User login
FDA okays first biosimilar for multiple sclerosis
including clinically isolated syndrome, relapsing remitting MS, and active secondary progressive disease.
“Biosimilar medications offer additional effective treatment options that have the potential to increase access for people living with relapsing forms of multiple sclerosis. [This] approval could have a meaningful impact for patients managing their disease,” Paul R. Lee, MD, PhD, director of the division of neurology II, FDA Center for Drug Evaluation and Research, said in a statement.
The natalizumab biosimilar is given using the same dosing and administration schedule. Like the reference product, it is indicated for adults with moderately to severely active Crohn’s disease unresponsive to other medications.
The approval of the natalizumab biosimilar is based on results of the phase 3 Antelope trial, which showed no clinically meaningful differences between it and the reference product.
The trial included 264 adults (mean age, 36 years; 61% women) with relapsing remitting MS from 48 centers in seven Eastern European countries.
All were randomly assigned to receive intravenous infusions every 4 weeks of 300 mg of the natalizumab biosimilar or the reference product for a total of 12 infusions.
At 24 and 48 weeks, there were no between-group differences in annualized relapse rates or Expanded Disability Status Scale scores, which were similar between treatment groups at baseline. There were also no significant differences in safety, tolerability, or immunogenicity.
The prescribing information for both natalizumab products includes a boxed warning about the increased risk of progressive multifocal leukoencephalopathy (PML), a viral infection of the brain that usually leads to death or severe disability.
Risk factors for the development of PML include the presence of antibodies to the JC virus, longer duration of therapy, and prior use of immunosuppressants.
“These factors should be considered in the context of expected benefit when initiating and continuing treatment with natalizumab products, and health care providers should monitor patients and withhold treatment immediately at the first sign or symptom suggestive of PML,” the FDA advises.
Because of the risks of PML, natalizumab products are available only through a restricted drug distribution program under a risk evaluation and mitigation strategy.
In a statement, Sandoz said it’s committed to having the product available in the United States “as soon as possible.”
A version of this article appeared on Medscape.com.
including clinically isolated syndrome, relapsing remitting MS, and active secondary progressive disease.
“Biosimilar medications offer additional effective treatment options that have the potential to increase access for people living with relapsing forms of multiple sclerosis. [This] approval could have a meaningful impact for patients managing their disease,” Paul R. Lee, MD, PhD, director of the division of neurology II, FDA Center for Drug Evaluation and Research, said in a statement.
The natalizumab biosimilar is given using the same dosing and administration schedule. Like the reference product, it is indicated for adults with moderately to severely active Crohn’s disease unresponsive to other medications.
The approval of the natalizumab biosimilar is based on results of the phase 3 Antelope trial, which showed no clinically meaningful differences between it and the reference product.
The trial included 264 adults (mean age, 36 years; 61% women) with relapsing remitting MS from 48 centers in seven Eastern European countries.
All were randomly assigned to receive intravenous infusions every 4 weeks of 300 mg of the natalizumab biosimilar or the reference product for a total of 12 infusions.
At 24 and 48 weeks, there were no between-group differences in annualized relapse rates or Expanded Disability Status Scale scores, which were similar between treatment groups at baseline. There were also no significant differences in safety, tolerability, or immunogenicity.
The prescribing information for both natalizumab products includes a boxed warning about the increased risk of progressive multifocal leukoencephalopathy (PML), a viral infection of the brain that usually leads to death or severe disability.
Risk factors for the development of PML include the presence of antibodies to the JC virus, longer duration of therapy, and prior use of immunosuppressants.
“These factors should be considered in the context of expected benefit when initiating and continuing treatment with natalizumab products, and health care providers should monitor patients and withhold treatment immediately at the first sign or symptom suggestive of PML,” the FDA advises.
Because of the risks of PML, natalizumab products are available only through a restricted drug distribution program under a risk evaluation and mitigation strategy.
In a statement, Sandoz said it’s committed to having the product available in the United States “as soon as possible.”
A version of this article appeared on Medscape.com.
including clinically isolated syndrome, relapsing remitting MS, and active secondary progressive disease.
“Biosimilar medications offer additional effective treatment options that have the potential to increase access for people living with relapsing forms of multiple sclerosis. [This] approval could have a meaningful impact for patients managing their disease,” Paul R. Lee, MD, PhD, director of the division of neurology II, FDA Center for Drug Evaluation and Research, said in a statement.
The natalizumab biosimilar is given using the same dosing and administration schedule. Like the reference product, it is indicated for adults with moderately to severely active Crohn’s disease unresponsive to other medications.
The approval of the natalizumab biosimilar is based on results of the phase 3 Antelope trial, which showed no clinically meaningful differences between it and the reference product.
The trial included 264 adults (mean age, 36 years; 61% women) with relapsing remitting MS from 48 centers in seven Eastern European countries.
All were randomly assigned to receive intravenous infusions every 4 weeks of 300 mg of the natalizumab biosimilar or the reference product for a total of 12 infusions.
At 24 and 48 weeks, there were no between-group differences in annualized relapse rates or Expanded Disability Status Scale scores, which were similar between treatment groups at baseline. There were also no significant differences in safety, tolerability, or immunogenicity.
The prescribing information for both natalizumab products includes a boxed warning about the increased risk of progressive multifocal leukoencephalopathy (PML), a viral infection of the brain that usually leads to death or severe disability.
Risk factors for the development of PML include the presence of antibodies to the JC virus, longer duration of therapy, and prior use of immunosuppressants.
“These factors should be considered in the context of expected benefit when initiating and continuing treatment with natalizumab products, and health care providers should monitor patients and withhold treatment immediately at the first sign or symptom suggestive of PML,” the FDA advises.
Because of the risks of PML, natalizumab products are available only through a restricted drug distribution program under a risk evaluation and mitigation strategy.
In a statement, Sandoz said it’s committed to having the product available in the United States “as soon as possible.”
A version of this article appeared on Medscape.com.
Gene therapy offers new way to fight alcohol use disorder
Researchers from Oregon Health & Science University, Portland implanted the therapy directly into the brains of rhesus monkeys that had been conditioned to drink 8-10 alcoholic drinks a day. A harmless virus that carried a specific gene was placed in the region of the brain that regulates dopamine, which provides feelings of reward and pleasure.
“We wanted to see if we could normalize the dopamine in these motivational areas – if, indeed, motivation to overdrink or drink heavily would be mitigated,” said study author Kathleen Grant, PhD, a professor and chief of the division of neuroscience at the university’s Oregon National Primate Research Center.
The need for new alcohol use disorder treatments may be more dire than ever. Alcohol-related deaths in the United States increased dramatically between 2007 and 2020, especially in women, according to research published in the journal JAMA Network Open. The next year, they spiked again, to 108,791 alcohol-related deaths in 2021 alone, according to the National Institutes of Health. That’s slightly more than the number of drug overdoses recorded in 2021.
For the 29.5 million Americans with alcohol use disorder, also known as alcohol abuse or dependence, the road to recovery can be challenging. One reason is that the reward systems in their brains are working against them.
At the first taste of alcohol, the body releases dopamine. But if a person drinks too much for too long, the brain reduces dopamine production and even more alcohol is needed to feel good again.
The gene researchers placed in the monkeys’ brains is called glial-derived neurotrophic factor. It is a growth factor, stimulating cells to multiply. It may help improve function of brain cells that synthesize dopamine, effectively resetting the whole system and reducing the urge to drink.
The study was surprisingly successful. Compared with primates that received a placebo, those that received the growth factor gene decreased their drinking by about 90%. They basically quit drinking, while the primates that got the placebo resumed their habit.
A similar procedure is already used in patients with Parkinson’s disease. But more animal studies, and human clinical trials, would be needed before this therapy could be used in humans with alcohol use disorder. This invasive treatment involves brain surgery, which has risks, so it would likely be reserved for those with the most severe, dangerous drinking habits.
“I think it’d be appropriate for individuals where other treatment modalities just weren’t effective, and they’re worried for their lives,” Dr. Grant said.
Alcohol use disorder treatments
Today, treatment for alcohol use disorder ranges from a brief conversation with a health care provider, in mild cases, to psychiatric treatment or medication in moderate or severe cases.
There are four Food and Drug Administration–approved treatments for alcohol use disorder and a few more medications that health care providers can prescribe off label.
“They’re not widely used,” said Henry Kranzler, MD, a professor of psychiatry and director of the Center for Studies of Addiction at the University of Pennsylvania, Philadelphia. “They’re shockingly underutilized.”
One reason: Just 4.6% of people with alcohol use disorder seek treatment each year, according to NIH data.
“Some of the issues include the ubiquity of alcohol, and its acceptance in American culture – and the fact that that makes it difficult for people to acknowledge that they have a problem with alcohol,” said Dr. Kranzler.
But another problem is that many health care professionals don’t recognize and treat alcohol use disorder in patients who do seek care. Those seeking treatment for alcohol use disorder can find a qualified provider at the American Academy of Addiction Psychiatry or American Society of Addiction Medicine directories.
The future of treatment
Ongoing research could lead to more treatments, and make them more available and more appealing.
Unlike many other drugs that work on a single receptor in the body – like opioids that target opioid receptors, or nicotine, which targets choline receptors – alcohol affects many different receptors, said Robert Swift, MD, PhD, a professor of psychiatry and human behavior at Brown University, Providence, R.I. It also penetrates cells at high doses.
“There are so many different effects of alcohol, which makes it very hard to treat,” he said. “But on the other hand, it gives us an advantage, and there are probably different points that we can attack.”
Other exciting developments are underway, although more research, including clinical trials in humans, is needed before they arrive.
Some of the most promising:
- Hallucinogens. In the 1950s, before they became illegal, these drugs helped people drink less. Even Bill Wilson, cofounder of Alcoholics Anonymous, used hallucinogenic treatment in his recovery; it helped him envision overcoming a challenge. Today, there is renewed interest in hallucinogens for alcohol use disorder. In a study published in , people with alcohol use disorder who were given the hallucinogen psilocybin along with therapy spent fewer days drinking heavily over the following 32 weeks than people who received a different medication. Don’t try to do this yourself, though. “It’s not just taking a hallucinogen and having a trip,” Dr. Swift said. “It’s a therapy-guided session, so it’s a combination of using the hallucinogenic substance with a skilled therapist, and sometimes two skilled therapists, helping to guide the experience.”
- Epigenetic editing. Alcohol exposure can affect the activity of a gene in the amygdala, a brain region involved in emotional processing. found that, by editing that gene in rats through an intravenous line of genetic material, they reduced the rodents’ drinking and anxiety.
- Oxytocin. The so-called love hormone could help reset the dopamine system to make alcohol less appealing. “There are oxytocin receptors on dopamine neurons, and oxytocin makes your dopamine system more effective,” Dr. Swift said. In a from the Medical University of South Carolina, Charleston, mice injected with oxytocin didn’t drink during a stressful situation that could have otherwise led to relapse.
- Ghrelin. This stomach hormone could help curb drinking. In a study published in , mice that received drugs that increased ghrelin reduced their alcohol intake.
A version of this article first appeared on WebMD.com.
Researchers from Oregon Health & Science University, Portland implanted the therapy directly into the brains of rhesus monkeys that had been conditioned to drink 8-10 alcoholic drinks a day. A harmless virus that carried a specific gene was placed in the region of the brain that regulates dopamine, which provides feelings of reward and pleasure.
“We wanted to see if we could normalize the dopamine in these motivational areas – if, indeed, motivation to overdrink or drink heavily would be mitigated,” said study author Kathleen Grant, PhD, a professor and chief of the division of neuroscience at the university’s Oregon National Primate Research Center.
The need for new alcohol use disorder treatments may be more dire than ever. Alcohol-related deaths in the United States increased dramatically between 2007 and 2020, especially in women, according to research published in the journal JAMA Network Open. The next year, they spiked again, to 108,791 alcohol-related deaths in 2021 alone, according to the National Institutes of Health. That’s slightly more than the number of drug overdoses recorded in 2021.
For the 29.5 million Americans with alcohol use disorder, also known as alcohol abuse or dependence, the road to recovery can be challenging. One reason is that the reward systems in their brains are working against them.
At the first taste of alcohol, the body releases dopamine. But if a person drinks too much for too long, the brain reduces dopamine production and even more alcohol is needed to feel good again.
The gene researchers placed in the monkeys’ brains is called glial-derived neurotrophic factor. It is a growth factor, stimulating cells to multiply. It may help improve function of brain cells that synthesize dopamine, effectively resetting the whole system and reducing the urge to drink.
The study was surprisingly successful. Compared with primates that received a placebo, those that received the growth factor gene decreased their drinking by about 90%. They basically quit drinking, while the primates that got the placebo resumed their habit.
A similar procedure is already used in patients with Parkinson’s disease. But more animal studies, and human clinical trials, would be needed before this therapy could be used in humans with alcohol use disorder. This invasive treatment involves brain surgery, which has risks, so it would likely be reserved for those with the most severe, dangerous drinking habits.
“I think it’d be appropriate for individuals where other treatment modalities just weren’t effective, and they’re worried for their lives,” Dr. Grant said.
Alcohol use disorder treatments
Today, treatment for alcohol use disorder ranges from a brief conversation with a health care provider, in mild cases, to psychiatric treatment or medication in moderate or severe cases.
There are four Food and Drug Administration–approved treatments for alcohol use disorder and a few more medications that health care providers can prescribe off label.
“They’re not widely used,” said Henry Kranzler, MD, a professor of psychiatry and director of the Center for Studies of Addiction at the University of Pennsylvania, Philadelphia. “They’re shockingly underutilized.”
One reason: Just 4.6% of people with alcohol use disorder seek treatment each year, according to NIH data.
“Some of the issues include the ubiquity of alcohol, and its acceptance in American culture – and the fact that that makes it difficult for people to acknowledge that they have a problem with alcohol,” said Dr. Kranzler.
But another problem is that many health care professionals don’t recognize and treat alcohol use disorder in patients who do seek care. Those seeking treatment for alcohol use disorder can find a qualified provider at the American Academy of Addiction Psychiatry or American Society of Addiction Medicine directories.
The future of treatment
Ongoing research could lead to more treatments, and make them more available and more appealing.
Unlike many other drugs that work on a single receptor in the body – like opioids that target opioid receptors, or nicotine, which targets choline receptors – alcohol affects many different receptors, said Robert Swift, MD, PhD, a professor of psychiatry and human behavior at Brown University, Providence, R.I. It also penetrates cells at high doses.
“There are so many different effects of alcohol, which makes it very hard to treat,” he said. “But on the other hand, it gives us an advantage, and there are probably different points that we can attack.”
Other exciting developments are underway, although more research, including clinical trials in humans, is needed before they arrive.
Some of the most promising:
- Hallucinogens. In the 1950s, before they became illegal, these drugs helped people drink less. Even Bill Wilson, cofounder of Alcoholics Anonymous, used hallucinogenic treatment in his recovery; it helped him envision overcoming a challenge. Today, there is renewed interest in hallucinogens for alcohol use disorder. In a study published in , people with alcohol use disorder who were given the hallucinogen psilocybin along with therapy spent fewer days drinking heavily over the following 32 weeks than people who received a different medication. Don’t try to do this yourself, though. “It’s not just taking a hallucinogen and having a trip,” Dr. Swift said. “It’s a therapy-guided session, so it’s a combination of using the hallucinogenic substance with a skilled therapist, and sometimes two skilled therapists, helping to guide the experience.”
- Epigenetic editing. Alcohol exposure can affect the activity of a gene in the amygdala, a brain region involved in emotional processing. found that, by editing that gene in rats through an intravenous line of genetic material, they reduced the rodents’ drinking and anxiety.
- Oxytocin. The so-called love hormone could help reset the dopamine system to make alcohol less appealing. “There are oxytocin receptors on dopamine neurons, and oxytocin makes your dopamine system more effective,” Dr. Swift said. In a from the Medical University of South Carolina, Charleston, mice injected with oxytocin didn’t drink during a stressful situation that could have otherwise led to relapse.
- Ghrelin. This stomach hormone could help curb drinking. In a study published in , mice that received drugs that increased ghrelin reduced their alcohol intake.
A version of this article first appeared on WebMD.com.
Researchers from Oregon Health & Science University, Portland implanted the therapy directly into the brains of rhesus monkeys that had been conditioned to drink 8-10 alcoholic drinks a day. A harmless virus that carried a specific gene was placed in the region of the brain that regulates dopamine, which provides feelings of reward and pleasure.
“We wanted to see if we could normalize the dopamine in these motivational areas – if, indeed, motivation to overdrink or drink heavily would be mitigated,” said study author Kathleen Grant, PhD, a professor and chief of the division of neuroscience at the university’s Oregon National Primate Research Center.
The need for new alcohol use disorder treatments may be more dire than ever. Alcohol-related deaths in the United States increased dramatically between 2007 and 2020, especially in women, according to research published in the journal JAMA Network Open. The next year, they spiked again, to 108,791 alcohol-related deaths in 2021 alone, according to the National Institutes of Health. That’s slightly more than the number of drug overdoses recorded in 2021.
For the 29.5 million Americans with alcohol use disorder, also known as alcohol abuse or dependence, the road to recovery can be challenging. One reason is that the reward systems in their brains are working against them.
At the first taste of alcohol, the body releases dopamine. But if a person drinks too much for too long, the brain reduces dopamine production and even more alcohol is needed to feel good again.
The gene researchers placed in the monkeys’ brains is called glial-derived neurotrophic factor. It is a growth factor, stimulating cells to multiply. It may help improve function of brain cells that synthesize dopamine, effectively resetting the whole system and reducing the urge to drink.
The study was surprisingly successful. Compared with primates that received a placebo, those that received the growth factor gene decreased their drinking by about 90%. They basically quit drinking, while the primates that got the placebo resumed their habit.
A similar procedure is already used in patients with Parkinson’s disease. But more animal studies, and human clinical trials, would be needed before this therapy could be used in humans with alcohol use disorder. This invasive treatment involves brain surgery, which has risks, so it would likely be reserved for those with the most severe, dangerous drinking habits.
“I think it’d be appropriate for individuals where other treatment modalities just weren’t effective, and they’re worried for their lives,” Dr. Grant said.
Alcohol use disorder treatments
Today, treatment for alcohol use disorder ranges from a brief conversation with a health care provider, in mild cases, to psychiatric treatment or medication in moderate or severe cases.
There are four Food and Drug Administration–approved treatments for alcohol use disorder and a few more medications that health care providers can prescribe off label.
“They’re not widely used,” said Henry Kranzler, MD, a professor of psychiatry and director of the Center for Studies of Addiction at the University of Pennsylvania, Philadelphia. “They’re shockingly underutilized.”
One reason: Just 4.6% of people with alcohol use disorder seek treatment each year, according to NIH data.
“Some of the issues include the ubiquity of alcohol, and its acceptance in American culture – and the fact that that makes it difficult for people to acknowledge that they have a problem with alcohol,” said Dr. Kranzler.
But another problem is that many health care professionals don’t recognize and treat alcohol use disorder in patients who do seek care. Those seeking treatment for alcohol use disorder can find a qualified provider at the American Academy of Addiction Psychiatry or American Society of Addiction Medicine directories.
The future of treatment
Ongoing research could lead to more treatments, and make them more available and more appealing.
Unlike many other drugs that work on a single receptor in the body – like opioids that target opioid receptors, or nicotine, which targets choline receptors – alcohol affects many different receptors, said Robert Swift, MD, PhD, a professor of psychiatry and human behavior at Brown University, Providence, R.I. It also penetrates cells at high doses.
“There are so many different effects of alcohol, which makes it very hard to treat,” he said. “But on the other hand, it gives us an advantage, and there are probably different points that we can attack.”
Other exciting developments are underway, although more research, including clinical trials in humans, is needed before they arrive.
Some of the most promising:
- Hallucinogens. In the 1950s, before they became illegal, these drugs helped people drink less. Even Bill Wilson, cofounder of Alcoholics Anonymous, used hallucinogenic treatment in his recovery; it helped him envision overcoming a challenge. Today, there is renewed interest in hallucinogens for alcohol use disorder. In a study published in , people with alcohol use disorder who were given the hallucinogen psilocybin along with therapy spent fewer days drinking heavily over the following 32 weeks than people who received a different medication. Don’t try to do this yourself, though. “It’s not just taking a hallucinogen and having a trip,” Dr. Swift said. “It’s a therapy-guided session, so it’s a combination of using the hallucinogenic substance with a skilled therapist, and sometimes two skilled therapists, helping to guide the experience.”
- Epigenetic editing. Alcohol exposure can affect the activity of a gene in the amygdala, a brain region involved in emotional processing. found that, by editing that gene in rats through an intravenous line of genetic material, they reduced the rodents’ drinking and anxiety.
- Oxytocin. The so-called love hormone could help reset the dopamine system to make alcohol less appealing. “There are oxytocin receptors on dopamine neurons, and oxytocin makes your dopamine system more effective,” Dr. Swift said. In a from the Medical University of South Carolina, Charleston, mice injected with oxytocin didn’t drink during a stressful situation that could have otherwise led to relapse.
- Ghrelin. This stomach hormone could help curb drinking. In a study published in , mice that received drugs that increased ghrelin reduced their alcohol intake.
A version of this article first appeared on WebMD.com.
FROM NATURE MEDICINE
Dementia diagnosis a good time to reduce polypharmacy
Physicians may be missing opportunities to reduce harmful polypharmacy in elderly patients with newly diagnosed dementia, investigators for a large study of Medicare beneficiaries reported.
They found that those with an incident dementia diagnosis were somewhat more likely to initiate central nervous system–active medications and slightly more likely to discontinue cardiometabolic and anticholinergic medications, compared with controls.
According to the authors, time of diagnosis can be a potential inflexion point for deprescribing long-term medications with high safety risks, limited likelihood of benefit, or possible association with impaired cognition.
“Understanding the chronology of medication changes following a first dementia diagnosis may identify targets for deprescribing interventions to reduce preventable medication-related harms, said Timothy S. Anderson, MD, MAS, of the division of general medicine at Beth Israel Deaconess Medical Center, Boston, and colleagues in JAMA Internal Medicine.
“Our results provide a baseline to inform efforts to rethink the clinical approach to medication use at the time of a new dementia diagnosis.”
Hundreds of thousands of Americans are diagnosed annually with Alzheimer’s and related dementias, the authors pointed out, and the majority have multiple other chronic conditions. Worsening cognitive impairment may alter the risk-benefit balance of medications taken for these conditions.
Matched cohort study
The sample consisted of adults 67 years or older enrolled in traditional Medicare and Medicare Part D. Patients with an initial incident dementia diagnosis between January 2012 and December 2018 were matched with controls (as of last doctor’s office visit) based on demographics, geographic location, and baseline medication count. Data were analyzed from 2021 to June 2023.
The study included 266,675 adults with incident dementia and 266,675 controls. In both groups, 65.1% were 80 years or older (mean age, 82.2) and 67.8% were female. At baseline, patients with incident dementia were more likely than controls to use CNS-active medications (54.32% vs. 48.39%) and anticholinergic medications (17.79% vs. 15.96%) and less likely to use most cardiometabolic medications (for example, antidiabetics, 31.19% vs. 36.45%).
Immediately following the index diagnosis, the dementia cohort had greater increases in the mean number of medications used: 0.41 vs. –0.06 (95% confidence interval, 0.27-0.66) and in the proportion using CNS-active medications (absolute change, 3.44% vs. 0.79%; 95% CI, 0.85%-4.45%). The rise was because of an increased use of antipsychotics, antidepressants, and antiepileptics.
The affected cohort showed a modestly greater decline in anticholinergic medications: quarterly change in use: −0.53% vs. −0.21% (95% CI, −0.55% to −0.08%); and in most cardiometabolic medications: for example, quarterly change in antihypertensive use: –0.84% vs. –0.40% (95% CI, –0.64% to –0.25%). Still, a year post diagnosis, 75.2% of dementia patients were using five or more medications, for a 2.8% increase.
The drug classes with the steepest rate of discontinuation – such as lipid-lowering and antihypertensive medications – had low risks for adverse drug events, while higher-risk classes – such as insulins and antiplatelet and anticoagulant agents – had smaller or no reductions in use.
While the findings point to opportunities to reduce polypharmacy by deprescribing long-term medications of dubious benefit, interventions to reduce polypharmacy and inappropriate medications have been modestly successful for patients without dementia, the authors said. But the recent OPTIMIZE trial, an educational effort aimed at primary care clinicians and patients with cognitive impairment, reduced neither polypharmacy nor potentially inappropriate medications.
Luke D. Kim, MD, a geriatrician at the Cleveland Clinic in Ohio, agreed that seniors with dementia can benefit from reassessment of their pharmacologic therapies. “Older adults in general are more prone to have side effects from medications as their renal and hepatic clearance and metabolism are different and lower than those of younger individuals. But they tend to take multiple medications owing to more comorbidities,” said Dr. Kim, who was not involved in the study. “While all older adults need to be more careful about medication management, those with dementia need an even more careful approach as they have diminished cognitive reserve and risk more potential harm from medications.”
The authors noted that since decision-making models aligned with patient priorities for older adults without dementia led to reductions in overall medication use, that may be a path forward in populations with dementia.
The study was supported by grants from the National Institute on Aging, National Institutes of Health. The authors had no competing interests to disclose. Dr. Kim disclosed no competing interests relevant to his comments.
Physicians may be missing opportunities to reduce harmful polypharmacy in elderly patients with newly diagnosed dementia, investigators for a large study of Medicare beneficiaries reported.
They found that those with an incident dementia diagnosis were somewhat more likely to initiate central nervous system–active medications and slightly more likely to discontinue cardiometabolic and anticholinergic medications, compared with controls.
According to the authors, time of diagnosis can be a potential inflexion point for deprescribing long-term medications with high safety risks, limited likelihood of benefit, or possible association with impaired cognition.
“Understanding the chronology of medication changes following a first dementia diagnosis may identify targets for deprescribing interventions to reduce preventable medication-related harms, said Timothy S. Anderson, MD, MAS, of the division of general medicine at Beth Israel Deaconess Medical Center, Boston, and colleagues in JAMA Internal Medicine.
“Our results provide a baseline to inform efforts to rethink the clinical approach to medication use at the time of a new dementia diagnosis.”
Hundreds of thousands of Americans are diagnosed annually with Alzheimer’s and related dementias, the authors pointed out, and the majority have multiple other chronic conditions. Worsening cognitive impairment may alter the risk-benefit balance of medications taken for these conditions.
Matched cohort study
The sample consisted of adults 67 years or older enrolled in traditional Medicare and Medicare Part D. Patients with an initial incident dementia diagnosis between January 2012 and December 2018 were matched with controls (as of last doctor’s office visit) based on demographics, geographic location, and baseline medication count. Data were analyzed from 2021 to June 2023.
The study included 266,675 adults with incident dementia and 266,675 controls. In both groups, 65.1% were 80 years or older (mean age, 82.2) and 67.8% were female. At baseline, patients with incident dementia were more likely than controls to use CNS-active medications (54.32% vs. 48.39%) and anticholinergic medications (17.79% vs. 15.96%) and less likely to use most cardiometabolic medications (for example, antidiabetics, 31.19% vs. 36.45%).
Immediately following the index diagnosis, the dementia cohort had greater increases in the mean number of medications used: 0.41 vs. –0.06 (95% confidence interval, 0.27-0.66) and in the proportion using CNS-active medications (absolute change, 3.44% vs. 0.79%; 95% CI, 0.85%-4.45%). The rise was because of an increased use of antipsychotics, antidepressants, and antiepileptics.
The affected cohort showed a modestly greater decline in anticholinergic medications: quarterly change in use: −0.53% vs. −0.21% (95% CI, −0.55% to −0.08%); and in most cardiometabolic medications: for example, quarterly change in antihypertensive use: –0.84% vs. –0.40% (95% CI, –0.64% to –0.25%). Still, a year post diagnosis, 75.2% of dementia patients were using five or more medications, for a 2.8% increase.
The drug classes with the steepest rate of discontinuation – such as lipid-lowering and antihypertensive medications – had low risks for adverse drug events, while higher-risk classes – such as insulins and antiplatelet and anticoagulant agents – had smaller or no reductions in use.
While the findings point to opportunities to reduce polypharmacy by deprescribing long-term medications of dubious benefit, interventions to reduce polypharmacy and inappropriate medications have been modestly successful for patients without dementia, the authors said. But the recent OPTIMIZE trial, an educational effort aimed at primary care clinicians and patients with cognitive impairment, reduced neither polypharmacy nor potentially inappropriate medications.
Luke D. Kim, MD, a geriatrician at the Cleveland Clinic in Ohio, agreed that seniors with dementia can benefit from reassessment of their pharmacologic therapies. “Older adults in general are more prone to have side effects from medications as their renal and hepatic clearance and metabolism are different and lower than those of younger individuals. But they tend to take multiple medications owing to more comorbidities,” said Dr. Kim, who was not involved in the study. “While all older adults need to be more careful about medication management, those with dementia need an even more careful approach as they have diminished cognitive reserve and risk more potential harm from medications.”
The authors noted that since decision-making models aligned with patient priorities for older adults without dementia led to reductions in overall medication use, that may be a path forward in populations with dementia.
The study was supported by grants from the National Institute on Aging, National Institutes of Health. The authors had no competing interests to disclose. Dr. Kim disclosed no competing interests relevant to his comments.
Physicians may be missing opportunities to reduce harmful polypharmacy in elderly patients with newly diagnosed dementia, investigators for a large study of Medicare beneficiaries reported.
They found that those with an incident dementia diagnosis were somewhat more likely to initiate central nervous system–active medications and slightly more likely to discontinue cardiometabolic and anticholinergic medications, compared with controls.
According to the authors, time of diagnosis can be a potential inflexion point for deprescribing long-term medications with high safety risks, limited likelihood of benefit, or possible association with impaired cognition.
“Understanding the chronology of medication changes following a first dementia diagnosis may identify targets for deprescribing interventions to reduce preventable medication-related harms, said Timothy S. Anderson, MD, MAS, of the division of general medicine at Beth Israel Deaconess Medical Center, Boston, and colleagues in JAMA Internal Medicine.
“Our results provide a baseline to inform efforts to rethink the clinical approach to medication use at the time of a new dementia diagnosis.”
Hundreds of thousands of Americans are diagnosed annually with Alzheimer’s and related dementias, the authors pointed out, and the majority have multiple other chronic conditions. Worsening cognitive impairment may alter the risk-benefit balance of medications taken for these conditions.
Matched cohort study
The sample consisted of adults 67 years or older enrolled in traditional Medicare and Medicare Part D. Patients with an initial incident dementia diagnosis between January 2012 and December 2018 were matched with controls (as of last doctor’s office visit) based on demographics, geographic location, and baseline medication count. Data were analyzed from 2021 to June 2023.
The study included 266,675 adults with incident dementia and 266,675 controls. In both groups, 65.1% were 80 years or older (mean age, 82.2) and 67.8% were female. At baseline, patients with incident dementia were more likely than controls to use CNS-active medications (54.32% vs. 48.39%) and anticholinergic medications (17.79% vs. 15.96%) and less likely to use most cardiometabolic medications (for example, antidiabetics, 31.19% vs. 36.45%).
Immediately following the index diagnosis, the dementia cohort had greater increases in the mean number of medications used: 0.41 vs. –0.06 (95% confidence interval, 0.27-0.66) and in the proportion using CNS-active medications (absolute change, 3.44% vs. 0.79%; 95% CI, 0.85%-4.45%). The rise was because of an increased use of antipsychotics, antidepressants, and antiepileptics.
The affected cohort showed a modestly greater decline in anticholinergic medications: quarterly change in use: −0.53% vs. −0.21% (95% CI, −0.55% to −0.08%); and in most cardiometabolic medications: for example, quarterly change in antihypertensive use: –0.84% vs. –0.40% (95% CI, –0.64% to –0.25%). Still, a year post diagnosis, 75.2% of dementia patients were using five or more medications, for a 2.8% increase.
The drug classes with the steepest rate of discontinuation – such as lipid-lowering and antihypertensive medications – had low risks for adverse drug events, while higher-risk classes – such as insulins and antiplatelet and anticoagulant agents – had smaller or no reductions in use.
While the findings point to opportunities to reduce polypharmacy by deprescribing long-term medications of dubious benefit, interventions to reduce polypharmacy and inappropriate medications have been modestly successful for patients without dementia, the authors said. But the recent OPTIMIZE trial, an educational effort aimed at primary care clinicians and patients with cognitive impairment, reduced neither polypharmacy nor potentially inappropriate medications.
Luke D. Kim, MD, a geriatrician at the Cleveland Clinic in Ohio, agreed that seniors with dementia can benefit from reassessment of their pharmacologic therapies. “Older adults in general are more prone to have side effects from medications as their renal and hepatic clearance and metabolism are different and lower than those of younger individuals. But they tend to take multiple medications owing to more comorbidities,” said Dr. Kim, who was not involved in the study. “While all older adults need to be more careful about medication management, those with dementia need an even more careful approach as they have diminished cognitive reserve and risk more potential harm from medications.”
The authors noted that since decision-making models aligned with patient priorities for older adults without dementia led to reductions in overall medication use, that may be a path forward in populations with dementia.
The study was supported by grants from the National Institute on Aging, National Institutes of Health. The authors had no competing interests to disclose. Dr. Kim disclosed no competing interests relevant to his comments.
FROM JAMA INTERNAL MEDICINE
Most with early AD not eligible for new antiamyloid drugs
Only a small fraction of older adults in the early stages of Alzheimer’s disease (AD) meet eligibility criteria to receive treatment with newly approved antiamyloid drugs, largely because of the presence of medical conditions or neuroimaging findings, new research shows.
Applying the clinical trial criteria, only about 8%-17% of amyloid-positive individuals with early AD would be eligible for lecanemab (Leqembi), and even fewer, 5%-9%, would be eligible for aducanumab (Aduhelm), the researchers found.
This study highlights the “limited suitability” of most adults with mild cognitive impairment (MCI) or mild dementia with elevated brain amyloid for treatment with these anti–beta amyloid monoclonal antibodies, write Maria Vassilaki, MD, PhD, and colleagues with Mayo Clinic, Rochester, Minn.
The study was published online in Neurology
The authors of an accompanying editorial write that this study “provides an important estimate of treatment eligibility for amyloid-lowering monoclonal antibodies for early AD to help health systems make realistic plans for providing these treatments.”
More real-world data needed
Dr. Vassilaki and colleagues applied eligibility criteria for lecanemab and aducanumab to 237 older adults with MCI or mild dementia and increased brain amyloid burden from the Mayo Clinic Study of Aging (MCSA). Their mean age was 80.9 years, 55% were men, and most were White.
After applying lecanemab’s inclusion criteria, less than half of the study population was eligible to receive treatment (112 of 237, or 47%).
A total of 21 people were excluded because of a body mass index less than 17 or greater than or equal to 35; 48 due to a Clinical Dementia Rating (CDR) global score other than 0.5 or 1.0; 46 because they did not meet WMS-R Logical Memory II scores for age; 8 because of a Mini Mental State Examination (MMSE) score outside the bounds of 22-30; and two because of a CDR memory score less than 0.5.
Applying lecanemab’s exclusion criteria further narrowed the number of eligible participants from 112 to 19 (8% of 237).
Notable exclusions included cardiopulmonary contraindications, central nervous system–related exclusions such as brain cancer, Parkinson’s disease, epilepsy or brain injury, imaging findings, and history of cancer.
The results were similar for aducanumab, with 104 of the 237 participants (44%) meeting the trial’s inclusion criteria. Applying aducanumab’s exclusion criteria further reduced the number of eligible participants to 12 (5% of 237).
A sensitivity analysis including participants with MCI, without CDR global, MMSE, or WMS-R Logical Memory II score restrictions, resulted in a somewhat higher percentage of eligible participants (17.4% for lecanemab and 8.9% for aducanumab).
Shared decision-making
“Clinicians and health systems should be aware that by applying the clinical trial criteria, a smaller percentage might be eligible for these treatments than originally anticipated,” Dr. Vassilaki told this news organization. To help clinicians, there are published recommendations for the appropriate use of these treatments, she noted.
Given that clinical trial participants are typically healthier than the general population, Dr. Vassilaki said that research is needed to examine the safety and efficacy of antiamyloid therapies in larger, more diverse populations as well as in less healthy populations, before these therapies may be more widely available to people with AD.
“We can take advantage of the postmarketing surveillance of side effects, and also enrollment of patients receiving these treatments to registries could provide us with data useful for any necessary adjustment to drug use,” Dr. Vassilaki told this news organization.
‘Sharp focus’
This study “brings the issue of eligibility for amyloid-lowering antibody treatment into sharp focus,” Matthew Howe, MD, PhD, with Butler Hospital Memory & Aging Program, Providence, R.I., and colleagues note in their editorial.
“The results underscore the importance of careful patient selection to help identify patients most likely to benefit from treatment and exclude those at risk for serious outcomes,” they write.
They also write that appropriate use recommendations for lecanemab and aducanumab “will be revisited as more real-world data emerge, especially about safety.”
For now, clinicians “must exercise clinical judgment in selecting patients for treatment with shared decision-making with patients and families,” they add.
The study was supported by the National Institutes of Health, the National Institute on Aging, the Alexander Family Alzheimer’s Disease Research Professorship of the Mayo Clinic, the Mayo Foundation for Medical Education and Research, the Liston Award, the GHR Foundation and the Schuler Foundation. Dr. Vassilaki has consulted for F. Hoffmann-La Roche and has equity ownership in Abbott Laboratories, Johnson & Johnson, Medtronic, Merck, and Amgen. Dr. Howe has no conflicts of interest.
A version of this article first appeared on Medscape.com.
Only a small fraction of older adults in the early stages of Alzheimer’s disease (AD) meet eligibility criteria to receive treatment with newly approved antiamyloid drugs, largely because of the presence of medical conditions or neuroimaging findings, new research shows.
Applying the clinical trial criteria, only about 8%-17% of amyloid-positive individuals with early AD would be eligible for lecanemab (Leqembi), and even fewer, 5%-9%, would be eligible for aducanumab (Aduhelm), the researchers found.
This study highlights the “limited suitability” of most adults with mild cognitive impairment (MCI) or mild dementia with elevated brain amyloid for treatment with these anti–beta amyloid monoclonal antibodies, write Maria Vassilaki, MD, PhD, and colleagues with Mayo Clinic, Rochester, Minn.
The study was published online in Neurology
The authors of an accompanying editorial write that this study “provides an important estimate of treatment eligibility for amyloid-lowering monoclonal antibodies for early AD to help health systems make realistic plans for providing these treatments.”
More real-world data needed
Dr. Vassilaki and colleagues applied eligibility criteria for lecanemab and aducanumab to 237 older adults with MCI or mild dementia and increased brain amyloid burden from the Mayo Clinic Study of Aging (MCSA). Their mean age was 80.9 years, 55% were men, and most were White.
After applying lecanemab’s inclusion criteria, less than half of the study population was eligible to receive treatment (112 of 237, or 47%).
A total of 21 people were excluded because of a body mass index less than 17 or greater than or equal to 35; 48 due to a Clinical Dementia Rating (CDR) global score other than 0.5 or 1.0; 46 because they did not meet WMS-R Logical Memory II scores for age; 8 because of a Mini Mental State Examination (MMSE) score outside the bounds of 22-30; and two because of a CDR memory score less than 0.5.
Applying lecanemab’s exclusion criteria further narrowed the number of eligible participants from 112 to 19 (8% of 237).
Notable exclusions included cardiopulmonary contraindications, central nervous system–related exclusions such as brain cancer, Parkinson’s disease, epilepsy or brain injury, imaging findings, and history of cancer.
The results were similar for aducanumab, with 104 of the 237 participants (44%) meeting the trial’s inclusion criteria. Applying aducanumab’s exclusion criteria further reduced the number of eligible participants to 12 (5% of 237).
A sensitivity analysis including participants with MCI, without CDR global, MMSE, or WMS-R Logical Memory II score restrictions, resulted in a somewhat higher percentage of eligible participants (17.4% for lecanemab and 8.9% for aducanumab).
Shared decision-making
“Clinicians and health systems should be aware that by applying the clinical trial criteria, a smaller percentage might be eligible for these treatments than originally anticipated,” Dr. Vassilaki told this news organization. To help clinicians, there are published recommendations for the appropriate use of these treatments, she noted.
Given that clinical trial participants are typically healthier than the general population, Dr. Vassilaki said that research is needed to examine the safety and efficacy of antiamyloid therapies in larger, more diverse populations as well as in less healthy populations, before these therapies may be more widely available to people with AD.
“We can take advantage of the postmarketing surveillance of side effects, and also enrollment of patients receiving these treatments to registries could provide us with data useful for any necessary adjustment to drug use,” Dr. Vassilaki told this news organization.
‘Sharp focus’
This study “brings the issue of eligibility for amyloid-lowering antibody treatment into sharp focus,” Matthew Howe, MD, PhD, with Butler Hospital Memory & Aging Program, Providence, R.I., and colleagues note in their editorial.
“The results underscore the importance of careful patient selection to help identify patients most likely to benefit from treatment and exclude those at risk for serious outcomes,” they write.
They also write that appropriate use recommendations for lecanemab and aducanumab “will be revisited as more real-world data emerge, especially about safety.”
For now, clinicians “must exercise clinical judgment in selecting patients for treatment with shared decision-making with patients and families,” they add.
The study was supported by the National Institutes of Health, the National Institute on Aging, the Alexander Family Alzheimer’s Disease Research Professorship of the Mayo Clinic, the Mayo Foundation for Medical Education and Research, the Liston Award, the GHR Foundation and the Schuler Foundation. Dr. Vassilaki has consulted for F. Hoffmann-La Roche and has equity ownership in Abbott Laboratories, Johnson & Johnson, Medtronic, Merck, and Amgen. Dr. Howe has no conflicts of interest.
A version of this article first appeared on Medscape.com.
Only a small fraction of older adults in the early stages of Alzheimer’s disease (AD) meet eligibility criteria to receive treatment with newly approved antiamyloid drugs, largely because of the presence of medical conditions or neuroimaging findings, new research shows.
Applying the clinical trial criteria, only about 8%-17% of amyloid-positive individuals with early AD would be eligible for lecanemab (Leqembi), and even fewer, 5%-9%, would be eligible for aducanumab (Aduhelm), the researchers found.
This study highlights the “limited suitability” of most adults with mild cognitive impairment (MCI) or mild dementia with elevated brain amyloid for treatment with these anti–beta amyloid monoclonal antibodies, write Maria Vassilaki, MD, PhD, and colleagues with Mayo Clinic, Rochester, Minn.
The study was published online in Neurology
The authors of an accompanying editorial write that this study “provides an important estimate of treatment eligibility for amyloid-lowering monoclonal antibodies for early AD to help health systems make realistic plans for providing these treatments.”
More real-world data needed
Dr. Vassilaki and colleagues applied eligibility criteria for lecanemab and aducanumab to 237 older adults with MCI or mild dementia and increased brain amyloid burden from the Mayo Clinic Study of Aging (MCSA). Their mean age was 80.9 years, 55% were men, and most were White.
After applying lecanemab’s inclusion criteria, less than half of the study population was eligible to receive treatment (112 of 237, or 47%).
A total of 21 people were excluded because of a body mass index less than 17 or greater than or equal to 35; 48 due to a Clinical Dementia Rating (CDR) global score other than 0.5 or 1.0; 46 because they did not meet WMS-R Logical Memory II scores for age; 8 because of a Mini Mental State Examination (MMSE) score outside the bounds of 22-30; and two because of a CDR memory score less than 0.5.
Applying lecanemab’s exclusion criteria further narrowed the number of eligible participants from 112 to 19 (8% of 237).
Notable exclusions included cardiopulmonary contraindications, central nervous system–related exclusions such as brain cancer, Parkinson’s disease, epilepsy or brain injury, imaging findings, and history of cancer.
The results were similar for aducanumab, with 104 of the 237 participants (44%) meeting the trial’s inclusion criteria. Applying aducanumab’s exclusion criteria further reduced the number of eligible participants to 12 (5% of 237).
A sensitivity analysis including participants with MCI, without CDR global, MMSE, or WMS-R Logical Memory II score restrictions, resulted in a somewhat higher percentage of eligible participants (17.4% for lecanemab and 8.9% for aducanumab).
Shared decision-making
“Clinicians and health systems should be aware that by applying the clinical trial criteria, a smaller percentage might be eligible for these treatments than originally anticipated,” Dr. Vassilaki told this news organization. To help clinicians, there are published recommendations for the appropriate use of these treatments, she noted.
Given that clinical trial participants are typically healthier than the general population, Dr. Vassilaki said that research is needed to examine the safety and efficacy of antiamyloid therapies in larger, more diverse populations as well as in less healthy populations, before these therapies may be more widely available to people with AD.
“We can take advantage of the postmarketing surveillance of side effects, and also enrollment of patients receiving these treatments to registries could provide us with data useful for any necessary adjustment to drug use,” Dr. Vassilaki told this news organization.
‘Sharp focus’
This study “brings the issue of eligibility for amyloid-lowering antibody treatment into sharp focus,” Matthew Howe, MD, PhD, with Butler Hospital Memory & Aging Program, Providence, R.I., and colleagues note in their editorial.
“The results underscore the importance of careful patient selection to help identify patients most likely to benefit from treatment and exclude those at risk for serious outcomes,” they write.
They also write that appropriate use recommendations for lecanemab and aducanumab “will be revisited as more real-world data emerge, especially about safety.”
For now, clinicians “must exercise clinical judgment in selecting patients for treatment with shared decision-making with patients and families,” they add.
The study was supported by the National Institutes of Health, the National Institute on Aging, the Alexander Family Alzheimer’s Disease Research Professorship of the Mayo Clinic, the Mayo Foundation for Medical Education and Research, the Liston Award, the GHR Foundation and the Schuler Foundation. Dr. Vassilaki has consulted for F. Hoffmann-La Roche and has equity ownership in Abbott Laboratories, Johnson & Johnson, Medtronic, Merck, and Amgen. Dr. Howe has no conflicts of interest.
A version of this article first appeared on Medscape.com.
FROM NEUROLOGY
Few meet eligibility for newer Alzheimer’s drugs
, a cross sectional study has found.
Reporting in the journal Neurology, researchers from the Mayo Clinic in Rochester, Minn., and the University of Chicago found that only a small percentage of patients in the Mayo Clinic Study of Aging (MCSA) with mild cognitive impairment (MCI) or mild dementia due to Alzheimer’s disease would meet the clinical trial eligibility requirements of either agent.
“Our study results show only a small percentage of people with early Alzheimer’s disease may be eligible to receive treatment, mostly due to chronic health conditions and brain scan abnormalities common in older adults,” said lead researcher Maria Vassilaki, MD, PhD, an epidemiologist at Mayo Clinic in Rochester, Minn.
Applying clinical trial exclusion criteria to a broader population
The study included 237 people aged 50-90, 222 who had MCI and 15 with mild dementia, and whose brain scans showed increased amounts of amyloid-beta plaques. Average age of the participants was 80.9 years and 97.5% were White (99.6% not Hispanic or Latino).
The researchers then looked at the eligibility criteria for the pivotal clinical trials for lecanemab, which the U.S. Food and Drug Administration approved in January this year, and aducanumab, which the FDA cleared in 2021. Both drugs received FDA accelerated approval.
For lecanemab, clinical trial inclusion required specific scores for the Clinical Dementia Rating (CDR) (other than 0.5 or 1.0), Wechsler Memory Scale (WMS-R) Logical Memory II (which varied with age group), or Mini-Mental State Examination (MMSE) (22 to 30). A body mass index between 17 and 35 kg/m2 was also an inclusion criteria. Only 112 people, or 47%, met the inclusion criteria. Exclusion criteria included a history of cardiovascular disease or cancer, Parkinson’s disease, or brain injury, or a positive brain scan. When the exclusion criteria were applied, only 19 people, or 8%, qualified for the lecanemab trial.
When the researchers modified the exclusion criteria to include all study participants with MCI but not applying results from additional cognitive tests, 17.4% of MCSA patients would have been eligible for the lecanemab trial.
Aducanumab clinical trial inclusion criteria were a CDR global score other than 0.5 and an MMSE below 24, with an age cutoff of 85 years. Only 104 of the MCSA population, or 44%, met the clinical trial criteria. When the researchers applied the exclusion criteria for cardiovascular disease, central nervous system-related exclusions (such as brain cancer or epilepsy), a history of cancer, or brain scan abnormalities, they found that only 12 people, or 5%, would have been eligible for an aducanumab trial.
“Clinical trials often have strict eligibility criteria and could exclude those with other conditions that could be common in older adults,” Dr. Vassilaki said in emailed comments. “Thus, we wanted to examine if we apply these criteria to a study that recruits participants from the community, how many of the individuals in the early symptomatic stages, mild cognitive impairment or mild dementia due to Alzheimer’s disease, would be eligible for the treatment.”
Dr. Vassilaki said these drugs need to be studied in larger, more diverse populations, as well as in less healthy populations, before they’re more widely available to people with Alzheimer’s disease. “In addition,” she said, “we can learn more from the postmarketing surveillance of side effects and also from registries of patients receiving these treatments.”
One limitation of the study Dr. Vassilaki pointed out is the overwhelmingly White population. Evaluating the clinical trial eligibility criteria in more diverse populations is crucial, she said.
Estimating the number of patients who would qualify for treatment
In an accompanying commentary, Matthew Howes, MD, of Butler Hospital and Brown University in Providence, R.I., and colleagues wrote that the study findings provide health systems planning to offer amyloid-lowering antibodies for Alzheimer’s disease an estimate of how many patients would be eligible for the treatments. “Providers must exercise clinical judgment in selecting patients for treatment with shared decision-making with patients and families,” the commentators wrote.
The study was supported by the National Institutes of Health, the National Institute on Aging, the Alexander Family Alzheimer’s Disease Research Professorship of the Mayo Clinic, the Mayo Foundation for Medical Education and Research, the Liston Award, the GHR Foundation, and the Schuler Foundation. Dr. Vassilaki disclosed relationships with F. Hoffmann-La Roche, Abbott Laboratories, Johnson & Johnson, Medtronic, Merck, and Amgen. Dr. Howe has no relevant disclosures.
, a cross sectional study has found.
Reporting in the journal Neurology, researchers from the Mayo Clinic in Rochester, Minn., and the University of Chicago found that only a small percentage of patients in the Mayo Clinic Study of Aging (MCSA) with mild cognitive impairment (MCI) or mild dementia due to Alzheimer’s disease would meet the clinical trial eligibility requirements of either agent.
“Our study results show only a small percentage of people with early Alzheimer’s disease may be eligible to receive treatment, mostly due to chronic health conditions and brain scan abnormalities common in older adults,” said lead researcher Maria Vassilaki, MD, PhD, an epidemiologist at Mayo Clinic in Rochester, Minn.
Applying clinical trial exclusion criteria to a broader population
The study included 237 people aged 50-90, 222 who had MCI and 15 with mild dementia, and whose brain scans showed increased amounts of amyloid-beta plaques. Average age of the participants was 80.9 years and 97.5% were White (99.6% not Hispanic or Latino).
The researchers then looked at the eligibility criteria for the pivotal clinical trials for lecanemab, which the U.S. Food and Drug Administration approved in January this year, and aducanumab, which the FDA cleared in 2021. Both drugs received FDA accelerated approval.
For lecanemab, clinical trial inclusion required specific scores for the Clinical Dementia Rating (CDR) (other than 0.5 or 1.0), Wechsler Memory Scale (WMS-R) Logical Memory II (which varied with age group), or Mini-Mental State Examination (MMSE) (22 to 30). A body mass index between 17 and 35 kg/m2 was also an inclusion criteria. Only 112 people, or 47%, met the inclusion criteria. Exclusion criteria included a history of cardiovascular disease or cancer, Parkinson’s disease, or brain injury, or a positive brain scan. When the exclusion criteria were applied, only 19 people, or 8%, qualified for the lecanemab trial.
When the researchers modified the exclusion criteria to include all study participants with MCI but not applying results from additional cognitive tests, 17.4% of MCSA patients would have been eligible for the lecanemab trial.
Aducanumab clinical trial inclusion criteria were a CDR global score other than 0.5 and an MMSE below 24, with an age cutoff of 85 years. Only 104 of the MCSA population, or 44%, met the clinical trial criteria. When the researchers applied the exclusion criteria for cardiovascular disease, central nervous system-related exclusions (such as brain cancer or epilepsy), a history of cancer, or brain scan abnormalities, they found that only 12 people, or 5%, would have been eligible for an aducanumab trial.
“Clinical trials often have strict eligibility criteria and could exclude those with other conditions that could be common in older adults,” Dr. Vassilaki said in emailed comments. “Thus, we wanted to examine if we apply these criteria to a study that recruits participants from the community, how many of the individuals in the early symptomatic stages, mild cognitive impairment or mild dementia due to Alzheimer’s disease, would be eligible for the treatment.”
Dr. Vassilaki said these drugs need to be studied in larger, more diverse populations, as well as in less healthy populations, before they’re more widely available to people with Alzheimer’s disease. “In addition,” she said, “we can learn more from the postmarketing surveillance of side effects and also from registries of patients receiving these treatments.”
One limitation of the study Dr. Vassilaki pointed out is the overwhelmingly White population. Evaluating the clinical trial eligibility criteria in more diverse populations is crucial, she said.
Estimating the number of patients who would qualify for treatment
In an accompanying commentary, Matthew Howes, MD, of Butler Hospital and Brown University in Providence, R.I., and colleagues wrote that the study findings provide health systems planning to offer amyloid-lowering antibodies for Alzheimer’s disease an estimate of how many patients would be eligible for the treatments. “Providers must exercise clinical judgment in selecting patients for treatment with shared decision-making with patients and families,” the commentators wrote.
The study was supported by the National Institutes of Health, the National Institute on Aging, the Alexander Family Alzheimer’s Disease Research Professorship of the Mayo Clinic, the Mayo Foundation for Medical Education and Research, the Liston Award, the GHR Foundation, and the Schuler Foundation. Dr. Vassilaki disclosed relationships with F. Hoffmann-La Roche, Abbott Laboratories, Johnson & Johnson, Medtronic, Merck, and Amgen. Dr. Howe has no relevant disclosures.
, a cross sectional study has found.
Reporting in the journal Neurology, researchers from the Mayo Clinic in Rochester, Minn., and the University of Chicago found that only a small percentage of patients in the Mayo Clinic Study of Aging (MCSA) with mild cognitive impairment (MCI) or mild dementia due to Alzheimer’s disease would meet the clinical trial eligibility requirements of either agent.
“Our study results show only a small percentage of people with early Alzheimer’s disease may be eligible to receive treatment, mostly due to chronic health conditions and brain scan abnormalities common in older adults,” said lead researcher Maria Vassilaki, MD, PhD, an epidemiologist at Mayo Clinic in Rochester, Minn.
Applying clinical trial exclusion criteria to a broader population
The study included 237 people aged 50-90, 222 who had MCI and 15 with mild dementia, and whose brain scans showed increased amounts of amyloid-beta plaques. Average age of the participants was 80.9 years and 97.5% were White (99.6% not Hispanic or Latino).
The researchers then looked at the eligibility criteria for the pivotal clinical trials for lecanemab, which the U.S. Food and Drug Administration approved in January this year, and aducanumab, which the FDA cleared in 2021. Both drugs received FDA accelerated approval.
For lecanemab, clinical trial inclusion required specific scores for the Clinical Dementia Rating (CDR) (other than 0.5 or 1.0), Wechsler Memory Scale (WMS-R) Logical Memory II (which varied with age group), or Mini-Mental State Examination (MMSE) (22 to 30). A body mass index between 17 and 35 kg/m2 was also an inclusion criteria. Only 112 people, or 47%, met the inclusion criteria. Exclusion criteria included a history of cardiovascular disease or cancer, Parkinson’s disease, or brain injury, or a positive brain scan. When the exclusion criteria were applied, only 19 people, or 8%, qualified for the lecanemab trial.
When the researchers modified the exclusion criteria to include all study participants with MCI but not applying results from additional cognitive tests, 17.4% of MCSA patients would have been eligible for the lecanemab trial.
Aducanumab clinical trial inclusion criteria were a CDR global score other than 0.5 and an MMSE below 24, with an age cutoff of 85 years. Only 104 of the MCSA population, or 44%, met the clinical trial criteria. When the researchers applied the exclusion criteria for cardiovascular disease, central nervous system-related exclusions (such as brain cancer or epilepsy), a history of cancer, or brain scan abnormalities, they found that only 12 people, or 5%, would have been eligible for an aducanumab trial.
“Clinical trials often have strict eligibility criteria and could exclude those with other conditions that could be common in older adults,” Dr. Vassilaki said in emailed comments. “Thus, we wanted to examine if we apply these criteria to a study that recruits participants from the community, how many of the individuals in the early symptomatic stages, mild cognitive impairment or mild dementia due to Alzheimer’s disease, would be eligible for the treatment.”
Dr. Vassilaki said these drugs need to be studied in larger, more diverse populations, as well as in less healthy populations, before they’re more widely available to people with Alzheimer’s disease. “In addition,” she said, “we can learn more from the postmarketing surveillance of side effects and also from registries of patients receiving these treatments.”
One limitation of the study Dr. Vassilaki pointed out is the overwhelmingly White population. Evaluating the clinical trial eligibility criteria in more diverse populations is crucial, she said.
Estimating the number of patients who would qualify for treatment
In an accompanying commentary, Matthew Howes, MD, of Butler Hospital and Brown University in Providence, R.I., and colleagues wrote that the study findings provide health systems planning to offer amyloid-lowering antibodies for Alzheimer’s disease an estimate of how many patients would be eligible for the treatments. “Providers must exercise clinical judgment in selecting patients for treatment with shared decision-making with patients and families,” the commentators wrote.
The study was supported by the National Institutes of Health, the National Institute on Aging, the Alexander Family Alzheimer’s Disease Research Professorship of the Mayo Clinic, the Mayo Foundation for Medical Education and Research, the Liston Award, the GHR Foundation, and the Schuler Foundation. Dr. Vassilaki disclosed relationships with F. Hoffmann-La Roche, Abbott Laboratories, Johnson & Johnson, Medtronic, Merck, and Amgen. Dr. Howe has no relevant disclosures.
FROM NEUROLOGY
Playing football linked to higher Parkinson’s risk
In a cross-sectional study of older men, former tackle football players had a 61% higher likelihood of reporting a diagnosis of parkinsonism or PD, compared with men who played non-football sports.
Longer duration of football participation and higher level of play (college and professional) were associated with higher risk.
Lead researcher Michael L. Alosco, PhD, director of the Boston University Alzheimer’s Disease Research Center, said it’s important to note that the findings are from a cohort of men “enriched” for having PD.
“These are people who are likely already concerned for or at risk for having this disease. We don’t yet know how our findings translate to the general population,” Dr. Alosco said in an interview.
The study was published online in JAMA Network Open.
Repetitive head impacts
Dating back to the 1920s, PD and parkinsonism an umbrella term that refers to motor symptoms associated with PD and other conditions have long been described in boxers who suffer repetitive head impacts.
Multiple studies have linked tackle football with progressive brain diseases such as chronic traumatic encephalopathy. Few studies, however, have investigated the association between participation in football and PD.
For their study, Dr. Alosco and colleagues leveraged data from Fox Insight, a longitudinal online study of some people with and some without PD that is sponsored by the Michael J. Fox Foundation for Parkinson’s Research.
They focused their analyses on 1,875 men (mean age, 67 years) who reported playing any organized sport. As noted, the cohort was enriched for parkinsonism or PD. A total of 1,602 (85%) had received a diagnosis of parkinsonism/PD, and 273 had not.
Altogether, 729 men had a history of playing tackle football, and 1,146 men played non-football sports (control group). Among the football players, 82% played at youth sports or at the high school level; 17% played at the college level; and fewer than 1% played at the pro or semi-pro level.
Among the football players, 648 (89%) reported a parkinsonism/PD diagnosis.
A history of playing football was associated with higher odds of reporting a parkinsonism/PD diagnosis (odds ratio, 1.61; 95% confidence interval, 1.19-2.17) after accounting for age, education level, history of diabetes and heart disease, body mass index (BMI), traumatic brain injury with loss of consciousness, and family history of PD.
Football players who had longer careers and who played at higher levels of competition were at increased risk of having parkinsonism or PD.
Playing one to four seasons yielded an OR of 1.39 (95% CI, 0.98-1.98). The OR was 2.18 (95% CI, 1.36-3.49) for playing five or more seasons.
Football players who competed at the college or professional level had nearly triple the odds of reporting a parkinsonism/PD diagnosis (OR, 2.93; 95% CI, 1.28-6.73), compared with athletes who played at the youth or high school level.
Age at first exposure to football was not associated with a parkinsonism/PD diagnosis.
The researchers cautioned that this was a convenience sample of mostly White people, and the sample was enriched for having PD – factors that limit the generalizability of the findings.
Also, diagnosis of PD was self-reported by participants through online assessments, and objective in-person evaluations were not conducted.
Unequivocal link?
“This is among the first and largest to look at the relationship between football and having a diagnosis of PD in a large cohort of people from the Fox Insight online study,” Dr. Alosco said.
He cautioned that “not all people who play football will develop later-life neurological problems. That being said, the study adds to the accumulating evidence that suggests playing football is one risk factor for the development of later-life brain diseases.
“This represents an opportunity to educate the communities on the potential risks of playing football (short and long term), including what we know and what we don’t know, so that people can make informed decisions on participating in tackle football and develop additional ways to mitigate risk,” Dr. Alosco said.
In a comment, Shaheen Lakhan, MD, PhD, a neurologist and researcher from Boston, said: “The emerging body of research leaves little doubt that engaging in football raises the risk of developing Parkinson’s disease and parkinsonism.
“This progressive line of investigation serves to enhance our understanding, unequivocally demonstrating that even participation in amateur football, including at the youth and high school levels, constitutes a significant risk factor for the onset of Parkinson’s disease,” said Dr. Lakhan, who was not involved in the study.
However, he said it’s “crucial to underscore that the statistics reveal a notable distinction: individuals who have a history of college or professional football play face odds nearly three times higher of receiving a diagnosis of parkinsonism or Parkinson’s disease when compared to their counterparts who engaged in football during their youth or high-school years.
“Ultimately, determinations regarding involvement in sports should be a collaborative endeavor involving parents, young athletes, and health care providers. It is incumbent upon physicians to equip parents and youth with a comprehensive comprehension of the potential risks and rewards inherent in football participation,” Dr. Lakhan said.
He added, though, that there are multifaceted advantages to playing football. “This pursuit nurtures cardiovascular well-being, fosters invaluable social interactions, cultivates teamwork, instills discipline through regimented routines, and hones a spectrum of physical proficiencies,” Dr. Lakhan said.
“It’s worth noting that a constellation of alternative sports, including track and field, swimming, soccer, baseball, and tennis, can be cogently discussed as substitutes, all while preserving the manifold benefits of athletic engagement,” Dr. Lakhan added.
The Fox Insight Study is funded by the Michael J. Fox Foundation for Parkinson’s Research. The study was conducted in collaboration with the Michael J. Fox Foundation for Parkinson’s Research, the sponsor of the Fox Insight study, which collected and aggregated data used in the study. It was also supported by the National Institute of Neurological Disorders and Stroke. Dr. Alosco received grants from the National Institutes of Health during the conduct of the study, an honorarium from the Michael J. Fox Foundation for work unrelated to the study, and royalties from Oxford University Press outside the submitted work. Dr. Lakhan disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In a cross-sectional study of older men, former tackle football players had a 61% higher likelihood of reporting a diagnosis of parkinsonism or PD, compared with men who played non-football sports.
Longer duration of football participation and higher level of play (college and professional) were associated with higher risk.
Lead researcher Michael L. Alosco, PhD, director of the Boston University Alzheimer’s Disease Research Center, said it’s important to note that the findings are from a cohort of men “enriched” for having PD.
“These are people who are likely already concerned for or at risk for having this disease. We don’t yet know how our findings translate to the general population,” Dr. Alosco said in an interview.
The study was published online in JAMA Network Open.
Repetitive head impacts
Dating back to the 1920s, PD and parkinsonism an umbrella term that refers to motor symptoms associated with PD and other conditions have long been described in boxers who suffer repetitive head impacts.
Multiple studies have linked tackle football with progressive brain diseases such as chronic traumatic encephalopathy. Few studies, however, have investigated the association between participation in football and PD.
For their study, Dr. Alosco and colleagues leveraged data from Fox Insight, a longitudinal online study of some people with and some without PD that is sponsored by the Michael J. Fox Foundation for Parkinson’s Research.
They focused their analyses on 1,875 men (mean age, 67 years) who reported playing any organized sport. As noted, the cohort was enriched for parkinsonism or PD. A total of 1,602 (85%) had received a diagnosis of parkinsonism/PD, and 273 had not.
Altogether, 729 men had a history of playing tackle football, and 1,146 men played non-football sports (control group). Among the football players, 82% played at youth sports or at the high school level; 17% played at the college level; and fewer than 1% played at the pro or semi-pro level.
Among the football players, 648 (89%) reported a parkinsonism/PD diagnosis.
A history of playing football was associated with higher odds of reporting a parkinsonism/PD diagnosis (odds ratio, 1.61; 95% confidence interval, 1.19-2.17) after accounting for age, education level, history of diabetes and heart disease, body mass index (BMI), traumatic brain injury with loss of consciousness, and family history of PD.
Football players who had longer careers and who played at higher levels of competition were at increased risk of having parkinsonism or PD.
Playing one to four seasons yielded an OR of 1.39 (95% CI, 0.98-1.98). The OR was 2.18 (95% CI, 1.36-3.49) for playing five or more seasons.
Football players who competed at the college or professional level had nearly triple the odds of reporting a parkinsonism/PD diagnosis (OR, 2.93; 95% CI, 1.28-6.73), compared with athletes who played at the youth or high school level.
Age at first exposure to football was not associated with a parkinsonism/PD diagnosis.
The researchers cautioned that this was a convenience sample of mostly White people, and the sample was enriched for having PD – factors that limit the generalizability of the findings.
Also, diagnosis of PD was self-reported by participants through online assessments, and objective in-person evaluations were not conducted.
Unequivocal link?
“This is among the first and largest to look at the relationship between football and having a diagnosis of PD in a large cohort of people from the Fox Insight online study,” Dr. Alosco said.
He cautioned that “not all people who play football will develop later-life neurological problems. That being said, the study adds to the accumulating evidence that suggests playing football is one risk factor for the development of later-life brain diseases.
“This represents an opportunity to educate the communities on the potential risks of playing football (short and long term), including what we know and what we don’t know, so that people can make informed decisions on participating in tackle football and develop additional ways to mitigate risk,” Dr. Alosco said.
In a comment, Shaheen Lakhan, MD, PhD, a neurologist and researcher from Boston, said: “The emerging body of research leaves little doubt that engaging in football raises the risk of developing Parkinson’s disease and parkinsonism.
“This progressive line of investigation serves to enhance our understanding, unequivocally demonstrating that even participation in amateur football, including at the youth and high school levels, constitutes a significant risk factor for the onset of Parkinson’s disease,” said Dr. Lakhan, who was not involved in the study.
However, he said it’s “crucial to underscore that the statistics reveal a notable distinction: individuals who have a history of college or professional football play face odds nearly three times higher of receiving a diagnosis of parkinsonism or Parkinson’s disease when compared to their counterparts who engaged in football during their youth or high-school years.
“Ultimately, determinations regarding involvement in sports should be a collaborative endeavor involving parents, young athletes, and health care providers. It is incumbent upon physicians to equip parents and youth with a comprehensive comprehension of the potential risks and rewards inherent in football participation,” Dr. Lakhan said.
He added, though, that there are multifaceted advantages to playing football. “This pursuit nurtures cardiovascular well-being, fosters invaluable social interactions, cultivates teamwork, instills discipline through regimented routines, and hones a spectrum of physical proficiencies,” Dr. Lakhan said.
“It’s worth noting that a constellation of alternative sports, including track and field, swimming, soccer, baseball, and tennis, can be cogently discussed as substitutes, all while preserving the manifold benefits of athletic engagement,” Dr. Lakhan added.
The Fox Insight Study is funded by the Michael J. Fox Foundation for Parkinson’s Research. The study was conducted in collaboration with the Michael J. Fox Foundation for Parkinson’s Research, the sponsor of the Fox Insight study, which collected and aggregated data used in the study. It was also supported by the National Institute of Neurological Disorders and Stroke. Dr. Alosco received grants from the National Institutes of Health during the conduct of the study, an honorarium from the Michael J. Fox Foundation for work unrelated to the study, and royalties from Oxford University Press outside the submitted work. Dr. Lakhan disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In a cross-sectional study of older men, former tackle football players had a 61% higher likelihood of reporting a diagnosis of parkinsonism or PD, compared with men who played non-football sports.
Longer duration of football participation and higher level of play (college and professional) were associated with higher risk.
Lead researcher Michael L. Alosco, PhD, director of the Boston University Alzheimer’s Disease Research Center, said it’s important to note that the findings are from a cohort of men “enriched” for having PD.
“These are people who are likely already concerned for or at risk for having this disease. We don’t yet know how our findings translate to the general population,” Dr. Alosco said in an interview.
The study was published online in JAMA Network Open.
Repetitive head impacts
Dating back to the 1920s, PD and parkinsonism an umbrella term that refers to motor symptoms associated with PD and other conditions have long been described in boxers who suffer repetitive head impacts.
Multiple studies have linked tackle football with progressive brain diseases such as chronic traumatic encephalopathy. Few studies, however, have investigated the association between participation in football and PD.
For their study, Dr. Alosco and colleagues leveraged data from Fox Insight, a longitudinal online study of some people with and some without PD that is sponsored by the Michael J. Fox Foundation for Parkinson’s Research.
They focused their analyses on 1,875 men (mean age, 67 years) who reported playing any organized sport. As noted, the cohort was enriched for parkinsonism or PD. A total of 1,602 (85%) had received a diagnosis of parkinsonism/PD, and 273 had not.
Altogether, 729 men had a history of playing tackle football, and 1,146 men played non-football sports (control group). Among the football players, 82% played at youth sports or at the high school level; 17% played at the college level; and fewer than 1% played at the pro or semi-pro level.
Among the football players, 648 (89%) reported a parkinsonism/PD diagnosis.
A history of playing football was associated with higher odds of reporting a parkinsonism/PD diagnosis (odds ratio, 1.61; 95% confidence interval, 1.19-2.17) after accounting for age, education level, history of diabetes and heart disease, body mass index (BMI), traumatic brain injury with loss of consciousness, and family history of PD.
Football players who had longer careers and who played at higher levels of competition were at increased risk of having parkinsonism or PD.
Playing one to four seasons yielded an OR of 1.39 (95% CI, 0.98-1.98). The OR was 2.18 (95% CI, 1.36-3.49) for playing five or more seasons.
Football players who competed at the college or professional level had nearly triple the odds of reporting a parkinsonism/PD diagnosis (OR, 2.93; 95% CI, 1.28-6.73), compared with athletes who played at the youth or high school level.
Age at first exposure to football was not associated with a parkinsonism/PD diagnosis.
The researchers cautioned that this was a convenience sample of mostly White people, and the sample was enriched for having PD – factors that limit the generalizability of the findings.
Also, diagnosis of PD was self-reported by participants through online assessments, and objective in-person evaluations were not conducted.
Unequivocal link?
“This is among the first and largest to look at the relationship between football and having a diagnosis of PD in a large cohort of people from the Fox Insight online study,” Dr. Alosco said.
He cautioned that “not all people who play football will develop later-life neurological problems. That being said, the study adds to the accumulating evidence that suggests playing football is one risk factor for the development of later-life brain diseases.
“This represents an opportunity to educate the communities on the potential risks of playing football (short and long term), including what we know and what we don’t know, so that people can make informed decisions on participating in tackle football and develop additional ways to mitigate risk,” Dr. Alosco said.
In a comment, Shaheen Lakhan, MD, PhD, a neurologist and researcher from Boston, said: “The emerging body of research leaves little doubt that engaging in football raises the risk of developing Parkinson’s disease and parkinsonism.
“This progressive line of investigation serves to enhance our understanding, unequivocally demonstrating that even participation in amateur football, including at the youth and high school levels, constitutes a significant risk factor for the onset of Parkinson’s disease,” said Dr. Lakhan, who was not involved in the study.
However, he said it’s “crucial to underscore that the statistics reveal a notable distinction: individuals who have a history of college or professional football play face odds nearly three times higher of receiving a diagnosis of parkinsonism or Parkinson’s disease when compared to their counterparts who engaged in football during their youth or high-school years.
“Ultimately, determinations regarding involvement in sports should be a collaborative endeavor involving parents, young athletes, and health care providers. It is incumbent upon physicians to equip parents and youth with a comprehensive comprehension of the potential risks and rewards inherent in football participation,” Dr. Lakhan said.
He added, though, that there are multifaceted advantages to playing football. “This pursuit nurtures cardiovascular well-being, fosters invaluable social interactions, cultivates teamwork, instills discipline through regimented routines, and hones a spectrum of physical proficiencies,” Dr. Lakhan said.
“It’s worth noting that a constellation of alternative sports, including track and field, swimming, soccer, baseball, and tennis, can be cogently discussed as substitutes, all while preserving the manifold benefits of athletic engagement,” Dr. Lakhan added.
The Fox Insight Study is funded by the Michael J. Fox Foundation for Parkinson’s Research. The study was conducted in collaboration with the Michael J. Fox Foundation for Parkinson’s Research, the sponsor of the Fox Insight study, which collected and aggregated data used in the study. It was also supported by the National Institute of Neurological Disorders and Stroke. Dr. Alosco received grants from the National Institutes of Health during the conduct of the study, an honorarium from the Michael J. Fox Foundation for work unrelated to the study, and royalties from Oxford University Press outside the submitted work. Dr. Lakhan disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
Which factors distinguish superagers from the rest of us?
Even at an advanced age, superagers have the memory of someone 20 or 30 years their junior. But why is that? A new study shows that, in superagers, However, the study also emphasizes the importance of physical and mental fitness for a healthy aging process.
“One of the most important unanswered questions with regard to superagers is: ‘Are they resistant to age-related memory loss, or do they have coping mechanisms that allow them to better offset this memory loss?’ ” wrote Marta Garo-Pascual, a PhD candidate at the Autonomous University of Madrid, Spain, and colleagues in the Lancet Healthy Longevity. “Our results indicate that superagers are resistant to these processes.”
Six years’ monitoring
From a cohort of older adults who had participated in a study aiming to identify early indicators of Alzheimer’s disease, the research group chose 64 superagers and 55 normal senior citizens. The latter served as the control group. While the superagers performed just as well in a memory test as people 30 years their junior, the control group’s performance was in line with their age and level of education.
All study participants were over age 79 years. Both the group of superagers and the control group included more females than males. On average, they were monitored for 6 years. During this period, a checkup was scheduled annually with an MRI examination, clinical tests, blood tests, and documentation of lifestyle factors.
For Alessandro Cellerino, PhD, of the Leibniz Institute on Aging–Fritz Lipmann Institute in Jena, Germany, this is the most crucial aspect of the study. “Even before this study, we knew that superagers demonstrated less atrophy in certain areas of the brain, but this was always only ever based on a single measurement.”
Memory centers protected
The MRI examinations confirmed that in superagers, gray matter atrophy in the regions responsible for memory (such as the medial temporal lobe and cholinergic forebrain), as well in regions important for movement (such as the motor thalamus), was less pronounced. In addition, the volume of gray matter in these regions, especially in the medial temporal lobe, decreased much more slowly in the superagers than in the control subjects over the study period.
Ms. Garo-Pascual and associates used a machine-learning algorithm to differentiate between superagers and normal older adults. From the 89 demographic, lifestyle, and clinical factors entered into the algorithm, two were the most important for the classification: the ability to move and mental health.
Mobility and mental health
Clinical tests such as the Timed Up-and-Go Test and the Finger Tapping Test revealed that superagers can be distinguished from the normally aging control subjects with regard to their mobility and fine motor skills. Their physical condition was better, although they, by their own admission, did not move any more than the control subjects in day-to-day life. According to Dr. Cellerino, this finding confirms that physical activity is paramount for cognitive function. “These people were over 80 years old – the fact that there was not much difference between their levels of activity is not surprising. Much more relevant is the question of how you get there – i.e., how active you are at the ages of 40, 50 or even 60 years old.”
Remaining active is important
As a matter of fact, the superagers indicated that generally they had been more active than the control subjects during their middle years. “Attempting to stay physically fit is essential; even if it just means going for a walk or taking the stairs,” said Dr. Cellerino.
On average, the superagers also fared much better in tests on physical health than the control subjects. They suffered significantly less from depression or anxiety disorders. “Earlier studies suggest that depression and anxiety disorders may influence performance in memory tests across all ages and that they are risk factors for developing dementia,” said Dr. Cellerino.
To avoid mental health issues in later life, gerontologist Dr. Cellerino recommended remaining socially engaged and involved. “Depression and anxiety are commonly also a consequence of social isolation,” he said.
Potential genetic differences
Blood sample analyses demonstrated that the superagers exhibited lower concentrations of biomarkers for neurodegenerative diseases than the control group did. In contrast, there was no difference between the two groups in the prevalence of the apo e4 allele, one of the most important genetic risk factors for Alzheimer’s disease. Nevertheless, Ms. Garo-Pascual and associates assume that genetics also play a role. They found that, despite 89 variables employed, the algorithm used could only distinguish superagers from normal older adults 66% of the time. This suggests that additional factors must be in play, such as genetic differences.
Body and mind
Since this is an observational study, whether the determined factors have a direct effect on superaging cannot be ascertained, the authors wrote. However, the results are consistent with earlier findings.
“Regarding the management of old age, we actually haven’t learned anything more than what we already knew. But it does confirm that physical and mental function are closely entwined and that we must maintain both to age healthily,” Dr. Cellerino concluded.
This article was translated from the Medscape German Edition. A version appeared on Medscape.com.
Even at an advanced age, superagers have the memory of someone 20 or 30 years their junior. But why is that? A new study shows that, in superagers, However, the study also emphasizes the importance of physical and mental fitness for a healthy aging process.
“One of the most important unanswered questions with regard to superagers is: ‘Are they resistant to age-related memory loss, or do they have coping mechanisms that allow them to better offset this memory loss?’ ” wrote Marta Garo-Pascual, a PhD candidate at the Autonomous University of Madrid, Spain, and colleagues in the Lancet Healthy Longevity. “Our results indicate that superagers are resistant to these processes.”
Six years’ monitoring
From a cohort of older adults who had participated in a study aiming to identify early indicators of Alzheimer’s disease, the research group chose 64 superagers and 55 normal senior citizens. The latter served as the control group. While the superagers performed just as well in a memory test as people 30 years their junior, the control group’s performance was in line with their age and level of education.
All study participants were over age 79 years. Both the group of superagers and the control group included more females than males. On average, they were monitored for 6 years. During this period, a checkup was scheduled annually with an MRI examination, clinical tests, blood tests, and documentation of lifestyle factors.
For Alessandro Cellerino, PhD, of the Leibniz Institute on Aging–Fritz Lipmann Institute in Jena, Germany, this is the most crucial aspect of the study. “Even before this study, we knew that superagers demonstrated less atrophy in certain areas of the brain, but this was always only ever based on a single measurement.”
Memory centers protected
The MRI examinations confirmed that in superagers, gray matter atrophy in the regions responsible for memory (such as the medial temporal lobe and cholinergic forebrain), as well in regions important for movement (such as the motor thalamus), was less pronounced. In addition, the volume of gray matter in these regions, especially in the medial temporal lobe, decreased much more slowly in the superagers than in the control subjects over the study period.
Ms. Garo-Pascual and associates used a machine-learning algorithm to differentiate between superagers and normal older adults. From the 89 demographic, lifestyle, and clinical factors entered into the algorithm, two were the most important for the classification: the ability to move and mental health.
Mobility and mental health
Clinical tests such as the Timed Up-and-Go Test and the Finger Tapping Test revealed that superagers can be distinguished from the normally aging control subjects with regard to their mobility and fine motor skills. Their physical condition was better, although they, by their own admission, did not move any more than the control subjects in day-to-day life. According to Dr. Cellerino, this finding confirms that physical activity is paramount for cognitive function. “These people were over 80 years old – the fact that there was not much difference between their levels of activity is not surprising. Much more relevant is the question of how you get there – i.e., how active you are at the ages of 40, 50 or even 60 years old.”
Remaining active is important
As a matter of fact, the superagers indicated that generally they had been more active than the control subjects during their middle years. “Attempting to stay physically fit is essential; even if it just means going for a walk or taking the stairs,” said Dr. Cellerino.
On average, the superagers also fared much better in tests on physical health than the control subjects. They suffered significantly less from depression or anxiety disorders. “Earlier studies suggest that depression and anxiety disorders may influence performance in memory tests across all ages and that they are risk factors for developing dementia,” said Dr. Cellerino.
To avoid mental health issues in later life, gerontologist Dr. Cellerino recommended remaining socially engaged and involved. “Depression and anxiety are commonly also a consequence of social isolation,” he said.
Potential genetic differences
Blood sample analyses demonstrated that the superagers exhibited lower concentrations of biomarkers for neurodegenerative diseases than the control group did. In contrast, there was no difference between the two groups in the prevalence of the apo e4 allele, one of the most important genetic risk factors for Alzheimer’s disease. Nevertheless, Ms. Garo-Pascual and associates assume that genetics also play a role. They found that, despite 89 variables employed, the algorithm used could only distinguish superagers from normal older adults 66% of the time. This suggests that additional factors must be in play, such as genetic differences.
Body and mind
Since this is an observational study, whether the determined factors have a direct effect on superaging cannot be ascertained, the authors wrote. However, the results are consistent with earlier findings.
“Regarding the management of old age, we actually haven’t learned anything more than what we already knew. But it does confirm that physical and mental function are closely entwined and that we must maintain both to age healthily,” Dr. Cellerino concluded.
This article was translated from the Medscape German Edition. A version appeared on Medscape.com.
Even at an advanced age, superagers have the memory of someone 20 or 30 years their junior. But why is that? A new study shows that, in superagers, However, the study also emphasizes the importance of physical and mental fitness for a healthy aging process.
“One of the most important unanswered questions with regard to superagers is: ‘Are they resistant to age-related memory loss, or do they have coping mechanisms that allow them to better offset this memory loss?’ ” wrote Marta Garo-Pascual, a PhD candidate at the Autonomous University of Madrid, Spain, and colleagues in the Lancet Healthy Longevity. “Our results indicate that superagers are resistant to these processes.”
Six years’ monitoring
From a cohort of older adults who had participated in a study aiming to identify early indicators of Alzheimer’s disease, the research group chose 64 superagers and 55 normal senior citizens. The latter served as the control group. While the superagers performed just as well in a memory test as people 30 years their junior, the control group’s performance was in line with their age and level of education.
All study participants were over age 79 years. Both the group of superagers and the control group included more females than males. On average, they were monitored for 6 years. During this period, a checkup was scheduled annually with an MRI examination, clinical tests, blood tests, and documentation of lifestyle factors.
For Alessandro Cellerino, PhD, of the Leibniz Institute on Aging–Fritz Lipmann Institute in Jena, Germany, this is the most crucial aspect of the study. “Even before this study, we knew that superagers demonstrated less atrophy in certain areas of the brain, but this was always only ever based on a single measurement.”
Memory centers protected
The MRI examinations confirmed that in superagers, gray matter atrophy in the regions responsible for memory (such as the medial temporal lobe and cholinergic forebrain), as well in regions important for movement (such as the motor thalamus), was less pronounced. In addition, the volume of gray matter in these regions, especially in the medial temporal lobe, decreased much more slowly in the superagers than in the control subjects over the study period.
Ms. Garo-Pascual and associates used a machine-learning algorithm to differentiate between superagers and normal older adults. From the 89 demographic, lifestyle, and clinical factors entered into the algorithm, two were the most important for the classification: the ability to move and mental health.
Mobility and mental health
Clinical tests such as the Timed Up-and-Go Test and the Finger Tapping Test revealed that superagers can be distinguished from the normally aging control subjects with regard to their mobility and fine motor skills. Their physical condition was better, although they, by their own admission, did not move any more than the control subjects in day-to-day life. According to Dr. Cellerino, this finding confirms that physical activity is paramount for cognitive function. “These people were over 80 years old – the fact that there was not much difference between their levels of activity is not surprising. Much more relevant is the question of how you get there – i.e., how active you are at the ages of 40, 50 or even 60 years old.”
Remaining active is important
As a matter of fact, the superagers indicated that generally they had been more active than the control subjects during their middle years. “Attempting to stay physically fit is essential; even if it just means going for a walk or taking the stairs,” said Dr. Cellerino.
On average, the superagers also fared much better in tests on physical health than the control subjects. They suffered significantly less from depression or anxiety disorders. “Earlier studies suggest that depression and anxiety disorders may influence performance in memory tests across all ages and that they are risk factors for developing dementia,” said Dr. Cellerino.
To avoid mental health issues in later life, gerontologist Dr. Cellerino recommended remaining socially engaged and involved. “Depression and anxiety are commonly also a consequence of social isolation,” he said.
Potential genetic differences
Blood sample analyses demonstrated that the superagers exhibited lower concentrations of biomarkers for neurodegenerative diseases than the control group did. In contrast, there was no difference between the two groups in the prevalence of the apo e4 allele, one of the most important genetic risk factors for Alzheimer’s disease. Nevertheless, Ms. Garo-Pascual and associates assume that genetics also play a role. They found that, despite 89 variables employed, the algorithm used could only distinguish superagers from normal older adults 66% of the time. This suggests that additional factors must be in play, such as genetic differences.
Body and mind
Since this is an observational study, whether the determined factors have a direct effect on superaging cannot be ascertained, the authors wrote. However, the results are consistent with earlier findings.
“Regarding the management of old age, we actually haven’t learned anything more than what we already knew. But it does confirm that physical and mental function are closely entwined and that we must maintain both to age healthily,” Dr. Cellerino concluded.
This article was translated from the Medscape German Edition. A version appeared on Medscape.com.
FROM THE LANCET HEALTHY LONGEVITY
West Nile infections rising in the U.S.
Several signs are pointing to an impending surge in the number of human cases of West Nile virus in several regions of the United States.
West Nile virus is spread by infected mosquitoes and currently there is no cure or virus-specific treatment. In rare cases, it can be deadly. It can infect humans, birds, horses, and other mammals.
West Nile Virus is the leading cause of mosquito-borne disease in the continental United States. As of Aug. 8, 126 human cases had been identified across 22 states, according to the Centers for Disease Control and Prevention.
“Particularly here in California, it’s peak risk right now,” said Vicki Kramer, PhD, chief of vector-borne diseases in the California Department of Public Health. She said scientists there are seeing higher mosquito and infected mosquito numbers.
“Peak risk right now”
Dead birds are tested for the virus and by Aug. 4, 181 of the 913 birds tested in California have been positive, three times the total testing positive by this time in 2022.
“Last year at this time, we had 60 positive dead birds out of 817 tested,” Dr. Kramer said.
Severe flooding and high heat can contribute to the rise in mosquito populations and many parts of the country have seen plenty of both.
One of the ways scientists track infected mosquito patterns in California is by using flocks of strategically placed sentinel chickens.
“Chickens are a mosquito magnet,” Dr. Kramer said.
Chickens don’t get sick with the virus, but they do build antibodies to it. Surveillance teams check their blood every other week to track the virus.
Daniel Pastula, MD, MHS, chief of neuroinfectious diseases and global neurology at the University of Colorado School of Medicine and the Colorado School of Public Health, said the state is watching troubling signs as well.
“The concern this year,” Dr. Pastula said, “particularly along the Front Range in Colorado, is we’ve found many more mosquitoes [that are] positive for West Nile earlier in the season compared with other years.
“We’re bracing for higher-than-baseline human cases,” he said.
Asked about this year’s first human case, reported in Toronto, a region with a long winter and low incidence of the virus, he said that provides a further example that people need to be prepared even in climates not known to be mosquito-dense.
He added, however, that climate is only one factor in the severity of the season. Others include birds’ immunity and migratory patterns.
Dr. Pastula said that fluctuations in temperature and rainfall are rising with climate change and are disrupting normal baseline levels of West Nile.
“That shows we need to be prepared for West Nile virus and other mosquito-borne diseases in any place in North America or really the world. We recently saw malaria cases in the southern United States. It just shows you how dangerous mosquitoes can be.”
Avoid mosquito bites
Dr. Pastula and Dr. Kramer list the precautions people can take to protect themselves from West Nile virus:
- Limit outdoor exposure particularly at dusk and dawn.
- Wear protective clothing.
- Use .
- Repair window screens so mosquitoes cannot fly through.
- Dump and drain standing water on your property and maintain swimming pools.
Dr. Pastula noted that summer is the time human cases start to mount – typically from July and August to the first hard freeze.
“We have been warning people here up and down the Front Range of Colorado to take prevention very seriously,” Dr. Pastula said.
He pointed out that 80% who are infected with West Nile will have no symptoms.
About 20% will have flu-like illness – high fever, body and joint aches, rash, diarrhea, or headaches. Symptoms may last for weeks. About 1% of the time, he said, people can get neuroinvasive West Nile.
Dr. Pastula explained that the virus can infect the covering of the brain and spinal cord causing meningitis with very high fever, severe headaches, stiff neck, and sensitivity to light.
So far this year, there have been 89 neuroinvasive cases reported nationally, according to the CDC.
With West Nile encephalitis, the virus “can infect the brain itself causing altered mental status, movement disorders, or weakness,” Dr. Pastula said.
Sometimes it can infect the gray matter of the spinal cord causing a West Nile virus poliomyelitis, which brings polio-like symptoms.
“The West Nile encephalitis and poliomyelitis can cause permanent deficits or even death,” he said. “It’s uncommon but it’s not trivial.”
Several vaccine candidates are in development, Dr. Pastula said, but none has reached clinical trials. Part of the reason for that, he said, is that scientists must be able to predict the timing of an outbreak.
“We’re not really great at predicting outbreaks,” he said.
Although the risk for neuroinvasive disease is small, it can be higher in certain groups, he said – those who are over age 60 years or are immunocompromised; those who have diabetes, cancer, or kidney disease; or those who have undergone organ transplants.
Those infected should see a health care professional and may be able to get relief with the usual medications for flu-like illness.
Some with severe infection may need to go to the hospital, Dr. Pastula said.
A version of this article first appeared on Medscape.com.
Several signs are pointing to an impending surge in the number of human cases of West Nile virus in several regions of the United States.
West Nile virus is spread by infected mosquitoes and currently there is no cure or virus-specific treatment. In rare cases, it can be deadly. It can infect humans, birds, horses, and other mammals.
West Nile Virus is the leading cause of mosquito-borne disease in the continental United States. As of Aug. 8, 126 human cases had been identified across 22 states, according to the Centers for Disease Control and Prevention.
“Particularly here in California, it’s peak risk right now,” said Vicki Kramer, PhD, chief of vector-borne diseases in the California Department of Public Health. She said scientists there are seeing higher mosquito and infected mosquito numbers.
“Peak risk right now”
Dead birds are tested for the virus and by Aug. 4, 181 of the 913 birds tested in California have been positive, three times the total testing positive by this time in 2022.
“Last year at this time, we had 60 positive dead birds out of 817 tested,” Dr. Kramer said.
Severe flooding and high heat can contribute to the rise in mosquito populations and many parts of the country have seen plenty of both.
One of the ways scientists track infected mosquito patterns in California is by using flocks of strategically placed sentinel chickens.
“Chickens are a mosquito magnet,” Dr. Kramer said.
Chickens don’t get sick with the virus, but they do build antibodies to it. Surveillance teams check their blood every other week to track the virus.
Daniel Pastula, MD, MHS, chief of neuroinfectious diseases and global neurology at the University of Colorado School of Medicine and the Colorado School of Public Health, said the state is watching troubling signs as well.
“The concern this year,” Dr. Pastula said, “particularly along the Front Range in Colorado, is we’ve found many more mosquitoes [that are] positive for West Nile earlier in the season compared with other years.
“We’re bracing for higher-than-baseline human cases,” he said.
Asked about this year’s first human case, reported in Toronto, a region with a long winter and low incidence of the virus, he said that provides a further example that people need to be prepared even in climates not known to be mosquito-dense.
He added, however, that climate is only one factor in the severity of the season. Others include birds’ immunity and migratory patterns.
Dr. Pastula said that fluctuations in temperature and rainfall are rising with climate change and are disrupting normal baseline levels of West Nile.
“That shows we need to be prepared for West Nile virus and other mosquito-borne diseases in any place in North America or really the world. We recently saw malaria cases in the southern United States. It just shows you how dangerous mosquitoes can be.”
Avoid mosquito bites
Dr. Pastula and Dr. Kramer list the precautions people can take to protect themselves from West Nile virus:
- Limit outdoor exposure particularly at dusk and dawn.
- Wear protective clothing.
- Use .
- Repair window screens so mosquitoes cannot fly through.
- Dump and drain standing water on your property and maintain swimming pools.
Dr. Pastula noted that summer is the time human cases start to mount – typically from July and August to the first hard freeze.
“We have been warning people here up and down the Front Range of Colorado to take prevention very seriously,” Dr. Pastula said.
He pointed out that 80% who are infected with West Nile will have no symptoms.
About 20% will have flu-like illness – high fever, body and joint aches, rash, diarrhea, or headaches. Symptoms may last for weeks. About 1% of the time, he said, people can get neuroinvasive West Nile.
Dr. Pastula explained that the virus can infect the covering of the brain and spinal cord causing meningitis with very high fever, severe headaches, stiff neck, and sensitivity to light.
So far this year, there have been 89 neuroinvasive cases reported nationally, according to the CDC.
With West Nile encephalitis, the virus “can infect the brain itself causing altered mental status, movement disorders, or weakness,” Dr. Pastula said.
Sometimes it can infect the gray matter of the spinal cord causing a West Nile virus poliomyelitis, which brings polio-like symptoms.
“The West Nile encephalitis and poliomyelitis can cause permanent deficits or even death,” he said. “It’s uncommon but it’s not trivial.”
Several vaccine candidates are in development, Dr. Pastula said, but none has reached clinical trials. Part of the reason for that, he said, is that scientists must be able to predict the timing of an outbreak.
“We’re not really great at predicting outbreaks,” he said.
Although the risk for neuroinvasive disease is small, it can be higher in certain groups, he said – those who are over age 60 years or are immunocompromised; those who have diabetes, cancer, or kidney disease; or those who have undergone organ transplants.
Those infected should see a health care professional and may be able to get relief with the usual medications for flu-like illness.
Some with severe infection may need to go to the hospital, Dr. Pastula said.
A version of this article first appeared on Medscape.com.
Several signs are pointing to an impending surge in the number of human cases of West Nile virus in several regions of the United States.
West Nile virus is spread by infected mosquitoes and currently there is no cure or virus-specific treatment. In rare cases, it can be deadly. It can infect humans, birds, horses, and other mammals.
West Nile Virus is the leading cause of mosquito-borne disease in the continental United States. As of Aug. 8, 126 human cases had been identified across 22 states, according to the Centers for Disease Control and Prevention.
“Particularly here in California, it’s peak risk right now,” said Vicki Kramer, PhD, chief of vector-borne diseases in the California Department of Public Health. She said scientists there are seeing higher mosquito and infected mosquito numbers.
“Peak risk right now”
Dead birds are tested for the virus and by Aug. 4, 181 of the 913 birds tested in California have been positive, three times the total testing positive by this time in 2022.
“Last year at this time, we had 60 positive dead birds out of 817 tested,” Dr. Kramer said.
Severe flooding and high heat can contribute to the rise in mosquito populations and many parts of the country have seen plenty of both.
One of the ways scientists track infected mosquito patterns in California is by using flocks of strategically placed sentinel chickens.
“Chickens are a mosquito magnet,” Dr. Kramer said.
Chickens don’t get sick with the virus, but they do build antibodies to it. Surveillance teams check their blood every other week to track the virus.
Daniel Pastula, MD, MHS, chief of neuroinfectious diseases and global neurology at the University of Colorado School of Medicine and the Colorado School of Public Health, said the state is watching troubling signs as well.
“The concern this year,” Dr. Pastula said, “particularly along the Front Range in Colorado, is we’ve found many more mosquitoes [that are] positive for West Nile earlier in the season compared with other years.
“We’re bracing for higher-than-baseline human cases,” he said.
Asked about this year’s first human case, reported in Toronto, a region with a long winter and low incidence of the virus, he said that provides a further example that people need to be prepared even in climates not known to be mosquito-dense.
He added, however, that climate is only one factor in the severity of the season. Others include birds’ immunity and migratory patterns.
Dr. Pastula said that fluctuations in temperature and rainfall are rising with climate change and are disrupting normal baseline levels of West Nile.
“That shows we need to be prepared for West Nile virus and other mosquito-borne diseases in any place in North America or really the world. We recently saw malaria cases in the southern United States. It just shows you how dangerous mosquitoes can be.”
Avoid mosquito bites
Dr. Pastula and Dr. Kramer list the precautions people can take to protect themselves from West Nile virus:
- Limit outdoor exposure particularly at dusk and dawn.
- Wear protective clothing.
- Use .
- Repair window screens so mosquitoes cannot fly through.
- Dump and drain standing water on your property and maintain swimming pools.
Dr. Pastula noted that summer is the time human cases start to mount – typically from July and August to the first hard freeze.
“We have been warning people here up and down the Front Range of Colorado to take prevention very seriously,” Dr. Pastula said.
He pointed out that 80% who are infected with West Nile will have no symptoms.
About 20% will have flu-like illness – high fever, body and joint aches, rash, diarrhea, or headaches. Symptoms may last for weeks. About 1% of the time, he said, people can get neuroinvasive West Nile.
Dr. Pastula explained that the virus can infect the covering of the brain and spinal cord causing meningitis with very high fever, severe headaches, stiff neck, and sensitivity to light.
So far this year, there have been 89 neuroinvasive cases reported nationally, according to the CDC.
With West Nile encephalitis, the virus “can infect the brain itself causing altered mental status, movement disorders, or weakness,” Dr. Pastula said.
Sometimes it can infect the gray matter of the spinal cord causing a West Nile virus poliomyelitis, which brings polio-like symptoms.
“The West Nile encephalitis and poliomyelitis can cause permanent deficits or even death,” he said. “It’s uncommon but it’s not trivial.”
Several vaccine candidates are in development, Dr. Pastula said, but none has reached clinical trials. Part of the reason for that, he said, is that scientists must be able to predict the timing of an outbreak.
“We’re not really great at predicting outbreaks,” he said.
Although the risk for neuroinvasive disease is small, it can be higher in certain groups, he said – those who are over age 60 years or are immunocompromised; those who have diabetes, cancer, or kidney disease; or those who have undergone organ transplants.
Those infected should see a health care professional and may be able to get relief with the usual medications for flu-like illness.
Some with severe infection may need to go to the hospital, Dr. Pastula said.
A version of this article first appeared on Medscape.com.
TBI tied to increased mental health diagnoses, time to suicide
Investigators also found that increases in new mental health diagnoses are significantly higher in soldiers with a history of TBI – in some cases, strikingly higher. For example, cases of substance use disorder rose by 100% among veterans with TBI compared to just 14.5% in those with no brain injury.
“We had had pieces of these findings for a long time but to be able to lay out this longitudinal story over time is the part that’s new and important to really switch the focus to people’s whole lives and things that happen over time, both psychological and physical,” lead author Lisa Brenner, PhD, director of the Veterans Health Administration (VHA) Rocky Mountain Mental Illness Research Education and Clinical Center, Aurora, Colo., said in an interview.
“If we take that life-course view, it’s a very different way about thinking about conceptualizing exposures and conceptualizing risk and it’s a different way of thinking about treatment and prevention,” added Dr. Brenner, professor of physical medicine and rehabilitation, psychiatry, and neurology at the University of Colorado, Aurora. “I think that definitely applies to civilian populations.”
The findings were published online in JAMA Network Open.
Largest, longest study to date
Researchers have long suspected that TBI and a higher rate of new mental illness and a shorter time to suicide are all somehow linked. But this study examined all three components longitudinally, in what is thought to be the largest and longest study on the topic to date, including more than 860,000 people who were followed for up to a decade.
Investigators studied health data from the Substance Use and Psychological Injury Combat Study database on 860,892 U.S. Army soldiers who returned from deployment in Iraq or Afghanistan between 2008 and 2014 and were 18-24 years old at the end of that deployment. They then examined new mental health diagnoses and suicide trends over time.
Nearly 109,000 (12.6%) experienced a TBI during deployment, and 2,695 had died by suicide through the end of 2018.
New-onset diagnoses of anxiety, mood disorders, posttraumatic stress disorder, alcohol use, and substance use disorder (SUD) after deployment were all more common in soldiers who experienced PTSD while serving compared with those with no history of TBI.
There was a 67.7% increase in mood disorders in participants with TBI compared with a 37.5% increase in those without TBI. The increase in new cases of alcohol use disorder was also greater in the TBI group (a 31.9% increase vs. a 10.3% increase).
But the sharpest difference was the increase in substance use disorder among those with TBI, which rose 100% compared with a 14.5% increase in solders with no history of TBI.
Sharp differences in time to suicide
Death by suicide was only slightly more common in those with TBI compared with those without (0.4% vs. 0.3%, respectively). But those with a brain injury committed suicide 21.3% sooner than did those without a head injury, after the researchers controlled for sex, age, race, ethnicity, and fiscal year of return from deployment.
Time to suicide was faster in those with a TBI and two or more new mental health diagnoses and fastest among those with TBI and a new SUD diagnosis, who took their own lives 62.8% faster than did those without a TBI.
The findings offer an important message to medical professionals in many different specialties, Dr. Brenner said.
“Folks in mental health probably have a lot of patients who have brain injury in their practice, and they don’t know it and that’s an important thing to know,” she said, adding that “neurologists should screen for depression and other mental health conditions and make sure those people have evidence-based treatments for those mental health conditions while they’re addressing the TBI-related symptoms.”
Applicable to civilians?
“The complex interplay between TBI, its potential effects on mental health, and risk of suicide remains a vexing focus of ongoing investigations and academic inquiry,” Ross Zafonte, DO, president of Spaulding Rehabilitation Hospital Network and professor and chair of physical medicine and rehabilitation at Harvard Medical School, Boston, and colleagues, wrote in an accompanying editorial.
The study builds on earlier work, they added, and praised the study’s longitudinal design and large cohort as key to the findings. The data on increased rates of new-onset substance use disorder, which was also associated with a faster time to suicide in the TBI group, were of particular interest.
“In this work, Brenner and colleagues identified substance use disorder as a key factor in faster time to suicide for active-duty service members with a history of TBI compared with those without TBI and theorized that a multiple stress or exposure burden may enhance risk,” they wrote. “This theory is reasonable and has been postulated among individuals with medical sequelae linked to TBI.”
However, the authors caution against applying these findings in military veterans to civilians.
“While this work is critical in the military population, caution should be given to avoid direct generalization to other populations, such as athletes, for whom the linkage to suicidal ideation is less understood,” they wrote.
The study was funded by National Institute of Mental Health and Office of the Director at National Institutes of Health. Dr. Brenner has received personal fees from Wolters Kluwer, Rand, American Psychological Association, and Oxford University Press and serves as a consultant to sports leagues via her university affiliation. Dr. Zafonte reported receiving royalties from Springer/Demos; serving as a member of the editorial boards of Journal of Neurotrauma and Frontiers in Neurology and scientific advisory boards of Myomo, Nanodiagnostics, Onecare.ai, and Kisbee; and evaluating patients in the MGH Brain and Body-TRUST Program, which is funded by the National Football League Players Association.
A version of this article first appeared on Medscape.com.
Investigators also found that increases in new mental health diagnoses are significantly higher in soldiers with a history of TBI – in some cases, strikingly higher. For example, cases of substance use disorder rose by 100% among veterans with TBI compared to just 14.5% in those with no brain injury.
“We had had pieces of these findings for a long time but to be able to lay out this longitudinal story over time is the part that’s new and important to really switch the focus to people’s whole lives and things that happen over time, both psychological and physical,” lead author Lisa Brenner, PhD, director of the Veterans Health Administration (VHA) Rocky Mountain Mental Illness Research Education and Clinical Center, Aurora, Colo., said in an interview.
“If we take that life-course view, it’s a very different way about thinking about conceptualizing exposures and conceptualizing risk and it’s a different way of thinking about treatment and prevention,” added Dr. Brenner, professor of physical medicine and rehabilitation, psychiatry, and neurology at the University of Colorado, Aurora. “I think that definitely applies to civilian populations.”
The findings were published online in JAMA Network Open.
Largest, longest study to date
Researchers have long suspected that TBI and a higher rate of new mental illness and a shorter time to suicide are all somehow linked. But this study examined all three components longitudinally, in what is thought to be the largest and longest study on the topic to date, including more than 860,000 people who were followed for up to a decade.
Investigators studied health data from the Substance Use and Psychological Injury Combat Study database on 860,892 U.S. Army soldiers who returned from deployment in Iraq or Afghanistan between 2008 and 2014 and were 18-24 years old at the end of that deployment. They then examined new mental health diagnoses and suicide trends over time.
Nearly 109,000 (12.6%) experienced a TBI during deployment, and 2,695 had died by suicide through the end of 2018.
New-onset diagnoses of anxiety, mood disorders, posttraumatic stress disorder, alcohol use, and substance use disorder (SUD) after deployment were all more common in soldiers who experienced PTSD while serving compared with those with no history of TBI.
There was a 67.7% increase in mood disorders in participants with TBI compared with a 37.5% increase in those without TBI. The increase in new cases of alcohol use disorder was also greater in the TBI group (a 31.9% increase vs. a 10.3% increase).
But the sharpest difference was the increase in substance use disorder among those with TBI, which rose 100% compared with a 14.5% increase in solders with no history of TBI.
Sharp differences in time to suicide
Death by suicide was only slightly more common in those with TBI compared with those without (0.4% vs. 0.3%, respectively). But those with a brain injury committed suicide 21.3% sooner than did those without a head injury, after the researchers controlled for sex, age, race, ethnicity, and fiscal year of return from deployment.
Time to suicide was faster in those with a TBI and two or more new mental health diagnoses and fastest among those with TBI and a new SUD diagnosis, who took their own lives 62.8% faster than did those without a TBI.
The findings offer an important message to medical professionals in many different specialties, Dr. Brenner said.
“Folks in mental health probably have a lot of patients who have brain injury in their practice, and they don’t know it and that’s an important thing to know,” she said, adding that “neurologists should screen for depression and other mental health conditions and make sure those people have evidence-based treatments for those mental health conditions while they’re addressing the TBI-related symptoms.”
Applicable to civilians?
“The complex interplay between TBI, its potential effects on mental health, and risk of suicide remains a vexing focus of ongoing investigations and academic inquiry,” Ross Zafonte, DO, president of Spaulding Rehabilitation Hospital Network and professor and chair of physical medicine and rehabilitation at Harvard Medical School, Boston, and colleagues, wrote in an accompanying editorial.
The study builds on earlier work, they added, and praised the study’s longitudinal design and large cohort as key to the findings. The data on increased rates of new-onset substance use disorder, which was also associated with a faster time to suicide in the TBI group, were of particular interest.
“In this work, Brenner and colleagues identified substance use disorder as a key factor in faster time to suicide for active-duty service members with a history of TBI compared with those without TBI and theorized that a multiple stress or exposure burden may enhance risk,” they wrote. “This theory is reasonable and has been postulated among individuals with medical sequelae linked to TBI.”
However, the authors caution against applying these findings in military veterans to civilians.
“While this work is critical in the military population, caution should be given to avoid direct generalization to other populations, such as athletes, for whom the linkage to suicidal ideation is less understood,” they wrote.
The study was funded by National Institute of Mental Health and Office of the Director at National Institutes of Health. Dr. Brenner has received personal fees from Wolters Kluwer, Rand, American Psychological Association, and Oxford University Press and serves as a consultant to sports leagues via her university affiliation. Dr. Zafonte reported receiving royalties from Springer/Demos; serving as a member of the editorial boards of Journal of Neurotrauma and Frontiers in Neurology and scientific advisory boards of Myomo, Nanodiagnostics, Onecare.ai, and Kisbee; and evaluating patients in the MGH Brain and Body-TRUST Program, which is funded by the National Football League Players Association.
A version of this article first appeared on Medscape.com.
Investigators also found that increases in new mental health diagnoses are significantly higher in soldiers with a history of TBI – in some cases, strikingly higher. For example, cases of substance use disorder rose by 100% among veterans with TBI compared to just 14.5% in those with no brain injury.
“We had had pieces of these findings for a long time but to be able to lay out this longitudinal story over time is the part that’s new and important to really switch the focus to people’s whole lives and things that happen over time, both psychological and physical,” lead author Lisa Brenner, PhD, director of the Veterans Health Administration (VHA) Rocky Mountain Mental Illness Research Education and Clinical Center, Aurora, Colo., said in an interview.
“If we take that life-course view, it’s a very different way about thinking about conceptualizing exposures and conceptualizing risk and it’s a different way of thinking about treatment and prevention,” added Dr. Brenner, professor of physical medicine and rehabilitation, psychiatry, and neurology at the University of Colorado, Aurora. “I think that definitely applies to civilian populations.”
The findings were published online in JAMA Network Open.
Largest, longest study to date
Researchers have long suspected that TBI and a higher rate of new mental illness and a shorter time to suicide are all somehow linked. But this study examined all three components longitudinally, in what is thought to be the largest and longest study on the topic to date, including more than 860,000 people who were followed for up to a decade.
Investigators studied health data from the Substance Use and Psychological Injury Combat Study database on 860,892 U.S. Army soldiers who returned from deployment in Iraq or Afghanistan between 2008 and 2014 and were 18-24 years old at the end of that deployment. They then examined new mental health diagnoses and suicide trends over time.
Nearly 109,000 (12.6%) experienced a TBI during deployment, and 2,695 had died by suicide through the end of 2018.
New-onset diagnoses of anxiety, mood disorders, posttraumatic stress disorder, alcohol use, and substance use disorder (SUD) after deployment were all more common in soldiers who experienced PTSD while serving compared with those with no history of TBI.
There was a 67.7% increase in mood disorders in participants with TBI compared with a 37.5% increase in those without TBI. The increase in new cases of alcohol use disorder was also greater in the TBI group (a 31.9% increase vs. a 10.3% increase).
But the sharpest difference was the increase in substance use disorder among those with TBI, which rose 100% compared with a 14.5% increase in solders with no history of TBI.
Sharp differences in time to suicide
Death by suicide was only slightly more common in those with TBI compared with those without (0.4% vs. 0.3%, respectively). But those with a brain injury committed suicide 21.3% sooner than did those without a head injury, after the researchers controlled for sex, age, race, ethnicity, and fiscal year of return from deployment.
Time to suicide was faster in those with a TBI and two or more new mental health diagnoses and fastest among those with TBI and a new SUD diagnosis, who took their own lives 62.8% faster than did those without a TBI.
The findings offer an important message to medical professionals in many different specialties, Dr. Brenner said.
“Folks in mental health probably have a lot of patients who have brain injury in their practice, and they don’t know it and that’s an important thing to know,” she said, adding that “neurologists should screen for depression and other mental health conditions and make sure those people have evidence-based treatments for those mental health conditions while they’re addressing the TBI-related symptoms.”
Applicable to civilians?
“The complex interplay between TBI, its potential effects on mental health, and risk of suicide remains a vexing focus of ongoing investigations and academic inquiry,” Ross Zafonte, DO, president of Spaulding Rehabilitation Hospital Network and professor and chair of physical medicine and rehabilitation at Harvard Medical School, Boston, and colleagues, wrote in an accompanying editorial.
The study builds on earlier work, they added, and praised the study’s longitudinal design and large cohort as key to the findings. The data on increased rates of new-onset substance use disorder, which was also associated with a faster time to suicide in the TBI group, were of particular interest.
“In this work, Brenner and colleagues identified substance use disorder as a key factor in faster time to suicide for active-duty service members with a history of TBI compared with those without TBI and theorized that a multiple stress or exposure burden may enhance risk,” they wrote. “This theory is reasonable and has been postulated among individuals with medical sequelae linked to TBI.”
However, the authors caution against applying these findings in military veterans to civilians.
“While this work is critical in the military population, caution should be given to avoid direct generalization to other populations, such as athletes, for whom the linkage to suicidal ideation is less understood,” they wrote.
The study was funded by National Institute of Mental Health and Office of the Director at National Institutes of Health. Dr. Brenner has received personal fees from Wolters Kluwer, Rand, American Psychological Association, and Oxford University Press and serves as a consultant to sports leagues via her university affiliation. Dr. Zafonte reported receiving royalties from Springer/Demos; serving as a member of the editorial boards of Journal of Neurotrauma and Frontiers in Neurology and scientific advisory boards of Myomo, Nanodiagnostics, Onecare.ai, and Kisbee; and evaluating patients in the MGH Brain and Body-TRUST Program, which is funded by the National Football League Players Association.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
‘Emerging’ biomarker may predict mild cognitive impairment years before symptoms
, new research indicates.
“Our study shows that low NPTX2 levels are predictive of MCI symptom onset more than 7 years in advance, including among individuals who are in late middle age,” said study investigator Anja Soldan, PhD, associate professor of neurology, Johns Hopkins University School of Medicine, Baltimore.
NPTX2 is still considered an “emerging biomarker” because knowledge about this protein is limited, Dr. Soldan noted.
Prior studies have shown that levels of NPTX2 are lower in people with MCI and dementia than in those with normal cognition and that low levels of this protein in people with MCI are associated with an increased risk of developing dementia.
“Our study extends these prior findings by showing that low protein levels are also associated with the onset of MCI symptoms,” Dr. Soldan said.
The study was published online in Annals of Neurology.
New therapeutic target?
The researchers measured NPTX2, as well as amyloid beta 42/40, phosphorylated (p)-tau181, and total (t)-tau in CSF collected longitudinally from 269 cognitively normal adults from the BIOCARD study.
The average age at baseline was 57.7 years. Nearly all were White, 59% were women, most were college educated, and three-quarters had a close relative with Alzheimer’s disease.
During a mean follow-up average of 16 years, 77 participants progressed to MCI or dementia within or after 7 years of baseline measurements.
In Cox regression models, lower baseline NPTX2 levels were associated with an earlier time to MCI symptom onset (hazard ratio, 0.76; P = .023). This association was significant for progression within 7 years (P = .036) and after 7 years from baseline (P = .001), the investigators reported.
Adults who progressed to MCI had, on average, about 15% lower levels of NPTX2 at baseline, compared with adults who remained cognitively normal.
Baseline NPTX2 levels improved prediction of time to MCI symptom onset after accounting for baseline Alzheimer’s disease biomarker levels (P < .01), and NPTX2 did not interact with the CSF Alzheimer’s disease biomarkers or APOE-ε4 genetic status.
Higher baseline levels of p-tau181 and t-tau were associated with higher baseline NPTX2 levels (both P < .001) and with greater declines in NPTX2 over time, suggesting that NPTX2 may decline in response to tau pathology, the investigators suggested.
Dr. Soldan said NPTX2 may be “a novel target” for developing new therapeutics for Alzheimer’s disease and other dementing and neurodegenerative disorders, as it is not an Alzheimer’s disease–specific protein.
“Efforts are underway for developing a sensitive way to measure NPTX2 brain levels in blood, which could then help clinicians identify individuals at greatest risk for cognitive decline,” she explained.
“Other next steps are to examine how changes in NPTX2 over time relate to changes in brain structure and function and to identify factors that alter levels of NPTX2, including genetic factors and potentially modifiable lifestyle factors,” Dr. Soldan said.
“If having higher levels of NPTX2 in the brain provides some resilience against developing symptoms of Alzheimer’s disease, it would be great if we could somehow increase levels of the protein,” she noted.
Caveats, cautionary notes
Commenting on this research, Christopher Weber, PhD, Alzheimer’s Association director of global science initiatives, said, “Research has shown that when NPTX2 levels are low, it may lead to weaker connections between neurons and could potentially affect cognitive functions, including memory and learning.”
“This new study found an association between lower levels of NPTX2 in CSF and earlier time to MCI symptom onset, and when combined with other established Alzheimer’s biomarkers, they found that NPTX2 improved the prediction of Alzheimer’s symptom onset,” Dr. Weber said.
“This is in line with previous research that suggests NPTX2 levels are associated with an increased risk of progression from MCI to Alzheimer’s dementia,” Dr. Weber said.
However, he noted some limitations of the study. “Participants were primarily White [and] highly educated, and therefore findings may not be generalizable to a real-world population,” he cautioned.
Dr. Weber said it’s also important to note that NPTX2 is not considered an Alzheimer’s-specific biomarker but rather a marker of synaptic activity and neurodegeneration. “The exact role of NPTX2 in predicting dementia is unknown,” Dr. Weber said.
He said that more studies with larger, more diverse cohorts are needed to fully understand its significance as a biomarker or therapeutic target for neurodegenerative diseases, as well as to develop a blood test for NPTX2.
The study was supported by the National Institutes of Health. Dr. Soldan and Dr. Weber report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research indicates.
“Our study shows that low NPTX2 levels are predictive of MCI symptom onset more than 7 years in advance, including among individuals who are in late middle age,” said study investigator Anja Soldan, PhD, associate professor of neurology, Johns Hopkins University School of Medicine, Baltimore.
NPTX2 is still considered an “emerging biomarker” because knowledge about this protein is limited, Dr. Soldan noted.
Prior studies have shown that levels of NPTX2 are lower in people with MCI and dementia than in those with normal cognition and that low levels of this protein in people with MCI are associated with an increased risk of developing dementia.
“Our study extends these prior findings by showing that low protein levels are also associated with the onset of MCI symptoms,” Dr. Soldan said.
The study was published online in Annals of Neurology.
New therapeutic target?
The researchers measured NPTX2, as well as amyloid beta 42/40, phosphorylated (p)-tau181, and total (t)-tau in CSF collected longitudinally from 269 cognitively normal adults from the BIOCARD study.
The average age at baseline was 57.7 years. Nearly all were White, 59% were women, most were college educated, and three-quarters had a close relative with Alzheimer’s disease.
During a mean follow-up average of 16 years, 77 participants progressed to MCI or dementia within or after 7 years of baseline measurements.
In Cox regression models, lower baseline NPTX2 levels were associated with an earlier time to MCI symptom onset (hazard ratio, 0.76; P = .023). This association was significant for progression within 7 years (P = .036) and after 7 years from baseline (P = .001), the investigators reported.
Adults who progressed to MCI had, on average, about 15% lower levels of NPTX2 at baseline, compared with adults who remained cognitively normal.
Baseline NPTX2 levels improved prediction of time to MCI symptom onset after accounting for baseline Alzheimer’s disease biomarker levels (P < .01), and NPTX2 did not interact with the CSF Alzheimer’s disease biomarkers or APOE-ε4 genetic status.
Higher baseline levels of p-tau181 and t-tau were associated with higher baseline NPTX2 levels (both P < .001) and with greater declines in NPTX2 over time, suggesting that NPTX2 may decline in response to tau pathology, the investigators suggested.
Dr. Soldan said NPTX2 may be “a novel target” for developing new therapeutics for Alzheimer’s disease and other dementing and neurodegenerative disorders, as it is not an Alzheimer’s disease–specific protein.
“Efforts are underway for developing a sensitive way to measure NPTX2 brain levels in blood, which could then help clinicians identify individuals at greatest risk for cognitive decline,” she explained.
“Other next steps are to examine how changes in NPTX2 over time relate to changes in brain structure and function and to identify factors that alter levels of NPTX2, including genetic factors and potentially modifiable lifestyle factors,” Dr. Soldan said.
“If having higher levels of NPTX2 in the brain provides some resilience against developing symptoms of Alzheimer’s disease, it would be great if we could somehow increase levels of the protein,” she noted.
Caveats, cautionary notes
Commenting on this research, Christopher Weber, PhD, Alzheimer’s Association director of global science initiatives, said, “Research has shown that when NPTX2 levels are low, it may lead to weaker connections between neurons and could potentially affect cognitive functions, including memory and learning.”
“This new study found an association between lower levels of NPTX2 in CSF and earlier time to MCI symptom onset, and when combined with other established Alzheimer’s biomarkers, they found that NPTX2 improved the prediction of Alzheimer’s symptom onset,” Dr. Weber said.
“This is in line with previous research that suggests NPTX2 levels are associated with an increased risk of progression from MCI to Alzheimer’s dementia,” Dr. Weber said.
However, he noted some limitations of the study. “Participants were primarily White [and] highly educated, and therefore findings may not be generalizable to a real-world population,” he cautioned.
Dr. Weber said it’s also important to note that NPTX2 is not considered an Alzheimer’s-specific biomarker but rather a marker of synaptic activity and neurodegeneration. “The exact role of NPTX2 in predicting dementia is unknown,” Dr. Weber said.
He said that more studies with larger, more diverse cohorts are needed to fully understand its significance as a biomarker or therapeutic target for neurodegenerative diseases, as well as to develop a blood test for NPTX2.
The study was supported by the National Institutes of Health. Dr. Soldan and Dr. Weber report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research indicates.
“Our study shows that low NPTX2 levels are predictive of MCI symptom onset more than 7 years in advance, including among individuals who are in late middle age,” said study investigator Anja Soldan, PhD, associate professor of neurology, Johns Hopkins University School of Medicine, Baltimore.
NPTX2 is still considered an “emerging biomarker” because knowledge about this protein is limited, Dr. Soldan noted.
Prior studies have shown that levels of NPTX2 are lower in people with MCI and dementia than in those with normal cognition and that low levels of this protein in people with MCI are associated with an increased risk of developing dementia.
“Our study extends these prior findings by showing that low protein levels are also associated with the onset of MCI symptoms,” Dr. Soldan said.
The study was published online in Annals of Neurology.
New therapeutic target?
The researchers measured NPTX2, as well as amyloid beta 42/40, phosphorylated (p)-tau181, and total (t)-tau in CSF collected longitudinally from 269 cognitively normal adults from the BIOCARD study.
The average age at baseline was 57.7 years. Nearly all were White, 59% were women, most were college educated, and three-quarters had a close relative with Alzheimer’s disease.
During a mean follow-up average of 16 years, 77 participants progressed to MCI or dementia within or after 7 years of baseline measurements.
In Cox regression models, lower baseline NPTX2 levels were associated with an earlier time to MCI symptom onset (hazard ratio, 0.76; P = .023). This association was significant for progression within 7 years (P = .036) and after 7 years from baseline (P = .001), the investigators reported.
Adults who progressed to MCI had, on average, about 15% lower levels of NPTX2 at baseline, compared with adults who remained cognitively normal.
Baseline NPTX2 levels improved prediction of time to MCI symptom onset after accounting for baseline Alzheimer’s disease biomarker levels (P < .01), and NPTX2 did not interact with the CSF Alzheimer’s disease biomarkers or APOE-ε4 genetic status.
Higher baseline levels of p-tau181 and t-tau were associated with higher baseline NPTX2 levels (both P < .001) and with greater declines in NPTX2 over time, suggesting that NPTX2 may decline in response to tau pathology, the investigators suggested.
Dr. Soldan said NPTX2 may be “a novel target” for developing new therapeutics for Alzheimer’s disease and other dementing and neurodegenerative disorders, as it is not an Alzheimer’s disease–specific protein.
“Efforts are underway for developing a sensitive way to measure NPTX2 brain levels in blood, which could then help clinicians identify individuals at greatest risk for cognitive decline,” she explained.
“Other next steps are to examine how changes in NPTX2 over time relate to changes in brain structure and function and to identify factors that alter levels of NPTX2, including genetic factors and potentially modifiable lifestyle factors,” Dr. Soldan said.
“If having higher levels of NPTX2 in the brain provides some resilience against developing symptoms of Alzheimer’s disease, it would be great if we could somehow increase levels of the protein,” she noted.
Caveats, cautionary notes
Commenting on this research, Christopher Weber, PhD, Alzheimer’s Association director of global science initiatives, said, “Research has shown that when NPTX2 levels are low, it may lead to weaker connections between neurons and could potentially affect cognitive functions, including memory and learning.”
“This new study found an association between lower levels of NPTX2 in CSF and earlier time to MCI symptom onset, and when combined with other established Alzheimer’s biomarkers, they found that NPTX2 improved the prediction of Alzheimer’s symptom onset,” Dr. Weber said.
“This is in line with previous research that suggests NPTX2 levels are associated with an increased risk of progression from MCI to Alzheimer’s dementia,” Dr. Weber said.
However, he noted some limitations of the study. “Participants were primarily White [and] highly educated, and therefore findings may not be generalizable to a real-world population,” he cautioned.
Dr. Weber said it’s also important to note that NPTX2 is not considered an Alzheimer’s-specific biomarker but rather a marker of synaptic activity and neurodegeneration. “The exact role of NPTX2 in predicting dementia is unknown,” Dr. Weber said.
He said that more studies with larger, more diverse cohorts are needed to fully understand its significance as a biomarker or therapeutic target for neurodegenerative diseases, as well as to develop a blood test for NPTX2.
The study was supported by the National Institutes of Health. Dr. Soldan and Dr. Weber report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ANNALS OF NEUROLOGY