk for AD—exercise regularly by following the guidelines of the American Heart Association or the American College of Sports Medicine.13 These include muscle-strengthening activities (legs, hips, back, abdomen, shoulders, and arms) at least 2 days/week, in addition to either 30 minutes/day of moderate-intensity aerobic activity such as brisk walking, 5 days/week; or 25 minutes of vigorous aerobic activity such as jogging and running, 3 days/week14 (level IA evidence for overall improvement in cognitive function; level III evidence for AD delay/risk reduction). Neuromotor exercise, such as yoga and tai chi, and flexibility exercise such as muscle stretching, especially after a hot bath, 2 to 3 days/week are also recommended (level III).15
Mental activity
Nineteen percent of AD cases worldwide and 7% in the United States. can be attributed to low educational attainment, which is associated with low brain cognitive reserve.5 Cognitive resilience in later life may be enhanced by building brain reserves through intellectual stimulation, which affects neuronal branching and plasticity.16 Higher levels of complex mental activities measured across the lifespan, such as education, occupation, reading, and writing, are correlated with significantly less hippocampal volume shrinkage over time.17 Frequent participation in mentally stimulating activities—such as listening to the radio; reading newspapers, magazines, or books; playing games (cards, checkers, crosswords or other puzzles); and visiting museums—was associated with an up to 64% reduction in the odds of developing AD in a cohort of cognitively intact older adults followed for 4 years.18 The correlation between mental activity and AD was found to be independent of physical activity, social activity, or baseline cognitive function.19
In a large cohort of cognitively intact older adults (mean age 70), engaging in a mentally stimulating activity (craft activities, computer use, or going to the theater/movies) once to twice a week was significantly associated with a reduced incidence of amnestic MCI.20 Another prospective 21-year study demonstrated a significant reduction in AD risk in community-dwelling cognitively intact older adults (age 75 to 85) who participated in cognitively stimulating activities, such as reading books or newspapers, writing for pleasure, doing crossword puzzles, playing board games or cards, or playing musical instruments, several times/week.21
Growing scientific evidence also suggests that lifelong multilingualism can delay AD onset by 4 to 5 years.22 Multilingualism is associated with greater cognitive reserve, gray matter volume, functional connectivity and white matter density.23
Continue to: Physicians should encourage their patients...
Physicians should encourage their patients to engage in intellectually stimulating activities and creative leisure-time activities several times/week to enhance their cognitive reserves and delay AD onset (level III evidence with respect to AD risk reduction/delay).
Social activity
Social engagement may be an additional protective factor against AD. In a large 4-year prospective study, increased loneliness in cognitively intact older adults doubled the risk of AD.24 Data from the large French cohort PAQUID (Personnes Agées QUID) emphasized the importance of a patient’s social network as a protective factor against AD. In this cohort, the perception of reciprocity in relationships with others (the perception that a person had received more than he or she had given) was associated with a 53% reduction in AD risk (level III).25 In another longitudinal cohort study, social activity was found to decrease the incidence of subjective cognitive decline, which is a prodromal syndrome for MCI and AD (level III).26
A major confounder in studies assessing for social activity is the uncertainty if social withdrawal is a modifiable risk factor or an early manifestation of AD, since apathetic patients with AD tend to be socially withdrawn.27 Another limitation of measuring the impact of social activity relative to AD risk is the difficulty in isolating social activities from activities that have physical and mental activity components, such as leisure-time activities.28
Meditation/spiritual activity
Chronic psychological stress is believed to compromise limbic structures that regulate stress-related behaviors and the memory network, which might explain how being prone to psychological distress may be associated with MCI or AD.29 Cognitive stress may increase the oxidative stress and telomere shortening implicated in the neurodegenerative processes of AD.30 In one study, participants who were highly prone to psychological distress were found to be at 3 times increased risk for developing AD, after adjusting for depression symptoms and physical and mental activities (level III).31 By reducing chronic psychological stress, meditation techniques offer a promising preventive option against AD.
Mindfulness-based interventions (MBI) have gained increased attention in the past decade. They entail directing one’s attention towards the present moment, thereby decreasing ruminative thoughts and stress arousal.32 Recent RCTs have shown that MBI may promote brain health in older adults not only by improving psychological well-being but also by improving attentional control33 and functional connectivity in brain regions implicated in executive functioning,34 as well as by modulating inflammatory processes implicated in AD.35 Furthermore, an RCT of patients diagnosed with MCI found that compared with memory enhancement training, a weekly 60-minute yoga session improved memory and executive functioning.36
Continue to: Kirtan Kriya is a medication technique...
Kirtan Kriya is a meditation technique that is easy to learn and practice by older adults and can improve memory in patients at risk for developing AD.37 However, more rigorous RCTs conducted in larger samples of older adults are needed to better evaluate the effect of all meditation techniques for delaying or preventing AD (level IB with respect to improvement in cognitive functioning/level III for AD delay/risk reduction).38
Spiritual activities, such as going to places of worship or religious meditation, have been associated with a lower prevalence of AD. Attending religious services, gatherings, or retreats involves a social component because these activities often are practiced in groups. They also confer a method of dealing with psychological distress and depression. Additionally, frequent readings of religious texts represents a mentally stimulating activity that may also contribute to delaying/preventing AD (level III).39
Diet
In the past decade, a growing body of evidence has linked diet to cognition. Individuals with a higher intake of calories and fat are at higher risk for developing AD.40 The incidence of AD rose in Japan after the country transitioned to a more Westernized diet.41 A modern Western diet rich in saturated fatty acids and simple carbohydrates may negatively impact hippocampus-mediated functions such as memory and learning, and is associated with an increased risk of AD.42 In contrast with high-glycemic and fatty diets, a “healthy diet” is associated with a decrease in beta-amyloid burden, inflammation, and oxidative stress.43,44
Studies focusing on dietary patterns rather than a single nutrient for delaying or preventing AD have yielded more robust and consistent results.45 In a recent meta-analysis, adhering to a Mediterranean diet—which is rich in fruits and vegetables, whole grains, olive oil, and fish; moderate in some dairy products and wine; and low in red meat—was associated with a decreased risk of AD; this evidence was derived mostly from epidemiologic studies.46 Scarmeas et al8 found that high adherence to the Mediterranean diet was associated with 32% to 40% reduced risk of AD. Combining this diet with physical exercise was associated with an up to 67% reduced risk (level III). The Dietary Approaches to Stop Hypertension (DASH) diet, which is rich in total grains, fruits, vegetables, and dairy products, but low in sodium and sweets, correlated with neurocognitive improvement in patients with hypertension.47 Both the Mediterranean and DASH diets have been associated with better cognitive function48 and slower cognitive decline.49 Thus, an attempt to combine the neuroprotective components from both diets led to the creation of the MIND (Mediterranean-DASH Intervention for Neurodegenerative Delay) diet, which also has been associated with a lower incidence of AD.50
Besides specific diets, some food groups have also been found to promote brain health and may help delay or prevent AD. Berries have the highest amount of antioxidants of all fruit. Among vegetables, tomatoes and green leafy vegetables have the highest amount of nutrients for the brain. Nuts, such as walnuts, which are rich in omega-3 fatty acids, are also considered “power foods” for the brain; however, they should be consumed in moderation because they are also rich in fat. Monounsaturated fatty acids, which are found in olives and olive oil, are also beneficial for the brain. Among the 3 types of omega-3 fatty acids, the most important for cognition is docosahexaenoic acid (DHA) because it constitutes 40% of all fatty acids in the brain. Mainly found in oily fish, DHA has antioxidant and anti-inflammatory properties that may delay or prevent AD. Low levels of DHA have been found in patients with AD.51
Continue to: Curcumin, which is derived from...
Curcumin, which is derived from the curry spice turmeric, is a polyphenol with anti-inflammatory, antioxidant, and anti-amyloid properties that may have a promising role in preventing AD in cognitively intact individuals. Initial trials with curcumin have yielded mixed results on cognition, which was partly related to the low solubility and bioavailability of its formulation.52 However, a recent 18-month double-blind randomized placebo-controlled trial found positive effects on memory and attention, as well as reduction of amyloid plaques and tau tangles deposition in the brain, in non-demented older adults age 51 to 84 who took Theracumin, a highly absorptive oral form of curcumin dispersed with colloidal nanoparticles.53 A longer follow-up is required to determine if curcumin can delay or prevent AD.
Alcohol
The role of alcohol in AD prevention is controversial. Overall, data from prospective studies has shown that low to moderate alcohol consumption may be associated with a reduced risk of AD (level III).54 Alcohol drinking in mid-life showed a U-shaped relationship with cognitive impairment; both abstainers and heavy drinkers had an increased risk of cognitive decline compared with light to moderate drinkers (level III).55 Binge drinking significantly increased the odds of cognitive decline, even after controlling for total alcohol consumption per week.55
The definition of low-to-moderate drinking varies substantially among countries. In addition, the size and amount of alcohol contained in a standard drink may differ.56 According to the National Institute on Alcohol Abuse and Alcoholism (NIAAA),57 moderate drinking is defined as up to 1 drink daily for women and 2 drinks daily for men. Binge drinking involves drinking >4 drinks for women and >5 drinks for men, in approximately 2 hours, at least monthly. In the United States, one standard drink contains 14 grams of pure alcohol, which is usually found in 12 ounces of regular beer, 5 ounces of wine, and 1.5 ounces of distilled spirits (vodka or whiskey).58
In a 5-year prospective Canadian study, having 1 drink weekly (especially wine) was associated with an up to 50% reduced risk of AD (level III).59 In the French cohort PAQUID, mild drinkers (<1 to 2 drinks/day) and moderate drinkers (3 to 4 drinks daily) had a reduced incidence of AD compared with non-drinkers. Wine was the most frequently consumed beverage in this study.60 Other studies have found cognitive benefits from mild to moderate drinking regardless of beverage type.54 However, a recent study that included a 30-year follow-up failed to find a significant protective effect of light drinking over abstinence in terms of hippocampal atrophy.61 Atrophy of the hippocampus was correlated with increasing alcohol amounts in a dose-dependent manner, starting at 7 to 14 drinks/week (level III).61
Research has shown that moderate and heavy alcohol use or misuse can directly induce microglial activation and inflammatory mediators’ release, which induce amyloid beta pathology and leads to brain atrophy.62 Hence, non-drinkers should not be advised to begin drinking, because of the lack of RCTs and the concern that beginning to drink may lead to heavy drinking. All drinkers should be advised to adhere to the NIAAA recommendations.13
Continue to: Coffee/tea
Coffee/tea
Although studies of caffeinated coffee have been heterogeneous and yielded mixed results (beneficial effect vs no effect on delaying cognitive decline), systematic reviews and meta-analyses of cross-sectional, case-control, and longitudinal cohort studies have found a general trend towards a favorable preventive role (level III).63-65 Caffeine exhibits its neuroprotective effect by increasing brain serotonin and acetylcholine, and by stabilizing blood-brain-barrier integrity.66 Moreover, in an animal study, mice given caffeine in their drinking water from young adulthood into older age had lower amyloid beta plasma levels compared with those given decaffeinated water.67 These findings suggest that in humans, 5 cups of regular caffeinated coffee daily, equivalent to 500 mg of caffeine,
An Italian study showed that older adults who don’t or rarely drink coffee (<1 cup daily) and those who recently increased their consumption pattern to >1 cup daily had a higher incidence of MCI than those who habitually consumed 1 to 2 cups daily.69 Therefore, it is not recommended to advise a change in coffee drinking pattern in old age. Older adults who are coffee drinkers should, however, be educated about the association between heavier caffeine intake and anxiety, insomnia, and cardiac arrhythmias.70
Despite its more modest caffeine levels, green tea is rich in polyphenols, which belong to the family of catechins and are characterized by antioxidant and anti-inflammatory properties.71 In a Japanese cohort, higher green tea consumption (up to 1 cup daily) was associated with a decreased incidence of MCI in older adults.72 More studies are needed to confirm its potential preventative role in AD.
Which lifestyle change is the most important?
Focusing on a single lifestyle change may be insufficient, especially because the bulk of evidence for individual interventions comes from population-based cohort studies (level III), rather than strong RCTs with a long follow-up. There is increasing evidence that combining multiple lifestyle modifications may yield better outcomes in maintaining or improving cognition.73
The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), a large, 2-year RCT that included community-dwelling older adults (age 60 to 77) with no diagnosis of major neurocognitive disorder, found that compared with regular health advice, multi-domain interventions reduced cognitive decline and improved overall cognition, executive functioning, and processing speed. The interventions evaluated in this study combined the following 4 modalities74:
- a healthy diet according to the Finnish nutrition recommendations (eating vegetables, fruits, and berries [minimum: 500 g/d], whole grain cereals [several times a day], and fish [2 to 3 times/week]; using low-salt products; consuming fat-free or low-fat milk products; and limiting red meat consumption to <500 g/week
- regular physical exercise tailored for improving muscle strength (1 to 3 times/week) coupled with aerobic exercise (2 to 5 times/week)
- cognitive training, including group sessions that have a social activity component and computer-based individual sessions 3 times/week that target episodic and working memory and executive functioning
- optimal management of cardiovascular risk factors.
Continue to: This multi-domain approach...
This multi-domain approach for lifestyle modification should be strongly recommended to cognitively intact older patients (level IB).
Modeled after the FINGER study, the Alzheimer’s Association U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER) is a 2-year, multicenter, controlled clinical trial aimed at testing the ability of a multidimensional lifestyle intervention to prevent AD in at-risk older adults (age 60 to 79, with established metabolic and cardiovascular risk factors). Interventions include a combination of physical exercise, nutritional counseling and management, cognitive and social stimulation, and improved management of cardiovascular risk factors. Recruitment for this large-scale trial was estimated to begin in January 2019 (NCT03688126).75
On a practical basis, Desai et al13 have proposed a checklist (Table 213) that physicians can use in their routine consultations to improve primary prevention of AD among their older patients.
Bottom Line
Advise patients that pursuing a healthy lifestyle is a key to delaying or preventing Alzheimer’s disease. This involves managing cardiovascular risk factors and a combination of staying physically, mentally, socially, and spiritually active, in addition to adhering to a healthy diet such as the Mediterranean diet.
Related Resources
- Anderson K, Grossberg GT. Brain games to slow cognitive decline in Alzheimer’s disease. J Am Med Dir Assoc. 2014;15(8):536-537.
- Small G, Vorgan G. The memory prescription: Dr. Garry Small’s 14-day plan to keep your brain and body young. New York, NY: Hyperion; 2004.
- Small G, Vorgan G. The Alzheimer’s prevention program; keep your brain healthy for the rest of your life. New York, NY: Workman Publishing Company, Inc.; 2012.
Drug Brand Name
Curcumin • Theracurmin
1. Mehta D, Jackson R, Paul G, et al. Why do trials for Alzheimer’s disease drugs keep failing? A discontinued drug perspective for 2010-2015. Expert Opin Investig Drugs. 2017;26(6):735-739.
2. Norton S, Matthews FE, Barnes DE, et al. Potential for primary prevention of Alzheimer’s disease: an analysis of population-based data. Lancet Neurol. 2014;13(8):788-794.
3. Meng XF, Yu JT, Wang HF, et al. Midlife vascular risk factors and the risk of Alzheimer’s disease: a systematic review and meta-analysis. J Alzheimers Dis. 2014;42(4):1295-1310.
4. Shekelle PG, Woolf SH, Eccles M, et al. Developing clinical guidelines. West J Med. 1999;170(6):348-351.
5. Barnes DE, Yaffe Y. The projected impact of risk factor reduction on Alzheimer’s disease prevalence. Lancet Neurol. 2011;10(9):819-828.
6. Cotman CW, Berchtold NC, Christie LA. Exercise builds brain health: key roles of growth factor cascades and inflammation. Trends Neurosci. 2007;30(9):464-472.
7. Ahlskog JE, Geda YE, Graff-Radford NR, et al. Physical exercise as a preventive or disease-modifying treatment of dementia and brain aging. Mayo Clin Proc. 2011;86(9):876-884.
8. Scarmeas N, Luchsinger JA, Schupf N, et al. Physical activity, diet, and risk of Alzheimer Disease. JAMA. 2009;302(6):627-637.
9. Rovio S, Kåreholt I, Helkala EL, et al. Leisure-time physical activity at midlife and the risk of dementia and Alzheimer’s disease. Lancet Neurol. 2005;4(11):705-711.
10. Smith PJ et al. Aerobic exercise and neurocognitive performance: a meta-analytic review of randomized controlled trials. Psychosom Med. 2010;72(3):239-252.
11. Brown BM, Peiffer JJ, Taddei K, et al. Physical activity and amyloid-beta plasma and brain levels: results from the Australian imaging, biomarkers and lifestyle study of ageing. Mol Psychiatry. 2013;18(8):875-881.
12. Brown BM, Sohrabi HR, Taddei K, et al. Habitual exercise levels are associated with cerebral amyloid load in presymptomatic autosomal dominant Alzheimer’s disease. Alzheimers Dement. 2017;13(11):1197-1206.
13. Desai AK, Grossberg GT, Chibnall JT. Healthy brain aging: a road map. Clin Geriatr Med. 2010;26(1):1-16.
14. Centers for Disease Control and Prevention. Physical activity: how much physical activity do older adults need?
15. Garber CE, Blissmer B, Deschenes MR, et al; American College of Sports Medicine. American College of Sports Medicine position stand. Quantity and quality of exercise for developing and maintaining cardiorespiratory, musculoskeletal, and neuromotor fitness in apparently healthy adults: guidance for prescribing exercise. Med Sci Sports Exerc. 2011;43(7):1334-1359.
16. Livingston G, Sommerlad A, Orgeta V, et al. Dementia prevention, intervention, and care. Lancet. 2017;390(10113);2673-2734.
17. Valenzuela MJ, Sachdev P, Wen W, et al. Lifespan mental activity predicts diminished rate of hippocampal atrophy. PLoS One. 2008;3(7):e2598. doi.org/10.1371/journal.pone.0002598.
18. Wilson RS, Bennett DA, Bienias JL, et al. Cognitive activity and incident AD in a population-based sample of older persons. Neurology. 2002;59(12):1910-1914.
19. Wilson RS, Scherr PA, Schneider JA, et al. Relation of cognitive activity to risk of developing Alzheimer disease. Neurology. 2007;69(20):1911-1920.
20. Krell-Roesch J, Vemuri P, Pink A, et al. Association between mentally stimulating activities in late life and the outcome of incident mild cognitive impairment, with an analysis of the apoe ε4 genotype. JAMA Neurol. 2017;74(3):332-338.
21. Verghese J, Lipton RB, Katz MJ, et al. Leisure activities and the risk of dementia in the elderly. N Engl J Med. 2003;348(25):2508-2516.
22. Klein RM, Christie J, Parkvall M. Does multilingualism affect the incidence of Alzheimer’s disease?: a worldwide analysis by country. SSM Popul Health. 2016;2:463-467.
23. Grundy JG, Anderson JAE, Bialystok E. Neural correlates of cognitive processing in monolinguals and bilinguals. Ann N Y Acad Sci. 2017;1396(1):183-201.
24. Wilson RS, Krueger KR, Arnold SE, et al. Loneliness and risk of Alzheimer disease. Arch Gen Psychiatry. 2007;64(2):234-240.
25. Amieva H, Stoykova R, Matharan F, et al. What aspects of social network are protective for dementia? Not the quantity but the quality of social interactions is protective up to 15 years later. Psychosom Med. 2010;72(9):905-911.
26. Kuiper JS, Oude Voshaar RC, Zuidema SU, et al. The relationship between social functioning and subjective memory complaints in older persons: a population-based longitudinal cohort study. Int J Geriatr Psychiatry. 2017;32(10):1059-1071.
27. Robert P, Onyike CU, Leentjens AF, et al. Proposed diagnostic criteria for apathy in Alzheimer’s disease and other neuropsychiatric disorders. Eur Psychiatry. 2009;24(2):98-104.
28. Marioni RE, Proust-Lima C, Amieva H, et al. Social activity, cognitive decline and dementia risk: a 20-year prospective cohort study. BMC Public Health. 2015;15:1089.
29. Wilson RS, Schneider JA, Boyle PA, et al. Chronic distress and incidence of mild cognitive impairment. Neurology. 2007;68(24):2085-2092.
30. Cai Z, Yan LJ, Ratka A. Telomere shortening and Alzheimer’s disease. Neuromolecular Med. 2013;15(1):25-48.
31. Wilson RS, Arnold SE, Schneider JA, et al. Chronic psychological distress and risk of Alzheimer’s disease in old age. Neuroepidemiology. 2006;27(3):143-153.
32. Epel E, Daubenmier J, Moskowitz JT, et al. Can meditation slow rate of cellular aging? Cognitive stress, mindfulness, and telomeres. Ann N Y Acad Sci. 2009;1172:34-53.
33. Malinowski P, Moore AW, Mead Br, et al. Mindful aging: the effects of regular brief mindfulness practice on electrophysiological markers of cognitive and affective processing in older adults. Mindfulness (N Y). 2017;8(1):78-94.
34. Taren AA, Gianaros PJ, Greco CM, et al. Mindfulness meditation training and executive control network resting state functional connectivity: a randomized controlled trial. Psychosom Med. 2017;79(6):674-683.
35. Fountain-Zaragoza S, Prakash RS. Mindfulness training for healthy aging: impact on attention, well-being, and inflammation. Front in Aging Neurosci. 2017;9:11.
36. Eyre HA, Siddarth P, Acevedo B, et al. A randomized controlled trial of Kundalini yoga in mild cognitive impairment. Int Psychogeriatr. 2017;29(4):557-567.
37. Khalsa DS. Stress, meditation, and Alzheimer’s disease prevention: where the evidence stands. J Alzheimers Dis. 2015;48(1):1-12.
38. Berk L, van Boxtel M, van Os J. Can mindfulness-based interventions influence cognitive functioning in older adults? A review and considerations for future research. Aging Ment Health. 2017;21(11):1113-1120.
39. Hosseini S, Chaurasia A, Oremus M. The effect of religion and spirituality on cognitive function: a systematic review. Gerontologist. 2017. doi: 10.1093/geront/gnx024.
40. Luchsinger JA, Tang MX, Shea S, et al. Caloric intake and the risk of Alzheimer disease. Arch Neurol. 2002;59(8):1258-1263.
41. Grant WB. Trends in diet and Alzheimer’s disease during the nutrition transition in Japan and developing countries. J Alzheimers Dis. 2014;38(3):611-620.
42. Kanoski SE, Davidson TL. Western diet consumption and cognitive impairment: links to hippocampal dysfunction and obesity. Physiol Behav. 2011;103(1):59-68.
43. Hu N, Yu JT, Tan L, et al. Nutrition and the risk of Alzheimer’s disease. Biomed Res Int. 2013;2013:524820. doi: 10.1155/2013/524820.
44. Taylor MK, Sullivan DK, Swerdlow RH, et al. A high-glycemic diet is associated with cerebral amyloid burden in cognitively normal older adults. Am J Clin Nutr. 2017;106(6):1463-1470.
45. van de Rest O, Berendsen AM, Haveman-Nies A, et al. Dietary patterns, cognitive decline, and dementia: a systematic review. Adv Nutr. 2015;6(2):154-168.
46. Petersson SD, Philippou E. Mediterranean diet, cognitive function, and dementia: a systematic review of the evidence. Adv Nutr. 2016;7(5):889-904.
47. Smith PJ, Blumenthal JA, Babyak MA, et al. Effects of the dietary approaches to stop hypertension diet, exercise, and caloric restriction on neurocognition in overweight adults with high blood pressure. Hypertension. 2010;55(6):1331-1338.
48. Wengreen H, Munger RG, Cutler A, et al. Prospective study of dietary approaches to stop hypertension- and Mediterranean-style dietary patterns and age-related cognitive change: the Cache County study on memory, health and aging. Am J Clin Nutr. 2013;98(5):1263-1271.
49. Tangney CC, Li H, Wang Y, et al. Relation of DASH- and Mediterranean-like dietary patterns to cognitive decline in older persons. Neurology. 2014;83(16):1410-1416.
50. Morris MC, Tangney CC, Wang Y, et al. MIND diet associated with reduced incidence of Alzheimer’s disease. Alzheimers Dement. 2015;11(9):1007-1014.
51. Desai AK, Rush J, Naveen L, et al. Nutrition and nutritional supplements to promote brain health. In: Hartman-Stein PE, Rue AL, eds. Enhancing cognitive fitness in adults: a guide to the use and development of community-based programs. New York, NY: Springer; 2011:249-269.
52. Goozee KG, Shah TM, Sohrabi HR, et al. Examining the potential clinical value of curcumin in the prevention and diagnosis of Alzheimer’s disease. Br J Nutr. 2016;115(3):449-465.
53. Small GW, Siddarth P, Li Z, et al. Memory and brain amyloid and tau effects of a bioavailable form of curcumin in non-demented adults: a double-blind, placebo-controlled 18-month trial. Am J Geriatr Psychiatry. 2018;26(3):266-277.
54. Kim JW, Lee DY, Lee BC, et al. Alcohol and cognition in the elderly: a review. Psychiatry Investig. 2012;9(1):8-16.
55. Virtaa JJ, Järvenpää T, Heikkilä K, et al. Midlife alcohol consumption and later risk of cognitive impairment: a twin follow-up study. J Alzheimers Dis. 2010;22(3):939-948.
56. Kerr WC, Stockwell T. Understanding standard drinks and drinking guidelines. Drug and Alcohol Rev. 2012;31(2):200-205.
57. National Institute on Alcohol Abuse and Alcoholism. Drinking levels defined. https://www.niaaa.nih.gov/alcohol-health/overview-alcohol-consumption/moderate-binge-drinking. Accessed December 9, 2017.
58. National Institute on Alcohol Abuse and Alcoholism. What is a standard drink? https://www.niaaa.nih.gov/alcohol-health/overview-alcohol-consumption/what-standard-drink. Accessed November 9, 2017.
59. Lindsay J, Laurin D, Verreault R, et al. Risk factors for Alzheimer’s disease: a prospective analysis from the Canadian study of health and aging. Am J Epidemiol. 2002;156(5):445-453.
60. Orgogozo JM, Dartigues JF, Lafont S, et al. Wine consumption and dementia in the elderly: a prospective community study in the Bordeaux area. Rev Neurol (Paris). 1997;153(3):185-192.
61. Topiwala A, Allan CL, Valkanova V, et al. Moderate alcohol consumption as risk factor for adverse brain outcomes and cognitive decline: longitudinal cohort study. BMJ. 2017;357.
62. Venkataraman A, Kalk N, Sewell G, et al. Alcohol and Alzheimer’s disease-does alcohol dependence contribute to beta-amyloid deposition, neuroinflammation and neurodegeneration in Alzheimer’s Disease? Alcohol Alcohol. 2017;52(2):151-158.
63. Ma QP, Huang C, Cui QY, et al. Meta-analysis of the association between tea intake and the risk of cognitive disorders. PLoS One. 2016;11(11):e0165861. doi: 10.1371/journal.pone.0165861.
64. Santos C, Costa J, Santos J, et al. Caffeine intake and dementia: systematic review and meta-analysis. J Alzheimers Dis. 2010;20(Suppl 1):S187-204.
65. Panza F, Solfrizzi V, Barulli MR, et al. Coffee, tea, and caffeine consumption and prevention of late-life cognitive decline and dementia: a systematic review. J Nutr Health Aging. 2015;19(3):313-328.
66. Wierzejska R. Can coffee consumption lower the risk of Alzheimer’s disease and Parkinson’s disease? A literature review. Arch Med Sci. 2017;13(3):507-514.
67. Arendash GW, Cao C. Caffeine and coffee as therapeutics against Alzheimer’s disease. J Alzheimers Dis. 2010;20 (Suppl 1):S117-S126.
68. Eskelinen MH, Ngandu T, Tuomilehto J, et al. Midlife coffee and tea drinking and the risk of late-life dementia: a population-based CAIDE study. J Alzheimers Dis. 2009;16(1):85-91.
69. Solfrizzi V, Panza F, Imbimbo BP, et al. Coffee consumption habits and the risk of mild cognitive impairment: the Italian longitudinal study on aging. J Alzheimers Dis. 2015;47(4):889-899.
70. Vittoria Mattioli. Beverages of daily life: impact of caffeine on atrial fibrillation. J Atr Fibrillation. 2014;7(2):1133.
71. Chacko SM, Thambi PT, Kuttan R, et al. Beneficial effects of green tea: a literature review. Chin Med. 2010;5:13.
72. Noguchi-Shinohara M, Yuki S, Dohmoto C, et al. Consumption of green tea, but not black tea or coffee, is associated with reduced risk of cognitive decline. PLoS One. 2014;9(5):e96013. doi: 10.1371/journal.pone.0096013.
73. Schneider N, Yvon C. A review of multidomain interventions to support healthy cognitive ageing. J Nutr Health Aging. 2013;17(3):252-257.
74. Ngandu T, Lehitsalo J, Solomon A, et al. A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial. Lancet. 2015;385(9984):2255-2263.
75. U.S. National Library of Medicing. ClinicalTrials.gov. U.S. study to protect brain health through lifestyle intervention to reduce risk (POINTER). https://clinicaltrials.gov/ct2/show/NCT03688126?term=pointer&cond=Alzheimer+Disease&rank=1. Published September 28, 2018. Accessed November 3, 2018.
Clinicians have devoted strenuous efforts to secondary prevention of Alzheimer’s disease (AD) by diagnosing and treating patients as early as possible. Unfortunately, there is no cure for AD, and the field has witnessed recurrent failures of several pharmacotherapy candidates with either symptomatic or disease-modifying properties.1 An estimated one-third of AD cases can be attributed to modifiable risk factors.2 Thus, implementing primary prevention measures by addressing modifiable risk factors thought to contribute to the disease, with the goal of reducing the risk of developing AD, or at least delaying its onset, is a crucial public health strategy.
Cardiovascular risk factors, such as hypertension, hyperlipidemia, diabetes, hyperhomocysteinemia, obesity, and smoking, have emerged as substantive risk factors for AD.3 Optimal management of these major risk factors, especially in mid-life, may be a preventive approach against AD. Although detailing the evidence on the impact of managing cardiovascular risk factors to delay or prevent AD is beyond the scope of this article, it is becoming clear that “what is good for the heart is good for the brain.”
Additional modifiable risk factors are related to lifestyle habits, such as physical exercise, mental and social activity, meditation/spiritual activity, and diet. This article reviews the importance of pursuing a healthy lifestyle in delaying AD, with the corresponding levels of evidence that support each specific lifestyle modification. The levels of evidence are defined in Table 1.4
Physical exercise
Twenty-one percent of AD cases in the United States are attributable to physical inactivity.5 In addition to its beneficial effect on metabolic syndrome, in animal and human research, regular exercise has been shown to have direct neuroprotective effects. High levels of physical activity increase hippocampal neurogenesis and neuroplasticity, increase vascular circulation in the brain regions implicated in AD, and modulate inflammatory mediators as well as brain growth factors such as brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1).6
The definition of regular physical exercise varies across the literature, but usually implies aerobic exercise—an ongoing activity sufficient to increase the heart rate and the need for oxygen, sustained for 20 to 30 minutes per session.7 Modalities include household activities and leisure-time activities. In a large prospective cohort study, Scarmeas et al8 categorized leisure-time activities into 3 types:
- light (walking, dancing, calisthenics, golfing, bowling, gardening, horseback riding)
- moderate (bicycling, swimming, hiking, playing tennis)
- vigorous (aerobic dancing, jogging, playing handball).
These types of physical exercise were weighed by the frequency of participation per week. Compared with being physically inactive, low levels of weekly physical activity (0.1 hours of vigorous, 0.8 hours of moderate, or 1.3 hours of light exercise) were associated with a 29% to 41% lower risk of developing AD, while higher weekly physical activity (1.3 hours of vigorous, 2.3 hours of moderate, or 3.8 hours of light exercise) were associated with a 37% to 50% lower risk (level III).8
In another 20-year cohort study, engaging in leisure-time physical activity at least twice a week in mid-life was significantly associated with a reduced risk of AD, after adjusting for age, sex, education, follow-up time, locomotor disorders, apolipoprotein E (ApoE) genotype, vascular disorders, smoking, and alcohol intake (level III).9 Moreover, a systematic review of 29 randomized controlled trials (RCTs) showed that aerobic exercise training, such as brisk walking, jogging, and biking, was associated with improvements in attention, processing speed, executive function, and memory among healthy older adults and those with mild cognitive impairment (MCI; level IA).10
Continue to: From a pathophysiological standpoint...
From a pathophysiological standpoint, higher levels of physical exercise in cognitively intact older adults have been associated with reduced brain amyloid beta deposits, especially in ApoE4 carriers.11 This inverse relationship also has been demonstrated in patients who are presymptomatic who carry 1 of the 3 known autosomal dominant mutations for the familial forms of AD.12
Overall, physicians should recommend that patients—especially those with cardiovascular risk factors that increase their risk for AD—exercise regularly by following the guidelines of the American Heart Association or the American College of Sports Medicine.13 These include muscle-strengthening activities (legs, hips, back, abdomen, shoulders, and arms) at least 2 days/week, in addition to either 30 minutes/day of moderate-intensity aerobic activity such as brisk walking, 5 days/week; or 25 minutes of vigorous aerobic activity such as jogging and running, 3 days/week14 (level IA evidence for overall improvement in cognitive function; level III evidence for AD delay/risk reduction). Neuromotor exercise, such as yoga and tai chi, and flexibility exercise such as muscle stretching, especially after a hot bath, 2 to 3 days/week are also recommended (level III).15
Mental activity
Nineteen percent of AD cases worldwide and 7% in the United States. can be attributed to low educational attainment, which is associated with low brain cognitive reserve.5 Cognitive resilience in later life may be enhanced by building brain reserves through intellectual stimulation, which affects neuronal branching and plasticity.16 Higher levels of complex mental activities measured across the lifespan, such as education, occupation, reading, and writing, are correlated with significantly less hippocampal volume shrinkage over time.17 Frequent participation in mentally stimulating activities—such as listening to the radio; reading newspapers, magazines, or books; playing games (cards, checkers, crosswords or other puzzles); and visiting museums—was associated with an up to 64% reduction in the odds of developing AD in a cohort of cognitively intact older adults followed for 4 years.18 The correlation between mental activity and AD was found to be independent of physical activity, social activity, or baseline cognitive function.19
In a large cohort of cognitively intact older adults (mean age 70), engaging in a mentally stimulating activity (craft activities, computer use, or going to the theater/movies) once to twice a week was significantly associated with a reduced incidence of amnestic MCI.20 Another prospective 21-year study demonstrated a significant reduction in AD risk in community-dwelling cognitively intact older adults (age 75 to 85) who participated in cognitively stimulating activities, such as reading books or newspapers, writing for pleasure, doing crossword puzzles, playing board games or cards, or playing musical instruments, several times/week.21
Growing scientific evidence also suggests that lifelong multilingualism can delay AD onset by 4 to 5 years.22 Multilingualism is associated with greater cognitive reserve, gray matter volume, functional connectivity and white matter density.23
Continue to: Physicians should encourage their patients...
Physicians should encourage their patients to engage in intellectually stimulating activities and creative leisure-time activities several times/week to enhance their cognitive reserves and delay AD onset (level III evidence with respect to AD risk reduction/delay).
Social activity
Social engagement may be an additional protective factor against AD. In a large 4-year prospective study, increased loneliness in cognitively intact older adults doubled the risk of AD.24 Data from the large French cohort PAQUID (Personnes Agées QUID) emphasized the importance of a patient’s social network as a protective factor against AD. In this cohort, the perception of reciprocity in relationships with others (the perception that a person had received more than he or she had given) was associated with a 53% reduction in AD risk (level III).25 In another longitudinal cohort study, social activity was found to decrease the incidence of subjective cognitive decline, which is a prodromal syndrome for MCI and AD (level III).26
A major confounder in studies assessing for social activity is the uncertainty if social withdrawal is a modifiable risk factor or an early manifestation of AD, since apathetic patients with AD tend to be socially withdrawn.27 Another limitation of measuring the impact of social activity relative to AD risk is the difficulty in isolating social activities from activities that have physical and mental activity components, such as leisure-time activities.28
Meditation/spiritual activity
Chronic psychological stress is believed to compromise limbic structures that regulate stress-related behaviors and the memory network, which might explain how being prone to psychological distress may be associated with MCI or AD.29 Cognitive stress may increase the oxidative stress and telomere shortening implicated in the neurodegenerative processes of AD.30 In one study, participants who were highly prone to psychological distress were found to be at 3 times increased risk for developing AD, after adjusting for depression symptoms and physical and mental activities (level III).31 By reducing chronic psychological stress, meditation techniques offer a promising preventive option against AD.
Mindfulness-based interventions (MBI) have gained increased attention in the past decade. They entail directing one’s attention towards the present moment, thereby decreasing ruminative thoughts and stress arousal.32 Recent RCTs have shown that MBI may promote brain health in older adults not only by improving psychological well-being but also by improving attentional control33 and functional connectivity in brain regions implicated in executive functioning,34 as well as by modulating inflammatory processes implicated in AD.35 Furthermore, an RCT of patients diagnosed with MCI found that compared with memory enhancement training, a weekly 60-minute yoga session improved memory and executive functioning.36
Continue to: Kirtan Kriya is a medication technique...
Kirtan Kriya is a meditation technique that is easy to learn and practice by older adults and can improve memory in patients at risk for developing AD.37 However, more rigorous RCTs conducted in larger samples of older adults are needed to better evaluate the effect of all meditation techniques for delaying or preventing AD (level IB with respect to improvement in cognitive functioning/level III for AD delay/risk reduction).38
Spiritual activities, such as going to places of worship or religious meditation, have been associated with a lower prevalence of AD. Attending religious services, gatherings, or retreats involves a social component because these activities often are practiced in groups. They also confer a method of dealing with psychological distress and depression. Additionally, frequent readings of religious texts represents a mentally stimulating activity that may also contribute to delaying/preventing AD (level III).39
Diet
In the past decade, a growing body of evidence has linked diet to cognition. Individuals with a higher intake of calories and fat are at higher risk for developing AD.40 The incidence of AD rose in Japan after the country transitioned to a more Westernized diet.41 A modern Western diet rich in saturated fatty acids and simple carbohydrates may negatively impact hippocampus-mediated functions such as memory and learning, and is associated with an increased risk of AD.42 In contrast with high-glycemic and fatty diets, a “healthy diet” is associated with a decrease in beta-amyloid burden, inflammation, and oxidative stress.43,44
Studies focusing on dietary patterns rather than a single nutrient for delaying or preventing AD have yielded more robust and consistent results.45 In a recent meta-analysis, adhering to a Mediterranean diet—which is rich in fruits and vegetables, whole grains, olive oil, and fish; moderate in some dairy products and wine; and low in red meat—was associated with a decreased risk of AD; this evidence was derived mostly from epidemiologic studies.46 Scarmeas et al8 found that high adherence to the Mediterranean diet was associated with 32% to 40% reduced risk of AD. Combining this diet with physical exercise was associated with an up to 67% reduced risk (level III). The Dietary Approaches to Stop Hypertension (DASH) diet, which is rich in total grains, fruits, vegetables, and dairy products, but low in sodium and sweets, correlated with neurocognitive improvement in patients with hypertension.47 Both the Mediterranean and DASH diets have been associated with better cognitive function48 and slower cognitive decline.49 Thus, an attempt to combine the neuroprotective components from both diets led to the creation of the MIND (Mediterranean-DASH Intervention for Neurodegenerative Delay) diet, which also has been associated with a lower incidence of AD.50
Besides specific diets, some food groups have also been found to promote brain health and may help delay or prevent AD. Berries have the highest amount of antioxidants of all fruit. Among vegetables, tomatoes and green leafy vegetables have the highest amount of nutrients for the brain. Nuts, such as walnuts, which are rich in omega-3 fatty acids, are also considered “power foods” for the brain; however, they should be consumed in moderation because they are also rich in fat. Monounsaturated fatty acids, which are found in olives and olive oil, are also beneficial for the brain. Among the 3 types of omega-3 fatty acids, the most important for cognition is docosahexaenoic acid (DHA) because it constitutes 40% of all fatty acids in the brain. Mainly found in oily fish, DHA has antioxidant and anti-inflammatory properties that may delay or prevent AD. Low levels of DHA have been found in patients with AD.51
Continue to: Curcumin, which is derived from...
Curcumin, which is derived from the curry spice turmeric, is a polyphenol with anti-inflammatory, antioxidant, and anti-amyloid properties that may have a promising role in preventing AD in cognitively intact individuals. Initial trials with curcumin have yielded mixed results on cognition, which was partly related to the low solubility and bioavailability of its formulation.52 However, a recent 18-month double-blind randomized placebo-controlled trial found positive effects on memory and attention, as well as reduction of amyloid plaques and tau tangles deposition in the brain, in non-demented older adults age 51 to 84 who took Theracumin, a highly absorptive oral form of curcumin dispersed with colloidal nanoparticles.53 A longer follow-up is required to determine if curcumin can delay or prevent AD.
Alcohol
The role of alcohol in AD prevention is controversial. Overall, data from prospective studies has shown that low to moderate alcohol consumption may be associated with a reduced risk of AD (level III).54 Alcohol drinking in mid-life showed a U-shaped relationship with cognitive impairment; both abstainers and heavy drinkers had an increased risk of cognitive decline compared with light to moderate drinkers (level III).55 Binge drinking significantly increased the odds of cognitive decline, even after controlling for total alcohol consumption per week.55
The definition of low-to-moderate drinking varies substantially among countries. In addition, the size and amount of alcohol contained in a standard drink may differ.56 According to the National Institute on Alcohol Abuse and Alcoholism (NIAAA),57 moderate drinking is defined as up to 1 drink daily for women and 2 drinks daily for men. Binge drinking involves drinking >4 drinks for women and >5 drinks for men, in approximately 2 hours, at least monthly. In the United States, one standard drink contains 14 grams of pure alcohol, which is usually found in 12 ounces of regular beer, 5 ounces of wine, and 1.5 ounces of distilled spirits (vodka or whiskey).58
In a 5-year prospective Canadian study, having 1 drink weekly (especially wine) was associated with an up to 50% reduced risk of AD (level III).59 In the French cohort PAQUID, mild drinkers (<1 to 2 drinks/day) and moderate drinkers (3 to 4 drinks daily) had a reduced incidence of AD compared with non-drinkers. Wine was the most frequently consumed beverage in this study.60 Other studies have found cognitive benefits from mild to moderate drinking regardless of beverage type.54 However, a recent study that included a 30-year follow-up failed to find a significant protective effect of light drinking over abstinence in terms of hippocampal atrophy.61 Atrophy of the hippocampus was correlated with increasing alcohol amounts in a dose-dependent manner, starting at 7 to 14 drinks/week (level III).61
Research has shown that moderate and heavy alcohol use or misuse can directly induce microglial activation and inflammatory mediators’ release, which induce amyloid beta pathology and leads to brain atrophy.62 Hence, non-drinkers should not be advised to begin drinking, because of the lack of RCTs and the concern that beginning to drink may lead to heavy drinking. All drinkers should be advised to adhere to the NIAAA recommendations.13
Continue to: Coffee/tea
Coffee/tea
Although studies of caffeinated coffee have been heterogeneous and yielded mixed results (beneficial effect vs no effect on delaying cognitive decline), systematic reviews and meta-analyses of cross-sectional, case-control, and longitudinal cohort studies have found a general trend towards a favorable preventive role (level III).63-65 Caffeine exhibits its neuroprotective effect by increasing brain serotonin and acetylcholine, and by stabilizing blood-brain-barrier integrity.66 Moreover, in an animal study, mice given caffeine in their drinking water from young adulthood into older age had lower amyloid beta plasma levels compared with those given decaffeinated water.67 These findings suggest that in humans, 5 cups of regular caffeinated coffee daily, equivalent to 500 mg of caffeine,
An Italian study showed that older adults who don’t or rarely drink coffee (<1 cup daily) and those who recently increased their consumption pattern to >1 cup daily had a higher incidence of MCI than those who habitually consumed 1 to 2 cups daily.69 Therefore, it is not recommended to advise a change in coffee drinking pattern in old age. Older adults who are coffee drinkers should, however, be educated about the association between heavier caffeine intake and anxiety, insomnia, and cardiac arrhythmias.70
Despite its more modest caffeine levels, green tea is rich in polyphenols, which belong to the family of catechins and are characterized by antioxidant and anti-inflammatory properties.71 In a Japanese cohort, higher green tea consumption (up to 1 cup daily) was associated with a decreased incidence of MCI in older adults.72 More studies are needed to confirm its potential preventative role in AD.
Which lifestyle change is the most important?
Focusing on a single lifestyle change may be insufficient, especially because the bulk of evidence for individual interventions comes from population-based cohort studies (level III), rather than strong RCTs with a long follow-up. There is increasing evidence that combining multiple lifestyle modifications may yield better outcomes in maintaining or improving cognition.73
The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), a large, 2-year RCT that included community-dwelling older adults (age 60 to 77) with no diagnosis of major neurocognitive disorder, found that compared with regular health advice, multi-domain interventions reduced cognitive decline and improved overall cognition, executive functioning, and processing speed. The interventions evaluated in this study combined the following 4 modalities74:
- a healthy diet according to the Finnish nutrition recommendations (eating vegetables, fruits, and berries [minimum: 500 g/d], whole grain cereals [several times a day], and fish [2 to 3 times/week]; using low-salt products; consuming fat-free or low-fat milk products; and limiting red meat consumption to <500 g/week
- regular physical exercise tailored for improving muscle strength (1 to 3 times/week) coupled with aerobic exercise (2 to 5 times/week)
- cognitive training, including group sessions that have a social activity component and computer-based individual sessions 3 times/week that target episodic and working memory and executive functioning
- optimal management of cardiovascular risk factors.
Continue to: This multi-domain approach...
This multi-domain approach for lifestyle modification should be strongly recommended to cognitively intact older patients (level IB).
Modeled after the FINGER study, the Alzheimer’s Association U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER) is a 2-year, multicenter, controlled clinical trial aimed at testing the ability of a multidimensional lifestyle intervention to prevent AD in at-risk older adults (age 60 to 79, with established metabolic and cardiovascular risk factors). Interventions include a combination of physical exercise, nutritional counseling and management, cognitive and social stimulation, and improved management of cardiovascular risk factors. Recruitment for this large-scale trial was estimated to begin in January 2019 (NCT03688126).75
On a practical basis, Desai et al13 have proposed a checklist (Table 213) that physicians can use in their routine consultations to improve primary prevention of AD among their older patients.
Bottom Line
Advise patients that pursuing a healthy lifestyle is a key to delaying or preventing Alzheimer’s disease. This involves managing cardiovascular risk factors and a combination of staying physically, mentally, socially, and spiritually active, in addition to adhering to a healthy diet such as the Mediterranean diet.
Related Resources
- Anderson K, Grossberg GT. Brain games to slow cognitive decline in Alzheimer’s disease. J Am Med Dir Assoc. 2014;15(8):536-537.
- Small G, Vorgan G. The memory prescription: Dr. Garry Small’s 14-day plan to keep your brain and body young. New York, NY: Hyperion; 2004.
- Small G, Vorgan G. The Alzheimer’s prevention program; keep your brain healthy for the rest of your life. New York, NY: Workman Publishing Company, Inc.; 2012.
Drug Brand Name
Curcumin • Theracurmin
Clinicians have devoted strenuous efforts to secondary prevention of Alzheimer’s disease (AD) by diagnosing and treating patients as early as possible. Unfortunately, there is no cure for AD, and the field has witnessed recurrent failures of several pharmacotherapy candidates with either symptomatic or disease-modifying properties.1 An estimated one-third of AD cases can be attributed to modifiable risk factors.2 Thus, implementing primary prevention measures by addressing modifiable risk factors thought to contribute to the disease, with the goal of reducing the risk of developing AD, or at least delaying its onset, is a crucial public health strategy.
Cardiovascular risk factors, such as hypertension, hyperlipidemia, diabetes, hyperhomocysteinemia, obesity, and smoking, have emerged as substantive risk factors for AD.3 Optimal management of these major risk factors, especially in mid-life, may be a preventive approach against AD. Although detailing the evidence on the impact of managing cardiovascular risk factors to delay or prevent AD is beyond the scope of this article, it is becoming clear that “what is good for the heart is good for the brain.”
Additional modifiable risk factors are related to lifestyle habits, such as physical exercise, mental and social activity, meditation/spiritual activity, and diet. This article reviews the importance of pursuing a healthy lifestyle in delaying AD, with the corresponding levels of evidence that support each specific lifestyle modification. The levels of evidence are defined in Table 1.4
Physical exercise
Twenty-one percent of AD cases in the United States are attributable to physical inactivity.5 In addition to its beneficial effect on metabolic syndrome, in animal and human research, regular exercise has been shown to have direct neuroprotective effects. High levels of physical activity increase hippocampal neurogenesis and neuroplasticity, increase vascular circulation in the brain regions implicated in AD, and modulate inflammatory mediators as well as brain growth factors such as brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1).6
The definition of regular physical exercise varies across the literature, but usually implies aerobic exercise—an ongoing activity sufficient to increase the heart rate and the need for oxygen, sustained for 20 to 30 minutes per session.7 Modalities include household activities and leisure-time activities. In a large prospective cohort study, Scarmeas et al8 categorized leisure-time activities into 3 types:
- light (walking, dancing, calisthenics, golfing, bowling, gardening, horseback riding)
- moderate (bicycling, swimming, hiking, playing tennis)
- vigorous (aerobic dancing, jogging, playing handball).
These types of physical exercise were weighed by the frequency of participation per week. Compared with being physically inactive, low levels of weekly physical activity (0.1 hours of vigorous, 0.8 hours of moderate, or 1.3 hours of light exercise) were associated with a 29% to 41% lower risk of developing AD, while higher weekly physical activity (1.3 hours of vigorous, 2.3 hours of moderate, or 3.8 hours of light exercise) were associated with a 37% to 50% lower risk (level III).8
In another 20-year cohort study, engaging in leisure-time physical activity at least twice a week in mid-life was significantly associated with a reduced risk of AD, after adjusting for age, sex, education, follow-up time, locomotor disorders, apolipoprotein E (ApoE) genotype, vascular disorders, smoking, and alcohol intake (level III).9 Moreover, a systematic review of 29 randomized controlled trials (RCTs) showed that aerobic exercise training, such as brisk walking, jogging, and biking, was associated with improvements in attention, processing speed, executive function, and memory among healthy older adults and those with mild cognitive impairment (MCI; level IA).10
Continue to: From a pathophysiological standpoint...
From a pathophysiological standpoint, higher levels of physical exercise in cognitively intact older adults have been associated with reduced brain amyloid beta deposits, especially in ApoE4 carriers.11 This inverse relationship also has been demonstrated in patients who are presymptomatic who carry 1 of the 3 known autosomal dominant mutations for the familial forms of AD.12
Overall, physicians should recommend that patients—especially those with cardiovascular risk factors that increase their risk for AD—exercise regularly by following the guidelines of the American Heart Association or the American College of Sports Medicine.13 These include muscle-strengthening activities (legs, hips, back, abdomen, shoulders, and arms) at least 2 days/week, in addition to either 30 minutes/day of moderate-intensity aerobic activity such as brisk walking, 5 days/week; or 25 minutes of vigorous aerobic activity such as jogging and running, 3 days/week14 (level IA evidence for overall improvement in cognitive function; level III evidence for AD delay/risk reduction). Neuromotor exercise, such as yoga and tai chi, and flexibility exercise such as muscle stretching, especially after a hot bath, 2 to 3 days/week are also recommended (level III).15
Mental activity
Nineteen percent of AD cases worldwide and 7% in the United States. can be attributed to low educational attainment, which is associated with low brain cognitive reserve.5 Cognitive resilience in later life may be enhanced by building brain reserves through intellectual stimulation, which affects neuronal branching and plasticity.16 Higher levels of complex mental activities measured across the lifespan, such as education, occupation, reading, and writing, are correlated with significantly less hippocampal volume shrinkage over time.17 Frequent participation in mentally stimulating activities—such as listening to the radio; reading newspapers, magazines, or books; playing games (cards, checkers, crosswords or other puzzles); and visiting museums—was associated with an up to 64% reduction in the odds of developing AD in a cohort of cognitively intact older adults followed for 4 years.18 The correlation between mental activity and AD was found to be independent of physical activity, social activity, or baseline cognitive function.19
In a large cohort of cognitively intact older adults (mean age 70), engaging in a mentally stimulating activity (craft activities, computer use, or going to the theater/movies) once to twice a week was significantly associated with a reduced incidence of amnestic MCI.20 Another prospective 21-year study demonstrated a significant reduction in AD risk in community-dwelling cognitively intact older adults (age 75 to 85) who participated in cognitively stimulating activities, such as reading books or newspapers, writing for pleasure, doing crossword puzzles, playing board games or cards, or playing musical instruments, several times/week.21
Growing scientific evidence also suggests that lifelong multilingualism can delay AD onset by 4 to 5 years.22 Multilingualism is associated with greater cognitive reserve, gray matter volume, functional connectivity and white matter density.23
Continue to: Physicians should encourage their patients...
Physicians should encourage their patients to engage in intellectually stimulating activities and creative leisure-time activities several times/week to enhance their cognitive reserves and delay AD onset (level III evidence with respect to AD risk reduction/delay).
Social activity
Social engagement may be an additional protective factor against AD. In a large 4-year prospective study, increased loneliness in cognitively intact older adults doubled the risk of AD.24 Data from the large French cohort PAQUID (Personnes Agées QUID) emphasized the importance of a patient’s social network as a protective factor against AD. In this cohort, the perception of reciprocity in relationships with others (the perception that a person had received more than he or she had given) was associated with a 53% reduction in AD risk (level III).25 In another longitudinal cohort study, social activity was found to decrease the incidence of subjective cognitive decline, which is a prodromal syndrome for MCI and AD (level III).26
A major confounder in studies assessing for social activity is the uncertainty if social withdrawal is a modifiable risk factor or an early manifestation of AD, since apathetic patients with AD tend to be socially withdrawn.27 Another limitation of measuring the impact of social activity relative to AD risk is the difficulty in isolating social activities from activities that have physical and mental activity components, such as leisure-time activities.28
Meditation/spiritual activity
Chronic psychological stress is believed to compromise limbic structures that regulate stress-related behaviors and the memory network, which might explain how being prone to psychological distress may be associated with MCI or AD.29 Cognitive stress may increase the oxidative stress and telomere shortening implicated in the neurodegenerative processes of AD.30 In one study, participants who were highly prone to psychological distress were found to be at 3 times increased risk for developing AD, after adjusting for depression symptoms and physical and mental activities (level III).31 By reducing chronic psychological stress, meditation techniques offer a promising preventive option against AD.
Mindfulness-based interventions (MBI) have gained increased attention in the past decade. They entail directing one’s attention towards the present moment, thereby decreasing ruminative thoughts and stress arousal.32 Recent RCTs have shown that MBI may promote brain health in older adults not only by improving psychological well-being but also by improving attentional control33 and functional connectivity in brain regions implicated in executive functioning,34 as well as by modulating inflammatory processes implicated in AD.35 Furthermore, an RCT of patients diagnosed with MCI found that compared with memory enhancement training, a weekly 60-minute yoga session improved memory and executive functioning.36
Continue to: Kirtan Kriya is a medication technique...
Kirtan Kriya is a meditation technique that is easy to learn and practice by older adults and can improve memory in patients at risk for developing AD.37 However, more rigorous RCTs conducted in larger samples of older adults are needed to better evaluate the effect of all meditation techniques for delaying or preventing AD (level IB with respect to improvement in cognitive functioning/level III for AD delay/risk reduction).38
Spiritual activities, such as going to places of worship or religious meditation, have been associated with a lower prevalence of AD. Attending religious services, gatherings, or retreats involves a social component because these activities often are practiced in groups. They also confer a method of dealing with psychological distress and depression. Additionally, frequent readings of religious texts represents a mentally stimulating activity that may also contribute to delaying/preventing AD (level III).39
Diet
In the past decade, a growing body of evidence has linked diet to cognition. Individuals with a higher intake of calories and fat are at higher risk for developing AD.40 The incidence of AD rose in Japan after the country transitioned to a more Westernized diet.41 A modern Western diet rich in saturated fatty acids and simple carbohydrates may negatively impact hippocampus-mediated functions such as memory and learning, and is associated with an increased risk of AD.42 In contrast with high-glycemic and fatty diets, a “healthy diet” is associated with a decrease in beta-amyloid burden, inflammation, and oxidative stress.43,44
Studies focusing on dietary patterns rather than a single nutrient for delaying or preventing AD have yielded more robust and consistent results.45 In a recent meta-analysis, adhering to a Mediterranean diet—which is rich in fruits and vegetables, whole grains, olive oil, and fish; moderate in some dairy products and wine; and low in red meat—was associated with a decreased risk of AD; this evidence was derived mostly from epidemiologic studies.46 Scarmeas et al8 found that high adherence to the Mediterranean diet was associated with 32% to 40% reduced risk of AD. Combining this diet with physical exercise was associated with an up to 67% reduced risk (level III). The Dietary Approaches to Stop Hypertension (DASH) diet, which is rich in total grains, fruits, vegetables, and dairy products, but low in sodium and sweets, correlated with neurocognitive improvement in patients with hypertension.47 Both the Mediterranean and DASH diets have been associated with better cognitive function48 and slower cognitive decline.49 Thus, an attempt to combine the neuroprotective components from both diets led to the creation of the MIND (Mediterranean-DASH Intervention for Neurodegenerative Delay) diet, which also has been associated with a lower incidence of AD.50
Besides specific diets, some food groups have also been found to promote brain health and may help delay or prevent AD. Berries have the highest amount of antioxidants of all fruit. Among vegetables, tomatoes and green leafy vegetables have the highest amount of nutrients for the brain. Nuts, such as walnuts, which are rich in omega-3 fatty acids, are also considered “power foods” for the brain; however, they should be consumed in moderation because they are also rich in fat. Monounsaturated fatty acids, which are found in olives and olive oil, are also beneficial for the brain. Among the 3 types of omega-3 fatty acids, the most important for cognition is docosahexaenoic acid (DHA) because it constitutes 40% of all fatty acids in the brain. Mainly found in oily fish, DHA has antioxidant and anti-inflammatory properties that may delay or prevent AD. Low levels of DHA have been found in patients with AD.51
Continue to: Curcumin, which is derived from...
Curcumin, which is derived from the curry spice turmeric, is a polyphenol with anti-inflammatory, antioxidant, and anti-amyloid properties that may have a promising role in preventing AD in cognitively intact individuals. Initial trials with curcumin have yielded mixed results on cognition, which was partly related to the low solubility and bioavailability of its formulation.52 However, a recent 18-month double-blind randomized placebo-controlled trial found positive effects on memory and attention, as well as reduction of amyloid plaques and tau tangles deposition in the brain, in non-demented older adults age 51 to 84 who took Theracumin, a highly absorptive oral form of curcumin dispersed with colloidal nanoparticles.53 A longer follow-up is required to determine if curcumin can delay or prevent AD.
Alcohol
The role of alcohol in AD prevention is controversial. Overall, data from prospective studies has shown that low to moderate alcohol consumption may be associated with a reduced risk of AD (level III).54 Alcohol drinking in mid-life showed a U-shaped relationship with cognitive impairment; both abstainers and heavy drinkers had an increased risk of cognitive decline compared with light to moderate drinkers (level III).55 Binge drinking significantly increased the odds of cognitive decline, even after controlling for total alcohol consumption per week.55
The definition of low-to-moderate drinking varies substantially among countries. In addition, the size and amount of alcohol contained in a standard drink may differ.56 According to the National Institute on Alcohol Abuse and Alcoholism (NIAAA),57 moderate drinking is defined as up to 1 drink daily for women and 2 drinks daily for men. Binge drinking involves drinking >4 drinks for women and >5 drinks for men, in approximately 2 hours, at least monthly. In the United States, one standard drink contains 14 grams of pure alcohol, which is usually found in 12 ounces of regular beer, 5 ounces of wine, and 1.5 ounces of distilled spirits (vodka or whiskey).58
In a 5-year prospective Canadian study, having 1 drink weekly (especially wine) was associated with an up to 50% reduced risk of AD (level III).59 In the French cohort PAQUID, mild drinkers (<1 to 2 drinks/day) and moderate drinkers (3 to 4 drinks daily) had a reduced incidence of AD compared with non-drinkers. Wine was the most frequently consumed beverage in this study.60 Other studies have found cognitive benefits from mild to moderate drinking regardless of beverage type.54 However, a recent study that included a 30-year follow-up failed to find a significant protective effect of light drinking over abstinence in terms of hippocampal atrophy.61 Atrophy of the hippocampus was correlated with increasing alcohol amounts in a dose-dependent manner, starting at 7 to 14 drinks/week (level III).61
Research has shown that moderate and heavy alcohol use or misuse can directly induce microglial activation and inflammatory mediators’ release, which induce amyloid beta pathology and leads to brain atrophy.62 Hence, non-drinkers should not be advised to begin drinking, because of the lack of RCTs and the concern that beginning to drink may lead to heavy drinking. All drinkers should be advised to adhere to the NIAAA recommendations.13
Continue to: Coffee/tea
Coffee/tea
Although studies of caffeinated coffee have been heterogeneous and yielded mixed results (beneficial effect vs no effect on delaying cognitive decline), systematic reviews and meta-analyses of cross-sectional, case-control, and longitudinal cohort studies have found a general trend towards a favorable preventive role (level III).63-65 Caffeine exhibits its neuroprotective effect by increasing brain serotonin and acetylcholine, and by stabilizing blood-brain-barrier integrity.66 Moreover, in an animal study, mice given caffeine in their drinking water from young adulthood into older age had lower amyloid beta plasma levels compared with those given decaffeinated water.67 These findings suggest that in humans, 5 cups of regular caffeinated coffee daily, equivalent to 500 mg of caffeine,
An Italian study showed that older adults who don’t or rarely drink coffee (<1 cup daily) and those who recently increased their consumption pattern to >1 cup daily had a higher incidence of MCI than those who habitually consumed 1 to 2 cups daily.69 Therefore, it is not recommended to advise a change in coffee drinking pattern in old age. Older adults who are coffee drinkers should, however, be educated about the association between heavier caffeine intake and anxiety, insomnia, and cardiac arrhythmias.70
Despite its more modest caffeine levels, green tea is rich in polyphenols, which belong to the family of catechins and are characterized by antioxidant and anti-inflammatory properties.71 In a Japanese cohort, higher green tea consumption (up to 1 cup daily) was associated with a decreased incidence of MCI in older adults.72 More studies are needed to confirm its potential preventative role in AD.
Which lifestyle change is the most important?
Focusing on a single lifestyle change may be insufficient, especially because the bulk of evidence for individual interventions comes from population-based cohort studies (level III), rather than strong RCTs with a long follow-up. There is increasing evidence that combining multiple lifestyle modifications may yield better outcomes in maintaining or improving cognition.73
The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), a large, 2-year RCT that included community-dwelling older adults (age 60 to 77) with no diagnosis of major neurocognitive disorder, found that compared with regular health advice, multi-domain interventions reduced cognitive decline and improved overall cognition, executive functioning, and processing speed. The interventions evaluated in this study combined the following 4 modalities74:
- a healthy diet according to the Finnish nutrition recommendations (eating vegetables, fruits, and berries [minimum: 500 g/d], whole grain cereals [several times a day], and fish [2 to 3 times/week]; using low-salt products; consuming fat-free or low-fat milk products; and limiting red meat consumption to <500 g/week
- regular physical exercise tailored for improving muscle strength (1 to 3 times/week) coupled with aerobic exercise (2 to 5 times/week)
- cognitive training, including group sessions that have a social activity component and computer-based individual sessions 3 times/week that target episodic and working memory and executive functioning
- optimal management of cardiovascular risk factors.
Continue to: This multi-domain approach...
This multi-domain approach for lifestyle modification should be strongly recommended to cognitively intact older patients (level IB).
Modeled after the FINGER study, the Alzheimer’s Association U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER) is a 2-year, multicenter, controlled clinical trial aimed at testing the ability of a multidimensional lifestyle intervention to prevent AD in at-risk older adults (age 60 to 79, with established metabolic and cardiovascular risk factors). Interventions include a combination of physical exercise, nutritional counseling and management, cognitive and social stimulation, and improved management of cardiovascular risk factors. Recruitment for this large-scale trial was estimated to begin in January 2019 (NCT03688126).75
On a practical basis, Desai et al13 have proposed a checklist (Table 213) that physicians can use in their routine consultations to improve primary prevention of AD among their older patients.
Bottom Line
Advise patients that pursuing a healthy lifestyle is a key to delaying or preventing Alzheimer’s disease. This involves managing cardiovascular risk factors and a combination of staying physically, mentally, socially, and spiritually active, in addition to adhering to a healthy diet such as the Mediterranean diet.
Related Resources
- Anderson K, Grossberg GT. Brain games to slow cognitive decline in Alzheimer’s disease. J Am Med Dir Assoc. 2014;15(8):536-537.
- Small G, Vorgan G. The memory prescription: Dr. Garry Small’s 14-day plan to keep your brain and body young. New York, NY: Hyperion; 2004.
- Small G, Vorgan G. The Alzheimer’s prevention program; keep your brain healthy for the rest of your life. New York, NY: Workman Publishing Company, Inc.; 2012.
Drug Brand Name
Curcumin • Theracurmin
1. Mehta D, Jackson R, Paul G, et al. Why do trials for Alzheimer’s disease drugs keep failing? A discontinued drug perspective for 2010-2015. Expert Opin Investig Drugs. 2017;26(6):735-739.
2. Norton S, Matthews FE, Barnes DE, et al. Potential for primary prevention of Alzheimer’s disease: an analysis of population-based data. Lancet Neurol. 2014;13(8):788-794.
3. Meng XF, Yu JT, Wang HF, et al. Midlife vascular risk factors and the risk of Alzheimer’s disease: a systematic review and meta-analysis. J Alzheimers Dis. 2014;42(4):1295-1310.
4. Shekelle PG, Woolf SH, Eccles M, et al. Developing clinical guidelines. West J Med. 1999;170(6):348-351.
5. Barnes DE, Yaffe Y. The projected impact of risk factor reduction on Alzheimer’s disease prevalence. Lancet Neurol. 2011;10(9):819-828.
6. Cotman CW, Berchtold NC, Christie LA. Exercise builds brain health: key roles of growth factor cascades and inflammation. Trends Neurosci. 2007;30(9):464-472.
7. Ahlskog JE, Geda YE, Graff-Radford NR, et al. Physical exercise as a preventive or disease-modifying treatment of dementia and brain aging. Mayo Clin Proc. 2011;86(9):876-884.
8. Scarmeas N, Luchsinger JA, Schupf N, et al. Physical activity, diet, and risk of Alzheimer Disease. JAMA. 2009;302(6):627-637.
9. Rovio S, Kåreholt I, Helkala EL, et al. Leisure-time physical activity at midlife and the risk of dementia and Alzheimer’s disease. Lancet Neurol. 2005;4(11):705-711.
10. Smith PJ et al. Aerobic exercise and neurocognitive performance: a meta-analytic review of randomized controlled trials. Psychosom Med. 2010;72(3):239-252.
11. Brown BM, Peiffer JJ, Taddei K, et al. Physical activity and amyloid-beta plasma and brain levels: results from the Australian imaging, biomarkers and lifestyle study of ageing. Mol Psychiatry. 2013;18(8):875-881.
12. Brown BM, Sohrabi HR, Taddei K, et al. Habitual exercise levels are associated with cerebral amyloid load in presymptomatic autosomal dominant Alzheimer’s disease. Alzheimers Dement. 2017;13(11):1197-1206.
13. Desai AK, Grossberg GT, Chibnall JT. Healthy brain aging: a road map. Clin Geriatr Med. 2010;26(1):1-16.
14. Centers for Disease Control and Prevention. Physical activity: how much physical activity do older adults need?
15. Garber CE, Blissmer B, Deschenes MR, et al; American College of Sports Medicine. American College of Sports Medicine position stand. Quantity and quality of exercise for developing and maintaining cardiorespiratory, musculoskeletal, and neuromotor fitness in apparently healthy adults: guidance for prescribing exercise. Med Sci Sports Exerc. 2011;43(7):1334-1359.
16. Livingston G, Sommerlad A, Orgeta V, et al. Dementia prevention, intervention, and care. Lancet. 2017;390(10113);2673-2734.
17. Valenzuela MJ, Sachdev P, Wen W, et al. Lifespan mental activity predicts diminished rate of hippocampal atrophy. PLoS One. 2008;3(7):e2598. doi.org/10.1371/journal.pone.0002598.
18. Wilson RS, Bennett DA, Bienias JL, et al. Cognitive activity and incident AD in a population-based sample of older persons. Neurology. 2002;59(12):1910-1914.
19. Wilson RS, Scherr PA, Schneider JA, et al. Relation of cognitive activity to risk of developing Alzheimer disease. Neurology. 2007;69(20):1911-1920.
20. Krell-Roesch J, Vemuri P, Pink A, et al. Association between mentally stimulating activities in late life and the outcome of incident mild cognitive impairment, with an analysis of the apoe ε4 genotype. JAMA Neurol. 2017;74(3):332-338.
21. Verghese J, Lipton RB, Katz MJ, et al. Leisure activities and the risk of dementia in the elderly. N Engl J Med. 2003;348(25):2508-2516.
22. Klein RM, Christie J, Parkvall M. Does multilingualism affect the incidence of Alzheimer’s disease?: a worldwide analysis by country. SSM Popul Health. 2016;2:463-467.
23. Grundy JG, Anderson JAE, Bialystok E. Neural correlates of cognitive processing in monolinguals and bilinguals. Ann N Y Acad Sci. 2017;1396(1):183-201.
24. Wilson RS, Krueger KR, Arnold SE, et al. Loneliness and risk of Alzheimer disease. Arch Gen Psychiatry. 2007;64(2):234-240.
25. Amieva H, Stoykova R, Matharan F, et al. What aspects of social network are protective for dementia? Not the quantity but the quality of social interactions is protective up to 15 years later. Psychosom Med. 2010;72(9):905-911.
26. Kuiper JS, Oude Voshaar RC, Zuidema SU, et al. The relationship between social functioning and subjective memory complaints in older persons: a population-based longitudinal cohort study. Int J Geriatr Psychiatry. 2017;32(10):1059-1071.
27. Robert P, Onyike CU, Leentjens AF, et al. Proposed diagnostic criteria for apathy in Alzheimer’s disease and other neuropsychiatric disorders. Eur Psychiatry. 2009;24(2):98-104.
28. Marioni RE, Proust-Lima C, Amieva H, et al. Social activity, cognitive decline and dementia risk: a 20-year prospective cohort study. BMC Public Health. 2015;15:1089.
29. Wilson RS, Schneider JA, Boyle PA, et al. Chronic distress and incidence of mild cognitive impairment. Neurology. 2007;68(24):2085-2092.
30. Cai Z, Yan LJ, Ratka A. Telomere shortening and Alzheimer’s disease. Neuromolecular Med. 2013;15(1):25-48.
31. Wilson RS, Arnold SE, Schneider JA, et al. Chronic psychological distress and risk of Alzheimer’s disease in old age. Neuroepidemiology. 2006;27(3):143-153.
32. Epel E, Daubenmier J, Moskowitz JT, et al. Can meditation slow rate of cellular aging? Cognitive stress, mindfulness, and telomeres. Ann N Y Acad Sci. 2009;1172:34-53.
33. Malinowski P, Moore AW, Mead Br, et al. Mindful aging: the effects of regular brief mindfulness practice on electrophysiological markers of cognitive and affective processing in older adults. Mindfulness (N Y). 2017;8(1):78-94.
34. Taren AA, Gianaros PJ, Greco CM, et al. Mindfulness meditation training and executive control network resting state functional connectivity: a randomized controlled trial. Psychosom Med. 2017;79(6):674-683.
35. Fountain-Zaragoza S, Prakash RS. Mindfulness training for healthy aging: impact on attention, well-being, and inflammation. Front in Aging Neurosci. 2017;9:11.
36. Eyre HA, Siddarth P, Acevedo B, et al. A randomized controlled trial of Kundalini yoga in mild cognitive impairment. Int Psychogeriatr. 2017;29(4):557-567.
37. Khalsa DS. Stress, meditation, and Alzheimer’s disease prevention: where the evidence stands. J Alzheimers Dis. 2015;48(1):1-12.
38. Berk L, van Boxtel M, van Os J. Can mindfulness-based interventions influence cognitive functioning in older adults? A review and considerations for future research. Aging Ment Health. 2017;21(11):1113-1120.
39. Hosseini S, Chaurasia A, Oremus M. The effect of religion and spirituality on cognitive function: a systematic review. Gerontologist. 2017. doi: 10.1093/geront/gnx024.
40. Luchsinger JA, Tang MX, Shea S, et al. Caloric intake and the risk of Alzheimer disease. Arch Neurol. 2002;59(8):1258-1263.
41. Grant WB. Trends in diet and Alzheimer’s disease during the nutrition transition in Japan and developing countries. J Alzheimers Dis. 2014;38(3):611-620.
42. Kanoski SE, Davidson TL. Western diet consumption and cognitive impairment: links to hippocampal dysfunction and obesity. Physiol Behav. 2011;103(1):59-68.
43. Hu N, Yu JT, Tan L, et al. Nutrition and the risk of Alzheimer’s disease. Biomed Res Int. 2013;2013:524820. doi: 10.1155/2013/524820.
44. Taylor MK, Sullivan DK, Swerdlow RH, et al. A high-glycemic diet is associated with cerebral amyloid burden in cognitively normal older adults. Am J Clin Nutr. 2017;106(6):1463-1470.
45. van de Rest O, Berendsen AM, Haveman-Nies A, et al. Dietary patterns, cognitive decline, and dementia: a systematic review. Adv Nutr. 2015;6(2):154-168.
46. Petersson SD, Philippou E. Mediterranean diet, cognitive function, and dementia: a systematic review of the evidence. Adv Nutr. 2016;7(5):889-904.
47. Smith PJ, Blumenthal JA, Babyak MA, et al. Effects of the dietary approaches to stop hypertension diet, exercise, and caloric restriction on neurocognition in overweight adults with high blood pressure. Hypertension. 2010;55(6):1331-1338.
48. Wengreen H, Munger RG, Cutler A, et al. Prospective study of dietary approaches to stop hypertension- and Mediterranean-style dietary patterns and age-related cognitive change: the Cache County study on memory, health and aging. Am J Clin Nutr. 2013;98(5):1263-1271.
49. Tangney CC, Li H, Wang Y, et al. Relation of DASH- and Mediterranean-like dietary patterns to cognitive decline in older persons. Neurology. 2014;83(16):1410-1416.
50. Morris MC, Tangney CC, Wang Y, et al. MIND diet associated with reduced incidence of Alzheimer’s disease. Alzheimers Dement. 2015;11(9):1007-1014.
51. Desai AK, Rush J, Naveen L, et al. Nutrition and nutritional supplements to promote brain health. In: Hartman-Stein PE, Rue AL, eds. Enhancing cognitive fitness in adults: a guide to the use and development of community-based programs. New York, NY: Springer; 2011:249-269.
52. Goozee KG, Shah TM, Sohrabi HR, et al. Examining the potential clinical value of curcumin in the prevention and diagnosis of Alzheimer’s disease. Br J Nutr. 2016;115(3):449-465.
53. Small GW, Siddarth P, Li Z, et al. Memory and brain amyloid and tau effects of a bioavailable form of curcumin in non-demented adults: a double-blind, placebo-controlled 18-month trial. Am J Geriatr Psychiatry. 2018;26(3):266-277.
54. Kim JW, Lee DY, Lee BC, et al. Alcohol and cognition in the elderly: a review. Psychiatry Investig. 2012;9(1):8-16.
55. Virtaa JJ, Järvenpää T, Heikkilä K, et al. Midlife alcohol consumption and later risk of cognitive impairment: a twin follow-up study. J Alzheimers Dis. 2010;22(3):939-948.
56. Kerr WC, Stockwell T. Understanding standard drinks and drinking guidelines. Drug and Alcohol Rev. 2012;31(2):200-205.
57. National Institute on Alcohol Abuse and Alcoholism. Drinking levels defined. https://www.niaaa.nih.gov/alcohol-health/overview-alcohol-consumption/moderate-binge-drinking. Accessed December 9, 2017.
58. National Institute on Alcohol Abuse and Alcoholism. What is a standard drink? https://www.niaaa.nih.gov/alcohol-health/overview-alcohol-consumption/what-standard-drink. Accessed November 9, 2017.
59. Lindsay J, Laurin D, Verreault R, et al. Risk factors for Alzheimer’s disease: a prospective analysis from the Canadian study of health and aging. Am J Epidemiol. 2002;156(5):445-453.
60. Orgogozo JM, Dartigues JF, Lafont S, et al. Wine consumption and dementia in the elderly: a prospective community study in the Bordeaux area. Rev Neurol (Paris). 1997;153(3):185-192.
61. Topiwala A, Allan CL, Valkanova V, et al. Moderate alcohol consumption as risk factor for adverse brain outcomes and cognitive decline: longitudinal cohort study. BMJ. 2017;357.
62. Venkataraman A, Kalk N, Sewell G, et al. Alcohol and Alzheimer’s disease-does alcohol dependence contribute to beta-amyloid deposition, neuroinflammation and neurodegeneration in Alzheimer’s Disease? Alcohol Alcohol. 2017;52(2):151-158.
63. Ma QP, Huang C, Cui QY, et al. Meta-analysis of the association between tea intake and the risk of cognitive disorders. PLoS One. 2016;11(11):e0165861. doi: 10.1371/journal.pone.0165861.
64. Santos C, Costa J, Santos J, et al. Caffeine intake and dementia: systematic review and meta-analysis. J Alzheimers Dis. 2010;20(Suppl 1):S187-204.
65. Panza F, Solfrizzi V, Barulli MR, et al. Coffee, tea, and caffeine consumption and prevention of late-life cognitive decline and dementia: a systematic review. J Nutr Health Aging. 2015;19(3):313-328.
66. Wierzejska R. Can coffee consumption lower the risk of Alzheimer’s disease and Parkinson’s disease? A literature review. Arch Med Sci. 2017;13(3):507-514.
67. Arendash GW, Cao C. Caffeine and coffee as therapeutics against Alzheimer’s disease. J Alzheimers Dis. 2010;20 (Suppl 1):S117-S126.
68. Eskelinen MH, Ngandu T, Tuomilehto J, et al. Midlife coffee and tea drinking and the risk of late-life dementia: a population-based CAIDE study. J Alzheimers Dis. 2009;16(1):85-91.
69. Solfrizzi V, Panza F, Imbimbo BP, et al. Coffee consumption habits and the risk of mild cognitive impairment: the Italian longitudinal study on aging. J Alzheimers Dis. 2015;47(4):889-899.
70. Vittoria Mattioli. Beverages of daily life: impact of caffeine on atrial fibrillation. J Atr Fibrillation. 2014;7(2):1133.
71. Chacko SM, Thambi PT, Kuttan R, et al. Beneficial effects of green tea: a literature review. Chin Med. 2010;5:13.
72. Noguchi-Shinohara M, Yuki S, Dohmoto C, et al. Consumption of green tea, but not black tea or coffee, is associated with reduced risk of cognitive decline. PLoS One. 2014;9(5):e96013. doi: 10.1371/journal.pone.0096013.
73. Schneider N, Yvon C. A review of multidomain interventions to support healthy cognitive ageing. J Nutr Health Aging. 2013;17(3):252-257.
74. Ngandu T, Lehitsalo J, Solomon A, et al. A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial. Lancet. 2015;385(9984):2255-2263.
75. U.S. National Library of Medicing. ClinicalTrials.gov. U.S. study to protect brain health through lifestyle intervention to reduce risk (POINTER). https://clinicaltrials.gov/ct2/show/NCT03688126?term=pointer&cond=Alzheimer+Disease&rank=1. Published September 28, 2018. Accessed November 3, 2018.
1. Mehta D, Jackson R, Paul G, et al. Why do trials for Alzheimer’s disease drugs keep failing? A discontinued drug perspective for 2010-2015. Expert Opin Investig Drugs. 2017;26(6):735-739.
2. Norton S, Matthews FE, Barnes DE, et al. Potential for primary prevention of Alzheimer’s disease: an analysis of population-based data. Lancet Neurol. 2014;13(8):788-794.
3. Meng XF, Yu JT, Wang HF, et al. Midlife vascular risk factors and the risk of Alzheimer’s disease: a systematic review and meta-analysis. J Alzheimers Dis. 2014;42(4):1295-1310.
4. Shekelle PG, Woolf SH, Eccles M, et al. Developing clinical guidelines. West J Med. 1999;170(6):348-351.
5. Barnes DE, Yaffe Y. The projected impact of risk factor reduction on Alzheimer’s disease prevalence. Lancet Neurol. 2011;10(9):819-828.
6. Cotman CW, Berchtold NC, Christie LA. Exercise builds brain health: key roles of growth factor cascades and inflammation. Trends Neurosci. 2007;30(9):464-472.
7. Ahlskog JE, Geda YE, Graff-Radford NR, et al. Physical exercise as a preventive or disease-modifying treatment of dementia and brain aging. Mayo Clin Proc. 2011;86(9):876-884.
8. Scarmeas N, Luchsinger JA, Schupf N, et al. Physical activity, diet, and risk of Alzheimer Disease. JAMA. 2009;302(6):627-637.
9. Rovio S, Kåreholt I, Helkala EL, et al. Leisure-time physical activity at midlife and the risk of dementia and Alzheimer’s disease. Lancet Neurol. 2005;4(11):705-711.
10. Smith PJ et al. Aerobic exercise and neurocognitive performance: a meta-analytic review of randomized controlled trials. Psychosom Med. 2010;72(3):239-252.
11. Brown BM, Peiffer JJ, Taddei K, et al. Physical activity and amyloid-beta plasma and brain levels: results from the Australian imaging, biomarkers and lifestyle study of ageing. Mol Psychiatry. 2013;18(8):875-881.
12. Brown BM, Sohrabi HR, Taddei K, et al. Habitual exercise levels are associated with cerebral amyloid load in presymptomatic autosomal dominant Alzheimer’s disease. Alzheimers Dement. 2017;13(11):1197-1206.
13. Desai AK, Grossberg GT, Chibnall JT. Healthy brain aging: a road map. Clin Geriatr Med. 2010;26(1):1-16.
14. Centers for Disease Control and Prevention. Physical activity: how much physical activity do older adults need?
15. Garber CE, Blissmer B, Deschenes MR, et al; American College of Sports Medicine. American College of Sports Medicine position stand. Quantity and quality of exercise for developing and maintaining cardiorespiratory, musculoskeletal, and neuromotor fitness in apparently healthy adults: guidance for prescribing exercise. Med Sci Sports Exerc. 2011;43(7):1334-1359.
16. Livingston G, Sommerlad A, Orgeta V, et al. Dementia prevention, intervention, and care. Lancet. 2017;390(10113);2673-2734.
17. Valenzuela MJ, Sachdev P, Wen W, et al. Lifespan mental activity predicts diminished rate of hippocampal atrophy. PLoS One. 2008;3(7):e2598. doi.org/10.1371/journal.pone.0002598.
18. Wilson RS, Bennett DA, Bienias JL, et al. Cognitive activity and incident AD in a population-based sample of older persons. Neurology. 2002;59(12):1910-1914.
19. Wilson RS, Scherr PA, Schneider JA, et al. Relation of cognitive activity to risk of developing Alzheimer disease. Neurology. 2007;69(20):1911-1920.
20. Krell-Roesch J, Vemuri P, Pink A, et al. Association between mentally stimulating activities in late life and the outcome of incident mild cognitive impairment, with an analysis of the apoe ε4 genotype. JAMA Neurol. 2017;74(3):332-338.
21. Verghese J, Lipton RB, Katz MJ, et al. Leisure activities and the risk of dementia in the elderly. N Engl J Med. 2003;348(25):2508-2516.
22. Klein RM, Christie J, Parkvall M. Does multilingualism affect the incidence of Alzheimer’s disease?: a worldwide analysis by country. SSM Popul Health. 2016;2:463-467.
23. Grundy JG, Anderson JAE, Bialystok E. Neural correlates of cognitive processing in monolinguals and bilinguals. Ann N Y Acad Sci. 2017;1396(1):183-201.
24. Wilson RS, Krueger KR, Arnold SE, et al. Loneliness and risk of Alzheimer disease. Arch Gen Psychiatry. 2007;64(2):234-240.
25. Amieva H, Stoykova R, Matharan F, et al. What aspects of social network are protective for dementia? Not the quantity but the quality of social interactions is protective up to 15 years later. Psychosom Med. 2010;72(9):905-911.
26. Kuiper JS, Oude Voshaar RC, Zuidema SU, et al. The relationship between social functioning and subjective memory complaints in older persons: a population-based longitudinal cohort study. Int J Geriatr Psychiatry. 2017;32(10):1059-1071.
27. Robert P, Onyike CU, Leentjens AF, et al. Proposed diagnostic criteria for apathy in Alzheimer’s disease and other neuropsychiatric disorders. Eur Psychiatry. 2009;24(2):98-104.
28. Marioni RE, Proust-Lima C, Amieva H, et al. Social activity, cognitive decline and dementia risk: a 20-year prospective cohort study. BMC Public Health. 2015;15:1089.
29. Wilson RS, Schneider JA, Boyle PA, et al. Chronic distress and incidence of mild cognitive impairment. Neurology. 2007;68(24):2085-2092.
30. Cai Z, Yan LJ, Ratka A. Telomere shortening and Alzheimer’s disease. Neuromolecular Med. 2013;15(1):25-48.
31. Wilson RS, Arnold SE, Schneider JA, et al. Chronic psychological distress and risk of Alzheimer’s disease in old age. Neuroepidemiology. 2006;27(3):143-153.
32. Epel E, Daubenmier J, Moskowitz JT, et al. Can meditation slow rate of cellular aging? Cognitive stress, mindfulness, and telomeres. Ann N Y Acad Sci. 2009;1172:34-53.
33. Malinowski P, Moore AW, Mead Br, et al. Mindful aging: the effects of regular brief mindfulness practice on electrophysiological markers of cognitive and affective processing in older adults. Mindfulness (N Y). 2017;8(1):78-94.
34. Taren AA, Gianaros PJ, Greco CM, et al. Mindfulness meditation training and executive control network resting state functional connectivity: a randomized controlled trial. Psychosom Med. 2017;79(6):674-683.
35. Fountain-Zaragoza S, Prakash RS. Mindfulness training for healthy aging: impact on attention, well-being, and inflammation. Front in Aging Neurosci. 2017;9:11.
36. Eyre HA, Siddarth P, Acevedo B, et al. A randomized controlled trial of Kundalini yoga in mild cognitive impairment. Int Psychogeriatr. 2017;29(4):557-567.
37. Khalsa DS. Stress, meditation, and Alzheimer’s disease prevention: where the evidence stands. J Alzheimers Dis. 2015;48(1):1-12.
38. Berk L, van Boxtel M, van Os J. Can mindfulness-based interventions influence cognitive functioning in older adults? A review and considerations for future research. Aging Ment Health. 2017;21(11):1113-1120.
39. Hosseini S, Chaurasia A, Oremus M. The effect of religion and spirituality on cognitive function: a systematic review. Gerontologist. 2017. doi: 10.1093/geront/gnx024.
40. Luchsinger JA, Tang MX, Shea S, et al. Caloric intake and the risk of Alzheimer disease. Arch Neurol. 2002;59(8):1258-1263.
41. Grant WB. Trends in diet and Alzheimer’s disease during the nutrition transition in Japan and developing countries. J Alzheimers Dis. 2014;38(3):611-620.
42. Kanoski SE, Davidson TL. Western diet consumption and cognitive impairment: links to hippocampal dysfunction and obesity. Physiol Behav. 2011;103(1):59-68.
43. Hu N, Yu JT, Tan L, et al. Nutrition and the risk of Alzheimer’s disease. Biomed Res Int. 2013;2013:524820. doi: 10.1155/2013/524820.
44. Taylor MK, Sullivan DK, Swerdlow RH, et al. A high-glycemic diet is associated with cerebral amyloid burden in cognitively normal older adults. Am J Clin Nutr. 2017;106(6):1463-1470.
45. van de Rest O, Berendsen AM, Haveman-Nies A, et al. Dietary patterns, cognitive decline, and dementia: a systematic review. Adv Nutr. 2015;6(2):154-168.
46. Petersson SD, Philippou E. Mediterranean diet, cognitive function, and dementia: a systematic review of the evidence. Adv Nutr. 2016;7(5):889-904.
47. Smith PJ, Blumenthal JA, Babyak MA, et al. Effects of the dietary approaches to stop hypertension diet, exercise, and caloric restriction on neurocognition in overweight adults with high blood pressure. Hypertension. 2010;55(6):1331-1338.
48. Wengreen H, Munger RG, Cutler A, et al. Prospective study of dietary approaches to stop hypertension- and Mediterranean-style dietary patterns and age-related cognitive change: the Cache County study on memory, health and aging. Am J Clin Nutr. 2013;98(5):1263-1271.
49. Tangney CC, Li H, Wang Y, et al. Relation of DASH- and Mediterranean-like dietary patterns to cognitive decline in older persons. Neurology. 2014;83(16):1410-1416.
50. Morris MC, Tangney CC, Wang Y, et al. MIND diet associated with reduced incidence of Alzheimer’s disease. Alzheimers Dement. 2015;11(9):1007-1014.
51. Desai AK, Rush J, Naveen L, et al. Nutrition and nutritional supplements to promote brain health. In: Hartman-Stein PE, Rue AL, eds. Enhancing cognitive fitness in adults: a guide to the use and development of community-based programs. New York, NY: Springer; 2011:249-269.
52. Goozee KG, Shah TM, Sohrabi HR, et al. Examining the potential clinical value of curcumin in the prevention and diagnosis of Alzheimer’s disease. Br J Nutr. 2016;115(3):449-465.
53. Small GW, Siddarth P, Li Z, et al. Memory and brain amyloid and tau effects of a bioavailable form of curcumin in non-demented adults: a double-blind, placebo-controlled 18-month trial. Am J Geriatr Psychiatry. 2018;26(3):266-277.
54. Kim JW, Lee DY, Lee BC, et al. Alcohol and cognition in the elderly: a review. Psychiatry Investig. 2012;9(1):8-16.
55. Virtaa JJ, Järvenpää T, Heikkilä K, et al. Midlife alcohol consumption and later risk of cognitive impairment: a twin follow-up study. J Alzheimers Dis. 2010;22(3):939-948.
56. Kerr WC, Stockwell T. Understanding standard drinks and drinking guidelines. Drug and Alcohol Rev. 2012;31(2):200-205.
57. National Institute on Alcohol Abuse and Alcoholism. Drinking levels defined. https://www.niaaa.nih.gov/alcohol-health/overview-alcohol-consumption/moderate-binge-drinking. Accessed December 9, 2017.
58. National Institute on Alcohol Abuse and Alcoholism. What is a standard drink? https://www.niaaa.nih.gov/alcohol-health/overview-alcohol-consumption/what-standard-drink. Accessed November 9, 2017.
59. Lindsay J, Laurin D, Verreault R, et al. Risk factors for Alzheimer’s disease: a prospective analysis from the Canadian study of health and aging. Am J Epidemiol. 2002;156(5):445-453.
60. Orgogozo JM, Dartigues JF, Lafont S, et al. Wine consumption and dementia in the elderly: a prospective community study in the Bordeaux area. Rev Neurol (Paris). 1997;153(3):185-192.
61. Topiwala A, Allan CL, Valkanova V, et al. Moderate alcohol consumption as risk factor for adverse brain outcomes and cognitive decline: longitudinal cohort study. BMJ. 2017;357.
62. Venkataraman A, Kalk N, Sewell G, et al. Alcohol and Alzheimer’s disease-does alcohol dependence contribute to beta-amyloid deposition, neuroinflammation and neurodegeneration in Alzheimer’s Disease? Alcohol Alcohol. 2017;52(2):151-158.
63. Ma QP, Huang C, Cui QY, et al. Meta-analysis of the association between tea intake and the risk of cognitive disorders. PLoS One. 2016;11(11):e0165861. doi: 10.1371/journal.pone.0165861.
64. Santos C, Costa J, Santos J, et al. Caffeine intake and dementia: systematic review and meta-analysis. J Alzheimers Dis. 2010;20(Suppl 1):S187-204.
65. Panza F, Solfrizzi V, Barulli MR, et al. Coffee, tea, and caffeine consumption and prevention of late-life cognitive decline and dementia: a systematic review. J Nutr Health Aging. 2015;19(3):313-328.
66. Wierzejska R. Can coffee consumption lower the risk of Alzheimer’s disease and Parkinson’s disease? A literature review. Arch Med Sci. 2017;13(3):507-514.
67. Arendash GW, Cao C. Caffeine and coffee as therapeutics against Alzheimer’s disease. J Alzheimers Dis. 2010;20 (Suppl 1):S117-S126.
68. Eskelinen MH, Ngandu T, Tuomilehto J, et al. Midlife coffee and tea drinking and the risk of late-life dementia: a population-based CAIDE study. J Alzheimers Dis. 2009;16(1):85-91.
69. Solfrizzi V, Panza F, Imbimbo BP, et al. Coffee consumption habits and the risk of mild cognitive impairment: the Italian longitudinal study on aging. J Alzheimers Dis. 2015;47(4):889-899.
70. Vittoria Mattioli. Beverages of daily life: impact of caffeine on atrial fibrillation. J Atr Fibrillation. 2014;7(2):1133.
71. Chacko SM, Thambi PT, Kuttan R, et al. Beneficial effects of green tea: a literature review. Chin Med. 2010;5:13.
72. Noguchi-Shinohara M, Yuki S, Dohmoto C, et al. Consumption of green tea, but not black tea or coffee, is associated with reduced risk of cognitive decline. PLoS One. 2014;9(5):e96013. doi: 10.1371/journal.pone.0096013.
73. Schneider N, Yvon C. A review of multidomain interventions to support healthy cognitive ageing. J Nutr Health Aging. 2013;17(3):252-257.
74. Ngandu T, Lehitsalo J, Solomon A, et al. A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial. Lancet. 2015;385(9984):2255-2263.
75. U.S. National Library of Medicing. ClinicalTrials.gov. U.S. study to protect brain health through lifestyle intervention to reduce risk (POINTER). https://clinicaltrials.gov/ct2/show/NCT03688126?term=pointer&cond=Alzheimer+Disease&rank=1. Published September 28, 2018. Accessed November 3, 2018.
No change in postoperative pain with restrictive opioid protocol
Opioid prescriptions after gynecologic surgery can be significantly reduced without impacting postoperative pain scores or complication rates, according to a paper published in JAMA Network Open.
A tertiary care comprehensive care center implemented an ultrarestrictive opioid prescription protocol (UROPP) then evaluated the outcomes in a case-control study involving 605 women undergoing gynecologic surgery, compared with 626 controls treated before implementation of the new protocol.
The ultrarestrictive protocol was prompted by frequent inquiries from patients who had used very little of their prescribed opioids after surgery and wanted to know what to do with the unused pills.
The new protocol involved a short preoperative counseling session about postoperative pain management. Following that, ambulatory surgery, minimally invasive surgery, or laparotomy patients were prescribed a 7-day supply of nonopioid pain relief. Laparotomy patients were also prescribed a 3-day supply of an oral opioid.
Any patients who required more than five opioid doses in the 24 hours before discharge were also prescribed a 3-day supply of opioid pain medication as needed, and all patients had the option of requesting an additional 3-day opioid refill.
Researchers saw no significant differences between the two groups in mean postoperative pain scores 2 weeks after surgery, and a similar number of patients in each group requested an opioid refill. There was also no significant difference in the number of postoperative complications between groups.
Implementation of the ultrarestrictive protocol was associated with significant declines in the mean number of opioid pills prescribed dropped from 31.7 to 3.5 in all surgical cases, from 43.6 to 12.1 in the laparotomy group, from 38.4 to 1.3 in the minimally invasive surgery group, and from 13.9 to 0.2 in patients who underwent ambulatory surgery.
“These data suggest that the implementation of a UROPP in a large surgical service is feasible and safe and was associated with a significantly decreased number of opioids dispensed during the perioperative period, particularly among opioid-naive patients,” wrote Jaron Mark, MD, of the department of gynecologic oncology at Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., and his coauthors. “The opioid-sparing effect was also marked and statistically significant in the laparotomy group, where most patients remained physically active and recovered well with no negative sequelae or elevated pain score after surgery.”
The researchers also noted that patients who were discharged home with an opioid prescription were more likely to call and request a refill within 30 days, compared with patients who did not receive opioids at discharge.
The study was supported by the Roswell Park Comprehensive Cancer Center, the National Cancer Institute and the Roswell Park Alliance Foundation. Two authors reported receiving fees and nonfinancial support from the private sector unrelated to the study.
SOURCE: Mark J et al. JAMA Netw Open. 2018 Dec 7. doi: 10.1001/jamanetworkopen.2018.5452.
The ultrarestrictive postoperative opioid prescribing protocol described in this study is a promising strategy for reducing opioid prescribing without increasing pain and limiting the potential for diversion and misuse of opioids. An important element of this protocol is the preoperative counseling, because setting patient expectations is likely to be an important factor in improving postoperative outcomes.
It is also worth noting that this study focused on patients undergoing major and minor gynecologic surgery, so more research is needed to explore these outcomes particularly among patients undergoing procedures that may be associated with a higher risk of persistent postoperative pain and/or opioid use. It is also a management strategy explored in patients at low risk of chronic postoperative opioid use, but a similar pathway should be developed and explored in more high-risk patients.
Dr. Jennifer M. Hah is from the department of anesthesiology, perioperative, and pain management at Stanford University (Calif.). These comments are taken from an accompanying editorial (JAMA Network Open. 2018 Dec 7. doi: 10.1001/jamanetworkopen.2018.5432). No conflicts of interest were reported.
The ultrarestrictive postoperative opioid prescribing protocol described in this study is a promising strategy for reducing opioid prescribing without increasing pain and limiting the potential for diversion and misuse of opioids. An important element of this protocol is the preoperative counseling, because setting patient expectations is likely to be an important factor in improving postoperative outcomes.
It is also worth noting that this study focused on patients undergoing major and minor gynecologic surgery, so more research is needed to explore these outcomes particularly among patients undergoing procedures that may be associated with a higher risk of persistent postoperative pain and/or opioid use. It is also a management strategy explored in patients at low risk of chronic postoperative opioid use, but a similar pathway should be developed and explored in more high-risk patients.
Dr. Jennifer M. Hah is from the department of anesthesiology, perioperative, and pain management at Stanford University (Calif.). These comments are taken from an accompanying editorial (JAMA Network Open. 2018 Dec 7. doi: 10.1001/jamanetworkopen.2018.5432). No conflicts of interest were reported.
The ultrarestrictive postoperative opioid prescribing protocol described in this study is a promising strategy for reducing opioid prescribing without increasing pain and limiting the potential for diversion and misuse of opioids. An important element of this protocol is the preoperative counseling, because setting patient expectations is likely to be an important factor in improving postoperative outcomes.
It is also worth noting that this study focused on patients undergoing major and minor gynecologic surgery, so more research is needed to explore these outcomes particularly among patients undergoing procedures that may be associated with a higher risk of persistent postoperative pain and/or opioid use. It is also a management strategy explored in patients at low risk of chronic postoperative opioid use, but a similar pathway should be developed and explored in more high-risk patients.
Dr. Jennifer M. Hah is from the department of anesthesiology, perioperative, and pain management at Stanford University (Calif.). These comments are taken from an accompanying editorial (JAMA Network Open. 2018 Dec 7. doi: 10.1001/jamanetworkopen.2018.5432). No conflicts of interest were reported.
Opioid prescriptions after gynecologic surgery can be significantly reduced without impacting postoperative pain scores or complication rates, according to a paper published in JAMA Network Open.
A tertiary care comprehensive care center implemented an ultrarestrictive opioid prescription protocol (UROPP) then evaluated the outcomes in a case-control study involving 605 women undergoing gynecologic surgery, compared with 626 controls treated before implementation of the new protocol.
The ultrarestrictive protocol was prompted by frequent inquiries from patients who had used very little of their prescribed opioids after surgery and wanted to know what to do with the unused pills.
The new protocol involved a short preoperative counseling session about postoperative pain management. Following that, ambulatory surgery, minimally invasive surgery, or laparotomy patients were prescribed a 7-day supply of nonopioid pain relief. Laparotomy patients were also prescribed a 3-day supply of an oral opioid.
Any patients who required more than five opioid doses in the 24 hours before discharge were also prescribed a 3-day supply of opioid pain medication as needed, and all patients had the option of requesting an additional 3-day opioid refill.
Researchers saw no significant differences between the two groups in mean postoperative pain scores 2 weeks after surgery, and a similar number of patients in each group requested an opioid refill. There was also no significant difference in the number of postoperative complications between groups.
Implementation of the ultrarestrictive protocol was associated with significant declines in the mean number of opioid pills prescribed dropped from 31.7 to 3.5 in all surgical cases, from 43.6 to 12.1 in the laparotomy group, from 38.4 to 1.3 in the minimally invasive surgery group, and from 13.9 to 0.2 in patients who underwent ambulatory surgery.
“These data suggest that the implementation of a UROPP in a large surgical service is feasible and safe and was associated with a significantly decreased number of opioids dispensed during the perioperative period, particularly among opioid-naive patients,” wrote Jaron Mark, MD, of the department of gynecologic oncology at Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., and his coauthors. “The opioid-sparing effect was also marked and statistically significant in the laparotomy group, where most patients remained physically active and recovered well with no negative sequelae or elevated pain score after surgery.”
The researchers also noted that patients who were discharged home with an opioid prescription were more likely to call and request a refill within 30 days, compared with patients who did not receive opioids at discharge.
The study was supported by the Roswell Park Comprehensive Cancer Center, the National Cancer Institute and the Roswell Park Alliance Foundation. Two authors reported receiving fees and nonfinancial support from the private sector unrelated to the study.
SOURCE: Mark J et al. JAMA Netw Open. 2018 Dec 7. doi: 10.1001/jamanetworkopen.2018.5452.
Opioid prescriptions after gynecologic surgery can be significantly reduced without impacting postoperative pain scores or complication rates, according to a paper published in JAMA Network Open.
A tertiary care comprehensive care center implemented an ultrarestrictive opioid prescription protocol (UROPP) then evaluated the outcomes in a case-control study involving 605 women undergoing gynecologic surgery, compared with 626 controls treated before implementation of the new protocol.
The ultrarestrictive protocol was prompted by frequent inquiries from patients who had used very little of their prescribed opioids after surgery and wanted to know what to do with the unused pills.
The new protocol involved a short preoperative counseling session about postoperative pain management. Following that, ambulatory surgery, minimally invasive surgery, or laparotomy patients were prescribed a 7-day supply of nonopioid pain relief. Laparotomy patients were also prescribed a 3-day supply of an oral opioid.
Any patients who required more than five opioid doses in the 24 hours before discharge were also prescribed a 3-day supply of opioid pain medication as needed, and all patients had the option of requesting an additional 3-day opioid refill.
Researchers saw no significant differences between the two groups in mean postoperative pain scores 2 weeks after surgery, and a similar number of patients in each group requested an opioid refill. There was also no significant difference in the number of postoperative complications between groups.
Implementation of the ultrarestrictive protocol was associated with significant declines in the mean number of opioid pills prescribed dropped from 31.7 to 3.5 in all surgical cases, from 43.6 to 12.1 in the laparotomy group, from 38.4 to 1.3 in the minimally invasive surgery group, and from 13.9 to 0.2 in patients who underwent ambulatory surgery.
“These data suggest that the implementation of a UROPP in a large surgical service is feasible and safe and was associated with a significantly decreased number of opioids dispensed during the perioperative period, particularly among opioid-naive patients,” wrote Jaron Mark, MD, of the department of gynecologic oncology at Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., and his coauthors. “The opioid-sparing effect was also marked and statistically significant in the laparotomy group, where most patients remained physically active and recovered well with no negative sequelae or elevated pain score after surgery.”
The researchers also noted that patients who were discharged home with an opioid prescription were more likely to call and request a refill within 30 days, compared with patients who did not receive opioids at discharge.
The study was supported by the Roswell Park Comprehensive Cancer Center, the National Cancer Institute and the Roswell Park Alliance Foundation. Two authors reported receiving fees and nonfinancial support from the private sector unrelated to the study.
SOURCE: Mark J et al. JAMA Netw Open. 2018 Dec 7. doi: 10.1001/jamanetworkopen.2018.5452.
Key clinical point: A ultrarestrictive postoperative opioid protocol is not associated with higher postoperative pain scores.
Major finding: The protocol achieves significant reductions in opioid use.
Study details: A case-control study in 1,231 women undergoing gynecologic surgery.
Disclosures: The study was supported by the Roswell Park Comprehensive Cancer Center, the National Cancer Institute, and the Roswell Park Alliance Foundation. Two authors reported receiving fees and nonfinancial support from the private sector unrelated to the study.
Source: Mark J et al. JAMA Netw Open. 2018 Dec 7. doi: 10.1001/jamanetworkopen.2018.5452.