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Controversial Alzheimer’s drug unlikely to get the OK in Europe
At its November meeting, , making it highly unlikely the drug will be recommended for approval at its December meeting.
In a news release issued Nov. 17, Biogen said the company received a “negative trend vote” on the aducanumab marketing authorization application in Europe.
“While we are disappointed with the trend vote, we strongly believe in the strength of our data and that aducanumab has the potential to make a positive and meaningful difference for people and families affected by Alzheimer’s disease [AD],” Priya Singhal, MD, MPH, head of global safety and regulatory sciences and interim head of research and development at Biogen, said in the release.
The EMA committee is expected to adopt a formal opinion on the marketing application at its December meeting (Dec. 13-16, 2021).
“Biogen will continue to engage with the EMA and CHMP as it considers next steps towards the goal of providing access to aducanumab to patients in Europe,” the company said.
At the recent Clinical Trials on Alzheimer’s Disease conference, Biogen announced new phase 3 findings that “provide further evidence of aducanumab’s effect on lowering amyloid beta plaque and downstream tau pathology, the two defining pathologies of Alzheimer’s disease,” the company said.
No clinically meaningful effect
In a statement from the nonprofit U.K. Science Media Centre, Prof. Robert Howard, from University College London, said the result of the CHMP vote “is absolutely the decision that we should have expected from the EMA’s expert advisory panel and is consistent with the FDA’s [U.S. Food and Drug Administration’s] Advisory Committee who voted unanimously 12 months ago against approval of aducanumab because of a lack of demonstrable efficacy in the pivotal phase 3 trials ENGAGE and EMERGE.”
“The FDA’s accelerated approval of aducanumab, solely on the grounds that it was reasonable to expect that reduction in amyloid would lead to improvement in the course of Alzheimer’s disease, despite all the evidence indicating no meaningful correlation between amyloid reduction and symptom improvement, has been highly controversial and has called into question the impartiality of the FDA and its staff,” Prof. Howard noted.
He anticipates that when the EMA panel meets in December they will not grant a license to aducanumab.
“Aducanumab is a treatment without convincing efficacy, with serious associated adverse effects and a high financial cost. On the basis of the available evidence and in the best interests of people with Alzheimer’s disease, their families and those who care for them, EMA and MHRA [Medicines and Healthcare products Regulatory Agency] should not approve a license for aducanumab,” Prof. Howard said.
Also weighing in, David Thomas, head of policy at Alzheimer’s Research UK, said the need for new AD treatments is “urgent,” but added that “it’s vital that regulators judge that any new treatment is safe and effective.”
“Results of aducanumab’s phase 3 trials, EMERGE and ENGAGE, have sparked much debate among the research community about how to judge the effectiveness of any new Alzheimer’s treatment,” Mr. Thomas noted.
“The FDA’s approval of aducanumab in the U.S. was based on the drug’s ability to clear the hallmark Alzheimer’s protein amyloid from the brain. As part of this approval the regulator now requires further trials to be carried out to ensure that aducanumab brings long-term improvement to people’s memory, thinking and day-to-day lives,” Mr. Thomas said.
EMA is now undertaking its own review of the data and “it’s important that we wait for the committee’s official recommendation, which is expected next month. In the meantime, we must continue to work at pace to ensure researchers are developing a broad pipeline of potential new treatments for diseases like Alzheimer’s, and that health systems like the NHS [National Health Service] will be ready to deliver them in the years ahead,” he added.
‘Reckless’ FDA decision
In related news, the Centers for Medicare and Medicaid Services (CMS) has announced that the Medicare Part B standard premium would rise to $170 per month for all enrollees, a 15% spike over the 2021 premium level.
“All Part B Medicare beneficiaries soon will be forced to bear significant financial burden as a direct result of the FDA’s reckless decision to approve aducanumab, a drug that has not been proven to provide any clinically meaningful benefit to Alzheimer’s patients but nevertheless carries an indefensible annual price tag set by Biogen at $56,000 per year for just the drug alone,” Michael Carome, MD, director of Public Citizen’s Health Research Group, said in a statement.
“To protect the many Medicare beneficiaries who cannot afford the unacceptable 15% jump in Part B premiums, CMS must promptly announce that it will exclude aducanumab from coverage under the Medicare program until there is definitive evidence that the drug provides substantial evidence of cognitive benefit to Alzheimer’s disease patients,” Dr. Carome said.
A version of this article first appeared on Medscape.com.
At its November meeting, , making it highly unlikely the drug will be recommended for approval at its December meeting.
In a news release issued Nov. 17, Biogen said the company received a “negative trend vote” on the aducanumab marketing authorization application in Europe.
“While we are disappointed with the trend vote, we strongly believe in the strength of our data and that aducanumab has the potential to make a positive and meaningful difference for people and families affected by Alzheimer’s disease [AD],” Priya Singhal, MD, MPH, head of global safety and regulatory sciences and interim head of research and development at Biogen, said in the release.
The EMA committee is expected to adopt a formal opinion on the marketing application at its December meeting (Dec. 13-16, 2021).
“Biogen will continue to engage with the EMA and CHMP as it considers next steps towards the goal of providing access to aducanumab to patients in Europe,” the company said.
At the recent Clinical Trials on Alzheimer’s Disease conference, Biogen announced new phase 3 findings that “provide further evidence of aducanumab’s effect on lowering amyloid beta plaque and downstream tau pathology, the two defining pathologies of Alzheimer’s disease,” the company said.
No clinically meaningful effect
In a statement from the nonprofit U.K. Science Media Centre, Prof. Robert Howard, from University College London, said the result of the CHMP vote “is absolutely the decision that we should have expected from the EMA’s expert advisory panel and is consistent with the FDA’s [U.S. Food and Drug Administration’s] Advisory Committee who voted unanimously 12 months ago against approval of aducanumab because of a lack of demonstrable efficacy in the pivotal phase 3 trials ENGAGE and EMERGE.”
“The FDA’s accelerated approval of aducanumab, solely on the grounds that it was reasonable to expect that reduction in amyloid would lead to improvement in the course of Alzheimer’s disease, despite all the evidence indicating no meaningful correlation between amyloid reduction and symptom improvement, has been highly controversial and has called into question the impartiality of the FDA and its staff,” Prof. Howard noted.
He anticipates that when the EMA panel meets in December they will not grant a license to aducanumab.
“Aducanumab is a treatment without convincing efficacy, with serious associated adverse effects and a high financial cost. On the basis of the available evidence and in the best interests of people with Alzheimer’s disease, their families and those who care for them, EMA and MHRA [Medicines and Healthcare products Regulatory Agency] should not approve a license for aducanumab,” Prof. Howard said.
Also weighing in, David Thomas, head of policy at Alzheimer’s Research UK, said the need for new AD treatments is “urgent,” but added that “it’s vital that regulators judge that any new treatment is safe and effective.”
“Results of aducanumab’s phase 3 trials, EMERGE and ENGAGE, have sparked much debate among the research community about how to judge the effectiveness of any new Alzheimer’s treatment,” Mr. Thomas noted.
“The FDA’s approval of aducanumab in the U.S. was based on the drug’s ability to clear the hallmark Alzheimer’s protein amyloid from the brain. As part of this approval the regulator now requires further trials to be carried out to ensure that aducanumab brings long-term improvement to people’s memory, thinking and day-to-day lives,” Mr. Thomas said.
EMA is now undertaking its own review of the data and “it’s important that we wait for the committee’s official recommendation, which is expected next month. In the meantime, we must continue to work at pace to ensure researchers are developing a broad pipeline of potential new treatments for diseases like Alzheimer’s, and that health systems like the NHS [National Health Service] will be ready to deliver them in the years ahead,” he added.
‘Reckless’ FDA decision
In related news, the Centers for Medicare and Medicaid Services (CMS) has announced that the Medicare Part B standard premium would rise to $170 per month for all enrollees, a 15% spike over the 2021 premium level.
“All Part B Medicare beneficiaries soon will be forced to bear significant financial burden as a direct result of the FDA’s reckless decision to approve aducanumab, a drug that has not been proven to provide any clinically meaningful benefit to Alzheimer’s patients but nevertheless carries an indefensible annual price tag set by Biogen at $56,000 per year for just the drug alone,” Michael Carome, MD, director of Public Citizen’s Health Research Group, said in a statement.
“To protect the many Medicare beneficiaries who cannot afford the unacceptable 15% jump in Part B premiums, CMS must promptly announce that it will exclude aducanumab from coverage under the Medicare program until there is definitive evidence that the drug provides substantial evidence of cognitive benefit to Alzheimer’s disease patients,” Dr. Carome said.
A version of this article first appeared on Medscape.com.
At its November meeting, , making it highly unlikely the drug will be recommended for approval at its December meeting.
In a news release issued Nov. 17, Biogen said the company received a “negative trend vote” on the aducanumab marketing authorization application in Europe.
“While we are disappointed with the trend vote, we strongly believe in the strength of our data and that aducanumab has the potential to make a positive and meaningful difference for people and families affected by Alzheimer’s disease [AD],” Priya Singhal, MD, MPH, head of global safety and regulatory sciences and interim head of research and development at Biogen, said in the release.
The EMA committee is expected to adopt a formal opinion on the marketing application at its December meeting (Dec. 13-16, 2021).
“Biogen will continue to engage with the EMA and CHMP as it considers next steps towards the goal of providing access to aducanumab to patients in Europe,” the company said.
At the recent Clinical Trials on Alzheimer’s Disease conference, Biogen announced new phase 3 findings that “provide further evidence of aducanumab’s effect on lowering amyloid beta plaque and downstream tau pathology, the two defining pathologies of Alzheimer’s disease,” the company said.
No clinically meaningful effect
In a statement from the nonprofit U.K. Science Media Centre, Prof. Robert Howard, from University College London, said the result of the CHMP vote “is absolutely the decision that we should have expected from the EMA’s expert advisory panel and is consistent with the FDA’s [U.S. Food and Drug Administration’s] Advisory Committee who voted unanimously 12 months ago against approval of aducanumab because of a lack of demonstrable efficacy in the pivotal phase 3 trials ENGAGE and EMERGE.”
“The FDA’s accelerated approval of aducanumab, solely on the grounds that it was reasonable to expect that reduction in amyloid would lead to improvement in the course of Alzheimer’s disease, despite all the evidence indicating no meaningful correlation between amyloid reduction and symptom improvement, has been highly controversial and has called into question the impartiality of the FDA and its staff,” Prof. Howard noted.
He anticipates that when the EMA panel meets in December they will not grant a license to aducanumab.
“Aducanumab is a treatment without convincing efficacy, with serious associated adverse effects and a high financial cost. On the basis of the available evidence and in the best interests of people with Alzheimer’s disease, their families and those who care for them, EMA and MHRA [Medicines and Healthcare products Regulatory Agency] should not approve a license for aducanumab,” Prof. Howard said.
Also weighing in, David Thomas, head of policy at Alzheimer’s Research UK, said the need for new AD treatments is “urgent,” but added that “it’s vital that regulators judge that any new treatment is safe and effective.”
“Results of aducanumab’s phase 3 trials, EMERGE and ENGAGE, have sparked much debate among the research community about how to judge the effectiveness of any new Alzheimer’s treatment,” Mr. Thomas noted.
“The FDA’s approval of aducanumab in the U.S. was based on the drug’s ability to clear the hallmark Alzheimer’s protein amyloid from the brain. As part of this approval the regulator now requires further trials to be carried out to ensure that aducanumab brings long-term improvement to people’s memory, thinking and day-to-day lives,” Mr. Thomas said.
EMA is now undertaking its own review of the data and “it’s important that we wait for the committee’s official recommendation, which is expected next month. In the meantime, we must continue to work at pace to ensure researchers are developing a broad pipeline of potential new treatments for diseases like Alzheimer’s, and that health systems like the NHS [National Health Service] will be ready to deliver them in the years ahead,” he added.
‘Reckless’ FDA decision
In related news, the Centers for Medicare and Medicaid Services (CMS) has announced that the Medicare Part B standard premium would rise to $170 per month for all enrollees, a 15% spike over the 2021 premium level.
“All Part B Medicare beneficiaries soon will be forced to bear significant financial burden as a direct result of the FDA’s reckless decision to approve aducanumab, a drug that has not been proven to provide any clinically meaningful benefit to Alzheimer’s patients but nevertheless carries an indefensible annual price tag set by Biogen at $56,000 per year for just the drug alone,” Michael Carome, MD, director of Public Citizen’s Health Research Group, said in a statement.
“To protect the many Medicare beneficiaries who cannot afford the unacceptable 15% jump in Part B premiums, CMS must promptly announce that it will exclude aducanumab from coverage under the Medicare program until there is definitive evidence that the drug provides substantial evidence of cognitive benefit to Alzheimer’s disease patients,” Dr. Carome said.
A version of this article first appeared on Medscape.com.
Coffee or tea? Drinking both tied to lower stroke, dementia risk
Drinking coffee or tea is associated with reduced risk for stroke and dementia, with the biggest benefit associated with consuming both beverages, new research suggests.
Investigators found that individuals who drank two to three cups of coffee and two to three cups of tea per day had a 30% decrease in incidence of stroke and a 28% lower risk for dementia compared with those who did not.
“From a public health perspective, because regular tea and coffee drinkers comprise such a large proportion of the population and because these beverages tend to be consumed habitually throughout adult life, even small potential health benefits or risks associated with tea and coffee intake may have important public health implications,” the investigators wrote.
The study was published online Nov. 16 in PLOS Medicine.
Synergistic effect?
Whereas earlier studies have shown significant health benefits from moderate coffee and tea intake separately, few have examined the effect of drinking both.
Researchers enrolled 365,682 participants from the UK Biobank for the analysis of coffee and tea consumption and stroke and dementia risk and 13,352 participants for the analysis of poststroke dementia.
During a median follow-up of 11.4 years, 2.8% of participants experienced a stroke and 1.4% developed dementia.
After adjustment for confounders, stroke risk was 10% lower in those who drank a half-cup to a cup of coffee per day (P < .001) and 8% lower in those who had more than two cups a day (P = .009). Tea drinkers who had more than two cups a day saw a 16% reduction in stroke (P < .001).
Those who drank both coffee and tea during the day saw the greatest benefit. Drinking two to three cups of coffee and two to three cups of tea lowered stroke risk by 32% (P < .001) and dementia risk by 28% (P = .002).
Drinking both beverages offered significantly greater benefits than drinking just coffee or tea alone, with an 11% lower risk for stroke (P < .001), an 8% lower risk for dementia (P = .001), and 18% lower risk for vascular dementia (P = .001).
Among those participants who experienced a stroke during the follow-up period, drinking two to three cups of coffee was associated with 20% lower risk for poststroke dementia (P = .044), and for those who drank both coffee and tea (half to one cup of coffee and two to three cups of tea per day) the risk for poststroke dementia was lowered by 50% (P =.006).
There was no significant association between coffee and tea consumption and risk for hemorrhagic stroke or Alzheimer’s disease.
The study was funded by the National Natural Science Foundation of China. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Drinking coffee or tea is associated with reduced risk for stroke and dementia, with the biggest benefit associated with consuming both beverages, new research suggests.
Investigators found that individuals who drank two to three cups of coffee and two to three cups of tea per day had a 30% decrease in incidence of stroke and a 28% lower risk for dementia compared with those who did not.
“From a public health perspective, because regular tea and coffee drinkers comprise such a large proportion of the population and because these beverages tend to be consumed habitually throughout adult life, even small potential health benefits or risks associated with tea and coffee intake may have important public health implications,” the investigators wrote.
The study was published online Nov. 16 in PLOS Medicine.
Synergistic effect?
Whereas earlier studies have shown significant health benefits from moderate coffee and tea intake separately, few have examined the effect of drinking both.
Researchers enrolled 365,682 participants from the UK Biobank for the analysis of coffee and tea consumption and stroke and dementia risk and 13,352 participants for the analysis of poststroke dementia.
During a median follow-up of 11.4 years, 2.8% of participants experienced a stroke and 1.4% developed dementia.
After adjustment for confounders, stroke risk was 10% lower in those who drank a half-cup to a cup of coffee per day (P < .001) and 8% lower in those who had more than two cups a day (P = .009). Tea drinkers who had more than two cups a day saw a 16% reduction in stroke (P < .001).
Those who drank both coffee and tea during the day saw the greatest benefit. Drinking two to three cups of coffee and two to three cups of tea lowered stroke risk by 32% (P < .001) and dementia risk by 28% (P = .002).
Drinking both beverages offered significantly greater benefits than drinking just coffee or tea alone, with an 11% lower risk for stroke (P < .001), an 8% lower risk for dementia (P = .001), and 18% lower risk for vascular dementia (P = .001).
Among those participants who experienced a stroke during the follow-up period, drinking two to three cups of coffee was associated with 20% lower risk for poststroke dementia (P = .044), and for those who drank both coffee and tea (half to one cup of coffee and two to three cups of tea per day) the risk for poststroke dementia was lowered by 50% (P =.006).
There was no significant association between coffee and tea consumption and risk for hemorrhagic stroke or Alzheimer’s disease.
The study was funded by the National Natural Science Foundation of China. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Drinking coffee or tea is associated with reduced risk for stroke and dementia, with the biggest benefit associated with consuming both beverages, new research suggests.
Investigators found that individuals who drank two to three cups of coffee and two to three cups of tea per day had a 30% decrease in incidence of stroke and a 28% lower risk for dementia compared with those who did not.
“From a public health perspective, because regular tea and coffee drinkers comprise such a large proportion of the population and because these beverages tend to be consumed habitually throughout adult life, even small potential health benefits or risks associated with tea and coffee intake may have important public health implications,” the investigators wrote.
The study was published online Nov. 16 in PLOS Medicine.
Synergistic effect?
Whereas earlier studies have shown significant health benefits from moderate coffee and tea intake separately, few have examined the effect of drinking both.
Researchers enrolled 365,682 participants from the UK Biobank for the analysis of coffee and tea consumption and stroke and dementia risk and 13,352 participants for the analysis of poststroke dementia.
During a median follow-up of 11.4 years, 2.8% of participants experienced a stroke and 1.4% developed dementia.
After adjustment for confounders, stroke risk was 10% lower in those who drank a half-cup to a cup of coffee per day (P < .001) and 8% lower in those who had more than two cups a day (P = .009). Tea drinkers who had more than two cups a day saw a 16% reduction in stroke (P < .001).
Those who drank both coffee and tea during the day saw the greatest benefit. Drinking two to three cups of coffee and two to three cups of tea lowered stroke risk by 32% (P < .001) and dementia risk by 28% (P = .002).
Drinking both beverages offered significantly greater benefits than drinking just coffee or tea alone, with an 11% lower risk for stroke (P < .001), an 8% lower risk for dementia (P = .001), and 18% lower risk for vascular dementia (P = .001).
Among those participants who experienced a stroke during the follow-up period, drinking two to three cups of coffee was associated with 20% lower risk for poststroke dementia (P = .044), and for those who drank both coffee and tea (half to one cup of coffee and two to three cups of tea per day) the risk for poststroke dementia was lowered by 50% (P =.006).
There was no significant association between coffee and tea consumption and risk for hemorrhagic stroke or Alzheimer’s disease.
The study was funded by the National Natural Science Foundation of China. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
ASCEND: Aspirin shows hint of dementia protection in T2D
A regimen of daily, low-dose aspirin failed to produce a significant reduction in the incidence of dementia or cognitive impairment in ASCEND, a randomized, multicenter trial with more than 15,000 people with diabetes followed for an average of more than 9 years, but the results hinted at enough of a benefit to warrant further study, some experts said.
“The question remains open,” said Jane Armitage, MBBS, FRCP, as she presented the findings at the American Heart Association scientific sessions. “The rate ratios suggest some benefit. It’s encouraging,” added Dr. Armitage, professor of clinical trials and epidemiology at Oxford (England) University.
The study tallied dementia outcomes three different ways: It applied a narrow definition that relied on a specific diagnosis of dementia in a person’s EHR or in their death record. (Dr. Armitage and her associates tracked outcomes for 99% of the enrolled participants by linking to their U.K. national health records and death records.)
A second metric used a broader outcome definition that tracked EHR entries for not only dementia but also diagnoses of cognitive impairment, delirium, confusion, prescription of dementia medications, and referral to a memory clinic or geriatric psychiatry. The third assessment was a cognitive-function test given to participants at the end of follow-up, but only 58% of enrolled participants completed this part of the study, and it’s also possible that some subjects missed this assessment because of dementia onset. These limitations hamper clear interpretation of this third metric, Dr. Armitage said.
The main findings for the other two, more reliable measures of incident dementia or cognitive deterioration showed a nonsignificant 9% relative risk reduction linked with aspirin use compared with placebo for the more inclusive endpoint, and a nonsignificant 11% relative risk reduction with aspirin using the narrow definition for dementia only, she reported. The third method, a directly administered assessment of dementia and cognition, also showed a small, nonsignificant effect from daily aspirin use relative to placebo.
Results can’t rule out modest aspirin effect
Dr. Armitage highlighted that the two more reliable measures both appeared to rule out risk for neurologic harm from aspirin because the upper limit of the 95% confidence interval for relative effect reached only 1.02 using the broad outcomes, and 1.06 for the narrower endpoint of dementia only. On the other hand, focus on the low end of the 95% confidence interval suggested potentially meaningful benefits, with a possible reduction by aspirin in events relative to placebo of as much as 19% by the broad outcome definition and by 25% with the narrow definition.
“Even if it was only a 15% relative risk reduction, that would be important,” given the high dementia incidence worldwide, Dr. Armitage said during a press briefing. “It’s entirely possible, with our results, that a modest benefit exists.”
This take on the findings won some support. Further studies with more people, longer follow-up, and perhaps enrolling a more selected, higher risk cohort may better address potential neurologic benefit from aspirin, suggested Amytis Towfighi, MD, a stroke neurologist and professor of neurology at the University of Southern California, Los Angeles, and a designated discussant for the report.
The result “was rather encouraging. I was a little surprised” by the findings, commented Chrystie M. Ballantyne, MD, professor and director of the Center for Cardiometabolic Disease Prevention at Baylor College of Medicine, Houston, also a discussant.
The results “don’t mean that no one benefits from aspirin. Perhaps certain people at risk would benefit from dementia protection. It’s an open question,” commented Erin D. Michos, MD, director of Women’s Cardiovascular Health at Johns Hopkins Medicine, Baltimore.
But others saw the findings as more unequivocally neutral. “This gives us an early, preliminary answer, that aspirin does not seem to improve dementia,” commented Amit Khera, MD, professor and director of Preventive Cardiology at UT Southwestern Medical Center, Dallas, and a third discussant at the meeting.
Evidence against routine, widespread primary prevention with aspirin
ASCEND had the primary goal of assessing a daily, 100-mg aspirin dose for its safety and efficacy for preventing vascular events such as MIs and ischemic strokes in 15,480 people with diabetes who were at least 40 years old at enrollment and had no history of cardiovascular disease. The main results came out in 2018 and showed that while aspirin produced a significant benefit by reducing thrombotic events, it also resulted in significantly more major bleeding events compared with placebo, and overall the magnitude of benefit roughly matched magnitude of risk.
These findings, along with similar results from two other high-profile aspirin studies reported at about the same time (ASPREE, and ARRIVE), led to recommendations from groups like the U.S. Preventive Services Task Force and from the American College of Cardiology and American Heart Association that caution against widespread, routine aspirin use for primary prevention of atherosclerotic cardiovascular disease events in most adults.
The groups instead endorsed a tailored strategy of targeting aspirin to people with a higher than average risk for ischemic thrombotic events and a lower than average bleeding risk. (The most recent aspirin recommendations from the USPSTF, currently in draft form, substantially curtail aspirin’s appropriate use, eliminating it in those over age 60 years.)
However, experts and prevailing practice recommendations continue to endorse routine aspirin use for secondary prevention in patients with an established history of cardiovascular disease.
The new findings reported by Dr. Armitage came from additional analyses of dementia and cognitive impairment overlaid on the main ASCEND outcome analyses. ASCEND actively treated and followed study participants for an average of 7.4 years, then researchers tracked further dementia outcomes based on medical-record entries for an average of another 1.8 years.
ASCEND received partial funding or support from Abbott, Bayer, Mylan, and Solvay. Dr. Armitage had no disclosures. Dr. Towfighi, Dr. Khera, and Dr. Michos had no disclosures. Dr. Ballantyne has had financial relationships with numerous companies.
A regimen of daily, low-dose aspirin failed to produce a significant reduction in the incidence of dementia or cognitive impairment in ASCEND, a randomized, multicenter trial with more than 15,000 people with diabetes followed for an average of more than 9 years, but the results hinted at enough of a benefit to warrant further study, some experts said.
“The question remains open,” said Jane Armitage, MBBS, FRCP, as she presented the findings at the American Heart Association scientific sessions. “The rate ratios suggest some benefit. It’s encouraging,” added Dr. Armitage, professor of clinical trials and epidemiology at Oxford (England) University.
The study tallied dementia outcomes three different ways: It applied a narrow definition that relied on a specific diagnosis of dementia in a person’s EHR or in their death record. (Dr. Armitage and her associates tracked outcomes for 99% of the enrolled participants by linking to their U.K. national health records and death records.)
A second metric used a broader outcome definition that tracked EHR entries for not only dementia but also diagnoses of cognitive impairment, delirium, confusion, prescription of dementia medications, and referral to a memory clinic or geriatric psychiatry. The third assessment was a cognitive-function test given to participants at the end of follow-up, but only 58% of enrolled participants completed this part of the study, and it’s also possible that some subjects missed this assessment because of dementia onset. These limitations hamper clear interpretation of this third metric, Dr. Armitage said.
The main findings for the other two, more reliable measures of incident dementia or cognitive deterioration showed a nonsignificant 9% relative risk reduction linked with aspirin use compared with placebo for the more inclusive endpoint, and a nonsignificant 11% relative risk reduction with aspirin using the narrow definition for dementia only, she reported. The third method, a directly administered assessment of dementia and cognition, also showed a small, nonsignificant effect from daily aspirin use relative to placebo.
Results can’t rule out modest aspirin effect
Dr. Armitage highlighted that the two more reliable measures both appeared to rule out risk for neurologic harm from aspirin because the upper limit of the 95% confidence interval for relative effect reached only 1.02 using the broad outcomes, and 1.06 for the narrower endpoint of dementia only. On the other hand, focus on the low end of the 95% confidence interval suggested potentially meaningful benefits, with a possible reduction by aspirin in events relative to placebo of as much as 19% by the broad outcome definition and by 25% with the narrow definition.
“Even if it was only a 15% relative risk reduction, that would be important,” given the high dementia incidence worldwide, Dr. Armitage said during a press briefing. “It’s entirely possible, with our results, that a modest benefit exists.”
This take on the findings won some support. Further studies with more people, longer follow-up, and perhaps enrolling a more selected, higher risk cohort may better address potential neurologic benefit from aspirin, suggested Amytis Towfighi, MD, a stroke neurologist and professor of neurology at the University of Southern California, Los Angeles, and a designated discussant for the report.
The result “was rather encouraging. I was a little surprised” by the findings, commented Chrystie M. Ballantyne, MD, professor and director of the Center for Cardiometabolic Disease Prevention at Baylor College of Medicine, Houston, also a discussant.
The results “don’t mean that no one benefits from aspirin. Perhaps certain people at risk would benefit from dementia protection. It’s an open question,” commented Erin D. Michos, MD, director of Women’s Cardiovascular Health at Johns Hopkins Medicine, Baltimore.
But others saw the findings as more unequivocally neutral. “This gives us an early, preliminary answer, that aspirin does not seem to improve dementia,” commented Amit Khera, MD, professor and director of Preventive Cardiology at UT Southwestern Medical Center, Dallas, and a third discussant at the meeting.
Evidence against routine, widespread primary prevention with aspirin
ASCEND had the primary goal of assessing a daily, 100-mg aspirin dose for its safety and efficacy for preventing vascular events such as MIs and ischemic strokes in 15,480 people with diabetes who were at least 40 years old at enrollment and had no history of cardiovascular disease. The main results came out in 2018 and showed that while aspirin produced a significant benefit by reducing thrombotic events, it also resulted in significantly more major bleeding events compared with placebo, and overall the magnitude of benefit roughly matched magnitude of risk.
These findings, along with similar results from two other high-profile aspirin studies reported at about the same time (ASPREE, and ARRIVE), led to recommendations from groups like the U.S. Preventive Services Task Force and from the American College of Cardiology and American Heart Association that caution against widespread, routine aspirin use for primary prevention of atherosclerotic cardiovascular disease events in most adults.
The groups instead endorsed a tailored strategy of targeting aspirin to people with a higher than average risk for ischemic thrombotic events and a lower than average bleeding risk. (The most recent aspirin recommendations from the USPSTF, currently in draft form, substantially curtail aspirin’s appropriate use, eliminating it in those over age 60 years.)
However, experts and prevailing practice recommendations continue to endorse routine aspirin use for secondary prevention in patients with an established history of cardiovascular disease.
The new findings reported by Dr. Armitage came from additional analyses of dementia and cognitive impairment overlaid on the main ASCEND outcome analyses. ASCEND actively treated and followed study participants for an average of 7.4 years, then researchers tracked further dementia outcomes based on medical-record entries for an average of another 1.8 years.
ASCEND received partial funding or support from Abbott, Bayer, Mylan, and Solvay. Dr. Armitage had no disclosures. Dr. Towfighi, Dr. Khera, and Dr. Michos had no disclosures. Dr. Ballantyne has had financial relationships with numerous companies.
A regimen of daily, low-dose aspirin failed to produce a significant reduction in the incidence of dementia or cognitive impairment in ASCEND, a randomized, multicenter trial with more than 15,000 people with diabetes followed for an average of more than 9 years, but the results hinted at enough of a benefit to warrant further study, some experts said.
“The question remains open,” said Jane Armitage, MBBS, FRCP, as she presented the findings at the American Heart Association scientific sessions. “The rate ratios suggest some benefit. It’s encouraging,” added Dr. Armitage, professor of clinical trials and epidemiology at Oxford (England) University.
The study tallied dementia outcomes three different ways: It applied a narrow definition that relied on a specific diagnosis of dementia in a person’s EHR or in their death record. (Dr. Armitage and her associates tracked outcomes for 99% of the enrolled participants by linking to their U.K. national health records and death records.)
A second metric used a broader outcome definition that tracked EHR entries for not only dementia but also diagnoses of cognitive impairment, delirium, confusion, prescription of dementia medications, and referral to a memory clinic or geriatric psychiatry. The third assessment was a cognitive-function test given to participants at the end of follow-up, but only 58% of enrolled participants completed this part of the study, and it’s also possible that some subjects missed this assessment because of dementia onset. These limitations hamper clear interpretation of this third metric, Dr. Armitage said.
The main findings for the other two, more reliable measures of incident dementia or cognitive deterioration showed a nonsignificant 9% relative risk reduction linked with aspirin use compared with placebo for the more inclusive endpoint, and a nonsignificant 11% relative risk reduction with aspirin using the narrow definition for dementia only, she reported. The third method, a directly administered assessment of dementia and cognition, also showed a small, nonsignificant effect from daily aspirin use relative to placebo.
Results can’t rule out modest aspirin effect
Dr. Armitage highlighted that the two more reliable measures both appeared to rule out risk for neurologic harm from aspirin because the upper limit of the 95% confidence interval for relative effect reached only 1.02 using the broad outcomes, and 1.06 for the narrower endpoint of dementia only. On the other hand, focus on the low end of the 95% confidence interval suggested potentially meaningful benefits, with a possible reduction by aspirin in events relative to placebo of as much as 19% by the broad outcome definition and by 25% with the narrow definition.
“Even if it was only a 15% relative risk reduction, that would be important,” given the high dementia incidence worldwide, Dr. Armitage said during a press briefing. “It’s entirely possible, with our results, that a modest benefit exists.”
This take on the findings won some support. Further studies with more people, longer follow-up, and perhaps enrolling a more selected, higher risk cohort may better address potential neurologic benefit from aspirin, suggested Amytis Towfighi, MD, a stroke neurologist and professor of neurology at the University of Southern California, Los Angeles, and a designated discussant for the report.
The result “was rather encouraging. I was a little surprised” by the findings, commented Chrystie M. Ballantyne, MD, professor and director of the Center for Cardiometabolic Disease Prevention at Baylor College of Medicine, Houston, also a discussant.
The results “don’t mean that no one benefits from aspirin. Perhaps certain people at risk would benefit from dementia protection. It’s an open question,” commented Erin D. Michos, MD, director of Women’s Cardiovascular Health at Johns Hopkins Medicine, Baltimore.
But others saw the findings as more unequivocally neutral. “This gives us an early, preliminary answer, that aspirin does not seem to improve dementia,” commented Amit Khera, MD, professor and director of Preventive Cardiology at UT Southwestern Medical Center, Dallas, and a third discussant at the meeting.
Evidence against routine, widespread primary prevention with aspirin
ASCEND had the primary goal of assessing a daily, 100-mg aspirin dose for its safety and efficacy for preventing vascular events such as MIs and ischemic strokes in 15,480 people with diabetes who were at least 40 years old at enrollment and had no history of cardiovascular disease. The main results came out in 2018 and showed that while aspirin produced a significant benefit by reducing thrombotic events, it also resulted in significantly more major bleeding events compared with placebo, and overall the magnitude of benefit roughly matched magnitude of risk.
These findings, along with similar results from two other high-profile aspirin studies reported at about the same time (ASPREE, and ARRIVE), led to recommendations from groups like the U.S. Preventive Services Task Force and from the American College of Cardiology and American Heart Association that caution against widespread, routine aspirin use for primary prevention of atherosclerotic cardiovascular disease events in most adults.
The groups instead endorsed a tailored strategy of targeting aspirin to people with a higher than average risk for ischemic thrombotic events and a lower than average bleeding risk. (The most recent aspirin recommendations from the USPSTF, currently in draft form, substantially curtail aspirin’s appropriate use, eliminating it in those over age 60 years.)
However, experts and prevailing practice recommendations continue to endorse routine aspirin use for secondary prevention in patients with an established history of cardiovascular disease.
The new findings reported by Dr. Armitage came from additional analyses of dementia and cognitive impairment overlaid on the main ASCEND outcome analyses. ASCEND actively treated and followed study participants for an average of 7.4 years, then researchers tracked further dementia outcomes based on medical-record entries for an average of another 1.8 years.
ASCEND received partial funding or support from Abbott, Bayer, Mylan, and Solvay. Dr. Armitage had no disclosures. Dr. Towfighi, Dr. Khera, and Dr. Michos had no disclosures. Dr. Ballantyne has had financial relationships with numerous companies.
FROM AHA 2021
Multivitamins, but not cocoa, tied to slowed brain aging
, with the effects especially pronounced in patients with cardiovascular (CVD) disease, new research suggests.
In addition to testing the effect of a daily multivitamin on cognition, the COSMOS-Mind study examined the effect of cocoa flavanols, but showed no beneficial effect.
The findings “may have important public health implications, particularly for brain health, given the accessibility of multivitamins and minerals, and their low cost and safety,” said study investigator Laura D. Baker, PhD, professor, gerontology and geriatric medicine, Wake Forest University, Winston-Salem, N.C.
The findings were presented at the 14th Clinical Trials on Alzheimer’s Disease (CTAD) conference.
Placebo-controlled study
The study is a substudy of a large parent trial that compared the effects of cocoa extract (500 mg/day cocoa flavanols) and a standard multivitamin-mineral (MVM) to placebo on cardiovascular and cancer outcomes in more than 21,000 older participants.
COSMOS-Mind included 2,262 adults aged 65 and over without dementia who underwent cognitive testing at baseline and annually for 3 years. The mean age at baseline was 73 years, and 40.4% were men. Most participants (88.7%) were non-Hispanic White and almost half (49.2%) had some post-college education.
All study groups were balanced with respect to demographics, CVD history, diabetes, depression, smoking status, alcohol intake, chocolate intake, and prior multivitamin use. Baseline cognitive scores were similar between study groups. Researchers had complete data on 77% of study participants.
The primary endpoint was the effect of cocoa extract (CE) vs. placebo on Global Cognitive Function composite score. The secondary outcome was the effect of MVM vs. placebo on global cognitive function.
Additional outcomes included the impact of supplements on executive function and memory and the treatment effects for prespecified subgroups, including subjects with a history of CVD.
Using a graph of change over time, Dr. Baker showed there was no effect of cocoa on global cognitive function (effect: 0.03; 95% confidence interval, –0.02 to 0.08; P = .28). “We see the to-be-expected practice effects, but there’s no separation between the active and placebo groups,” she said.
It was a different story for MVM. Here, there was the same practice effect, but the graph showed the lines separated for global cognitive function composite score (effect: 0.07; 95% CI, 0.02-0.12; P = .007).
“We see a positive effect of multivitamins for the active group relative to placebo, peaking at 2 years and then remaining stable over time,” said Dr. Baker.
There were similar findings with MVM for the memory composite score, and the executive function composite score. “We have significance in all three, where the two lines do separate over and above the practice effects,” said Dr. Baker.
New evidence
Investigators found a baseline history of CVD, including transient ischemic attack, heart failure, coronary artery bypass graft, percutaneous transluminal coronary angioplasty, and stent, but not myocardial infarction or stroke as these were excluded in the parent trial because they affected the response to multivitamins.
As expected, those with CVD had lower cognitive scores at baseline. “But after an initial bump due to practice effect, at year 1, the cardiovascular disease history folks continue to benefit from multivitamins, whereas those who got placebo multivitamins continue to decline over time,” said Dr. Baker.
Based on information from a baseline scatter plot of cognitive function scores by age, the study’s modeling estimated the multivitamin treatment effect had a positive benefit of .028 standard deviations (SD) per year.
“Daily multivitamin-mineral supplementation appears to slow cognitive aging by 60% or by 1.8 years,” Dr. Baker added.
To date, the effect of MVM supplementation on cognition has been tested in only one large randomized clinical trial – the Physicians Health Study II. That study did not show an effect, but included only older male physicians – and cognitive testing began 2.5 years after randomization, said Dr. Baker.
“Our study provides new evidence that daily multivitamin supplementation may benefit cognitive function in older women and men, and the multivitamin effects may be more pronounced in participants with cardiovascular disease,” she noted.
For effects of multivitamins on Alzheimer’s disease prevalence and progression, “stay tuned,” Dr. Baker concluded.
Following the presentation, session cochair Suzanne Schindler, MD, PhD, instructor in the department of neurology at Washington University, St. Louis, said she and her colleagues “always check vitamin B12 levels” in patients with memory and cognitive difficulties and wondered if study subjects with a low level or deficiency of vitamin B12 benefited from the intervention.
“We are asking ourselves that as well,” said Dr. Baker.
“Some of this is a work in progress,” Dr. Baker added. “We still need to look at that more in-depth to understand whether it might be a mechanism for improvement. I think the results are still out on that topic.”
The study received support from the National Institute on Aging. Pfizer Consumer Healthcare (now GSK Consumer Healthcare) provided study pills and packaging. Dr. Baker has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, with the effects especially pronounced in patients with cardiovascular (CVD) disease, new research suggests.
In addition to testing the effect of a daily multivitamin on cognition, the COSMOS-Mind study examined the effect of cocoa flavanols, but showed no beneficial effect.
The findings “may have important public health implications, particularly for brain health, given the accessibility of multivitamins and minerals, and their low cost and safety,” said study investigator Laura D. Baker, PhD, professor, gerontology and geriatric medicine, Wake Forest University, Winston-Salem, N.C.
The findings were presented at the 14th Clinical Trials on Alzheimer’s Disease (CTAD) conference.
Placebo-controlled study
The study is a substudy of a large parent trial that compared the effects of cocoa extract (500 mg/day cocoa flavanols) and a standard multivitamin-mineral (MVM) to placebo on cardiovascular and cancer outcomes in more than 21,000 older participants.
COSMOS-Mind included 2,262 adults aged 65 and over without dementia who underwent cognitive testing at baseline and annually for 3 years. The mean age at baseline was 73 years, and 40.4% were men. Most participants (88.7%) were non-Hispanic White and almost half (49.2%) had some post-college education.
All study groups were balanced with respect to demographics, CVD history, diabetes, depression, smoking status, alcohol intake, chocolate intake, and prior multivitamin use. Baseline cognitive scores were similar between study groups. Researchers had complete data on 77% of study participants.
The primary endpoint was the effect of cocoa extract (CE) vs. placebo on Global Cognitive Function composite score. The secondary outcome was the effect of MVM vs. placebo on global cognitive function.
Additional outcomes included the impact of supplements on executive function and memory and the treatment effects for prespecified subgroups, including subjects with a history of CVD.
Using a graph of change over time, Dr. Baker showed there was no effect of cocoa on global cognitive function (effect: 0.03; 95% confidence interval, –0.02 to 0.08; P = .28). “We see the to-be-expected practice effects, but there’s no separation between the active and placebo groups,” she said.
It was a different story for MVM. Here, there was the same practice effect, but the graph showed the lines separated for global cognitive function composite score (effect: 0.07; 95% CI, 0.02-0.12; P = .007).
“We see a positive effect of multivitamins for the active group relative to placebo, peaking at 2 years and then remaining stable over time,” said Dr. Baker.
There were similar findings with MVM for the memory composite score, and the executive function composite score. “We have significance in all three, where the two lines do separate over and above the practice effects,” said Dr. Baker.
New evidence
Investigators found a baseline history of CVD, including transient ischemic attack, heart failure, coronary artery bypass graft, percutaneous transluminal coronary angioplasty, and stent, but not myocardial infarction or stroke as these were excluded in the parent trial because they affected the response to multivitamins.
As expected, those with CVD had lower cognitive scores at baseline. “But after an initial bump due to practice effect, at year 1, the cardiovascular disease history folks continue to benefit from multivitamins, whereas those who got placebo multivitamins continue to decline over time,” said Dr. Baker.
Based on information from a baseline scatter plot of cognitive function scores by age, the study’s modeling estimated the multivitamin treatment effect had a positive benefit of .028 standard deviations (SD) per year.
“Daily multivitamin-mineral supplementation appears to slow cognitive aging by 60% or by 1.8 years,” Dr. Baker added.
To date, the effect of MVM supplementation on cognition has been tested in only one large randomized clinical trial – the Physicians Health Study II. That study did not show an effect, but included only older male physicians – and cognitive testing began 2.5 years after randomization, said Dr. Baker.
“Our study provides new evidence that daily multivitamin supplementation may benefit cognitive function in older women and men, and the multivitamin effects may be more pronounced in participants with cardiovascular disease,” she noted.
For effects of multivitamins on Alzheimer’s disease prevalence and progression, “stay tuned,” Dr. Baker concluded.
Following the presentation, session cochair Suzanne Schindler, MD, PhD, instructor in the department of neurology at Washington University, St. Louis, said she and her colleagues “always check vitamin B12 levels” in patients with memory and cognitive difficulties and wondered if study subjects with a low level or deficiency of vitamin B12 benefited from the intervention.
“We are asking ourselves that as well,” said Dr. Baker.
“Some of this is a work in progress,” Dr. Baker added. “We still need to look at that more in-depth to understand whether it might be a mechanism for improvement. I think the results are still out on that topic.”
The study received support from the National Institute on Aging. Pfizer Consumer Healthcare (now GSK Consumer Healthcare) provided study pills and packaging. Dr. Baker has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, with the effects especially pronounced in patients with cardiovascular (CVD) disease, new research suggests.
In addition to testing the effect of a daily multivitamin on cognition, the COSMOS-Mind study examined the effect of cocoa flavanols, but showed no beneficial effect.
The findings “may have important public health implications, particularly for brain health, given the accessibility of multivitamins and minerals, and their low cost and safety,” said study investigator Laura D. Baker, PhD, professor, gerontology and geriatric medicine, Wake Forest University, Winston-Salem, N.C.
The findings were presented at the 14th Clinical Trials on Alzheimer’s Disease (CTAD) conference.
Placebo-controlled study
The study is a substudy of a large parent trial that compared the effects of cocoa extract (500 mg/day cocoa flavanols) and a standard multivitamin-mineral (MVM) to placebo on cardiovascular and cancer outcomes in more than 21,000 older participants.
COSMOS-Mind included 2,262 adults aged 65 and over without dementia who underwent cognitive testing at baseline and annually for 3 years. The mean age at baseline was 73 years, and 40.4% were men. Most participants (88.7%) were non-Hispanic White and almost half (49.2%) had some post-college education.
All study groups were balanced with respect to demographics, CVD history, diabetes, depression, smoking status, alcohol intake, chocolate intake, and prior multivitamin use. Baseline cognitive scores were similar between study groups. Researchers had complete data on 77% of study participants.
The primary endpoint was the effect of cocoa extract (CE) vs. placebo on Global Cognitive Function composite score. The secondary outcome was the effect of MVM vs. placebo on global cognitive function.
Additional outcomes included the impact of supplements on executive function and memory and the treatment effects for prespecified subgroups, including subjects with a history of CVD.
Using a graph of change over time, Dr. Baker showed there was no effect of cocoa on global cognitive function (effect: 0.03; 95% confidence interval, –0.02 to 0.08; P = .28). “We see the to-be-expected practice effects, but there’s no separation between the active and placebo groups,” she said.
It was a different story for MVM. Here, there was the same practice effect, but the graph showed the lines separated for global cognitive function composite score (effect: 0.07; 95% CI, 0.02-0.12; P = .007).
“We see a positive effect of multivitamins for the active group relative to placebo, peaking at 2 years and then remaining stable over time,” said Dr. Baker.
There were similar findings with MVM for the memory composite score, and the executive function composite score. “We have significance in all three, where the two lines do separate over and above the practice effects,” said Dr. Baker.
New evidence
Investigators found a baseline history of CVD, including transient ischemic attack, heart failure, coronary artery bypass graft, percutaneous transluminal coronary angioplasty, and stent, but not myocardial infarction or stroke as these were excluded in the parent trial because they affected the response to multivitamins.
As expected, those with CVD had lower cognitive scores at baseline. “But after an initial bump due to practice effect, at year 1, the cardiovascular disease history folks continue to benefit from multivitamins, whereas those who got placebo multivitamins continue to decline over time,” said Dr. Baker.
Based on information from a baseline scatter plot of cognitive function scores by age, the study’s modeling estimated the multivitamin treatment effect had a positive benefit of .028 standard deviations (SD) per year.
“Daily multivitamin-mineral supplementation appears to slow cognitive aging by 60% or by 1.8 years,” Dr. Baker added.
To date, the effect of MVM supplementation on cognition has been tested in only one large randomized clinical trial – the Physicians Health Study II. That study did not show an effect, but included only older male physicians – and cognitive testing began 2.5 years after randomization, said Dr. Baker.
“Our study provides new evidence that daily multivitamin supplementation may benefit cognitive function in older women and men, and the multivitamin effects may be more pronounced in participants with cardiovascular disease,” she noted.
For effects of multivitamins on Alzheimer’s disease prevalence and progression, “stay tuned,” Dr. Baker concluded.
Following the presentation, session cochair Suzanne Schindler, MD, PhD, instructor in the department of neurology at Washington University, St. Louis, said she and her colleagues “always check vitamin B12 levels” in patients with memory and cognitive difficulties and wondered if study subjects with a low level or deficiency of vitamin B12 benefited from the intervention.
“We are asking ourselves that as well,” said Dr. Baker.
“Some of this is a work in progress,” Dr. Baker added. “We still need to look at that more in-depth to understand whether it might be a mechanism for improvement. I think the results are still out on that topic.”
The study received support from the National Institute on Aging. Pfizer Consumer Healthcare (now GSK Consumer Healthcare) provided study pills and packaging. Dr. Baker has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Antihypertensives tied to lower Alzheimer’s disease pathology
new research shows.
Investigators found that use of any antihypertensive was associated with an 18% decrease in Alzheimer’s disease neuropathology, a 22% decrease in Lewy bodies, and a 40% decrease in TAR DNA-binding protein 43 (TDP-43), a protein relevant to several neurodegenerative diseases. Diuretics in particular appear to be driving the association.
Although diuretics might be a better option for preventing brain neuropathology, it’s too early to make firm recommendations solely on the basis of these results as to what blood pressure–lowering agent to prescribe a particular patient, said study investigator Ahmad Sajjadi, MD, assistant professor of neurology, University of California, Irvine.
“This is early stages and preliminary results,” said Dr. Sajjadi, “but it’s food for thought.”
The findings were presented at the 2021 annual meeting of the American Neurological Association.
Autopsy data
The study included 3,315 individuals who had donated their brains to research. The National Alzheimer’s Coordinating Center maintains a database that includes data from 32 Alzheimer’s disease research centers in the United States. Participants in the study must have visited one of these centers within 4 years of death. Each person whose brain was included in the study underwent two or more BP measurements on at least 50% of visits.
The mean age at death was 81.7 years, and the mean time between last visit and death was 13.1 months. About 44.4% of participants were women, 57.0% had at least a college degree, and 84.7% had cognitive impairment.
Researchers defined hypertension as systolic BP of at least 130 mm Hg, diastolic BP of at least 80 mm Hg, mean arterial pressure of at least 100 mm Hg, and pulse pressure of at least 60 mm Hg.
Antihypertensive medications that were evaluated included antiadrenergic agents, ACE inhibitors, angiotensin II receptor blockers, beta blockers, calcium channel blockers, diuretics, vasodilators, and combination therapies.
The investigators assessed the number of neuropathologies. In addition to Alzheimer’s disease neuropathology, which included amyloid-beta, tau, Lewy bodies, and TDP-43, they also assessed for atherosclerosis, arteriolosclerosis, cerebral amyloid angiopathy, frontotemporal lobar degeneration, and hippocampal sclerosis.
Results showed that use of any antihypertensive was associated with a lower likelihood of Alzheimer’s disease neuropathology (odds ratio, 0.822), Lewy bodies (OR, 0.786), and TDP 43 (OR, 0.597). Use of antihypertensives was also associated with increased odds of atherosclerosis (OR, 1.217) (all P < .5.)
The study showed that hypertensive systolic BP was associated with higher odds of Alzheimer’s disease neuropathology (OR, 1.28; P < .5).
Differences by drug type
Results differed in accordance with antihypertensive class. Angiotensin II receptor blockers decreased the odds of Alzheimer’s disease neuropathology by 40% (OR, 0.60; P < .5). Diuretics decreased the odds of Alzheimer’s disease by 36% (OR, 0.64; P < .001) and of hippocampal sclerosis by 32% (OR, 0.68; P < .5).
“We see diuretics are a main driver, especially for lower odds of Alzheimer’s disease and lower odds of hippocampal sclerosis,” said lead author Hanna L. Nguyen, a first-year medical student at the University of California, Irvine.
The results indicate that it is the medications, not BP levels, that account for these associations, she added.
One potential mechanism linking antihypertensives to brain pathology is that with these agents, BP is maintained in the target zone. Blood pressure that’s too high can damage blood vessels, whereas BP that’s too low may result in less than adequate perfusion, said Ms. Nguyen.
These medications may also alter pathways leading to degeneration and could, for example, affect the apo E mechanism of Alzheimer’s disease, she added.
The researchers plan to conduct subset analyses using apo E genetic status and age of death.
Although this is a “massive database,” it has limitations. For example, said Dr. Sajjadi, it does not reveal when patients started taking BP medication, how long they had been taking it, or why.
“We don’t know the exact the reason they were taking these medications. Was it just hypertension, or did they also have heart disease, stroke, a kidney problem, or was there another explanation,” he said.
Following the study presentation, session comoderator Krish Sathian, MBBS, PhD, professor of neurology, neural, and behavioral sciences, and psychology and director of the Neuroscience Institute, Penn State University, Hershey, called this work “fascinating. It provides a lot of data that really touches on everyday practice,” inasmuch as clinicians often prescribe antihypertensive medications and see patients with these kinds of brain disorders.
The investigators and Dr. Sathian reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new research shows.
Investigators found that use of any antihypertensive was associated with an 18% decrease in Alzheimer’s disease neuropathology, a 22% decrease in Lewy bodies, and a 40% decrease in TAR DNA-binding protein 43 (TDP-43), a protein relevant to several neurodegenerative diseases. Diuretics in particular appear to be driving the association.
Although diuretics might be a better option for preventing brain neuropathology, it’s too early to make firm recommendations solely on the basis of these results as to what blood pressure–lowering agent to prescribe a particular patient, said study investigator Ahmad Sajjadi, MD, assistant professor of neurology, University of California, Irvine.
“This is early stages and preliminary results,” said Dr. Sajjadi, “but it’s food for thought.”
The findings were presented at the 2021 annual meeting of the American Neurological Association.
Autopsy data
The study included 3,315 individuals who had donated their brains to research. The National Alzheimer’s Coordinating Center maintains a database that includes data from 32 Alzheimer’s disease research centers in the United States. Participants in the study must have visited one of these centers within 4 years of death. Each person whose brain was included in the study underwent two or more BP measurements on at least 50% of visits.
The mean age at death was 81.7 years, and the mean time between last visit and death was 13.1 months. About 44.4% of participants were women, 57.0% had at least a college degree, and 84.7% had cognitive impairment.
Researchers defined hypertension as systolic BP of at least 130 mm Hg, diastolic BP of at least 80 mm Hg, mean arterial pressure of at least 100 mm Hg, and pulse pressure of at least 60 mm Hg.
Antihypertensive medications that were evaluated included antiadrenergic agents, ACE inhibitors, angiotensin II receptor blockers, beta blockers, calcium channel blockers, diuretics, vasodilators, and combination therapies.
The investigators assessed the number of neuropathologies. In addition to Alzheimer’s disease neuropathology, which included amyloid-beta, tau, Lewy bodies, and TDP-43, they also assessed for atherosclerosis, arteriolosclerosis, cerebral amyloid angiopathy, frontotemporal lobar degeneration, and hippocampal sclerosis.
Results showed that use of any antihypertensive was associated with a lower likelihood of Alzheimer’s disease neuropathology (odds ratio, 0.822), Lewy bodies (OR, 0.786), and TDP 43 (OR, 0.597). Use of antihypertensives was also associated with increased odds of atherosclerosis (OR, 1.217) (all P < .5.)
The study showed that hypertensive systolic BP was associated with higher odds of Alzheimer’s disease neuropathology (OR, 1.28; P < .5).
Differences by drug type
Results differed in accordance with antihypertensive class. Angiotensin II receptor blockers decreased the odds of Alzheimer’s disease neuropathology by 40% (OR, 0.60; P < .5). Diuretics decreased the odds of Alzheimer’s disease by 36% (OR, 0.64; P < .001) and of hippocampal sclerosis by 32% (OR, 0.68; P < .5).
“We see diuretics are a main driver, especially for lower odds of Alzheimer’s disease and lower odds of hippocampal sclerosis,” said lead author Hanna L. Nguyen, a first-year medical student at the University of California, Irvine.
The results indicate that it is the medications, not BP levels, that account for these associations, she added.
One potential mechanism linking antihypertensives to brain pathology is that with these agents, BP is maintained in the target zone. Blood pressure that’s too high can damage blood vessels, whereas BP that’s too low may result in less than adequate perfusion, said Ms. Nguyen.
These medications may also alter pathways leading to degeneration and could, for example, affect the apo E mechanism of Alzheimer’s disease, she added.
The researchers plan to conduct subset analyses using apo E genetic status and age of death.
Although this is a “massive database,” it has limitations. For example, said Dr. Sajjadi, it does not reveal when patients started taking BP medication, how long they had been taking it, or why.
“We don’t know the exact the reason they were taking these medications. Was it just hypertension, or did they also have heart disease, stroke, a kidney problem, or was there another explanation,” he said.
Following the study presentation, session comoderator Krish Sathian, MBBS, PhD, professor of neurology, neural, and behavioral sciences, and psychology and director of the Neuroscience Institute, Penn State University, Hershey, called this work “fascinating. It provides a lot of data that really touches on everyday practice,” inasmuch as clinicians often prescribe antihypertensive medications and see patients with these kinds of brain disorders.
The investigators and Dr. Sathian reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new research shows.
Investigators found that use of any antihypertensive was associated with an 18% decrease in Alzheimer’s disease neuropathology, a 22% decrease in Lewy bodies, and a 40% decrease in TAR DNA-binding protein 43 (TDP-43), a protein relevant to several neurodegenerative diseases. Diuretics in particular appear to be driving the association.
Although diuretics might be a better option for preventing brain neuropathology, it’s too early to make firm recommendations solely on the basis of these results as to what blood pressure–lowering agent to prescribe a particular patient, said study investigator Ahmad Sajjadi, MD, assistant professor of neurology, University of California, Irvine.
“This is early stages and preliminary results,” said Dr. Sajjadi, “but it’s food for thought.”
The findings were presented at the 2021 annual meeting of the American Neurological Association.
Autopsy data
The study included 3,315 individuals who had donated their brains to research. The National Alzheimer’s Coordinating Center maintains a database that includes data from 32 Alzheimer’s disease research centers in the United States. Participants in the study must have visited one of these centers within 4 years of death. Each person whose brain was included in the study underwent two or more BP measurements on at least 50% of visits.
The mean age at death was 81.7 years, and the mean time between last visit and death was 13.1 months. About 44.4% of participants were women, 57.0% had at least a college degree, and 84.7% had cognitive impairment.
Researchers defined hypertension as systolic BP of at least 130 mm Hg, diastolic BP of at least 80 mm Hg, mean arterial pressure of at least 100 mm Hg, and pulse pressure of at least 60 mm Hg.
Antihypertensive medications that were evaluated included antiadrenergic agents, ACE inhibitors, angiotensin II receptor blockers, beta blockers, calcium channel blockers, diuretics, vasodilators, and combination therapies.
The investigators assessed the number of neuropathologies. In addition to Alzheimer’s disease neuropathology, which included amyloid-beta, tau, Lewy bodies, and TDP-43, they also assessed for atherosclerosis, arteriolosclerosis, cerebral amyloid angiopathy, frontotemporal lobar degeneration, and hippocampal sclerosis.
Results showed that use of any antihypertensive was associated with a lower likelihood of Alzheimer’s disease neuropathology (odds ratio, 0.822), Lewy bodies (OR, 0.786), and TDP 43 (OR, 0.597). Use of antihypertensives was also associated with increased odds of atherosclerosis (OR, 1.217) (all P < .5.)
The study showed that hypertensive systolic BP was associated with higher odds of Alzheimer’s disease neuropathology (OR, 1.28; P < .5).
Differences by drug type
Results differed in accordance with antihypertensive class. Angiotensin II receptor blockers decreased the odds of Alzheimer’s disease neuropathology by 40% (OR, 0.60; P < .5). Diuretics decreased the odds of Alzheimer’s disease by 36% (OR, 0.64; P < .001) and of hippocampal sclerosis by 32% (OR, 0.68; P < .5).
“We see diuretics are a main driver, especially for lower odds of Alzheimer’s disease and lower odds of hippocampal sclerosis,” said lead author Hanna L. Nguyen, a first-year medical student at the University of California, Irvine.
The results indicate that it is the medications, not BP levels, that account for these associations, she added.
One potential mechanism linking antihypertensives to brain pathology is that with these agents, BP is maintained in the target zone. Blood pressure that’s too high can damage blood vessels, whereas BP that’s too low may result in less than adequate perfusion, said Ms. Nguyen.
These medications may also alter pathways leading to degeneration and could, for example, affect the apo E mechanism of Alzheimer’s disease, she added.
The researchers plan to conduct subset analyses using apo E genetic status and age of death.
Although this is a “massive database,” it has limitations. For example, said Dr. Sajjadi, it does not reveal when patients started taking BP medication, how long they had been taking it, or why.
“We don’t know the exact the reason they were taking these medications. Was it just hypertension, or did they also have heart disease, stroke, a kidney problem, or was there another explanation,” he said.
Following the study presentation, session comoderator Krish Sathian, MBBS, PhD, professor of neurology, neural, and behavioral sciences, and psychology and director of the Neuroscience Institute, Penn State University, Hershey, called this work “fascinating. It provides a lot of data that really touches on everyday practice,” inasmuch as clinicians often prescribe antihypertensive medications and see patients with these kinds of brain disorders.
The investigators and Dr. Sathian reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ANA 2021
Alopecia tied to a threefold increased risk for dementia
Alopecia areata (AA) has been linked to a significantly increased risk for dementia, new research shows.
After controlling for an array of potential confounders, investigators found a threefold higher risk of developing any form of dementia and a fourfold higher risk of developing Alzheimer’s disease (AD) in those with AA versus the controls.
“AA shares a similar inflammatory signature with dementia and has great psychological impacts that lead to poor social engagement,” lead author Cheng-Yuan Li, MD, MSc, of the department of dermatology, Taipei (Taiwan) Veterans General Hospital.
“Poor social engagement and shared inflammatory cytokines might both be important links between AA and dementia,” said Dr. Li, who is also affiliated with the School of Medicine and the Institute of Brain Science at National Yang Ming Chiao Tung University, Taipei.
The study was published online Oct. 26, 2021, in the Journal of Clinical Psychiatry (doi: 10.4088/JCP.21m13931).
Significant psychological impact
Patients with AA often experience anxiety and depression, possibly caused by the negative emotional and psychological impact of the hair loss and partial or even complete baldness associated with the disease, the authors noted.
However, AA is also associated with an array of other atopic and autoimmune diseases, including psoriasis and systemic lupus erythematosus (SLE).
Epidemiologic research has suggested a link between dementia and autoimmune diseases such as psoriasis and SLE, with some evidence suggesting that autoimmune and inflammatory mechanisms may “play a role” in the development of AD.
Dementia in general and AD in particular, “have been shown to include an inflammatory component” that may share some of the same mediators seen in AA (eg, IL-1 beta, IL-6, and tumor necrosis factor–alpha).
Moreover, “the great negative psychosocial impact of AA might result in poor social engagement, a typical risk factor for dementia,” said Dr. Li. The investigators sought to investigate whether patients with AA actually do have a higher dementia risk than individuals without AA.
The researchers used data from the Taiwan National Health Insurance Research Database, comparing 2,534 patients with AA against 25,340 controls matched for age, sex, residence, income, dementia-related comorbidities, systemic steroid use, and annual outpatient visits. Participants were enrolled between 1998 and 2011 and followed to the end of 2013.
The mean age of the cohort was 53.9 years, and a little over half (57.6%) were female. The most common comorbidity was hypertension (32.3%), followed by dyslipidemia (27%) and diabetes (15.4%).
Dual intervention
After adjusting for potential confounders, those with AA were more likely to develop dementia, AD, and unspecified dementia, compared with controls. They also had a numerically higher risk for vascular dementia, compared with controls, but it was not statistically significant.
When participants were stratified by age, investigators found a significant association between AA and higher risk for any dementia as well as unspecified dementia in individuals of all ages and an increased risk for AD in patients with dementia age at onset of 65 years and older.
The mean age of dementia diagnosis was considerably younger in patients with AA versus controls (73.4 vs. 78.9 years, P = .002). The risk for any dementia and unspecified dementia was higher in patients of both sexes, but the risk for AD was higher only in male patients.
Sensitivity analyses that excluded the first year or first 3 years of observation yielded similar and consistent findings.
“Intervention targeting poor social engagement and inflammatory cytokines may be beneficial to AA-associated dementia,” said Dr. Li.
“Physicians should be more aware of this possible association, help reduce disease discrimination among the public, and encourage more social engagement for AA patients,” he said.
“Further studies are needed to elucidate the underlying pathophysiology between AA and dementia risk,” he added.
No cause and effect
Commenting on the study, Heather M. Snyder, PhD, vice president of medical and scientific affairs, Alzheimer’s Association, said, “We continue to learn about and better understand factors that may increase or decrease a person’s risk of dementia.”
“While we know the immune system plays a role in Alzheimer’s and other dementia, we are still investigating links between, and impact of, autoimmune diseases – like alopecia areata, rheumatoid arthritis, and others – on our overall health and our brains, [which] may eventually give us important information on risk reduction strategies as well,” said Dr. Snyder, who was not involved in the research.
She cautioned that although the study did show a correlation between AA and dementia risk, this does not equate to a demonstration of cause and effect.
At present, “the message for clinicians is that when a patient comes to your office with complaints about their memory, they should, No. 1, be taken seriously; and, No. 2, receive a thorough evaluation that takes into account the many factors that may lead to cognitive decline,” Dr. Snyder said.
The study was supported by a grant from Taipei Veterans General Hospital and the Ministry of Science and Technology, Taiwan. Dr. Li, coauthors, and Dr. Snyder disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Alopecia areata (AA) has been linked to a significantly increased risk for dementia, new research shows.
After controlling for an array of potential confounders, investigators found a threefold higher risk of developing any form of dementia and a fourfold higher risk of developing Alzheimer’s disease (AD) in those with AA versus the controls.
“AA shares a similar inflammatory signature with dementia and has great psychological impacts that lead to poor social engagement,” lead author Cheng-Yuan Li, MD, MSc, of the department of dermatology, Taipei (Taiwan) Veterans General Hospital.
“Poor social engagement and shared inflammatory cytokines might both be important links between AA and dementia,” said Dr. Li, who is also affiliated with the School of Medicine and the Institute of Brain Science at National Yang Ming Chiao Tung University, Taipei.
The study was published online Oct. 26, 2021, in the Journal of Clinical Psychiatry (doi: 10.4088/JCP.21m13931).
Significant psychological impact
Patients with AA often experience anxiety and depression, possibly caused by the negative emotional and psychological impact of the hair loss and partial or even complete baldness associated with the disease, the authors noted.
However, AA is also associated with an array of other atopic and autoimmune diseases, including psoriasis and systemic lupus erythematosus (SLE).
Epidemiologic research has suggested a link between dementia and autoimmune diseases such as psoriasis and SLE, with some evidence suggesting that autoimmune and inflammatory mechanisms may “play a role” in the development of AD.
Dementia in general and AD in particular, “have been shown to include an inflammatory component” that may share some of the same mediators seen in AA (eg, IL-1 beta, IL-6, and tumor necrosis factor–alpha).
Moreover, “the great negative psychosocial impact of AA might result in poor social engagement, a typical risk factor for dementia,” said Dr. Li. The investigators sought to investigate whether patients with AA actually do have a higher dementia risk than individuals without AA.
The researchers used data from the Taiwan National Health Insurance Research Database, comparing 2,534 patients with AA against 25,340 controls matched for age, sex, residence, income, dementia-related comorbidities, systemic steroid use, and annual outpatient visits. Participants were enrolled between 1998 and 2011 and followed to the end of 2013.
The mean age of the cohort was 53.9 years, and a little over half (57.6%) were female. The most common comorbidity was hypertension (32.3%), followed by dyslipidemia (27%) and diabetes (15.4%).
Dual intervention
After adjusting for potential confounders, those with AA were more likely to develop dementia, AD, and unspecified dementia, compared with controls. They also had a numerically higher risk for vascular dementia, compared with controls, but it was not statistically significant.
When participants were stratified by age, investigators found a significant association between AA and higher risk for any dementia as well as unspecified dementia in individuals of all ages and an increased risk for AD in patients with dementia age at onset of 65 years and older.
The mean age of dementia diagnosis was considerably younger in patients with AA versus controls (73.4 vs. 78.9 years, P = .002). The risk for any dementia and unspecified dementia was higher in patients of both sexes, but the risk for AD was higher only in male patients.
Sensitivity analyses that excluded the first year or first 3 years of observation yielded similar and consistent findings.
“Intervention targeting poor social engagement and inflammatory cytokines may be beneficial to AA-associated dementia,” said Dr. Li.
“Physicians should be more aware of this possible association, help reduce disease discrimination among the public, and encourage more social engagement for AA patients,” he said.
“Further studies are needed to elucidate the underlying pathophysiology between AA and dementia risk,” he added.
No cause and effect
Commenting on the study, Heather M. Snyder, PhD, vice president of medical and scientific affairs, Alzheimer’s Association, said, “We continue to learn about and better understand factors that may increase or decrease a person’s risk of dementia.”
“While we know the immune system plays a role in Alzheimer’s and other dementia, we are still investigating links between, and impact of, autoimmune diseases – like alopecia areata, rheumatoid arthritis, and others – on our overall health and our brains, [which] may eventually give us important information on risk reduction strategies as well,” said Dr. Snyder, who was not involved in the research.
She cautioned that although the study did show a correlation between AA and dementia risk, this does not equate to a demonstration of cause and effect.
At present, “the message for clinicians is that when a patient comes to your office with complaints about their memory, they should, No. 1, be taken seriously; and, No. 2, receive a thorough evaluation that takes into account the many factors that may lead to cognitive decline,” Dr. Snyder said.
The study was supported by a grant from Taipei Veterans General Hospital and the Ministry of Science and Technology, Taiwan. Dr. Li, coauthors, and Dr. Snyder disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Alopecia areata (AA) has been linked to a significantly increased risk for dementia, new research shows.
After controlling for an array of potential confounders, investigators found a threefold higher risk of developing any form of dementia and a fourfold higher risk of developing Alzheimer’s disease (AD) in those with AA versus the controls.
“AA shares a similar inflammatory signature with dementia and has great psychological impacts that lead to poor social engagement,” lead author Cheng-Yuan Li, MD, MSc, of the department of dermatology, Taipei (Taiwan) Veterans General Hospital.
“Poor social engagement and shared inflammatory cytokines might both be important links between AA and dementia,” said Dr. Li, who is also affiliated with the School of Medicine and the Institute of Brain Science at National Yang Ming Chiao Tung University, Taipei.
The study was published online Oct. 26, 2021, in the Journal of Clinical Psychiatry (doi: 10.4088/JCP.21m13931).
Significant psychological impact
Patients with AA often experience anxiety and depression, possibly caused by the negative emotional and psychological impact of the hair loss and partial or even complete baldness associated with the disease, the authors noted.
However, AA is also associated with an array of other atopic and autoimmune diseases, including psoriasis and systemic lupus erythematosus (SLE).
Epidemiologic research has suggested a link between dementia and autoimmune diseases such as psoriasis and SLE, with some evidence suggesting that autoimmune and inflammatory mechanisms may “play a role” in the development of AD.
Dementia in general and AD in particular, “have been shown to include an inflammatory component” that may share some of the same mediators seen in AA (eg, IL-1 beta, IL-6, and tumor necrosis factor–alpha).
Moreover, “the great negative psychosocial impact of AA might result in poor social engagement, a typical risk factor for dementia,” said Dr. Li. The investigators sought to investigate whether patients with AA actually do have a higher dementia risk than individuals without AA.
The researchers used data from the Taiwan National Health Insurance Research Database, comparing 2,534 patients with AA against 25,340 controls matched for age, sex, residence, income, dementia-related comorbidities, systemic steroid use, and annual outpatient visits. Participants were enrolled between 1998 and 2011 and followed to the end of 2013.
The mean age of the cohort was 53.9 years, and a little over half (57.6%) were female. The most common comorbidity was hypertension (32.3%), followed by dyslipidemia (27%) and diabetes (15.4%).
Dual intervention
After adjusting for potential confounders, those with AA were more likely to develop dementia, AD, and unspecified dementia, compared with controls. They also had a numerically higher risk for vascular dementia, compared with controls, but it was not statistically significant.
When participants were stratified by age, investigators found a significant association between AA and higher risk for any dementia as well as unspecified dementia in individuals of all ages and an increased risk for AD in patients with dementia age at onset of 65 years and older.
The mean age of dementia diagnosis was considerably younger in patients with AA versus controls (73.4 vs. 78.9 years, P = .002). The risk for any dementia and unspecified dementia was higher in patients of both sexes, but the risk for AD was higher only in male patients.
Sensitivity analyses that excluded the first year or first 3 years of observation yielded similar and consistent findings.
“Intervention targeting poor social engagement and inflammatory cytokines may be beneficial to AA-associated dementia,” said Dr. Li.
“Physicians should be more aware of this possible association, help reduce disease discrimination among the public, and encourage more social engagement for AA patients,” he said.
“Further studies are needed to elucidate the underlying pathophysiology between AA and dementia risk,” he added.
No cause and effect
Commenting on the study, Heather M. Snyder, PhD, vice president of medical and scientific affairs, Alzheimer’s Association, said, “We continue to learn about and better understand factors that may increase or decrease a person’s risk of dementia.”
“While we know the immune system plays a role in Alzheimer’s and other dementia, we are still investigating links between, and impact of, autoimmune diseases – like alopecia areata, rheumatoid arthritis, and others – on our overall health and our brains, [which] may eventually give us important information on risk reduction strategies as well,” said Dr. Snyder, who was not involved in the research.
She cautioned that although the study did show a correlation between AA and dementia risk, this does not equate to a demonstration of cause and effect.
At present, “the message for clinicians is that when a patient comes to your office with complaints about their memory, they should, No. 1, be taken seriously; and, No. 2, receive a thorough evaluation that takes into account the many factors that may lead to cognitive decline,” Dr. Snyder said.
The study was supported by a grant from Taipei Veterans General Hospital and the Ministry of Science and Technology, Taiwan. Dr. Li, coauthors, and Dr. Snyder disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FDA not recognizing efficacy of psychopharmacologic therapies
Many years ago, drug development in psychiatry turned to control of specific symptoms across disorders rather than within disorders, but regulatory agencies are still not yet on board, according to an expert psychopharmacologist outlining the ongoing evolution at the virtual Psychopharmacology Update presented by Current Psychiatry and the American Academy of Clinical Psychiatrists, sponsored by Medscape Live.
If this reorientation is going to lead to the broad indications the newer drugs likely deserve, which is control of specific types of symptoms regardless of the diagnosis, “we have to move the [Food and Drug Administration] along,” said Stephen M. Stahl, MD, PhD, chairman of the Neuroscience Institute and an adjunct professor of psychiatry at the University of California, San Diego.
On the side of drug development and clinical practice, the reorientation has already taken place. Dr. Stahl described numerous brain circuits known to produce symptoms when function is altered that are now treatment targets. This includes the ventral medial prefrontal cortex where deficient information processing leads to depression and the orbital frontal cortex where altered function leads to impulsivity.
“It is not like each part of the brain does a little bit of everything. Rather, each part of the brain has an assignment and duty and function,” Dr. Stahl explained. By addressing the disturbed signaling in brain circuits that lead to depression, impulsivity, agitation, or other symptoms, there is an opportunity for control, regardless of the psychiatric diagnosis with which the symptom is associated.
For example, Dr. Stahl predicted that pimavanserin, a highly selective 5-HT2A inverse agonist that is already approved for psychosis in Parkinson’s disease, is now likely to be approved for psychosis associated with other conditions on the basis of recent positive clinical studies in these other disorders.
Brexpiprazole, a serotonin-dopamine activity modulator already known to be useful for control of the agitation characteristic of schizophrenia, is now showing the same type of activity against agitation when it is associated with Alzheimer’s disease. Again, Dr. Stahl thinks this drug is on course for an indication across diseases once studies are conducted in each disease individually.
Another drug being evaluated for agitation, the N-methyl-D-aspartate receptor antagonist dextromethorphan bupropion, is also being tested for treatment of symptoms across multiple disorders, he reported.
However, the FDA has so far taken the position that each drug must be tested separately for a given symptom in each disorder for which it is being considered despite the underlying premise that it is the symptom, not the disease, that is important.
Unlike physiological diseases where symptoms, like a fever or abdominal cramps, are the product of a disease, psychiatric symptoms are the disease and a fundamental target – regardless of the DSM-based diagnosis.
To some degree, the symptoms of psychiatric disorders have always been the focus of treatment, but a pivot toward developing therapies that will control a symptom regardless of the underlying diagnosis is an important conceptual change. It is being made possible by advances in the detail with which the neuropathology of these symptoms is understood .
“By my count, 79 symptoms are described in DSM-5, but they are spread across hundreds of syndromes because they are grouped together in different ways,” Dr. Stahl observed.
He noted that clinicians make a diagnosis on the basis symptom groupings, but their interventions are selected to address the manifestations of the disease, not the disease itself.
“If you are a real psychopharmacologist treating real patients, you are treating the specific symptoms of the specific patient,” according to Dr. Stahl.
So far, the FDA has not made this leap, insisting on trials in these categorical disorders rather than permitting trial designs that allow benefit to be demonstrated against a symptom regardless of the syndrome with which it is associated.
Of egregious examples, Dr. Stahl recounted a recent trial of a 5-HT2 antagonist that looked so promising against psychosis in Alzheimer’s disease that the trialists enrolled patients with psychosis regardless of type of dementia, such as vascular dementia and Lewy body disease. The efficacy was impressive.
“It worked so well that they stopped the trial, but the FDA declined to approve it,” Dr. Stahl recounted. Despite clear evidence of benefit, the regulators insisted that the investigators needed to show a significant benefit in each condition individually.
While the trial investigators acknowledged that there was not enough power in the trial to show a statistically significant benefit in each category, they argued that the overall benefit and the consistent response across categories required them to stop the trial for ethical reasons.
“That’s your problem, the FDA said to the investigators,” according to Dr. Stahl.
The failure of the FDA to recognize the efficacy of psychopharmacologic therapies across symptoms regardless of the associated disease is a failure to stay current with an important evolution in medicine, Dr. Stahl indicated.
“What we have come to understand is the neurobiology of any given symptom is likely to be the same across disorders,” he said.
Agency’s arbitrary decisions cited
“I completely agree with Dr. Stahl,” said Henry A. Nasrallah, MD, professor of psychiatry, neurology, and neuroscience, University of Cincinnati.
In addition to the fact that symptoms are present across multiple categories, many patients manifest multiple symptoms at one time, Dr. Nasrallah pointed out. For neurodegenerative disorders associated with psychosis, depression, anxiety, aggression, and other symptoms, it is already well known that the heterogeneous symptoms “cannot be treated with a single drug,” he said. Rather different drugs targeting each symptom individually is essential for effective management.
Dr. Nasrallah, who chaired the Psychopharmacology Update meeting, has made this point many times in the past, including in his role as the editor of Current Psychiatry. In one editorial 10 years ago, he wrote that “it makes little sense for the FDA to mandate that a drug must work for a DSM diagnosis instead of specific symptoms.”
“The FDA must update its old policy, which has led to the widespread off-label use of psychiatric drugs, an artificial concept, simply because the FDA arbitrarily decided a long time ago that new drugs must be approved for a specific DSM diagnosis,” Dr. Nasrallah said.
Dr. Stahl reported financial relationships with more than 20 pharmaceutical companies, including those that are involved in the development of drugs included in his talk. Medscape Live and this news organization are owned by the same parent company.
Many years ago, drug development in psychiatry turned to control of specific symptoms across disorders rather than within disorders, but regulatory agencies are still not yet on board, according to an expert psychopharmacologist outlining the ongoing evolution at the virtual Psychopharmacology Update presented by Current Psychiatry and the American Academy of Clinical Psychiatrists, sponsored by Medscape Live.
If this reorientation is going to lead to the broad indications the newer drugs likely deserve, which is control of specific types of symptoms regardless of the diagnosis, “we have to move the [Food and Drug Administration] along,” said Stephen M. Stahl, MD, PhD, chairman of the Neuroscience Institute and an adjunct professor of psychiatry at the University of California, San Diego.
On the side of drug development and clinical practice, the reorientation has already taken place. Dr. Stahl described numerous brain circuits known to produce symptoms when function is altered that are now treatment targets. This includes the ventral medial prefrontal cortex where deficient information processing leads to depression and the orbital frontal cortex where altered function leads to impulsivity.
“It is not like each part of the brain does a little bit of everything. Rather, each part of the brain has an assignment and duty and function,” Dr. Stahl explained. By addressing the disturbed signaling in brain circuits that lead to depression, impulsivity, agitation, or other symptoms, there is an opportunity for control, regardless of the psychiatric diagnosis with which the symptom is associated.
For example, Dr. Stahl predicted that pimavanserin, a highly selective 5-HT2A inverse agonist that is already approved for psychosis in Parkinson’s disease, is now likely to be approved for psychosis associated with other conditions on the basis of recent positive clinical studies in these other disorders.
Brexpiprazole, a serotonin-dopamine activity modulator already known to be useful for control of the agitation characteristic of schizophrenia, is now showing the same type of activity against agitation when it is associated with Alzheimer’s disease. Again, Dr. Stahl thinks this drug is on course for an indication across diseases once studies are conducted in each disease individually.
Another drug being evaluated for agitation, the N-methyl-D-aspartate receptor antagonist dextromethorphan bupropion, is also being tested for treatment of symptoms across multiple disorders, he reported.
However, the FDA has so far taken the position that each drug must be tested separately for a given symptom in each disorder for which it is being considered despite the underlying premise that it is the symptom, not the disease, that is important.
Unlike physiological diseases where symptoms, like a fever or abdominal cramps, are the product of a disease, psychiatric symptoms are the disease and a fundamental target – regardless of the DSM-based diagnosis.
To some degree, the symptoms of psychiatric disorders have always been the focus of treatment, but a pivot toward developing therapies that will control a symptom regardless of the underlying diagnosis is an important conceptual change. It is being made possible by advances in the detail with which the neuropathology of these symptoms is understood .
“By my count, 79 symptoms are described in DSM-5, but they are spread across hundreds of syndromes because they are grouped together in different ways,” Dr. Stahl observed.
He noted that clinicians make a diagnosis on the basis symptom groupings, but their interventions are selected to address the manifestations of the disease, not the disease itself.
“If you are a real psychopharmacologist treating real patients, you are treating the specific symptoms of the specific patient,” according to Dr. Stahl.
So far, the FDA has not made this leap, insisting on trials in these categorical disorders rather than permitting trial designs that allow benefit to be demonstrated against a symptom regardless of the syndrome with which it is associated.
Of egregious examples, Dr. Stahl recounted a recent trial of a 5-HT2 antagonist that looked so promising against psychosis in Alzheimer’s disease that the trialists enrolled patients with psychosis regardless of type of dementia, such as vascular dementia and Lewy body disease. The efficacy was impressive.
“It worked so well that they stopped the trial, but the FDA declined to approve it,” Dr. Stahl recounted. Despite clear evidence of benefit, the regulators insisted that the investigators needed to show a significant benefit in each condition individually.
While the trial investigators acknowledged that there was not enough power in the trial to show a statistically significant benefit in each category, they argued that the overall benefit and the consistent response across categories required them to stop the trial for ethical reasons.
“That’s your problem, the FDA said to the investigators,” according to Dr. Stahl.
The failure of the FDA to recognize the efficacy of psychopharmacologic therapies across symptoms regardless of the associated disease is a failure to stay current with an important evolution in medicine, Dr. Stahl indicated.
“What we have come to understand is the neurobiology of any given symptom is likely to be the same across disorders,” he said.
Agency’s arbitrary decisions cited
“I completely agree with Dr. Stahl,” said Henry A. Nasrallah, MD, professor of psychiatry, neurology, and neuroscience, University of Cincinnati.
In addition to the fact that symptoms are present across multiple categories, many patients manifest multiple symptoms at one time, Dr. Nasrallah pointed out. For neurodegenerative disorders associated with psychosis, depression, anxiety, aggression, and other symptoms, it is already well known that the heterogeneous symptoms “cannot be treated with a single drug,” he said. Rather different drugs targeting each symptom individually is essential for effective management.
Dr. Nasrallah, who chaired the Psychopharmacology Update meeting, has made this point many times in the past, including in his role as the editor of Current Psychiatry. In one editorial 10 years ago, he wrote that “it makes little sense for the FDA to mandate that a drug must work for a DSM diagnosis instead of specific symptoms.”
“The FDA must update its old policy, which has led to the widespread off-label use of psychiatric drugs, an artificial concept, simply because the FDA arbitrarily decided a long time ago that new drugs must be approved for a specific DSM diagnosis,” Dr. Nasrallah said.
Dr. Stahl reported financial relationships with more than 20 pharmaceutical companies, including those that are involved in the development of drugs included in his talk. Medscape Live and this news organization are owned by the same parent company.
Many years ago, drug development in psychiatry turned to control of specific symptoms across disorders rather than within disorders, but regulatory agencies are still not yet on board, according to an expert psychopharmacologist outlining the ongoing evolution at the virtual Psychopharmacology Update presented by Current Psychiatry and the American Academy of Clinical Psychiatrists, sponsored by Medscape Live.
If this reorientation is going to lead to the broad indications the newer drugs likely deserve, which is control of specific types of symptoms regardless of the diagnosis, “we have to move the [Food and Drug Administration] along,” said Stephen M. Stahl, MD, PhD, chairman of the Neuroscience Institute and an adjunct professor of psychiatry at the University of California, San Diego.
On the side of drug development and clinical practice, the reorientation has already taken place. Dr. Stahl described numerous brain circuits known to produce symptoms when function is altered that are now treatment targets. This includes the ventral medial prefrontal cortex where deficient information processing leads to depression and the orbital frontal cortex where altered function leads to impulsivity.
“It is not like each part of the brain does a little bit of everything. Rather, each part of the brain has an assignment and duty and function,” Dr. Stahl explained. By addressing the disturbed signaling in brain circuits that lead to depression, impulsivity, agitation, or other symptoms, there is an opportunity for control, regardless of the psychiatric diagnosis with which the symptom is associated.
For example, Dr. Stahl predicted that pimavanserin, a highly selective 5-HT2A inverse agonist that is already approved for psychosis in Parkinson’s disease, is now likely to be approved for psychosis associated with other conditions on the basis of recent positive clinical studies in these other disorders.
Brexpiprazole, a serotonin-dopamine activity modulator already known to be useful for control of the agitation characteristic of schizophrenia, is now showing the same type of activity against agitation when it is associated with Alzheimer’s disease. Again, Dr. Stahl thinks this drug is on course for an indication across diseases once studies are conducted in each disease individually.
Another drug being evaluated for agitation, the N-methyl-D-aspartate receptor antagonist dextromethorphan bupropion, is also being tested for treatment of symptoms across multiple disorders, he reported.
However, the FDA has so far taken the position that each drug must be tested separately for a given symptom in each disorder for which it is being considered despite the underlying premise that it is the symptom, not the disease, that is important.
Unlike physiological diseases where symptoms, like a fever or abdominal cramps, are the product of a disease, psychiatric symptoms are the disease and a fundamental target – regardless of the DSM-based diagnosis.
To some degree, the symptoms of psychiatric disorders have always been the focus of treatment, but a pivot toward developing therapies that will control a symptom regardless of the underlying diagnosis is an important conceptual change. It is being made possible by advances in the detail with which the neuropathology of these symptoms is understood .
“By my count, 79 symptoms are described in DSM-5, but they are spread across hundreds of syndromes because they are grouped together in different ways,” Dr. Stahl observed.
He noted that clinicians make a diagnosis on the basis symptom groupings, but their interventions are selected to address the manifestations of the disease, not the disease itself.
“If you are a real psychopharmacologist treating real patients, you are treating the specific symptoms of the specific patient,” according to Dr. Stahl.
So far, the FDA has not made this leap, insisting on trials in these categorical disorders rather than permitting trial designs that allow benefit to be demonstrated against a symptom regardless of the syndrome with which it is associated.
Of egregious examples, Dr. Stahl recounted a recent trial of a 5-HT2 antagonist that looked so promising against psychosis in Alzheimer’s disease that the trialists enrolled patients with psychosis regardless of type of dementia, such as vascular dementia and Lewy body disease. The efficacy was impressive.
“It worked so well that they stopped the trial, but the FDA declined to approve it,” Dr. Stahl recounted. Despite clear evidence of benefit, the regulators insisted that the investigators needed to show a significant benefit in each condition individually.
While the trial investigators acknowledged that there was not enough power in the trial to show a statistically significant benefit in each category, they argued that the overall benefit and the consistent response across categories required them to stop the trial for ethical reasons.
“That’s your problem, the FDA said to the investigators,” according to Dr. Stahl.
The failure of the FDA to recognize the efficacy of psychopharmacologic therapies across symptoms regardless of the associated disease is a failure to stay current with an important evolution in medicine, Dr. Stahl indicated.
“What we have come to understand is the neurobiology of any given symptom is likely to be the same across disorders,” he said.
Agency’s arbitrary decisions cited
“I completely agree with Dr. Stahl,” said Henry A. Nasrallah, MD, professor of psychiatry, neurology, and neuroscience, University of Cincinnati.
In addition to the fact that symptoms are present across multiple categories, many patients manifest multiple symptoms at one time, Dr. Nasrallah pointed out. For neurodegenerative disorders associated with psychosis, depression, anxiety, aggression, and other symptoms, it is already well known that the heterogeneous symptoms “cannot be treated with a single drug,” he said. Rather different drugs targeting each symptom individually is essential for effective management.
Dr. Nasrallah, who chaired the Psychopharmacology Update meeting, has made this point many times in the past, including in his role as the editor of Current Psychiatry. In one editorial 10 years ago, he wrote that “it makes little sense for the FDA to mandate that a drug must work for a DSM diagnosis instead of specific symptoms.”
“The FDA must update its old policy, which has led to the widespread off-label use of psychiatric drugs, an artificial concept, simply because the FDA arbitrarily decided a long time ago that new drugs must be approved for a specific DSM diagnosis,” Dr. Nasrallah said.
Dr. Stahl reported financial relationships with more than 20 pharmaceutical companies, including those that are involved in the development of drugs included in his talk. Medscape Live and this news organization are owned by the same parent company.
FROM PSYCHOPHARMACOLOGY UPDATE
Sleep time ‘sweet spot’ to slow cognitive decline identified?
In a longitudinal study, investigators found older adults who slept less than 4.5 hours or more than 6.5 hours a night reported significant cognitive decline over time, but cognitive scores for those with sleep duration in between that range remained stable.
“This really suggests that there’s this middle range, a ‘sweet spot,’ where your sleep is really optimal,” lead author Brendan Lucey, MD, MSCI, associate professor of neurology and director of the Washington University Sleep Medicine Center, St. Louis, said in an interview.
The study, published online Oct. 20, 2021, in the journal Brain, is part of a growing body of research that seeks to determine if sleep can be used as a marker of Alzheimer’s disease progression.
A complex relationship
Studies suggest a strong relationship between sleep patterns and Alzheimer’s disease, which affects nearly 6 million Americans. The challenge, Dr. Lucey said, is unwinding the complex links between sleep, AD, and cognitive function.
An earlier study by Dr. Lucey and colleagues found that poor sleep quality is associated with early signs of AD, and a report published in September found that elderly people who slept less than 6 hours a night had a greater burden of amyloid-beta, a hallmark sign of AD.
For this new study, researchers monitored sleep-wake activity over 4-6 nights in 100 participants who underwent annual cognitive assessments and clinical studies, including APOE genotyping, as part of a longitudinal study at the Knight Alzheimer Disease Research Center at Washington University.
Participants also provided cerebrospinal fluid (CSF) total tau and amyloid-beta 42 and wore a small EEG device on their forehead while they slept.
The majority of participants had a clinical dementia rating (CDR) score of 0, indicating no cognitive impairment. Twelve individuals had a CDR greater than 0, with most reporting mild cognitive impairment.
As expected, CSF analysis showed greater evidence of AD pathology in those with a baseline CDR greater than 0.
Changes in cognitive function were measured using a Preclinical Alzheimer Cognitive Composite (PACC) score, a composite of results from a neuropsychological testing battery that included the Free and Cued Selective Reminding Test, the Logical Memory Delayed Recall Test from the Wechsler Memory Scale–Revised, the Digit Symbol Substitution Test from the Wechsler Adult Intelligence Scale–Revised, and the Mini-Mental State Examination.
Researchers found an upside-down U-shaped relationship between PACC scores and sleep duration, with dramatic cognitive decline in those who slept less than 4.5 hours or more than 6.5 hours a night (P < .001 for both).
The U-shaped relationship was also found with measures of sleep phases, including time spent in rapid eye movement and in non-REM sleep (P < .001 for both).
The findings persisted even after controlling for confounders that can affect sleep and cognition, such as age, CSF total tau/amyloid-beta 42 ratio, apo E four-allele carrier status, years of education, and sex.
Understanding how sleep changes at different stages of AD could help researchers determine if sleep can be used as a marker of disease progression, Dr. Lucey said. That could lead to interventions to slow that process.
“We’re not at the point yet where we can say that we need to monitor someone’s sleep time and then do an intervention to see if it would improve their risk for cognitive decline,” said Dr. Lucey, who plans to repeat this sleep study with the same cohort to track changes in sleep patterns and cognitive function over time. “But that’s a question I’m very excited to try to answer.”
A component of cognitive health
Commenting on the findings for this news organization, Heather Snyder, PhD, vice president of medical and scientific relations for the Alzheimer’s Association, noted that the study adds to a body of evidence linking sleep and cognition, especially how sleep quality can optimize brain function.
“We’ve seen previous research that’s shown poor sleep contributes to dementia risk, as well as research showing sleep duration may play a role in cognition,” she said.
“We also need studies that look at sleep as an intervention for cognitive health,” Dr. Snyder said. “Sleep is an important aspect of our overall health. Clinicians should have conversations with their patients about sleep as part of standard discussions about their health habits and wellness.”
The study was funded by the National Institutes of Health, the American Sleep Medicine Foundation, the Roger and Paula Riney Fund, and the Daniel J. Brennan, MD Fund. Dr. Lucey consults for Merck and Eli Lilly. Dr. Snyder has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In a longitudinal study, investigators found older adults who slept less than 4.5 hours or more than 6.5 hours a night reported significant cognitive decline over time, but cognitive scores for those with sleep duration in between that range remained stable.
“This really suggests that there’s this middle range, a ‘sweet spot,’ where your sleep is really optimal,” lead author Brendan Lucey, MD, MSCI, associate professor of neurology and director of the Washington University Sleep Medicine Center, St. Louis, said in an interview.
The study, published online Oct. 20, 2021, in the journal Brain, is part of a growing body of research that seeks to determine if sleep can be used as a marker of Alzheimer’s disease progression.
A complex relationship
Studies suggest a strong relationship between sleep patterns and Alzheimer’s disease, which affects nearly 6 million Americans. The challenge, Dr. Lucey said, is unwinding the complex links between sleep, AD, and cognitive function.
An earlier study by Dr. Lucey and colleagues found that poor sleep quality is associated with early signs of AD, and a report published in September found that elderly people who slept less than 6 hours a night had a greater burden of amyloid-beta, a hallmark sign of AD.
For this new study, researchers monitored sleep-wake activity over 4-6 nights in 100 participants who underwent annual cognitive assessments and clinical studies, including APOE genotyping, as part of a longitudinal study at the Knight Alzheimer Disease Research Center at Washington University.
Participants also provided cerebrospinal fluid (CSF) total tau and amyloid-beta 42 and wore a small EEG device on their forehead while they slept.
The majority of participants had a clinical dementia rating (CDR) score of 0, indicating no cognitive impairment. Twelve individuals had a CDR greater than 0, with most reporting mild cognitive impairment.
As expected, CSF analysis showed greater evidence of AD pathology in those with a baseline CDR greater than 0.
Changes in cognitive function were measured using a Preclinical Alzheimer Cognitive Composite (PACC) score, a composite of results from a neuropsychological testing battery that included the Free and Cued Selective Reminding Test, the Logical Memory Delayed Recall Test from the Wechsler Memory Scale–Revised, the Digit Symbol Substitution Test from the Wechsler Adult Intelligence Scale–Revised, and the Mini-Mental State Examination.
Researchers found an upside-down U-shaped relationship between PACC scores and sleep duration, with dramatic cognitive decline in those who slept less than 4.5 hours or more than 6.5 hours a night (P < .001 for both).
The U-shaped relationship was also found with measures of sleep phases, including time spent in rapid eye movement and in non-REM sleep (P < .001 for both).
The findings persisted even after controlling for confounders that can affect sleep and cognition, such as age, CSF total tau/amyloid-beta 42 ratio, apo E four-allele carrier status, years of education, and sex.
Understanding how sleep changes at different stages of AD could help researchers determine if sleep can be used as a marker of disease progression, Dr. Lucey said. That could lead to interventions to slow that process.
“We’re not at the point yet where we can say that we need to monitor someone’s sleep time and then do an intervention to see if it would improve their risk for cognitive decline,” said Dr. Lucey, who plans to repeat this sleep study with the same cohort to track changes in sleep patterns and cognitive function over time. “But that’s a question I’m very excited to try to answer.”
A component of cognitive health
Commenting on the findings for this news organization, Heather Snyder, PhD, vice president of medical and scientific relations for the Alzheimer’s Association, noted that the study adds to a body of evidence linking sleep and cognition, especially how sleep quality can optimize brain function.
“We’ve seen previous research that’s shown poor sleep contributes to dementia risk, as well as research showing sleep duration may play a role in cognition,” she said.
“We also need studies that look at sleep as an intervention for cognitive health,” Dr. Snyder said. “Sleep is an important aspect of our overall health. Clinicians should have conversations with their patients about sleep as part of standard discussions about their health habits and wellness.”
The study was funded by the National Institutes of Health, the American Sleep Medicine Foundation, the Roger and Paula Riney Fund, and the Daniel J. Brennan, MD Fund. Dr. Lucey consults for Merck and Eli Lilly. Dr. Snyder has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In a longitudinal study, investigators found older adults who slept less than 4.5 hours or more than 6.5 hours a night reported significant cognitive decline over time, but cognitive scores for those with sleep duration in between that range remained stable.
“This really suggests that there’s this middle range, a ‘sweet spot,’ where your sleep is really optimal,” lead author Brendan Lucey, MD, MSCI, associate professor of neurology and director of the Washington University Sleep Medicine Center, St. Louis, said in an interview.
The study, published online Oct. 20, 2021, in the journal Brain, is part of a growing body of research that seeks to determine if sleep can be used as a marker of Alzheimer’s disease progression.
A complex relationship
Studies suggest a strong relationship between sleep patterns and Alzheimer’s disease, which affects nearly 6 million Americans. The challenge, Dr. Lucey said, is unwinding the complex links between sleep, AD, and cognitive function.
An earlier study by Dr. Lucey and colleagues found that poor sleep quality is associated with early signs of AD, and a report published in September found that elderly people who slept less than 6 hours a night had a greater burden of amyloid-beta, a hallmark sign of AD.
For this new study, researchers monitored sleep-wake activity over 4-6 nights in 100 participants who underwent annual cognitive assessments and clinical studies, including APOE genotyping, as part of a longitudinal study at the Knight Alzheimer Disease Research Center at Washington University.
Participants also provided cerebrospinal fluid (CSF) total tau and amyloid-beta 42 and wore a small EEG device on their forehead while they slept.
The majority of participants had a clinical dementia rating (CDR) score of 0, indicating no cognitive impairment. Twelve individuals had a CDR greater than 0, with most reporting mild cognitive impairment.
As expected, CSF analysis showed greater evidence of AD pathology in those with a baseline CDR greater than 0.
Changes in cognitive function were measured using a Preclinical Alzheimer Cognitive Composite (PACC) score, a composite of results from a neuropsychological testing battery that included the Free and Cued Selective Reminding Test, the Logical Memory Delayed Recall Test from the Wechsler Memory Scale–Revised, the Digit Symbol Substitution Test from the Wechsler Adult Intelligence Scale–Revised, and the Mini-Mental State Examination.
Researchers found an upside-down U-shaped relationship between PACC scores and sleep duration, with dramatic cognitive decline in those who slept less than 4.5 hours or more than 6.5 hours a night (P < .001 for both).
The U-shaped relationship was also found with measures of sleep phases, including time spent in rapid eye movement and in non-REM sleep (P < .001 for both).
The findings persisted even after controlling for confounders that can affect sleep and cognition, such as age, CSF total tau/amyloid-beta 42 ratio, apo E four-allele carrier status, years of education, and sex.
Understanding how sleep changes at different stages of AD could help researchers determine if sleep can be used as a marker of disease progression, Dr. Lucey said. That could lead to interventions to slow that process.
“We’re not at the point yet where we can say that we need to monitor someone’s sleep time and then do an intervention to see if it would improve their risk for cognitive decline,” said Dr. Lucey, who plans to repeat this sleep study with the same cohort to track changes in sleep patterns and cognitive function over time. “But that’s a question I’m very excited to try to answer.”
A component of cognitive health
Commenting on the findings for this news organization, Heather Snyder, PhD, vice president of medical and scientific relations for the Alzheimer’s Association, noted that the study adds to a body of evidence linking sleep and cognition, especially how sleep quality can optimize brain function.
“We’ve seen previous research that’s shown poor sleep contributes to dementia risk, as well as research showing sleep duration may play a role in cognition,” she said.
“We also need studies that look at sleep as an intervention for cognitive health,” Dr. Snyder said. “Sleep is an important aspect of our overall health. Clinicians should have conversations with their patients about sleep as part of standard discussions about their health habits and wellness.”
The study was funded by the National Institutes of Health, the American Sleep Medicine Foundation, the Roger and Paula Riney Fund, and the Daniel J. Brennan, MD Fund. Dr. Lucey consults for Merck and Eli Lilly. Dr. Snyder has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Sleep time ‘sweet spot’ to slow cognitive decline identified?
In a longitudinal study, investigators found older adults who slept less than 4.5 hours or more than 6.5 hours a night reported significant cognitive decline over time, but cognitive scores for those with sleep duration in between that range remained stable.
“This really suggests that there’s this middle range, a ‘sweet spot,’ where your sleep is really optimal,” said lead author Brendan Lucey, MD, MSCI, associate professor of neurology and director of the Washington University Sleep Medicine Center, St. Louis.
The study, published online Oct. 20 in Brain, is part of a growing body of research that seeks to determine if sleep can be used as a marker of Alzheimer’s disease progression.
A complex relationship
Studies suggest a strong relationship between sleep patterns and Alzheimer’s disease, which affects nearly 6 million Americans. The challenge, Dr. Lucey said, is unwinding the complex links between sleep, Alzheimer’s disease, and cognitive function.
An earlier study by Dr. Lucey and colleagues found that poor sleep quality is associated with early signs of Alzheimer’s disease, and a report published in September found that elderly people who slept less than 6 hours a night had a greater burden of amyloid beta, a hallmark sign of Alzheimer’s disease.
For this new study, researchers monitored sleep-wake activity over 4-6 nights in 100 participants who underwent annual cognitive assessments and clinical studies, including APOE genotyping, as part of a longitudinal study at the Knight Alzheimer Disease Research Center at Washington University. Participants also provided cerebrospinal fluid (CSF) total tau and amyloid-beta42 and wore a small EEG device on their forehead while they slept.
The majority of participants had a clinical dementia rating (CDR) score of 0, indicating no cognitive impairment. Twelve individuals had a CDR >0, with most reporting mild cognitive impairment.
As expected, CSF analysis showed greater evidence of Alzheimer’s disease pathology in those with a baseline CDR greater than 0.
Changes in cognitive function were measured using a Preclinical Alzheimer Cognitive Composite (PACC) score, a composite of results from a neuropsychological testing battery that included the Free and Cued Selective Reminding Test, the Logical Memory Delayed Recall Test from the Wechsler Memory Scale-Revised, the Digit Symbol Substitution Test from the Wechsler Adult Intelligence Scale-Revised, and the Mini-Mental State Examination.
Researchers found an upside-down U-shaped relationship between PACC scores and sleep duration, with dramatic cognitive decline in those who slept less than 4.5 hours or more than 6.5 hours a night (P < .001 for both). The U-shaped relationship was also found with measures of sleep phases, including time spent in rapid eye movement and in non-REM sleep (P < .001 for both).
The findings persisted even after controlling for confounders that can affect sleep and cognition, such as age, CSF total tau/amyloid-beta-42 ratio, APOE ε4 allele carrier status, years of education, and sex.
Understanding how sleep changes at different stages of Alzheimer’s disease could help researchers determine if sleep can be used as a marker of disease progression, Dr. Lucey said. That could lead to interventions to slow that process.
“We’re not at the point yet where we can say that we need to monitor someone’s sleep time and then do an intervention to see if it would improve their risk for cognitive decline,” said Dr. Lucey, who plans to repeat this sleep study with the same cohort to track changes in sleep patterns and cognitive function over time. “But that’s a question I’m very excited to try to answer.”
A component of cognitive health
Commenting on the findings, Heather Snyder, PhD, vice president of medical and scientific relations for the Alzheimer’s Association, noted that the study adds to a body of evidence linking sleep and cognition, especially how sleep quality can optimize brain function.
“We’ve seen previous research that’s shown poor sleep contributes to dementia risk, as well as research showing sleep duration may play a role in cognition,” she said.
“We also need studies that look at sleep as an intervention for cognitive health,” Dr. Snyder said. “Sleep is an important aspect of our overall health. Clinicians should have conversations with their patients about sleep as part of standard discussions about their health habits and wellness.”
The study was funded by the National Institutes of Health, the American Sleep Medicine Foundation, the Roger and Paula Riney Fund, and the Daniel J. Brennan, MD Fund. Dr. Lucey consults for Merck and Eli Lilly. Dr. Snyder has disclosed no relevant financial relationships. Full disclosures are included in the original article.
A version of this article first appeared on Medscape.com.
In a longitudinal study, investigators found older adults who slept less than 4.5 hours or more than 6.5 hours a night reported significant cognitive decline over time, but cognitive scores for those with sleep duration in between that range remained stable.
“This really suggests that there’s this middle range, a ‘sweet spot,’ where your sleep is really optimal,” said lead author Brendan Lucey, MD, MSCI, associate professor of neurology and director of the Washington University Sleep Medicine Center, St. Louis.
The study, published online Oct. 20 in Brain, is part of a growing body of research that seeks to determine if sleep can be used as a marker of Alzheimer’s disease progression.
A complex relationship
Studies suggest a strong relationship between sleep patterns and Alzheimer’s disease, which affects nearly 6 million Americans. The challenge, Dr. Lucey said, is unwinding the complex links between sleep, Alzheimer’s disease, and cognitive function.
An earlier study by Dr. Lucey and colleagues found that poor sleep quality is associated with early signs of Alzheimer’s disease, and a report published in September found that elderly people who slept less than 6 hours a night had a greater burden of amyloid beta, a hallmark sign of Alzheimer’s disease.
For this new study, researchers monitored sleep-wake activity over 4-6 nights in 100 participants who underwent annual cognitive assessments and clinical studies, including APOE genotyping, as part of a longitudinal study at the Knight Alzheimer Disease Research Center at Washington University. Participants also provided cerebrospinal fluid (CSF) total tau and amyloid-beta42 and wore a small EEG device on their forehead while they slept.
The majority of participants had a clinical dementia rating (CDR) score of 0, indicating no cognitive impairment. Twelve individuals had a CDR >0, with most reporting mild cognitive impairment.
As expected, CSF analysis showed greater evidence of Alzheimer’s disease pathology in those with a baseline CDR greater than 0.
Changes in cognitive function were measured using a Preclinical Alzheimer Cognitive Composite (PACC) score, a composite of results from a neuropsychological testing battery that included the Free and Cued Selective Reminding Test, the Logical Memory Delayed Recall Test from the Wechsler Memory Scale-Revised, the Digit Symbol Substitution Test from the Wechsler Adult Intelligence Scale-Revised, and the Mini-Mental State Examination.
Researchers found an upside-down U-shaped relationship between PACC scores and sleep duration, with dramatic cognitive decline in those who slept less than 4.5 hours or more than 6.5 hours a night (P < .001 for both). The U-shaped relationship was also found with measures of sleep phases, including time spent in rapid eye movement and in non-REM sleep (P < .001 for both).
The findings persisted even after controlling for confounders that can affect sleep and cognition, such as age, CSF total tau/amyloid-beta-42 ratio, APOE ε4 allele carrier status, years of education, and sex.
Understanding how sleep changes at different stages of Alzheimer’s disease could help researchers determine if sleep can be used as a marker of disease progression, Dr. Lucey said. That could lead to interventions to slow that process.
“We’re not at the point yet where we can say that we need to monitor someone’s sleep time and then do an intervention to see if it would improve their risk for cognitive decline,” said Dr. Lucey, who plans to repeat this sleep study with the same cohort to track changes in sleep patterns and cognitive function over time. “But that’s a question I’m very excited to try to answer.”
A component of cognitive health
Commenting on the findings, Heather Snyder, PhD, vice president of medical and scientific relations for the Alzheimer’s Association, noted that the study adds to a body of evidence linking sleep and cognition, especially how sleep quality can optimize brain function.
“We’ve seen previous research that’s shown poor sleep contributes to dementia risk, as well as research showing sleep duration may play a role in cognition,” she said.
“We also need studies that look at sleep as an intervention for cognitive health,” Dr. Snyder said. “Sleep is an important aspect of our overall health. Clinicians should have conversations with their patients about sleep as part of standard discussions about their health habits and wellness.”
The study was funded by the National Institutes of Health, the American Sleep Medicine Foundation, the Roger and Paula Riney Fund, and the Daniel J. Brennan, MD Fund. Dr. Lucey consults for Merck and Eli Lilly. Dr. Snyder has disclosed no relevant financial relationships. Full disclosures are included in the original article.
A version of this article first appeared on Medscape.com.
In a longitudinal study, investigators found older adults who slept less than 4.5 hours or more than 6.5 hours a night reported significant cognitive decline over time, but cognitive scores for those with sleep duration in between that range remained stable.
“This really suggests that there’s this middle range, a ‘sweet spot,’ where your sleep is really optimal,” said lead author Brendan Lucey, MD, MSCI, associate professor of neurology and director of the Washington University Sleep Medicine Center, St. Louis.
The study, published online Oct. 20 in Brain, is part of a growing body of research that seeks to determine if sleep can be used as a marker of Alzheimer’s disease progression.
A complex relationship
Studies suggest a strong relationship between sleep patterns and Alzheimer’s disease, which affects nearly 6 million Americans. The challenge, Dr. Lucey said, is unwinding the complex links between sleep, Alzheimer’s disease, and cognitive function.
An earlier study by Dr. Lucey and colleagues found that poor sleep quality is associated with early signs of Alzheimer’s disease, and a report published in September found that elderly people who slept less than 6 hours a night had a greater burden of amyloid beta, a hallmark sign of Alzheimer’s disease.
For this new study, researchers monitored sleep-wake activity over 4-6 nights in 100 participants who underwent annual cognitive assessments and clinical studies, including APOE genotyping, as part of a longitudinal study at the Knight Alzheimer Disease Research Center at Washington University. Participants also provided cerebrospinal fluid (CSF) total tau and amyloid-beta42 and wore a small EEG device on their forehead while they slept.
The majority of participants had a clinical dementia rating (CDR) score of 0, indicating no cognitive impairment. Twelve individuals had a CDR >0, with most reporting mild cognitive impairment.
As expected, CSF analysis showed greater evidence of Alzheimer’s disease pathology in those with a baseline CDR greater than 0.
Changes in cognitive function were measured using a Preclinical Alzheimer Cognitive Composite (PACC) score, a composite of results from a neuropsychological testing battery that included the Free and Cued Selective Reminding Test, the Logical Memory Delayed Recall Test from the Wechsler Memory Scale-Revised, the Digit Symbol Substitution Test from the Wechsler Adult Intelligence Scale-Revised, and the Mini-Mental State Examination.
Researchers found an upside-down U-shaped relationship between PACC scores and sleep duration, with dramatic cognitive decline in those who slept less than 4.5 hours or more than 6.5 hours a night (P < .001 for both). The U-shaped relationship was also found with measures of sleep phases, including time spent in rapid eye movement and in non-REM sleep (P < .001 for both).
The findings persisted even after controlling for confounders that can affect sleep and cognition, such as age, CSF total tau/amyloid-beta-42 ratio, APOE ε4 allele carrier status, years of education, and sex.
Understanding how sleep changes at different stages of Alzheimer’s disease could help researchers determine if sleep can be used as a marker of disease progression, Dr. Lucey said. That could lead to interventions to slow that process.
“We’re not at the point yet where we can say that we need to monitor someone’s sleep time and then do an intervention to see if it would improve their risk for cognitive decline,” said Dr. Lucey, who plans to repeat this sleep study with the same cohort to track changes in sleep patterns and cognitive function over time. “But that’s a question I’m very excited to try to answer.”
A component of cognitive health
Commenting on the findings, Heather Snyder, PhD, vice president of medical and scientific relations for the Alzheimer’s Association, noted that the study adds to a body of evidence linking sleep and cognition, especially how sleep quality can optimize brain function.
“We’ve seen previous research that’s shown poor sleep contributes to dementia risk, as well as research showing sleep duration may play a role in cognition,” she said.
“We also need studies that look at sleep as an intervention for cognitive health,” Dr. Snyder said. “Sleep is an important aspect of our overall health. Clinicians should have conversations with their patients about sleep as part of standard discussions about their health habits and wellness.”
The study was funded by the National Institutes of Health, the American Sleep Medicine Foundation, the Roger and Paula Riney Fund, and the Daniel J. Brennan, MD Fund. Dr. Lucey consults for Merck and Eli Lilly. Dr. Snyder has disclosed no relevant financial relationships. Full disclosures are included in the original article.
A version of this article first appeared on Medscape.com.
From Brain
Novel light therapy helmet boosts brain function
Near-infrared light delivered to the brain using a specially designed helmet appears to improve memory, motor function, and processing skills in cognitively healthy older adults, in new findings that suggest potential benefit in patients with dementia.
Studies in animals and people have shown “many positive effects” with near-infrared transcranial photobiomodulation therapy (PBM-T), study investigator Paul Chazot, PhD, department of biosciences, Durham University, United Kingdom, told this news organization.
For example, PBM-T has been shown to increase blood circulation (which keeps the brain well oxygenated), boost mitochondria function in neurons, protect neurons from oxidative stress, and help maintain neuronal connectivity, Dr. Chazot explained.
PBM-T has also been shown to reduce amyloid and phosphorylated tau load, pathological signs of Alzheimer’s disease.
“All these in combination improve memory performance and mobility,” Dr. Chazot said.
The study was published online October 18 in Photobiomodulation, Photomedicine and Laser Surgery.
Promising early data
In the study, 14 healthy adults, aged 45 to 70 years, received 6 minutes of transcranial PBM-T twice daily at a wavelength of 1,068 nanometers over 4 weeks. PBM-T was delivered via a helmet that comprised 14 air-cooled light emitting diode panel arrays. A control group of 13 adults used a sham PBM-T helmet.
Before and after active and sham treatment, all participants completed the automated neuropsychological assessment metrics (ANAM) – a computer-based tool designed to detect speed and accuracy of attention, memory, and thinking ability.
According to the research team, compared with sham PBM-T, those receiving active PBM-T showed significant improvement in motor function (finger tapping), working memory, delayed memory, and brain processing speed, the research team reports. No adverse effects were reported.
“This study complements our other recent studies, which showed improvement in memory performance with no obvious side effects,” said Dr. Chazot.
“While this is a pilot study and more research is needed, there are promising indications that therapy involving infrared light might also be beneficial for people living with dementia, and this is worth exploring,” Dr. Chazot added in a news release.
The PBM-T helmet was devised by first author Gordon Dougal, MBChB, of Maculume in the U.K., and a general practitioner based in Durham.
A recent study by Mr. Dougal, Dr. Chazot, and collaborators in the United States provides early evidence that PBM-T can improve memory in adults with dementia.
In that study, 39 patients received 6 minutes of PBM-T twice a day for 8 weeks, alongside a control group of 17 patients who received sham PBM-T.
After 8 weeks, there was about a 20% improvement in Mini-Mental State Exam (MMSE) scores in the active PBM-T group compared with roughly a 6% improvement in the control group, the researchers report in the journal Cureus.
More research needed
Reached for comment, Rebecca Edelmayer, PhD, Alzheimer’s Association senior director of scientific engagement, said using light to stimulate the brain is “an emerging technology.”
“However, ,” Dr. Edelmayer told this news organization.
“That being said, we’re starting to see companies looking at similar, noninvasive methods of stimulating the brain. For example, brain stimulation devices have been applied to other neurodegenerative diseases like Parkinson’s to try to prevent degeneration of brain cells,” Dr. Edelmayer noted.
She said more research is needed to understand how photobiomodulation might be used as a therapy or prevention for cognitive decline and dementia.
“Specifically, we need to understand what parts of the brain need to be targeted and at what point(s) in the disease course this treatment would be most impactful. If proven to be effective, this could possibly be part of an approach that’s combined with other treatments, like drugs and lifestyle interventions,” said Dr. Edelmayer.
The Alzheimer’s Association is funding a number of projects looking at noninvasive treatments for Alzheimer’s disease, including two clinical trials looking at deep brain stimulation and photobiomodulation.
Maculume provided funding for the study. Mr. Dougal is a majority shareholder in the company, which manufactures the helmet device used in the study. Dr. Chazot, study co-authors, and Dr. Edelmayer have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Near-infrared light delivered to the brain using a specially designed helmet appears to improve memory, motor function, and processing skills in cognitively healthy older adults, in new findings that suggest potential benefit in patients with dementia.
Studies in animals and people have shown “many positive effects” with near-infrared transcranial photobiomodulation therapy (PBM-T), study investigator Paul Chazot, PhD, department of biosciences, Durham University, United Kingdom, told this news organization.
For example, PBM-T has been shown to increase blood circulation (which keeps the brain well oxygenated), boost mitochondria function in neurons, protect neurons from oxidative stress, and help maintain neuronal connectivity, Dr. Chazot explained.
PBM-T has also been shown to reduce amyloid and phosphorylated tau load, pathological signs of Alzheimer’s disease.
“All these in combination improve memory performance and mobility,” Dr. Chazot said.
The study was published online October 18 in Photobiomodulation, Photomedicine and Laser Surgery.
Promising early data
In the study, 14 healthy adults, aged 45 to 70 years, received 6 minutes of transcranial PBM-T twice daily at a wavelength of 1,068 nanometers over 4 weeks. PBM-T was delivered via a helmet that comprised 14 air-cooled light emitting diode panel arrays. A control group of 13 adults used a sham PBM-T helmet.
Before and after active and sham treatment, all participants completed the automated neuropsychological assessment metrics (ANAM) – a computer-based tool designed to detect speed and accuracy of attention, memory, and thinking ability.
According to the research team, compared with sham PBM-T, those receiving active PBM-T showed significant improvement in motor function (finger tapping), working memory, delayed memory, and brain processing speed, the research team reports. No adverse effects were reported.
“This study complements our other recent studies, which showed improvement in memory performance with no obvious side effects,” said Dr. Chazot.
“While this is a pilot study and more research is needed, there are promising indications that therapy involving infrared light might also be beneficial for people living with dementia, and this is worth exploring,” Dr. Chazot added in a news release.
The PBM-T helmet was devised by first author Gordon Dougal, MBChB, of Maculume in the U.K., and a general practitioner based in Durham.
A recent study by Mr. Dougal, Dr. Chazot, and collaborators in the United States provides early evidence that PBM-T can improve memory in adults with dementia.
In that study, 39 patients received 6 minutes of PBM-T twice a day for 8 weeks, alongside a control group of 17 patients who received sham PBM-T.
After 8 weeks, there was about a 20% improvement in Mini-Mental State Exam (MMSE) scores in the active PBM-T group compared with roughly a 6% improvement in the control group, the researchers report in the journal Cureus.
More research needed
Reached for comment, Rebecca Edelmayer, PhD, Alzheimer’s Association senior director of scientific engagement, said using light to stimulate the brain is “an emerging technology.”
“However, ,” Dr. Edelmayer told this news organization.
“That being said, we’re starting to see companies looking at similar, noninvasive methods of stimulating the brain. For example, brain stimulation devices have been applied to other neurodegenerative diseases like Parkinson’s to try to prevent degeneration of brain cells,” Dr. Edelmayer noted.
She said more research is needed to understand how photobiomodulation might be used as a therapy or prevention for cognitive decline and dementia.
“Specifically, we need to understand what parts of the brain need to be targeted and at what point(s) in the disease course this treatment would be most impactful. If proven to be effective, this could possibly be part of an approach that’s combined with other treatments, like drugs and lifestyle interventions,” said Dr. Edelmayer.
The Alzheimer’s Association is funding a number of projects looking at noninvasive treatments for Alzheimer’s disease, including two clinical trials looking at deep brain stimulation and photobiomodulation.
Maculume provided funding for the study. Mr. Dougal is a majority shareholder in the company, which manufactures the helmet device used in the study. Dr. Chazot, study co-authors, and Dr. Edelmayer have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Near-infrared light delivered to the brain using a specially designed helmet appears to improve memory, motor function, and processing skills in cognitively healthy older adults, in new findings that suggest potential benefit in patients with dementia.
Studies in animals and people have shown “many positive effects” with near-infrared transcranial photobiomodulation therapy (PBM-T), study investigator Paul Chazot, PhD, department of biosciences, Durham University, United Kingdom, told this news organization.
For example, PBM-T has been shown to increase blood circulation (which keeps the brain well oxygenated), boost mitochondria function in neurons, protect neurons from oxidative stress, and help maintain neuronal connectivity, Dr. Chazot explained.
PBM-T has also been shown to reduce amyloid and phosphorylated tau load, pathological signs of Alzheimer’s disease.
“All these in combination improve memory performance and mobility,” Dr. Chazot said.
The study was published online October 18 in Photobiomodulation, Photomedicine and Laser Surgery.
Promising early data
In the study, 14 healthy adults, aged 45 to 70 years, received 6 minutes of transcranial PBM-T twice daily at a wavelength of 1,068 nanometers over 4 weeks. PBM-T was delivered via a helmet that comprised 14 air-cooled light emitting diode panel arrays. A control group of 13 adults used a sham PBM-T helmet.
Before and after active and sham treatment, all participants completed the automated neuropsychological assessment metrics (ANAM) – a computer-based tool designed to detect speed and accuracy of attention, memory, and thinking ability.
According to the research team, compared with sham PBM-T, those receiving active PBM-T showed significant improvement in motor function (finger tapping), working memory, delayed memory, and brain processing speed, the research team reports. No adverse effects were reported.
“This study complements our other recent studies, which showed improvement in memory performance with no obvious side effects,” said Dr. Chazot.
“While this is a pilot study and more research is needed, there are promising indications that therapy involving infrared light might also be beneficial for people living with dementia, and this is worth exploring,” Dr. Chazot added in a news release.
The PBM-T helmet was devised by first author Gordon Dougal, MBChB, of Maculume in the U.K., and a general practitioner based in Durham.
A recent study by Mr. Dougal, Dr. Chazot, and collaborators in the United States provides early evidence that PBM-T can improve memory in adults with dementia.
In that study, 39 patients received 6 minutes of PBM-T twice a day for 8 weeks, alongside a control group of 17 patients who received sham PBM-T.
After 8 weeks, there was about a 20% improvement in Mini-Mental State Exam (MMSE) scores in the active PBM-T group compared with roughly a 6% improvement in the control group, the researchers report in the journal Cureus.
More research needed
Reached for comment, Rebecca Edelmayer, PhD, Alzheimer’s Association senior director of scientific engagement, said using light to stimulate the brain is “an emerging technology.”
“However, ,” Dr. Edelmayer told this news organization.
“That being said, we’re starting to see companies looking at similar, noninvasive methods of stimulating the brain. For example, brain stimulation devices have been applied to other neurodegenerative diseases like Parkinson’s to try to prevent degeneration of brain cells,” Dr. Edelmayer noted.
She said more research is needed to understand how photobiomodulation might be used as a therapy or prevention for cognitive decline and dementia.
“Specifically, we need to understand what parts of the brain need to be targeted and at what point(s) in the disease course this treatment would be most impactful. If proven to be effective, this could possibly be part of an approach that’s combined with other treatments, like drugs and lifestyle interventions,” said Dr. Edelmayer.
The Alzheimer’s Association is funding a number of projects looking at noninvasive treatments for Alzheimer’s disease, including two clinical trials looking at deep brain stimulation and photobiomodulation.
Maculume provided funding for the study. Mr. Dougal is a majority shareholder in the company, which manufactures the helmet device used in the study. Dr. Chazot, study co-authors, and Dr. Edelmayer have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.