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A New and Early Predictor of Dementia?
, in new findings that may provide a potential opportunity to identify high-risk populations for targeted enrollment in clinical trials of dementia prevention and treatment.
Results of an international study assessing frailty trajectories showed frailty levels notably increased in the 4-9 years before dementia diagnosis. Even among study participants whose baseline frailty measurement was taken prior to that acceleration period, frailty was still positively associated with dementia risk, the investigators noted.
“We found that with every four to five additional health problems, there is on average a 40% higher risk of developing dementia, while the risk is lower for people who are more physically fit,” said study investigator David Ward, PhD, of the Centre for Health Services Research, The University of Queensland, Brisbane, Australia.
The findings were published online in JAMA Neurology.
A Promising Biomarker
An accessible biomarker for both biologic age and dementia risk is essential for advancing dementia prevention and treatment strategies, the investigators noted, adding that growing evidence suggests frailty may be a promising candidate for this role.
To learn more about the association between frailty and dementia, Ward and his team analyzed data on 29,849 participants aged 60 years or above (mean age, 71.6 years; 62% women) who participated in four cohort studies: the English Longitudinal Study of Ageing (ELSA; n = 6771), the Health and Retirement Study (HRS; n = 9045), the Rush Memory and Aging Project (MAP; n = 1451), and the National Alzheimer’s Coordinating Center (NACC; n = 12,582).
The primary outcome was all-cause dementia. Depending on the cohort, dementia diagnoses were determined through cognitive testing, self- or family report of physician diagnosis, or a diagnosis by the study physician. Participants were excluded if they had cognitive impairment at baseline.
Investigators retrospectively determined frailty index scores by gathering information on health and functional outcomes for participants from each cohort. Only participants with frailty data on at least 30 deficits were included.
Commonly included deficits included high blood pressure, cancer, and chronic pain, as well as functional problems such as hearing impairment, difficulty with mobility, and challenges managing finances.
Investigators conducted follow-up visits with participants until they developed dementia or until the study ended, with follow-up periods varying across cohorts.
After adjustment for potential confounders, frailty scores were modeled using backward time scales.
Among participants who developed incident dementia (n = 3154), covariate-adjusted expected frailty index scores were, on average, higher in women than in men by 18.5% in ELSA, 20.9% in HRS, and 16.2% in MAP. There were no differences in frailty scores between sexes in the NACC cohort.
When measured on a timeline, as compared with those who didn’t develop dementia, frailty scores were significantly and consistently higher in the dementia groups 8-20 before dementia onset (20 years in HRS; 13 in MAP; 12 in ELSA; 8 in NACC).
Increases in the rates of frailty index scores began accelerating 4-9 years before dementia onset for the various cohorts, investigators noted.
In all four cohorts, each 0.1 increase in frailty scores was positively associated with increased dementia risk.
Adjusted hazard ratios [aHRs] ranged from 1.18 in the HRS cohort to 1.73 in the NACC cohort, which showed the strongest association.
In participants whose baseline frailty measurement was conducted before the predementia acceleration period began, the association of frailty scores and dementia risk was positive. These aHRs ranged from 1.18 in the HRS cohort to 1.43 in the NACC cohort.
The ‘Four Pillars’ of Prevention
The good news, investigators said, is that the long trajectory of frailty symptoms preceding dementia onset provides plenty of opportunity for intervention.
To slow the development of frailty, Ward suggested adhering to the “four pillars of frailty prevention and management,” which include good nutrition with plenty of protein, exercise, optimizing medications for chronic conditions, and maintaining a strong social network.
Ward suggested neurologists track frailty in their patients and pointed to a recent article focused on helping neurologists use frailty measures to influence care planning.
Study limitations include the possibility of reverse causality and the fact that investigators could not adjust for genetic risk for dementia.
Unclear Pathway
Commenting on the findings, Lycia Neumann, PhD, senior director of Health Services Research at the Alzheimer’s Association, noted that many studies over the years have shown a link between frailty and dementia. However, she cautioned that a link does not imply causation.
The pathway from frailty to dementia is not 100% clear, and both are complex conditions, said Neumann, who was not part of the study.
“Adopting healthy lifestyle behaviors early and consistently can help decrease the risk of — or postpone the onset of — both frailty and cognitive decline,” she said. Neumann added that physical activity, a healthy diet, social engagement, and controlling diabetes and blood pressure can also reduce the risk for dementia as well as cardiovascular disease.
The study was funded in part by the Deep Dementia Phenotyping Network through the Frailty and Dementia Special Interest Group. Ward and Neumann reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
, in new findings that may provide a potential opportunity to identify high-risk populations for targeted enrollment in clinical trials of dementia prevention and treatment.
Results of an international study assessing frailty trajectories showed frailty levels notably increased in the 4-9 years before dementia diagnosis. Even among study participants whose baseline frailty measurement was taken prior to that acceleration period, frailty was still positively associated with dementia risk, the investigators noted.
“We found that with every four to five additional health problems, there is on average a 40% higher risk of developing dementia, while the risk is lower for people who are more physically fit,” said study investigator David Ward, PhD, of the Centre for Health Services Research, The University of Queensland, Brisbane, Australia.
The findings were published online in JAMA Neurology.
A Promising Biomarker
An accessible biomarker for both biologic age and dementia risk is essential for advancing dementia prevention and treatment strategies, the investigators noted, adding that growing evidence suggests frailty may be a promising candidate for this role.
To learn more about the association between frailty and dementia, Ward and his team analyzed data on 29,849 participants aged 60 years or above (mean age, 71.6 years; 62% women) who participated in four cohort studies: the English Longitudinal Study of Ageing (ELSA; n = 6771), the Health and Retirement Study (HRS; n = 9045), the Rush Memory and Aging Project (MAP; n = 1451), and the National Alzheimer’s Coordinating Center (NACC; n = 12,582).
The primary outcome was all-cause dementia. Depending on the cohort, dementia diagnoses were determined through cognitive testing, self- or family report of physician diagnosis, or a diagnosis by the study physician. Participants were excluded if they had cognitive impairment at baseline.
Investigators retrospectively determined frailty index scores by gathering information on health and functional outcomes for participants from each cohort. Only participants with frailty data on at least 30 deficits were included.
Commonly included deficits included high blood pressure, cancer, and chronic pain, as well as functional problems such as hearing impairment, difficulty with mobility, and challenges managing finances.
Investigators conducted follow-up visits with participants until they developed dementia or until the study ended, with follow-up periods varying across cohorts.
After adjustment for potential confounders, frailty scores were modeled using backward time scales.
Among participants who developed incident dementia (n = 3154), covariate-adjusted expected frailty index scores were, on average, higher in women than in men by 18.5% in ELSA, 20.9% in HRS, and 16.2% in MAP. There were no differences in frailty scores between sexes in the NACC cohort.
When measured on a timeline, as compared with those who didn’t develop dementia, frailty scores were significantly and consistently higher in the dementia groups 8-20 before dementia onset (20 years in HRS; 13 in MAP; 12 in ELSA; 8 in NACC).
Increases in the rates of frailty index scores began accelerating 4-9 years before dementia onset for the various cohorts, investigators noted.
In all four cohorts, each 0.1 increase in frailty scores was positively associated with increased dementia risk.
Adjusted hazard ratios [aHRs] ranged from 1.18 in the HRS cohort to 1.73 in the NACC cohort, which showed the strongest association.
In participants whose baseline frailty measurement was conducted before the predementia acceleration period began, the association of frailty scores and dementia risk was positive. These aHRs ranged from 1.18 in the HRS cohort to 1.43 in the NACC cohort.
The ‘Four Pillars’ of Prevention
The good news, investigators said, is that the long trajectory of frailty symptoms preceding dementia onset provides plenty of opportunity for intervention.
To slow the development of frailty, Ward suggested adhering to the “four pillars of frailty prevention and management,” which include good nutrition with plenty of protein, exercise, optimizing medications for chronic conditions, and maintaining a strong social network.
Ward suggested neurologists track frailty in their patients and pointed to a recent article focused on helping neurologists use frailty measures to influence care planning.
Study limitations include the possibility of reverse causality and the fact that investigators could not adjust for genetic risk for dementia.
Unclear Pathway
Commenting on the findings, Lycia Neumann, PhD, senior director of Health Services Research at the Alzheimer’s Association, noted that many studies over the years have shown a link between frailty and dementia. However, she cautioned that a link does not imply causation.
The pathway from frailty to dementia is not 100% clear, and both are complex conditions, said Neumann, who was not part of the study.
“Adopting healthy lifestyle behaviors early and consistently can help decrease the risk of — or postpone the onset of — both frailty and cognitive decline,” she said. Neumann added that physical activity, a healthy diet, social engagement, and controlling diabetes and blood pressure can also reduce the risk for dementia as well as cardiovascular disease.
The study was funded in part by the Deep Dementia Phenotyping Network through the Frailty and Dementia Special Interest Group. Ward and Neumann reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
, in new findings that may provide a potential opportunity to identify high-risk populations for targeted enrollment in clinical trials of dementia prevention and treatment.
Results of an international study assessing frailty trajectories showed frailty levels notably increased in the 4-9 years before dementia diagnosis. Even among study participants whose baseline frailty measurement was taken prior to that acceleration period, frailty was still positively associated with dementia risk, the investigators noted.
“We found that with every four to five additional health problems, there is on average a 40% higher risk of developing dementia, while the risk is lower for people who are more physically fit,” said study investigator David Ward, PhD, of the Centre for Health Services Research, The University of Queensland, Brisbane, Australia.
The findings were published online in JAMA Neurology.
A Promising Biomarker
An accessible biomarker for both biologic age and dementia risk is essential for advancing dementia prevention and treatment strategies, the investigators noted, adding that growing evidence suggests frailty may be a promising candidate for this role.
To learn more about the association between frailty and dementia, Ward and his team analyzed data on 29,849 participants aged 60 years or above (mean age, 71.6 years; 62% women) who participated in four cohort studies: the English Longitudinal Study of Ageing (ELSA; n = 6771), the Health and Retirement Study (HRS; n = 9045), the Rush Memory and Aging Project (MAP; n = 1451), and the National Alzheimer’s Coordinating Center (NACC; n = 12,582).
The primary outcome was all-cause dementia. Depending on the cohort, dementia diagnoses were determined through cognitive testing, self- or family report of physician diagnosis, or a diagnosis by the study physician. Participants were excluded if they had cognitive impairment at baseline.
Investigators retrospectively determined frailty index scores by gathering information on health and functional outcomes for participants from each cohort. Only participants with frailty data on at least 30 deficits were included.
Commonly included deficits included high blood pressure, cancer, and chronic pain, as well as functional problems such as hearing impairment, difficulty with mobility, and challenges managing finances.
Investigators conducted follow-up visits with participants until they developed dementia or until the study ended, with follow-up periods varying across cohorts.
After adjustment for potential confounders, frailty scores were modeled using backward time scales.
Among participants who developed incident dementia (n = 3154), covariate-adjusted expected frailty index scores were, on average, higher in women than in men by 18.5% in ELSA, 20.9% in HRS, and 16.2% in MAP. There were no differences in frailty scores between sexes in the NACC cohort.
When measured on a timeline, as compared with those who didn’t develop dementia, frailty scores were significantly and consistently higher in the dementia groups 8-20 before dementia onset (20 years in HRS; 13 in MAP; 12 in ELSA; 8 in NACC).
Increases in the rates of frailty index scores began accelerating 4-9 years before dementia onset for the various cohorts, investigators noted.
In all four cohorts, each 0.1 increase in frailty scores was positively associated with increased dementia risk.
Adjusted hazard ratios [aHRs] ranged from 1.18 in the HRS cohort to 1.73 in the NACC cohort, which showed the strongest association.
In participants whose baseline frailty measurement was conducted before the predementia acceleration period began, the association of frailty scores and dementia risk was positive. These aHRs ranged from 1.18 in the HRS cohort to 1.43 in the NACC cohort.
The ‘Four Pillars’ of Prevention
The good news, investigators said, is that the long trajectory of frailty symptoms preceding dementia onset provides plenty of opportunity for intervention.
To slow the development of frailty, Ward suggested adhering to the “four pillars of frailty prevention and management,” which include good nutrition with plenty of protein, exercise, optimizing medications for chronic conditions, and maintaining a strong social network.
Ward suggested neurologists track frailty in their patients and pointed to a recent article focused on helping neurologists use frailty measures to influence care planning.
Study limitations include the possibility of reverse causality and the fact that investigators could not adjust for genetic risk for dementia.
Unclear Pathway
Commenting on the findings, Lycia Neumann, PhD, senior director of Health Services Research at the Alzheimer’s Association, noted that many studies over the years have shown a link between frailty and dementia. However, she cautioned that a link does not imply causation.
The pathway from frailty to dementia is not 100% clear, and both are complex conditions, said Neumann, who was not part of the study.
“Adopting healthy lifestyle behaviors early and consistently can help decrease the risk of — or postpone the onset of — both frailty and cognitive decline,” she said. Neumann added that physical activity, a healthy diet, social engagement, and controlling diabetes and blood pressure can also reduce the risk for dementia as well as cardiovascular disease.
The study was funded in part by the Deep Dementia Phenotyping Network through the Frailty and Dementia Special Interest Group. Ward and Neumann reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
Faster Brain Atrophy Linked to MCI
While some brain atrophy is expected in aging, high levels of atrophy in the white matter and high enlargement in the ventricles are associated with earlier progression from normal cognition to MCI, the study found. The researchers also identified diabetes and atypical levels of amyloid beta protein in the cerebrospinal fluid as risk factors for brain atrophy and MCI.
For their research, published online on JAMA Network Open, Yuto Uchida, MD, PhD, and his colleagues at the Johns Hopkins University School of Medicine in Baltimore, Maryland, looked at data for 185 individuals (mean age, 55.4 years; 63% women) who were cognitively normal at baseline and followed for a median of 20 years.
All had been enrolled in a longitudinal cohort study on biomarkers of cognitive decline conducted at Johns Hopkins. Each participant underwent a median of five structural MRI studies during the follow-up period as well as annual cognitive testing. Altogether 60 individuals developed MCI, with eight of them progressing to dementia.
“We hypothesized that annual rates of change of segmental brain volumes would be associated with vascular risk factors among middle-aged and older adults and that these trends would be associated with the progression from normal cognition to MCI,” Uchida and colleagues wrote.
Uniquely Long Follow-Up
Most longitudinal studies using structural MRI count a decade or less of follow-up, the study authors noted. This makes it difficult to discern whether the annual rates of change of brain volumes are affected by vascular risk factors or are useful in predicting MCI, they said. Individual differences in brain aging make population-based studies less informative.
This study’s long timeframe allowed for tracking of brain changes “on an individual basis, which facilitates the differentiation between interindividual and intraindividual variations and leads to more accurate estimations of rates of brain atrophy,” Uchida and colleagues wrote.
People with high levels of atrophy in the white matter and enlargement in the ventricles saw earlier progression to MCI (hazard ratio [HR], 1.86; 95% CI, 1.24-2.49; P = .001). Diabetes mellitus was associated with progression to MCI (HR, 1.41; 95% CI, 1.06-1.76; P = .04), as was a low CSF Abeta42:Abeta40 ratio (HR, 1.48; 95% CI, 1.09-1.88; P = .04).
People with both diabetes and an abnormal amyloid profile were even more vulnerable to developing MCI (HR, 1.55; 95% CI, 1.13-1.98; P = .03). This indicated “a synergic association of diabetes and amyloid pathology with MCI progression,” Uchida and colleagues wrote, noting that insulin resistance has been shown to promote the formation of amyloid plaques, a hallmark of Alzheimer’s disease.
The findings also underscore that “white matter volume changes are closely associated with cognitive function in aging, suggesting that white matter degeneration may play a crucial role in cognitive decline,” the authors noted.
Uchida and colleagues acknowledged the modest size and imbalanced sex ratio of their study cohort as potential weaknesses, as well as the fact that the imaging technologies had changed over the course of the study. Most of the participants were White with family histories of dementia.
Findings May Lead to Targeted Interventions
In an editorial comment accompanying Uchida and colleagues’ study, Shohei Fujita, MD, PhD, of Massachusetts General Hospital, Boston, said that, while a more diverse population sample would be desirable and should be sought for future studies, the results nonetheless highlight “the potential of long-term longitudinal brain MRI datasets in elucidating the interplay of risk factors underlying cognitive decline and the potential benefits of controlling diabetes to reduce the risk of progression” along the Alzheimer’s disease continuum.
The findings may prove informative, Fujita said, in developing “targeted interventions for those most susceptible to progressive brain changes, potentially combining lifestyle modifications and pharmacological treatments.”
Uchida and colleagues’ study was funded by the Alzheimer’s Association, the National Alzheimer’s Coordinating Center, and the National Institutes of Health. The study’s corresponding author, Kenichi Oishi, disclosed funding from the Richman Family Foundation, Richman, the Sharp Family Foundation, and others. Uchida and Fujita reported no relevant financial conflicts of interest.
A version of this article first appeared on Medscape.com.
While some brain atrophy is expected in aging, high levels of atrophy in the white matter and high enlargement in the ventricles are associated with earlier progression from normal cognition to MCI, the study found. The researchers also identified diabetes and atypical levels of amyloid beta protein in the cerebrospinal fluid as risk factors for brain atrophy and MCI.
For their research, published online on JAMA Network Open, Yuto Uchida, MD, PhD, and his colleagues at the Johns Hopkins University School of Medicine in Baltimore, Maryland, looked at data for 185 individuals (mean age, 55.4 years; 63% women) who were cognitively normal at baseline and followed for a median of 20 years.
All had been enrolled in a longitudinal cohort study on biomarkers of cognitive decline conducted at Johns Hopkins. Each participant underwent a median of five structural MRI studies during the follow-up period as well as annual cognitive testing. Altogether 60 individuals developed MCI, with eight of them progressing to dementia.
“We hypothesized that annual rates of change of segmental brain volumes would be associated with vascular risk factors among middle-aged and older adults and that these trends would be associated with the progression from normal cognition to MCI,” Uchida and colleagues wrote.
Uniquely Long Follow-Up
Most longitudinal studies using structural MRI count a decade or less of follow-up, the study authors noted. This makes it difficult to discern whether the annual rates of change of brain volumes are affected by vascular risk factors or are useful in predicting MCI, they said. Individual differences in brain aging make population-based studies less informative.
This study’s long timeframe allowed for tracking of brain changes “on an individual basis, which facilitates the differentiation between interindividual and intraindividual variations and leads to more accurate estimations of rates of brain atrophy,” Uchida and colleagues wrote.
People with high levels of atrophy in the white matter and enlargement in the ventricles saw earlier progression to MCI (hazard ratio [HR], 1.86; 95% CI, 1.24-2.49; P = .001). Diabetes mellitus was associated with progression to MCI (HR, 1.41; 95% CI, 1.06-1.76; P = .04), as was a low CSF Abeta42:Abeta40 ratio (HR, 1.48; 95% CI, 1.09-1.88; P = .04).
People with both diabetes and an abnormal amyloid profile were even more vulnerable to developing MCI (HR, 1.55; 95% CI, 1.13-1.98; P = .03). This indicated “a synergic association of diabetes and amyloid pathology with MCI progression,” Uchida and colleagues wrote, noting that insulin resistance has been shown to promote the formation of amyloid plaques, a hallmark of Alzheimer’s disease.
The findings also underscore that “white matter volume changes are closely associated with cognitive function in aging, suggesting that white matter degeneration may play a crucial role in cognitive decline,” the authors noted.
Uchida and colleagues acknowledged the modest size and imbalanced sex ratio of their study cohort as potential weaknesses, as well as the fact that the imaging technologies had changed over the course of the study. Most of the participants were White with family histories of dementia.
Findings May Lead to Targeted Interventions
In an editorial comment accompanying Uchida and colleagues’ study, Shohei Fujita, MD, PhD, of Massachusetts General Hospital, Boston, said that, while a more diverse population sample would be desirable and should be sought for future studies, the results nonetheless highlight “the potential of long-term longitudinal brain MRI datasets in elucidating the interplay of risk factors underlying cognitive decline and the potential benefits of controlling diabetes to reduce the risk of progression” along the Alzheimer’s disease continuum.
The findings may prove informative, Fujita said, in developing “targeted interventions for those most susceptible to progressive brain changes, potentially combining lifestyle modifications and pharmacological treatments.”
Uchida and colleagues’ study was funded by the Alzheimer’s Association, the National Alzheimer’s Coordinating Center, and the National Institutes of Health. The study’s corresponding author, Kenichi Oishi, disclosed funding from the Richman Family Foundation, Richman, the Sharp Family Foundation, and others. Uchida and Fujita reported no relevant financial conflicts of interest.
A version of this article first appeared on Medscape.com.
While some brain atrophy is expected in aging, high levels of atrophy in the white matter and high enlargement in the ventricles are associated with earlier progression from normal cognition to MCI, the study found. The researchers also identified diabetes and atypical levels of amyloid beta protein in the cerebrospinal fluid as risk factors for brain atrophy and MCI.
For their research, published online on JAMA Network Open, Yuto Uchida, MD, PhD, and his colleagues at the Johns Hopkins University School of Medicine in Baltimore, Maryland, looked at data for 185 individuals (mean age, 55.4 years; 63% women) who were cognitively normal at baseline and followed for a median of 20 years.
All had been enrolled in a longitudinal cohort study on biomarkers of cognitive decline conducted at Johns Hopkins. Each participant underwent a median of five structural MRI studies during the follow-up period as well as annual cognitive testing. Altogether 60 individuals developed MCI, with eight of them progressing to dementia.
“We hypothesized that annual rates of change of segmental brain volumes would be associated with vascular risk factors among middle-aged and older adults and that these trends would be associated with the progression from normal cognition to MCI,” Uchida and colleagues wrote.
Uniquely Long Follow-Up
Most longitudinal studies using structural MRI count a decade or less of follow-up, the study authors noted. This makes it difficult to discern whether the annual rates of change of brain volumes are affected by vascular risk factors or are useful in predicting MCI, they said. Individual differences in brain aging make population-based studies less informative.
This study’s long timeframe allowed for tracking of brain changes “on an individual basis, which facilitates the differentiation between interindividual and intraindividual variations and leads to more accurate estimations of rates of brain atrophy,” Uchida and colleagues wrote.
People with high levels of atrophy in the white matter and enlargement in the ventricles saw earlier progression to MCI (hazard ratio [HR], 1.86; 95% CI, 1.24-2.49; P = .001). Diabetes mellitus was associated with progression to MCI (HR, 1.41; 95% CI, 1.06-1.76; P = .04), as was a low CSF Abeta42:Abeta40 ratio (HR, 1.48; 95% CI, 1.09-1.88; P = .04).
People with both diabetes and an abnormal amyloid profile were even more vulnerable to developing MCI (HR, 1.55; 95% CI, 1.13-1.98; P = .03). This indicated “a synergic association of diabetes and amyloid pathology with MCI progression,” Uchida and colleagues wrote, noting that insulin resistance has been shown to promote the formation of amyloid plaques, a hallmark of Alzheimer’s disease.
The findings also underscore that “white matter volume changes are closely associated with cognitive function in aging, suggesting that white matter degeneration may play a crucial role in cognitive decline,” the authors noted.
Uchida and colleagues acknowledged the modest size and imbalanced sex ratio of their study cohort as potential weaknesses, as well as the fact that the imaging technologies had changed over the course of the study. Most of the participants were White with family histories of dementia.
Findings May Lead to Targeted Interventions
In an editorial comment accompanying Uchida and colleagues’ study, Shohei Fujita, MD, PhD, of Massachusetts General Hospital, Boston, said that, while a more diverse population sample would be desirable and should be sought for future studies, the results nonetheless highlight “the potential of long-term longitudinal brain MRI datasets in elucidating the interplay of risk factors underlying cognitive decline and the potential benefits of controlling diabetes to reduce the risk of progression” along the Alzheimer’s disease continuum.
The findings may prove informative, Fujita said, in developing “targeted interventions for those most susceptible to progressive brain changes, potentially combining lifestyle modifications and pharmacological treatments.”
Uchida and colleagues’ study was funded by the Alzheimer’s Association, the National Alzheimer’s Coordinating Center, and the National Institutes of Health. The study’s corresponding author, Kenichi Oishi, disclosed funding from the Richman Family Foundation, Richman, the Sharp Family Foundation, and others. Uchida and Fujita reported no relevant financial conflicts of interest.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
Experts Challenge New Diagnostic Criteria for Alzheimer’s disease
In a paper published online in JAMA Neurology, the International Working Group (IWG), which includes 46 experts from 17 countries, is recommending that the diagnosis of Alzheimer’s disease be limited to individuals with mild cognitive impairment or dementia and not be applied to cognitively normal individuals with Alzheimer’s disease biomarkers such as amyloid-beta 42/40 or p-tau.
Clinicians should be “very careful” about using the “A” word (Alzheimer’s) for cognitively unimpaired people with Alzheimer’s disease biomarkers, said the paper’s first author Bruno Dubois, MD, professor of neurology, Sorbonne University and Department of Neurology, Pitié-Salpêtrière Hospital, Paris, France.
Providing an Alzheimer’s disease diagnosis to those who have a high chance of never developing cognitive impairment can be psychologically harmful, said Dubois.
“It’s not something small like telling someone they have a fever. Just imagine you’re 65 years old and are amyloid positive, and you’re told you have Alzheimer’s disease. It affects the decisions you make for the rest of your life and changes your vision of your future, even though you may never develop the disease,” he added.
Divergent View
The IWG’s perspective on Alzheimer’s disease contrasts with a recent proposal from the Alzheimer’s Association. The Alzheimer’s Association criteria suggest that Alzheimer’s disease should be regarded solely as a biological entity, which could include cognitively normal individuals with one core Alzheimer’s disease biomarker.
The IWG noted that its concerns regarding the application of a purely biological definition of Alzheimer’s disease in clinical practice prompted the group to consider updating its guidelines, potentially offering “an alternative definitional view of Alzheimer’s disease as a clinical-biological construct for clinical use.”
The group conducted a PubMed search for relevant Alzheimer’s disease articles, and included references, published between July 2020 and March 2024. The research showed the majority of biomarker-positive, cognitively normal individuals will not become symptomatic during their lifetime.
The risk of a 55-year-old who is amyloid positive developing Alzheimer’s disease is not that much higher than that for an individual of a similar age who is amyloid negative, Dubois noted. “There’s an 83% chance that person will never develop Alzheimer’s disease.”
Disclosing a diagnosis of Alzheimer’s disease to cognitively normal people with only one core Alzheimer’s disease biomarker represents “the most problematic implication of a purely biological definition of the disease,” the authors noted.
“A biomarker is a marker of pathology, not a biomarker of disease,” said Dubois, adding that a person may have markers for several different brain diseases.
The IWG recommends the following nomenclature: At risk for Alzheimer’s disease for those with Alzheimer’s disease biomarkers but low lifetime risk and presymptomatic Alzheimer’s disease for those with Alzheimer’s disease biomarkers with a very high lifetime risk for progression such as individuals with autosomal dominant genetic mutations and other distinct biomarker profiles that put them at extremely high lifetime risk of developing the disease.
Dubois emphasized the difference between those showing typical Alzheimer’s disease symptoms with positive biomarkers who should be considered to have the disease and those with positive biomarkers but no typical Alzheimer’s disease symptoms who should be considered at risk.
This is an important distinction as it affects research approaches and assessment of risks, he said.
For low-risk asymptomatic individuals, the IWG does not recommend routine diagnostic testing outside of the research setting. “There’s no reason to send a 65-year-old cognitively normal subject off to collect biomarker information,” said Dubois.
He reiterated the importance of clinicians using appropriate and sensitive language surrounding Alzheimer’s disease when face to face with patients. This issue “is not purely semantic; this is real life.”
For these patients in the clinical setting, “we have to be very careful about proposing treatments that may have side effects,” he said.
However, this does not mean asymptomatic at-risk people should not be studied to determine what pharmacological interventions might prevent or delay the onset of clinical disease, he noted.
Presymptomatic individuals who are at a high risk of developing Alzheimer’s disease “should be the target for clinical trials in the future” to determine best ways to delay the conversion to Alzheimer’s disease, he said.
The main focus of such research should be to better understand the “biomarker pattern profile” that is associated with a high risk of developing Alzheimer’s disease, said Dubois.
Plea for Unity
In an accompanying editorial, Ronald C. Petersen, PhD, MD, director, Mayo Clinic Alzheimer’s Disease Research Center and Mayo Clinic Study of Aging, Rochester, Minnesota, and colleagues outline the difference between the IWG and Alzheimer’s Association positions.
As the IWG uses Alzheimer’s disease to define those with cognitive impairment and the Alzheimer’s Association group uses Alzheimer’s disease to define those with the pathology of the disease, the field is now at a crossroads. “Do we name the disease before clinical symptoms?” they asked.
They note that Alzheimer’s Association criteria distinguish between a disease and an illness, whereas the IWG does not. “As such, although the primary disagreement between the groups is semantic, the ramifications of the labeling can be significant.”
It is “incumbent” that the field “come together” on an Alzheimer’s disease definition, the editorial concluded. “Neither the Alzheimer’s Association or IWG documents are appropriate to serve as a guide for how to apply biomarkers in a clinical setting. Appropriate-use criteria are needed to form a bridge between biological frameworks and real-world clinical practice so we can all maximally help all of our patients with this disorder.”
In a comment, Reisa Sperling, MD, professor of neurology, Harvard Medical School, and director, Center for Alzheimer Research and Treatment, Brigham and Women’s Hospital and Massachusetts General Hospital, all in Boston, who is part of the Alzheimer’s Association work group that published the revised criteria for diagnosis and staging of Alzheimer’s disease, likened Alzheimer’s disease, which begins in the brain many years before dementia onset, to cardiovascular disease in that it involves multiple processes. She noted the World Health Organization classifies cardiovascular disease as a “disease” prior to clinical manifestations such as stroke and myocardial infarction.
“If someone has Alzheimer’s disease pathology in their brain, they are at risk for dementia or clinical manifestations of the disease — just like vascular disease quantifies the risk of stroke or heart attack, not risk of developing ‘vascular disease’ if the underlying vascular disease is already present,” said Sperling.
A large part of the controversy is related to terminology and the “stigma” of the “A” word in the same way there used to be fear around using the “C” word — cancer, said Sperling.
“Once people began talking about cancer publicly as a potentially treatable disease and began getting screened and diagnosed before symptoms of cancer were manifest, this has had a tremendous impact on public health.”
She clarified that her work group does not recommend screening asymptomatic people with Alzheimer’s disease biomarkers. “We actually need to prove that treating at the preclinical stage of the disease is able to prevent clinical impairment and dementia,” she said, adding “hopefully, we are getting closer to this.”
Dubois reported no relevant disclosures. Petersen reported receiving personal fees from Roche, Genentech, Eli Lilly and Company, Eisai, and Novo Nordisk outside the submitted work and royalties from Oxford University Press, UpToDate, and Medscape educational activities.
A version of this article appeared on Medscape.com.
In a paper published online in JAMA Neurology, the International Working Group (IWG), which includes 46 experts from 17 countries, is recommending that the diagnosis of Alzheimer’s disease be limited to individuals with mild cognitive impairment or dementia and not be applied to cognitively normal individuals with Alzheimer’s disease biomarkers such as amyloid-beta 42/40 or p-tau.
Clinicians should be “very careful” about using the “A” word (Alzheimer’s) for cognitively unimpaired people with Alzheimer’s disease biomarkers, said the paper’s first author Bruno Dubois, MD, professor of neurology, Sorbonne University and Department of Neurology, Pitié-Salpêtrière Hospital, Paris, France.
Providing an Alzheimer’s disease diagnosis to those who have a high chance of never developing cognitive impairment can be psychologically harmful, said Dubois.
“It’s not something small like telling someone they have a fever. Just imagine you’re 65 years old and are amyloid positive, and you’re told you have Alzheimer’s disease. It affects the decisions you make for the rest of your life and changes your vision of your future, even though you may never develop the disease,” he added.
Divergent View
The IWG’s perspective on Alzheimer’s disease contrasts with a recent proposal from the Alzheimer’s Association. The Alzheimer’s Association criteria suggest that Alzheimer’s disease should be regarded solely as a biological entity, which could include cognitively normal individuals with one core Alzheimer’s disease biomarker.
The IWG noted that its concerns regarding the application of a purely biological definition of Alzheimer’s disease in clinical practice prompted the group to consider updating its guidelines, potentially offering “an alternative definitional view of Alzheimer’s disease as a clinical-biological construct for clinical use.”
The group conducted a PubMed search for relevant Alzheimer’s disease articles, and included references, published between July 2020 and March 2024. The research showed the majority of biomarker-positive, cognitively normal individuals will not become symptomatic during their lifetime.
The risk of a 55-year-old who is amyloid positive developing Alzheimer’s disease is not that much higher than that for an individual of a similar age who is amyloid negative, Dubois noted. “There’s an 83% chance that person will never develop Alzheimer’s disease.”
Disclosing a diagnosis of Alzheimer’s disease to cognitively normal people with only one core Alzheimer’s disease biomarker represents “the most problematic implication of a purely biological definition of the disease,” the authors noted.
“A biomarker is a marker of pathology, not a biomarker of disease,” said Dubois, adding that a person may have markers for several different brain diseases.
The IWG recommends the following nomenclature: At risk for Alzheimer’s disease for those with Alzheimer’s disease biomarkers but low lifetime risk and presymptomatic Alzheimer’s disease for those with Alzheimer’s disease biomarkers with a very high lifetime risk for progression such as individuals with autosomal dominant genetic mutations and other distinct biomarker profiles that put them at extremely high lifetime risk of developing the disease.
Dubois emphasized the difference between those showing typical Alzheimer’s disease symptoms with positive biomarkers who should be considered to have the disease and those with positive biomarkers but no typical Alzheimer’s disease symptoms who should be considered at risk.
This is an important distinction as it affects research approaches and assessment of risks, he said.
For low-risk asymptomatic individuals, the IWG does not recommend routine diagnostic testing outside of the research setting. “There’s no reason to send a 65-year-old cognitively normal subject off to collect biomarker information,” said Dubois.
He reiterated the importance of clinicians using appropriate and sensitive language surrounding Alzheimer’s disease when face to face with patients. This issue “is not purely semantic; this is real life.”
For these patients in the clinical setting, “we have to be very careful about proposing treatments that may have side effects,” he said.
However, this does not mean asymptomatic at-risk people should not be studied to determine what pharmacological interventions might prevent or delay the onset of clinical disease, he noted.
Presymptomatic individuals who are at a high risk of developing Alzheimer’s disease “should be the target for clinical trials in the future” to determine best ways to delay the conversion to Alzheimer’s disease, he said.
The main focus of such research should be to better understand the “biomarker pattern profile” that is associated with a high risk of developing Alzheimer’s disease, said Dubois.
Plea for Unity
In an accompanying editorial, Ronald C. Petersen, PhD, MD, director, Mayo Clinic Alzheimer’s Disease Research Center and Mayo Clinic Study of Aging, Rochester, Minnesota, and colleagues outline the difference between the IWG and Alzheimer’s Association positions.
As the IWG uses Alzheimer’s disease to define those with cognitive impairment and the Alzheimer’s Association group uses Alzheimer’s disease to define those with the pathology of the disease, the field is now at a crossroads. “Do we name the disease before clinical symptoms?” they asked.
They note that Alzheimer’s Association criteria distinguish between a disease and an illness, whereas the IWG does not. “As such, although the primary disagreement between the groups is semantic, the ramifications of the labeling can be significant.”
It is “incumbent” that the field “come together” on an Alzheimer’s disease definition, the editorial concluded. “Neither the Alzheimer’s Association or IWG documents are appropriate to serve as a guide for how to apply biomarkers in a clinical setting. Appropriate-use criteria are needed to form a bridge between biological frameworks and real-world clinical practice so we can all maximally help all of our patients with this disorder.”
In a comment, Reisa Sperling, MD, professor of neurology, Harvard Medical School, and director, Center for Alzheimer Research and Treatment, Brigham and Women’s Hospital and Massachusetts General Hospital, all in Boston, who is part of the Alzheimer’s Association work group that published the revised criteria for diagnosis and staging of Alzheimer’s disease, likened Alzheimer’s disease, which begins in the brain many years before dementia onset, to cardiovascular disease in that it involves multiple processes. She noted the World Health Organization classifies cardiovascular disease as a “disease” prior to clinical manifestations such as stroke and myocardial infarction.
“If someone has Alzheimer’s disease pathology in their brain, they are at risk for dementia or clinical manifestations of the disease — just like vascular disease quantifies the risk of stroke or heart attack, not risk of developing ‘vascular disease’ if the underlying vascular disease is already present,” said Sperling.
A large part of the controversy is related to terminology and the “stigma” of the “A” word in the same way there used to be fear around using the “C” word — cancer, said Sperling.
“Once people began talking about cancer publicly as a potentially treatable disease and began getting screened and diagnosed before symptoms of cancer were manifest, this has had a tremendous impact on public health.”
She clarified that her work group does not recommend screening asymptomatic people with Alzheimer’s disease biomarkers. “We actually need to prove that treating at the preclinical stage of the disease is able to prevent clinical impairment and dementia,” she said, adding “hopefully, we are getting closer to this.”
Dubois reported no relevant disclosures. Petersen reported receiving personal fees from Roche, Genentech, Eli Lilly and Company, Eisai, and Novo Nordisk outside the submitted work and royalties from Oxford University Press, UpToDate, and Medscape educational activities.
A version of this article appeared on Medscape.com.
In a paper published online in JAMA Neurology, the International Working Group (IWG), which includes 46 experts from 17 countries, is recommending that the diagnosis of Alzheimer’s disease be limited to individuals with mild cognitive impairment or dementia and not be applied to cognitively normal individuals with Alzheimer’s disease biomarkers such as amyloid-beta 42/40 or p-tau.
Clinicians should be “very careful” about using the “A” word (Alzheimer’s) for cognitively unimpaired people with Alzheimer’s disease biomarkers, said the paper’s first author Bruno Dubois, MD, professor of neurology, Sorbonne University and Department of Neurology, Pitié-Salpêtrière Hospital, Paris, France.
Providing an Alzheimer’s disease diagnosis to those who have a high chance of never developing cognitive impairment can be psychologically harmful, said Dubois.
“It’s not something small like telling someone they have a fever. Just imagine you’re 65 years old and are amyloid positive, and you’re told you have Alzheimer’s disease. It affects the decisions you make for the rest of your life and changes your vision of your future, even though you may never develop the disease,” he added.
Divergent View
The IWG’s perspective on Alzheimer’s disease contrasts with a recent proposal from the Alzheimer’s Association. The Alzheimer’s Association criteria suggest that Alzheimer’s disease should be regarded solely as a biological entity, which could include cognitively normal individuals with one core Alzheimer’s disease biomarker.
The IWG noted that its concerns regarding the application of a purely biological definition of Alzheimer’s disease in clinical practice prompted the group to consider updating its guidelines, potentially offering “an alternative definitional view of Alzheimer’s disease as a clinical-biological construct for clinical use.”
The group conducted a PubMed search for relevant Alzheimer’s disease articles, and included references, published between July 2020 and March 2024. The research showed the majority of biomarker-positive, cognitively normal individuals will not become symptomatic during their lifetime.
The risk of a 55-year-old who is amyloid positive developing Alzheimer’s disease is not that much higher than that for an individual of a similar age who is amyloid negative, Dubois noted. “There’s an 83% chance that person will never develop Alzheimer’s disease.”
Disclosing a diagnosis of Alzheimer’s disease to cognitively normal people with only one core Alzheimer’s disease biomarker represents “the most problematic implication of a purely biological definition of the disease,” the authors noted.
“A biomarker is a marker of pathology, not a biomarker of disease,” said Dubois, adding that a person may have markers for several different brain diseases.
The IWG recommends the following nomenclature: At risk for Alzheimer’s disease for those with Alzheimer’s disease biomarkers but low lifetime risk and presymptomatic Alzheimer’s disease for those with Alzheimer’s disease biomarkers with a very high lifetime risk for progression such as individuals with autosomal dominant genetic mutations and other distinct biomarker profiles that put them at extremely high lifetime risk of developing the disease.
Dubois emphasized the difference between those showing typical Alzheimer’s disease symptoms with positive biomarkers who should be considered to have the disease and those with positive biomarkers but no typical Alzheimer’s disease symptoms who should be considered at risk.
This is an important distinction as it affects research approaches and assessment of risks, he said.
For low-risk asymptomatic individuals, the IWG does not recommend routine diagnostic testing outside of the research setting. “There’s no reason to send a 65-year-old cognitively normal subject off to collect biomarker information,” said Dubois.
He reiterated the importance of clinicians using appropriate and sensitive language surrounding Alzheimer’s disease when face to face with patients. This issue “is not purely semantic; this is real life.”
For these patients in the clinical setting, “we have to be very careful about proposing treatments that may have side effects,” he said.
However, this does not mean asymptomatic at-risk people should not be studied to determine what pharmacological interventions might prevent or delay the onset of clinical disease, he noted.
Presymptomatic individuals who are at a high risk of developing Alzheimer’s disease “should be the target for clinical trials in the future” to determine best ways to delay the conversion to Alzheimer’s disease, he said.
The main focus of such research should be to better understand the “biomarker pattern profile” that is associated with a high risk of developing Alzheimer’s disease, said Dubois.
Plea for Unity
In an accompanying editorial, Ronald C. Petersen, PhD, MD, director, Mayo Clinic Alzheimer’s Disease Research Center and Mayo Clinic Study of Aging, Rochester, Minnesota, and colleagues outline the difference between the IWG and Alzheimer’s Association positions.
As the IWG uses Alzheimer’s disease to define those with cognitive impairment and the Alzheimer’s Association group uses Alzheimer’s disease to define those with the pathology of the disease, the field is now at a crossroads. “Do we name the disease before clinical symptoms?” they asked.
They note that Alzheimer’s Association criteria distinguish between a disease and an illness, whereas the IWG does not. “As such, although the primary disagreement between the groups is semantic, the ramifications of the labeling can be significant.”
It is “incumbent” that the field “come together” on an Alzheimer’s disease definition, the editorial concluded. “Neither the Alzheimer’s Association or IWG documents are appropriate to serve as a guide for how to apply biomarkers in a clinical setting. Appropriate-use criteria are needed to form a bridge between biological frameworks and real-world clinical practice so we can all maximally help all of our patients with this disorder.”
In a comment, Reisa Sperling, MD, professor of neurology, Harvard Medical School, and director, Center for Alzheimer Research and Treatment, Brigham and Women’s Hospital and Massachusetts General Hospital, all in Boston, who is part of the Alzheimer’s Association work group that published the revised criteria for diagnosis and staging of Alzheimer’s disease, likened Alzheimer’s disease, which begins in the brain many years before dementia onset, to cardiovascular disease in that it involves multiple processes. She noted the World Health Organization classifies cardiovascular disease as a “disease” prior to clinical manifestations such as stroke and myocardial infarction.
“If someone has Alzheimer’s disease pathology in their brain, they are at risk for dementia or clinical manifestations of the disease — just like vascular disease quantifies the risk of stroke or heart attack, not risk of developing ‘vascular disease’ if the underlying vascular disease is already present,” said Sperling.
A large part of the controversy is related to terminology and the “stigma” of the “A” word in the same way there used to be fear around using the “C” word — cancer, said Sperling.
“Once people began talking about cancer publicly as a potentially treatable disease and began getting screened and diagnosed before symptoms of cancer were manifest, this has had a tremendous impact on public health.”
She clarified that her work group does not recommend screening asymptomatic people with Alzheimer’s disease biomarkers. “We actually need to prove that treating at the preclinical stage of the disease is able to prevent clinical impairment and dementia,” she said, adding “hopefully, we are getting closer to this.”
Dubois reported no relevant disclosures. Petersen reported receiving personal fees from Roche, Genentech, Eli Lilly and Company, Eisai, and Novo Nordisk outside the submitted work and royalties from Oxford University Press, UpToDate, and Medscape educational activities.
A version of this article appeared on Medscape.com.
From JAMA Neurology
Being a Weekend Warrior Linked to Lower Dementia Risk
TOPLINE:
, a new study shows. Investigators say the findings suggest even limited physical activity may offer protective cognitive benefits.
METHODOLOGY:
- Researchers analyzed the data of 10,033 participants in the Mexico City Prospective Study who were aged 35 years or older.
- Physical activity patterns were categorized into four groups: No exercise, weekend warriors (one or two sessions per week), regularly active (three or more sessions per week), and a combined group.
- Cognitive function was assessed using the Mini-Mental State Examination (MMSE).
- The analysis adjusted for confounders such as age, sex, education, income, blood pressure, smoking status, body mass index, civil status, sleep duration, diet, and alcohol intake.
- The mean follow-up duration was 16 years.
TAKEAWAY:
- When mild dementia was defined as an MMSE score ≤ 22, dementia prevalence was 26% in those who did not exercise, 14% in weekend warriors, and 18.5% in the regularly active group.
- When mild dementia was defined as an MMSE score ≤ 23, dementia prevalence was 30% in those who did not exercise, 20% in weekend warriors, and 22% in the regularly active group.
- Compared with people who did not exercise and after adjusting for confounding factors, risk for mild dementia was 13%-25% lower in weekend warriors, 11%-12% lower in the regular activity group, and 12%-16% lower in the two groups combined.
- The findings were consistent in men and women.
IN PRACTICE:
“To the best of our knowledge, this is the first prospective cohort study to show that the weekend warrior physical activity pattern and the regularly active physical activity pattern are associated with similar reductions in the risk of mild dementia. This study has important implications for policy and practice because the weekend warrior physical activity pattern may be a more convenient option for busy people around the world,” the authors wrote.
SOURCE:
The study was led by Gary O’Donovan, Faculty of Medicine, University of the Andes, Bogotá, Colombia. It was published online in the British Journal of Sports Medicine.
LIMITATIONS:
The survey respondents may not have been truly representative of middle-aged adults. Further, there were no objective measures of physical activity. The observational nature of the study does not provide insights into causality.
DISCLOSURES:
The study was funded by the Mexican Health Ministry, the National Council of Science and Technology for Mexico, Wellcome, and the UK Medical Research Council. No conflicts of interest were disclosed.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article appeared on Medscape.com.
TOPLINE:
, a new study shows. Investigators say the findings suggest even limited physical activity may offer protective cognitive benefits.
METHODOLOGY:
- Researchers analyzed the data of 10,033 participants in the Mexico City Prospective Study who were aged 35 years or older.
- Physical activity patterns were categorized into four groups: No exercise, weekend warriors (one or two sessions per week), regularly active (three or more sessions per week), and a combined group.
- Cognitive function was assessed using the Mini-Mental State Examination (MMSE).
- The analysis adjusted for confounders such as age, sex, education, income, blood pressure, smoking status, body mass index, civil status, sleep duration, diet, and alcohol intake.
- The mean follow-up duration was 16 years.
TAKEAWAY:
- When mild dementia was defined as an MMSE score ≤ 22, dementia prevalence was 26% in those who did not exercise, 14% in weekend warriors, and 18.5% in the regularly active group.
- When mild dementia was defined as an MMSE score ≤ 23, dementia prevalence was 30% in those who did not exercise, 20% in weekend warriors, and 22% in the regularly active group.
- Compared with people who did not exercise and after adjusting for confounding factors, risk for mild dementia was 13%-25% lower in weekend warriors, 11%-12% lower in the regular activity group, and 12%-16% lower in the two groups combined.
- The findings were consistent in men and women.
IN PRACTICE:
“To the best of our knowledge, this is the first prospective cohort study to show that the weekend warrior physical activity pattern and the regularly active physical activity pattern are associated with similar reductions in the risk of mild dementia. This study has important implications for policy and practice because the weekend warrior physical activity pattern may be a more convenient option for busy people around the world,” the authors wrote.
SOURCE:
The study was led by Gary O’Donovan, Faculty of Medicine, University of the Andes, Bogotá, Colombia. It was published online in the British Journal of Sports Medicine.
LIMITATIONS:
The survey respondents may not have been truly representative of middle-aged adults. Further, there were no objective measures of physical activity. The observational nature of the study does not provide insights into causality.
DISCLOSURES:
The study was funded by the Mexican Health Ministry, the National Council of Science and Technology for Mexico, Wellcome, and the UK Medical Research Council. No conflicts of interest were disclosed.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article appeared on Medscape.com.
TOPLINE:
, a new study shows. Investigators say the findings suggest even limited physical activity may offer protective cognitive benefits.
METHODOLOGY:
- Researchers analyzed the data of 10,033 participants in the Mexico City Prospective Study who were aged 35 years or older.
- Physical activity patterns were categorized into four groups: No exercise, weekend warriors (one or two sessions per week), regularly active (three or more sessions per week), and a combined group.
- Cognitive function was assessed using the Mini-Mental State Examination (MMSE).
- The analysis adjusted for confounders such as age, sex, education, income, blood pressure, smoking status, body mass index, civil status, sleep duration, diet, and alcohol intake.
- The mean follow-up duration was 16 years.
TAKEAWAY:
- When mild dementia was defined as an MMSE score ≤ 22, dementia prevalence was 26% in those who did not exercise, 14% in weekend warriors, and 18.5% in the regularly active group.
- When mild dementia was defined as an MMSE score ≤ 23, dementia prevalence was 30% in those who did not exercise, 20% in weekend warriors, and 22% in the regularly active group.
- Compared with people who did not exercise and after adjusting for confounding factors, risk for mild dementia was 13%-25% lower in weekend warriors, 11%-12% lower in the regular activity group, and 12%-16% lower in the two groups combined.
- The findings were consistent in men and women.
IN PRACTICE:
“To the best of our knowledge, this is the first prospective cohort study to show that the weekend warrior physical activity pattern and the regularly active physical activity pattern are associated with similar reductions in the risk of mild dementia. This study has important implications for policy and practice because the weekend warrior physical activity pattern may be a more convenient option for busy people around the world,” the authors wrote.
SOURCE:
The study was led by Gary O’Donovan, Faculty of Medicine, University of the Andes, Bogotá, Colombia. It was published online in the British Journal of Sports Medicine.
LIMITATIONS:
The survey respondents may not have been truly representative of middle-aged adults. Further, there were no objective measures of physical activity. The observational nature of the study does not provide insights into causality.
DISCLOSURES:
The study was funded by the Mexican Health Ministry, the National Council of Science and Technology for Mexico, Wellcome, and the UK Medical Research Council. No conflicts of interest were disclosed.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article appeared on Medscape.com.
Novel Intervention Slows Cognitive Decline in At-Risk Adults
new research suggests.
The cognitive remediation intervention included a series of progressively difficult computer-based and facilitator-monitored mental exercises designed to sharpen cognitive function.
Researchers found that using cognitive remediation with tDCS slowed decline in executive function and verbal memory more than other cognitive functions. The effect was stronger among people with rMDD versus those with MCI and in those at low genetic risk for Alzheimer’s disease.
“We have developed a novel intervention, combining two interventions that if used separately have a weak effect but together have substantial and clinically meaningful effect of slowing the progression of cognitive decline,” said study author Benoit H. Mulsant, MD, chair of the Department of Psychiatry, University of Toronto, Ontario, Canada, and senior scientist at the Center for Addiction and Mental Health, also in Toronto.
The findings were published online in JAMA Psychiatry.
High-Risk Group
Research shows that older adults with MDD or MCI are at high risk for cognitive decline and dementia. Evidence also suggests that depression in early or mid-life significantly increases the risk for dementia in late life, even if the depression has been in remission for decades.
A potential mechanism underlying this increased risk for dementia could be impaired cortical plasticity, or the ability of the brain to compensate for damage.
The PACt-MD trial included 375 older adults with rMDD, MCI, or both (mean age, 72 years; 62% women) at five academic hospitals in Toronto.
Participants received either cognitive remediation plus tDCS or sham intervention 5 days per week for 8 weeks (acute phase), followed by 5-day “boosters” every 6 months.
tDCS was administered by trained personnel and involved active stimulation for 30 minutes at the beginning of each cognitive remediation group session. The intervention targets the prefrontal cortex, a critical region for cognitive compensation in normal cognitive aging.
The sham group received a weakened version of cognitive remediation, with exercises that did not get progressively more difficult. For the sham stimulation, the current flowed at full intensity for only 54 seconds before and after 30-second ramp-up and ramp-down phases, to create a blinding effect, the authors noted.
A geriatric psychiatrist followed all participants throughout the study, conducting assessments at baseline, month 2, and yearly for 3-7 years (mean follow-up, 48.3 months).
Participants’ depressive symptoms were evaluated at baseline and at all follow-ups and underwent neuropsychological testing to assess six cognitive domains: processing speed, working memory, executive functioning, verbal memory, visual memory, and language.
To get a norm for the cognitive tests, researchers recruited a comparator group of 75 subjects similar in age, gender, and years of education, with no neuropsychiatric disorder or cognitive impairment. They completed the same assessments but not the intervention.
Study participants and assessors were blinded to treatment assignment.
Slower Cognitive Decline
Participants in the intervention group had a significantly slower decline in cognitive function, compared with those in the sham group (adjusted z score difference [active – sham] at month 60, 0.21; P = .006). This is equivalent to slowing cognitive decline by about 4 years, researchers reported. The intervention also showed a positive effect on executive function and verbal memory.
“If I can push dementia from 85 to 89 years and you die at 86, in practice, I have prevented you from ever developing dementia,” Mulsant said.
The efficacy of cognitive remediation plus tDCS in rMDD could be tied to enhanced neuroplasticity, said Mulsant.
The treatment worked well in people with a history of depression, regardless of MCI status, but was not as effective for people with just MCI, researchers noted. The intervention also did not work as well among people at genetic risk for Alzheimer’s disease.
“We don’t believe we have discovered an intervention to prevent dementia in people who are at high risk for Alzheimer disease, but we have discovered an intervention that could prevent dementia in people who have an history of depression,” said Mulsant.
These results suggest the pathways to dementia among people with MCI and rMDD are different, he added.
Because previous research showed either treatment alone demonstrated little efficacy, researchers said the new results indicate that there may be a synergistic effect of combining the two.
The ideal amount of treatment and optimal age for initiation still need to be determined, said Mulsant. The study did not include a comparator group without rMDD or MCI, so the observed cognitive benefits might be specific to people with these high-risk conditions. Another study limitation is lack of diversity in terms of ethnicity, race, and education.
Promising, Important Findings
Commenting on the research, Badr Ratnakaran, MD, assistant professor and division director of geriatric psychiatry at Carilion Clinic–Virginia Tech Carilion School of Medicine, Roanoke, said the results are promising and important because there are so few treatment options for the increasing number of older patients with depression and dementia.
The side-effect profile of the combined treatment is better than that of many pharmacologic treatments, Ratnakaran noted. As more research like this comes out, Ratnakaran predicts that cognitive remediation and tCDS will become more readily available.
“This is telling us that the field of psychiatry, and also dementia, is progressing beyond your usual pharmacotherapy treatments,” said Ratnakaran, who also is chair of the American Psychiatric Association’s Council on Geriatric Psychiatry.
The study received support from the Canada Brain Research Fund of Brain Canada, Health Canada, the Chagnon Family, and the Centre for Addiction and Mental Health Discovery Fund. Mulsant reported holding and receiving support from the Labatt Family Chair in Biology of Depression in Late-Life Adults at the University of Toronto; being a member of the Center for Addiction and Mental Health Board of Trustees; research support from Brain Canada, Canadian Institutes of Health Research, Center for Addiction and Mental Health Foundation, Patient-Centered Outcomes Research Institute, and National Institutes of Health; and nonfinancial support from Capital Solution Design and HappyNeuron. Ratnakaran reported no relevant conflicts.
A version of this article appeared on Medscape.com.
new research suggests.
The cognitive remediation intervention included a series of progressively difficult computer-based and facilitator-monitored mental exercises designed to sharpen cognitive function.
Researchers found that using cognitive remediation with tDCS slowed decline in executive function and verbal memory more than other cognitive functions. The effect was stronger among people with rMDD versus those with MCI and in those at low genetic risk for Alzheimer’s disease.
“We have developed a novel intervention, combining two interventions that if used separately have a weak effect but together have substantial and clinically meaningful effect of slowing the progression of cognitive decline,” said study author Benoit H. Mulsant, MD, chair of the Department of Psychiatry, University of Toronto, Ontario, Canada, and senior scientist at the Center for Addiction and Mental Health, also in Toronto.
The findings were published online in JAMA Psychiatry.
High-Risk Group
Research shows that older adults with MDD or MCI are at high risk for cognitive decline and dementia. Evidence also suggests that depression in early or mid-life significantly increases the risk for dementia in late life, even if the depression has been in remission for decades.
A potential mechanism underlying this increased risk for dementia could be impaired cortical plasticity, or the ability of the brain to compensate for damage.
The PACt-MD trial included 375 older adults with rMDD, MCI, or both (mean age, 72 years; 62% women) at five academic hospitals in Toronto.
Participants received either cognitive remediation plus tDCS or sham intervention 5 days per week for 8 weeks (acute phase), followed by 5-day “boosters” every 6 months.
tDCS was administered by trained personnel and involved active stimulation for 30 minutes at the beginning of each cognitive remediation group session. The intervention targets the prefrontal cortex, a critical region for cognitive compensation in normal cognitive aging.
The sham group received a weakened version of cognitive remediation, with exercises that did not get progressively more difficult. For the sham stimulation, the current flowed at full intensity for only 54 seconds before and after 30-second ramp-up and ramp-down phases, to create a blinding effect, the authors noted.
A geriatric psychiatrist followed all participants throughout the study, conducting assessments at baseline, month 2, and yearly for 3-7 years (mean follow-up, 48.3 months).
Participants’ depressive symptoms were evaluated at baseline and at all follow-ups and underwent neuropsychological testing to assess six cognitive domains: processing speed, working memory, executive functioning, verbal memory, visual memory, and language.
To get a norm for the cognitive tests, researchers recruited a comparator group of 75 subjects similar in age, gender, and years of education, with no neuropsychiatric disorder or cognitive impairment. They completed the same assessments but not the intervention.
Study participants and assessors were blinded to treatment assignment.
Slower Cognitive Decline
Participants in the intervention group had a significantly slower decline in cognitive function, compared with those in the sham group (adjusted z score difference [active – sham] at month 60, 0.21; P = .006). This is equivalent to slowing cognitive decline by about 4 years, researchers reported. The intervention also showed a positive effect on executive function and verbal memory.
“If I can push dementia from 85 to 89 years and you die at 86, in practice, I have prevented you from ever developing dementia,” Mulsant said.
The efficacy of cognitive remediation plus tDCS in rMDD could be tied to enhanced neuroplasticity, said Mulsant.
The treatment worked well in people with a history of depression, regardless of MCI status, but was not as effective for people with just MCI, researchers noted. The intervention also did not work as well among people at genetic risk for Alzheimer’s disease.
“We don’t believe we have discovered an intervention to prevent dementia in people who are at high risk for Alzheimer disease, but we have discovered an intervention that could prevent dementia in people who have an history of depression,” said Mulsant.
These results suggest the pathways to dementia among people with MCI and rMDD are different, he added.
Because previous research showed either treatment alone demonstrated little efficacy, researchers said the new results indicate that there may be a synergistic effect of combining the two.
The ideal amount of treatment and optimal age for initiation still need to be determined, said Mulsant. The study did not include a comparator group without rMDD or MCI, so the observed cognitive benefits might be specific to people with these high-risk conditions. Another study limitation is lack of diversity in terms of ethnicity, race, and education.
Promising, Important Findings
Commenting on the research, Badr Ratnakaran, MD, assistant professor and division director of geriatric psychiatry at Carilion Clinic–Virginia Tech Carilion School of Medicine, Roanoke, said the results are promising and important because there are so few treatment options for the increasing number of older patients with depression and dementia.
The side-effect profile of the combined treatment is better than that of many pharmacologic treatments, Ratnakaran noted. As more research like this comes out, Ratnakaran predicts that cognitive remediation and tCDS will become more readily available.
“This is telling us that the field of psychiatry, and also dementia, is progressing beyond your usual pharmacotherapy treatments,” said Ratnakaran, who also is chair of the American Psychiatric Association’s Council on Geriatric Psychiatry.
The study received support from the Canada Brain Research Fund of Brain Canada, Health Canada, the Chagnon Family, and the Centre for Addiction and Mental Health Discovery Fund. Mulsant reported holding and receiving support from the Labatt Family Chair in Biology of Depression in Late-Life Adults at the University of Toronto; being a member of the Center for Addiction and Mental Health Board of Trustees; research support from Brain Canada, Canadian Institutes of Health Research, Center for Addiction and Mental Health Foundation, Patient-Centered Outcomes Research Institute, and National Institutes of Health; and nonfinancial support from Capital Solution Design and HappyNeuron. Ratnakaran reported no relevant conflicts.
A version of this article appeared on Medscape.com.
new research suggests.
The cognitive remediation intervention included a series of progressively difficult computer-based and facilitator-monitored mental exercises designed to sharpen cognitive function.
Researchers found that using cognitive remediation with tDCS slowed decline in executive function and verbal memory more than other cognitive functions. The effect was stronger among people with rMDD versus those with MCI and in those at low genetic risk for Alzheimer’s disease.
“We have developed a novel intervention, combining two interventions that if used separately have a weak effect but together have substantial and clinically meaningful effect of slowing the progression of cognitive decline,” said study author Benoit H. Mulsant, MD, chair of the Department of Psychiatry, University of Toronto, Ontario, Canada, and senior scientist at the Center for Addiction and Mental Health, also in Toronto.
The findings were published online in JAMA Psychiatry.
High-Risk Group
Research shows that older adults with MDD or MCI are at high risk for cognitive decline and dementia. Evidence also suggests that depression in early or mid-life significantly increases the risk for dementia in late life, even if the depression has been in remission for decades.
A potential mechanism underlying this increased risk for dementia could be impaired cortical plasticity, or the ability of the brain to compensate for damage.
The PACt-MD trial included 375 older adults with rMDD, MCI, or both (mean age, 72 years; 62% women) at five academic hospitals in Toronto.
Participants received either cognitive remediation plus tDCS or sham intervention 5 days per week for 8 weeks (acute phase), followed by 5-day “boosters” every 6 months.
tDCS was administered by trained personnel and involved active stimulation for 30 minutes at the beginning of each cognitive remediation group session. The intervention targets the prefrontal cortex, a critical region for cognitive compensation in normal cognitive aging.
The sham group received a weakened version of cognitive remediation, with exercises that did not get progressively more difficult. For the sham stimulation, the current flowed at full intensity for only 54 seconds before and after 30-second ramp-up and ramp-down phases, to create a blinding effect, the authors noted.
A geriatric psychiatrist followed all participants throughout the study, conducting assessments at baseline, month 2, and yearly for 3-7 years (mean follow-up, 48.3 months).
Participants’ depressive symptoms were evaluated at baseline and at all follow-ups and underwent neuropsychological testing to assess six cognitive domains: processing speed, working memory, executive functioning, verbal memory, visual memory, and language.
To get a norm for the cognitive tests, researchers recruited a comparator group of 75 subjects similar in age, gender, and years of education, with no neuropsychiatric disorder or cognitive impairment. They completed the same assessments but not the intervention.
Study participants and assessors were blinded to treatment assignment.
Slower Cognitive Decline
Participants in the intervention group had a significantly slower decline in cognitive function, compared with those in the sham group (adjusted z score difference [active – sham] at month 60, 0.21; P = .006). This is equivalent to slowing cognitive decline by about 4 years, researchers reported. The intervention also showed a positive effect on executive function and verbal memory.
“If I can push dementia from 85 to 89 years and you die at 86, in practice, I have prevented you from ever developing dementia,” Mulsant said.
The efficacy of cognitive remediation plus tDCS in rMDD could be tied to enhanced neuroplasticity, said Mulsant.
The treatment worked well in people with a history of depression, regardless of MCI status, but was not as effective for people with just MCI, researchers noted. The intervention also did not work as well among people at genetic risk for Alzheimer’s disease.
“We don’t believe we have discovered an intervention to prevent dementia in people who are at high risk for Alzheimer disease, but we have discovered an intervention that could prevent dementia in people who have an history of depression,” said Mulsant.
These results suggest the pathways to dementia among people with MCI and rMDD are different, he added.
Because previous research showed either treatment alone demonstrated little efficacy, researchers said the new results indicate that there may be a synergistic effect of combining the two.
The ideal amount of treatment and optimal age for initiation still need to be determined, said Mulsant. The study did not include a comparator group without rMDD or MCI, so the observed cognitive benefits might be specific to people with these high-risk conditions. Another study limitation is lack of diversity in terms of ethnicity, race, and education.
Promising, Important Findings
Commenting on the research, Badr Ratnakaran, MD, assistant professor and division director of geriatric psychiatry at Carilion Clinic–Virginia Tech Carilion School of Medicine, Roanoke, said the results are promising and important because there are so few treatment options for the increasing number of older patients with depression and dementia.
The side-effect profile of the combined treatment is better than that of many pharmacologic treatments, Ratnakaran noted. As more research like this comes out, Ratnakaran predicts that cognitive remediation and tCDS will become more readily available.
“This is telling us that the field of psychiatry, and also dementia, is progressing beyond your usual pharmacotherapy treatments,” said Ratnakaran, who also is chair of the American Psychiatric Association’s Council on Geriatric Psychiatry.
The study received support from the Canada Brain Research Fund of Brain Canada, Health Canada, the Chagnon Family, and the Centre for Addiction and Mental Health Discovery Fund. Mulsant reported holding and receiving support from the Labatt Family Chair in Biology of Depression in Late-Life Adults at the University of Toronto; being a member of the Center for Addiction and Mental Health Board of Trustees; research support from Brain Canada, Canadian Institutes of Health Research, Center for Addiction and Mental Health Foundation, Patient-Centered Outcomes Research Institute, and National Institutes of Health; and nonfinancial support from Capital Solution Design and HappyNeuron. Ratnakaran reported no relevant conflicts.
A version of this article appeared on Medscape.com.
FROM JAMA PSYCHIATRY
A Finger-Prick Test for Alzheimer’s Disease?
In a pilot study, researchers found a good correlation of p-tau217 levels from blood obtained via standard venous sampling and from a single finger prick.
“We see the potential that capillary p-tau217 from dried blood spots could overcome the limitations of standard venous collection of being invasive, dependent on centrifuges and ultra-low temperature freezers, and also requiring less volume than standard plasma analysis,” said lead investigator Hanna Huber, PhD, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg, Sweden.
The findings were presented at the 17th Clinical Trials on Alzheimer’s Disease (CTAD) conference.
Strong Link Between Venous and Capillary Samples
p-tau217 has emerged as the most effective blood test to identify Alzheimer’s disease. However, traditional venous blood sampling requires certain infrastructure and immediate processing. Increased and simplified access to this blood biomarker could be crucial for early diagnosis, proper patient management, and prompt initiation of disease-modifying treatments.
The DROP-AD project is investigating the diagnostic performance of finger-prick collection to accurately measure p-tau217. In the current study, the research team obtained paired venous blood and capillary blood samples from 206 adults (mean age, 71.8 years; 59% women), with or without cognitive impairment, from five European centers. A subset of participants provided a second finger-prick sample collected without any supervision.
The capillary blood samples were obtained via a single finger prick, and then single blood drops were applied to a dried plasma spot (DPS) card, which was then shipped to a lab (without temperature control or cooling) for p-tau217 measurement. Cerebrospinal fluid biomarkers were available for a subset of individuals.
Throughout the entire study population, there was a “very convincing correlation” between p-tau217 levels from capillary DPS and venous plasma, Huber told conference attendees.
Additionally, capillary DPS p-tau217 levels were able to discriminate amyloid-positive from amyloid-negative individuals, with levels of this biomarker increasing in a stepwise fashion, “from cognitively unimpaired individuals to individuals with mild cognitive impairment and, finally, to dementia patients,” Huber said.
Of note, capillary p-tau217 levels from DPS samples that were collected by research staff did not differ from unsupervised self-collected samples.
What about the stability of the samples? Capillary DPS p-tau-217 is “stable over 2 weeks at room temperature,” Huber said.
Ready for Prime Time?
Preliminary data from the DROP-AD project highlight the potential of using finger-prick blood collection to identify neurofilament light (NfL) and glial fibrillary acidic protein (GFAP), two other Alzheimer’s disease biomarkers.
“We think that capillary p-tau217, but also other biomarkers, could be a widely accessible and cheap alternative for clinical practice and clinical trials in individuals with cognitive decline if the results are confirmed in longitudinal and home-sampling cohorts,” Huber concluded.
“Measuring biomarkers by a simple finger prick could facilitate regular and autonomous sampling at home, which would be particularly useful in remote and rural settings,” she noted.
The findings in this study confirm and extend earlier findings that the study team reported last year at the Alzheimer’s Association International Conference (AAIC).
“The data shared at CTAD 2024, along with the related material previously presented at AAIC 2023, reporting on a ‘finger prick’ blood test approach is interesting and emerging work but not yet ready for clinical use,” said Rebecca M. Edelmayer, PhD, Alzheimer’s Association vice president of scientific engagement.
“That said, the idea of a highly accessible and scalable tool that can aid in easier and more equitable diagnosis would be welcomed by researchers, clinicians, and individuals and families affected by Alzheimer’s disease and all other dementias,” Edelmayer said.
“This finger-prick blood testing technology for Alzheimer’s biomarkers still has to be validated more broadly, but it is very promising. Advancements in technology and practice demonstrate the simplicity, transportability, and diagnostic value of blood-based biomarkers for Alzheimer’s,” she added.
The Alzheimer’s Association is currently conducting a systematic review of the evidence and preparing clinical practice guidelines on blood-based biomarker tests for specialized healthcare settings, with publications, clinical resources, and tools anticipated in 2025, Edelmayer noted.
The study had no commercial funding. Huber and Edelmayer report no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
In a pilot study, researchers found a good correlation of p-tau217 levels from blood obtained via standard venous sampling and from a single finger prick.
“We see the potential that capillary p-tau217 from dried blood spots could overcome the limitations of standard venous collection of being invasive, dependent on centrifuges and ultra-low temperature freezers, and also requiring less volume than standard plasma analysis,” said lead investigator Hanna Huber, PhD, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg, Sweden.
The findings were presented at the 17th Clinical Trials on Alzheimer’s Disease (CTAD) conference.
Strong Link Between Venous and Capillary Samples
p-tau217 has emerged as the most effective blood test to identify Alzheimer’s disease. However, traditional venous blood sampling requires certain infrastructure and immediate processing. Increased and simplified access to this blood biomarker could be crucial for early diagnosis, proper patient management, and prompt initiation of disease-modifying treatments.
The DROP-AD project is investigating the diagnostic performance of finger-prick collection to accurately measure p-tau217. In the current study, the research team obtained paired venous blood and capillary blood samples from 206 adults (mean age, 71.8 years; 59% women), with or without cognitive impairment, from five European centers. A subset of participants provided a second finger-prick sample collected without any supervision.
The capillary blood samples were obtained via a single finger prick, and then single blood drops were applied to a dried plasma spot (DPS) card, which was then shipped to a lab (without temperature control or cooling) for p-tau217 measurement. Cerebrospinal fluid biomarkers were available for a subset of individuals.
Throughout the entire study population, there was a “very convincing correlation” between p-tau217 levels from capillary DPS and venous plasma, Huber told conference attendees.
Additionally, capillary DPS p-tau217 levels were able to discriminate amyloid-positive from amyloid-negative individuals, with levels of this biomarker increasing in a stepwise fashion, “from cognitively unimpaired individuals to individuals with mild cognitive impairment and, finally, to dementia patients,” Huber said.
Of note, capillary p-tau217 levels from DPS samples that were collected by research staff did not differ from unsupervised self-collected samples.
What about the stability of the samples? Capillary DPS p-tau-217 is “stable over 2 weeks at room temperature,” Huber said.
Ready for Prime Time?
Preliminary data from the DROP-AD project highlight the potential of using finger-prick blood collection to identify neurofilament light (NfL) and glial fibrillary acidic protein (GFAP), two other Alzheimer’s disease biomarkers.
“We think that capillary p-tau217, but also other biomarkers, could be a widely accessible and cheap alternative for clinical practice and clinical trials in individuals with cognitive decline if the results are confirmed in longitudinal and home-sampling cohorts,” Huber concluded.
“Measuring biomarkers by a simple finger prick could facilitate regular and autonomous sampling at home, which would be particularly useful in remote and rural settings,” she noted.
The findings in this study confirm and extend earlier findings that the study team reported last year at the Alzheimer’s Association International Conference (AAIC).
“The data shared at CTAD 2024, along with the related material previously presented at AAIC 2023, reporting on a ‘finger prick’ blood test approach is interesting and emerging work but not yet ready for clinical use,” said Rebecca M. Edelmayer, PhD, Alzheimer’s Association vice president of scientific engagement.
“That said, the idea of a highly accessible and scalable tool that can aid in easier and more equitable diagnosis would be welcomed by researchers, clinicians, and individuals and families affected by Alzheimer’s disease and all other dementias,” Edelmayer said.
“This finger-prick blood testing technology for Alzheimer’s biomarkers still has to be validated more broadly, but it is very promising. Advancements in technology and practice demonstrate the simplicity, transportability, and diagnostic value of blood-based biomarkers for Alzheimer’s,” she added.
The Alzheimer’s Association is currently conducting a systematic review of the evidence and preparing clinical practice guidelines on blood-based biomarker tests for specialized healthcare settings, with publications, clinical resources, and tools anticipated in 2025, Edelmayer noted.
The study had no commercial funding. Huber and Edelmayer report no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
In a pilot study, researchers found a good correlation of p-tau217 levels from blood obtained via standard venous sampling and from a single finger prick.
“We see the potential that capillary p-tau217 from dried blood spots could overcome the limitations of standard venous collection of being invasive, dependent on centrifuges and ultra-low temperature freezers, and also requiring less volume than standard plasma analysis,” said lead investigator Hanna Huber, PhD, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg, Sweden.
The findings were presented at the 17th Clinical Trials on Alzheimer’s Disease (CTAD) conference.
Strong Link Between Venous and Capillary Samples
p-tau217 has emerged as the most effective blood test to identify Alzheimer’s disease. However, traditional venous blood sampling requires certain infrastructure and immediate processing. Increased and simplified access to this blood biomarker could be crucial for early diagnosis, proper patient management, and prompt initiation of disease-modifying treatments.
The DROP-AD project is investigating the diagnostic performance of finger-prick collection to accurately measure p-tau217. In the current study, the research team obtained paired venous blood and capillary blood samples from 206 adults (mean age, 71.8 years; 59% women), with or without cognitive impairment, from five European centers. A subset of participants provided a second finger-prick sample collected without any supervision.
The capillary blood samples were obtained via a single finger prick, and then single blood drops were applied to a dried plasma spot (DPS) card, which was then shipped to a lab (without temperature control or cooling) for p-tau217 measurement. Cerebrospinal fluid biomarkers were available for a subset of individuals.
Throughout the entire study population, there was a “very convincing correlation” between p-tau217 levels from capillary DPS and venous plasma, Huber told conference attendees.
Additionally, capillary DPS p-tau217 levels were able to discriminate amyloid-positive from amyloid-negative individuals, with levels of this biomarker increasing in a stepwise fashion, “from cognitively unimpaired individuals to individuals with mild cognitive impairment and, finally, to dementia patients,” Huber said.
Of note, capillary p-tau217 levels from DPS samples that were collected by research staff did not differ from unsupervised self-collected samples.
What about the stability of the samples? Capillary DPS p-tau-217 is “stable over 2 weeks at room temperature,” Huber said.
Ready for Prime Time?
Preliminary data from the DROP-AD project highlight the potential of using finger-prick blood collection to identify neurofilament light (NfL) and glial fibrillary acidic protein (GFAP), two other Alzheimer’s disease biomarkers.
“We think that capillary p-tau217, but also other biomarkers, could be a widely accessible and cheap alternative for clinical practice and clinical trials in individuals with cognitive decline if the results are confirmed in longitudinal and home-sampling cohorts,” Huber concluded.
“Measuring biomarkers by a simple finger prick could facilitate regular and autonomous sampling at home, which would be particularly useful in remote and rural settings,” she noted.
The findings in this study confirm and extend earlier findings that the study team reported last year at the Alzheimer’s Association International Conference (AAIC).
“The data shared at CTAD 2024, along with the related material previously presented at AAIC 2023, reporting on a ‘finger prick’ blood test approach is interesting and emerging work but not yet ready for clinical use,” said Rebecca M. Edelmayer, PhD, Alzheimer’s Association vice president of scientific engagement.
“That said, the idea of a highly accessible and scalable tool that can aid in easier and more equitable diagnosis would be welcomed by researchers, clinicians, and individuals and families affected by Alzheimer’s disease and all other dementias,” Edelmayer said.
“This finger-prick blood testing technology for Alzheimer’s biomarkers still has to be validated more broadly, but it is very promising. Advancements in technology and practice demonstrate the simplicity, transportability, and diagnostic value of blood-based biomarkers for Alzheimer’s,” she added.
The Alzheimer’s Association is currently conducting a systematic review of the evidence and preparing clinical practice guidelines on blood-based biomarker tests for specialized healthcare settings, with publications, clinical resources, and tools anticipated in 2025, Edelmayer noted.
The study had no commercial funding. Huber and Edelmayer report no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
FROM CTAD 2024
More Evidence Ties Semaglutide to Reduced Alzheimer’s Risk
Adults with type 2 diabetes who were prescribed the GLP-1 RA semaglutide had a significantly lower risk for Alzheimer’s disease compared with their peers who were prescribed any of seven other antidiabetic medications, including other types of GLP-1 receptor–targeting medications.
“These findings support further clinical trials to assess semaglutide’s potential in delaying or preventing Alzheimer’s disease,” wrote the investigators, led by Rong Xu, PhD, with Case Western Reserve School of Medicine, Cleveland, Ohio.
The study was published online on October 24 in Alzheimer’s & Dementia.
Real-World Data
Semaglutide has shown neuroprotective effects in animal models of neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. In animal models of Alzheimer’s disease, the drug reduced beta-amyloid deposition and improved spatial learning and memory, as well as glucose metabolism in the brain.
In a real-world analysis, Xu and colleagues used electronic health record data to identify 17,104 new users of semaglutide and 1,077,657 new users of seven other antidiabetic medications, including other GLP-1 RAs, insulin, metformin, dipeptidyl peptidase 4 inhibitors, sodium-glucose cotransporter 2 inhibitors, sulfonylurea, and thiazolidinedione.
Over 3 years, treatment with semaglutide was associated with significantly reduced risk of developing Alzheimer’s disease, most strongly compared with insulin (hazard ratio [HR], 0.33) and most weakly compared with other GLP-1 RAs (HR, 0.59).
Compared with the other medications, semaglutide was associated with a 40%-70% reduced risk for first-time diagnosis of Alzheimer’s disease in patients with type 2 diabetes, with similar reductions seen across obesity status and gender and age groups, the authors reported.
The findings align with recent evidence suggesting GLP-1 RAs may protect cognitive function.
For example, as previously reported, in the phase 2b ELAD clinical trial, adults with early-stage Alzheimer’s disease taking the GLP-1 RA liraglutide exhibited slower decline in memory and thinking and experienced less brain atrophy over 12 months compared with placebo.
Promising, but Preliminary
Reached for comment, Courtney Kloske, PhD, Alzheimer’s Association director of scientific engagement, noted that diabetes is a known risk factor for AD and managing diabetes with drugs such as semaglutide “could benefit brain health simply by managing diabetes.”
“However, we still need large clinical trials in representative populations to determine if semaglutide specifically lowers the risk of Alzheimer’s, so it is too early to recommend it for prevention,” Kloske said.
She noted that some research suggests that GLP-1 RAs “may help reduce inflammation and positively impact brain energy use. However, more research is needed to fully understand how these processes might contribute to preventing cognitive decline or Alzheimer’s,” Kloske cautioned.
The Alzheimer’s Association’s “Part the Cloud” initiative has invested more than $68 million to advance 65 clinical trials targeting a variety of compounds, including repurposed drugs that may address known and potential new aspects of the disease, Kloske said.
The study was supported by grants from the National Institute on Aging and the National Center for Advancing Translational Sciences. Xu and Kloske have no relevant conflicts.
A version of this article appeared on Medscape.com.
Adults with type 2 diabetes who were prescribed the GLP-1 RA semaglutide had a significantly lower risk for Alzheimer’s disease compared with their peers who were prescribed any of seven other antidiabetic medications, including other types of GLP-1 receptor–targeting medications.
“These findings support further clinical trials to assess semaglutide’s potential in delaying or preventing Alzheimer’s disease,” wrote the investigators, led by Rong Xu, PhD, with Case Western Reserve School of Medicine, Cleveland, Ohio.
The study was published online on October 24 in Alzheimer’s & Dementia.
Real-World Data
Semaglutide has shown neuroprotective effects in animal models of neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. In animal models of Alzheimer’s disease, the drug reduced beta-amyloid deposition and improved spatial learning and memory, as well as glucose metabolism in the brain.
In a real-world analysis, Xu and colleagues used electronic health record data to identify 17,104 new users of semaglutide and 1,077,657 new users of seven other antidiabetic medications, including other GLP-1 RAs, insulin, metformin, dipeptidyl peptidase 4 inhibitors, sodium-glucose cotransporter 2 inhibitors, sulfonylurea, and thiazolidinedione.
Over 3 years, treatment with semaglutide was associated with significantly reduced risk of developing Alzheimer’s disease, most strongly compared with insulin (hazard ratio [HR], 0.33) and most weakly compared with other GLP-1 RAs (HR, 0.59).
Compared with the other medications, semaglutide was associated with a 40%-70% reduced risk for first-time diagnosis of Alzheimer’s disease in patients with type 2 diabetes, with similar reductions seen across obesity status and gender and age groups, the authors reported.
The findings align with recent evidence suggesting GLP-1 RAs may protect cognitive function.
For example, as previously reported, in the phase 2b ELAD clinical trial, adults with early-stage Alzheimer’s disease taking the GLP-1 RA liraglutide exhibited slower decline in memory and thinking and experienced less brain atrophy over 12 months compared with placebo.
Promising, but Preliminary
Reached for comment, Courtney Kloske, PhD, Alzheimer’s Association director of scientific engagement, noted that diabetes is a known risk factor for AD and managing diabetes with drugs such as semaglutide “could benefit brain health simply by managing diabetes.”
“However, we still need large clinical trials in representative populations to determine if semaglutide specifically lowers the risk of Alzheimer’s, so it is too early to recommend it for prevention,” Kloske said.
She noted that some research suggests that GLP-1 RAs “may help reduce inflammation and positively impact brain energy use. However, more research is needed to fully understand how these processes might contribute to preventing cognitive decline or Alzheimer’s,” Kloske cautioned.
The Alzheimer’s Association’s “Part the Cloud” initiative has invested more than $68 million to advance 65 clinical trials targeting a variety of compounds, including repurposed drugs that may address known and potential new aspects of the disease, Kloske said.
The study was supported by grants from the National Institute on Aging and the National Center for Advancing Translational Sciences. Xu and Kloske have no relevant conflicts.
A version of this article appeared on Medscape.com.
Adults with type 2 diabetes who were prescribed the GLP-1 RA semaglutide had a significantly lower risk for Alzheimer’s disease compared with their peers who were prescribed any of seven other antidiabetic medications, including other types of GLP-1 receptor–targeting medications.
“These findings support further clinical trials to assess semaglutide’s potential in delaying or preventing Alzheimer’s disease,” wrote the investigators, led by Rong Xu, PhD, with Case Western Reserve School of Medicine, Cleveland, Ohio.
The study was published online on October 24 in Alzheimer’s & Dementia.
Real-World Data
Semaglutide has shown neuroprotective effects in animal models of neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. In animal models of Alzheimer’s disease, the drug reduced beta-amyloid deposition and improved spatial learning and memory, as well as glucose metabolism in the brain.
In a real-world analysis, Xu and colleagues used electronic health record data to identify 17,104 new users of semaglutide and 1,077,657 new users of seven other antidiabetic medications, including other GLP-1 RAs, insulin, metformin, dipeptidyl peptidase 4 inhibitors, sodium-glucose cotransporter 2 inhibitors, sulfonylurea, and thiazolidinedione.
Over 3 years, treatment with semaglutide was associated with significantly reduced risk of developing Alzheimer’s disease, most strongly compared with insulin (hazard ratio [HR], 0.33) and most weakly compared with other GLP-1 RAs (HR, 0.59).
Compared with the other medications, semaglutide was associated with a 40%-70% reduced risk for first-time diagnosis of Alzheimer’s disease in patients with type 2 diabetes, with similar reductions seen across obesity status and gender and age groups, the authors reported.
The findings align with recent evidence suggesting GLP-1 RAs may protect cognitive function.
For example, as previously reported, in the phase 2b ELAD clinical trial, adults with early-stage Alzheimer’s disease taking the GLP-1 RA liraglutide exhibited slower decline in memory and thinking and experienced less brain atrophy over 12 months compared with placebo.
Promising, but Preliminary
Reached for comment, Courtney Kloske, PhD, Alzheimer’s Association director of scientific engagement, noted that diabetes is a known risk factor for AD and managing diabetes with drugs such as semaglutide “could benefit brain health simply by managing diabetes.”
“However, we still need large clinical trials in representative populations to determine if semaglutide specifically lowers the risk of Alzheimer’s, so it is too early to recommend it for prevention,” Kloske said.
She noted that some research suggests that GLP-1 RAs “may help reduce inflammation and positively impact brain energy use. However, more research is needed to fully understand how these processes might contribute to preventing cognitive decline or Alzheimer’s,” Kloske cautioned.
The Alzheimer’s Association’s “Part the Cloud” initiative has invested more than $68 million to advance 65 clinical trials targeting a variety of compounds, including repurposed drugs that may address known and potential new aspects of the disease, Kloske said.
The study was supported by grants from the National Institute on Aging and the National Center for Advancing Translational Sciences. Xu and Kloske have no relevant conflicts.
A version of this article appeared on Medscape.com.
FROM ALZHEIMER’S & DEMENTIA
Why Scientists Are Linking More Diseases to Light at Night
This October, millions of Americans missed out on two of the most spectacular shows in the universe: the northern lights and a rare comet. Even if you were aware of them, light pollution made them difficult to see, unless you went to a dark area and let your eyes adjust.
It’s not getting any easier — the night sky over North America has been growing brighter by about 10% per year since 2011. More and more research is linking all that light pollution to a surprising range of health consequences: cancer, heart disease, diabetes, Alzheimer’s disease, and even low sperm quality, though the reasons for these troubling associations are not always clear.
“We’ve lost the contrast between light and dark, and we are confusing our physiology on a regular basis,” said John Hanifin, PhD, associate director of Thomas Jefferson University’s Light Research Program.
Our own galaxy is invisible to nearly 80% of people in North America. In 1994, an earthquake-triggered blackout in Los Angeles led to calls to the Griffith Observatory from people wondering about that hazy blob of light in the night sky. It was the Milky Way.
Glaring headlights, illuminated buildings, blazing billboards, and streetlights fill our urban skies with a glow that even affects rural residents. Inside, since the invention of the lightbulb, we’ve kept our homes bright at night. Now, we’ve also added blue light-emitting devices — smartphones, television screens, tablets — which have been linked to sleep problems.
But outdoor light may matter for our health, too. “Every photon counts,” Hanifin said.
Bright Lights, Big Problems
For one 2024 study researchers used satellite data to measure light pollution at residential addresses of over 13,000 people. They found that those who lived in places with the brightest skies at night had a 31% higher risk of high blood pressure. Another study out of Hong Kong showed a 29% higher risk of death from coronary heart disease. And yet another found a 17%higher risk of cerebrovascular disease, such as strokes or brain aneurysms.
Of course, urban areas also have air pollution, noise, and a lack of greenery. So, for some studies, scientists controlled for these factors, and the correlation remained strong (although air pollution with fine particulate matter appeared to be worse for heart health than outdoor light).
Research has found links between the nighttime glow outside and other diseases:
Breast cancer. “It’s a very strong correlation,” said Randy Nelson, PhD, a neuroscientist at West Virginia University. A study of over 100,000 teachers in California revealed that women living in areas with the most light pollution had a 12%higher risk. That effect is comparable to increasing your intake of ultra-processed foods by 10%.
Alzheimer’s disease. In a study published this fall, outdoor light at night was more strongly linked to the disease than even alcohol misuse or obesity.
Diabetes. In one recent study, people living in the most illuminated areas had a 28% higher risk of diabetes than those residing in much darker places. In a country like China, scientists concluded that 9 million cases of diabetes could be linked to light pollution.
What Happens in Your Body When You’re Exposed to Light at Night
, the “hormone of darkness.” “Darkness is very important,” Hanifin said. When he and his colleagues decades ago started studying the effects of light on human physiology, “people thought we were borderline crazy,” he said.
Nighttime illumination affects the health and behavior of species as diverse as Siberian hamsters, zebra finches, mice, crickets, and mosquitoes. Like most creatures on Earth, humans have internal clocks that are synced to the 24-hour cycle of day and night. The master clock is in your hypothalamus, a diamond-shaped part of the brain, but every cell in your body has its own clock, too. Many physiological processes run on circadian rhythms (a term derived from a Latin phrase meaning “about a day”), from sleep-wake cycle to hormone secretion, as well as processes involved in cancer progression, such as cell division.
“There are special photoreceptors in the eye that don’t deal with visual information. They just send light information,” Nelson said. “If you get light at the wrong time, you’re resetting the clocks.”
This internal clock “prepares the body for various recurrent challenges, such as eating,” said Christian Benedict, PhD, a sleep researcher at Uppsala University, Sweden. “Light exposure [at night] can mess up this very important system.” This could mean, for instance, that your insulin is released at the wrong time, Benedict said, causing “a jet lag-ish condition that will then impair the ability to handle blood sugar.” Animal studies confirm that exposure to light at night can reduce glucose tolerance and alter insulin secretion – potential pathways to diabetes.
The hormone melatonin, produced when it’s dark by the pineal gland in the brain, is a key player in this modern struggle. Melatonin helps you sleep, synchronizes the body’s circadian rhythms, protects neurons from damage, regulates the immune system, and fights inflammation. But even a sliver of light at night can suppress its secretion. Less than 30 lux of light, about the level of a pedestrian street at night, can slash melatonin by half.
When lab animals are exposed to nighttime light, they “show enormous neuroinflammation” — that is, inflammation of nervous tissue, Nelson said. In one experiment on humans, those who slept immersed in weak light had higher levels of C-reactive protein in their blood, a marker of inflammation.
Low melatonin has also been linked to cancer. It “allows the metabolic machinery of the cancer cells to be active,” Hanifin said. One of melatonin’s effects is stimulation of natural killer cells, which can recognize and destroy cancer cells. What’s more, when melatonin plunges, estrogen may go up, which could explain the link between light at night and breast cancer (estrogen fuels tumor growth in breast cancers).
Researchers concede that satellite data might be too coarse to estimate how much light people are actually exposed to while they sleep. Plus, many of us are staring at bright screens. “But the studies keep coming,” Nelson said, suggesting that outdoor light pollution does have an impact.
When researchers put wrist-worn light sensors on over 80,000 British people, they found that the more light the device registered between half-past midnight and 6 a.m., the more its wearer was at risk of having diabetes several years down the road — no matter how long they’ve actually slept. This, according to the study’s authors, supports the findings of satellite data.
A similar study that used actigraphy with built-in light sensors, measuring whether people had been sleeping in complete darkness for at least five hours, found that light pollution upped the risk of heart disease by 74%.
What Can You Do About This?
Not everyone’s melatonin is affected by nighttime light to the same degree. “Some people are very much sensitive to very dim light, whereas others are not as sensitive and need far, far more light stimulation [to impact melatonin],” Benedict said. In one study, some volunteers needed 350 lux to lower their melatonin by half. For such people, flipping on the light in the bathroom at night wouldn’t matter; for others, though, a mere 6 lux was already as harmful – which is darker than twilight.
You can protect yourself by keeping your bedroom lights off and your screens stashed away, but avoiding outdoor light pollution may be harder. You can invest in high-quality blackout curtains, of course, although some light may still seep inside. You can plant trees in front of your windows, reorient any motion-detector lights, and even petition your local government to reduce over-illumination of buildings and to choose better streetlights. You can support organizations, such as the International Dark-Sky Association, that work to preserve darkness.
Last but not least, you might want to change your habits. If you live in a particularly light-polluted area, such as the District of Columbia, America’s top place for urban blaze, you might reconsider late-night walks or drives around the neighborhood. Instead, Hanifin said, read a book in bed, while keeping the light “as dim as you can.” It’s “a much better idea versus being outside in midtown Manhattan,” he said. According to recent recommendations published by Hanifin and his colleagues, when you sleep, there should be no more than 1 lux of illumination at the level of your eyes — about as much as you’d get from having a lit candle 1 meter away.
And if we manage to preserve outdoor darkness, and the stars reappear (including the breathtaking Milky Way), we could reap more benefits — some research suggests that stargazing can elicit positive emotions, a sense of personal growth, and “a variety of transcendent thoughts and experiences.”
A version of this article appeared on WebMD.com.
This October, millions of Americans missed out on two of the most spectacular shows in the universe: the northern lights and a rare comet. Even if you were aware of them, light pollution made them difficult to see, unless you went to a dark area and let your eyes adjust.
It’s not getting any easier — the night sky over North America has been growing brighter by about 10% per year since 2011. More and more research is linking all that light pollution to a surprising range of health consequences: cancer, heart disease, diabetes, Alzheimer’s disease, and even low sperm quality, though the reasons for these troubling associations are not always clear.
“We’ve lost the contrast between light and dark, and we are confusing our physiology on a regular basis,” said John Hanifin, PhD, associate director of Thomas Jefferson University’s Light Research Program.
Our own galaxy is invisible to nearly 80% of people in North America. In 1994, an earthquake-triggered blackout in Los Angeles led to calls to the Griffith Observatory from people wondering about that hazy blob of light in the night sky. It was the Milky Way.
Glaring headlights, illuminated buildings, blazing billboards, and streetlights fill our urban skies with a glow that even affects rural residents. Inside, since the invention of the lightbulb, we’ve kept our homes bright at night. Now, we’ve also added blue light-emitting devices — smartphones, television screens, tablets — which have been linked to sleep problems.
But outdoor light may matter for our health, too. “Every photon counts,” Hanifin said.
Bright Lights, Big Problems
For one 2024 study researchers used satellite data to measure light pollution at residential addresses of over 13,000 people. They found that those who lived in places with the brightest skies at night had a 31% higher risk of high blood pressure. Another study out of Hong Kong showed a 29% higher risk of death from coronary heart disease. And yet another found a 17%higher risk of cerebrovascular disease, such as strokes or brain aneurysms.
Of course, urban areas also have air pollution, noise, and a lack of greenery. So, for some studies, scientists controlled for these factors, and the correlation remained strong (although air pollution with fine particulate matter appeared to be worse for heart health than outdoor light).
Research has found links between the nighttime glow outside and other diseases:
Breast cancer. “It’s a very strong correlation,” said Randy Nelson, PhD, a neuroscientist at West Virginia University. A study of over 100,000 teachers in California revealed that women living in areas with the most light pollution had a 12%higher risk. That effect is comparable to increasing your intake of ultra-processed foods by 10%.
Alzheimer’s disease. In a study published this fall, outdoor light at night was more strongly linked to the disease than even alcohol misuse or obesity.
Diabetes. In one recent study, people living in the most illuminated areas had a 28% higher risk of diabetes than those residing in much darker places. In a country like China, scientists concluded that 9 million cases of diabetes could be linked to light pollution.
What Happens in Your Body When You’re Exposed to Light at Night
, the “hormone of darkness.” “Darkness is very important,” Hanifin said. When he and his colleagues decades ago started studying the effects of light on human physiology, “people thought we were borderline crazy,” he said.
Nighttime illumination affects the health and behavior of species as diverse as Siberian hamsters, zebra finches, mice, crickets, and mosquitoes. Like most creatures on Earth, humans have internal clocks that are synced to the 24-hour cycle of day and night. The master clock is in your hypothalamus, a diamond-shaped part of the brain, but every cell in your body has its own clock, too. Many physiological processes run on circadian rhythms (a term derived from a Latin phrase meaning “about a day”), from sleep-wake cycle to hormone secretion, as well as processes involved in cancer progression, such as cell division.
“There are special photoreceptors in the eye that don’t deal with visual information. They just send light information,” Nelson said. “If you get light at the wrong time, you’re resetting the clocks.”
This internal clock “prepares the body for various recurrent challenges, such as eating,” said Christian Benedict, PhD, a sleep researcher at Uppsala University, Sweden. “Light exposure [at night] can mess up this very important system.” This could mean, for instance, that your insulin is released at the wrong time, Benedict said, causing “a jet lag-ish condition that will then impair the ability to handle blood sugar.” Animal studies confirm that exposure to light at night can reduce glucose tolerance and alter insulin secretion – potential pathways to diabetes.
The hormone melatonin, produced when it’s dark by the pineal gland in the brain, is a key player in this modern struggle. Melatonin helps you sleep, synchronizes the body’s circadian rhythms, protects neurons from damage, regulates the immune system, and fights inflammation. But even a sliver of light at night can suppress its secretion. Less than 30 lux of light, about the level of a pedestrian street at night, can slash melatonin by half.
When lab animals are exposed to nighttime light, they “show enormous neuroinflammation” — that is, inflammation of nervous tissue, Nelson said. In one experiment on humans, those who slept immersed in weak light had higher levels of C-reactive protein in their blood, a marker of inflammation.
Low melatonin has also been linked to cancer. It “allows the metabolic machinery of the cancer cells to be active,” Hanifin said. One of melatonin’s effects is stimulation of natural killer cells, which can recognize and destroy cancer cells. What’s more, when melatonin plunges, estrogen may go up, which could explain the link between light at night and breast cancer (estrogen fuels tumor growth in breast cancers).
Researchers concede that satellite data might be too coarse to estimate how much light people are actually exposed to while they sleep. Plus, many of us are staring at bright screens. “But the studies keep coming,” Nelson said, suggesting that outdoor light pollution does have an impact.
When researchers put wrist-worn light sensors on over 80,000 British people, they found that the more light the device registered between half-past midnight and 6 a.m., the more its wearer was at risk of having diabetes several years down the road — no matter how long they’ve actually slept. This, according to the study’s authors, supports the findings of satellite data.
A similar study that used actigraphy with built-in light sensors, measuring whether people had been sleeping in complete darkness for at least five hours, found that light pollution upped the risk of heart disease by 74%.
What Can You Do About This?
Not everyone’s melatonin is affected by nighttime light to the same degree. “Some people are very much sensitive to very dim light, whereas others are not as sensitive and need far, far more light stimulation [to impact melatonin],” Benedict said. In one study, some volunteers needed 350 lux to lower their melatonin by half. For such people, flipping on the light in the bathroom at night wouldn’t matter; for others, though, a mere 6 lux was already as harmful – which is darker than twilight.
You can protect yourself by keeping your bedroom lights off and your screens stashed away, but avoiding outdoor light pollution may be harder. You can invest in high-quality blackout curtains, of course, although some light may still seep inside. You can plant trees in front of your windows, reorient any motion-detector lights, and even petition your local government to reduce over-illumination of buildings and to choose better streetlights. You can support organizations, such as the International Dark-Sky Association, that work to preserve darkness.
Last but not least, you might want to change your habits. If you live in a particularly light-polluted area, such as the District of Columbia, America’s top place for urban blaze, you might reconsider late-night walks or drives around the neighborhood. Instead, Hanifin said, read a book in bed, while keeping the light “as dim as you can.” It’s “a much better idea versus being outside in midtown Manhattan,” he said. According to recent recommendations published by Hanifin and his colleagues, when you sleep, there should be no more than 1 lux of illumination at the level of your eyes — about as much as you’d get from having a lit candle 1 meter away.
And if we manage to preserve outdoor darkness, and the stars reappear (including the breathtaking Milky Way), we could reap more benefits — some research suggests that stargazing can elicit positive emotions, a sense of personal growth, and “a variety of transcendent thoughts and experiences.”
A version of this article appeared on WebMD.com.
This October, millions of Americans missed out on two of the most spectacular shows in the universe: the northern lights and a rare comet. Even if you were aware of them, light pollution made them difficult to see, unless you went to a dark area and let your eyes adjust.
It’s not getting any easier — the night sky over North America has been growing brighter by about 10% per year since 2011. More and more research is linking all that light pollution to a surprising range of health consequences: cancer, heart disease, diabetes, Alzheimer’s disease, and even low sperm quality, though the reasons for these troubling associations are not always clear.
“We’ve lost the contrast between light and dark, and we are confusing our physiology on a regular basis,” said John Hanifin, PhD, associate director of Thomas Jefferson University’s Light Research Program.
Our own galaxy is invisible to nearly 80% of people in North America. In 1994, an earthquake-triggered blackout in Los Angeles led to calls to the Griffith Observatory from people wondering about that hazy blob of light in the night sky. It was the Milky Way.
Glaring headlights, illuminated buildings, blazing billboards, and streetlights fill our urban skies with a glow that even affects rural residents. Inside, since the invention of the lightbulb, we’ve kept our homes bright at night. Now, we’ve also added blue light-emitting devices — smartphones, television screens, tablets — which have been linked to sleep problems.
But outdoor light may matter for our health, too. “Every photon counts,” Hanifin said.
Bright Lights, Big Problems
For one 2024 study researchers used satellite data to measure light pollution at residential addresses of over 13,000 people. They found that those who lived in places with the brightest skies at night had a 31% higher risk of high blood pressure. Another study out of Hong Kong showed a 29% higher risk of death from coronary heart disease. And yet another found a 17%higher risk of cerebrovascular disease, such as strokes or brain aneurysms.
Of course, urban areas also have air pollution, noise, and a lack of greenery. So, for some studies, scientists controlled for these factors, and the correlation remained strong (although air pollution with fine particulate matter appeared to be worse for heart health than outdoor light).
Research has found links between the nighttime glow outside and other diseases:
Breast cancer. “It’s a very strong correlation,” said Randy Nelson, PhD, a neuroscientist at West Virginia University. A study of over 100,000 teachers in California revealed that women living in areas with the most light pollution had a 12%higher risk. That effect is comparable to increasing your intake of ultra-processed foods by 10%.
Alzheimer’s disease. In a study published this fall, outdoor light at night was more strongly linked to the disease than even alcohol misuse or obesity.
Diabetes. In one recent study, people living in the most illuminated areas had a 28% higher risk of diabetes than those residing in much darker places. In a country like China, scientists concluded that 9 million cases of diabetes could be linked to light pollution.
What Happens in Your Body When You’re Exposed to Light at Night
, the “hormone of darkness.” “Darkness is very important,” Hanifin said. When he and his colleagues decades ago started studying the effects of light on human physiology, “people thought we were borderline crazy,” he said.
Nighttime illumination affects the health and behavior of species as diverse as Siberian hamsters, zebra finches, mice, crickets, and mosquitoes. Like most creatures on Earth, humans have internal clocks that are synced to the 24-hour cycle of day and night. The master clock is in your hypothalamus, a diamond-shaped part of the brain, but every cell in your body has its own clock, too. Many physiological processes run on circadian rhythms (a term derived from a Latin phrase meaning “about a day”), from sleep-wake cycle to hormone secretion, as well as processes involved in cancer progression, such as cell division.
“There are special photoreceptors in the eye that don’t deal with visual information. They just send light information,” Nelson said. “If you get light at the wrong time, you’re resetting the clocks.”
This internal clock “prepares the body for various recurrent challenges, such as eating,” said Christian Benedict, PhD, a sleep researcher at Uppsala University, Sweden. “Light exposure [at night] can mess up this very important system.” This could mean, for instance, that your insulin is released at the wrong time, Benedict said, causing “a jet lag-ish condition that will then impair the ability to handle blood sugar.” Animal studies confirm that exposure to light at night can reduce glucose tolerance and alter insulin secretion – potential pathways to diabetes.
The hormone melatonin, produced when it’s dark by the pineal gland in the brain, is a key player in this modern struggle. Melatonin helps you sleep, synchronizes the body’s circadian rhythms, protects neurons from damage, regulates the immune system, and fights inflammation. But even a sliver of light at night can suppress its secretion. Less than 30 lux of light, about the level of a pedestrian street at night, can slash melatonin by half.
When lab animals are exposed to nighttime light, they “show enormous neuroinflammation” — that is, inflammation of nervous tissue, Nelson said. In one experiment on humans, those who slept immersed in weak light had higher levels of C-reactive protein in their blood, a marker of inflammation.
Low melatonin has also been linked to cancer. It “allows the metabolic machinery of the cancer cells to be active,” Hanifin said. One of melatonin’s effects is stimulation of natural killer cells, which can recognize and destroy cancer cells. What’s more, when melatonin plunges, estrogen may go up, which could explain the link between light at night and breast cancer (estrogen fuels tumor growth in breast cancers).
Researchers concede that satellite data might be too coarse to estimate how much light people are actually exposed to while they sleep. Plus, many of us are staring at bright screens. “But the studies keep coming,” Nelson said, suggesting that outdoor light pollution does have an impact.
When researchers put wrist-worn light sensors on over 80,000 British people, they found that the more light the device registered between half-past midnight and 6 a.m., the more its wearer was at risk of having diabetes several years down the road — no matter how long they’ve actually slept. This, according to the study’s authors, supports the findings of satellite data.
A similar study that used actigraphy with built-in light sensors, measuring whether people had been sleeping in complete darkness for at least five hours, found that light pollution upped the risk of heart disease by 74%.
What Can You Do About This?
Not everyone’s melatonin is affected by nighttime light to the same degree. “Some people are very much sensitive to very dim light, whereas others are not as sensitive and need far, far more light stimulation [to impact melatonin],” Benedict said. In one study, some volunteers needed 350 lux to lower their melatonin by half. For such people, flipping on the light in the bathroom at night wouldn’t matter; for others, though, a mere 6 lux was already as harmful – which is darker than twilight.
You can protect yourself by keeping your bedroom lights off and your screens stashed away, but avoiding outdoor light pollution may be harder. You can invest in high-quality blackout curtains, of course, although some light may still seep inside. You can plant trees in front of your windows, reorient any motion-detector lights, and even petition your local government to reduce over-illumination of buildings and to choose better streetlights. You can support organizations, such as the International Dark-Sky Association, that work to preserve darkness.
Last but not least, you might want to change your habits. If you live in a particularly light-polluted area, such as the District of Columbia, America’s top place for urban blaze, you might reconsider late-night walks or drives around the neighborhood. Instead, Hanifin said, read a book in bed, while keeping the light “as dim as you can.” It’s “a much better idea versus being outside in midtown Manhattan,” he said. According to recent recommendations published by Hanifin and his colleagues, when you sleep, there should be no more than 1 lux of illumination at the level of your eyes — about as much as you’d get from having a lit candle 1 meter away.
And if we manage to preserve outdoor darkness, and the stars reappear (including the breathtaking Milky Way), we could reap more benefits — some research suggests that stargazing can elicit positive emotions, a sense of personal growth, and “a variety of transcendent thoughts and experiences.”
A version of this article appeared on WebMD.com.
Blood Tests for Alzheimer’s Are Here... Are Clinicians Ready?
With the approval of anti-amyloid monoclonal antibodies to treat early-stage Alzheimer’s disease, the need for accurate and early diagnosis is crucial.
Recently, an expert workgroup convened by the Global CEO Initiative on Alzheimer’s Disease published recommendations for the clinical implementation of Alzheimer’s disease blood-based biomarkers.
“Our hope was to provide some recommendations that clinicians could use to develop the best pathways for their clinical practice,” said workgroup co-chair Michelle M. Mielke, PhD, with Wake Forest University School of Medicine, Winston-Salem, North Carolina.
Triage and Confirmatory Pathways
The group recommends two implementation pathways for Alzheimer’s disease blood biomarkers — one for current use for triaging and another for future use to confirm amyloid pathology once blood biomarker tests have reached sufficient performance for this purpose.
In the triage pathway, a negative blood biomarker test would flag individuals unlikely to have detectable brain amyloid pathology. This outcome would prompt clinicians to focus on evaluating non–Alzheimer’s disease-related causes of cognitive impairment, which may streamline the diagnosis of other causes of cognitive impairment, the authors said.
A positive triage blood test would suggest a higher likelihood of amyloid pathology and prompt referral to secondary care for further assessment and consideration for a second, more accurate test, such as amyloid PET or CSF for amyloid confirmation.
In the confirmatory pathway, a positive blood biomarker test result would identify amyloid pathology without the need for a second test, providing a faster route to diagnosis, the authors noted.
Mielke emphasized that these recommendations represent a “first step” and will need to be updated as experiences with the Alzheimer’s disease blood biomarkers in clinical care increase and additional barriers and facilitators are identified.
“These updates will likely include community-informed approaches that incorporate feedback from patients as well as healthcare providers, alongside results from validation in diverse real-world settings,” said workgroup co-chair Chi Udeh-Momoh, PhD, MSc, with Wake Forest University School of Medicine and the Brain and Mind Institute, Aga Khan University, Nairobi, Kenya.
The Alzheimer’s Association published “appropriate use” recommendations for blood biomarkers in 2022.
“Currently, the Alzheimer’s Association is building an updated library of clinical guidance that distills the scientific evidence using de novo systematic reviews and translates them into clear and actionable recommendations for clinical practice,” said Rebecca M. Edelmayer, PhD, vice president of scientific engagement, Alzheimer’s Association.
“The first major effort with our new process will be the upcoming Evidence-based Clinical Practice Guideline on the Use of Blood-based Biomarkers (BBMs) in Specialty Care Settings. This guideline’s recommendations will be published in early 2025,” Edelmayer said.
Availability and Accuracy
Research has shown that amyloid beta and tau protein blood biomarkers — especially a high plasma phosphorylated (p)–tau217 levels — are highly accurate in identifying Alzheimer’s disease in patients with cognitive symptoms attending primary and secondary care clinics.
Several tests targeting plasma p-tau217 are now available for use. They include the PrecivityAD2 blood test from C2N Diagnostics and the Simoa p-Tau 217 Planar Kit and LucentAD p-Tau 217 — both from Quanterix.
In a recent head-to-head comparison of seven leading blood tests for AD pathology, measures of plasma p-tau217, either individually or in combination with other plasma biomarkers, had the strongest relationships with Alzheimer’s disease outcomes.
A recent Swedish study showed that the PrecivityAD2 test had an accuracy of 91% for correctly classifying clinical, biomarker-verified Alzheimer’s disease.
“We’ve been using these blood biomarkers in research for a long time and we’re now taking the jump to start using them in clinic to risk stratify patients,” said Fanny Elahi, MD, PhD, director of fluid biomarker research for the Barbara and Maurice Deane Center for Wellness and Cognitive Health at Icahn Mount Sinai in New York City.
New York’s Mount Sinai Health System is among the first in the northeast to offer blood tests across primary and specialty care settings for early diagnosis of AD and related dementias.
Edelmayer cautioned, “There is no single, stand-alone test to diagnose Alzheimer’s disease today. Blood testing is one piece of the diagnostic process.”
“Currently, physicians use well-established diagnostic tools combined with medical history and other information, including neurological exams, cognitive and functional assessments as well as brain imaging and spinal fluid analysis and blood to make an accurate diagnosis and to understand which patients are eligible for approved treatments,” she said.
There are also emerging biomarkers in the research pipeline, Edelmayer said.
“For example, some researchers think retinal imaging has the potential to detect biological signs of Alzheimer’s disease within certain areas of the eye,” she explained.
“Other emerging biomarkers include examining components in saliva and the skin for signals that may indicate early biological changes in the brain. These biomarkers are still very exploratory, and more research is needed before these tests or biomarkers can be used more routinely to study risk or aid in diagnosis,” Edelmayer said.
Ideal Candidates for Alzheimer’s Disease Blood Testing?
Experts agree that blood tests represent a convenient and scalable option to address the anticipated surge in demand for biomarker testing with the availability of disease-modifying treatments. For now, however, they are not for all older adults worried about their memory.
“Current practice should focus on using these blood biomarkers in individuals with cognitive impairment rather than in those with normal cognition or subjective cognitive decline until further research demonstrates effective interventions for individuals considered cognitively normal with elevated levels of amyloid,” the authors of a recent JAMA editorial noted.
At Mount Sinai, “we’re not starting with stone-cold asymptomatic individuals. But ultimately, this is what the blood tests are intended for — screening,” Elahi noted.
She also noted that Mount Sinai has a “very diverse population” — some with young onset cognitive symptoms, so the entry criteria for testing are “very wide.”
“Anyone above age 40 with symptoms can qualify to get a blood test. We do ask at this stage that either the individual report symptoms or someone in their life or their clinician be worried about their cognition or their brain function,” Elahi said.
Ethical Considerations, Counseling
Elahi emphasized the importance of counseling patients who come to the clinic seeking an Alzheimer’s disease blood test. This should include how the diagnostic process will unfold and what the next steps are with a given result.
Elahi said patients need to be informed that Alzheimer’s disease blood biomarkers are still “relatively new,” and a test can help a patient “know the likelihood of having the disease, but it won’t be 100% definitive.”
To ensure the ethical principle of “do no harm,” counseling should ensure that patients are fully prepared for the implications of the test results and ensure that the decision to test aligns with the patient’s readiness and well-being, Elahi said.
Edelmayer said the forthcoming clinical practice guidelines will provide “evidence-based recommendations for physicians to help guide them through the decision-making process around who should be tested and when. In the meantime, the Alzheimer’s Association urges providers to refer to the 2022 appropriate use recommendations for blood tests in clinical practice and trial settings.”
Mielke has served on scientific advisory boards and/or having consulted for Acadia, Biogen, Eisai, LabCorp, Lilly, Merck, PeerView Institute, Roche, Siemens Healthineers, and Sunbird Bio. Edelmayer and Elahi had no relevant disclosures.
A version of this article appeared on Medscape.com.
With the approval of anti-amyloid monoclonal antibodies to treat early-stage Alzheimer’s disease, the need for accurate and early diagnosis is crucial.
Recently, an expert workgroup convened by the Global CEO Initiative on Alzheimer’s Disease published recommendations for the clinical implementation of Alzheimer’s disease blood-based biomarkers.
“Our hope was to provide some recommendations that clinicians could use to develop the best pathways for their clinical practice,” said workgroup co-chair Michelle M. Mielke, PhD, with Wake Forest University School of Medicine, Winston-Salem, North Carolina.
Triage and Confirmatory Pathways
The group recommends two implementation pathways for Alzheimer’s disease blood biomarkers — one for current use for triaging and another for future use to confirm amyloid pathology once blood biomarker tests have reached sufficient performance for this purpose.
In the triage pathway, a negative blood biomarker test would flag individuals unlikely to have detectable brain amyloid pathology. This outcome would prompt clinicians to focus on evaluating non–Alzheimer’s disease-related causes of cognitive impairment, which may streamline the diagnosis of other causes of cognitive impairment, the authors said.
A positive triage blood test would suggest a higher likelihood of amyloid pathology and prompt referral to secondary care for further assessment and consideration for a second, more accurate test, such as amyloid PET or CSF for amyloid confirmation.
In the confirmatory pathway, a positive blood biomarker test result would identify amyloid pathology without the need for a second test, providing a faster route to diagnosis, the authors noted.
Mielke emphasized that these recommendations represent a “first step” and will need to be updated as experiences with the Alzheimer’s disease blood biomarkers in clinical care increase and additional barriers and facilitators are identified.
“These updates will likely include community-informed approaches that incorporate feedback from patients as well as healthcare providers, alongside results from validation in diverse real-world settings,” said workgroup co-chair Chi Udeh-Momoh, PhD, MSc, with Wake Forest University School of Medicine and the Brain and Mind Institute, Aga Khan University, Nairobi, Kenya.
The Alzheimer’s Association published “appropriate use” recommendations for blood biomarkers in 2022.
“Currently, the Alzheimer’s Association is building an updated library of clinical guidance that distills the scientific evidence using de novo systematic reviews and translates them into clear and actionable recommendations for clinical practice,” said Rebecca M. Edelmayer, PhD, vice president of scientific engagement, Alzheimer’s Association.
“The first major effort with our new process will be the upcoming Evidence-based Clinical Practice Guideline on the Use of Blood-based Biomarkers (BBMs) in Specialty Care Settings. This guideline’s recommendations will be published in early 2025,” Edelmayer said.
Availability and Accuracy
Research has shown that amyloid beta and tau protein blood biomarkers — especially a high plasma phosphorylated (p)–tau217 levels — are highly accurate in identifying Alzheimer’s disease in patients with cognitive symptoms attending primary and secondary care clinics.
Several tests targeting plasma p-tau217 are now available for use. They include the PrecivityAD2 blood test from C2N Diagnostics and the Simoa p-Tau 217 Planar Kit and LucentAD p-Tau 217 — both from Quanterix.
In a recent head-to-head comparison of seven leading blood tests for AD pathology, measures of plasma p-tau217, either individually or in combination with other plasma biomarkers, had the strongest relationships with Alzheimer’s disease outcomes.
A recent Swedish study showed that the PrecivityAD2 test had an accuracy of 91% for correctly classifying clinical, biomarker-verified Alzheimer’s disease.
“We’ve been using these blood biomarkers in research for a long time and we’re now taking the jump to start using them in clinic to risk stratify patients,” said Fanny Elahi, MD, PhD, director of fluid biomarker research for the Barbara and Maurice Deane Center for Wellness and Cognitive Health at Icahn Mount Sinai in New York City.
New York’s Mount Sinai Health System is among the first in the northeast to offer blood tests across primary and specialty care settings for early diagnosis of AD and related dementias.
Edelmayer cautioned, “There is no single, stand-alone test to diagnose Alzheimer’s disease today. Blood testing is one piece of the diagnostic process.”
“Currently, physicians use well-established diagnostic tools combined with medical history and other information, including neurological exams, cognitive and functional assessments as well as brain imaging and spinal fluid analysis and blood to make an accurate diagnosis and to understand which patients are eligible for approved treatments,” she said.
There are also emerging biomarkers in the research pipeline, Edelmayer said.
“For example, some researchers think retinal imaging has the potential to detect biological signs of Alzheimer’s disease within certain areas of the eye,” she explained.
“Other emerging biomarkers include examining components in saliva and the skin for signals that may indicate early biological changes in the brain. These biomarkers are still very exploratory, and more research is needed before these tests or biomarkers can be used more routinely to study risk or aid in diagnosis,” Edelmayer said.
Ideal Candidates for Alzheimer’s Disease Blood Testing?
Experts agree that blood tests represent a convenient and scalable option to address the anticipated surge in demand for biomarker testing with the availability of disease-modifying treatments. For now, however, they are not for all older adults worried about their memory.
“Current practice should focus on using these blood biomarkers in individuals with cognitive impairment rather than in those with normal cognition or subjective cognitive decline until further research demonstrates effective interventions for individuals considered cognitively normal with elevated levels of amyloid,” the authors of a recent JAMA editorial noted.
At Mount Sinai, “we’re not starting with stone-cold asymptomatic individuals. But ultimately, this is what the blood tests are intended for — screening,” Elahi noted.
She also noted that Mount Sinai has a “very diverse population” — some with young onset cognitive symptoms, so the entry criteria for testing are “very wide.”
“Anyone above age 40 with symptoms can qualify to get a blood test. We do ask at this stage that either the individual report symptoms or someone in their life or their clinician be worried about their cognition or their brain function,” Elahi said.
Ethical Considerations, Counseling
Elahi emphasized the importance of counseling patients who come to the clinic seeking an Alzheimer’s disease blood test. This should include how the diagnostic process will unfold and what the next steps are with a given result.
Elahi said patients need to be informed that Alzheimer’s disease blood biomarkers are still “relatively new,” and a test can help a patient “know the likelihood of having the disease, but it won’t be 100% definitive.”
To ensure the ethical principle of “do no harm,” counseling should ensure that patients are fully prepared for the implications of the test results and ensure that the decision to test aligns with the patient’s readiness and well-being, Elahi said.
Edelmayer said the forthcoming clinical practice guidelines will provide “evidence-based recommendations for physicians to help guide them through the decision-making process around who should be tested and when. In the meantime, the Alzheimer’s Association urges providers to refer to the 2022 appropriate use recommendations for blood tests in clinical practice and trial settings.”
Mielke has served on scientific advisory boards and/or having consulted for Acadia, Biogen, Eisai, LabCorp, Lilly, Merck, PeerView Institute, Roche, Siemens Healthineers, and Sunbird Bio. Edelmayer and Elahi had no relevant disclosures.
A version of this article appeared on Medscape.com.
With the approval of anti-amyloid monoclonal antibodies to treat early-stage Alzheimer’s disease, the need for accurate and early diagnosis is crucial.
Recently, an expert workgroup convened by the Global CEO Initiative on Alzheimer’s Disease published recommendations for the clinical implementation of Alzheimer’s disease blood-based biomarkers.
“Our hope was to provide some recommendations that clinicians could use to develop the best pathways for their clinical practice,” said workgroup co-chair Michelle M. Mielke, PhD, with Wake Forest University School of Medicine, Winston-Salem, North Carolina.
Triage and Confirmatory Pathways
The group recommends two implementation pathways for Alzheimer’s disease blood biomarkers — one for current use for triaging and another for future use to confirm amyloid pathology once blood biomarker tests have reached sufficient performance for this purpose.
In the triage pathway, a negative blood biomarker test would flag individuals unlikely to have detectable brain amyloid pathology. This outcome would prompt clinicians to focus on evaluating non–Alzheimer’s disease-related causes of cognitive impairment, which may streamline the diagnosis of other causes of cognitive impairment, the authors said.
A positive triage blood test would suggest a higher likelihood of amyloid pathology and prompt referral to secondary care for further assessment and consideration for a second, more accurate test, such as amyloid PET or CSF for amyloid confirmation.
In the confirmatory pathway, a positive blood biomarker test result would identify amyloid pathology without the need for a second test, providing a faster route to diagnosis, the authors noted.
Mielke emphasized that these recommendations represent a “first step” and will need to be updated as experiences with the Alzheimer’s disease blood biomarkers in clinical care increase and additional barriers and facilitators are identified.
“These updates will likely include community-informed approaches that incorporate feedback from patients as well as healthcare providers, alongside results from validation in diverse real-world settings,” said workgroup co-chair Chi Udeh-Momoh, PhD, MSc, with Wake Forest University School of Medicine and the Brain and Mind Institute, Aga Khan University, Nairobi, Kenya.
The Alzheimer’s Association published “appropriate use” recommendations for blood biomarkers in 2022.
“Currently, the Alzheimer’s Association is building an updated library of clinical guidance that distills the scientific evidence using de novo systematic reviews and translates them into clear and actionable recommendations for clinical practice,” said Rebecca M. Edelmayer, PhD, vice president of scientific engagement, Alzheimer’s Association.
“The first major effort with our new process will be the upcoming Evidence-based Clinical Practice Guideline on the Use of Blood-based Biomarkers (BBMs) in Specialty Care Settings. This guideline’s recommendations will be published in early 2025,” Edelmayer said.
Availability and Accuracy
Research has shown that amyloid beta and tau protein blood biomarkers — especially a high plasma phosphorylated (p)–tau217 levels — are highly accurate in identifying Alzheimer’s disease in patients with cognitive symptoms attending primary and secondary care clinics.
Several tests targeting plasma p-tau217 are now available for use. They include the PrecivityAD2 blood test from C2N Diagnostics and the Simoa p-Tau 217 Planar Kit and LucentAD p-Tau 217 — both from Quanterix.
In a recent head-to-head comparison of seven leading blood tests for AD pathology, measures of plasma p-tau217, either individually or in combination with other plasma biomarkers, had the strongest relationships with Alzheimer’s disease outcomes.
A recent Swedish study showed that the PrecivityAD2 test had an accuracy of 91% for correctly classifying clinical, biomarker-verified Alzheimer’s disease.
“We’ve been using these blood biomarkers in research for a long time and we’re now taking the jump to start using them in clinic to risk stratify patients,” said Fanny Elahi, MD, PhD, director of fluid biomarker research for the Barbara and Maurice Deane Center for Wellness and Cognitive Health at Icahn Mount Sinai in New York City.
New York’s Mount Sinai Health System is among the first in the northeast to offer blood tests across primary and specialty care settings for early diagnosis of AD and related dementias.
Edelmayer cautioned, “There is no single, stand-alone test to diagnose Alzheimer’s disease today. Blood testing is one piece of the diagnostic process.”
“Currently, physicians use well-established diagnostic tools combined with medical history and other information, including neurological exams, cognitive and functional assessments as well as brain imaging and spinal fluid analysis and blood to make an accurate diagnosis and to understand which patients are eligible for approved treatments,” she said.
There are also emerging biomarkers in the research pipeline, Edelmayer said.
“For example, some researchers think retinal imaging has the potential to detect biological signs of Alzheimer’s disease within certain areas of the eye,” she explained.
“Other emerging biomarkers include examining components in saliva and the skin for signals that may indicate early biological changes in the brain. These biomarkers are still very exploratory, and more research is needed before these tests or biomarkers can be used more routinely to study risk or aid in diagnosis,” Edelmayer said.
Ideal Candidates for Alzheimer’s Disease Blood Testing?
Experts agree that blood tests represent a convenient and scalable option to address the anticipated surge in demand for biomarker testing with the availability of disease-modifying treatments. For now, however, they are not for all older adults worried about their memory.
“Current practice should focus on using these blood biomarkers in individuals with cognitive impairment rather than in those with normal cognition or subjective cognitive decline until further research demonstrates effective interventions for individuals considered cognitively normal with elevated levels of amyloid,” the authors of a recent JAMA editorial noted.
At Mount Sinai, “we’re not starting with stone-cold asymptomatic individuals. But ultimately, this is what the blood tests are intended for — screening,” Elahi noted.
She also noted that Mount Sinai has a “very diverse population” — some with young onset cognitive symptoms, so the entry criteria for testing are “very wide.”
“Anyone above age 40 with symptoms can qualify to get a blood test. We do ask at this stage that either the individual report symptoms or someone in their life or their clinician be worried about their cognition or their brain function,” Elahi said.
Ethical Considerations, Counseling
Elahi emphasized the importance of counseling patients who come to the clinic seeking an Alzheimer’s disease blood test. This should include how the diagnostic process will unfold and what the next steps are with a given result.
Elahi said patients need to be informed that Alzheimer’s disease blood biomarkers are still “relatively new,” and a test can help a patient “know the likelihood of having the disease, but it won’t be 100% definitive.”
To ensure the ethical principle of “do no harm,” counseling should ensure that patients are fully prepared for the implications of the test results and ensure that the decision to test aligns with the patient’s readiness and well-being, Elahi said.
Edelmayer said the forthcoming clinical practice guidelines will provide “evidence-based recommendations for physicians to help guide them through the decision-making process around who should be tested and when. In the meantime, the Alzheimer’s Association urges providers to refer to the 2022 appropriate use recommendations for blood tests in clinical practice and trial settings.”
Mielke has served on scientific advisory boards and/or having consulted for Acadia, Biogen, Eisai, LabCorp, Lilly, Merck, PeerView Institute, Roche, Siemens Healthineers, and Sunbird Bio. Edelmayer and Elahi had no relevant disclosures.
A version of this article appeared on Medscape.com.
AHA Scientific Statement Links Three Common Cardiovascular Diseases to Cognitive Decline, Dementia
The statement includes an extensive research review and offers compelling evidence of the inextricable link between heart health and brain health, which investigators said underscores the benefit of early intervention.
The cumulative evidence “confirms that the trajectories of cardiac health and brain health are inextricably intertwined through modifiable and nonmodifiable factors,” the authors wrote.
Investigators say the findings reinforce the message that addressing cardiovascular health early in life may deter the onset or progression of cognitive impairment later on.
And the earlier this is done, the better, said lead author Fernando D. Testai, MD, PhD, a professor of neurology and the vascular neurology section head, Department of Neurology and Rehabilitation, University of Illinois, Chicago.
The statement was published online in Stroke.
Bridging the Research Gap
It’s well known that there’s a bidirectional relationship between heart and brain function. For example, heart failure can lead to decreased blood flow that can damage the brain, and stroke in some areas of the brain can affect the heart.
However, that’s only part of the puzzle and doesn’t address all the gaps in the understanding of how cardiovascular disease contributes to cognition, said Testai.
“What we’re trying to do here is to go one step further and describe other connections between the heart and the brain,” he said.
Investigators carried out an extensive PubMed search for heart failure, atrial fibrillation, and coronary heart disease. Researchers detailed the frequency of each condition, mechanisms by which they might cause cognitive impairment, and prospects for prevention and treatment to maintain brain health.
A recurring theme in the paper is the role of inflammation. Evidence shows there are “remarkable similarities in the inflammatory response that takes place,” with both cardiac disease and cognitive decline, said Testai.
Another potential shared mechanism relates to biomarkers, particularly amyloid, which is strongly linked to Alzheimer’s disease.
“But some studies show amyloid can also be present in the heart, especially in patients who have decreased ejection fraction,” said Testai.
Robust Heart-Brain Connection
The statement’s authors collected a substantial amount of evidence showing vascular risk factors such as hypertension and diabetes “can change how the brain processes and clears up amyloid,” Testai added.
The paper also provides a compilation of evidence of shared genetic predispositions when it comes to heart and brain disorders.
“We noticed that some genetic signatures that have historically been associated with heart disease seem to also correlate with structural changes in the brain. That means that at the end of the day, some patients may be born with a genetic predisposition to developing both conditions,” said Testai.
This indicates that the link between the two organs “begins as early as conception” and underscores the importance of adopting healthy lifestyle habits as early as possible, he added.
“That means you can avoid bad habits that eventually lead to hypertension, diabetes, and cholesterol, that eventually will lead to cardiac disease, which eventually will lead to stroke, which eventually will lead to cognitive decline,” Testai noted.
However, cardiovascular health is more complicated than having good genes and adhering to a healthy lifestyle. It’s not clear, for example, why some people who should be predisposed to developing heart disease do not develop it, something Testai refers to as enhanced “resilience.”
For example, Hispanic or Latino patients, who have relatively poor cardiovascular risk factor profiles, seem to be less susceptible to developing cardiac disease.
More Research Needed
While genetics may partly explain the paradox, Testai believes other protective factors are at play, including strong social support networks.
Testai referred to the AHA’s “Life’s Essential 8” — the eight components of cardiovascular health. These include a healthy diet, participation in physical activity, nicotine avoidance, healthy sleep, healthy weight, and healthy levels of blood lipids, blood glucose, and blood pressure.
More evidence is needed to show that effective management of cardiac disease positively affects cognition. Currently, cognitive measures are rarely included in studies examining various heart disease treatments, said Testai.
“There should probably be an effort to include brain health outcomes in some of the cardiac literature to make sure we can also measure whether the intervention in the heart leads to an advantage for the brain,” he said.
More research is also needed to determine whether immunomodulation has a beneficial effect on the cognitive trajectory, the statement’s authors noted.
They point out that the interpretation and generalizability of the studies described in the statement are confounded by disparate methodologies, including small sample sizes, cross-sectional designs, and underrepresentation of Black and Hispanic individuals.
‘An Important Step’
Reached for a comment, Natalia S. Rost, MD, Chief of the Stroke Division at Massachusetts General Hospital and professor of neurology at Harvard Medical School, both in Boston, said this paper “is an important step” in terms of pulling together pertinent information on the topic of heart-brain health.
She praised the authors for gathering evidence on risk factors related to atrial fibrillation, heart failure, and coronary heart disease, which is “the part of the puzzle that is controllable.”
This helps reinforce the message that controlling vascular risk factors helps with brain health, said Rost.
But brain health is “much more complex than just vascular health,” she said. It includes other elements such as freedom from epilepsy, migraine, traumatic brain injury, and adult learning disabilities.
No relevant conflicts of interest were disclosed.
A version of this article first appeared on Medscape.com.
The statement includes an extensive research review and offers compelling evidence of the inextricable link between heart health and brain health, which investigators said underscores the benefit of early intervention.
The cumulative evidence “confirms that the trajectories of cardiac health and brain health are inextricably intertwined through modifiable and nonmodifiable factors,” the authors wrote.
Investigators say the findings reinforce the message that addressing cardiovascular health early in life may deter the onset or progression of cognitive impairment later on.
And the earlier this is done, the better, said lead author Fernando D. Testai, MD, PhD, a professor of neurology and the vascular neurology section head, Department of Neurology and Rehabilitation, University of Illinois, Chicago.
The statement was published online in Stroke.
Bridging the Research Gap
It’s well known that there’s a bidirectional relationship between heart and brain function. For example, heart failure can lead to decreased blood flow that can damage the brain, and stroke in some areas of the brain can affect the heart.
However, that’s only part of the puzzle and doesn’t address all the gaps in the understanding of how cardiovascular disease contributes to cognition, said Testai.
“What we’re trying to do here is to go one step further and describe other connections between the heart and the brain,” he said.
Investigators carried out an extensive PubMed search for heart failure, atrial fibrillation, and coronary heart disease. Researchers detailed the frequency of each condition, mechanisms by which they might cause cognitive impairment, and prospects for prevention and treatment to maintain brain health.
A recurring theme in the paper is the role of inflammation. Evidence shows there are “remarkable similarities in the inflammatory response that takes place,” with both cardiac disease and cognitive decline, said Testai.
Another potential shared mechanism relates to biomarkers, particularly amyloid, which is strongly linked to Alzheimer’s disease.
“But some studies show amyloid can also be present in the heart, especially in patients who have decreased ejection fraction,” said Testai.
Robust Heart-Brain Connection
The statement’s authors collected a substantial amount of evidence showing vascular risk factors such as hypertension and diabetes “can change how the brain processes and clears up amyloid,” Testai added.
The paper also provides a compilation of evidence of shared genetic predispositions when it comes to heart and brain disorders.
“We noticed that some genetic signatures that have historically been associated with heart disease seem to also correlate with structural changes in the brain. That means that at the end of the day, some patients may be born with a genetic predisposition to developing both conditions,” said Testai.
This indicates that the link between the two organs “begins as early as conception” and underscores the importance of adopting healthy lifestyle habits as early as possible, he added.
“That means you can avoid bad habits that eventually lead to hypertension, diabetes, and cholesterol, that eventually will lead to cardiac disease, which eventually will lead to stroke, which eventually will lead to cognitive decline,” Testai noted.
However, cardiovascular health is more complicated than having good genes and adhering to a healthy lifestyle. It’s not clear, for example, why some people who should be predisposed to developing heart disease do not develop it, something Testai refers to as enhanced “resilience.”
For example, Hispanic or Latino patients, who have relatively poor cardiovascular risk factor profiles, seem to be less susceptible to developing cardiac disease.
More Research Needed
While genetics may partly explain the paradox, Testai believes other protective factors are at play, including strong social support networks.
Testai referred to the AHA’s “Life’s Essential 8” — the eight components of cardiovascular health. These include a healthy diet, participation in physical activity, nicotine avoidance, healthy sleep, healthy weight, and healthy levels of blood lipids, blood glucose, and blood pressure.
More evidence is needed to show that effective management of cardiac disease positively affects cognition. Currently, cognitive measures are rarely included in studies examining various heart disease treatments, said Testai.
“There should probably be an effort to include brain health outcomes in some of the cardiac literature to make sure we can also measure whether the intervention in the heart leads to an advantage for the brain,” he said.
More research is also needed to determine whether immunomodulation has a beneficial effect on the cognitive trajectory, the statement’s authors noted.
They point out that the interpretation and generalizability of the studies described in the statement are confounded by disparate methodologies, including small sample sizes, cross-sectional designs, and underrepresentation of Black and Hispanic individuals.
‘An Important Step’
Reached for a comment, Natalia S. Rost, MD, Chief of the Stroke Division at Massachusetts General Hospital and professor of neurology at Harvard Medical School, both in Boston, said this paper “is an important step” in terms of pulling together pertinent information on the topic of heart-brain health.
She praised the authors for gathering evidence on risk factors related to atrial fibrillation, heart failure, and coronary heart disease, which is “the part of the puzzle that is controllable.”
This helps reinforce the message that controlling vascular risk factors helps with brain health, said Rost.
But brain health is “much more complex than just vascular health,” she said. It includes other elements such as freedom from epilepsy, migraine, traumatic brain injury, and adult learning disabilities.
No relevant conflicts of interest were disclosed.
A version of this article first appeared on Medscape.com.
The statement includes an extensive research review and offers compelling evidence of the inextricable link between heart health and brain health, which investigators said underscores the benefit of early intervention.
The cumulative evidence “confirms that the trajectories of cardiac health and brain health are inextricably intertwined through modifiable and nonmodifiable factors,” the authors wrote.
Investigators say the findings reinforce the message that addressing cardiovascular health early in life may deter the onset or progression of cognitive impairment later on.
And the earlier this is done, the better, said lead author Fernando D. Testai, MD, PhD, a professor of neurology and the vascular neurology section head, Department of Neurology and Rehabilitation, University of Illinois, Chicago.
The statement was published online in Stroke.
Bridging the Research Gap
It’s well known that there’s a bidirectional relationship between heart and brain function. For example, heart failure can lead to decreased blood flow that can damage the brain, and stroke in some areas of the brain can affect the heart.
However, that’s only part of the puzzle and doesn’t address all the gaps in the understanding of how cardiovascular disease contributes to cognition, said Testai.
“What we’re trying to do here is to go one step further and describe other connections between the heart and the brain,” he said.
Investigators carried out an extensive PubMed search for heart failure, atrial fibrillation, and coronary heart disease. Researchers detailed the frequency of each condition, mechanisms by which they might cause cognitive impairment, and prospects for prevention and treatment to maintain brain health.
A recurring theme in the paper is the role of inflammation. Evidence shows there are “remarkable similarities in the inflammatory response that takes place,” with both cardiac disease and cognitive decline, said Testai.
Another potential shared mechanism relates to biomarkers, particularly amyloid, which is strongly linked to Alzheimer’s disease.
“But some studies show amyloid can also be present in the heart, especially in patients who have decreased ejection fraction,” said Testai.
Robust Heart-Brain Connection
The statement’s authors collected a substantial amount of evidence showing vascular risk factors such as hypertension and diabetes “can change how the brain processes and clears up amyloid,” Testai added.
The paper also provides a compilation of evidence of shared genetic predispositions when it comes to heart and brain disorders.
“We noticed that some genetic signatures that have historically been associated with heart disease seem to also correlate with structural changes in the brain. That means that at the end of the day, some patients may be born with a genetic predisposition to developing both conditions,” said Testai.
This indicates that the link between the two organs “begins as early as conception” and underscores the importance of adopting healthy lifestyle habits as early as possible, he added.
“That means you can avoid bad habits that eventually lead to hypertension, diabetes, and cholesterol, that eventually will lead to cardiac disease, which eventually will lead to stroke, which eventually will lead to cognitive decline,” Testai noted.
However, cardiovascular health is more complicated than having good genes and adhering to a healthy lifestyle. It’s not clear, for example, why some people who should be predisposed to developing heart disease do not develop it, something Testai refers to as enhanced “resilience.”
For example, Hispanic or Latino patients, who have relatively poor cardiovascular risk factor profiles, seem to be less susceptible to developing cardiac disease.
More Research Needed
While genetics may partly explain the paradox, Testai believes other protective factors are at play, including strong social support networks.
Testai referred to the AHA’s “Life’s Essential 8” — the eight components of cardiovascular health. These include a healthy diet, participation in physical activity, nicotine avoidance, healthy sleep, healthy weight, and healthy levels of blood lipids, blood glucose, and blood pressure.
More evidence is needed to show that effective management of cardiac disease positively affects cognition. Currently, cognitive measures are rarely included in studies examining various heart disease treatments, said Testai.
“There should probably be an effort to include brain health outcomes in some of the cardiac literature to make sure we can also measure whether the intervention in the heart leads to an advantage for the brain,” he said.
More research is also needed to determine whether immunomodulation has a beneficial effect on the cognitive trajectory, the statement’s authors noted.
They point out that the interpretation and generalizability of the studies described in the statement are confounded by disparate methodologies, including small sample sizes, cross-sectional designs, and underrepresentation of Black and Hispanic individuals.
‘An Important Step’
Reached for a comment, Natalia S. Rost, MD, Chief of the Stroke Division at Massachusetts General Hospital and professor of neurology at Harvard Medical School, both in Boston, said this paper “is an important step” in terms of pulling together pertinent information on the topic of heart-brain health.
She praised the authors for gathering evidence on risk factors related to atrial fibrillation, heart failure, and coronary heart disease, which is “the part of the puzzle that is controllable.”
This helps reinforce the message that controlling vascular risk factors helps with brain health, said Rost.
But brain health is “much more complex than just vascular health,” she said. It includes other elements such as freedom from epilepsy, migraine, traumatic brain injury, and adult learning disabilities.
No relevant conflicts of interest were disclosed.
A version of this article first appeared on Medscape.com.
FROM STROKE