Alzheimer's & Cognition

Leading a healthy lifestyle, including regular exercise, eating fruits and vegetables, and minimal alcohol consumption, is associated with better cognitive function in older adults, new research showed.

The study, which combined longitudinal and cohort data with postmortem brain pathology reports, found that the association held even in those with Alzheimer’s disease (AD) pathology, suggesting that lifestyle factors may provide cognitive reserve and improve cognitive abilities in older age.

“While we must use caution in interpreting our findings, in part due to its cross-sectional design, these results support the role of lifestyle in providing cognitive reserve to maintain cognitive function in older adults despite the accumulation of common dementia-related brain pathologies,” Klodian Dhana, MD, of the Rush University Medical Center in Chicago, Illinois, and colleagues wrote.

The study was published online in JAMA Neurology.
 

Better Cognition

The study included 586 participants (71% female) who were followed from 1997 until 2022 as part of the Rush Memory and Aging Project longitudinal cohort study.

Investigators collected information on lifestyle and demographic factors at regular intervals, as well as information on diet, alcohol intake, and time spent participating in moderate or vigorous physical activity such as gardening, walking, calisthenics, biking, or swimming. Participants also received annual cognitive tests.

In later years, participants answered questions about whether they played card games or checkers, read, visited a museum, or did other cognitively stimulating activities.

Postmortem exams allowed the researchers to assess brain pathology (mean age at death, 91 years).

Participants were categorized as living a healthy lifestyle if they scored well in five categories: They exercised moderately or vigorously for 150 minutes per week, did not smoke, consumed one to two drinks per week, regularly played card games or did puzzles, and followed the Mediterranean-DASH Diet Intervention for Neurodegenerative Delay diet.

For every one-point increase in the healthy lifestyle score, there were 0.120 fewer units of beta-amyloid load in the brain and a 0.22 standardized unit higher score in cognitive performance (P < .001).

After adjusting for the beta-amyloid load, phosphorated tau tangle, or other dementia-related brain pathologies, the healthy lifestyle score remained independently associated with cognition (P < .001).

More than 88% of a person’s global cognition score was a “direct association of lifestyle,” investigators noted, leaving slightly less than 12% affected by the presence of beta-amyloid.

“The mechanistic link between lifestyle and cognition could be attributed in part to the antioxidant and anti-inflammatory capacities of each lifestyle factor (eg, nutrition and physical activity) and cognitive reserve (eg, cognitive activities) that contribute to less inflammation and oxidative stress,” the authors wrote.

Further studies are necessary, they added, especially research investigating the association of lifestyle factors with markers for inflammation to understand the mechanisms of how lifestyle is associated with better cognitive scores in old age.

Study limitations include the reliance on self-reported data because cognitive impairment could interfere with inaccurate reporting. In addition, the authors noted that cognitive abilities may affect adherence to lifestyle factors.
 

‘Important Evidence’

In an accompanying editorial, Yue Leng, MD, and Kristine Yaffe, MD, of the University of San Francisco in San Francisco, California, noted that the new study adds “important evidence” to the debate over modifiable risk factors and reduction of AD risk.

“These interesting results add strength to the concept that health and lifestyle factors are important strategies for prevention and suggest that several mechanisms may be at work,” they wrote, adding that the study is “one of the first to harness brain pathology to investigate these mechanisms and is a crucial step forward in addressing these important questions.”

Still, critical questions remain regarding the mechanistic pathways linking modifiable risk factors and cognitive aging, Drs. Leng and Yaffe wrote.

“There is an urgent need for more well-designed randomized controlled trials to pave the way for dementia risk reduction in the era of precision medicine,” they wrote. “These strategies should be offered in conjunction with AD medications, similar to the approach in cardiovascular disease prevention and treatment in which medications along with lifestyle strategies are the standard of care.”

The study was funded by the National Institute on Aging. Dr. Dhana reported grants paid to his institution from the Alzheimer’s Association. No other disclosures were reported.

A version of this article appeared on Medscape.com.

Leading a healthy lifestyle, including regular exercise, eating fruits and vegetables, and minimal alcohol consumption, is associated with better cognitive function in older adults, new research showed.

The study, which combined longitudinal and cohort data with postmortem brain pathology reports, found that the association held even in those with Alzheimer’s disease (AD) pathology, suggesting that lifestyle factors may provide cognitive reserve and improve cognitive abilities in older age.

“While we must use caution in interpreting our findings, in part due to its cross-sectional design, these results support the role of lifestyle in providing cognitive reserve to maintain cognitive function in older adults despite the accumulation of common dementia-related brain pathologies,” Klodian Dhana, MD, of the Rush University Medical Center in Chicago, Illinois, and colleagues wrote.

The study was published online in JAMA Neurology.
 

Better Cognition

The study included 586 participants (71% female) who were followed from 1997 until 2022 as part of the Rush Memory and Aging Project longitudinal cohort study.

Investigators collected information on lifestyle and demographic factors at regular intervals, as well as information on diet, alcohol intake, and time spent participating in moderate or vigorous physical activity such as gardening, walking, calisthenics, biking, or swimming. Participants also received annual cognitive tests.

In later years, participants answered questions about whether they played card games or checkers, read, visited a museum, or did other cognitively stimulating activities.

Postmortem exams allowed the researchers to assess brain pathology (mean age at death, 91 years).

Participants were categorized as living a healthy lifestyle if they scored well in five categories: They exercised moderately or vigorously for 150 minutes per week, did not smoke, consumed one to two drinks per week, regularly played card games or did puzzles, and followed the Mediterranean-DASH Diet Intervention for Neurodegenerative Delay diet.

For every one-point increase in the healthy lifestyle score, there were 0.120 fewer units of beta-amyloid load in the brain and a 0.22 standardized unit higher score in cognitive performance (P < .001).

After adjusting for the beta-amyloid load, phosphorated tau tangle, or other dementia-related brain pathologies, the healthy lifestyle score remained independently associated with cognition (P < .001).

More than 88% of a person’s global cognition score was a “direct association of lifestyle,” investigators noted, leaving slightly less than 12% affected by the presence of beta-amyloid.

“The mechanistic link between lifestyle and cognition could be attributed in part to the antioxidant and anti-inflammatory capacities of each lifestyle factor (eg, nutrition and physical activity) and cognitive reserve (eg, cognitive activities) that contribute to less inflammation and oxidative stress,” the authors wrote.

Further studies are necessary, they added, especially research investigating the association of lifestyle factors with markers for inflammation to understand the mechanisms of how lifestyle is associated with better cognitive scores in old age.

Study limitations include the reliance on self-reported data because cognitive impairment could interfere with inaccurate reporting. In addition, the authors noted that cognitive abilities may affect adherence to lifestyle factors.
 

‘Important Evidence’

In an accompanying editorial, Yue Leng, MD, and Kristine Yaffe, MD, of the University of San Francisco in San Francisco, California, noted that the new study adds “important evidence” to the debate over modifiable risk factors and reduction of AD risk.

“These interesting results add strength to the concept that health and lifestyle factors are important strategies for prevention and suggest that several mechanisms may be at work,” they wrote, adding that the study is “one of the first to harness brain pathology to investigate these mechanisms and is a crucial step forward in addressing these important questions.”

Still, critical questions remain regarding the mechanistic pathways linking modifiable risk factors and cognitive aging, Drs. Leng and Yaffe wrote.

“There is an urgent need for more well-designed randomized controlled trials to pave the way for dementia risk reduction in the era of precision medicine,” they wrote. “These strategies should be offered in conjunction with AD medications, similar to the approach in cardiovascular disease prevention and treatment in which medications along with lifestyle strategies are the standard of care.”

The study was funded by the National Institute on Aging. Dr. Dhana reported grants paid to his institution from the Alzheimer’s Association. No other disclosures were reported.

A version of this article appeared on Medscape.com.

Leading a healthy lifestyle, including regular exercise, eating fruits and vegetables, and minimal alcohol consumption, is associated with better cognitive function in older adults, new research showed.

The study, which combined longitudinal and cohort data with postmortem brain pathology reports, found that the association held even in those with Alzheimer’s disease (AD) pathology, suggesting that lifestyle factors may provide cognitive reserve and improve cognitive abilities in older age.

“While we must use caution in interpreting our findings, in part due to its cross-sectional design, these results support the role of lifestyle in providing cognitive reserve to maintain cognitive function in older adults despite the accumulation of common dementia-related brain pathologies,” Klodian Dhana, MD, of the Rush University Medical Center in Chicago, Illinois, and colleagues wrote.

The study was published online in JAMA Neurology.
 

Better Cognition

The study included 586 participants (71% female) who were followed from 1997 until 2022 as part of the Rush Memory and Aging Project longitudinal cohort study.

Investigators collected information on lifestyle and demographic factors at regular intervals, as well as information on diet, alcohol intake, and time spent participating in moderate or vigorous physical activity such as gardening, walking, calisthenics, biking, or swimming. Participants also received annual cognitive tests.

In later years, participants answered questions about whether they played card games or checkers, read, visited a museum, or did other cognitively stimulating activities.

Postmortem exams allowed the researchers to assess brain pathology (mean age at death, 91 years).

Participants were categorized as living a healthy lifestyle if they scored well in five categories: They exercised moderately or vigorously for 150 minutes per week, did not smoke, consumed one to two drinks per week, regularly played card games or did puzzles, and followed the Mediterranean-DASH Diet Intervention for Neurodegenerative Delay diet.

For every one-point increase in the healthy lifestyle score, there were 0.120 fewer units of beta-amyloid load in the brain and a 0.22 standardized unit higher score in cognitive performance (P < .001).

After adjusting for the beta-amyloid load, phosphorated tau tangle, or other dementia-related brain pathologies, the healthy lifestyle score remained independently associated with cognition (P < .001).

More than 88% of a person’s global cognition score was a “direct association of lifestyle,” investigators noted, leaving slightly less than 12% affected by the presence of beta-amyloid.

“The mechanistic link between lifestyle and cognition could be attributed in part to the antioxidant and anti-inflammatory capacities of each lifestyle factor (eg, nutrition and physical activity) and cognitive reserve (eg, cognitive activities) that contribute to less inflammation and oxidative stress,” the authors wrote.

Further studies are necessary, they added, especially research investigating the association of lifestyle factors with markers for inflammation to understand the mechanisms of how lifestyle is associated with better cognitive scores in old age.

Study limitations include the reliance on self-reported data because cognitive impairment could interfere with inaccurate reporting. In addition, the authors noted that cognitive abilities may affect adherence to lifestyle factors.
 

‘Important Evidence’

In an accompanying editorial, Yue Leng, MD, and Kristine Yaffe, MD, of the University of San Francisco in San Francisco, California, noted that the new study adds “important evidence” to the debate over modifiable risk factors and reduction of AD risk.

“These interesting results add strength to the concept that health and lifestyle factors are important strategies for prevention and suggest that several mechanisms may be at work,” they wrote, adding that the study is “one of the first to harness brain pathology to investigate these mechanisms and is a crucial step forward in addressing these important questions.”

Still, critical questions remain regarding the mechanistic pathways linking modifiable risk factors and cognitive aging, Drs. Leng and Yaffe wrote.

“There is an urgent need for more well-designed randomized controlled trials to pave the way for dementia risk reduction in the era of precision medicine,” they wrote. “These strategies should be offered in conjunction with AD medications, similar to the approach in cardiovascular disease prevention and treatment in which medications along with lifestyle strategies are the standard of care.”

The study was funded by the National Institute on Aging. Dr. Dhana reported grants paid to his institution from the Alzheimer’s Association. No other disclosures were reported.

A version of this article appeared on Medscape.com.

Men prescribed drugs to treat newly diagnosed erectile dysfunction (ED) are 18% less likely to develop Alzheimer’s disease (AD) during a 5-year follow-up period, new research shows. 

The study is the second in recent years to suggest an association between the use of phosphodiesterase type 5 inhibitors (PDE5Is) such as sildenafil (Viagra) or tadalafil (Cialis) and AD risk. The findings contradict those in a third study, reported by this news organization, that showed no link between the two. 

Although the research is interesting, outside experts noted that there is no evidence that the drugs can treat AD and urge caution when interpreting the findings. 

Investigators agree but believe that the results offer a direction for future studies and underscore the importance of investigating whether existing approved therapies can be repurposed to treat AD. 

“The positive findings from our large study in over 250,000 men is promising and can be used to enhance research capacity and knowledge, with a potential future impact on clinical use and public health policy,” senior author Ruth Brauer, PhD, of the University College London, told this news organization.

“However, before recommending PDE5I are used to reduce the risk of AD, more work is required to validate the findings of our work, particularly in a more generalizable population that includes women and men without erectile dysfunction,” she continued.

The findings were published online February 7 in Neurology.

Strong Association

The study drew on primary healthcare data from the United Kingdom and included 269,725 men (average age, 59 years) with newly diagnosed ED, 55% of whom had received prescriptions for PDE5Is. 

Participants were free from memory or cognitive issues when the study began and were followed for a median of 5.1 years. Investigators accounted for a range of potential AD risk factors, including smoking status, alcohol use, body mass index, hypertension, diabetes, depression, anxiety, and concomitant medication use.

During the study period, 749 in the PDE5I group were diagnosed with AD, corresponding to a rate of 8.1 cases per 10,000 person-years. Among those who did not take the drugs, 370 developed AD, corresponding to a rate of 9.7 cases per 10,000 person-years.

Overall, initiation of a PDE5I was associated with an 18% lower risk for AD (adjusted hazard ration [aHR], 0.82; 95% CI, 0.72-0.93) compared with those with no prescriptions. 

The association was stronger in people aged 70 years or older and those with a history of hypertension or diabetes. The greatest risk reduction was found in people with the most prescriptions during the study period. Those with 21-50 prescriptions had a 44% lower risk for AD (aHR, 0.56; 95% CI, 0.43-0.73) and those with more than 50 were 35% less likely to be diagnosed with AD (aHR, 0.65; 95% CI, 0.49-0.87).

There was no association with AD risk in individuals who received fewer than 20 prescriptions. 

Investigators also analyzed associations after introducing a 1- and 3-year lag period after cohort entry to address the latent period between AD onset and diagnosis. The primary findings held with a 1-year lag period but lost significance with the inclusion of a 3-year lag period.

In subgroup analyses, investigators found evidence of reduced AD risk in those who received prescriptions for sildenafil (aHR, 0.81; 95% CI, 0.71-0.93), but there was no evidence for reduced risk compared with nonusers in those who received tadalafil and vardenafil.

Lower AD risk was found in patients with hypertension, diabetes, and in men aged 70 years or older, but there was no association in younger men or those with no history of hypertension or diabetes. 

Although investigators controlled for a wide range of potential risk factors, Dr. Brauer noted that unmeasured confounders such as physical and sexual activity, which were not tracked and may predict PDE5I exposure, may have affected the results. 

Interpret With Caution

Commenting on the findings, Ozama Ismail, PhD, Alzheimer’s Association director of scientific programs, noted that in addition to the limitations cited by the study authors, AD diagnoses were not made with the “gold standard” testing that typically includes imaging biomarkers and postmortem assessments. 

“While this study is interesting and adds to a potential association, there is no evidence that these drugs are able to treat Alzheimer’s disease,” said Dr. Brauer, who was not part of the current study. 

“People should not use over-the-counter phosphodiesterase type 5 inhibitors for prevention of Alzheimer’s or other dementias based on this very preliminary finding. Always consult with your physician before starting or changing your medications,” he cautioned.

However, Dr. Ismael added that the study does highlight a potential new avenue for drug repurposing. 

“Repurposing of existing, already-approved treatments can be a valuable part of drug development because, through already-completed testing, we know much about their safety and side effects,” which can decrease cost and time needed for studies, he said. 

“When considering repurposing an existing drug to an Alzheimer’s treatment, however, it is often important to conduct new studies over longer periods of time and in older people that reflect the diversity of individuals living with Alzheimer’s disease,” Dr. Ismael said.

Randomized Trials Needed

Dr. Brauer agreed, offering that such a trial should also include people with mild cognitive impairment and measure the effects of PDE5Is given in predefined doses plus an acetylcholinesterase inhibitor or placebo plus an acetylcholinesterase inhibitor. 

“The primary outcome would be the change in baseline cognitive function,” she said. “This approach would provide a comprehensive understanding of the potential therapeutic benefits of PDE5I and AD.”

Studies are also needed to better understand the mechanisms by which these drugs might influence AD risk, Sevil Yasar, MD, PhD, and Lolita Nidadavolu, MD, PhD, from the Division of Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine, Baltimore, noted in an accompanying editorial.

The strong association between PDE5I use and AD risk in people with a history of hypertension or diabetes suggests “a potential neuroprotective effect through a vascular pathway,” they wrote.

In vitro studies on the role of inflammation and clearance of beta-amyloid could strengthen findings from studies like this one, and in vivo studies could help explain the mechanisms behind PDE5I use and lower AD risk, Dr. Yasar and Dr. Nidadavolu noted. 

“In the end, however, further observational studies exploring mechanisms will not prove a causal association,” they wrote. “A well-designed randomized controlled trial is needed before PDE5I drugs can be prescribed for AD prevention.”

The study was unfunded. The study and editorial authors and Dr. Ismail report no relevant financial conflicts. 
 

A version of this article appeared on Medscape.com.

Men prescribed drugs to treat newly diagnosed erectile dysfunction (ED) are 18% less likely to develop Alzheimer’s disease (AD) during a 5-year follow-up period, new research shows. 

The study is the second in recent years to suggest an association between the use of phosphodiesterase type 5 inhibitors (PDE5Is) such as sildenafil (Viagra) or tadalafil (Cialis) and AD risk. The findings contradict those in a third study, reported by this news organization, that showed no link between the two. 

Although the research is interesting, outside experts noted that there is no evidence that the drugs can treat AD and urge caution when interpreting the findings. 

Investigators agree but believe that the results offer a direction for future studies and underscore the importance of investigating whether existing approved therapies can be repurposed to treat AD. 

“The positive findings from our large study in over 250,000 men is promising and can be used to enhance research capacity and knowledge, with a potential future impact on clinical use and public health policy,” senior author Ruth Brauer, PhD, of the University College London, told this news organization.

“However, before recommending PDE5I are used to reduce the risk of AD, more work is required to validate the findings of our work, particularly in a more generalizable population that includes women and men without erectile dysfunction,” she continued.

The findings were published online February 7 in Neurology.

Strong Association

The study drew on primary healthcare data from the United Kingdom and included 269,725 men (average age, 59 years) with newly diagnosed ED, 55% of whom had received prescriptions for PDE5Is. 

Participants were free from memory or cognitive issues when the study began and were followed for a median of 5.1 years. Investigators accounted for a range of potential AD risk factors, including smoking status, alcohol use, body mass index, hypertension, diabetes, depression, anxiety, and concomitant medication use.

During the study period, 749 in the PDE5I group were diagnosed with AD, corresponding to a rate of 8.1 cases per 10,000 person-years. Among those who did not take the drugs, 370 developed AD, corresponding to a rate of 9.7 cases per 10,000 person-years.

Overall, initiation of a PDE5I was associated with an 18% lower risk for AD (adjusted hazard ration [aHR], 0.82; 95% CI, 0.72-0.93) compared with those with no prescriptions. 

The association was stronger in people aged 70 years or older and those with a history of hypertension or diabetes. The greatest risk reduction was found in people with the most prescriptions during the study period. Those with 21-50 prescriptions had a 44% lower risk for AD (aHR, 0.56; 95% CI, 0.43-0.73) and those with more than 50 were 35% less likely to be diagnosed with AD (aHR, 0.65; 95% CI, 0.49-0.87).

There was no association with AD risk in individuals who received fewer than 20 prescriptions. 

Investigators also analyzed associations after introducing a 1- and 3-year lag period after cohort entry to address the latent period between AD onset and diagnosis. The primary findings held with a 1-year lag period but lost significance with the inclusion of a 3-year lag period.

In subgroup analyses, investigators found evidence of reduced AD risk in those who received prescriptions for sildenafil (aHR, 0.81; 95% CI, 0.71-0.93), but there was no evidence for reduced risk compared with nonusers in those who received tadalafil and vardenafil.

Lower AD risk was found in patients with hypertension, diabetes, and in men aged 70 years or older, but there was no association in younger men or those with no history of hypertension or diabetes. 

Although investigators controlled for a wide range of potential risk factors, Dr. Brauer noted that unmeasured confounders such as physical and sexual activity, which were not tracked and may predict PDE5I exposure, may have affected the results. 

Interpret With Caution

Commenting on the findings, Ozama Ismail, PhD, Alzheimer’s Association director of scientific programs, noted that in addition to the limitations cited by the study authors, AD diagnoses were not made with the “gold standard” testing that typically includes imaging biomarkers and postmortem assessments. 

“While this study is interesting and adds to a potential association, there is no evidence that these drugs are able to treat Alzheimer’s disease,” said Dr. Brauer, who was not part of the current study. 

“People should not use over-the-counter phosphodiesterase type 5 inhibitors for prevention of Alzheimer’s or other dementias based on this very preliminary finding. Always consult with your physician before starting or changing your medications,” he cautioned.

However, Dr. Ismael added that the study does highlight a potential new avenue for drug repurposing. 

“Repurposing of existing, already-approved treatments can be a valuable part of drug development because, through already-completed testing, we know much about their safety and side effects,” which can decrease cost and time needed for studies, he said. 

“When considering repurposing an existing drug to an Alzheimer’s treatment, however, it is often important to conduct new studies over longer periods of time and in older people that reflect the diversity of individuals living with Alzheimer’s disease,” Dr. Ismael said.

Randomized Trials Needed

Dr. Brauer agreed, offering that such a trial should also include people with mild cognitive impairment and measure the effects of PDE5Is given in predefined doses plus an acetylcholinesterase inhibitor or placebo plus an acetylcholinesterase inhibitor. 

“The primary outcome would be the change in baseline cognitive function,” she said. “This approach would provide a comprehensive understanding of the potential therapeutic benefits of PDE5I and AD.”

Studies are also needed to better understand the mechanisms by which these drugs might influence AD risk, Sevil Yasar, MD, PhD, and Lolita Nidadavolu, MD, PhD, from the Division of Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine, Baltimore, noted in an accompanying editorial.

The strong association between PDE5I use and AD risk in people with a history of hypertension or diabetes suggests “a potential neuroprotective effect through a vascular pathway,” they wrote.

In vitro studies on the role of inflammation and clearance of beta-amyloid could strengthen findings from studies like this one, and in vivo studies could help explain the mechanisms behind PDE5I use and lower AD risk, Dr. Yasar and Dr. Nidadavolu noted. 

“In the end, however, further observational studies exploring mechanisms will not prove a causal association,” they wrote. “A well-designed randomized controlled trial is needed before PDE5I drugs can be prescribed for AD prevention.”

The study was unfunded. The study and editorial authors and Dr. Ismail report no relevant financial conflicts. 
 

A version of this article appeared on Medscape.com.

Men prescribed drugs to treat newly diagnosed erectile dysfunction (ED) are 18% less likely to develop Alzheimer’s disease (AD) during a 5-year follow-up period, new research shows. 

The study is the second in recent years to suggest an association between the use of phosphodiesterase type 5 inhibitors (PDE5Is) such as sildenafil (Viagra) or tadalafil (Cialis) and AD risk. The findings contradict those in a third study, reported by this news organization, that showed no link between the two. 

Although the research is interesting, outside experts noted that there is no evidence that the drugs can treat AD and urge caution when interpreting the findings. 

Investigators agree but believe that the results offer a direction for future studies and underscore the importance of investigating whether existing approved therapies can be repurposed to treat AD. 

“The positive findings from our large study in over 250,000 men is promising and can be used to enhance research capacity and knowledge, with a potential future impact on clinical use and public health policy,” senior author Ruth Brauer, PhD, of the University College London, told this news organization.

“However, before recommending PDE5I are used to reduce the risk of AD, more work is required to validate the findings of our work, particularly in a more generalizable population that includes women and men without erectile dysfunction,” she continued.

The findings were published online February 7 in Neurology.

Strong Association

The study drew on primary healthcare data from the United Kingdom and included 269,725 men (average age, 59 years) with newly diagnosed ED, 55% of whom had received prescriptions for PDE5Is. 

Participants were free from memory or cognitive issues when the study began and were followed for a median of 5.1 years. Investigators accounted for a range of potential AD risk factors, including smoking status, alcohol use, body mass index, hypertension, diabetes, depression, anxiety, and concomitant medication use.

During the study period, 749 in the PDE5I group were diagnosed with AD, corresponding to a rate of 8.1 cases per 10,000 person-years. Among those who did not take the drugs, 370 developed AD, corresponding to a rate of 9.7 cases per 10,000 person-years.

Overall, initiation of a PDE5I was associated with an 18% lower risk for AD (adjusted hazard ration [aHR], 0.82; 95% CI, 0.72-0.93) compared with those with no prescriptions. 

The association was stronger in people aged 70 years or older and those with a history of hypertension or diabetes. The greatest risk reduction was found in people with the most prescriptions during the study period. Those with 21-50 prescriptions had a 44% lower risk for AD (aHR, 0.56; 95% CI, 0.43-0.73) and those with more than 50 were 35% less likely to be diagnosed with AD (aHR, 0.65; 95% CI, 0.49-0.87).

There was no association with AD risk in individuals who received fewer than 20 prescriptions. 

Investigators also analyzed associations after introducing a 1- and 3-year lag period after cohort entry to address the latent period between AD onset and diagnosis. The primary findings held with a 1-year lag period but lost significance with the inclusion of a 3-year lag period.

In subgroup analyses, investigators found evidence of reduced AD risk in those who received prescriptions for sildenafil (aHR, 0.81; 95% CI, 0.71-0.93), but there was no evidence for reduced risk compared with nonusers in those who received tadalafil and vardenafil.

Lower AD risk was found in patients with hypertension, diabetes, and in men aged 70 years or older, but there was no association in younger men or those with no history of hypertension or diabetes. 

Although investigators controlled for a wide range of potential risk factors, Dr. Brauer noted that unmeasured confounders such as physical and sexual activity, which were not tracked and may predict PDE5I exposure, may have affected the results. 

Interpret With Caution

Commenting on the findings, Ozama Ismail, PhD, Alzheimer’s Association director of scientific programs, noted that in addition to the limitations cited by the study authors, AD diagnoses were not made with the “gold standard” testing that typically includes imaging biomarkers and postmortem assessments. 

“While this study is interesting and adds to a potential association, there is no evidence that these drugs are able to treat Alzheimer’s disease,” said Dr. Brauer, who was not part of the current study. 

“People should not use over-the-counter phosphodiesterase type 5 inhibitors for prevention of Alzheimer’s or other dementias based on this very preliminary finding. Always consult with your physician before starting or changing your medications,” he cautioned.

However, Dr. Ismael added that the study does highlight a potential new avenue for drug repurposing. 

“Repurposing of existing, already-approved treatments can be a valuable part of drug development because, through already-completed testing, we know much about their safety and side effects,” which can decrease cost and time needed for studies, he said. 

“When considering repurposing an existing drug to an Alzheimer’s treatment, however, it is often important to conduct new studies over longer periods of time and in older people that reflect the diversity of individuals living with Alzheimer’s disease,” Dr. Ismael said.

Randomized Trials Needed

Dr. Brauer agreed, offering that such a trial should also include people with mild cognitive impairment and measure the effects of PDE5Is given in predefined doses plus an acetylcholinesterase inhibitor or placebo plus an acetylcholinesterase inhibitor. 

“The primary outcome would be the change in baseline cognitive function,” she said. “This approach would provide a comprehensive understanding of the potential therapeutic benefits of PDE5I and AD.”

Studies are also needed to better understand the mechanisms by which these drugs might influence AD risk, Sevil Yasar, MD, PhD, and Lolita Nidadavolu, MD, PhD, from the Division of Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine, Baltimore, noted in an accompanying editorial.

The strong association between PDE5I use and AD risk in people with a history of hypertension or diabetes suggests “a potential neuroprotective effect through a vascular pathway,” they wrote.

In vitro studies on the role of inflammation and clearance of beta-amyloid could strengthen findings from studies like this one, and in vivo studies could help explain the mechanisms behind PDE5I use and lower AD risk, Dr. Yasar and Dr. Nidadavolu noted. 

“In the end, however, further observational studies exploring mechanisms will not prove a causal association,” they wrote. “A well-designed randomized controlled trial is needed before PDE5I drugs can be prescribed for AD prevention.”

The study was unfunded. The study and editorial authors and Dr. Ismail report no relevant financial conflicts. 
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has cleared NM-101 (Terran Biosciences), a cloud-based software platform to analyze neuromelanin-sensitive MRI scans, which could aid in the diagnosis of neurodegenerative diseases. 

Research has suggested that neuromelanin is a potential biomarker for neurologic disorders such as Parkinson’s disease.

A recent meta-analysis of 12 neuromelanin MRI studies with 403 patients with Parkinson’s disease and 298 control participants found that neuromelanin MRI had “favorable” diagnostic performance in discriminating patients with Parkinson’s disease from healthy controls.

Until now, there were no FDA-approved devices capable of providing clinicians with analysis of neuromelanin MRI due to a lack of automation and standardization. NM-101 contains algorithms that enable fully automated analysis and the cross-scanner harmonization of neuromelanin MRI scans, the company explains in a news release.

NM-101 is designed to “seamlessly” integrate into existing workflows at hospitals and imaging centers, the company says. 

The platform allows clinicians to send neuromelanin MRI images to Terran directly through the hospital picture archiving and communication system and receive results in less than 1 hour. 

When interpreted by a neuroradiologist, NM-101 could provide information that may be helpful in determining neuromelanin association as an adjunct to diagnosis.

“We believe this technology could become very important in the clinical workflow of patients with neurological and psychiatric disorders,” Terran Biosciences Founder and CEO Sam Clark, MD, PhD, said in the release. 

Neuromelanin MRI has the potential to become “part of the standard of care for the workup of all patients suspected of Parkinson’s and related diseases,” David Sulzer, PhD, professor of neurobiology at Columbia University Vagelos College of Physicians and Surgeons, New York, and co-author of multiple studies using neuromelanin MRI, commented in the news release.

“It’s great to see neuromelanin MRI become more accessible in clinical settings. We hope this opens the door for the adoption of neuromelanin MRI into the clinical workflow for patients with neuropsychiatric disorders,” added Guillermo Horga, MD, PhD, associate professor of psychiatry at Columbia University Vagelos College of Physicians and Surgeons.

Terran Biosciences has an exclusive license to the CNS biomarker software platform and related patents co-owned by Columbia University and Research Foundation for Mental Hygiene. Dr. Horga will receive a portion of the royalties paid to Columbia University for sales of the product.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has cleared NM-101 (Terran Biosciences), a cloud-based software platform to analyze neuromelanin-sensitive MRI scans, which could aid in the diagnosis of neurodegenerative diseases. 

Research has suggested that neuromelanin is a potential biomarker for neurologic disorders such as Parkinson’s disease.

A recent meta-analysis of 12 neuromelanin MRI studies with 403 patients with Parkinson’s disease and 298 control participants found that neuromelanin MRI had “favorable” diagnostic performance in discriminating patients with Parkinson’s disease from healthy controls.

Until now, there were no FDA-approved devices capable of providing clinicians with analysis of neuromelanin MRI due to a lack of automation and standardization. NM-101 contains algorithms that enable fully automated analysis and the cross-scanner harmonization of neuromelanin MRI scans, the company explains in a news release.

NM-101 is designed to “seamlessly” integrate into existing workflows at hospitals and imaging centers, the company says. 

The platform allows clinicians to send neuromelanin MRI images to Terran directly through the hospital picture archiving and communication system and receive results in less than 1 hour. 

When interpreted by a neuroradiologist, NM-101 could provide information that may be helpful in determining neuromelanin association as an adjunct to diagnosis.

“We believe this technology could become very important in the clinical workflow of patients with neurological and psychiatric disorders,” Terran Biosciences Founder and CEO Sam Clark, MD, PhD, said in the release. 

Neuromelanin MRI has the potential to become “part of the standard of care for the workup of all patients suspected of Parkinson’s and related diseases,” David Sulzer, PhD, professor of neurobiology at Columbia University Vagelos College of Physicians and Surgeons, New York, and co-author of multiple studies using neuromelanin MRI, commented in the news release.

“It’s great to see neuromelanin MRI become more accessible in clinical settings. We hope this opens the door for the adoption of neuromelanin MRI into the clinical workflow for patients with neuropsychiatric disorders,” added Guillermo Horga, MD, PhD, associate professor of psychiatry at Columbia University Vagelos College of Physicians and Surgeons.

Terran Biosciences has an exclusive license to the CNS biomarker software platform and related patents co-owned by Columbia University and Research Foundation for Mental Hygiene. Dr. Horga will receive a portion of the royalties paid to Columbia University for sales of the product.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has cleared NM-101 (Terran Biosciences), a cloud-based software platform to analyze neuromelanin-sensitive MRI scans, which could aid in the diagnosis of neurodegenerative diseases. 

Research has suggested that neuromelanin is a potential biomarker for neurologic disorders such as Parkinson’s disease.

A recent meta-analysis of 12 neuromelanin MRI studies with 403 patients with Parkinson’s disease and 298 control participants found that neuromelanin MRI had “favorable” diagnostic performance in discriminating patients with Parkinson’s disease from healthy controls.

Until now, there were no FDA-approved devices capable of providing clinicians with analysis of neuromelanin MRI due to a lack of automation and standardization. NM-101 contains algorithms that enable fully automated analysis and the cross-scanner harmonization of neuromelanin MRI scans, the company explains in a news release.

NM-101 is designed to “seamlessly” integrate into existing workflows at hospitals and imaging centers, the company says. 

The platform allows clinicians to send neuromelanin MRI images to Terran directly through the hospital picture archiving and communication system and receive results in less than 1 hour. 

When interpreted by a neuroradiologist, NM-101 could provide information that may be helpful in determining neuromelanin association as an adjunct to diagnosis.

“We believe this technology could become very important in the clinical workflow of patients with neurological and psychiatric disorders,” Terran Biosciences Founder and CEO Sam Clark, MD, PhD, said in the release. 

Neuromelanin MRI has the potential to become “part of the standard of care for the workup of all patients suspected of Parkinson’s and related diseases,” David Sulzer, PhD, professor of neurobiology at Columbia University Vagelos College of Physicians and Surgeons, New York, and co-author of multiple studies using neuromelanin MRI, commented in the news release.

“It’s great to see neuromelanin MRI become more accessible in clinical settings. We hope this opens the door for the adoption of neuromelanin MRI into the clinical workflow for patients with neuropsychiatric disorders,” added Guillermo Horga, MD, PhD, associate professor of psychiatry at Columbia University Vagelos College of Physicians and Surgeons.

Terran Biosciences has an exclusive license to the CNS biomarker software platform and related patents co-owned by Columbia University and Research Foundation for Mental Hygiene. Dr. Horga will receive a portion of the royalties paid to Columbia University for sales of the product.

A version of this article appeared on Medscape.com.

Biogen’s announcement on January 31 that it will discontinue development and commercialization of the anti-amyloid agent, aducanumab (Aduhelm), for Alzheimer’s disease came as no surprise to many experts in the field. 

“Clearly, the drug was a commercial failure,” Dave Knopman, MD, professor of neurology, Mayo Clinic, Rochester, Minnesota, said. “Despite the accelerated approval, the uncertainty of clinical benefits was transparent, and the public failed to generate any enthusiasm for the drug.”

Aducanumab received accelerated approval from the US Food and Drug Administration (FDA) in June 2021 despite a recommendation by its own advisory panel not to approve the drug. Dr. Knopman was a member of that panel and one of three members who resigned after the agency’s decision to approve the drug. 

“The decision by Biogen to cancel the aducanumab program was not surprising, as the company steadily withdrew their engagement in the program over the past year,” Dr. Knopman noted. 

“This was a commercial decision — not so much a scientific decision,” Howard Fillit, MD, founding executive director of the Alzheimer’s Drug Discovery Foundation, said. 

“The process by which the [aducanumab] program was handled and some of the conflicting opinions at the FDA led to uncertainty about the efficacy of the drug, and it wasn’t being prescribed,” Dr. Fillit said. 

After its approval, the Centers for Medicare & Medicaid Services restricted coverage of aducanumab to patients enrolled in clinical trials, which experts say likely contributed to Biogen’s decision to ditch the drug. 

It also limited the number of people living with Alzheimer’s disease who could get access to the treatment and “created significant confusion for patients and doctors,” the Alzheimer’s Association said in a statement on Biogen’s decision. 

Biogen will also terminate the post-approval clinical trial known as ENVISION, which sought to confirm aducanumab’s benefits in patients with early Alzheimer’s disease. 

Going forward, Biogen said that it will now focus on advancing lecanemab (Leqembi), the first anti-amyloid to receive traditional FDA approval.

“We have learned much from the mistakes and misjudgments that plagued aducanumab, but the field has moved on and is a little the wiser,” Dr. Knopman said. “With the standard approval of lecanemab, which showed clear, albeit modest, clinical benefits, we are focusing on providing safe and efficient access to lecanemab.” 

Biogen plans to accelerate the development of potential new treatment modalities. These include BIIB080, an investigational antisense oligonucleotide therapy targeting tau, and BIIB113, an oral small-molecule inhibitor of tau aggregation.

Dr. Fillit said that he’s “very excited” about the current pipeline of Alzheimer’s disease drugs, starting with donanemab, which is currently under review at the FDA, and “looks like it has somewhat better efficacy data than lecanemab.”

A version of this article appeared on Medscape.com.

Biogen’s announcement on January 31 that it will discontinue development and commercialization of the anti-amyloid agent, aducanumab (Aduhelm), for Alzheimer’s disease came as no surprise to many experts in the field. 

“Clearly, the drug was a commercial failure,” Dave Knopman, MD, professor of neurology, Mayo Clinic, Rochester, Minnesota, said. “Despite the accelerated approval, the uncertainty of clinical benefits was transparent, and the public failed to generate any enthusiasm for the drug.”

Aducanumab received accelerated approval from the US Food and Drug Administration (FDA) in June 2021 despite a recommendation by its own advisory panel not to approve the drug. Dr. Knopman was a member of that panel and one of three members who resigned after the agency’s decision to approve the drug. 

“The decision by Biogen to cancel the aducanumab program was not surprising, as the company steadily withdrew their engagement in the program over the past year,” Dr. Knopman noted. 

“This was a commercial decision — not so much a scientific decision,” Howard Fillit, MD, founding executive director of the Alzheimer’s Drug Discovery Foundation, said. 

“The process by which the [aducanumab] program was handled and some of the conflicting opinions at the FDA led to uncertainty about the efficacy of the drug, and it wasn’t being prescribed,” Dr. Fillit said. 

After its approval, the Centers for Medicare & Medicaid Services restricted coverage of aducanumab to patients enrolled in clinical trials, which experts say likely contributed to Biogen’s decision to ditch the drug. 

It also limited the number of people living with Alzheimer’s disease who could get access to the treatment and “created significant confusion for patients and doctors,” the Alzheimer’s Association said in a statement on Biogen’s decision. 

Biogen will also terminate the post-approval clinical trial known as ENVISION, which sought to confirm aducanumab’s benefits in patients with early Alzheimer’s disease. 

Going forward, Biogen said that it will now focus on advancing lecanemab (Leqembi), the first anti-amyloid to receive traditional FDA approval.

“We have learned much from the mistakes and misjudgments that plagued aducanumab, but the field has moved on and is a little the wiser,” Dr. Knopman said. “With the standard approval of lecanemab, which showed clear, albeit modest, clinical benefits, we are focusing on providing safe and efficient access to lecanemab.” 

Biogen plans to accelerate the development of potential new treatment modalities. These include BIIB080, an investigational antisense oligonucleotide therapy targeting tau, and BIIB113, an oral small-molecule inhibitor of tau aggregation.

Dr. Fillit said that he’s “very excited” about the current pipeline of Alzheimer’s disease drugs, starting with donanemab, which is currently under review at the FDA, and “looks like it has somewhat better efficacy data than lecanemab.”

A version of this article appeared on Medscape.com.

Biogen’s announcement on January 31 that it will discontinue development and commercialization of the anti-amyloid agent, aducanumab (Aduhelm), for Alzheimer’s disease came as no surprise to many experts in the field. 

“Clearly, the drug was a commercial failure,” Dave Knopman, MD, professor of neurology, Mayo Clinic, Rochester, Minnesota, said. “Despite the accelerated approval, the uncertainty of clinical benefits was transparent, and the public failed to generate any enthusiasm for the drug.”

Aducanumab received accelerated approval from the US Food and Drug Administration (FDA) in June 2021 despite a recommendation by its own advisory panel not to approve the drug. Dr. Knopman was a member of that panel and one of three members who resigned after the agency’s decision to approve the drug. 

“The decision by Biogen to cancel the aducanumab program was not surprising, as the company steadily withdrew their engagement in the program over the past year,” Dr. Knopman noted. 

“This was a commercial decision — not so much a scientific decision,” Howard Fillit, MD, founding executive director of the Alzheimer’s Drug Discovery Foundation, said. 

“The process by which the [aducanumab] program was handled and some of the conflicting opinions at the FDA led to uncertainty about the efficacy of the drug, and it wasn’t being prescribed,” Dr. Fillit said. 

After its approval, the Centers for Medicare & Medicaid Services restricted coverage of aducanumab to patients enrolled in clinical trials, which experts say likely contributed to Biogen’s decision to ditch the drug. 

It also limited the number of people living with Alzheimer’s disease who could get access to the treatment and “created significant confusion for patients and doctors,” the Alzheimer’s Association said in a statement on Biogen’s decision. 

Biogen will also terminate the post-approval clinical trial known as ENVISION, which sought to confirm aducanumab’s benefits in patients with early Alzheimer’s disease. 

Going forward, Biogen said that it will now focus on advancing lecanemab (Leqembi), the first anti-amyloid to receive traditional FDA approval.

“We have learned much from the mistakes and misjudgments that plagued aducanumab, but the field has moved on and is a little the wiser,” Dr. Knopman said. “With the standard approval of lecanemab, which showed clear, albeit modest, clinical benefits, we are focusing on providing safe and efficient access to lecanemab.” 

Biogen plans to accelerate the development of potential new treatment modalities. These include BIIB080, an investigational antisense oligonucleotide therapy targeting tau, and BIIB113, an oral small-molecule inhibitor of tau aggregation.

Dr. Fillit said that he’s “very excited” about the current pipeline of Alzheimer’s disease drugs, starting with donanemab, which is currently under review at the FDA, and “looks like it has somewhat better efficacy data than lecanemab.”

A version of this article appeared on Medscape.com.

TOPLINE:

People with polycystic ovary syndrome (PCOS) may score lower on cognitive tests than people without the condition, a research showed. They also may have worse integrity of brain tissue as evident on an MRI.

METHODOLOGY:

• Researchers used data from the Coronary Artery Risk Development in Young Adults Women’s Study; individuals were 18-30 years old at the beginning of the study and were followed over 30 years.
• A little over 900 women were included in the study, of which 66 had PCOS, which was defined as having elevated androgen levels or self-reported hirsutism and irregular menstrual cycles more than 32 days apart.
• Study participants completed tests measuring verbal learning and memory, processing speed and executive function, attention and cognitive control, and semantics and attention.
• Researchers analyzed brain white matter integrity for 291 of the individuals, including 25 with PCOS, who underwent MRI.

TAKEAWAY:

• Individuals with PCOS had worse memory, attention, and verbal ability scores than those without the disorder.
• MRI scans showed that those with PCOS had lower white matter integrity, an indicator of cognitive deficits, including poorer decision-making abilities.
• Those in the PCOS group were more likely to be White and have diabetes than those in the control group.

IN PRACTICE:

“This report of midlife cognition in PCOS raises a new concern about another potential comorbidity for individuals with this common disorder; given that up to 10% of women may be affected by PCOS, these results have important implications for public health at large,” the authors concluded.

SOURCE:

Heather G. Huddleston, MD, director of the PCOS Clinic at the UCSF Health, San Francisco, California, is the lead author of the study published in Neurology.

LIMITATIONS:

PCOS was determined on the basis of serum androgen levels and self-reporting of hirsutism and oligomenorrhea, so some cases may have been misclassified without the official diagnosis of a clinician.

DISCLOSURES:

The authors did not report any relevant financial conflicts. The study was funded by a grant from the University of California, San Francisco, California.

A version of this article appeared on Medscape.com.

TOPLINE:

People with polycystic ovary syndrome (PCOS) may score lower on cognitive tests than people without the condition, a research showed. They also may have worse integrity of brain tissue as evident on an MRI.

METHODOLOGY:

• Researchers used data from the Coronary Artery Risk Development in Young Adults Women’s Study; individuals were 18-30 years old at the beginning of the study and were followed over 30 years.
• A little over 900 women were included in the study, of which 66 had PCOS, which was defined as having elevated androgen levels or self-reported hirsutism and irregular menstrual cycles more than 32 days apart.
• Study participants completed tests measuring verbal learning and memory, processing speed and executive function, attention and cognitive control, and semantics and attention.
• Researchers analyzed brain white matter integrity for 291 of the individuals, including 25 with PCOS, who underwent MRI.

TAKEAWAY:

• Individuals with PCOS had worse memory, attention, and verbal ability scores than those without the disorder.
• MRI scans showed that those with PCOS had lower white matter integrity, an indicator of cognitive deficits, including poorer decision-making abilities.
• Those in the PCOS group were more likely to be White and have diabetes than those in the control group.

IN PRACTICE:

“This report of midlife cognition in PCOS raises a new concern about another potential comorbidity for individuals with this common disorder; given that up to 10% of women may be affected by PCOS, these results have important implications for public health at large,” the authors concluded.

SOURCE:

Heather G. Huddleston, MD, director of the PCOS Clinic at the UCSF Health, San Francisco, California, is the lead author of the study published in Neurology.

LIMITATIONS:

PCOS was determined on the basis of serum androgen levels and self-reporting of hirsutism and oligomenorrhea, so some cases may have been misclassified without the official diagnosis of a clinician.

DISCLOSURES:

The authors did not report any relevant financial conflicts. The study was funded by a grant from the University of California, San Francisco, California.

A version of this article appeared on Medscape.com.

TOPLINE:

People with polycystic ovary syndrome (PCOS) may score lower on cognitive tests than people without the condition, a research showed. They also may have worse integrity of brain tissue as evident on an MRI.

METHODOLOGY:

• Researchers used data from the Coronary Artery Risk Development in Young Adults Women’s Study; individuals were 18-30 years old at the beginning of the study and were followed over 30 years.
• A little over 900 women were included in the study, of which 66 had PCOS, which was defined as having elevated androgen levels or self-reported hirsutism and irregular menstrual cycles more than 32 days apart.
• Study participants completed tests measuring verbal learning and memory, processing speed and executive function, attention and cognitive control, and semantics and attention.
• Researchers analyzed brain white matter integrity for 291 of the individuals, including 25 with PCOS, who underwent MRI.

TAKEAWAY:

• Individuals with PCOS had worse memory, attention, and verbal ability scores than those without the disorder.
• MRI scans showed that those with PCOS had lower white matter integrity, an indicator of cognitive deficits, including poorer decision-making abilities.
• Those in the PCOS group were more likely to be White and have diabetes than those in the control group.

IN PRACTICE:

“This report of midlife cognition in PCOS raises a new concern about another potential comorbidity for individuals with this common disorder; given that up to 10% of women may be affected by PCOS, these results have important implications for public health at large,” the authors concluded.

SOURCE:

Heather G. Huddleston, MD, director of the PCOS Clinic at the UCSF Health, San Francisco, California, is the lead author of the study published in Neurology.

LIMITATIONS:

PCOS was determined on the basis of serum androgen levels and self-reporting of hirsutism and oligomenorrhea, so some cases may have been misclassified without the official diagnosis of a clinician.

DISCLOSURES:

The authors did not report any relevant financial conflicts. The study was funded by a grant from the University of California, San Francisco, California.

A version of this article appeared on Medscape.com.

TOPLINE:

Social frailty, the lack of resources to meet basic social needs, is associated with an increased risk for motoric cognitive risk syndrome (MCR), a predementia syndrome characterized by cognitive complaints and slow gait, results of a large, population-based study suggested.

METHODOLOGY:

• The study used 2011 (Round 1) to 2018 (Round 8) data on a discovery sample of 4657 individuals without MCR or dementia at baseline from the National Health and Aging Trends Study (NHATS), a longitudinal survey of older adult Medicare beneficiaries.
• Researchers also collected data on 3075 newly recruited individuals in Round 5 and followed to Round 8 as an independent validation sample to create a pooled sample of 7732 older adults, mean age 76.06, without MCR at baseline.
• Social frailty, assessed at baseline, included five social items: Going out less, not feeling confident, rarely visiting friends/family, not talking with others, and without live-in partner/spouse (researchers divided participants into normal [zero to one items] and social frailty [two to five items] groups).
• Individuals were considered to have MCR if they had both subjective cognitive complaints and slow gait speed (greater than 1 standard deviation below age-specific level) without dementia or mobility disability.
• Covariates included demographic and lifestyle data, presence of depression and/or anxiety symptoms, and number of chronic diseases.

TAKEAWAY:

• During a median follow-up period of 4 years, 10.35% individuals were diagnosed with MCR.
• After the researchers controlled for confounding factors, those with social frailty had an increased risk for MCR compared with the normal group (pooled sample: hazard ratio [HR], 1.57; 95% CI, 1.34-1.84; P < .001).
• Each additional unfavorable social item was associated with an increased risk for MCR (pooled sample: HR, 1.32; 95% CI, 1.22-1.43; P < .001).
• Results of stratified analyses across subgroups suggested individuals with social frailty had a significantly higher risk for incident MCR than that of those without social frailty, regardless of socioeconomic status, lifestyle factors, chronic diseases, and mental health.

IN PRACTICE:

The findings suggest assessing social frailty using simple questions “is an efficient tool for detecting older individuals with a high risk of MCR,” the authors wrote. They noted that the addition of such a tool in clinical practice may facilitate “timely implementation of prevention strategies.”

SOURCE:

The research was led by Hui Zhang, Human Phenome Institute, Zhangjiang Fudan International Innovation Centre, Fudan University, Shanghai, China. It was published online on January 29, 2024, in Alzheimer’s & Dementia.

LIMITATIONS:

The study was observational, so the association between social frailty and MCR is merely correlational. Due to the lack of genetic information in NHATS data, researchers didn’t evaluate the effect of genetic factors such as apolipoprotein E on the association between social frailty and MCR. Social frailty was assessed at a single time point. In addition, the researchers were unable examine the time sequence between social frailty and MCR and so could not determine the cause of this association.

DISCLOSURES:

The study was supported by the National Natural Science Foundation of China-Youth Science Fund, Shanghai Rising-Star Program, Shanghai Municipal Health Commission and Key Discipline Construction Project of Pudong Health, and Family Planning Commission of Shanghai. The authors reported no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Social frailty, the lack of resources to meet basic social needs, is associated with an increased risk for motoric cognitive risk syndrome (MCR), a predementia syndrome characterized by cognitive complaints and slow gait, results of a large, population-based study suggested.

METHODOLOGY:

• The study used 2011 (Round 1) to 2018 (Round 8) data on a discovery sample of 4657 individuals without MCR or dementia at baseline from the National Health and Aging Trends Study (NHATS), a longitudinal survey of older adult Medicare beneficiaries.
• Researchers also collected data on 3075 newly recruited individuals in Round 5 and followed to Round 8 as an independent validation sample to create a pooled sample of 7732 older adults, mean age 76.06, without MCR at baseline.
• Social frailty, assessed at baseline, included five social items: Going out less, not feeling confident, rarely visiting friends/family, not talking with others, and without live-in partner/spouse (researchers divided participants into normal [zero to one items] and social frailty [two to five items] groups).
• Individuals were considered to have MCR if they had both subjective cognitive complaints and slow gait speed (greater than 1 standard deviation below age-specific level) without dementia or mobility disability.
• Covariates included demographic and lifestyle data, presence of depression and/or anxiety symptoms, and number of chronic diseases.

TAKEAWAY:

• During a median follow-up period of 4 years, 10.35% individuals were diagnosed with MCR.
• After the researchers controlled for confounding factors, those with social frailty had an increased risk for MCR compared with the normal group (pooled sample: hazard ratio [HR], 1.57; 95% CI, 1.34-1.84; P < .001).
• Each additional unfavorable social item was associated with an increased risk for MCR (pooled sample: HR, 1.32; 95% CI, 1.22-1.43; P < .001).
• Results of stratified analyses across subgroups suggested individuals with social frailty had a significantly higher risk for incident MCR than that of those without social frailty, regardless of socioeconomic status, lifestyle factors, chronic diseases, and mental health.

IN PRACTICE:

The findings suggest assessing social frailty using simple questions “is an efficient tool for detecting older individuals with a high risk of MCR,” the authors wrote. They noted that the addition of such a tool in clinical practice may facilitate “timely implementation of prevention strategies.”

SOURCE:

The research was led by Hui Zhang, Human Phenome Institute, Zhangjiang Fudan International Innovation Centre, Fudan University, Shanghai, China. It was published online on January 29, 2024, in Alzheimer’s & Dementia.

LIMITATIONS:

The study was observational, so the association between social frailty and MCR is merely correlational. Due to the lack of genetic information in NHATS data, researchers didn’t evaluate the effect of genetic factors such as apolipoprotein E on the association between social frailty and MCR. Social frailty was assessed at a single time point. In addition, the researchers were unable examine the time sequence between social frailty and MCR and so could not determine the cause of this association.

DISCLOSURES:

The study was supported by the National Natural Science Foundation of China-Youth Science Fund, Shanghai Rising-Star Program, Shanghai Municipal Health Commission and Key Discipline Construction Project of Pudong Health, and Family Planning Commission of Shanghai. The authors reported no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Social frailty, the lack of resources to meet basic social needs, is associated with an increased risk for motoric cognitive risk syndrome (MCR), a predementia syndrome characterized by cognitive complaints and slow gait, results of a large, population-based study suggested.

METHODOLOGY:

• The study used 2011 (Round 1) to 2018 (Round 8) data on a discovery sample of 4657 individuals without MCR or dementia at baseline from the National Health and Aging Trends Study (NHATS), a longitudinal survey of older adult Medicare beneficiaries.
• Researchers also collected data on 3075 newly recruited individuals in Round 5 and followed to Round 8 as an independent validation sample to create a pooled sample of 7732 older adults, mean age 76.06, without MCR at baseline.
• Social frailty, assessed at baseline, included five social items: Going out less, not feeling confident, rarely visiting friends/family, not talking with others, and without live-in partner/spouse (researchers divided participants into normal [zero to one items] and social frailty [two to five items] groups).
• Individuals were considered to have MCR if they had both subjective cognitive complaints and slow gait speed (greater than 1 standard deviation below age-specific level) without dementia or mobility disability.
• Covariates included demographic and lifestyle data, presence of depression and/or anxiety symptoms, and number of chronic diseases.

TAKEAWAY:

• During a median follow-up period of 4 years, 10.35% individuals were diagnosed with MCR.
• After the researchers controlled for confounding factors, those with social frailty had an increased risk for MCR compared with the normal group (pooled sample: hazard ratio [HR], 1.57; 95% CI, 1.34-1.84; P < .001).
• Each additional unfavorable social item was associated with an increased risk for MCR (pooled sample: HR, 1.32; 95% CI, 1.22-1.43; P < .001).
• Results of stratified analyses across subgroups suggested individuals with social frailty had a significantly higher risk for incident MCR than that of those without social frailty, regardless of socioeconomic status, lifestyle factors, chronic diseases, and mental health.

IN PRACTICE:

The findings suggest assessing social frailty using simple questions “is an efficient tool for detecting older individuals with a high risk of MCR,” the authors wrote. They noted that the addition of such a tool in clinical practice may facilitate “timely implementation of prevention strategies.”

SOURCE:

The research was led by Hui Zhang, Human Phenome Institute, Zhangjiang Fudan International Innovation Centre, Fudan University, Shanghai, China. It was published online on January 29, 2024, in Alzheimer’s & Dementia.

LIMITATIONS:

The study was observational, so the association between social frailty and MCR is merely correlational. Due to the lack of genetic information in NHATS data, researchers didn’t evaluate the effect of genetic factors such as apolipoprotein E on the association between social frailty and MCR. Social frailty was assessed at a single time point. In addition, the researchers were unable examine the time sequence between social frailty and MCR and so could not determine the cause of this association.

DISCLOSURES:

The study was supported by the National Natural Science Foundation of China-Youth Science Fund, Shanghai Rising-Star Program, Shanghai Municipal Health Commission and Key Discipline Construction Project of Pudong Health, and Family Planning Commission of Shanghai. The authors reported no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

Five people in the United Kingdom have been diagnosed with Alzheimer’s disease resulting from a medical treatment they received decades earlier, new research shows. 

Investigators say they are the first known cases of medically acquired AD in living people, but outside experts say the findings should be interpreted cautiously.

The individuals received treatment as children with human growth hormone extracted from pituitary glands of cadavers (c-hGH). Between 1958-1985, an estimated 30,000 people worldwide, mostly children, were treated with c-hGH for genetic disorders and growth hormone deficiencies. 

The therapy was halted in 1985 after three patients in the US who received the treatment later died of Creutzfeldt-Jakob disease (CJD) transmitted through batches of c-hGH that were contaminated with disease-causing prions. 

The new study builds on the investigators’ earlier work that showed the batches of c-hGH also contained amyloid-beta protein and that the protein could be transmitted decades later. These five cases were referred to or reviewed by researchers and clinicians at a prion clinic led by one of the lead researchers.

There are no reports of amyloid-beta transmission through any other medical or surgical procedures, researchers stress, and there is no evidence that amyloid-beta can be passed on during routine patient care or in daily activities. 

“However, the recognition of transmission of amyloid-beta pathology in these rare situations should lead us to review measures to prevent accidental transmission via other medical or surgical procedures, in order to prevent such cases occurring in future,” lead author John Collinge, MD, director of the University of College London Institute of Prion Diseases, London, England, and leader of the UK’s National Prion Clinic, said in a press release. 

“Importantly, our findings also suggest that Alzheimer’s and some other neurological conditions share similar disease processes to CJD, and this may have important implications for understanding and treating Alzheimer’s disease in the future,” Dr. Collinge continued.

The findings were published online January 29 in Nature Medicine. 
 

Building on Earlier Work

The research builds on investigators’ previous 2015 work that found archived samples of c-hGH were also contaminated with amyloid-beta protein. In 2018, mouse studies showed that c-hGH samples stored for decades could still transmit amyloid-beta via injection. 

Researchers said the findings suggested that individuals exposed to contaminated c-hGH who did not die from CJD might eventually develop AD.

Patients in the new study developed neurological symptoms consistent with AD between the ages of 38 and 55 years. The individual cases were either referred to or reviewed by experts in the National Prion Clinic in the UK between 2017 and 2022. The clinic coordinates the National Prion Monitoring Cohort, a longitudinal study of individuals with confirmed prion diseases. 

Of the eight cases, three were diagnosed with AD before referral to the clinic; two others met criteria for an AD diagnosis; and three did not meet the criteria. Three of the patients — two of whom had AD — are now deceased. 

All patients in the study received c-hGH prepared using a method called Wilhelmi or Hartree-modified Wilhelmi preparation (HWP).

Biomarker analyses confirmed the AD diagnosis in two patients. Other cases showed either progressive brain volume loss on brain imaging or elevated cerebrospinal fluid total tau and phosphorylated tau, or evidence of amyloid-beta deposits on autopsy. 
 

‘Potentially Transmissible’

The cases offered diverse presentations. Some were not symptomatic and some failed to meet current diagnostic criteria for sporadic Alzheimer’s disease. Treatment duration and frequency differed among those in the study, as did their age at treatment onset and completion. That and other factors could contribute to the diverse phenotype recorded in individuals, investigators note. 

Investigators examined and ruled out other factors that might explain the individuals’ cognitive symptoms, including childhood intellectual disability, which has been linked to dementia risk, the underlying condition that prompted their treatment with c-hGH, growth hormone deficiency, and cranial radiotherapy, which four of the individuals had received. They also ruled out inherited disease in all five of the cases with samples available for testing. 

“Taken together, the only factor common to all of the patients whom we describe is treatment with the HWP subtype of c-hGH,” the authors write. “Given the strong experimental evidence for A-beta transmission from relevant archived HWP c-hGH batches, we conclude that this is the most plausible explanation for the findings observed.”

Investigators say the findings show that, like other prion diseases, AD has three etiologies: sporadic, inherited, and rare acquired forms, or iatrogenic AD. 

“The clinical syndrome developed by these individuals can, therefore, be termed iatrogenic Alzheimer’s disease, and Alzheimer’s disease should now be recognized as a potentially transmissible disorder,” the authors write. 

“Our cases suggest that, similarly to what is observed in human prion diseases, iatrogenic forms of Alzheimer’s disease differ phenotypically from sporadic and inherited forms, with some individuals remaining asymptomatic despite exposure to A-beta seeds due to protective factors that, at present, are unknown,” they continue
 

‘Measure of Skepticism’

In an accompanying editorial, Mathias Jucker, PhD, of the Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany, and Lary C. Walker, PhD, in the Department of Neurology at Emory University, Atlanta, write that the findings should be considered “with a measure of skepticism.”

“The cases presented are diverse and complicated; the individuals had undergone a variety of medical interventions for various disorders earlier in life, and it is difficult to exclude a contribution of these circumstances to the complex disease phenotypes that appeared many years later,” they write. 

However, they continue, “there is good reason to take the findings seriously.”

“From a practical standpoint, this report reinforces the potential of amyloid-beta seeds as targets for early prevention, and it underscores the importance of informed caution in the preparation of surgical instruments, handling of tissues, and implementation of therapeutic biologics, particularly those derived from human sources,” Dr. Jucker and Dr. Walker write. 

Commenting on the findings for this news organization, Christopher Weber, PhD, director of global science initiatives for the Alzheimer’s Association, says the idea that amyloid-beta is transmissible between individuals has been shown before. 

“We’ve known for a long time that it is possible to create abnormal amyloid buildup — similar to that seen in Alzheimer’s – in the brain of an animal by injecting it with amyloid-beta. We also transfer human Alzheimer’s genes into animals to initiate abnormal, Alzheimer’s-like processes in their brains,” he said. “Thus, the idea that amyloid is transferable between individuals is not so novel as implied in the new paper.”

However, the study does highlight the importance of safety measures to prevent the accidental transmission of amyloid-beta, Weber added. 

“It is a reasonable and actionable caution that the scientific and clinical communities must understand the possible risks and ensure that all methods of transmission are eliminated — for example, with complete and conscientious sterilization of surgical instruments,” he said. “Bottom line: We shouldn’t put amyloid-beta into people’s brains, either accidentally or on purpose, and appropriate measures should be in place to ensure that doesn’t happen.”

The study was supported by the Medical Research Council, the National Institute for Health and Care Research (NIHR), the NIHR University College of London Hospital Biomedical Research Centre, Alzheimer’s Research UK, and the Stroke Association. Dr. Collinge is a shareholder and director of D-Gen, Ltd., an academic spin-out company working in the field of prion disease diagnosis, decontamination and therapeutics. Dr. Jucker and Dr. Walker report no conflicts of interest. 

A version of this article appeared on Medscape.com.

Five people in the United Kingdom have been diagnosed with Alzheimer’s disease resulting from a medical treatment they received decades earlier, new research shows. 

Investigators say they are the first known cases of medically acquired AD in living people, but outside experts say the findings should be interpreted cautiously.

The individuals received treatment as children with human growth hormone extracted from pituitary glands of cadavers (c-hGH). Between 1958-1985, an estimated 30,000 people worldwide, mostly children, were treated with c-hGH for genetic disorders and growth hormone deficiencies. 

The therapy was halted in 1985 after three patients in the US who received the treatment later died of Creutzfeldt-Jakob disease (CJD) transmitted through batches of c-hGH that were contaminated with disease-causing prions. 

The new study builds on the investigators’ earlier work that showed the batches of c-hGH also contained amyloid-beta protein and that the protein could be transmitted decades later. These five cases were referred to or reviewed by researchers and clinicians at a prion clinic led by one of the lead researchers.

There are no reports of amyloid-beta transmission through any other medical or surgical procedures, researchers stress, and there is no evidence that amyloid-beta can be passed on during routine patient care or in daily activities. 

“However, the recognition of transmission of amyloid-beta pathology in these rare situations should lead us to review measures to prevent accidental transmission via other medical or surgical procedures, in order to prevent such cases occurring in future,” lead author John Collinge, MD, director of the University of College London Institute of Prion Diseases, London, England, and leader of the UK’s National Prion Clinic, said in a press release. 

“Importantly, our findings also suggest that Alzheimer’s and some other neurological conditions share similar disease processes to CJD, and this may have important implications for understanding and treating Alzheimer’s disease in the future,” Dr. Collinge continued.

The findings were published online January 29 in Nature Medicine. 
 

Building on Earlier Work

The research builds on investigators’ previous 2015 work that found archived samples of c-hGH were also contaminated with amyloid-beta protein. In 2018, mouse studies showed that c-hGH samples stored for decades could still transmit amyloid-beta via injection. 

Researchers said the findings suggested that individuals exposed to contaminated c-hGH who did not die from CJD might eventually develop AD.

Patients in the new study developed neurological symptoms consistent with AD between the ages of 38 and 55 years. The individual cases were either referred to or reviewed by experts in the National Prion Clinic in the UK between 2017 and 2022. The clinic coordinates the National Prion Monitoring Cohort, a longitudinal study of individuals with confirmed prion diseases. 

Of the eight cases, three were diagnosed with AD before referral to the clinic; two others met criteria for an AD diagnosis; and three did not meet the criteria. Three of the patients — two of whom had AD — are now deceased. 

All patients in the study received c-hGH prepared using a method called Wilhelmi or Hartree-modified Wilhelmi preparation (HWP).

Biomarker analyses confirmed the AD diagnosis in two patients. Other cases showed either progressive brain volume loss on brain imaging or elevated cerebrospinal fluid total tau and phosphorylated tau, or evidence of amyloid-beta deposits on autopsy. 
 

‘Potentially Transmissible’

The cases offered diverse presentations. Some were not symptomatic and some failed to meet current diagnostic criteria for sporadic Alzheimer’s disease. Treatment duration and frequency differed among those in the study, as did their age at treatment onset and completion. That and other factors could contribute to the diverse phenotype recorded in individuals, investigators note. 

Investigators examined and ruled out other factors that might explain the individuals’ cognitive symptoms, including childhood intellectual disability, which has been linked to dementia risk, the underlying condition that prompted their treatment with c-hGH, growth hormone deficiency, and cranial radiotherapy, which four of the individuals had received. They also ruled out inherited disease in all five of the cases with samples available for testing. 

“Taken together, the only factor common to all of the patients whom we describe is treatment with the HWP subtype of c-hGH,” the authors write. “Given the strong experimental evidence for A-beta transmission from relevant archived HWP c-hGH batches, we conclude that this is the most plausible explanation for the findings observed.”

Investigators say the findings show that, like other prion diseases, AD has three etiologies: sporadic, inherited, and rare acquired forms, or iatrogenic AD. 

“The clinical syndrome developed by these individuals can, therefore, be termed iatrogenic Alzheimer’s disease, and Alzheimer’s disease should now be recognized as a potentially transmissible disorder,” the authors write. 

“Our cases suggest that, similarly to what is observed in human prion diseases, iatrogenic forms of Alzheimer’s disease differ phenotypically from sporadic and inherited forms, with some individuals remaining asymptomatic despite exposure to A-beta seeds due to protective factors that, at present, are unknown,” they continue
 

‘Measure of Skepticism’

In an accompanying editorial, Mathias Jucker, PhD, of the Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany, and Lary C. Walker, PhD, in the Department of Neurology at Emory University, Atlanta, write that the findings should be considered “with a measure of skepticism.”

“The cases presented are diverse and complicated; the individuals had undergone a variety of medical interventions for various disorders earlier in life, and it is difficult to exclude a contribution of these circumstances to the complex disease phenotypes that appeared many years later,” they write. 

However, they continue, “there is good reason to take the findings seriously.”

“From a practical standpoint, this report reinforces the potential of amyloid-beta seeds as targets for early prevention, and it underscores the importance of informed caution in the preparation of surgical instruments, handling of tissues, and implementation of therapeutic biologics, particularly those derived from human sources,” Dr. Jucker and Dr. Walker write. 

Commenting on the findings for this news organization, Christopher Weber, PhD, director of global science initiatives for the Alzheimer’s Association, says the idea that amyloid-beta is transmissible between individuals has been shown before. 

“We’ve known for a long time that it is possible to create abnormal amyloid buildup — similar to that seen in Alzheimer’s – in the brain of an animal by injecting it with amyloid-beta. We also transfer human Alzheimer’s genes into animals to initiate abnormal, Alzheimer’s-like processes in their brains,” he said. “Thus, the idea that amyloid is transferable between individuals is not so novel as implied in the new paper.”

However, the study does highlight the importance of safety measures to prevent the accidental transmission of amyloid-beta, Weber added. 

“It is a reasonable and actionable caution that the scientific and clinical communities must understand the possible risks and ensure that all methods of transmission are eliminated — for example, with complete and conscientious sterilization of surgical instruments,” he said. “Bottom line: We shouldn’t put amyloid-beta into people’s brains, either accidentally or on purpose, and appropriate measures should be in place to ensure that doesn’t happen.”

The study was supported by the Medical Research Council, the National Institute for Health and Care Research (NIHR), the NIHR University College of London Hospital Biomedical Research Centre, Alzheimer’s Research UK, and the Stroke Association. Dr. Collinge is a shareholder and director of D-Gen, Ltd., an academic spin-out company working in the field of prion disease diagnosis, decontamination and therapeutics. Dr. Jucker and Dr. Walker report no conflicts of interest. 

A version of this article appeared on Medscape.com.

Five people in the United Kingdom have been diagnosed with Alzheimer’s disease resulting from a medical treatment they received decades earlier, new research shows. 

Investigators say they are the first known cases of medically acquired AD in living people, but outside experts say the findings should be interpreted cautiously.

The individuals received treatment as children with human growth hormone extracted from pituitary glands of cadavers (c-hGH). Between 1958-1985, an estimated 30,000 people worldwide, mostly children, were treated with c-hGH for genetic disorders and growth hormone deficiencies. 

The therapy was halted in 1985 after three patients in the US who received the treatment later died of Creutzfeldt-Jakob disease (CJD) transmitted through batches of c-hGH that were contaminated with disease-causing prions. 

The new study builds on the investigators’ earlier work that showed the batches of c-hGH also contained amyloid-beta protein and that the protein could be transmitted decades later. These five cases were referred to or reviewed by researchers and clinicians at a prion clinic led by one of the lead researchers.

There are no reports of amyloid-beta transmission through any other medical or surgical procedures, researchers stress, and there is no evidence that amyloid-beta can be passed on during routine patient care or in daily activities. 

“However, the recognition of transmission of amyloid-beta pathology in these rare situations should lead us to review measures to prevent accidental transmission via other medical or surgical procedures, in order to prevent such cases occurring in future,” lead author John Collinge, MD, director of the University of College London Institute of Prion Diseases, London, England, and leader of the UK’s National Prion Clinic, said in a press release. 

“Importantly, our findings also suggest that Alzheimer’s and some other neurological conditions share similar disease processes to CJD, and this may have important implications for understanding and treating Alzheimer’s disease in the future,” Dr. Collinge continued.

The findings were published online January 29 in Nature Medicine. 
 

Building on Earlier Work

The research builds on investigators’ previous 2015 work that found archived samples of c-hGH were also contaminated with amyloid-beta protein. In 2018, mouse studies showed that c-hGH samples stored for decades could still transmit amyloid-beta via injection. 

Researchers said the findings suggested that individuals exposed to contaminated c-hGH who did not die from CJD might eventually develop AD.

Patients in the new study developed neurological symptoms consistent with AD between the ages of 38 and 55 years. The individual cases were either referred to or reviewed by experts in the National Prion Clinic in the UK between 2017 and 2022. The clinic coordinates the National Prion Monitoring Cohort, a longitudinal study of individuals with confirmed prion diseases. 

Of the eight cases, three were diagnosed with AD before referral to the clinic; two others met criteria for an AD diagnosis; and three did not meet the criteria. Three of the patients — two of whom had AD — are now deceased. 

All patients in the study received c-hGH prepared using a method called Wilhelmi or Hartree-modified Wilhelmi preparation (HWP).

Biomarker analyses confirmed the AD diagnosis in two patients. Other cases showed either progressive brain volume loss on brain imaging or elevated cerebrospinal fluid total tau and phosphorylated tau, or evidence of amyloid-beta deposits on autopsy. 
 

‘Potentially Transmissible’

The cases offered diverse presentations. Some were not symptomatic and some failed to meet current diagnostic criteria for sporadic Alzheimer’s disease. Treatment duration and frequency differed among those in the study, as did their age at treatment onset and completion. That and other factors could contribute to the diverse phenotype recorded in individuals, investigators note. 

Investigators examined and ruled out other factors that might explain the individuals’ cognitive symptoms, including childhood intellectual disability, which has been linked to dementia risk, the underlying condition that prompted their treatment with c-hGH, growth hormone deficiency, and cranial radiotherapy, which four of the individuals had received. They also ruled out inherited disease in all five of the cases with samples available for testing. 

“Taken together, the only factor common to all of the patients whom we describe is treatment with the HWP subtype of c-hGH,” the authors write. “Given the strong experimental evidence for A-beta transmission from relevant archived HWP c-hGH batches, we conclude that this is the most plausible explanation for the findings observed.”

Investigators say the findings show that, like other prion diseases, AD has three etiologies: sporadic, inherited, and rare acquired forms, or iatrogenic AD. 

“The clinical syndrome developed by these individuals can, therefore, be termed iatrogenic Alzheimer’s disease, and Alzheimer’s disease should now be recognized as a potentially transmissible disorder,” the authors write. 

“Our cases suggest that, similarly to what is observed in human prion diseases, iatrogenic forms of Alzheimer’s disease differ phenotypically from sporadic and inherited forms, with some individuals remaining asymptomatic despite exposure to A-beta seeds due to protective factors that, at present, are unknown,” they continue
 

‘Measure of Skepticism’

In an accompanying editorial, Mathias Jucker, PhD, of the Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany, and Lary C. Walker, PhD, in the Department of Neurology at Emory University, Atlanta, write that the findings should be considered “with a measure of skepticism.”

“The cases presented are diverse and complicated; the individuals had undergone a variety of medical interventions for various disorders earlier in life, and it is difficult to exclude a contribution of these circumstances to the complex disease phenotypes that appeared many years later,” they write. 

However, they continue, “there is good reason to take the findings seriously.”

“From a practical standpoint, this report reinforces the potential of amyloid-beta seeds as targets for early prevention, and it underscores the importance of informed caution in the preparation of surgical instruments, handling of tissues, and implementation of therapeutic biologics, particularly those derived from human sources,” Dr. Jucker and Dr. Walker write. 

Commenting on the findings for this news organization, Christopher Weber, PhD, director of global science initiatives for the Alzheimer’s Association, says the idea that amyloid-beta is transmissible between individuals has been shown before. 

“We’ve known for a long time that it is possible to create abnormal amyloid buildup — similar to that seen in Alzheimer’s – in the brain of an animal by injecting it with amyloid-beta. We also transfer human Alzheimer’s genes into animals to initiate abnormal, Alzheimer’s-like processes in their brains,” he said. “Thus, the idea that amyloid is transferable between individuals is not so novel as implied in the new paper.”

However, the study does highlight the importance of safety measures to prevent the accidental transmission of amyloid-beta, Weber added. 

“It is a reasonable and actionable caution that the scientific and clinical communities must understand the possible risks and ensure that all methods of transmission are eliminated — for example, with complete and conscientious sterilization of surgical instruments,” he said. “Bottom line: We shouldn’t put amyloid-beta into people’s brains, either accidentally or on purpose, and appropriate measures should be in place to ensure that doesn’t happen.”

The study was supported by the Medical Research Council, the National Institute for Health and Care Research (NIHR), the NIHR University College of London Hospital Biomedical Research Centre, Alzheimer’s Research UK, and the Stroke Association. Dr. Collinge is a shareholder and director of D-Gen, Ltd., an academic spin-out company working in the field of prion disease diagnosis, decontamination and therapeutics. Dr. Jucker and Dr. Walker report no conflicts of interest. 

A version of this article appeared on Medscape.com.

TOPLINE: 

Pet ownership is associated with slower cognitive decline in seniors who live alone, a new longitudinal cohort study showed. Investigators note the findings are important because previous research suggests older adults who live alone are at higher risk for dementia.

METHODOLOGY:

• Investigators analyzed data on 7945 participants aged 50 years and older (56% female; mean age, 66 years) from the English Longitudinal Study of Ageing (ELSA) and determined whether they lived alone or had a pet.
• Every couple of years for the next 8 years after baseline, participants were assessed for verbal cognition, verbal memory, and verbal fluency. Information about covariates including age, sex, employment status, educational level, and health was also collected.
• 35% of participants were pet owners, and 27% lived alone.

TAKEAWAY: 

• Pet owners who lived alone had a slower rate of decline in verbal cognition (P = .009), verbal memory (P = .04), and verbal fluency (P = .03) compared with those without pets who lived alone.
• Stratified analysis showed that pet ownership was associated with slower rates of decline in composite verbal cognition, verbal memory, and verbal fluency but only among those who lived alone (all P < .001).
• There was no significant difference in rates of decline in composite verbal cognition, verbal memory, or verbal fluency between pet owners living alone and pet owners living with others.

IN PRACTICE:

“Pet ownership completely offset the associations of living alone with declining rates in verbal memory, verbal fluency, and composite verbal cognition. Our findings provide innovative insights for developing public health policies to slow cognitive decline in older adults living alone,” the authors wrote. 

SOURCE:

Ciyong Lu, PhD, of Sun Yat-sen University in Guangzhou, China, led the study, which was published online on December 26, 2023, in JAMA Network Open.

LIMITATIONS:

Whereas cognitive function includes multiple components, the study only assessed verbal memory and verbal fluency. Also, the study did not gather information on the duration of pet ownership after baseline.

DISCLOSURES:

The investigators reported no disclosures.
 

A version of this article appeared on Medscape.com.

TOPLINE: 

Pet ownership is associated with slower cognitive decline in seniors who live alone, a new longitudinal cohort study showed. Investigators note the findings are important because previous research suggests older adults who live alone are at higher risk for dementia.

METHODOLOGY:

• Investigators analyzed data on 7945 participants aged 50 years and older (56% female; mean age, 66 years) from the English Longitudinal Study of Ageing (ELSA) and determined whether they lived alone or had a pet.
• Every couple of years for the next 8 years after baseline, participants were assessed for verbal cognition, verbal memory, and verbal fluency. Information about covariates including age, sex, employment status, educational level, and health was also collected.
• 35% of participants were pet owners, and 27% lived alone.

TAKEAWAY: 

• Pet owners who lived alone had a slower rate of decline in verbal cognition (P = .009), verbal memory (P = .04), and verbal fluency (P = .03) compared with those without pets who lived alone.
• Stratified analysis showed that pet ownership was associated with slower rates of decline in composite verbal cognition, verbal memory, and verbal fluency but only among those who lived alone (all P < .001).
• There was no significant difference in rates of decline in composite verbal cognition, verbal memory, or verbal fluency between pet owners living alone and pet owners living with others.

IN PRACTICE:

“Pet ownership completely offset the associations of living alone with declining rates in verbal memory, verbal fluency, and composite verbal cognition. Our findings provide innovative insights for developing public health policies to slow cognitive decline in older adults living alone,” the authors wrote. 

SOURCE:

Ciyong Lu, PhD, of Sun Yat-sen University in Guangzhou, China, led the study, which was published online on December 26, 2023, in JAMA Network Open.

LIMITATIONS:

Whereas cognitive function includes multiple components, the study only assessed verbal memory and verbal fluency. Also, the study did not gather information on the duration of pet ownership after baseline.

DISCLOSURES:

The investigators reported no disclosures.
 

A version of this article appeared on Medscape.com.

TOPLINE: 

Pet ownership is associated with slower cognitive decline in seniors who live alone, a new longitudinal cohort study showed. Investigators note the findings are important because previous research suggests older adults who live alone are at higher risk for dementia.

METHODOLOGY:

• Investigators analyzed data on 7945 participants aged 50 years and older (56% female; mean age, 66 years) from the English Longitudinal Study of Ageing (ELSA) and determined whether they lived alone or had a pet.
• Every couple of years for the next 8 years after baseline, participants were assessed for verbal cognition, verbal memory, and verbal fluency. Information about covariates including age, sex, employment status, educational level, and health was also collected.
• 35% of participants were pet owners, and 27% lived alone.

TAKEAWAY: 

• Pet owners who lived alone had a slower rate of decline in verbal cognition (P = .009), verbal memory (P = .04), and verbal fluency (P = .03) compared with those without pets who lived alone.
• Stratified analysis showed that pet ownership was associated with slower rates of decline in composite verbal cognition, verbal memory, and verbal fluency but only among those who lived alone (all P < .001).
• There was no significant difference in rates of decline in composite verbal cognition, verbal memory, or verbal fluency between pet owners living alone and pet owners living with others.

IN PRACTICE:

“Pet ownership completely offset the associations of living alone with declining rates in verbal memory, verbal fluency, and composite verbal cognition. Our findings provide innovative insights for developing public health policies to slow cognitive decline in older adults living alone,” the authors wrote. 

SOURCE:

Ciyong Lu, PhD, of Sun Yat-sen University in Guangzhou, China, led the study, which was published online on December 26, 2023, in JAMA Network Open.

LIMITATIONS:

Whereas cognitive function includes multiple components, the study only assessed verbal memory and verbal fluency. Also, the study did not gather information on the duration of pet ownership after baseline.

DISCLOSURES:

The investigators reported no disclosures.
 

A version of this article appeared on Medscape.com.

Mr. Smith was once a nice guy.

These days, unfortunately, he’s anything but. The ravages of a neurodegenerative disease have left him demented, impulsive, and agitated.

His family is trying to find placement for him, and in the meantime I’m doing my best to keep his behavior controlled. Like many things in medicine, this is as much art as science. A tablet of this, a capsule of that, increase this slightly, add something for PRN use ... a witch’s brew of modern medicine.

Because of his worsening, his wife was calling us several times a week with updates, not in an annoying way but in an “I need help” way. I began answering the phone myself if I saw her number come up, because it was easier and faster for me to deal with her directly, and I knew she wasn’t calling for fun.

A few months ago I stopped a medication that didn’t seem to be doing much and started a different one.

And then things went quiet. His wife’s calls went from 3-4 a week to none.

This worried me. I mean, maybe the new medicine was working. ... but the sudden silence was deafening.

One week went by, then two ... I did a Google search to make sure he and his wife hadn’t died or been in the news.

Of course, I could have picked up the phone and called his wife, but why tempt fate?

Three weeks ... I was sure my MA, who handles far more calls than I do, had probably noticed this, too.

It would have been easy to mention it, but even with 16 years of school and 5 years of medical training, not to mention 3,000-4,000 years of hard-earned science behind me, there was the old grade school notion of jinxing myself. To say something is to invite trouble.

Four weeks. Finally, his wife called in and reached my MA. The medication had been working, but now was wearing off and the dose needed to be adjusted. So we did that.

Afterward I mentioned the time lapse to my MA, that I’d been afraid of jinxing it by saying something to her, and she told me she’d been thinking the same thing.

Funny when you think about it. We’re both educated people, believers in science, and (I hope) intelligent. We’re living in a (by human standards) technologically advanced time.

Yet, the old superstitions are still there, the idea that we somehow have magical control over time, space, random chance, and the actions of others by not talking about a phone call (or the lack of one).

Surprisingly (or maybe not), this is pretty normal. When on call we never say “quiet,” for fear of enraging the mysterious Call Gods. If needed, we use “the Q word.”

We still try not to walk under ladders, avoid stepping on sidewalk cracks, carry good luck charms, cross fingers, and fight over wishbones.

Superstitions such as saying “bless you” or “gesundheit” when someone sneezes are so ingrained into us that they’re now part of good manners and polite society.

I’ve worked in quite a few hospitals over the years. Not one of them had a room on any floor that ended in 13, always jumping from 12 to 14.

Civilization is roughly 10,000-15,000 years old. We have the internet and can travel to (relatively nearby) space and back. We have probes exploring — and even leaving — our solar system.

But it’s one thing to say a superstition is silly. It’s another to actually convince your primeval self of it.

I’m going to knock on wood now.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Mr. Smith was once a nice guy.

These days, unfortunately, he’s anything but. The ravages of a neurodegenerative disease have left him demented, impulsive, and agitated.

His family is trying to find placement for him, and in the meantime I’m doing my best to keep his behavior controlled. Like many things in medicine, this is as much art as science. A tablet of this, a capsule of that, increase this slightly, add something for PRN use ... a witch’s brew of modern medicine.

Because of his worsening, his wife was calling us several times a week with updates, not in an annoying way but in an “I need help” way. I began answering the phone myself if I saw her number come up, because it was easier and faster for me to deal with her directly, and I knew she wasn’t calling for fun.

A few months ago I stopped a medication that didn’t seem to be doing much and started a different one.

And then things went quiet. His wife’s calls went from 3-4 a week to none.

This worried me. I mean, maybe the new medicine was working. ... but the sudden silence was deafening.

One week went by, then two ... I did a Google search to make sure he and his wife hadn’t died or been in the news.

Of course, I could have picked up the phone and called his wife, but why tempt fate?

Three weeks ... I was sure my MA, who handles far more calls than I do, had probably noticed this, too.

It would have been easy to mention it, but even with 16 years of school and 5 years of medical training, not to mention 3,000-4,000 years of hard-earned science behind me, there was the old grade school notion of jinxing myself. To say something is to invite trouble.

Four weeks. Finally, his wife called in and reached my MA. The medication had been working, but now was wearing off and the dose needed to be adjusted. So we did that.

Afterward I mentioned the time lapse to my MA, that I’d been afraid of jinxing it by saying something to her, and she told me she’d been thinking the same thing.

Funny when you think about it. We’re both educated people, believers in science, and (I hope) intelligent. We’re living in a (by human standards) technologically advanced time.

Yet, the old superstitions are still there, the idea that we somehow have magical control over time, space, random chance, and the actions of others by not talking about a phone call (or the lack of one).

Surprisingly (or maybe not), this is pretty normal. When on call we never say “quiet,” for fear of enraging the mysterious Call Gods. If needed, we use “the Q word.”

We still try not to walk under ladders, avoid stepping on sidewalk cracks, carry good luck charms, cross fingers, and fight over wishbones.

Superstitions such as saying “bless you” or “gesundheit” when someone sneezes are so ingrained into us that they’re now part of good manners and polite society.

I’ve worked in quite a few hospitals over the years. Not one of them had a room on any floor that ended in 13, always jumping from 12 to 14.

Civilization is roughly 10,000-15,000 years old. We have the internet and can travel to (relatively nearby) space and back. We have probes exploring — and even leaving — our solar system.

But it’s one thing to say a superstition is silly. It’s another to actually convince your primeval self of it.

I’m going to knock on wood now.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Mr. Smith was once a nice guy.

These days, unfortunately, he’s anything but. The ravages of a neurodegenerative disease have left him demented, impulsive, and agitated.

His family is trying to find placement for him, and in the meantime I’m doing my best to keep his behavior controlled. Like many things in medicine, this is as much art as science. A tablet of this, a capsule of that, increase this slightly, add something for PRN use ... a witch’s brew of modern medicine.

Because of his worsening, his wife was calling us several times a week with updates, not in an annoying way but in an “I need help” way. I began answering the phone myself if I saw her number come up, because it was easier and faster for me to deal with her directly, and I knew she wasn’t calling for fun.

A few months ago I stopped a medication that didn’t seem to be doing much and started a different one.

And then things went quiet. His wife’s calls went from 3-4 a week to none.

This worried me. I mean, maybe the new medicine was working. ... but the sudden silence was deafening.

One week went by, then two ... I did a Google search to make sure he and his wife hadn’t died or been in the news.

Of course, I could have picked up the phone and called his wife, but why tempt fate?

Three weeks ... I was sure my MA, who handles far more calls than I do, had probably noticed this, too.

It would have been easy to mention it, but even with 16 years of school and 5 years of medical training, not to mention 3,000-4,000 years of hard-earned science behind me, there was the old grade school notion of jinxing myself. To say something is to invite trouble.

Four weeks. Finally, his wife called in and reached my MA. The medication had been working, but now was wearing off and the dose needed to be adjusted. So we did that.

Afterward I mentioned the time lapse to my MA, that I’d been afraid of jinxing it by saying something to her, and she told me she’d been thinking the same thing.

Funny when you think about it. We’re both educated people, believers in science, and (I hope) intelligent. We’re living in a (by human standards) technologically advanced time.

Yet, the old superstitions are still there, the idea that we somehow have magical control over time, space, random chance, and the actions of others by not talking about a phone call (or the lack of one).

Surprisingly (or maybe not), this is pretty normal. When on call we never say “quiet,” for fear of enraging the mysterious Call Gods. If needed, we use “the Q word.”

We still try not to walk under ladders, avoid stepping on sidewalk cracks, carry good luck charms, cross fingers, and fight over wishbones.

Superstitions such as saying “bless you” or “gesundheit” when someone sneezes are so ingrained into us that they’re now part of good manners and polite society.

I’ve worked in quite a few hospitals over the years. Not one of them had a room on any floor that ended in 13, always jumping from 12 to 14.

Civilization is roughly 10,000-15,000 years old. We have the internet and can travel to (relatively nearby) space and back. We have probes exploring — and even leaving — our solar system.

But it’s one thing to say a superstition is silly. It’s another to actually convince your primeval self of it.

I’m going to knock on wood now.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

New data from the Cocoa Supplement and Multivitamin Outcomes Study (COSMOS) suggest that a daily multivitamin may help protect the aging brain. However, at least one expert has concerns about the study’s methodology and, as a result, the interpretation of its findings. 

The meta-analysis of three separate cognition studies provides “strong and consistent evidence that taking a daily multivitamin, containing more than 20 essential micronutrients, can help prevent memory loss and slow down cognitive aging,” study investigator Chirag Vyas, MBBS, MPH, with Massachusetts General Hospital and Harvard Medical School, Boston, told this news organization. 

“We are not now recommending multivitamin use, but the evidence is compelling that supports the promise of multivitamins to help prevent cognitive decline,” Dr. Vyas said. 

The new data, from the cognitive substudies of COSMOS, were published online in the American Journal of Clinical Nutrition.
 

Clinically Meaningful Benefit?

To recap, COSMOS was a 2 x 2 factorial trial of coca extract (500 mg/d flavanols) and/or a daily commercial multivitamin-mineral (MVM) supplement for cardiovascular disease and cancer prevention among more than 21,000 US adults aged 60 years or older. 

Neither the cocoa extract nor the MVM supplement had a significant impact on cancer or cardiovascular disease events.

COMOS-Mind was a substudy of 2262 participants aged 65 or older without dementia who completed telephone-based cognitive assessments at baseline and annually for 3 years. 

As previously reported by this news organization in COSMOS-Mind, there was no cognitive benefit of daily cocoa extract, but daily MVM supplementation was associated with improved global cognition, episodic memory, and executive function. However, the difference in global cognitive function between MVM and placebo was small, with a mean 0.07-point improvement on the z-score at 3 years. 

COSMOS-Web was a substudy of 3562 original participants who were evaluated annually for 3 years using an internet-based battery of neuropsychological tests. 

In this analysis, those taking the MVM supplement performed better on a test for immediate memory recall (remembering a list of 20 words); they were able to remember an additional 0.71 word on average compared with 0.44 word in the placebo group. However, they did not improve on tests of memory retention, executive function, or novel object recognition.

The new data are from COSMOS-Clinic, an analysis of 573 participants who completed in-person cognitive assessments. 

COSMOS-Clinic showed a modest benefit of MVM, compared with placebo, on global cognition over 2 years (mean difference, 0.06 SD units [SU]), with a significantly more favorable change in episodic memory (mean difference, 0.12 SU) but not in executive function/attention (mean difference, 0.04 SU), the researchers reported. 

They also conducted a meta-analysis based on the three separate cognitive substudies, with 5200 nonoverlapping COSMOS participants. 

The results showed “clear evidence” of MVM benefits on global cognition (mean difference, 0.07 SU; P = .0009) and episodic memory (mean difference, 0.06 SU; P =.0007), they reported, with the magnitude of effect on global cognition equivalent to reducing cognitive aging by 2 years.

In a statement, JoAnn Manson, MD, DrPH, chief of the Division of Preventive Medicine at Brigham and Women’s Hospital, who led the overall COSMOS trial, said that “the finding that a daily multivitamin improved memory and slowed cognitive aging in three separate placebo-controlled studies in COSMOS is exciting and further supports the promise of multivitamins as a safe, accessible, and affordable approach to protecting cognitive health in older adults.”
 

Not a Meta-analysis?

In an interview with this news organization, Christopher Labos, MD CM, MSc, a cardiologist and epidemiologist based in Montreal, Canada, who wasn’t involved in COSMOS, cautioned that the evidence to date on multivitamins for memory and brain health are “not all that impressive.”

Dr. Labos is a columnist for this news organization and previously has written about the COSMOS trial. 

He said it is important to note that this “meta-analysis of COSMOS data, strictly speaking, is not a meta-analysis” because the patients were all from the original COSMOS study without including any additional patients, “so you don’t have any more data than what you started with.

“The fact that the results are consistent with the original trial is not surprising. In fact, it would be concerning if they were not consistent because they’re the same population. They were just assessed differently — by phone, online, or in person,” Dr. Labos explained. 

“It is hard to tell what the benefit with multivitamins actually means in terms of hard clinical endpoints that matter to patients. Scoring a little bit better on a standardized test — I guess that’s a good thing, but does that mean you’re less likely to get dementia? I’m not sure we’re there yet,” he told this news organization. 

The bottom line, said Dr. Labos, is that “at this point, the evidence does not support recommending multivitamins purely for brain health. There is also a cost and potential downside associated with their use.”

Also weighing in on the new analyses from COSMOS, Claire Sexton, DPhil, Alzheimer’s Association senior director of scientific programs and outreach, said while there are now “positive, large-scale, long-term studies that show that multivitamin-mineral supplementation for older adults may slow cognitive aging, the Alzheimer’s Association is not ready to recommend widespread use of a multivitamin supplement to reduce risk of cognitive decline in older adults.

“Independent confirmatory studies are needed in larger, more diverse, and representative study populations. COSMOS-Clinic, for example, had less than 2% non-White in the multivitamin group and 5% non-White in the placebo group. It is critical that future treatments and preventions are effective in all populations,” Dr. Sexton told this news organization.

She noted that multivitamin supplements are “generally easy to find and relatively affordable. With confirmation, these promising findings have the potential to significantly impact public health — improving brain health, lowering healthcare costs, reducing caregiver burden — especially among older adults.”

The Alzheimer’s Association, Dr. Sexton said, “envisions a future where there are multiple treatments available that address the disease in multiple ways — like heart disease and cancer — and that can be combined into powerful combination therapies, in conjunction with brain-healthy guidelines for lifestyle, like diet and physical activity.”

The Alzheimer’s Association is leading a 2-year clinical trial known as US POINTER to evaluate whether lifestyle interventions that target multiple risk factors can protect cognition in older adults at increased risk for cognitive decline.

COSMOS-Clinic and the cognition studies in the meta-analysis were supported by investigator-initiated grants from Mars Edge, a segment of Mars Inc., and the National Institutes of Health. Multivitamin and placebo tablets and packaging were donated by Pfizer, Inc Consumer Healthcare (now Haleon). Disclosures for the COSMOS investigators are available with the original article. Dr. Labos and Dr. Sexton have no relevant disclosures. 

A version of this article appeared on Medscape.com.

New data from the Cocoa Supplement and Multivitamin Outcomes Study (COSMOS) suggest that a daily multivitamin may help protect the aging brain. However, at least one expert has concerns about the study’s methodology and, as a result, the interpretation of its findings. 

The meta-analysis of three separate cognition studies provides “strong and consistent evidence that taking a daily multivitamin, containing more than 20 essential micronutrients, can help prevent memory loss and slow down cognitive aging,” study investigator Chirag Vyas, MBBS, MPH, with Massachusetts General Hospital and Harvard Medical School, Boston, told this news organization. 

“We are not now recommending multivitamin use, but the evidence is compelling that supports the promise of multivitamins to help prevent cognitive decline,” Dr. Vyas said. 

The new data, from the cognitive substudies of COSMOS, were published online in the American Journal of Clinical Nutrition.
 

Clinically Meaningful Benefit?

To recap, COSMOS was a 2 x 2 factorial trial of coca extract (500 mg/d flavanols) and/or a daily commercial multivitamin-mineral (MVM) supplement for cardiovascular disease and cancer prevention among more than 21,000 US adults aged 60 years or older. 

Neither the cocoa extract nor the MVM supplement had a significant impact on cancer or cardiovascular disease events.

COMOS-Mind was a substudy of 2262 participants aged 65 or older without dementia who completed telephone-based cognitive assessments at baseline and annually for 3 years. 

As previously reported by this news organization in COSMOS-Mind, there was no cognitive benefit of daily cocoa extract, but daily MVM supplementation was associated with improved global cognition, episodic memory, and executive function. However, the difference in global cognitive function between MVM and placebo was small, with a mean 0.07-point improvement on the z-score at 3 years. 

COSMOS-Web was a substudy of 3562 original participants who were evaluated annually for 3 years using an internet-based battery of neuropsychological tests. 

In this analysis, those taking the MVM supplement performed better on a test for immediate memory recall (remembering a list of 20 words); they were able to remember an additional 0.71 word on average compared with 0.44 word in the placebo group. However, they did not improve on tests of memory retention, executive function, or novel object recognition.

The new data are from COSMOS-Clinic, an analysis of 573 participants who completed in-person cognitive assessments. 

COSMOS-Clinic showed a modest benefit of MVM, compared with placebo, on global cognition over 2 years (mean difference, 0.06 SD units [SU]), with a significantly more favorable change in episodic memory (mean difference, 0.12 SU) but not in executive function/attention (mean difference, 0.04 SU), the researchers reported. 

They also conducted a meta-analysis based on the three separate cognitive substudies, with 5200 nonoverlapping COSMOS participants. 

The results showed “clear evidence” of MVM benefits on global cognition (mean difference, 0.07 SU; P = .0009) and episodic memory (mean difference, 0.06 SU; P =.0007), they reported, with the magnitude of effect on global cognition equivalent to reducing cognitive aging by 2 years.

In a statement, JoAnn Manson, MD, DrPH, chief of the Division of Preventive Medicine at Brigham and Women’s Hospital, who led the overall COSMOS trial, said that “the finding that a daily multivitamin improved memory and slowed cognitive aging in three separate placebo-controlled studies in COSMOS is exciting and further supports the promise of multivitamins as a safe, accessible, and affordable approach to protecting cognitive health in older adults.”
 

Not a Meta-analysis?

In an interview with this news organization, Christopher Labos, MD CM, MSc, a cardiologist and epidemiologist based in Montreal, Canada, who wasn’t involved in COSMOS, cautioned that the evidence to date on multivitamins for memory and brain health are “not all that impressive.”

Dr. Labos is a columnist for this news organization and previously has written about the COSMOS trial. 

He said it is important to note that this “meta-analysis of COSMOS data, strictly speaking, is not a meta-analysis” because the patients were all from the original COSMOS study without including any additional patients, “so you don’t have any more data than what you started with.

“The fact that the results are consistent with the original trial is not surprising. In fact, it would be concerning if they were not consistent because they’re the same population. They were just assessed differently — by phone, online, or in person,” Dr. Labos explained. 

“It is hard to tell what the benefit with multivitamins actually means in terms of hard clinical endpoints that matter to patients. Scoring a little bit better on a standardized test — I guess that’s a good thing, but does that mean you’re less likely to get dementia? I’m not sure we’re there yet,” he told this news organization. 

The bottom line, said Dr. Labos, is that “at this point, the evidence does not support recommending multivitamins purely for brain health. There is also a cost and potential downside associated with their use.”

Also weighing in on the new analyses from COSMOS, Claire Sexton, DPhil, Alzheimer’s Association senior director of scientific programs and outreach, said while there are now “positive, large-scale, long-term studies that show that multivitamin-mineral supplementation for older adults may slow cognitive aging, the Alzheimer’s Association is not ready to recommend widespread use of a multivitamin supplement to reduce risk of cognitive decline in older adults.

“Independent confirmatory studies are needed in larger, more diverse, and representative study populations. COSMOS-Clinic, for example, had less than 2% non-White in the multivitamin group and 5% non-White in the placebo group. It is critical that future treatments and preventions are effective in all populations,” Dr. Sexton told this news organization.

She noted that multivitamin supplements are “generally easy to find and relatively affordable. With confirmation, these promising findings have the potential to significantly impact public health — improving brain health, lowering healthcare costs, reducing caregiver burden — especially among older adults.”

The Alzheimer’s Association, Dr. Sexton said, “envisions a future where there are multiple treatments available that address the disease in multiple ways — like heart disease and cancer — and that can be combined into powerful combination therapies, in conjunction with brain-healthy guidelines for lifestyle, like diet and physical activity.”

The Alzheimer’s Association is leading a 2-year clinical trial known as US POINTER to evaluate whether lifestyle interventions that target multiple risk factors can protect cognition in older adults at increased risk for cognitive decline.

COSMOS-Clinic and the cognition studies in the meta-analysis were supported by investigator-initiated grants from Mars Edge, a segment of Mars Inc., and the National Institutes of Health. Multivitamin and placebo tablets and packaging were donated by Pfizer, Inc Consumer Healthcare (now Haleon). Disclosures for the COSMOS investigators are available with the original article. Dr. Labos and Dr. Sexton have no relevant disclosures. 

A version of this article appeared on Medscape.com.

New data from the Cocoa Supplement and Multivitamin Outcomes Study (COSMOS) suggest that a daily multivitamin may help protect the aging brain. However, at least one expert has concerns about the study’s methodology and, as a result, the interpretation of its findings. 

The meta-analysis of three separate cognition studies provides “strong and consistent evidence that taking a daily multivitamin, containing more than 20 essential micronutrients, can help prevent memory loss and slow down cognitive aging,” study investigator Chirag Vyas, MBBS, MPH, with Massachusetts General Hospital and Harvard Medical School, Boston, told this news organization. 

“We are not now recommending multivitamin use, but the evidence is compelling that supports the promise of multivitamins to help prevent cognitive decline,” Dr. Vyas said. 

The new data, from the cognitive substudies of COSMOS, were published online in the American Journal of Clinical Nutrition.
 

Clinically Meaningful Benefit?

To recap, COSMOS was a 2 x 2 factorial trial of coca extract (500 mg/d flavanols) and/or a daily commercial multivitamin-mineral (MVM) supplement for cardiovascular disease and cancer prevention among more than 21,000 US adults aged 60 years or older. 

Neither the cocoa extract nor the MVM supplement had a significant impact on cancer or cardiovascular disease events.

COMOS-Mind was a substudy of 2262 participants aged 65 or older without dementia who completed telephone-based cognitive assessments at baseline and annually for 3 years. 

As previously reported by this news organization in COSMOS-Mind, there was no cognitive benefit of daily cocoa extract, but daily MVM supplementation was associated with improved global cognition, episodic memory, and executive function. However, the difference in global cognitive function between MVM and placebo was small, with a mean 0.07-point improvement on the z-score at 3 years. 

COSMOS-Web was a substudy of 3562 original participants who were evaluated annually for 3 years using an internet-based battery of neuropsychological tests. 

In this analysis, those taking the MVM supplement performed better on a test for immediate memory recall (remembering a list of 20 words); they were able to remember an additional 0.71 word on average compared with 0.44 word in the placebo group. However, they did not improve on tests of memory retention, executive function, or novel object recognition.

The new data are from COSMOS-Clinic, an analysis of 573 participants who completed in-person cognitive assessments. 

COSMOS-Clinic showed a modest benefit of MVM, compared with placebo, on global cognition over 2 years (mean difference, 0.06 SD units [SU]), with a significantly more favorable change in episodic memory (mean difference, 0.12 SU) but not in executive function/attention (mean difference, 0.04 SU), the researchers reported. 

They also conducted a meta-analysis based on the three separate cognitive substudies, with 5200 nonoverlapping COSMOS participants. 

The results showed “clear evidence” of MVM benefits on global cognition (mean difference, 0.07 SU; P = .0009) and episodic memory (mean difference, 0.06 SU; P =.0007), they reported, with the magnitude of effect on global cognition equivalent to reducing cognitive aging by 2 years.

In a statement, JoAnn Manson, MD, DrPH, chief of the Division of Preventive Medicine at Brigham and Women’s Hospital, who led the overall COSMOS trial, said that “the finding that a daily multivitamin improved memory and slowed cognitive aging in three separate placebo-controlled studies in COSMOS is exciting and further supports the promise of multivitamins as a safe, accessible, and affordable approach to protecting cognitive health in older adults.”
 

Not a Meta-analysis?

In an interview with this news organization, Christopher Labos, MD CM, MSc, a cardiologist and epidemiologist based in Montreal, Canada, who wasn’t involved in COSMOS, cautioned that the evidence to date on multivitamins for memory and brain health are “not all that impressive.”

Dr. Labos is a columnist for this news organization and previously has written about the COSMOS trial. 

He said it is important to note that this “meta-analysis of COSMOS data, strictly speaking, is not a meta-analysis” because the patients were all from the original COSMOS study without including any additional patients, “so you don’t have any more data than what you started with.

“The fact that the results are consistent with the original trial is not surprising. In fact, it would be concerning if they were not consistent because they’re the same population. They were just assessed differently — by phone, online, or in person,” Dr. Labos explained. 

“It is hard to tell what the benefit with multivitamins actually means in terms of hard clinical endpoints that matter to patients. Scoring a little bit better on a standardized test — I guess that’s a good thing, but does that mean you’re less likely to get dementia? I’m not sure we’re there yet,” he told this news organization. 

The bottom line, said Dr. Labos, is that “at this point, the evidence does not support recommending multivitamins purely for brain health. There is also a cost and potential downside associated with their use.”

Also weighing in on the new analyses from COSMOS, Claire Sexton, DPhil, Alzheimer’s Association senior director of scientific programs and outreach, said while there are now “positive, large-scale, long-term studies that show that multivitamin-mineral supplementation for older adults may slow cognitive aging, the Alzheimer’s Association is not ready to recommend widespread use of a multivitamin supplement to reduce risk of cognitive decline in older adults.

“Independent confirmatory studies are needed in larger, more diverse, and representative study populations. COSMOS-Clinic, for example, had less than 2% non-White in the multivitamin group and 5% non-White in the placebo group. It is critical that future treatments and preventions are effective in all populations,” Dr. Sexton told this news organization.

She noted that multivitamin supplements are “generally easy to find and relatively affordable. With confirmation, these promising findings have the potential to significantly impact public health — improving brain health, lowering healthcare costs, reducing caregiver burden — especially among older adults.”

The Alzheimer’s Association, Dr. Sexton said, “envisions a future where there are multiple treatments available that address the disease in multiple ways — like heart disease and cancer — and that can be combined into powerful combination therapies, in conjunction with brain-healthy guidelines for lifestyle, like diet and physical activity.”

The Alzheimer’s Association is leading a 2-year clinical trial known as US POINTER to evaluate whether lifestyle interventions that target multiple risk factors can protect cognition in older adults at increased risk for cognitive decline.

COSMOS-Clinic and the cognition studies in the meta-analysis were supported by investigator-initiated grants from Mars Edge, a segment of Mars Inc., and the National Institutes of Health. Multivitamin and placebo tablets and packaging were donated by Pfizer, Inc Consumer Healthcare (now Haleon). Disclosures for the COSMOS investigators are available with the original article. Dr. Labos and Dr. Sexton have no relevant disclosures. 

A version of this article appeared on Medscape.com.