User login
Long COVID neuropsychiatric deficits greater than expected
NEW ORLEANS – , adding to mounting evidence of the significant toll the chronic condition can have on mental health.
“Many clinicians have observed the symptoms we describe in this study, however this report is among the first which identify the specific deficits using neuropsychological testing to better characterize the syndrome,” Sean T. Lynch, MD, first author of a study on the issue presented at the annual meeting of the American Psychiatric Association, said in an interview.
Dr. Lynch, of the department of psychiatry, Westchester Medical Center Health System, Valhalla, N.Y., and his colleagues enrolled 60 participants who had experienced acute COVID-19 disease 6-8 months earlier and had undergone neuropsychological, psychiatric, medical, functional, and quality-of-life assessments. Results from the study were published online in the Journal of the Academy of Consultation–Liaison Psychiatry (2022 Jan 25. doi: 10.1016/j.jaclp.2022.01.003).
Among the study participants, 32 were seeking treatment for brain fog in a clinical program for survivors of COVID-19, while the remaining 28 were part of an ongoing longitudinal investigation of neuropsychological, medical, and psychiatric sequelae of COVID-19, but were not seeking care for the persistent symptoms.
Assessments for neurocognitive impairment included a battery of tests used in infectious and other diseases, including the Test of Premorbid Function, the Patient Assessment of Own Function, the Trail Making Test parts A and B, the Stroop Color and Word Test, and others.
Overall, the battery of assessments showed that 37 (62%) of participants had neuropsychological test impairment, with results below the 16th percentile in two tests, while 16 (27%) showed scores indicative of severe impairment (below the second percentile in at least one test and below the 16th percentile in one test).
Those reporting brain fog had scores that were even lower than expected on tests of attention, processing speed, memory, and executive function. And among those reporting brain fog, significantly more had scores reflecting severe impairment compared with the controls (38% vs. 14%; P < .04).
“Based on what we’ve observed in our patients and what others have previously reported, we did expect to find some impairment in this study sample,” Dr. Lynch noted.
“However, we were surprised to find that 27% of the study sample had extremely low neuropsychological test scores, meaning that they scored at least two standard deviations below the expected score on at least one neuropsychological test based on their age and level of education.”
The brain fog group also reported significantly higher levels of depression, fatigue, PTSD, and functional difficulties, and lower quality of life.
Severe impairment on the neuropsychological tests correlated with the extent of acute COVID-19 symptoms, as well as depression scores, number of medical comorbidities, and subjective cognitive complaints.
An analysis of serum levels of the inflammatory markers among 50 of the 60 participants showed that 45% of the patients had an elevated IL-6, 20% had elevated TNF-alpha, and 41% had elevated CRP, compared with reference ranges.
IL-6 levels were found to correlate with acute COVID-19 symptoms, the number of medical comorbidities, fatigue, and measures of executive function, while C-reactive protein (CRP) correlated with current COVID-19 symptoms and depression scores.
In terms of clinical factors that might predict low neuropsychological test scores, Dr. Lynch noted that the “markers that we found to be significant included severity of acute COVID-19 illness, current post-COVID-19 symptoms, measures of depression and anxiety, level of fatigue, and number of medical comorbidities.”
Dr. Lynch noted that the ongoing study will include up to 18-month follow-ups that are currently underway. “The [follow-ups] will examine if symptoms improve over time and evaluate if any intervention that took place was successful,” he said.
Survey supports findings
The detrimental effects of mental health symptoms in long COVID were further supported in another study at the APA meeting, an online survey of 787 survivors of acute COVID-19.
In the community survey, presented by Michael Van Ameringen, MD, a professor in the department of psychiatry and behavioral neurosciences at McMaster University, in Hamilton, Ont., all respondents (100%) reported having persistent symptoms of the virus, and as many as 68% indicated that they had not returned to normal functioning, despite only 15% of the respondents having been hospitalized with COVID-19.
A large proportion showed significant depression, anxiety, and posttraumatic stress disorder (PTSD), and the most commonly reported persistent symptoms were fatigue in 75.9% of respondents, brain fog in 67.9%, concentration difficulties in 61.1%, and weakness in 51.2%.
As many as 88.2% of patients said they experienced persistent neurocognitive symptoms, with poor memory and concentration; 56% reported problems with word finding; and 54.1% had slowed thinking.
The respondents showed high rates of anxiety (41.7%) as well as depression (61.4%) as determined by scores above 9 on the Generalized Anxiety Disorder–7 (GAD-7) and Patient Health Questionnaires (PHQ-9).
As many as 40.5% of respondents showed probable PTSD, with scores above 30 on the PTSD checklist (PCL-5). Their mean resilience score on the Brief Resilient Coping Scale was 13.5, suggesting low resilience.
Among the respondents, 43.3% said they had received past treatment for mental health, while 33.5% were currently receiving mental health treatment.
Dr. Van Ameringen noted the important limitation of the study being an online survey with no control group, but said the responses nevertheless raise the question of the role of prior psychiatric disorders in long COVID.
“In our sample, 40% of respondents had a past psychiatric history, so you wonder if that also makes you vulnerable to long COVID,” he said in an interview.
“About a third were getting psychiatric help, but I think the more impaired you are, the more likely you are to seek help.”
Those who were hospitalized with COVID-19 were at a higher risk of PTSD compared with those not hospitalized (P < .001), as were those under the age of 30 (P < .05) or between 31 and 50 vs. over 50 (P < .01).
Dr. Van Ameringen noted that the survey’s high rate of subjects who had not returned to normal functioning was especially striking.
“This is not a minor issue – these are people who are no longer functioning in society,” he said.
In pandemics, the brain tends to be ‘overlooked’
Further addressing the neurological effects of COVID-19 at the APA meeting, Avindra Nath, MD, clinical director of the National Institutes of Neurologic Disorders and Stroke in Bethesda, Md., noted that the persisting cognitive and psychiatric symptoms after illness, such as brain fog and depression and anxiety, are not necessarily unique to COVID-19.
“We have seen this before,” he said. “There have been at least seven or eight human coronaviruses, and the interesting thing is each one affects the brain and causes neurological complications.”
The effects are classified differently and have slightly different receptors, “but the consequences are the same.”
Of note, however, research published in The Lancet Psychiatry (2021 May. doi: 10.1016/S2215-0366[21]00084-5) revealed that symptoms such as dementia, mood, and anxiety are significantly higher after COVID-19 compared with other respiratory infections, with the differences increasing at 180 days since the index event.
Dr. Nath noted that, over the decades, he has observed that in pandemics “the brain tends to get overlooked.” He explained that “what can be most important in the end is what happened in the brain, because those are the things that really cause the long-term consequences.”
“These patients are depressed; they have dementia, they have brain fog, and even now that we recognize these issues, we haven’t done a very good job of studying them,” he said. “There’s so much we still don’t know, and a lot of patients are left with these symptoms and nowhere to go.”
Dr. Lynch, Dr. Van Ameringen, and Dr. Nath had no disclosures to report.
NEW ORLEANS – , adding to mounting evidence of the significant toll the chronic condition can have on mental health.
“Many clinicians have observed the symptoms we describe in this study, however this report is among the first which identify the specific deficits using neuropsychological testing to better characterize the syndrome,” Sean T. Lynch, MD, first author of a study on the issue presented at the annual meeting of the American Psychiatric Association, said in an interview.
Dr. Lynch, of the department of psychiatry, Westchester Medical Center Health System, Valhalla, N.Y., and his colleagues enrolled 60 participants who had experienced acute COVID-19 disease 6-8 months earlier and had undergone neuropsychological, psychiatric, medical, functional, and quality-of-life assessments. Results from the study were published online in the Journal of the Academy of Consultation–Liaison Psychiatry (2022 Jan 25. doi: 10.1016/j.jaclp.2022.01.003).
Among the study participants, 32 were seeking treatment for brain fog in a clinical program for survivors of COVID-19, while the remaining 28 were part of an ongoing longitudinal investigation of neuropsychological, medical, and psychiatric sequelae of COVID-19, but were not seeking care for the persistent symptoms.
Assessments for neurocognitive impairment included a battery of tests used in infectious and other diseases, including the Test of Premorbid Function, the Patient Assessment of Own Function, the Trail Making Test parts A and B, the Stroop Color and Word Test, and others.
Overall, the battery of assessments showed that 37 (62%) of participants had neuropsychological test impairment, with results below the 16th percentile in two tests, while 16 (27%) showed scores indicative of severe impairment (below the second percentile in at least one test and below the 16th percentile in one test).
Those reporting brain fog had scores that were even lower than expected on tests of attention, processing speed, memory, and executive function. And among those reporting brain fog, significantly more had scores reflecting severe impairment compared with the controls (38% vs. 14%; P < .04).
“Based on what we’ve observed in our patients and what others have previously reported, we did expect to find some impairment in this study sample,” Dr. Lynch noted.
“However, we were surprised to find that 27% of the study sample had extremely low neuropsychological test scores, meaning that they scored at least two standard deviations below the expected score on at least one neuropsychological test based on their age and level of education.”
The brain fog group also reported significantly higher levels of depression, fatigue, PTSD, and functional difficulties, and lower quality of life.
Severe impairment on the neuropsychological tests correlated with the extent of acute COVID-19 symptoms, as well as depression scores, number of medical comorbidities, and subjective cognitive complaints.
An analysis of serum levels of the inflammatory markers among 50 of the 60 participants showed that 45% of the patients had an elevated IL-6, 20% had elevated TNF-alpha, and 41% had elevated CRP, compared with reference ranges.
IL-6 levels were found to correlate with acute COVID-19 symptoms, the number of medical comorbidities, fatigue, and measures of executive function, while C-reactive protein (CRP) correlated with current COVID-19 symptoms and depression scores.
In terms of clinical factors that might predict low neuropsychological test scores, Dr. Lynch noted that the “markers that we found to be significant included severity of acute COVID-19 illness, current post-COVID-19 symptoms, measures of depression and anxiety, level of fatigue, and number of medical comorbidities.”
Dr. Lynch noted that the ongoing study will include up to 18-month follow-ups that are currently underway. “The [follow-ups] will examine if symptoms improve over time and evaluate if any intervention that took place was successful,” he said.
Survey supports findings
The detrimental effects of mental health symptoms in long COVID were further supported in another study at the APA meeting, an online survey of 787 survivors of acute COVID-19.
In the community survey, presented by Michael Van Ameringen, MD, a professor in the department of psychiatry and behavioral neurosciences at McMaster University, in Hamilton, Ont., all respondents (100%) reported having persistent symptoms of the virus, and as many as 68% indicated that they had not returned to normal functioning, despite only 15% of the respondents having been hospitalized with COVID-19.
A large proportion showed significant depression, anxiety, and posttraumatic stress disorder (PTSD), and the most commonly reported persistent symptoms were fatigue in 75.9% of respondents, brain fog in 67.9%, concentration difficulties in 61.1%, and weakness in 51.2%.
As many as 88.2% of patients said they experienced persistent neurocognitive symptoms, with poor memory and concentration; 56% reported problems with word finding; and 54.1% had slowed thinking.
The respondents showed high rates of anxiety (41.7%) as well as depression (61.4%) as determined by scores above 9 on the Generalized Anxiety Disorder–7 (GAD-7) and Patient Health Questionnaires (PHQ-9).
As many as 40.5% of respondents showed probable PTSD, with scores above 30 on the PTSD checklist (PCL-5). Their mean resilience score on the Brief Resilient Coping Scale was 13.5, suggesting low resilience.
Among the respondents, 43.3% said they had received past treatment for mental health, while 33.5% were currently receiving mental health treatment.
Dr. Van Ameringen noted the important limitation of the study being an online survey with no control group, but said the responses nevertheless raise the question of the role of prior psychiatric disorders in long COVID.
“In our sample, 40% of respondents had a past psychiatric history, so you wonder if that also makes you vulnerable to long COVID,” he said in an interview.
“About a third were getting psychiatric help, but I think the more impaired you are, the more likely you are to seek help.”
Those who were hospitalized with COVID-19 were at a higher risk of PTSD compared with those not hospitalized (P < .001), as were those under the age of 30 (P < .05) or between 31 and 50 vs. over 50 (P < .01).
Dr. Van Ameringen noted that the survey’s high rate of subjects who had not returned to normal functioning was especially striking.
“This is not a minor issue – these are people who are no longer functioning in society,” he said.
In pandemics, the brain tends to be ‘overlooked’
Further addressing the neurological effects of COVID-19 at the APA meeting, Avindra Nath, MD, clinical director of the National Institutes of Neurologic Disorders and Stroke in Bethesda, Md., noted that the persisting cognitive and psychiatric symptoms after illness, such as brain fog and depression and anxiety, are not necessarily unique to COVID-19.
“We have seen this before,” he said. “There have been at least seven or eight human coronaviruses, and the interesting thing is each one affects the brain and causes neurological complications.”
The effects are classified differently and have slightly different receptors, “but the consequences are the same.”
Of note, however, research published in The Lancet Psychiatry (2021 May. doi: 10.1016/S2215-0366[21]00084-5) revealed that symptoms such as dementia, mood, and anxiety are significantly higher after COVID-19 compared with other respiratory infections, with the differences increasing at 180 days since the index event.
Dr. Nath noted that, over the decades, he has observed that in pandemics “the brain tends to get overlooked.” He explained that “what can be most important in the end is what happened in the brain, because those are the things that really cause the long-term consequences.”
“These patients are depressed; they have dementia, they have brain fog, and even now that we recognize these issues, we haven’t done a very good job of studying them,” he said. “There’s so much we still don’t know, and a lot of patients are left with these symptoms and nowhere to go.”
Dr. Lynch, Dr. Van Ameringen, and Dr. Nath had no disclosures to report.
NEW ORLEANS – , adding to mounting evidence of the significant toll the chronic condition can have on mental health.
“Many clinicians have observed the symptoms we describe in this study, however this report is among the first which identify the specific deficits using neuropsychological testing to better characterize the syndrome,” Sean T. Lynch, MD, first author of a study on the issue presented at the annual meeting of the American Psychiatric Association, said in an interview.
Dr. Lynch, of the department of psychiatry, Westchester Medical Center Health System, Valhalla, N.Y., and his colleagues enrolled 60 participants who had experienced acute COVID-19 disease 6-8 months earlier and had undergone neuropsychological, psychiatric, medical, functional, and quality-of-life assessments. Results from the study were published online in the Journal of the Academy of Consultation–Liaison Psychiatry (2022 Jan 25. doi: 10.1016/j.jaclp.2022.01.003).
Among the study participants, 32 were seeking treatment for brain fog in a clinical program for survivors of COVID-19, while the remaining 28 were part of an ongoing longitudinal investigation of neuropsychological, medical, and psychiatric sequelae of COVID-19, but were not seeking care for the persistent symptoms.
Assessments for neurocognitive impairment included a battery of tests used in infectious and other diseases, including the Test of Premorbid Function, the Patient Assessment of Own Function, the Trail Making Test parts A and B, the Stroop Color and Word Test, and others.
Overall, the battery of assessments showed that 37 (62%) of participants had neuropsychological test impairment, with results below the 16th percentile in two tests, while 16 (27%) showed scores indicative of severe impairment (below the second percentile in at least one test and below the 16th percentile in one test).
Those reporting brain fog had scores that were even lower than expected on tests of attention, processing speed, memory, and executive function. And among those reporting brain fog, significantly more had scores reflecting severe impairment compared with the controls (38% vs. 14%; P < .04).
“Based on what we’ve observed in our patients and what others have previously reported, we did expect to find some impairment in this study sample,” Dr. Lynch noted.
“However, we were surprised to find that 27% of the study sample had extremely low neuropsychological test scores, meaning that they scored at least two standard deviations below the expected score on at least one neuropsychological test based on their age and level of education.”
The brain fog group also reported significantly higher levels of depression, fatigue, PTSD, and functional difficulties, and lower quality of life.
Severe impairment on the neuropsychological tests correlated with the extent of acute COVID-19 symptoms, as well as depression scores, number of medical comorbidities, and subjective cognitive complaints.
An analysis of serum levels of the inflammatory markers among 50 of the 60 participants showed that 45% of the patients had an elevated IL-6, 20% had elevated TNF-alpha, and 41% had elevated CRP, compared with reference ranges.
IL-6 levels were found to correlate with acute COVID-19 symptoms, the number of medical comorbidities, fatigue, and measures of executive function, while C-reactive protein (CRP) correlated with current COVID-19 symptoms and depression scores.
In terms of clinical factors that might predict low neuropsychological test scores, Dr. Lynch noted that the “markers that we found to be significant included severity of acute COVID-19 illness, current post-COVID-19 symptoms, measures of depression and anxiety, level of fatigue, and number of medical comorbidities.”
Dr. Lynch noted that the ongoing study will include up to 18-month follow-ups that are currently underway. “The [follow-ups] will examine if symptoms improve over time and evaluate if any intervention that took place was successful,” he said.
Survey supports findings
The detrimental effects of mental health symptoms in long COVID were further supported in another study at the APA meeting, an online survey of 787 survivors of acute COVID-19.
In the community survey, presented by Michael Van Ameringen, MD, a professor in the department of psychiatry and behavioral neurosciences at McMaster University, in Hamilton, Ont., all respondents (100%) reported having persistent symptoms of the virus, and as many as 68% indicated that they had not returned to normal functioning, despite only 15% of the respondents having been hospitalized with COVID-19.
A large proportion showed significant depression, anxiety, and posttraumatic stress disorder (PTSD), and the most commonly reported persistent symptoms were fatigue in 75.9% of respondents, brain fog in 67.9%, concentration difficulties in 61.1%, and weakness in 51.2%.
As many as 88.2% of patients said they experienced persistent neurocognitive symptoms, with poor memory and concentration; 56% reported problems with word finding; and 54.1% had slowed thinking.
The respondents showed high rates of anxiety (41.7%) as well as depression (61.4%) as determined by scores above 9 on the Generalized Anxiety Disorder–7 (GAD-7) and Patient Health Questionnaires (PHQ-9).
As many as 40.5% of respondents showed probable PTSD, with scores above 30 on the PTSD checklist (PCL-5). Their mean resilience score on the Brief Resilient Coping Scale was 13.5, suggesting low resilience.
Among the respondents, 43.3% said they had received past treatment for mental health, while 33.5% were currently receiving mental health treatment.
Dr. Van Ameringen noted the important limitation of the study being an online survey with no control group, but said the responses nevertheless raise the question of the role of prior psychiatric disorders in long COVID.
“In our sample, 40% of respondents had a past psychiatric history, so you wonder if that also makes you vulnerable to long COVID,” he said in an interview.
“About a third were getting psychiatric help, but I think the more impaired you are, the more likely you are to seek help.”
Those who were hospitalized with COVID-19 were at a higher risk of PTSD compared with those not hospitalized (P < .001), as were those under the age of 30 (P < .05) or between 31 and 50 vs. over 50 (P < .01).
Dr. Van Ameringen noted that the survey’s high rate of subjects who had not returned to normal functioning was especially striking.
“This is not a minor issue – these are people who are no longer functioning in society,” he said.
In pandemics, the brain tends to be ‘overlooked’
Further addressing the neurological effects of COVID-19 at the APA meeting, Avindra Nath, MD, clinical director of the National Institutes of Neurologic Disorders and Stroke in Bethesda, Md., noted that the persisting cognitive and psychiatric symptoms after illness, such as brain fog and depression and anxiety, are not necessarily unique to COVID-19.
“We have seen this before,” he said. “There have been at least seven or eight human coronaviruses, and the interesting thing is each one affects the brain and causes neurological complications.”
The effects are classified differently and have slightly different receptors, “but the consequences are the same.”
Of note, however, research published in The Lancet Psychiatry (2021 May. doi: 10.1016/S2215-0366[21]00084-5) revealed that symptoms such as dementia, mood, and anxiety are significantly higher after COVID-19 compared with other respiratory infections, with the differences increasing at 180 days since the index event.
Dr. Nath noted that, over the decades, he has observed that in pandemics “the brain tends to get overlooked.” He explained that “what can be most important in the end is what happened in the brain, because those are the things that really cause the long-term consequences.”
“These patients are depressed; they have dementia, they have brain fog, and even now that we recognize these issues, we haven’t done a very good job of studying them,” he said. “There’s so much we still don’t know, and a lot of patients are left with these symptoms and nowhere to go.”
Dr. Lynch, Dr. Van Ameringen, and Dr. Nath had no disclosures to report.
AT APA 2022
More evidence dementia not linked to PPI use in older people
Controversy regarding the purported link between the use of proton pump inhibitors (PPIs) or histamine H2 receptor antagonists (H2RAs) and risk for dementia continues.
Adding to the “no link” column comes new evidence from a study presented at the annual Digestive Disease Week® (DDW) .
Among almost 19,000 people, no association was found between the use of these agents and a greater likelihood of incident dementia, Alzheimer’s disease, or cognitive decline in people older than 65 years.
“We found that baseline PPI or H2RA use in older adults was not associated with dementia, with mild cognitive impairment, or declines in cognitive scores over time,” said lead author Raaj Shishir Mehta, MD, a gastroenterology fellow at Massachusetts General Hospital in Boston.
“While deprescribing efforts are important, especially when medications are not indicated, these data provide reassurance about the cognitive impacts of long-term use of PPIs in older adults,” he added.
Growing use, growing concern
As PPI use has increased worldwide, so too have concerns over the adverse effects from their long-term use, Dr. Mehta said.
“One particular area of concern, especially among older adults, is the link between long-term PPI use and risk for dementia,” he said.
Igniting the controversy was a February 2016 study published in JAMA Neurology that showed a positive association between PPI use and dementia in residents of Germany aged 75 years and older. Researchers linked PPI use to a 44% increased risk of dementia over 5 years.
The 2016 study was based on claims data, which can introduce “inaccuracy or bias in defining dementia cases,” Dr. Mehta said. He noted that it and other previous studies also were limited by an inability to account for concomitant medications or comorbidities.
To overcome these limitations in their study, Dr. Mehta and colleagues analyzed medication data collected during in-person visits and asked experts to confirm dementia outcomes. The research data come from ASPREE, a large aspirin study of 18,846 people older than 65 years in the United States and Australia. Participants were enrolled from 2010 to 2014. A total of 566 people developed incident dementia during follow-up.
The researchers had data on alcohol consumption and other lifestyle factors, as well as information on comorbidities, hospitalizations, and overall well-being.
“Perhaps the biggest strength of our study is our rigorous neurocognitive assessments,” Dr. Mehta said.
They assessed cognition at baseline and at years 1, 3, 5, and 7 using a battery of tests. An expert panel of neurologists, neuropsychologists, and geriatricians adjudicated cases of dementia, in accordance with DSM-IV criteria. If the diagnosis was unclear, they referred people for additional workup, including neuroimaging.
Cox proportional hazards, regression, and/or mixed effects modeling were used to relate medication use with cognitive scores.
All analyses were adjusted for age, sex, body mass index, alcohol use, family history of dementia, medications, and other medical comorbidities.
At baseline, PPI users were more likely to be White, have fewer years of education, and have higher rates of hypertension, diabetes, and kidney disease. This group also was more likely to be taking five or more medications.
Key points
During 80,976 person-years of follow-up, there were 566 incident cases of dementia, including 235 probable cases of Alzheimer’s disease and 331 other dementias.
Baseline PPI use, in comparison with nonuse, was not associated with incident dementia (hazard ratio, 0.86; 95% confidence interval, 0.70-1.05).
“Similarly, when we look specifically at Alzheimer’s disease or mixed types of dementia, we find no association between baseline PPI use and dementia,” Dr. Mehta said.
When they excluded people already taking PPIs at baseline, they found no association between starting PPIs and developing dementia over time.
Secondary aims of the study included looking for a link between PPI use and mild cognitive impairment or significant changes in cognition over time. In both cases, no association emerged. PPI use at baseline also was not associated with cognitive impairment/no dementia (also known as mild cognitive impairment) or with changes in overall cognitive test scores over time.
To determine whether any association could be a class effect of acid suppression medication, they assessed use of H2RA medications and development of incident dementia. Again, the researchers found no link.
A diverse multinational population from urban and rural areas was a strength of the study, as was the “very rigorous cognitive testing with expert adjudication of our endpoints,” Dr. Mehta said. In addition, fewer than 5% of patients were lost to follow-up.
In terms of limitations, this was an observational study “so residual confounding is always possible,” he added. “But I’ll emphasize that we are among the largest studies to date with wealth of covariates.”
Why the different findings?
The study was “really well done,” session moderator Paul Moayyedi, MD, said during the Q&A session at DDW 2022.
Dr. Moayyedi, a professor of medicine at McMaster University, Hamilton, Ont., asked Dr. Mehta why he “found absolutely no signal, whereas the German study did.”
“It’s a good question,” Dr. Mehta responded. “If you look across the board, there have been conflicting results.”
The disparity could be related to how researchers conducting claims data studies classify dementia, he noted.
“If you look at the nitty-gritty details over 5 years, almost 40% of participants [in those studies] end up with a diagnosis of dementia, which is quite high,” Dr. Mehta said. “That raises questions about whether the diagnosis of dementia is truly accurate.”
Dr. Mehta and Dr. Moayyedi reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Controversy regarding the purported link between the use of proton pump inhibitors (PPIs) or histamine H2 receptor antagonists (H2RAs) and risk for dementia continues.
Adding to the “no link” column comes new evidence from a study presented at the annual Digestive Disease Week® (DDW) .
Among almost 19,000 people, no association was found between the use of these agents and a greater likelihood of incident dementia, Alzheimer’s disease, or cognitive decline in people older than 65 years.
“We found that baseline PPI or H2RA use in older adults was not associated with dementia, with mild cognitive impairment, or declines in cognitive scores over time,” said lead author Raaj Shishir Mehta, MD, a gastroenterology fellow at Massachusetts General Hospital in Boston.
“While deprescribing efforts are important, especially when medications are not indicated, these data provide reassurance about the cognitive impacts of long-term use of PPIs in older adults,” he added.
Growing use, growing concern
As PPI use has increased worldwide, so too have concerns over the adverse effects from their long-term use, Dr. Mehta said.
“One particular area of concern, especially among older adults, is the link between long-term PPI use and risk for dementia,” he said.
Igniting the controversy was a February 2016 study published in JAMA Neurology that showed a positive association between PPI use and dementia in residents of Germany aged 75 years and older. Researchers linked PPI use to a 44% increased risk of dementia over 5 years.
The 2016 study was based on claims data, which can introduce “inaccuracy or bias in defining dementia cases,” Dr. Mehta said. He noted that it and other previous studies also were limited by an inability to account for concomitant medications or comorbidities.
To overcome these limitations in their study, Dr. Mehta and colleagues analyzed medication data collected during in-person visits and asked experts to confirm dementia outcomes. The research data come from ASPREE, a large aspirin study of 18,846 people older than 65 years in the United States and Australia. Participants were enrolled from 2010 to 2014. A total of 566 people developed incident dementia during follow-up.
The researchers had data on alcohol consumption and other lifestyle factors, as well as information on comorbidities, hospitalizations, and overall well-being.
“Perhaps the biggest strength of our study is our rigorous neurocognitive assessments,” Dr. Mehta said.
They assessed cognition at baseline and at years 1, 3, 5, and 7 using a battery of tests. An expert panel of neurologists, neuropsychologists, and geriatricians adjudicated cases of dementia, in accordance with DSM-IV criteria. If the diagnosis was unclear, they referred people for additional workup, including neuroimaging.
Cox proportional hazards, regression, and/or mixed effects modeling were used to relate medication use with cognitive scores.
All analyses were adjusted for age, sex, body mass index, alcohol use, family history of dementia, medications, and other medical comorbidities.
At baseline, PPI users were more likely to be White, have fewer years of education, and have higher rates of hypertension, diabetes, and kidney disease. This group also was more likely to be taking five or more medications.
Key points
During 80,976 person-years of follow-up, there were 566 incident cases of dementia, including 235 probable cases of Alzheimer’s disease and 331 other dementias.
Baseline PPI use, in comparison with nonuse, was not associated with incident dementia (hazard ratio, 0.86; 95% confidence interval, 0.70-1.05).
“Similarly, when we look specifically at Alzheimer’s disease or mixed types of dementia, we find no association between baseline PPI use and dementia,” Dr. Mehta said.
When they excluded people already taking PPIs at baseline, they found no association between starting PPIs and developing dementia over time.
Secondary aims of the study included looking for a link between PPI use and mild cognitive impairment or significant changes in cognition over time. In both cases, no association emerged. PPI use at baseline also was not associated with cognitive impairment/no dementia (also known as mild cognitive impairment) or with changes in overall cognitive test scores over time.
To determine whether any association could be a class effect of acid suppression medication, they assessed use of H2RA medications and development of incident dementia. Again, the researchers found no link.
A diverse multinational population from urban and rural areas was a strength of the study, as was the “very rigorous cognitive testing with expert adjudication of our endpoints,” Dr. Mehta said. In addition, fewer than 5% of patients were lost to follow-up.
In terms of limitations, this was an observational study “so residual confounding is always possible,” he added. “But I’ll emphasize that we are among the largest studies to date with wealth of covariates.”
Why the different findings?
The study was “really well done,” session moderator Paul Moayyedi, MD, said during the Q&A session at DDW 2022.
Dr. Moayyedi, a professor of medicine at McMaster University, Hamilton, Ont., asked Dr. Mehta why he “found absolutely no signal, whereas the German study did.”
“It’s a good question,” Dr. Mehta responded. “If you look across the board, there have been conflicting results.”
The disparity could be related to how researchers conducting claims data studies classify dementia, he noted.
“If you look at the nitty-gritty details over 5 years, almost 40% of participants [in those studies] end up with a diagnosis of dementia, which is quite high,” Dr. Mehta said. “That raises questions about whether the diagnosis of dementia is truly accurate.”
Dr. Mehta and Dr. Moayyedi reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Controversy regarding the purported link between the use of proton pump inhibitors (PPIs) or histamine H2 receptor antagonists (H2RAs) and risk for dementia continues.
Adding to the “no link” column comes new evidence from a study presented at the annual Digestive Disease Week® (DDW) .
Among almost 19,000 people, no association was found between the use of these agents and a greater likelihood of incident dementia, Alzheimer’s disease, or cognitive decline in people older than 65 years.
“We found that baseline PPI or H2RA use in older adults was not associated with dementia, with mild cognitive impairment, or declines in cognitive scores over time,” said lead author Raaj Shishir Mehta, MD, a gastroenterology fellow at Massachusetts General Hospital in Boston.
“While deprescribing efforts are important, especially when medications are not indicated, these data provide reassurance about the cognitive impacts of long-term use of PPIs in older adults,” he added.
Growing use, growing concern
As PPI use has increased worldwide, so too have concerns over the adverse effects from their long-term use, Dr. Mehta said.
“One particular area of concern, especially among older adults, is the link between long-term PPI use and risk for dementia,” he said.
Igniting the controversy was a February 2016 study published in JAMA Neurology that showed a positive association between PPI use and dementia in residents of Germany aged 75 years and older. Researchers linked PPI use to a 44% increased risk of dementia over 5 years.
The 2016 study was based on claims data, which can introduce “inaccuracy or bias in defining dementia cases,” Dr. Mehta said. He noted that it and other previous studies also were limited by an inability to account for concomitant medications or comorbidities.
To overcome these limitations in their study, Dr. Mehta and colleagues analyzed medication data collected during in-person visits and asked experts to confirm dementia outcomes. The research data come from ASPREE, a large aspirin study of 18,846 people older than 65 years in the United States and Australia. Participants were enrolled from 2010 to 2014. A total of 566 people developed incident dementia during follow-up.
The researchers had data on alcohol consumption and other lifestyle factors, as well as information on comorbidities, hospitalizations, and overall well-being.
“Perhaps the biggest strength of our study is our rigorous neurocognitive assessments,” Dr. Mehta said.
They assessed cognition at baseline and at years 1, 3, 5, and 7 using a battery of tests. An expert panel of neurologists, neuropsychologists, and geriatricians adjudicated cases of dementia, in accordance with DSM-IV criteria. If the diagnosis was unclear, they referred people for additional workup, including neuroimaging.
Cox proportional hazards, regression, and/or mixed effects modeling were used to relate medication use with cognitive scores.
All analyses were adjusted for age, sex, body mass index, alcohol use, family history of dementia, medications, and other medical comorbidities.
At baseline, PPI users were more likely to be White, have fewer years of education, and have higher rates of hypertension, diabetes, and kidney disease. This group also was more likely to be taking five or more medications.
Key points
During 80,976 person-years of follow-up, there were 566 incident cases of dementia, including 235 probable cases of Alzheimer’s disease and 331 other dementias.
Baseline PPI use, in comparison with nonuse, was not associated with incident dementia (hazard ratio, 0.86; 95% confidence interval, 0.70-1.05).
“Similarly, when we look specifically at Alzheimer’s disease or mixed types of dementia, we find no association between baseline PPI use and dementia,” Dr. Mehta said.
When they excluded people already taking PPIs at baseline, they found no association between starting PPIs and developing dementia over time.
Secondary aims of the study included looking for a link between PPI use and mild cognitive impairment or significant changes in cognition over time. In both cases, no association emerged. PPI use at baseline also was not associated with cognitive impairment/no dementia (also known as mild cognitive impairment) or with changes in overall cognitive test scores over time.
To determine whether any association could be a class effect of acid suppression medication, they assessed use of H2RA medications and development of incident dementia. Again, the researchers found no link.
A diverse multinational population from urban and rural areas was a strength of the study, as was the “very rigorous cognitive testing with expert adjudication of our endpoints,” Dr. Mehta said. In addition, fewer than 5% of patients were lost to follow-up.
In terms of limitations, this was an observational study “so residual confounding is always possible,” he added. “But I’ll emphasize that we are among the largest studies to date with wealth of covariates.”
Why the different findings?
The study was “really well done,” session moderator Paul Moayyedi, MD, said during the Q&A session at DDW 2022.
Dr. Moayyedi, a professor of medicine at McMaster University, Hamilton, Ont., asked Dr. Mehta why he “found absolutely no signal, whereas the German study did.”
“It’s a good question,” Dr. Mehta responded. “If you look across the board, there have been conflicting results.”
The disparity could be related to how researchers conducting claims data studies classify dementia, he noted.
“If you look at the nitty-gritty details over 5 years, almost 40% of participants [in those studies] end up with a diagnosis of dementia, which is quite high,” Dr. Mehta said. “That raises questions about whether the diagnosis of dementia is truly accurate.”
Dr. Mehta and Dr. Moayyedi reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM DDW 2022
Many Americans missing an opportunity to prevent dementia
(ADRD), including hypertension, low levels of physical activity, and obesity, new research shows.
Data from the Centers for Disease Control and Prevention reveal that among nearly 162,000 adults aged 45 and older who were surveyed in 2019 as part of the Behavioral Risk Factor Surveillance System (BRFSS), nearly half had high blood pressure and did not achieve aerobic physical activity recommendations. These were the two most common modifiable risk factors for ADRD.
In addition, more than one-third (35%) of adults were obese, 19% had diabetes, 18% had depression, 15% were smokers, 11% had hearing loss, and 10% were binge drinkers.
The findings were published online in the CDC’s Morbidity and Mortality Weekly Report.
A missed prevention opportunity
More than 1 in 10 (11.3%) adults surveyed reported subjective cognitive decline (SCD), an early indicator of possible future ADRD.
The prevalence of SCD increased from about 4% among adults with no modifiable risk factors for ADRD to 25% for those with four or more risk factors.
Adults with SCD were more apt to report having almost all modifiable risk factors and were more likely to report four or more risk factors (34%) than were peers without SCD (13%)
The prevalence of SCD ranged from a high of about 29% in those with depression and 25% in those with hearing loss to 11% in those who reported binge drinking.
In line with previous research, the findings indicate that American Indian or Alaska Native, Black or African American, and Hispanic populations were more likely to have modifiable risk factors for ADRD than other racial groups, the researchers reported.
The CDC’s National Healthy Brain Initiative supports culturally tailored interventions that address ADRD risk factors specifically in these populations.
In 2021, the federal government’s National Plan to Address Alzheimer’s Disease was updated to include a new goal to reduce risk factors for ADRD.
“Given the prevalence of modifiable risk factors for ADRD and anticipated growth of the older adult population and those with ADRD, this new goal has the potential to benefit a large proportion of U.S. adults,” the investigators wrote.
“In addition to helping patients discuss concerns about memory loss, health care professionals should also screen patients for modifiable risk factors, counsel patients with risk factors, and refer them to effective programs and interventions where recommended,” they advised.
A recent report from the Lancet Commission on Dementia Prevention, Intervention, and Care found that modifying 12 risk factors over the life course could delay or prevent 40% of dementia cases.
A version of this article first appeared on Medscape.com.
(ADRD), including hypertension, low levels of physical activity, and obesity, new research shows.
Data from the Centers for Disease Control and Prevention reveal that among nearly 162,000 adults aged 45 and older who were surveyed in 2019 as part of the Behavioral Risk Factor Surveillance System (BRFSS), nearly half had high blood pressure and did not achieve aerobic physical activity recommendations. These were the two most common modifiable risk factors for ADRD.
In addition, more than one-third (35%) of adults were obese, 19% had diabetes, 18% had depression, 15% were smokers, 11% had hearing loss, and 10% were binge drinkers.
The findings were published online in the CDC’s Morbidity and Mortality Weekly Report.
A missed prevention opportunity
More than 1 in 10 (11.3%) adults surveyed reported subjective cognitive decline (SCD), an early indicator of possible future ADRD.
The prevalence of SCD increased from about 4% among adults with no modifiable risk factors for ADRD to 25% for those with four or more risk factors.
Adults with SCD were more apt to report having almost all modifiable risk factors and were more likely to report four or more risk factors (34%) than were peers without SCD (13%)
The prevalence of SCD ranged from a high of about 29% in those with depression and 25% in those with hearing loss to 11% in those who reported binge drinking.
In line with previous research, the findings indicate that American Indian or Alaska Native, Black or African American, and Hispanic populations were more likely to have modifiable risk factors for ADRD than other racial groups, the researchers reported.
The CDC’s National Healthy Brain Initiative supports culturally tailored interventions that address ADRD risk factors specifically in these populations.
In 2021, the federal government’s National Plan to Address Alzheimer’s Disease was updated to include a new goal to reduce risk factors for ADRD.
“Given the prevalence of modifiable risk factors for ADRD and anticipated growth of the older adult population and those with ADRD, this new goal has the potential to benefit a large proportion of U.S. adults,” the investigators wrote.
“In addition to helping patients discuss concerns about memory loss, health care professionals should also screen patients for modifiable risk factors, counsel patients with risk factors, and refer them to effective programs and interventions where recommended,” they advised.
A recent report from the Lancet Commission on Dementia Prevention, Intervention, and Care found that modifying 12 risk factors over the life course could delay or prevent 40% of dementia cases.
A version of this article first appeared on Medscape.com.
(ADRD), including hypertension, low levels of physical activity, and obesity, new research shows.
Data from the Centers for Disease Control and Prevention reveal that among nearly 162,000 adults aged 45 and older who were surveyed in 2019 as part of the Behavioral Risk Factor Surveillance System (BRFSS), nearly half had high blood pressure and did not achieve aerobic physical activity recommendations. These were the two most common modifiable risk factors for ADRD.
In addition, more than one-third (35%) of adults were obese, 19% had diabetes, 18% had depression, 15% were smokers, 11% had hearing loss, and 10% were binge drinkers.
The findings were published online in the CDC’s Morbidity and Mortality Weekly Report.
A missed prevention opportunity
More than 1 in 10 (11.3%) adults surveyed reported subjective cognitive decline (SCD), an early indicator of possible future ADRD.
The prevalence of SCD increased from about 4% among adults with no modifiable risk factors for ADRD to 25% for those with four or more risk factors.
Adults with SCD were more apt to report having almost all modifiable risk factors and were more likely to report four or more risk factors (34%) than were peers without SCD (13%)
The prevalence of SCD ranged from a high of about 29% in those with depression and 25% in those with hearing loss to 11% in those who reported binge drinking.
In line with previous research, the findings indicate that American Indian or Alaska Native, Black or African American, and Hispanic populations were more likely to have modifiable risk factors for ADRD than other racial groups, the researchers reported.
The CDC’s National Healthy Brain Initiative supports culturally tailored interventions that address ADRD risk factors specifically in these populations.
In 2021, the federal government’s National Plan to Address Alzheimer’s Disease was updated to include a new goal to reduce risk factors for ADRD.
“Given the prevalence of modifiable risk factors for ADRD and anticipated growth of the older adult population and those with ADRD, this new goal has the potential to benefit a large proportion of U.S. adults,” the investigators wrote.
“In addition to helping patients discuss concerns about memory loss, health care professionals should also screen patients for modifiable risk factors, counsel patients with risk factors, and refer them to effective programs and interventions where recommended,” they advised.
A recent report from the Lancet Commission on Dementia Prevention, Intervention, and Care found that modifying 12 risk factors over the life course could delay or prevent 40% of dementia cases.
A version of this article first appeared on Medscape.com.
FROM MMWR
Can fecal transplants help reverse aging?
Transplanting fecal microbiota from young mice into older mice can reverse signs of aging in the gut, brain, and eyes, a team of scientists from the United Kingdom has found. Conversely, transplanting microbiota from old mice to young mice has the opposite effect.
This research provides “tantalizing evidence for the direct involvement of gut microbes in aging and the functional decline of brain function and vision and offers a potential solution in the form of gut microbe replacement therapy,” Simon Carding, PhD, who heads the gut microbes and health research program at the Quadram Institute in Norwich, England, said in a news release.
The study was published online in the journal Microbiome.
The fountain of youth?
Age-related changes in diversity, composition, and function of the gut microbiota are associated with low-grade systemic inflammation, declining tissue function, and increased susceptibility to age-related chronic diseases.
Dr. Carding and colleagues at the Quadram Institute and the University of East Anglia used fecal microbiota transplant (FMT) to exchange the intestinal microbiota of young mice and aged mice.
Young mice who received aged microbiota showed increased intestinal barrier permeability (leaky gut) coupled with upregulated inflammation in the brain and retina, as well as loss of a key functional protein in the eye, they report.
Conversely, these detrimental effects were reversed when microbiota from young mice was transferred to aged mice. FMT with young microbiota also led to enrichment of beneficial taxa in aged mice.
“Our data support the suggestion that altered gut microbiota in old age contributes to intestinal and systemic inflammation, and so may contribute to driving inflammatory pathologies of aged organs,” the study team wrote.
“Targeting the gut-brain axis in aging, by modification of microbial composition to modulate immune and metabolic pathways, may therefore be a potential avenue for therapeutic approaches to age-associated inflammatory and functional decline,” they suggested.
In ongoing studies, the study team are working to understand how long the beneficial effects of young donor microbiota last, which will establish whether FMT can promote long-term health benefits in aged individuals and ameliorate age-associated neurodegeneration and retinal functional deterioration.
“Our results provide more evidence of the important links between microbes in the gut and healthy aging of tissues and organs around the body,” lead author Aimée Parker, PhD, from the Quadram Institute, said in the release.
“We hope that our findings will contribute ultimately to understanding how we can manipulate our diet and our gut bacteria to maximize good health in later life,” she added.
Support for this research was provided by the Biotechnology and Biological Sciences Research Council. The authors report no relevant financial relationships .
A version of this article first appeared on Medscape.com.
Transplanting fecal microbiota from young mice into older mice can reverse signs of aging in the gut, brain, and eyes, a team of scientists from the United Kingdom has found. Conversely, transplanting microbiota from old mice to young mice has the opposite effect.
This research provides “tantalizing evidence for the direct involvement of gut microbes in aging and the functional decline of brain function and vision and offers a potential solution in the form of gut microbe replacement therapy,” Simon Carding, PhD, who heads the gut microbes and health research program at the Quadram Institute in Norwich, England, said in a news release.
The study was published online in the journal Microbiome.
The fountain of youth?
Age-related changes in diversity, composition, and function of the gut microbiota are associated with low-grade systemic inflammation, declining tissue function, and increased susceptibility to age-related chronic diseases.
Dr. Carding and colleagues at the Quadram Institute and the University of East Anglia used fecal microbiota transplant (FMT) to exchange the intestinal microbiota of young mice and aged mice.
Young mice who received aged microbiota showed increased intestinal barrier permeability (leaky gut) coupled with upregulated inflammation in the brain and retina, as well as loss of a key functional protein in the eye, they report.
Conversely, these detrimental effects were reversed when microbiota from young mice was transferred to aged mice. FMT with young microbiota also led to enrichment of beneficial taxa in aged mice.
“Our data support the suggestion that altered gut microbiota in old age contributes to intestinal and systemic inflammation, and so may contribute to driving inflammatory pathologies of aged organs,” the study team wrote.
“Targeting the gut-brain axis in aging, by modification of microbial composition to modulate immune and metabolic pathways, may therefore be a potential avenue for therapeutic approaches to age-associated inflammatory and functional decline,” they suggested.
In ongoing studies, the study team are working to understand how long the beneficial effects of young donor microbiota last, which will establish whether FMT can promote long-term health benefits in aged individuals and ameliorate age-associated neurodegeneration and retinal functional deterioration.
“Our results provide more evidence of the important links between microbes in the gut and healthy aging of tissues and organs around the body,” lead author Aimée Parker, PhD, from the Quadram Institute, said in the release.
“We hope that our findings will contribute ultimately to understanding how we can manipulate our diet and our gut bacteria to maximize good health in later life,” she added.
Support for this research was provided by the Biotechnology and Biological Sciences Research Council. The authors report no relevant financial relationships .
A version of this article first appeared on Medscape.com.
Transplanting fecal microbiota from young mice into older mice can reverse signs of aging in the gut, brain, and eyes, a team of scientists from the United Kingdom has found. Conversely, transplanting microbiota from old mice to young mice has the opposite effect.
This research provides “tantalizing evidence for the direct involvement of gut microbes in aging and the functional decline of brain function and vision and offers a potential solution in the form of gut microbe replacement therapy,” Simon Carding, PhD, who heads the gut microbes and health research program at the Quadram Institute in Norwich, England, said in a news release.
The study was published online in the journal Microbiome.
The fountain of youth?
Age-related changes in diversity, composition, and function of the gut microbiota are associated with low-grade systemic inflammation, declining tissue function, and increased susceptibility to age-related chronic diseases.
Dr. Carding and colleagues at the Quadram Institute and the University of East Anglia used fecal microbiota transplant (FMT) to exchange the intestinal microbiota of young mice and aged mice.
Young mice who received aged microbiota showed increased intestinal barrier permeability (leaky gut) coupled with upregulated inflammation in the brain and retina, as well as loss of a key functional protein in the eye, they report.
Conversely, these detrimental effects were reversed when microbiota from young mice was transferred to aged mice. FMT with young microbiota also led to enrichment of beneficial taxa in aged mice.
“Our data support the suggestion that altered gut microbiota in old age contributes to intestinal and systemic inflammation, and so may contribute to driving inflammatory pathologies of aged organs,” the study team wrote.
“Targeting the gut-brain axis in aging, by modification of microbial composition to modulate immune and metabolic pathways, may therefore be a potential avenue for therapeutic approaches to age-associated inflammatory and functional decline,” they suggested.
In ongoing studies, the study team are working to understand how long the beneficial effects of young donor microbiota last, which will establish whether FMT can promote long-term health benefits in aged individuals and ameliorate age-associated neurodegeneration and retinal functional deterioration.
“Our results provide more evidence of the important links between microbes in the gut and healthy aging of tissues and organs around the body,” lead author Aimée Parker, PhD, from the Quadram Institute, said in the release.
“We hope that our findings will contribute ultimately to understanding how we can manipulate our diet and our gut bacteria to maximize good health in later life,” she added.
Support for this research was provided by the Biotechnology and Biological Sciences Research Council. The authors report no relevant financial relationships .
A version of this article first appeared on Medscape.com.
Neurology, psychiatry studies overlook sex as a variable
A large percentage of studies in neurology and psychiatry over the past decade have failed to account for differences between the sexes, according to a team of Canadian researchers.
“Despite the fact there are papers that are using males and females in the studies, they’re not using the males and females in the way that would optimally find the possibility of sex differences,” lead author Liisa A.M. Galea, PhD, told this news organization. Dr. Galea is a professor and distinguished scholar at the Djavad Mowafaghian Center for Brain Health at the University of British Columbia in Vancouver.
The study was published online in Nature Communications.
Optimal design uncommon
Differences in how neurologic and psychiatric diseases affect men and women have been well documented. Women, for example, are more susceptible to severe stroke, and men are more prone to cognitive decline with schizophrenia. With Alzheimer’s disease, women typically have more severe cognitive defects.
The researchers surveyed 3,193 papers that included a multitude of studies. Although most of the papers reported studies that included both sexes, only 19% of surveyed studies used what Dr. Galea called an optimal design for the discovery of sex differences. “What I mean by ‘optimally’ is the design of the experiments and the analysis of sex as a variable,” she said. And in 2019, only 5% of the studies used sex as a variable for determining differences between the sexes, the study found.
In the current research, two authors read the methods and results of each study described in each paper, Dr. Galea said. The readers noted whether the paper reported the study sample size and whether the studies used a balanced design. The surveyed journals include Nature Neuroscience, Neuron, Journal of Neuroscience, Molecular Psychiatry, Biological Psychiatry, and Neuropsychopharmacology.
‘Not much is changing’
“I had a suspicion that this was happening,” Dr. Galea said. “I didn’t know that it’s so bad, to be fair.” The “good news story,” she said, is that more papers considered sex as a factor in the later years surveyed. In 2019, more than 95% of papers across both disciplines reported participants’ sex, compared with about 70% in 2009. However, less than 20% of the papers in all study years reported studies that used sex optimally to determine differences between the sexes.
“The other thing that shocked me,” Dr. Galea said, “was that even despite the fact that we saw this increase in the number of papers that were using males and females, we didn’t see the sort of corresponding increase in those that were using ‘optimal design’ or ‘optimal analysis,’ ” Dr. Galea said. In 2009, 14% of papers used optimal design and 2% used optimal analysis for determining sex differences. By 2019, those percentages were 19% and 5%, respectively.
But even the papers that used both sexes had shortcomings, the study found. Just over one-third of these papers (34.5%) didn’t use a balanced design. Just over one-quarter (25.9%) didn’t identify the sample size, a shortcoming that marked 18% of these studies in 2009 and 33% in 2019. Fifteen percent of papers examined included studies that used both sexes inconsistently.
“That matters, because other studies have found that about 20% of papers are doing some kind of analysis with sex, but we had a suspicion that a lot of studies would include sex as a covariate,” Dr. Galea said. “Essentially what that does is, you remove that variable from the data. So, any statistical variation due to sex is then gone.
“The problem with that,” she added, “is you’re not actually looking to see if there’s an influence of sex; you’re removing it.”
Dr. Galea noted that this study points to a need for funding agencies to demand that researchers meet their mandates on sex- and gender-based analysis. “Despite the mandates, not much is really changing as far as the analysis or design of experiments, and we need to figure out how to change that,” she said. “We need to figure out how to get researchers more interested to use the power of studying sex differences.”
‘Not surprising, but disappointing’
Vladimir Hachinski, MD, professor of neurology and epidemiology at Western University in London, Ont., and former editor in chief of Stroke, told this news organization that women have almost twice the life risk of developing dementia, are at higher risk of stroke below age 35 years, and have more severe strokes and higher rates of disability at any age.
Commenting on the current study, Dr. Hachinski said, “It’s not surprising, but it’s disappointing, because we’ve known the difference for a long time.” He added, “The paper is very important because we were not aware that it was that bad.”
Dr. Hachinski also stated, “This paper needs a lot of reading. It’s a great resource, and it should be highlighted as one of those things that needs to be addressed, because it matters.”
The study was funded by a Natural Sciences and Engineering Research Council of Canada grant and by the British Columbia Women’s Foundation. Dr. Galea and Hachinski had no relevant disclosures.
A version of this article first appeared on Medscape.com.
A large percentage of studies in neurology and psychiatry over the past decade have failed to account for differences between the sexes, according to a team of Canadian researchers.
“Despite the fact there are papers that are using males and females in the studies, they’re not using the males and females in the way that would optimally find the possibility of sex differences,” lead author Liisa A.M. Galea, PhD, told this news organization. Dr. Galea is a professor and distinguished scholar at the Djavad Mowafaghian Center for Brain Health at the University of British Columbia in Vancouver.
The study was published online in Nature Communications.
Optimal design uncommon
Differences in how neurologic and psychiatric diseases affect men and women have been well documented. Women, for example, are more susceptible to severe stroke, and men are more prone to cognitive decline with schizophrenia. With Alzheimer’s disease, women typically have more severe cognitive defects.
The researchers surveyed 3,193 papers that included a multitude of studies. Although most of the papers reported studies that included both sexes, only 19% of surveyed studies used what Dr. Galea called an optimal design for the discovery of sex differences. “What I mean by ‘optimally’ is the design of the experiments and the analysis of sex as a variable,” she said. And in 2019, only 5% of the studies used sex as a variable for determining differences between the sexes, the study found.
In the current research, two authors read the methods and results of each study described in each paper, Dr. Galea said. The readers noted whether the paper reported the study sample size and whether the studies used a balanced design. The surveyed journals include Nature Neuroscience, Neuron, Journal of Neuroscience, Molecular Psychiatry, Biological Psychiatry, and Neuropsychopharmacology.
‘Not much is changing’
“I had a suspicion that this was happening,” Dr. Galea said. “I didn’t know that it’s so bad, to be fair.” The “good news story,” she said, is that more papers considered sex as a factor in the later years surveyed. In 2019, more than 95% of papers across both disciplines reported participants’ sex, compared with about 70% in 2009. However, less than 20% of the papers in all study years reported studies that used sex optimally to determine differences between the sexes.
“The other thing that shocked me,” Dr. Galea said, “was that even despite the fact that we saw this increase in the number of papers that were using males and females, we didn’t see the sort of corresponding increase in those that were using ‘optimal design’ or ‘optimal analysis,’ ” Dr. Galea said. In 2009, 14% of papers used optimal design and 2% used optimal analysis for determining sex differences. By 2019, those percentages were 19% and 5%, respectively.
But even the papers that used both sexes had shortcomings, the study found. Just over one-third of these papers (34.5%) didn’t use a balanced design. Just over one-quarter (25.9%) didn’t identify the sample size, a shortcoming that marked 18% of these studies in 2009 and 33% in 2019. Fifteen percent of papers examined included studies that used both sexes inconsistently.
“That matters, because other studies have found that about 20% of papers are doing some kind of analysis with sex, but we had a suspicion that a lot of studies would include sex as a covariate,” Dr. Galea said. “Essentially what that does is, you remove that variable from the data. So, any statistical variation due to sex is then gone.
“The problem with that,” she added, “is you’re not actually looking to see if there’s an influence of sex; you’re removing it.”
Dr. Galea noted that this study points to a need for funding agencies to demand that researchers meet their mandates on sex- and gender-based analysis. “Despite the mandates, not much is really changing as far as the analysis or design of experiments, and we need to figure out how to change that,” she said. “We need to figure out how to get researchers more interested to use the power of studying sex differences.”
‘Not surprising, but disappointing’
Vladimir Hachinski, MD, professor of neurology and epidemiology at Western University in London, Ont., and former editor in chief of Stroke, told this news organization that women have almost twice the life risk of developing dementia, are at higher risk of stroke below age 35 years, and have more severe strokes and higher rates of disability at any age.
Commenting on the current study, Dr. Hachinski said, “It’s not surprising, but it’s disappointing, because we’ve known the difference for a long time.” He added, “The paper is very important because we were not aware that it was that bad.”
Dr. Hachinski also stated, “This paper needs a lot of reading. It’s a great resource, and it should be highlighted as one of those things that needs to be addressed, because it matters.”
The study was funded by a Natural Sciences and Engineering Research Council of Canada grant and by the British Columbia Women’s Foundation. Dr. Galea and Hachinski had no relevant disclosures.
A version of this article first appeared on Medscape.com.
A large percentage of studies in neurology and psychiatry over the past decade have failed to account for differences between the sexes, according to a team of Canadian researchers.
“Despite the fact there are papers that are using males and females in the studies, they’re not using the males and females in the way that would optimally find the possibility of sex differences,” lead author Liisa A.M. Galea, PhD, told this news organization. Dr. Galea is a professor and distinguished scholar at the Djavad Mowafaghian Center for Brain Health at the University of British Columbia in Vancouver.
The study was published online in Nature Communications.
Optimal design uncommon
Differences in how neurologic and psychiatric diseases affect men and women have been well documented. Women, for example, are more susceptible to severe stroke, and men are more prone to cognitive decline with schizophrenia. With Alzheimer’s disease, women typically have more severe cognitive defects.
The researchers surveyed 3,193 papers that included a multitude of studies. Although most of the papers reported studies that included both sexes, only 19% of surveyed studies used what Dr. Galea called an optimal design for the discovery of sex differences. “What I mean by ‘optimally’ is the design of the experiments and the analysis of sex as a variable,” she said. And in 2019, only 5% of the studies used sex as a variable for determining differences between the sexes, the study found.
In the current research, two authors read the methods and results of each study described in each paper, Dr. Galea said. The readers noted whether the paper reported the study sample size and whether the studies used a balanced design. The surveyed journals include Nature Neuroscience, Neuron, Journal of Neuroscience, Molecular Psychiatry, Biological Psychiatry, and Neuropsychopharmacology.
‘Not much is changing’
“I had a suspicion that this was happening,” Dr. Galea said. “I didn’t know that it’s so bad, to be fair.” The “good news story,” she said, is that more papers considered sex as a factor in the later years surveyed. In 2019, more than 95% of papers across both disciplines reported participants’ sex, compared with about 70% in 2009. However, less than 20% of the papers in all study years reported studies that used sex optimally to determine differences between the sexes.
“The other thing that shocked me,” Dr. Galea said, “was that even despite the fact that we saw this increase in the number of papers that were using males and females, we didn’t see the sort of corresponding increase in those that were using ‘optimal design’ or ‘optimal analysis,’ ” Dr. Galea said. In 2009, 14% of papers used optimal design and 2% used optimal analysis for determining sex differences. By 2019, those percentages were 19% and 5%, respectively.
But even the papers that used both sexes had shortcomings, the study found. Just over one-third of these papers (34.5%) didn’t use a balanced design. Just over one-quarter (25.9%) didn’t identify the sample size, a shortcoming that marked 18% of these studies in 2009 and 33% in 2019. Fifteen percent of papers examined included studies that used both sexes inconsistently.
“That matters, because other studies have found that about 20% of papers are doing some kind of analysis with sex, but we had a suspicion that a lot of studies would include sex as a covariate,” Dr. Galea said. “Essentially what that does is, you remove that variable from the data. So, any statistical variation due to sex is then gone.
“The problem with that,” she added, “is you’re not actually looking to see if there’s an influence of sex; you’re removing it.”
Dr. Galea noted that this study points to a need for funding agencies to demand that researchers meet their mandates on sex- and gender-based analysis. “Despite the mandates, not much is really changing as far as the analysis or design of experiments, and we need to figure out how to change that,” she said. “We need to figure out how to get researchers more interested to use the power of studying sex differences.”
‘Not surprising, but disappointing’
Vladimir Hachinski, MD, professor of neurology and epidemiology at Western University in London, Ont., and former editor in chief of Stroke, told this news organization that women have almost twice the life risk of developing dementia, are at higher risk of stroke below age 35 years, and have more severe strokes and higher rates of disability at any age.
Commenting on the current study, Dr. Hachinski said, “It’s not surprising, but it’s disappointing, because we’ve known the difference for a long time.” He added, “The paper is very important because we were not aware that it was that bad.”
Dr. Hachinski also stated, “This paper needs a lot of reading. It’s a great resource, and it should be highlighted as one of those things that needs to be addressed, because it matters.”
The study was funded by a Natural Sciences and Engineering Research Council of Canada grant and by the British Columbia Women’s Foundation. Dr. Galea and Hachinski had no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM NATURE COMMUNICATIONS
Study casts doubt on safety, efficacy of L-serine supplementation for AD
When given to patients with AD, L-serine supplements could be driving abnormally increased serine levels in the brain even higher, potentially accelerating neuronal death, according to study author Xu Chen, PhD, of the University of California, San Diego, and colleagues.
This conclusion conflicts with a 2020 study by Juliette Le Douce, PhD, and colleagues, who reported that oral L-serine supplementation may act as a “ready-to-use therapy” for AD, based on their findings that patients with AD had low levels of PHGDH, an enzyme necessary for synthesizing serine, and AD-like mice had low levels of serine.
Writing in Cell Metabolism, Dr. Chen and colleagues framed the present study, and their findings, in this context.
“In contrast to the work of Le Douce et al., here we report that PHGDH mRNA and protein levels are increased in the brains of two mouse models of AD and/or tauopathy, and are also progressively increased in human brains with no, early, and late AD pathology, as well as in people with no, asymptomatic, and symptomatic AD,” they wrote.
They suggested adjusting clinical recommendations for L-serine, the form of the amino acid commonly found in supplements. In the body, L-serine is converted to D-serine, which acts on the NMDA receptor (NMDAR).
‘Long-term use of D-serine contributes to neuronal death’ suggests research
“We feel oral L-serine as a ready-to-use therapy to AD warrants precaution,” Dr. Chen and colleagues wrote. “This is because despite being a cognitive enhancer, some [research] suggests that long-term use of D-serine contributes to neuronal death in AD through excitotoxicity. Furthermore, D-serine, as a co-agonist of NMDAR, would be expected to oppose NMDAR antagonists, which have proven clinical benefits in treating AD.”
According to principal author Sheng Zhong, PhD, of the University of California, San Diego, “Research is needed to test if targeting PHGDH can ameliorate cognitive decline in AD.”
Dr. Zhong also noted that the present findings support the “promise of using a specific RNA in blood as a biomarker for early detection of Alzheimer’s disease.” This approach is currently being validated at UCSD Shiley-Marcos Alzheimer’s Disease Research Center, he added.
Roles of PHGDH and serine in Alzheimer’s disease require further study
Commenting on both studies, Steve W. Barger, PhD, of the University of Arkansas for Medical Sciences, Little Rock, suggested that more work is needed to better understand the roles of PHGDH and serine in AD before clinical applications can be considered.
“In the end, these two studies fail to provide the clarity we need in designing evidence-based therapeutic hypotheses,” Dr. Barger said in an interview. “We still do not have a firm grasp on the role that D-serine plays in AD. Indeed, the evidence regarding even a single enzyme contributing to its levels is ambiguous.”
Dr. Barger, who has published extensively on the topic of neuronal death, with a particular focus on Alzheimer’s disease, noted that “determination of what happens to D-serine levels in AD has been of interest for decades,” but levels of the amino acid have been notoriously challenging to measure because “D-serine can disappear rapidly from the brain and its fluids after death.”
While Dr. Le Douce and colleagues did measure levels of serine in mice, Dr. Barger noted that the study by Dr. Chen and colleagues was conducted with more “quantitatively rigorous methods.” Even though Dr. Chen and colleagues “did not assay the levels of D-serine itself ... the implication of their findings is that PHGDH is poised to elevate this critical neurotransmitter,” leading to their conclusion that serine supplementation is “potentially dangerous.”
At this point, it may be too early to tell, according to Dr. Barger.
He suggested that conclusions drawn from PHGDH levels alone are “always limited,” and conclusions based on serine levels may be equally dubious, considering that the activities and effects of serine “are quite complex,” and may be influenced by other physiologic processes, including the effects of gut bacteria.
Instead, Dr. Barger suggested that changes in PHGDH and serine may be interpreted as signals coming from a more relevant process upstream: glucose metabolism.
“What we can say confidently is that the glucose metabolism that PHGDH connects to D-serine is most definitely a factor in AD,” he said. “Countless studies have documented what now appears to be a universal decline in glucose delivery to the cerebral cortex, even before frank dementia sets in.”
Dr. Barger noted that declining glucose delivery coincides with some of the earliest events in the development of AD, perhaps “linking accumulation of amyloid β-peptide to subsequent neurofibrillary tangles and tissue atrophy.”
Dr. Barger’s own work recently demonstrated that AD is associated with “an irregularity in the insertion of a specific glucose transporter (GLUT1) into the cell surface” of astrocytes.
“It could be more effective to direct therapeutic interventions at these events lying upstream of PHGDH or serine,” he concluded.
The study was partly supported by a Kreuger v. Wyeth research award. The investigators and Dr. Barger reported no conflicts of interest.
When given to patients with AD, L-serine supplements could be driving abnormally increased serine levels in the brain even higher, potentially accelerating neuronal death, according to study author Xu Chen, PhD, of the University of California, San Diego, and colleagues.
This conclusion conflicts with a 2020 study by Juliette Le Douce, PhD, and colleagues, who reported that oral L-serine supplementation may act as a “ready-to-use therapy” for AD, based on their findings that patients with AD had low levels of PHGDH, an enzyme necessary for synthesizing serine, and AD-like mice had low levels of serine.
Writing in Cell Metabolism, Dr. Chen and colleagues framed the present study, and their findings, in this context.
“In contrast to the work of Le Douce et al., here we report that PHGDH mRNA and protein levels are increased in the brains of two mouse models of AD and/or tauopathy, and are also progressively increased in human brains with no, early, and late AD pathology, as well as in people with no, asymptomatic, and symptomatic AD,” they wrote.
They suggested adjusting clinical recommendations for L-serine, the form of the amino acid commonly found in supplements. In the body, L-serine is converted to D-serine, which acts on the NMDA receptor (NMDAR).
‘Long-term use of D-serine contributes to neuronal death’ suggests research
“We feel oral L-serine as a ready-to-use therapy to AD warrants precaution,” Dr. Chen and colleagues wrote. “This is because despite being a cognitive enhancer, some [research] suggests that long-term use of D-serine contributes to neuronal death in AD through excitotoxicity. Furthermore, D-serine, as a co-agonist of NMDAR, would be expected to oppose NMDAR antagonists, which have proven clinical benefits in treating AD.”
According to principal author Sheng Zhong, PhD, of the University of California, San Diego, “Research is needed to test if targeting PHGDH can ameliorate cognitive decline in AD.”
Dr. Zhong also noted that the present findings support the “promise of using a specific RNA in blood as a biomarker for early detection of Alzheimer’s disease.” This approach is currently being validated at UCSD Shiley-Marcos Alzheimer’s Disease Research Center, he added.
Roles of PHGDH and serine in Alzheimer’s disease require further study
Commenting on both studies, Steve W. Barger, PhD, of the University of Arkansas for Medical Sciences, Little Rock, suggested that more work is needed to better understand the roles of PHGDH and serine in AD before clinical applications can be considered.
“In the end, these two studies fail to provide the clarity we need in designing evidence-based therapeutic hypotheses,” Dr. Barger said in an interview. “We still do not have a firm grasp on the role that D-serine plays in AD. Indeed, the evidence regarding even a single enzyme contributing to its levels is ambiguous.”
Dr. Barger, who has published extensively on the topic of neuronal death, with a particular focus on Alzheimer’s disease, noted that “determination of what happens to D-serine levels in AD has been of interest for decades,” but levels of the amino acid have been notoriously challenging to measure because “D-serine can disappear rapidly from the brain and its fluids after death.”
While Dr. Le Douce and colleagues did measure levels of serine in mice, Dr. Barger noted that the study by Dr. Chen and colleagues was conducted with more “quantitatively rigorous methods.” Even though Dr. Chen and colleagues “did not assay the levels of D-serine itself ... the implication of their findings is that PHGDH is poised to elevate this critical neurotransmitter,” leading to their conclusion that serine supplementation is “potentially dangerous.”
At this point, it may be too early to tell, according to Dr. Barger.
He suggested that conclusions drawn from PHGDH levels alone are “always limited,” and conclusions based on serine levels may be equally dubious, considering that the activities and effects of serine “are quite complex,” and may be influenced by other physiologic processes, including the effects of gut bacteria.
Instead, Dr. Barger suggested that changes in PHGDH and serine may be interpreted as signals coming from a more relevant process upstream: glucose metabolism.
“What we can say confidently is that the glucose metabolism that PHGDH connects to D-serine is most definitely a factor in AD,” he said. “Countless studies have documented what now appears to be a universal decline in glucose delivery to the cerebral cortex, even before frank dementia sets in.”
Dr. Barger noted that declining glucose delivery coincides with some of the earliest events in the development of AD, perhaps “linking accumulation of amyloid β-peptide to subsequent neurofibrillary tangles and tissue atrophy.”
Dr. Barger’s own work recently demonstrated that AD is associated with “an irregularity in the insertion of a specific glucose transporter (GLUT1) into the cell surface” of astrocytes.
“It could be more effective to direct therapeutic interventions at these events lying upstream of PHGDH or serine,” he concluded.
The study was partly supported by a Kreuger v. Wyeth research award. The investigators and Dr. Barger reported no conflicts of interest.
When given to patients with AD, L-serine supplements could be driving abnormally increased serine levels in the brain even higher, potentially accelerating neuronal death, according to study author Xu Chen, PhD, of the University of California, San Diego, and colleagues.
This conclusion conflicts with a 2020 study by Juliette Le Douce, PhD, and colleagues, who reported that oral L-serine supplementation may act as a “ready-to-use therapy” for AD, based on their findings that patients with AD had low levels of PHGDH, an enzyme necessary for synthesizing serine, and AD-like mice had low levels of serine.
Writing in Cell Metabolism, Dr. Chen and colleagues framed the present study, and their findings, in this context.
“In contrast to the work of Le Douce et al., here we report that PHGDH mRNA and protein levels are increased in the brains of two mouse models of AD and/or tauopathy, and are also progressively increased in human brains with no, early, and late AD pathology, as well as in people with no, asymptomatic, and symptomatic AD,” they wrote.
They suggested adjusting clinical recommendations for L-serine, the form of the amino acid commonly found in supplements. In the body, L-serine is converted to D-serine, which acts on the NMDA receptor (NMDAR).
‘Long-term use of D-serine contributes to neuronal death’ suggests research
“We feel oral L-serine as a ready-to-use therapy to AD warrants precaution,” Dr. Chen and colleagues wrote. “This is because despite being a cognitive enhancer, some [research] suggests that long-term use of D-serine contributes to neuronal death in AD through excitotoxicity. Furthermore, D-serine, as a co-agonist of NMDAR, would be expected to oppose NMDAR antagonists, which have proven clinical benefits in treating AD.”
According to principal author Sheng Zhong, PhD, of the University of California, San Diego, “Research is needed to test if targeting PHGDH can ameliorate cognitive decline in AD.”
Dr. Zhong also noted that the present findings support the “promise of using a specific RNA in blood as a biomarker for early detection of Alzheimer’s disease.” This approach is currently being validated at UCSD Shiley-Marcos Alzheimer’s Disease Research Center, he added.
Roles of PHGDH and serine in Alzheimer’s disease require further study
Commenting on both studies, Steve W. Barger, PhD, of the University of Arkansas for Medical Sciences, Little Rock, suggested that more work is needed to better understand the roles of PHGDH and serine in AD before clinical applications can be considered.
“In the end, these two studies fail to provide the clarity we need in designing evidence-based therapeutic hypotheses,” Dr. Barger said in an interview. “We still do not have a firm grasp on the role that D-serine plays in AD. Indeed, the evidence regarding even a single enzyme contributing to its levels is ambiguous.”
Dr. Barger, who has published extensively on the topic of neuronal death, with a particular focus on Alzheimer’s disease, noted that “determination of what happens to D-serine levels in AD has been of interest for decades,” but levels of the amino acid have been notoriously challenging to measure because “D-serine can disappear rapidly from the brain and its fluids after death.”
While Dr. Le Douce and colleagues did measure levels of serine in mice, Dr. Barger noted that the study by Dr. Chen and colleagues was conducted with more “quantitatively rigorous methods.” Even though Dr. Chen and colleagues “did not assay the levels of D-serine itself ... the implication of their findings is that PHGDH is poised to elevate this critical neurotransmitter,” leading to their conclusion that serine supplementation is “potentially dangerous.”
At this point, it may be too early to tell, according to Dr. Barger.
He suggested that conclusions drawn from PHGDH levels alone are “always limited,” and conclusions based on serine levels may be equally dubious, considering that the activities and effects of serine “are quite complex,” and may be influenced by other physiologic processes, including the effects of gut bacteria.
Instead, Dr. Barger suggested that changes in PHGDH and serine may be interpreted as signals coming from a more relevant process upstream: glucose metabolism.
“What we can say confidently is that the glucose metabolism that PHGDH connects to D-serine is most definitely a factor in AD,” he said. “Countless studies have documented what now appears to be a universal decline in glucose delivery to the cerebral cortex, even before frank dementia sets in.”
Dr. Barger noted that declining glucose delivery coincides with some of the earliest events in the development of AD, perhaps “linking accumulation of amyloid β-peptide to subsequent neurofibrillary tangles and tissue atrophy.”
Dr. Barger’s own work recently demonstrated that AD is associated with “an irregularity in the insertion of a specific glucose transporter (GLUT1) into the cell surface” of astrocytes.
“It could be more effective to direct therapeutic interventions at these events lying upstream of PHGDH or serine,” he concluded.
The study was partly supported by a Kreuger v. Wyeth research award. The investigators and Dr. Barger reported no conflicts of interest.
FROM CELL METABOLISM
Higher industriousness reduces risk of predementia syndrome in older adults
Higher industriousness was associated with a 25% reduced risk of concurrent motoric cognitive risk syndrome (MCR), based on data from approximately 6,000 individuals.
Previous research supports an association between conscientiousness and a lower risk of MCR, a form of predementia that involves slow gait speed and cognitive complaints, wrote Yannick Stephan, PhD, of the University of Montpellier (France), and colleagues. However, the specific facets of conscientiousness that impact MCR have not been examined.
In a study published in the Journal of Psychiatric Research, the authors reviewed data from 6,001 dementia-free adults aged 65-99 years who were enrolled in the Health and Retirement Study, a nationally representative longitudinal study of adults aged 50 years and older in the United States.
Baseline data were collected between 2008 and 2010, and participants were assessed for MCR at follow-up points during 2012-2014 and 2016-2018. Six facets of conscientiousness were assessed using a 24-item scale that has been used in previous studies. The six facets were industriousness, self-control, order, traditionalism, virtue, and responsibility. The researchers controlled for variables including demographic factors, cognition, physical activity, disease burden, depressive symptoms, and body mass index.
Overall, increased industriousness was significantly associated with a lower likelihood of concurrent MCR (odds ratio, 0.75) and a reduced risk of incident MCR (hazard ratio, 0.63,; P < .001 for both).
The conscientiousness facets of order, self-control, and responsibility also were associated with a lower likelihood of both concurrent and incident MCR, with ORs ranging from 0.82-0.88 for concurrent and HRs ranging from 0.72-0.82 for incident.
Traditionalism and virtue were significantly associated with a lower risk of incident MCR, but not concurrent MCR (HR, 0.84; P < .01 for both).
The mechanism of action for the association may be explained by several cognitive, health-related, behavioral, and psychological pathways, the researchers wrote. With regard to industriousness, the relationship could be partly explained by cognition, physical activity, disease burden, BMI, and depressive symptoms. However, industriousness also has been associated with a reduced risk of systemic inflammation, which may in turn reduce MCR risk. Also, data suggest that industriousness and MCR share a common genetic cause.
The study findings were limited by several factors including the observational design and the positive selection effect from patients with complete follow-up data, as these patients likely have higher levels of order, industriousness, and responsibility, the researchers noted. However, the results support those from previous studies and were strengthened by the large sample and examination of six facets of conscientiousness.
“This study thus provides a more detailed understanding of the specific components of conscientiousness that are associated with risk of MCR among older adults,” and the facets could be targeted in interventions to reduce both MCR and dementia, they concluded.
The Health and Retirement Study is supported by the National Institute on Aging and conducted by the University of Michigan. The current study was supported in part by the National Institutes of Health. The researchers had no financial conflicts to disclose.
Higher industriousness was associated with a 25% reduced risk of concurrent motoric cognitive risk syndrome (MCR), based on data from approximately 6,000 individuals.
Previous research supports an association between conscientiousness and a lower risk of MCR, a form of predementia that involves slow gait speed and cognitive complaints, wrote Yannick Stephan, PhD, of the University of Montpellier (France), and colleagues. However, the specific facets of conscientiousness that impact MCR have not been examined.
In a study published in the Journal of Psychiatric Research, the authors reviewed data from 6,001 dementia-free adults aged 65-99 years who were enrolled in the Health and Retirement Study, a nationally representative longitudinal study of adults aged 50 years and older in the United States.
Baseline data were collected between 2008 and 2010, and participants were assessed for MCR at follow-up points during 2012-2014 and 2016-2018. Six facets of conscientiousness were assessed using a 24-item scale that has been used in previous studies. The six facets were industriousness, self-control, order, traditionalism, virtue, and responsibility. The researchers controlled for variables including demographic factors, cognition, physical activity, disease burden, depressive symptoms, and body mass index.
Overall, increased industriousness was significantly associated with a lower likelihood of concurrent MCR (odds ratio, 0.75) and a reduced risk of incident MCR (hazard ratio, 0.63,; P < .001 for both).
The conscientiousness facets of order, self-control, and responsibility also were associated with a lower likelihood of both concurrent and incident MCR, with ORs ranging from 0.82-0.88 for concurrent and HRs ranging from 0.72-0.82 for incident.
Traditionalism and virtue were significantly associated with a lower risk of incident MCR, but not concurrent MCR (HR, 0.84; P < .01 for both).
The mechanism of action for the association may be explained by several cognitive, health-related, behavioral, and psychological pathways, the researchers wrote. With regard to industriousness, the relationship could be partly explained by cognition, physical activity, disease burden, BMI, and depressive symptoms. However, industriousness also has been associated with a reduced risk of systemic inflammation, which may in turn reduce MCR risk. Also, data suggest that industriousness and MCR share a common genetic cause.
The study findings were limited by several factors including the observational design and the positive selection effect from patients with complete follow-up data, as these patients likely have higher levels of order, industriousness, and responsibility, the researchers noted. However, the results support those from previous studies and were strengthened by the large sample and examination of six facets of conscientiousness.
“This study thus provides a more detailed understanding of the specific components of conscientiousness that are associated with risk of MCR among older adults,” and the facets could be targeted in interventions to reduce both MCR and dementia, they concluded.
The Health and Retirement Study is supported by the National Institute on Aging and conducted by the University of Michigan. The current study was supported in part by the National Institutes of Health. The researchers had no financial conflicts to disclose.
Higher industriousness was associated with a 25% reduced risk of concurrent motoric cognitive risk syndrome (MCR), based on data from approximately 6,000 individuals.
Previous research supports an association between conscientiousness and a lower risk of MCR, a form of predementia that involves slow gait speed and cognitive complaints, wrote Yannick Stephan, PhD, of the University of Montpellier (France), and colleagues. However, the specific facets of conscientiousness that impact MCR have not been examined.
In a study published in the Journal of Psychiatric Research, the authors reviewed data from 6,001 dementia-free adults aged 65-99 years who were enrolled in the Health and Retirement Study, a nationally representative longitudinal study of adults aged 50 years and older in the United States.
Baseline data were collected between 2008 and 2010, and participants were assessed for MCR at follow-up points during 2012-2014 and 2016-2018. Six facets of conscientiousness were assessed using a 24-item scale that has been used in previous studies. The six facets were industriousness, self-control, order, traditionalism, virtue, and responsibility. The researchers controlled for variables including demographic factors, cognition, physical activity, disease burden, depressive symptoms, and body mass index.
Overall, increased industriousness was significantly associated with a lower likelihood of concurrent MCR (odds ratio, 0.75) and a reduced risk of incident MCR (hazard ratio, 0.63,; P < .001 for both).
The conscientiousness facets of order, self-control, and responsibility also were associated with a lower likelihood of both concurrent and incident MCR, with ORs ranging from 0.82-0.88 for concurrent and HRs ranging from 0.72-0.82 for incident.
Traditionalism and virtue were significantly associated with a lower risk of incident MCR, but not concurrent MCR (HR, 0.84; P < .01 for both).
The mechanism of action for the association may be explained by several cognitive, health-related, behavioral, and psychological pathways, the researchers wrote. With regard to industriousness, the relationship could be partly explained by cognition, physical activity, disease burden, BMI, and depressive symptoms. However, industriousness also has been associated with a reduced risk of systemic inflammation, which may in turn reduce MCR risk. Also, data suggest that industriousness and MCR share a common genetic cause.
The study findings were limited by several factors including the observational design and the positive selection effect from patients with complete follow-up data, as these patients likely have higher levels of order, industriousness, and responsibility, the researchers noted. However, the results support those from previous studies and were strengthened by the large sample and examination of six facets of conscientiousness.
“This study thus provides a more detailed understanding of the specific components of conscientiousness that are associated with risk of MCR among older adults,” and the facets could be targeted in interventions to reduce both MCR and dementia, they concluded.
The Health and Retirement Study is supported by the National Institute on Aging and conducted by the University of Michigan. The current study was supported in part by the National Institutes of Health. The researchers had no financial conflicts to disclose.
FROM PSYCHIATRIC RESEARCH
Best antioxidants to prevent age-related dementia identified?
Investigators found that individuals with the highest serum levels of lutein + zeaxanthin and beta-cryptoxanthin at baseline were less likely to have dementia decades later than were their peers with lower levels of these antioxidants.
Lutein and zeaxanthin are found in green leafy vegetables such as kale, spinach, broccoli, and peas. Beta-cryptoxanthin is found in fruits such as oranges, papaya, tangerines, and persimmons.
“Antioxidants may help protect the brain from oxidative stress, which can cause cell damage,” first author May A. Beydoun, PhD, with the National Institute on Aging (NIA), said in a news release.
“This is the first nationally representative study to analyze blood levels of antioxidants in relation to dementia risk,” NIA scientific director Luigi Ferrucci, MD, said in an interview.
“Blood test results may be more representative of the actual antioxidant level than a person’s report of what kind of foods they regularly consume,” Dr. Ferrucci added.
The study was published online in Neurology.
Reduced dementia risk
The researchers tested associations and interactions of serum vitamins A, C and E, and total and individual serum carotenoids and interactions with incident Alzheimer’s disease (AD) and all-cause dementia.
They analyzed data from 7,283 participants in the Third National Health and Nutrition Examination Survey (NHANES III) who were at least 45 years old at baseline and followed for an average of 16-17 years.
They found serum levels of lutein + zeaxanthin were associated with reduced risk of all-cause dementia among people aged 65 and older in models adjusted for lifestyle.
For lutein + zeaxanthin, every standard deviation (SD) increase (roughly 15.4 µmol/liter) was associated with a 7% decrease in risk for dementia (hazard ratio [HR] 0.93; 95% confidence interval [CI], 0.87-0.99, P = .037). This association was attenuated somewhat after adjustment for socioeconomic status.
Serum levels of beta-cryptoxanthin showed a “strong” inverse relationship with all-cause dementia in age- and sex-adjusted models.
For beta-cryptoxanthin, every SD increase (roughly 8.6 µmol/liter) was associated with a 14% reduced risk for dementia in people aged 45 and older (HR, 0.86; 95% CI, 0.80-0.93, P < .001) and 65 and older (HR, 0.86; 95% CI, 0.80-0.93, P = .001).
This relationship remained strong in models adjusted for sociodemographic and socioeconomic factors but attenuated in subsequent models.
No associations were found for lycopene, alpha-carotene, beta-carotene, or vitamins A, C, or E in the fully adjusted models.
Antagonistic interactions were observed for vitamin A and alpha-carotene, vitamin A and beta-carotene, vitamin E and lycopene, and lycopene and beta-carotene, suggesting putative protective effects of one antioxidant at lower levels of the other, the researchers noted.
“This analysis of an observational study found that the most important carotenoids in potentially protecting the brain may be lutein + zeaxanthin and beta-cryptoxanthin. However, randomized controlled trials are needed to prove causality,” said Dr. Ferrucci.
“Experts do not yet know the daily level of antioxidant intake to promote healthy aging of the brain. More research is needed to establish the necessary level of antioxidant intake – through the diet and/or supplements – to promote brain health and healthy aging,” he added.
An important step forward
In an accompanying editorial, Babak Hooshmand, MD, PhD, and Miia Kivipelto, MD, PhD, with Karolinska Institute, Stockholm, noted that while nutrition and dietary components are “potential targets” for dementia risk reduction, observational studies to date have reported “inconsistent findings.”
This study is “an important step towards exploring the complex relationship between antioxidants and dementia because it accounts for factors that could possibly influence the associations and considers interactions between different components,” they wrote.
The findings are “challenging,” they added, because they may lead to the hypothesis that inhibition of oxidative damage by antioxidants might have beneficial effects on preventing dementia.
However, clinical trials of antioxidant supplementation have been mainly “disappointing” and a recent Cochrane review found a lack of evidence for supplement use to preserve cognitive function or prevent dementia, Dr. Hooshmand and Dr. Kivipelto noted.
They added that the study contributes to the belief that antioxidants don’t act independently of each other or other factors, including socioeconomic status and lifestyle, in the mediation of dementia risk.
“A careful examination of the evidence is required to learn how antioxidants influence the complex pathology of dementia, because it appears to be more to it than meets the eye,”they concluded.
The research was supported in part by the Intramural Research Program of the National Institutes of Health and the National Institute on Aging. Dr. Beydoun, Dr. Ferrucci, and Dr. Hooshmand report no relevant disclosures. Dr. Kivipelto has supported advisory boards for Combinostics, Roche, and Biogen.
A version of this article first appeared on Medscape.com.
Investigators found that individuals with the highest serum levels of lutein + zeaxanthin and beta-cryptoxanthin at baseline were less likely to have dementia decades later than were their peers with lower levels of these antioxidants.
Lutein and zeaxanthin are found in green leafy vegetables such as kale, spinach, broccoli, and peas. Beta-cryptoxanthin is found in fruits such as oranges, papaya, tangerines, and persimmons.
“Antioxidants may help protect the brain from oxidative stress, which can cause cell damage,” first author May A. Beydoun, PhD, with the National Institute on Aging (NIA), said in a news release.
“This is the first nationally representative study to analyze blood levels of antioxidants in relation to dementia risk,” NIA scientific director Luigi Ferrucci, MD, said in an interview.
“Blood test results may be more representative of the actual antioxidant level than a person’s report of what kind of foods they regularly consume,” Dr. Ferrucci added.
The study was published online in Neurology.
Reduced dementia risk
The researchers tested associations and interactions of serum vitamins A, C and E, and total and individual serum carotenoids and interactions with incident Alzheimer’s disease (AD) and all-cause dementia.
They analyzed data from 7,283 participants in the Third National Health and Nutrition Examination Survey (NHANES III) who were at least 45 years old at baseline and followed for an average of 16-17 years.
They found serum levels of lutein + zeaxanthin were associated with reduced risk of all-cause dementia among people aged 65 and older in models adjusted for lifestyle.
For lutein + zeaxanthin, every standard deviation (SD) increase (roughly 15.4 µmol/liter) was associated with a 7% decrease in risk for dementia (hazard ratio [HR] 0.93; 95% confidence interval [CI], 0.87-0.99, P = .037). This association was attenuated somewhat after adjustment for socioeconomic status.
Serum levels of beta-cryptoxanthin showed a “strong” inverse relationship with all-cause dementia in age- and sex-adjusted models.
For beta-cryptoxanthin, every SD increase (roughly 8.6 µmol/liter) was associated with a 14% reduced risk for dementia in people aged 45 and older (HR, 0.86; 95% CI, 0.80-0.93, P < .001) and 65 and older (HR, 0.86; 95% CI, 0.80-0.93, P = .001).
This relationship remained strong in models adjusted for sociodemographic and socioeconomic factors but attenuated in subsequent models.
No associations were found for lycopene, alpha-carotene, beta-carotene, or vitamins A, C, or E in the fully adjusted models.
Antagonistic interactions were observed for vitamin A and alpha-carotene, vitamin A and beta-carotene, vitamin E and lycopene, and lycopene and beta-carotene, suggesting putative protective effects of one antioxidant at lower levels of the other, the researchers noted.
“This analysis of an observational study found that the most important carotenoids in potentially protecting the brain may be lutein + zeaxanthin and beta-cryptoxanthin. However, randomized controlled trials are needed to prove causality,” said Dr. Ferrucci.
“Experts do not yet know the daily level of antioxidant intake to promote healthy aging of the brain. More research is needed to establish the necessary level of antioxidant intake – through the diet and/or supplements – to promote brain health and healthy aging,” he added.
An important step forward
In an accompanying editorial, Babak Hooshmand, MD, PhD, and Miia Kivipelto, MD, PhD, with Karolinska Institute, Stockholm, noted that while nutrition and dietary components are “potential targets” for dementia risk reduction, observational studies to date have reported “inconsistent findings.”
This study is “an important step towards exploring the complex relationship between antioxidants and dementia because it accounts for factors that could possibly influence the associations and considers interactions between different components,” they wrote.
The findings are “challenging,” they added, because they may lead to the hypothesis that inhibition of oxidative damage by antioxidants might have beneficial effects on preventing dementia.
However, clinical trials of antioxidant supplementation have been mainly “disappointing” and a recent Cochrane review found a lack of evidence for supplement use to preserve cognitive function or prevent dementia, Dr. Hooshmand and Dr. Kivipelto noted.
They added that the study contributes to the belief that antioxidants don’t act independently of each other or other factors, including socioeconomic status and lifestyle, in the mediation of dementia risk.
“A careful examination of the evidence is required to learn how antioxidants influence the complex pathology of dementia, because it appears to be more to it than meets the eye,”they concluded.
The research was supported in part by the Intramural Research Program of the National Institutes of Health and the National Institute on Aging. Dr. Beydoun, Dr. Ferrucci, and Dr. Hooshmand report no relevant disclosures. Dr. Kivipelto has supported advisory boards for Combinostics, Roche, and Biogen.
A version of this article first appeared on Medscape.com.
Investigators found that individuals with the highest serum levels of lutein + zeaxanthin and beta-cryptoxanthin at baseline were less likely to have dementia decades later than were their peers with lower levels of these antioxidants.
Lutein and zeaxanthin are found in green leafy vegetables such as kale, spinach, broccoli, and peas. Beta-cryptoxanthin is found in fruits such as oranges, papaya, tangerines, and persimmons.
“Antioxidants may help protect the brain from oxidative stress, which can cause cell damage,” first author May A. Beydoun, PhD, with the National Institute on Aging (NIA), said in a news release.
“This is the first nationally representative study to analyze blood levels of antioxidants in relation to dementia risk,” NIA scientific director Luigi Ferrucci, MD, said in an interview.
“Blood test results may be more representative of the actual antioxidant level than a person’s report of what kind of foods they regularly consume,” Dr. Ferrucci added.
The study was published online in Neurology.
Reduced dementia risk
The researchers tested associations and interactions of serum vitamins A, C and E, and total and individual serum carotenoids and interactions with incident Alzheimer’s disease (AD) and all-cause dementia.
They analyzed data from 7,283 participants in the Third National Health and Nutrition Examination Survey (NHANES III) who were at least 45 years old at baseline and followed for an average of 16-17 years.
They found serum levels of lutein + zeaxanthin were associated with reduced risk of all-cause dementia among people aged 65 and older in models adjusted for lifestyle.
For lutein + zeaxanthin, every standard deviation (SD) increase (roughly 15.4 µmol/liter) was associated with a 7% decrease in risk for dementia (hazard ratio [HR] 0.93; 95% confidence interval [CI], 0.87-0.99, P = .037). This association was attenuated somewhat after adjustment for socioeconomic status.
Serum levels of beta-cryptoxanthin showed a “strong” inverse relationship with all-cause dementia in age- and sex-adjusted models.
For beta-cryptoxanthin, every SD increase (roughly 8.6 µmol/liter) was associated with a 14% reduced risk for dementia in people aged 45 and older (HR, 0.86; 95% CI, 0.80-0.93, P < .001) and 65 and older (HR, 0.86; 95% CI, 0.80-0.93, P = .001).
This relationship remained strong in models adjusted for sociodemographic and socioeconomic factors but attenuated in subsequent models.
No associations were found for lycopene, alpha-carotene, beta-carotene, or vitamins A, C, or E in the fully adjusted models.
Antagonistic interactions were observed for vitamin A and alpha-carotene, vitamin A and beta-carotene, vitamin E and lycopene, and lycopene and beta-carotene, suggesting putative protective effects of one antioxidant at lower levels of the other, the researchers noted.
“This analysis of an observational study found that the most important carotenoids in potentially protecting the brain may be lutein + zeaxanthin and beta-cryptoxanthin. However, randomized controlled trials are needed to prove causality,” said Dr. Ferrucci.
“Experts do not yet know the daily level of antioxidant intake to promote healthy aging of the brain. More research is needed to establish the necessary level of antioxidant intake – through the diet and/or supplements – to promote brain health and healthy aging,” he added.
An important step forward
In an accompanying editorial, Babak Hooshmand, MD, PhD, and Miia Kivipelto, MD, PhD, with Karolinska Institute, Stockholm, noted that while nutrition and dietary components are “potential targets” for dementia risk reduction, observational studies to date have reported “inconsistent findings.”
This study is “an important step towards exploring the complex relationship between antioxidants and dementia because it accounts for factors that could possibly influence the associations and considers interactions between different components,” they wrote.
The findings are “challenging,” they added, because they may lead to the hypothesis that inhibition of oxidative damage by antioxidants might have beneficial effects on preventing dementia.
However, clinical trials of antioxidant supplementation have been mainly “disappointing” and a recent Cochrane review found a lack of evidence for supplement use to preserve cognitive function or prevent dementia, Dr. Hooshmand and Dr. Kivipelto noted.
They added that the study contributes to the belief that antioxidants don’t act independently of each other or other factors, including socioeconomic status and lifestyle, in the mediation of dementia risk.
“A careful examination of the evidence is required to learn how antioxidants influence the complex pathology of dementia, because it appears to be more to it than meets the eye,”they concluded.
The research was supported in part by the Intramural Research Program of the National Institutes of Health and the National Institute on Aging. Dr. Beydoun, Dr. Ferrucci, and Dr. Hooshmand report no relevant disclosures. Dr. Kivipelto has supported advisory boards for Combinostics, Roche, and Biogen.
A version of this article first appeared on Medscape.com.
FROM NEUROLOGY
Residential green space linked to better cognitive function
Exposure to green space may boost cognitive function, new research suggests.
This association may be explained by a reduction in depression, researchers note. Scores for overall cognition and psychomotor speed/attention among women with high green-space exposure were equivalent to those of women an average of 1.2 years younger, they add.
“Despite the fact that the women in our study were relatively younger than those in previous studies, we were still able to detect protective associations between green space and cognition,” lead author Marcia Pescador Jimenez, PhD, assistant professor of epidemiology, Boston University School of Public Health, told this news organization.
“This may signal the public health importance of green space and the important clinical implications at the population level,” she said.
The findings were published online in JAMA Network Open.
Better psychomotor speed, attention
Recent studies on the benefits of green space have shown a link between higher exposure and reduced risks for schizophrenia and ischemic stroke. Other studies have explored the link between green space and dementia and Alzheimer’s disease.
Cognitive function in middle age is associated with subsequent dementia, so Dr. Jimenez said she and her colleagues wanted to analyze the effect of residential green space on cognitive function in middle-aged women.
The study included 13,594 women (median age, 61.2 years) who are participants in the ongoing Nurses’ Health Study II, one of the largest studies to examine risk factors for chronic illness in women.
To calculate the amount of green space, researchers used the Normalized Difference Vegetation Index (NDVI), a satellite-based indicator of green vegetation around a residential address. The data were based on each participant’s 2013 residence.
After adjusting for age at assessment, race, and childhood, adulthood, and neighborhood socioeconomic status, green space was associated with higher scores on the global CogState composite (mean difference per interquartile range in green space, 0.05; 95% confidence interval, .02-.07) and psychomotor speed and attention (mean difference in score, 0.05 standard units; 95% CI, .02-.08) scales.
There was no association between green-space exposure and learning and working memory. Investigators also found no differences based on urbanicity, suggesting the benefits were similar for urban versus rural settings.
Specific to cognitive domains
“We were surprised to see that while our study found that higher levels of residential green space were associated with higher scores on processing speed and attention and on overall cognition, we also found that higher levels of residential green space were not associated with learning/working memory battery scores,” Dr. Jimenez said.
“This is actually in-line with previous research suggesting differing associations between green space and cognition based on the cognitive domain examined,” she added.
About 98% of participants were White, limiting the generalizability of the findings, the researchers note. There was also no information on proximity to or size of green space, or how much time individuals spent in the green space and what kinds of activities they engaged in.
Dr. Jimenez said projects examining the amount of time of green-space exposure are underway.
In addition, the researchers found lower rates of depression might contribute to the cognitive benefits associated with green-space exposure, explaining 3.95% (95% CI, .35%-7.55%) of the association between green space and psychomotor speed/attention and 6.3% (95% CI, .77%-11.81%) of the association between green space and overall cognition.
Reduced air pollution and increased physical activity, which are other factors often thought to contribute to the cognitive benefits of green space, were not significant in this study.
‘Interesting and novel’
Commenting on the findings, Payam Dadvand, MD, PhD, associate research professor, Barcelona Institute for Global Health, called the finding that depression may mediate green-space benefits “quite interesting and novel.”
“The results of this study, given its large sample size and its geographical coverage, adds to an emerging body of evidence on the beneficial association of exposure to green space on aging, and in particular, cognitive aging in older adults,” said Dr. Dadvand, who was not involved with the research.
The study was funded by the National Institutes of Health. Dr. Jimenez and Dr. Dadvand have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Exposure to green space may boost cognitive function, new research suggests.
This association may be explained by a reduction in depression, researchers note. Scores for overall cognition and psychomotor speed/attention among women with high green-space exposure were equivalent to those of women an average of 1.2 years younger, they add.
“Despite the fact that the women in our study were relatively younger than those in previous studies, we were still able to detect protective associations between green space and cognition,” lead author Marcia Pescador Jimenez, PhD, assistant professor of epidemiology, Boston University School of Public Health, told this news organization.
“This may signal the public health importance of green space and the important clinical implications at the population level,” she said.
The findings were published online in JAMA Network Open.
Better psychomotor speed, attention
Recent studies on the benefits of green space have shown a link between higher exposure and reduced risks for schizophrenia and ischemic stroke. Other studies have explored the link between green space and dementia and Alzheimer’s disease.
Cognitive function in middle age is associated with subsequent dementia, so Dr. Jimenez said she and her colleagues wanted to analyze the effect of residential green space on cognitive function in middle-aged women.
The study included 13,594 women (median age, 61.2 years) who are participants in the ongoing Nurses’ Health Study II, one of the largest studies to examine risk factors for chronic illness in women.
To calculate the amount of green space, researchers used the Normalized Difference Vegetation Index (NDVI), a satellite-based indicator of green vegetation around a residential address. The data were based on each participant’s 2013 residence.
After adjusting for age at assessment, race, and childhood, adulthood, and neighborhood socioeconomic status, green space was associated with higher scores on the global CogState composite (mean difference per interquartile range in green space, 0.05; 95% confidence interval, .02-.07) and psychomotor speed and attention (mean difference in score, 0.05 standard units; 95% CI, .02-.08) scales.
There was no association between green-space exposure and learning and working memory. Investigators also found no differences based on urbanicity, suggesting the benefits were similar for urban versus rural settings.
Specific to cognitive domains
“We were surprised to see that while our study found that higher levels of residential green space were associated with higher scores on processing speed and attention and on overall cognition, we also found that higher levels of residential green space were not associated with learning/working memory battery scores,” Dr. Jimenez said.
“This is actually in-line with previous research suggesting differing associations between green space and cognition based on the cognitive domain examined,” she added.
About 98% of participants were White, limiting the generalizability of the findings, the researchers note. There was also no information on proximity to or size of green space, or how much time individuals spent in the green space and what kinds of activities they engaged in.
Dr. Jimenez said projects examining the amount of time of green-space exposure are underway.
In addition, the researchers found lower rates of depression might contribute to the cognitive benefits associated with green-space exposure, explaining 3.95% (95% CI, .35%-7.55%) of the association between green space and psychomotor speed/attention and 6.3% (95% CI, .77%-11.81%) of the association between green space and overall cognition.
Reduced air pollution and increased physical activity, which are other factors often thought to contribute to the cognitive benefits of green space, were not significant in this study.
‘Interesting and novel’
Commenting on the findings, Payam Dadvand, MD, PhD, associate research professor, Barcelona Institute for Global Health, called the finding that depression may mediate green-space benefits “quite interesting and novel.”
“The results of this study, given its large sample size and its geographical coverage, adds to an emerging body of evidence on the beneficial association of exposure to green space on aging, and in particular, cognitive aging in older adults,” said Dr. Dadvand, who was not involved with the research.
The study was funded by the National Institutes of Health. Dr. Jimenez and Dr. Dadvand have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Exposure to green space may boost cognitive function, new research suggests.
This association may be explained by a reduction in depression, researchers note. Scores for overall cognition and psychomotor speed/attention among women with high green-space exposure were equivalent to those of women an average of 1.2 years younger, they add.
“Despite the fact that the women in our study were relatively younger than those in previous studies, we were still able to detect protective associations between green space and cognition,” lead author Marcia Pescador Jimenez, PhD, assistant professor of epidemiology, Boston University School of Public Health, told this news organization.
“This may signal the public health importance of green space and the important clinical implications at the population level,” she said.
The findings were published online in JAMA Network Open.
Better psychomotor speed, attention
Recent studies on the benefits of green space have shown a link between higher exposure and reduced risks for schizophrenia and ischemic stroke. Other studies have explored the link between green space and dementia and Alzheimer’s disease.
Cognitive function in middle age is associated with subsequent dementia, so Dr. Jimenez said she and her colleagues wanted to analyze the effect of residential green space on cognitive function in middle-aged women.
The study included 13,594 women (median age, 61.2 years) who are participants in the ongoing Nurses’ Health Study II, one of the largest studies to examine risk factors for chronic illness in women.
To calculate the amount of green space, researchers used the Normalized Difference Vegetation Index (NDVI), a satellite-based indicator of green vegetation around a residential address. The data were based on each participant’s 2013 residence.
After adjusting for age at assessment, race, and childhood, adulthood, and neighborhood socioeconomic status, green space was associated with higher scores on the global CogState composite (mean difference per interquartile range in green space, 0.05; 95% confidence interval, .02-.07) and psychomotor speed and attention (mean difference in score, 0.05 standard units; 95% CI, .02-.08) scales.
There was no association between green-space exposure and learning and working memory. Investigators also found no differences based on urbanicity, suggesting the benefits were similar for urban versus rural settings.
Specific to cognitive domains
“We were surprised to see that while our study found that higher levels of residential green space were associated with higher scores on processing speed and attention and on overall cognition, we also found that higher levels of residential green space were not associated with learning/working memory battery scores,” Dr. Jimenez said.
“This is actually in-line with previous research suggesting differing associations between green space and cognition based on the cognitive domain examined,” she added.
About 98% of participants were White, limiting the generalizability of the findings, the researchers note. There was also no information on proximity to or size of green space, or how much time individuals spent in the green space and what kinds of activities they engaged in.
Dr. Jimenez said projects examining the amount of time of green-space exposure are underway.
In addition, the researchers found lower rates of depression might contribute to the cognitive benefits associated with green-space exposure, explaining 3.95% (95% CI, .35%-7.55%) of the association between green space and psychomotor speed/attention and 6.3% (95% CI, .77%-11.81%) of the association between green space and overall cognition.
Reduced air pollution and increased physical activity, which are other factors often thought to contribute to the cognitive benefits of green space, were not significant in this study.
‘Interesting and novel’
Commenting on the findings, Payam Dadvand, MD, PhD, associate research professor, Barcelona Institute for Global Health, called the finding that depression may mediate green-space benefits “quite interesting and novel.”
“The results of this study, given its large sample size and its geographical coverage, adds to an emerging body of evidence on the beneficial association of exposure to green space on aging, and in particular, cognitive aging in older adults,” said Dr. Dadvand, who was not involved with the research.
The study was funded by the National Institutes of Health. Dr. Jimenez and Dr. Dadvand have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FDA clears diagnostic test for early Alzheimer’s
The Lumipulse G β-Amyloid Ratio 1-42/1-40 (Fujirebio Diagnostics) test detects amyloid plaques associated with AD in adults age 55 or older who are under investigation for AD and other causes of cognitive decline.
“The availability of an in vitro diagnostic test that can potentially eliminate the need for time-consuming and expensive [positron emission tomography (PET)] scans is great news for individuals and families concerned with the possibility of an Alzheimer’s disease diagnosis,” Jeff Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological Health, said in a statement.
“With the Lumipulse test, there is a new option that can typically be completed the same day and can give doctors the same information regarding brain amyloid status, without the radiation risk, to help determine if a patient’s cognitive impairment is due to Alzheimer’s disease,” he added.
In its statement, the FDA notes that there is an “unmet need for a reliable and safe test that can accurately identify patients with amyloid plaques consistent with Alzheimer’s disease.”
The agency goes on to state that this new test may eliminate the need to use PET brain scans, a “potentially costly and cumbersome option” to visualize amyloid plaques for the diagnosis of AD.
The Lumipulse test measures the ratio of β-amyloid 1-42 and β-amyloid 1-40 concentrations in human cerebral spinal fluid (CSF). A positive Lumipulse G β-amyloid Ratio (1-42/1-40) test result is consistent with the presence of amyloid plaques, similar to that revealed in a PET scan. A negative result is consistent with a negative amyloid PET scan result.
However, the FDA notes that the test is not a stand-alone assay and should be used in conjunction with other clinical evaluations and additional tests to determine treatment options.
The FDA reports that it evaluated the safety and efficacy of the test in a clinical study of 292 CSF samples from the Alzheimer’s Disease Neuroimaging Initiative sample bank.
The samples were tested by the Lumipulse G β-amyloid Ratio (1-42/1-40) and compared with amyloid PET scan results. In this clinical study, 97% of individuals with Lumipulse G β-amyloid Ratio (1-42/1-40) positive results had the presence of amyloid plaques by PET scan and 84% of individuals with negative results had a negative amyloid PET scan.
The risks associated with the Lumipulse G β-amyloid Ratio (1-42/1-40) test are mainly the possibility of false-positive and false-negative test results.
False-positive results, in conjunction with other clinical information, could lead to an inappropriate diagnosis of, and unnecessary treatment for AD.
False-negative test results could result in additional unnecessary diagnostic tests and potential delay in effective treatment for AD.
The FDA reviewed the device through the De Novo premarket review pathway, a regulatory pathway for low- to moderate-risk devices of a new type.
The agency says this action “creates a new regulatory classification, which means that subsequent devices of the same type with the same intended use may go through FDA’s 510(k) premarket process, whereby devices can obtain marketing authorization by demonstrating substantial equivalence to a predicate device.”
The Lumipulse G β-amyloid Ratio (1-42/1-40) was granted Breakthrough Device designation, a process designed to expedite the development and review of devices that may provide for more effective treatment or diagnosis of life-threatening or irreversibly debilitating diseases or conditions.
A version of this article first appeared on Medscape.com.
The Lumipulse G β-Amyloid Ratio 1-42/1-40 (Fujirebio Diagnostics) test detects amyloid plaques associated with AD in adults age 55 or older who are under investigation for AD and other causes of cognitive decline.
“The availability of an in vitro diagnostic test that can potentially eliminate the need for time-consuming and expensive [positron emission tomography (PET)] scans is great news for individuals and families concerned with the possibility of an Alzheimer’s disease diagnosis,” Jeff Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological Health, said in a statement.
“With the Lumipulse test, there is a new option that can typically be completed the same day and can give doctors the same information regarding brain amyloid status, without the radiation risk, to help determine if a patient’s cognitive impairment is due to Alzheimer’s disease,” he added.
In its statement, the FDA notes that there is an “unmet need for a reliable and safe test that can accurately identify patients with amyloid plaques consistent with Alzheimer’s disease.”
The agency goes on to state that this new test may eliminate the need to use PET brain scans, a “potentially costly and cumbersome option” to visualize amyloid plaques for the diagnosis of AD.
The Lumipulse test measures the ratio of β-amyloid 1-42 and β-amyloid 1-40 concentrations in human cerebral spinal fluid (CSF). A positive Lumipulse G β-amyloid Ratio (1-42/1-40) test result is consistent with the presence of amyloid plaques, similar to that revealed in a PET scan. A negative result is consistent with a negative amyloid PET scan result.
However, the FDA notes that the test is not a stand-alone assay and should be used in conjunction with other clinical evaluations and additional tests to determine treatment options.
The FDA reports that it evaluated the safety and efficacy of the test in a clinical study of 292 CSF samples from the Alzheimer’s Disease Neuroimaging Initiative sample bank.
The samples were tested by the Lumipulse G β-amyloid Ratio (1-42/1-40) and compared with amyloid PET scan results. In this clinical study, 97% of individuals with Lumipulse G β-amyloid Ratio (1-42/1-40) positive results had the presence of amyloid plaques by PET scan and 84% of individuals with negative results had a negative amyloid PET scan.
The risks associated with the Lumipulse G β-amyloid Ratio (1-42/1-40) test are mainly the possibility of false-positive and false-negative test results.
False-positive results, in conjunction with other clinical information, could lead to an inappropriate diagnosis of, and unnecessary treatment for AD.
False-negative test results could result in additional unnecessary diagnostic tests and potential delay in effective treatment for AD.
The FDA reviewed the device through the De Novo premarket review pathway, a regulatory pathway for low- to moderate-risk devices of a new type.
The agency says this action “creates a new regulatory classification, which means that subsequent devices of the same type with the same intended use may go through FDA’s 510(k) premarket process, whereby devices can obtain marketing authorization by demonstrating substantial equivalence to a predicate device.”
The Lumipulse G β-amyloid Ratio (1-42/1-40) was granted Breakthrough Device designation, a process designed to expedite the development and review of devices that may provide for more effective treatment or diagnosis of life-threatening or irreversibly debilitating diseases or conditions.
A version of this article first appeared on Medscape.com.
The Lumipulse G β-Amyloid Ratio 1-42/1-40 (Fujirebio Diagnostics) test detects amyloid plaques associated with AD in adults age 55 or older who are under investigation for AD and other causes of cognitive decline.
“The availability of an in vitro diagnostic test that can potentially eliminate the need for time-consuming and expensive [positron emission tomography (PET)] scans is great news for individuals and families concerned with the possibility of an Alzheimer’s disease diagnosis,” Jeff Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological Health, said in a statement.
“With the Lumipulse test, there is a new option that can typically be completed the same day and can give doctors the same information regarding brain amyloid status, without the radiation risk, to help determine if a patient’s cognitive impairment is due to Alzheimer’s disease,” he added.
In its statement, the FDA notes that there is an “unmet need for a reliable and safe test that can accurately identify patients with amyloid plaques consistent with Alzheimer’s disease.”
The agency goes on to state that this new test may eliminate the need to use PET brain scans, a “potentially costly and cumbersome option” to visualize amyloid plaques for the diagnosis of AD.
The Lumipulse test measures the ratio of β-amyloid 1-42 and β-amyloid 1-40 concentrations in human cerebral spinal fluid (CSF). A positive Lumipulse G β-amyloid Ratio (1-42/1-40) test result is consistent with the presence of amyloid plaques, similar to that revealed in a PET scan. A negative result is consistent with a negative amyloid PET scan result.
However, the FDA notes that the test is not a stand-alone assay and should be used in conjunction with other clinical evaluations and additional tests to determine treatment options.
The FDA reports that it evaluated the safety and efficacy of the test in a clinical study of 292 CSF samples from the Alzheimer’s Disease Neuroimaging Initiative sample bank.
The samples were tested by the Lumipulse G β-amyloid Ratio (1-42/1-40) and compared with amyloid PET scan results. In this clinical study, 97% of individuals with Lumipulse G β-amyloid Ratio (1-42/1-40) positive results had the presence of amyloid plaques by PET scan and 84% of individuals with negative results had a negative amyloid PET scan.
The risks associated with the Lumipulse G β-amyloid Ratio (1-42/1-40) test are mainly the possibility of false-positive and false-negative test results.
False-positive results, in conjunction with other clinical information, could lead to an inappropriate diagnosis of, and unnecessary treatment for AD.
False-negative test results could result in additional unnecessary diagnostic tests and potential delay in effective treatment for AD.
The FDA reviewed the device through the De Novo premarket review pathway, a regulatory pathway for low- to moderate-risk devices of a new type.
The agency says this action “creates a new regulatory classification, which means that subsequent devices of the same type with the same intended use may go through FDA’s 510(k) premarket process, whereby devices can obtain marketing authorization by demonstrating substantial equivalence to a predicate device.”
The Lumipulse G β-amyloid Ratio (1-42/1-40) was granted Breakthrough Device designation, a process designed to expedite the development and review of devices that may provide for more effective treatment or diagnosis of life-threatening or irreversibly debilitating diseases or conditions.
A version of this article first appeared on Medscape.com.