Alzheimer's & Cognition

TOPLINE:

Adults diagnosed with coronary heart disease (CHD) are at an increased risk for dementia, including all-cause dementia, Alzheimer›s disease (AD), and vascular dementia (VD), with the risk highest — at 36% — if onset is before age 45, results of a large observational study show.

METHODOLOGY:

• The study included 432,667 of the more than 500,000 participants in the UK Biobank, with a mean age of 56.9 years, 50,685 (11.7%) of whom had CHD and 50,445 had data on age at CHD onset.
• Researchers divided participants into three groups according to age at CHD onset (below 45 years, 45-59 years, and 60 years and older), and carried out a propensity score matching analysis.
• Outcomes included all-cause dementia, AD, and VD.
• Covariates included age, sex, race, educational level, body mass index, low-density lipoprotein cholesterol, smoking status, alcohol intake, exercise, depressed mood, hypertension, diabetes, statin use, and apolipoprotein E4 status.

TAKEAWAY:

• During a median follow-up of 12.8 years, researchers identified 5876 cases of all-cause dementia, 2540 cases of AD, and 1220 cases of VD.
• Fully adjusted models showed participants with CHD had significantly higher risks than those without CHD of developing all-cause dementia (hazard ratio [HR], 1.36; 95% CI, 1.28-1.45; P < .001), AD (HR, 1.13; 95% CI, 1.02-1.24; P = .019), and VD (HR, 1.78; 95% CI, 1.56-2.02; P < .001). The higher risk for VD suggests CHD has a more profound influence on neuropathologic changes involved in this dementia type, said the authors.
• Those with CHD diagnosed at a younger age had higher risks of developing dementia (HR per 10-year decrease in age, 1.25; 95% CI, 1.20-1.30 for all-cause dementia, 1.29; 95% CI, 1.20-1.38 for AD, and 1.22; 95% CI, 1.13-1.31 for VD; P for all < .001).
• Propensity score matching analysis showed patients with CHD had significantly higher risks for dementia compared with matched controls, with the highest risk seen in patients diagnosed before age 45 (HR, 2.40; 95% CI, 1.79-3.20; P < .001), followed by those diagnosed between 45 and 59 years (HR, 1.46; 95% CI, 1.32-1.62; P < .001) and at or above 60 years (HR, 1.11; 95% CI, 1.03-1.19; P = .005), with similar results for AD and VD.

IN PRACTICE:

The findings suggest “additional attention should be paid to the cognitive status of patients with CHD, especially the ones diagnosed with CHD at a young age,” the authors conclude, noting that “timely intervention, such as cognitive training, could be implemented once signs of cognitive deteriorations are detected.”

SOURCE:

The study was conducted by Jie Liang, BS, School of Nursing, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, and colleagues. It was published online on November 29, 2023, in the Journal of the American Heart Association.

LIMITATIONS:

As this is an observational study, it can’t conclude a causal relationship. Although the authors adjusted for many potential confounders, unknown risk factors that also contribute to CHD can’t be ruled out. As the study excluded 69,744 participants, selection bias is possible. The study included a mostly White population.

DISCLOSURES:

The study was supported by the National Natural Science Foundation of China, the Non-Profit Central Research Institute Fund of the Chinese Academy of Medical Sciences, and the China Medical Board. The authors have no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

TOPLINE:

Adults diagnosed with coronary heart disease (CHD) are at an increased risk for dementia, including all-cause dementia, Alzheimer›s disease (AD), and vascular dementia (VD), with the risk highest — at 36% — if onset is before age 45, results of a large observational study show.

METHODOLOGY:

• The study included 432,667 of the more than 500,000 participants in the UK Biobank, with a mean age of 56.9 years, 50,685 (11.7%) of whom had CHD and 50,445 had data on age at CHD onset.
• Researchers divided participants into three groups according to age at CHD onset (below 45 years, 45-59 years, and 60 years and older), and carried out a propensity score matching analysis.
• Outcomes included all-cause dementia, AD, and VD.
• Covariates included age, sex, race, educational level, body mass index, low-density lipoprotein cholesterol, smoking status, alcohol intake, exercise, depressed mood, hypertension, diabetes, statin use, and apolipoprotein E4 status.

TAKEAWAY:

• During a median follow-up of 12.8 years, researchers identified 5876 cases of all-cause dementia, 2540 cases of AD, and 1220 cases of VD.
• Fully adjusted models showed participants with CHD had significantly higher risks than those without CHD of developing all-cause dementia (hazard ratio [HR], 1.36; 95% CI, 1.28-1.45; P < .001), AD (HR, 1.13; 95% CI, 1.02-1.24; P = .019), and VD (HR, 1.78; 95% CI, 1.56-2.02; P < .001). The higher risk for VD suggests CHD has a more profound influence on neuropathologic changes involved in this dementia type, said the authors.
• Those with CHD diagnosed at a younger age had higher risks of developing dementia (HR per 10-year decrease in age, 1.25; 95% CI, 1.20-1.30 for all-cause dementia, 1.29; 95% CI, 1.20-1.38 for AD, and 1.22; 95% CI, 1.13-1.31 for VD; P for all < .001).
• Propensity score matching analysis showed patients with CHD had significantly higher risks for dementia compared with matched controls, with the highest risk seen in patients diagnosed before age 45 (HR, 2.40; 95% CI, 1.79-3.20; P < .001), followed by those diagnosed between 45 and 59 years (HR, 1.46; 95% CI, 1.32-1.62; P < .001) and at or above 60 years (HR, 1.11; 95% CI, 1.03-1.19; P = .005), with similar results for AD and VD.

IN PRACTICE:

The findings suggest “additional attention should be paid to the cognitive status of patients with CHD, especially the ones diagnosed with CHD at a young age,” the authors conclude, noting that “timely intervention, such as cognitive training, could be implemented once signs of cognitive deteriorations are detected.”

SOURCE:

The study was conducted by Jie Liang, BS, School of Nursing, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, and colleagues. It was published online on November 29, 2023, in the Journal of the American Heart Association.

LIMITATIONS:

As this is an observational study, it can’t conclude a causal relationship. Although the authors adjusted for many potential confounders, unknown risk factors that also contribute to CHD can’t be ruled out. As the study excluded 69,744 participants, selection bias is possible. The study included a mostly White population.

DISCLOSURES:

The study was supported by the National Natural Science Foundation of China, the Non-Profit Central Research Institute Fund of the Chinese Academy of Medical Sciences, and the China Medical Board. The authors have no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

TOPLINE:

Adults diagnosed with coronary heart disease (CHD) are at an increased risk for dementia, including all-cause dementia, Alzheimer›s disease (AD), and vascular dementia (VD), with the risk highest — at 36% — if onset is before age 45, results of a large observational study show.

METHODOLOGY:

• The study included 432,667 of the more than 500,000 participants in the UK Biobank, with a mean age of 56.9 years, 50,685 (11.7%) of whom had CHD and 50,445 had data on age at CHD onset.
• Researchers divided participants into three groups according to age at CHD onset (below 45 years, 45-59 years, and 60 years and older), and carried out a propensity score matching analysis.
• Outcomes included all-cause dementia, AD, and VD.
• Covariates included age, sex, race, educational level, body mass index, low-density lipoprotein cholesterol, smoking status, alcohol intake, exercise, depressed mood, hypertension, diabetes, statin use, and apolipoprotein E4 status.

TAKEAWAY:

• During a median follow-up of 12.8 years, researchers identified 5876 cases of all-cause dementia, 2540 cases of AD, and 1220 cases of VD.
• Fully adjusted models showed participants with CHD had significantly higher risks than those without CHD of developing all-cause dementia (hazard ratio [HR], 1.36; 95% CI, 1.28-1.45; P < .001), AD (HR, 1.13; 95% CI, 1.02-1.24; P = .019), and VD (HR, 1.78; 95% CI, 1.56-2.02; P < .001). The higher risk for VD suggests CHD has a more profound influence on neuropathologic changes involved in this dementia type, said the authors.
• Those with CHD diagnosed at a younger age had higher risks of developing dementia (HR per 10-year decrease in age, 1.25; 95% CI, 1.20-1.30 for all-cause dementia, 1.29; 95% CI, 1.20-1.38 for AD, and 1.22; 95% CI, 1.13-1.31 for VD; P for all < .001).
• Propensity score matching analysis showed patients with CHD had significantly higher risks for dementia compared with matched controls, with the highest risk seen in patients diagnosed before age 45 (HR, 2.40; 95% CI, 1.79-3.20; P < .001), followed by those diagnosed between 45 and 59 years (HR, 1.46; 95% CI, 1.32-1.62; P < .001) and at or above 60 years (HR, 1.11; 95% CI, 1.03-1.19; P = .005), with similar results for AD and VD.

IN PRACTICE:

The findings suggest “additional attention should be paid to the cognitive status of patients with CHD, especially the ones diagnosed with CHD at a young age,” the authors conclude, noting that “timely intervention, such as cognitive training, could be implemented once signs of cognitive deteriorations are detected.”

SOURCE:

The study was conducted by Jie Liang, BS, School of Nursing, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, and colleagues. It was published online on November 29, 2023, in the Journal of the American Heart Association.

LIMITATIONS:

As this is an observational study, it can’t conclude a causal relationship. Although the authors adjusted for many potential confounders, unknown risk factors that also contribute to CHD can’t be ruled out. As the study excluded 69,744 participants, selection bias is possible. The study included a mostly White population.

DISCLOSURES:

The study was supported by the National Natural Science Foundation of China, the Non-Profit Central Research Institute Fund of the Chinese Academy of Medical Sciences, and the China Medical Board. The authors have no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

TOPLINE: 

Excessive television-watching is tied to an increased risk for dementia, Parkinson’s disease (PD), and depression, whereas a limited amount of daily computer use that is not work-related is linked to a lower risk for dementia.

METHODOLOGY:

• Investigators analyzed data on 473,184 people aged 39-72 years from the UK Biobank who were enrolled from 2006 to 2010 and followed until a diagnosis of dementia, PD, depression, death, or study end (2018 for Wales residents; 2021 for residents of England and Scotland).
• Participants reported on the number of hours they spent outside of work exercising, watching television, and using the computer.
• MRI was conducted to determine participants’ brain volume.

TAKEAWAY: 

• During the study, 6096 people developed dementia, 3000 developed PD, 23,600 developed depression, 1200 developed dementia and depression, and 486 developed PD and depression.
• Compared with those who watched TV for under 1 hour per day, those who reported watching 4 or more hours per day had a 28% higher risk for dementia (adjusted hazard ratio [aHR], 1.28; 95% CI, 1.17-1.39), a 35% higher risk for depression, (aHR, 1.35; 95% CI, 1.29-1.40) and a 16% greater risk for PD (aHR, 1.16; 95% CI, 1.03-1.29).
• However, moderate computer use outside of work seemed somewhat protective. Participants who used the computer for 30-60 minutes per day had lower risks for dementia (aHR, 0.68; 95% CI, 0.64-0.72), PD, (aHR, 0.86; 95% CI, 0.79-0.93), and depression (aHR, 0.85; 95% CI, 0.83-0.88) compared with those who reported the lowest levels of computer usage.
• Replacing 30 minutes per day of computer time with an equal amount of structured exercise was associated with decreased risk for dementia (aHR, 0.74; 95% CI, 0.85-0.95) and PD (aHR, 0.84; 95% CI, 0.78-0.90).

IN PRACTICE:

The association between extended periods of TV use and higher risk for PD and dementia could be explained by a lack of activity, the authors note. They add that sedentary behavior is, “associated with biomarkers of low-grade inflammation and changes in inflammation markers that could initiate and or worsen neuroinflammation and contribute to neurodegeneration.”

SOURCE:

Hanzhang Wu, PhD, of Tianjin University of Traditional Medicine in Tianjin, China, led the study, which was published online in the International Journal of Behavioral Nutrition and Physical Activity.

LIMITATIONS: 

Screen behaviors were assessed using self-report measures, which is subject to recall bias. Also, there may have been variables confounding the findings for which investigators did not account. 

DISCLOSURES:

The study was funded by the National Natural Science Foundation of China, the Tianjin Major Public Health Science and Technology Project, the National Health Commission of China, the Food Science and Technology Foundation of Chinese Institute of Food Science and Technology, the China Cohort Consortium, and the Chinese Nutrition Society Nutrition Research Foundation–DSM Research Fund, China. There were no disclosures reported.

Eve Bender has no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE: 

Excessive television-watching is tied to an increased risk for dementia, Parkinson’s disease (PD), and depression, whereas a limited amount of daily computer use that is not work-related is linked to a lower risk for dementia.

METHODOLOGY:

• Investigators analyzed data on 473,184 people aged 39-72 years from the UK Biobank who were enrolled from 2006 to 2010 and followed until a diagnosis of dementia, PD, depression, death, or study end (2018 for Wales residents; 2021 for residents of England and Scotland).
• Participants reported on the number of hours they spent outside of work exercising, watching television, and using the computer.
• MRI was conducted to determine participants’ brain volume.

TAKEAWAY: 

• During the study, 6096 people developed dementia, 3000 developed PD, 23,600 developed depression, 1200 developed dementia and depression, and 486 developed PD and depression.
• Compared with those who watched TV for under 1 hour per day, those who reported watching 4 or more hours per day had a 28% higher risk for dementia (adjusted hazard ratio [aHR], 1.28; 95% CI, 1.17-1.39), a 35% higher risk for depression, (aHR, 1.35; 95% CI, 1.29-1.40) and a 16% greater risk for PD (aHR, 1.16; 95% CI, 1.03-1.29).
• However, moderate computer use outside of work seemed somewhat protective. Participants who used the computer for 30-60 minutes per day had lower risks for dementia (aHR, 0.68; 95% CI, 0.64-0.72), PD, (aHR, 0.86; 95% CI, 0.79-0.93), and depression (aHR, 0.85; 95% CI, 0.83-0.88) compared with those who reported the lowest levels of computer usage.
• Replacing 30 minutes per day of computer time with an equal amount of structured exercise was associated with decreased risk for dementia (aHR, 0.74; 95% CI, 0.85-0.95) and PD (aHR, 0.84; 95% CI, 0.78-0.90).

IN PRACTICE:

The association between extended periods of TV use and higher risk for PD and dementia could be explained by a lack of activity, the authors note. They add that sedentary behavior is, “associated with biomarkers of low-grade inflammation and changes in inflammation markers that could initiate and or worsen neuroinflammation and contribute to neurodegeneration.”

SOURCE:

Hanzhang Wu, PhD, of Tianjin University of Traditional Medicine in Tianjin, China, led the study, which was published online in the International Journal of Behavioral Nutrition and Physical Activity.

LIMITATIONS: 

Screen behaviors were assessed using self-report measures, which is subject to recall bias. Also, there may have been variables confounding the findings for which investigators did not account. 

DISCLOSURES:

The study was funded by the National Natural Science Foundation of China, the Tianjin Major Public Health Science and Technology Project, the National Health Commission of China, the Food Science and Technology Foundation of Chinese Institute of Food Science and Technology, the China Cohort Consortium, and the Chinese Nutrition Society Nutrition Research Foundation–DSM Research Fund, China. There were no disclosures reported.

Eve Bender has no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE: 

Excessive television-watching is tied to an increased risk for dementia, Parkinson’s disease (PD), and depression, whereas a limited amount of daily computer use that is not work-related is linked to a lower risk for dementia.

METHODOLOGY:

• Investigators analyzed data on 473,184 people aged 39-72 years from the UK Biobank who were enrolled from 2006 to 2010 and followed until a diagnosis of dementia, PD, depression, death, or study end (2018 for Wales residents; 2021 for residents of England and Scotland).
• Participants reported on the number of hours they spent outside of work exercising, watching television, and using the computer.
• MRI was conducted to determine participants’ brain volume.

TAKEAWAY: 

• During the study, 6096 people developed dementia, 3000 developed PD, 23,600 developed depression, 1200 developed dementia and depression, and 486 developed PD and depression.
• Compared with those who watched TV for under 1 hour per day, those who reported watching 4 or more hours per day had a 28% higher risk for dementia (adjusted hazard ratio [aHR], 1.28; 95% CI, 1.17-1.39), a 35% higher risk for depression, (aHR, 1.35; 95% CI, 1.29-1.40) and a 16% greater risk for PD (aHR, 1.16; 95% CI, 1.03-1.29).
• However, moderate computer use outside of work seemed somewhat protective. Participants who used the computer for 30-60 minutes per day had lower risks for dementia (aHR, 0.68; 95% CI, 0.64-0.72), PD, (aHR, 0.86; 95% CI, 0.79-0.93), and depression (aHR, 0.85; 95% CI, 0.83-0.88) compared with those who reported the lowest levels of computer usage.
• Replacing 30 minutes per day of computer time with an equal amount of structured exercise was associated with decreased risk for dementia (aHR, 0.74; 95% CI, 0.85-0.95) and PD (aHR, 0.84; 95% CI, 0.78-0.90).

IN PRACTICE:

The association between extended periods of TV use and higher risk for PD and dementia could be explained by a lack of activity, the authors note. They add that sedentary behavior is, “associated with biomarkers of low-grade inflammation and changes in inflammation markers that could initiate and or worsen neuroinflammation and contribute to neurodegeneration.”

SOURCE:

Hanzhang Wu, PhD, of Tianjin University of Traditional Medicine in Tianjin, China, led the study, which was published online in the International Journal of Behavioral Nutrition and Physical Activity.

LIMITATIONS: 

Screen behaviors were assessed using self-report measures, which is subject to recall bias. Also, there may have been variables confounding the findings for which investigators did not account. 

DISCLOSURES:

The study was funded by the National Natural Science Foundation of China, the Tianjin Major Public Health Science and Technology Project, the National Health Commission of China, the Food Science and Technology Foundation of Chinese Institute of Food Science and Technology, the China Cohort Consortium, and the Chinese Nutrition Society Nutrition Research Foundation–DSM Research Fund, China. There were no disclosures reported.

Eve Bender has no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

Food insecurity among older adults is associated with increased dementia risk, poorer memory function, and faster memory decline, new research indicates.

METHODOLOGY:

• Researchers analyzed data on 7,012 adults (mean age, 67 years; 59% women) from the U.S. Health and Retirement Study.
• Food security status was assessed in 2013 using a validated survey, with cognitive outcomes evaluated between 2014 and 2018.
• Analyses were adjusted for demographics, socioeconomics, and health factors.

TAKEAWAY:

• About 18% of adults were food insecure, with 10% reporting low food security and 8% very low food security. About 11% of those aged 65+ in 2013 were food insecure.
• The odds of dementia were 38% higher (odds ratio, 1.38; 95% confidence interval [CI], 1.15-1.67) in adults with low food security and 37% higher (OR, 1.37; 95% CI, 1.11-1.59) in those with very low food security, compared with food-secure adults.
• Translated to years of excess cognitive aging, food insecurity was associated with increased dementia risk equivalent to roughly 1.3 excess years of aging.
• Low and very low food security were also associated with lower memory levels and faster age-related memory decline.

IN PRACTICE:

“Our study contributes to a limited literature by capitalizing on a large and diverse sample, validated exposure and outcome measures, and longitudinal data to robustly evaluate these associations, providing evidence in support of the connection between food insecurity in older adulthood and subsequent brain health,” the authors wrote. “Our findings highlight the need to improve food security in older adults and that doing so may protect individuals from cognitive decline and dementia.”

SOURCE:

The study, with first author Haobing Qian, PhD, with the University of California, San Francisco, was published online  in JAMA Network Open.

LIMITATIONS:

Residual confounding cannot be ruled out. Food insecurity was not assessed prior to 2013. The researchers lacked information on clinical dementia diagnoses.

DISCLOSURES:

The study was supported by grants from the National Institutes of Health. The authors reported no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

TOPLINE:

Food insecurity among older adults is associated with increased dementia risk, poorer memory function, and faster memory decline, new research indicates.

METHODOLOGY:

• Researchers analyzed data on 7,012 adults (mean age, 67 years; 59% women) from the U.S. Health and Retirement Study.
• Food security status was assessed in 2013 using a validated survey, with cognitive outcomes evaluated between 2014 and 2018.
• Analyses were adjusted for demographics, socioeconomics, and health factors.

TAKEAWAY:

• About 18% of adults were food insecure, with 10% reporting low food security and 8% very low food security. About 11% of those aged 65+ in 2013 were food insecure.
• The odds of dementia were 38% higher (odds ratio, 1.38; 95% confidence interval [CI], 1.15-1.67) in adults with low food security and 37% higher (OR, 1.37; 95% CI, 1.11-1.59) in those with very low food security, compared with food-secure adults.
• Translated to years of excess cognitive aging, food insecurity was associated with increased dementia risk equivalent to roughly 1.3 excess years of aging.
• Low and very low food security were also associated with lower memory levels and faster age-related memory decline.

IN PRACTICE:

“Our study contributes to a limited literature by capitalizing on a large and diverse sample, validated exposure and outcome measures, and longitudinal data to robustly evaluate these associations, providing evidence in support of the connection between food insecurity in older adulthood and subsequent brain health,” the authors wrote. “Our findings highlight the need to improve food security in older adults and that doing so may protect individuals from cognitive decline and dementia.”

SOURCE:

The study, with first author Haobing Qian, PhD, with the University of California, San Francisco, was published online  in JAMA Network Open.

LIMITATIONS:

Residual confounding cannot be ruled out. Food insecurity was not assessed prior to 2013. The researchers lacked information on clinical dementia diagnoses.

DISCLOSURES:

The study was supported by grants from the National Institutes of Health. The authors reported no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

TOPLINE:

Food insecurity among older adults is associated with increased dementia risk, poorer memory function, and faster memory decline, new research indicates.

METHODOLOGY:

• Researchers analyzed data on 7,012 adults (mean age, 67 years; 59% women) from the U.S. Health and Retirement Study.
• Food security status was assessed in 2013 using a validated survey, with cognitive outcomes evaluated between 2014 and 2018.
• Analyses were adjusted for demographics, socioeconomics, and health factors.

TAKEAWAY:

• About 18% of adults were food insecure, with 10% reporting low food security and 8% very low food security. About 11% of those aged 65+ in 2013 were food insecure.
• The odds of dementia were 38% higher (odds ratio, 1.38; 95% confidence interval [CI], 1.15-1.67) in adults with low food security and 37% higher (OR, 1.37; 95% CI, 1.11-1.59) in those with very low food security, compared with food-secure adults.
• Translated to years of excess cognitive aging, food insecurity was associated with increased dementia risk equivalent to roughly 1.3 excess years of aging.
• Low and very low food security were also associated with lower memory levels and faster age-related memory decline.

IN PRACTICE:

“Our study contributes to a limited literature by capitalizing on a large and diverse sample, validated exposure and outcome measures, and longitudinal data to robustly evaluate these associations, providing evidence in support of the connection between food insecurity in older adulthood and subsequent brain health,” the authors wrote. “Our findings highlight the need to improve food security in older adults and that doing so may protect individuals from cognitive decline and dementia.”

SOURCE:

The study, with first author Haobing Qian, PhD, with the University of California, San Francisco, was published online  in JAMA Network Open.

LIMITATIONS:

Residual confounding cannot be ruled out. Food insecurity was not assessed prior to 2013. The researchers lacked information on clinical dementia diagnoses.

DISCLOSURES:

The study was supported by grants from the National Institutes of Health. The authors reported no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

TOPLINE:

Posttraumatic stress disorder (PTSD) symptoms are associated with poorer cardiovascular and neurocognitive health among midlife women, particularly those who are APOEε4 carriers, new research suggests.

METHODOLOGY:

• Researchers conducted a cross-sectional study of 274 women (mean age, 59 years) participating in the MsBrain study of menopause and brain health.
• As part of the study, the women completed the PTSD Checklist–Civilian Version and underwent physical and neuropsychological testing, as well as carotid artery ultrasonography and brain MRI.
• Outcomes of interest were associations of PTSD symptoms with carotid intima media thickness (IMT), brain white matter hyperintensity volume (WMHV), and cognition, assessed in linear regression models.
• Interactions by APOEε4 were assessed; covariates included age, race/ethnicity, education, and CVD risk factors.

TAKEAWAY:

• Higher PTSD symptoms were associated with greater carotid IMT (P = .03); associations of PTSD symptoms with neurocognitive outcomes varied significantly by APOEε4 status.
• Among APOEε4 carriers, PTSD symptoms were associated with greater whole-brain WMHV (P = .009), periventricular WMHV (P = .02), deep WMHV (P = .01), and frontal WMHV (P = .04) in multivariable models.
• APOEε4 carriers with PTSD symptoms also had poorer cognition, specifically attention and working memory (P = .02), semantic fluency (P = .01), perceptual speed (P = .002) and processing speed (P = .002), in multivariable models.

IN PRACTICE:

“This study sheds important insight on the implications of PTSD symptoms to women’s cardiovascular and neurocognitive health. Our findings indicate that the APOEε4 genotype may identify a group of women with PTSD symptoms at particular risk for poor neurocognitive health,” the authors wrote.

SOURCE:

The study, with first author Rebecca Thurston, PhD, of the department of psychiatry, University of Pittsburgh, was published online  in JAMA Network Open.

LIMITATIONS:

No diagnostic clinical interviews were conducted, and PTSD treatment was not assessed. All participants identified as cisgender, and most were non-Hispanic Black or White. The study was observational and cross-sectional, precluding assertions about directionality or causality.

DISCLOSURES:

The study was funded by the National Institutes of Health, the University of Pittsburgh Clinical and Translational Science Institute, and the University of Pittsburgh Small Molecule Biomarker Core. Dr. Thurston reported receiving personal fees from Astellas Pharma, Bayer, Hello Therapeutics, Vira Health, and Happify Health outside the submitted work.

A version of this article first appeared on Medscape.com.

TOPLINE:

Posttraumatic stress disorder (PTSD) symptoms are associated with poorer cardiovascular and neurocognitive health among midlife women, particularly those who are APOEε4 carriers, new research suggests.

METHODOLOGY:

• Researchers conducted a cross-sectional study of 274 women (mean age, 59 years) participating in the MsBrain study of menopause and brain health.
• As part of the study, the women completed the PTSD Checklist–Civilian Version and underwent physical and neuropsychological testing, as well as carotid artery ultrasonography and brain MRI.
• Outcomes of interest were associations of PTSD symptoms with carotid intima media thickness (IMT), brain white matter hyperintensity volume (WMHV), and cognition, assessed in linear regression models.
• Interactions by APOEε4 were assessed; covariates included age, race/ethnicity, education, and CVD risk factors.

TAKEAWAY:

• Higher PTSD symptoms were associated with greater carotid IMT (P = .03); associations of PTSD symptoms with neurocognitive outcomes varied significantly by APOEε4 status.
• Among APOEε4 carriers, PTSD symptoms were associated with greater whole-brain WMHV (P = .009), periventricular WMHV (P = .02), deep WMHV (P = .01), and frontal WMHV (P = .04) in multivariable models.
• APOEε4 carriers with PTSD symptoms also had poorer cognition, specifically attention and working memory (P = .02), semantic fluency (P = .01), perceptual speed (P = .002) and processing speed (P = .002), in multivariable models.

IN PRACTICE:

“This study sheds important insight on the implications of PTSD symptoms to women’s cardiovascular and neurocognitive health. Our findings indicate that the APOEε4 genotype may identify a group of women with PTSD symptoms at particular risk for poor neurocognitive health,” the authors wrote.

SOURCE:

The study, with first author Rebecca Thurston, PhD, of the department of psychiatry, University of Pittsburgh, was published online  in JAMA Network Open.

LIMITATIONS:

No diagnostic clinical interviews were conducted, and PTSD treatment was not assessed. All participants identified as cisgender, and most were non-Hispanic Black or White. The study was observational and cross-sectional, precluding assertions about directionality or causality.

DISCLOSURES:

The study was funded by the National Institutes of Health, the University of Pittsburgh Clinical and Translational Science Institute, and the University of Pittsburgh Small Molecule Biomarker Core. Dr. Thurston reported receiving personal fees from Astellas Pharma, Bayer, Hello Therapeutics, Vira Health, and Happify Health outside the submitted work.

A version of this article first appeared on Medscape.com.

TOPLINE:

Posttraumatic stress disorder (PTSD) symptoms are associated with poorer cardiovascular and neurocognitive health among midlife women, particularly those who are APOEε4 carriers, new research suggests.

METHODOLOGY:

• Researchers conducted a cross-sectional study of 274 women (mean age, 59 years) participating in the MsBrain study of menopause and brain health.
• As part of the study, the women completed the PTSD Checklist–Civilian Version and underwent physical and neuropsychological testing, as well as carotid artery ultrasonography and brain MRI.
• Outcomes of interest were associations of PTSD symptoms with carotid intima media thickness (IMT), brain white matter hyperintensity volume (WMHV), and cognition, assessed in linear regression models.
• Interactions by APOEε4 were assessed; covariates included age, race/ethnicity, education, and CVD risk factors.

TAKEAWAY:

• Higher PTSD symptoms were associated with greater carotid IMT (P = .03); associations of PTSD symptoms with neurocognitive outcomes varied significantly by APOEε4 status.
• Among APOEε4 carriers, PTSD symptoms were associated with greater whole-brain WMHV (P = .009), periventricular WMHV (P = .02), deep WMHV (P = .01), and frontal WMHV (P = .04) in multivariable models.
• APOEε4 carriers with PTSD symptoms also had poorer cognition, specifically attention and working memory (P = .02), semantic fluency (P = .01), perceptual speed (P = .002) and processing speed (P = .002), in multivariable models.

IN PRACTICE:

“This study sheds important insight on the implications of PTSD symptoms to women’s cardiovascular and neurocognitive health. Our findings indicate that the APOEε4 genotype may identify a group of women with PTSD symptoms at particular risk for poor neurocognitive health,” the authors wrote.

SOURCE:

The study, with first author Rebecca Thurston, PhD, of the department of psychiatry, University of Pittsburgh, was published online  in JAMA Network Open.

LIMITATIONS:

No diagnostic clinical interviews were conducted, and PTSD treatment was not assessed. All participants identified as cisgender, and most were non-Hispanic Black or White. The study was observational and cross-sectional, precluding assertions about directionality or causality.

DISCLOSURES:

The study was funded by the National Institutes of Health, the University of Pittsburgh Clinical and Translational Science Institute, and the University of Pittsburgh Small Molecule Biomarker Core. Dr. Thurston reported receiving personal fees from Astellas Pharma, Bayer, Hello Therapeutics, Vira Health, and Happify Health outside the submitted work.

A version of this article first appeared on Medscape.com.

In the pursuit of optimal health, regular physical activity (PA) is recommended to protect against dementia, cardiovascular disease (CVD), cancer, and other noncommunicable diseases. A significant body of research suggests the benefits of PA are positively correlated with higher frequency and intensity – with more often deemed better. This research has spawned a focus on increasing step counts and investing in standing desks and other interventions aimed at keeping people active.

But for many people, PA is a work requirement over which they have little control, and emerging evidence suggests that these workers not only do not reap the benefits associated with leisure-time PA, but they also actually experience an increased risk for the very conditions that PA is intended to prevent.

A study published recently in The Lancet Regional Health – Europe used registry data from more than 7,000 adults in Norway, following them from age 33 to 65 years, to assess PA trajectories and risks for later-life mild cognitive impairment (MCI) and dementia at age 70 or older.

“Incorporating a life-course perspective gives a broader picture of how participants’ occupational histories relate to cognitive impairment later in life,” principal investigator Vegard Skirbekk, PhD, Columbia University Mailman School of Public Health, New York, said in an interview. Other studies typically have assessed occupational PA at a single time point, often close to the end of an individual’s career, and largely relied on self-report, he said.

Study participants worked in more than 300 different occupations. General physical activities performed on the included jobs required “considerable” use of arms and legs and moving the whole body, such as climbing, lifting, balancing, walking, stooping, and handling of materials.

Dr. Skirbekk and colleagues grouped participants into four PA trajectories over the 44-year study period: stable low, increasing then decreasing, stable intermediate, and stable high.

A total of 902 individuals were diagnosed with dementia and 2,407 with MCI at age 70 years or older. After adjustment, risks for MCI and dementia were 15.5% for those with higher occupational PA scores in the latter part of their working life and 9% for those with lower physical demands. The researchers concluded that “consistently working in an occupation with intermediate or high occupational PA was linked to an increased risk of cognitive impairment.”

The findings support those of the Copenhagen Male Study. Published in 2020, this longitudinal study compared leisure-time and occupational PA among more than 4,000 men in Denmark aged 40-59 at baseline in 1970-1971 and followed them until they turned 60. After adjustment, participants with high occupational PA had a 55% greater risk of developing dementia compared with those doing sedentary work.
 

Good vs. bad PA

“[T]he WHO [World Health Organization] guide to preventing dementia and disease on the whole mentions physical activity as an important factor. But our study suggests that it must be a ‘good’ form of physical activity, which hard physical work is not,” said Kirsten Nabe-Nielsen, PhD, lead author of this study

Beyond dementia, another recent study adds to a wealth of data on associations between occupational PA and cardiovascular risks. The cross-sectional analysis of U.S. data from the National Institute for Occupational Safety and Health showed that odds of CVD were higher when participants were “always” performing total occupational activity (odds ratio [OR], 1.99), occupational exertion (OR, 2.15), or occupational standing and walking around (OR, 1.84) compared with “never” engaging in these activities.

The contrasting effects of leisure-time vs. occupational PA constitute the “physical activity paradox” hypothesis. Starting in 2011, multiple studies by Andreas Holtermann, PhD, of the National Research Centre for the Working Environment lend support to the PA paradox theory, as do subsequent studies by others.

Although only “marginally considered” until a few years ago, recent large cohort studies seem to confirm the paradox, Pier Luigi Temporelli, MD wrote in a recent editorial.

In separate interviews, Dr. Skirbekk and lead author Tyler Quinn, PhD, MS, West Virginia University, Morgantown, pointed to the PA paradox as an explanation for their own recent findings, suggesting that the mechanisms that underlie it probably are responsible for the associated deleterious effects of occupational PA on the brain and heart, and even mortality.

“It’s well established that PA in your leisure time can be positive, but in the workplace, the results are quite the opposite,” Dr. Skirbekk said. “The specific mechanisms for why occupational PA is associated with elevated dementia risk are still not well understood and we need more knowledge. But we know that higher occupational physical demands have been linked to smaller hippocampal volume and poorer memory performance.”

Furthermore, he said, individuals working in jobs with high demands, both psychological and physical, combined with low job control perform more poorly on cognitive testing later in life.

“We looked mainly at professions where people have heavy workloads and you have much less autonomy, such as nursing assistants, office cleaners, childcare workers, and other personal care workers,” he said. “You cannot sit. You have somebody relying on you. It’s not all pleasure, and it can be very hard. That’s where we find the associations.”
 

Lack of autonomy

Specific characteristics indirectly associated with high occupational PA jobs – low cognitive stimuli, lifestyle factors, and socioeconomic influences – as well as factors directly related to high occupational PA, such as long hours, repetitive tasks, low levels of control, and stress, could also adversely affect cognitive trajectories, Dr. Skirbekk explained.

“By contrast, leisure-time physical activities tend to be of much shorter duration; are associated with socialization, play, [and] positive emotions; and [include] the opportunity to take breaks or shift to other types of activities if one prefers,” he said. “It may also be that too little or too much PA could be adversely related to cognitive outcomes – hence moderate activity levels, for example 10,000 steps a day, are still likely beneficial for cognitive functioning.”

Dr. Quinn said most of the CVD risk linked to occupational PA has to do with long periods of exertion such as lifting and carrying objects. While occupational standing and walking all day are also linked to CVD risk, they’re not as risky as lifting and carrying, he said.

Like Dr. Skirbekk, Dr. Quinn noted that individuals can take a break from leisure-time PA when they are tired, but occupational PA doesn’t have that same autonomy to allow for recovery.

“So, in many cases, individuals are not getting the recovery their body needs to actually experience PA benefits, because those benefits come during rest,” Dr. Quinn said.

“We’ve shown that PA at work raises acute cardiovascular responses, which are related to cardiovascular risk. For example, 24-hour and waking heart rate and diastolic blood pressure, as well as nonwork diastolic blood pressure, all were significantly higher on workdays versus non-workdays,” he said.

Dr. Quinn also said that psychological stress at work amplifies risk. “A person who does PA at work and is stressed is likely to be at greater risk than someone who has a physically active job but doesn’t have psychological stress combined with it.”
 

Research gaps

However, Dr. Skirbekk noted that there are strategies that can reduce the risk for MCI and dementia despite high levels of occupational PA. “It is often difficult to change professions, and even if you do, it won’t immediately affect cognition. But altering one’s lifestyle is likely to have effects on cognitive development across the life cycle.

“Many clinicians say they always advise lifestyle changes, but nothing happens. But it makes sense to emphasize that these changes – stopping smoking, eating well, getting proper sleep, etc. – affect not only cardiovascular risk but also cognition. And I think clinicians should also take a patient’s occupation into account during any evaluation,” Dr. Skirbekk noted.

Dr. Quinn said it isn’t realistic to expect workers to come up with solutions to the PA paradox because many don’t have the autonomy to be able to mitigate their occupational risk.

“I think administrative controls and policy changes eventually will be the levers of change. We’re not quite there yet, but those are the types of things we should do when we’re trying to reduce loads in some way, or reduce the time that people spend doing certain tasks we know are potentially bad,” he said.

However, not everyone agrees that occupational PA doesn’t confer the same benefits of leisure-time PA, at least with respect to cardiovascular risk. For example, the Prospective Urban Rural Epidemiology (PURE) study, which includes a cohort of 130,000 people from 17 high-income, middle-income, and low-income countries, concluded that both higher recreational and nonrecreational PA were associated with a lower risk for mortality and CVD events.

What additional research is needed to clarify the effects of occupational and leisure-time activity and to address conflicting findings?

“Even studies coming out now regarding the effects of occupational PA have mainly used older data,” Dr. Skirbekk noted. “Labor markets and job demands have changed over time. There are different types of tasks and skills required now than there were 20 or 40 years ago. And of course, working from home is a recent phenomenon that’s happened on a large scale and might affect daily routines, sleep patterns, and also cognition. We need a better understanding of what the consequences might be.”
 

Health inequity issue

More research is also necessary to understand the social determinants of cognitive decline, impairment, and dementia, he said. “Many of the studies we see today are based on self-report of what someone has done in the past, which is particularly problematic for individuals who are impaired or who give interviews with others, which can induce biases.”

Dr. Quinn suggests that PA guidelines may need to differentiate between occupational and leisure-time PA to better reflect current research findings.

Meanwhile, Dr. Skirbekk and Dr. Quinn both point to the toll that occupational PA takes on the brain and body in lower-income workers as an important health equity issue.

“Our national guidelines for PA include occupational activity,” said Dr. Quinn. “But it’s clear that a lot of people who are getting a lot of occupational PA, particularly socioeconomic and racial/ethnic minorities, are not benefiting from it.”

Dr. Holtermann, who has arguably done the most research to date on the PA paradox, noted in a recent editorial that the majority of workers with high occupational PA have a low socioeconomic position and therefore “improving our understanding of the underlying mechanisms behind the PA health paradox and identifying new intervention targets along those pathways will be an important step to reduce socioeconomic health inequalities across the globe.”
 

A version of this article first appeared on Medscape.com.

In the pursuit of optimal health, regular physical activity (PA) is recommended to protect against dementia, cardiovascular disease (CVD), cancer, and other noncommunicable diseases. A significant body of research suggests the benefits of PA are positively correlated with higher frequency and intensity – with more often deemed better. This research has spawned a focus on increasing step counts and investing in standing desks and other interventions aimed at keeping people active.

But for many people, PA is a work requirement over which they have little control, and emerging evidence suggests that these workers not only do not reap the benefits associated with leisure-time PA, but they also actually experience an increased risk for the very conditions that PA is intended to prevent.

A study published recently in The Lancet Regional Health – Europe used registry data from more than 7,000 adults in Norway, following them from age 33 to 65 years, to assess PA trajectories and risks for later-life mild cognitive impairment (MCI) and dementia at age 70 or older.

“Incorporating a life-course perspective gives a broader picture of how participants’ occupational histories relate to cognitive impairment later in life,” principal investigator Vegard Skirbekk, PhD, Columbia University Mailman School of Public Health, New York, said in an interview. Other studies typically have assessed occupational PA at a single time point, often close to the end of an individual’s career, and largely relied on self-report, he said.

Study participants worked in more than 300 different occupations. General physical activities performed on the included jobs required “considerable” use of arms and legs and moving the whole body, such as climbing, lifting, balancing, walking, stooping, and handling of materials.

Dr. Skirbekk and colleagues grouped participants into four PA trajectories over the 44-year study period: stable low, increasing then decreasing, stable intermediate, and stable high.

A total of 902 individuals were diagnosed with dementia and 2,407 with MCI at age 70 years or older. After adjustment, risks for MCI and dementia were 15.5% for those with higher occupational PA scores in the latter part of their working life and 9% for those with lower physical demands. The researchers concluded that “consistently working in an occupation with intermediate or high occupational PA was linked to an increased risk of cognitive impairment.”

The findings support those of the Copenhagen Male Study. Published in 2020, this longitudinal study compared leisure-time and occupational PA among more than 4,000 men in Denmark aged 40-59 at baseline in 1970-1971 and followed them until they turned 60. After adjustment, participants with high occupational PA had a 55% greater risk of developing dementia compared with those doing sedentary work.
 

Good vs. bad PA

“[T]he WHO [World Health Organization] guide to preventing dementia and disease on the whole mentions physical activity as an important factor. But our study suggests that it must be a ‘good’ form of physical activity, which hard physical work is not,” said Kirsten Nabe-Nielsen, PhD, lead author of this study

Beyond dementia, another recent study adds to a wealth of data on associations between occupational PA and cardiovascular risks. The cross-sectional analysis of U.S. data from the National Institute for Occupational Safety and Health showed that odds of CVD were higher when participants were “always” performing total occupational activity (odds ratio [OR], 1.99), occupational exertion (OR, 2.15), or occupational standing and walking around (OR, 1.84) compared with “never” engaging in these activities.

The contrasting effects of leisure-time vs. occupational PA constitute the “physical activity paradox” hypothesis. Starting in 2011, multiple studies by Andreas Holtermann, PhD, of the National Research Centre for the Working Environment lend support to the PA paradox theory, as do subsequent studies by others.

Although only “marginally considered” until a few years ago, recent large cohort studies seem to confirm the paradox, Pier Luigi Temporelli, MD wrote in a recent editorial.

In separate interviews, Dr. Skirbekk and lead author Tyler Quinn, PhD, MS, West Virginia University, Morgantown, pointed to the PA paradox as an explanation for their own recent findings, suggesting that the mechanisms that underlie it probably are responsible for the associated deleterious effects of occupational PA on the brain and heart, and even mortality.

“It’s well established that PA in your leisure time can be positive, but in the workplace, the results are quite the opposite,” Dr. Skirbekk said. “The specific mechanisms for why occupational PA is associated with elevated dementia risk are still not well understood and we need more knowledge. But we know that higher occupational physical demands have been linked to smaller hippocampal volume and poorer memory performance.”

Furthermore, he said, individuals working in jobs with high demands, both psychological and physical, combined with low job control perform more poorly on cognitive testing later in life.

“We looked mainly at professions where people have heavy workloads and you have much less autonomy, such as nursing assistants, office cleaners, childcare workers, and other personal care workers,” he said. “You cannot sit. You have somebody relying on you. It’s not all pleasure, and it can be very hard. That’s where we find the associations.”
 

Lack of autonomy

Specific characteristics indirectly associated with high occupational PA jobs – low cognitive stimuli, lifestyle factors, and socioeconomic influences – as well as factors directly related to high occupational PA, such as long hours, repetitive tasks, low levels of control, and stress, could also adversely affect cognitive trajectories, Dr. Skirbekk explained.

“By contrast, leisure-time physical activities tend to be of much shorter duration; are associated with socialization, play, [and] positive emotions; and [include] the opportunity to take breaks or shift to other types of activities if one prefers,” he said. “It may also be that too little or too much PA could be adversely related to cognitive outcomes – hence moderate activity levels, for example 10,000 steps a day, are still likely beneficial for cognitive functioning.”

Dr. Quinn said most of the CVD risk linked to occupational PA has to do with long periods of exertion such as lifting and carrying objects. While occupational standing and walking all day are also linked to CVD risk, they’re not as risky as lifting and carrying, he said.

Like Dr. Skirbekk, Dr. Quinn noted that individuals can take a break from leisure-time PA when they are tired, but occupational PA doesn’t have that same autonomy to allow for recovery.

“So, in many cases, individuals are not getting the recovery their body needs to actually experience PA benefits, because those benefits come during rest,” Dr. Quinn said.

“We’ve shown that PA at work raises acute cardiovascular responses, which are related to cardiovascular risk. For example, 24-hour and waking heart rate and diastolic blood pressure, as well as nonwork diastolic blood pressure, all were significantly higher on workdays versus non-workdays,” he said.

Dr. Quinn also said that psychological stress at work amplifies risk. “A person who does PA at work and is stressed is likely to be at greater risk than someone who has a physically active job but doesn’t have psychological stress combined with it.”
 

Research gaps

However, Dr. Skirbekk noted that there are strategies that can reduce the risk for MCI and dementia despite high levels of occupational PA. “It is often difficult to change professions, and even if you do, it won’t immediately affect cognition. But altering one’s lifestyle is likely to have effects on cognitive development across the life cycle.

“Many clinicians say they always advise lifestyle changes, but nothing happens. But it makes sense to emphasize that these changes – stopping smoking, eating well, getting proper sleep, etc. – affect not only cardiovascular risk but also cognition. And I think clinicians should also take a patient’s occupation into account during any evaluation,” Dr. Skirbekk noted.

Dr. Quinn said it isn’t realistic to expect workers to come up with solutions to the PA paradox because many don’t have the autonomy to be able to mitigate their occupational risk.

“I think administrative controls and policy changes eventually will be the levers of change. We’re not quite there yet, but those are the types of things we should do when we’re trying to reduce loads in some way, or reduce the time that people spend doing certain tasks we know are potentially bad,” he said.

However, not everyone agrees that occupational PA doesn’t confer the same benefits of leisure-time PA, at least with respect to cardiovascular risk. For example, the Prospective Urban Rural Epidemiology (PURE) study, which includes a cohort of 130,000 people from 17 high-income, middle-income, and low-income countries, concluded that both higher recreational and nonrecreational PA were associated with a lower risk for mortality and CVD events.

What additional research is needed to clarify the effects of occupational and leisure-time activity and to address conflicting findings?

“Even studies coming out now regarding the effects of occupational PA have mainly used older data,” Dr. Skirbekk noted. “Labor markets and job demands have changed over time. There are different types of tasks and skills required now than there were 20 or 40 years ago. And of course, working from home is a recent phenomenon that’s happened on a large scale and might affect daily routines, sleep patterns, and also cognition. We need a better understanding of what the consequences might be.”
 

Health inequity issue

More research is also necessary to understand the social determinants of cognitive decline, impairment, and dementia, he said. “Many of the studies we see today are based on self-report of what someone has done in the past, which is particularly problematic for individuals who are impaired or who give interviews with others, which can induce biases.”

Dr. Quinn suggests that PA guidelines may need to differentiate between occupational and leisure-time PA to better reflect current research findings.

Meanwhile, Dr. Skirbekk and Dr. Quinn both point to the toll that occupational PA takes on the brain and body in lower-income workers as an important health equity issue.

“Our national guidelines for PA include occupational activity,” said Dr. Quinn. “But it’s clear that a lot of people who are getting a lot of occupational PA, particularly socioeconomic and racial/ethnic minorities, are not benefiting from it.”

Dr. Holtermann, who has arguably done the most research to date on the PA paradox, noted in a recent editorial that the majority of workers with high occupational PA have a low socioeconomic position and therefore “improving our understanding of the underlying mechanisms behind the PA health paradox and identifying new intervention targets along those pathways will be an important step to reduce socioeconomic health inequalities across the globe.”
 

A version of this article first appeared on Medscape.com.

In the pursuit of optimal health, regular physical activity (PA) is recommended to protect against dementia, cardiovascular disease (CVD), cancer, and other noncommunicable diseases. A significant body of research suggests the benefits of PA are positively correlated with higher frequency and intensity – with more often deemed better. This research has spawned a focus on increasing step counts and investing in standing desks and other interventions aimed at keeping people active.

But for many people, PA is a work requirement over which they have little control, and emerging evidence suggests that these workers not only do not reap the benefits associated with leisure-time PA, but they also actually experience an increased risk for the very conditions that PA is intended to prevent.

A study published recently in The Lancet Regional Health – Europe used registry data from more than 7,000 adults in Norway, following them from age 33 to 65 years, to assess PA trajectories and risks for later-life mild cognitive impairment (MCI) and dementia at age 70 or older.

“Incorporating a life-course perspective gives a broader picture of how participants’ occupational histories relate to cognitive impairment later in life,” principal investigator Vegard Skirbekk, PhD, Columbia University Mailman School of Public Health, New York, said in an interview. Other studies typically have assessed occupational PA at a single time point, often close to the end of an individual’s career, and largely relied on self-report, he said.

Study participants worked in more than 300 different occupations. General physical activities performed on the included jobs required “considerable” use of arms and legs and moving the whole body, such as climbing, lifting, balancing, walking, stooping, and handling of materials.

Dr. Skirbekk and colleagues grouped participants into four PA trajectories over the 44-year study period: stable low, increasing then decreasing, stable intermediate, and stable high.

A total of 902 individuals were diagnosed with dementia and 2,407 with MCI at age 70 years or older. After adjustment, risks for MCI and dementia were 15.5% for those with higher occupational PA scores in the latter part of their working life and 9% for those with lower physical demands. The researchers concluded that “consistently working in an occupation with intermediate or high occupational PA was linked to an increased risk of cognitive impairment.”

The findings support those of the Copenhagen Male Study. Published in 2020, this longitudinal study compared leisure-time and occupational PA among more than 4,000 men in Denmark aged 40-59 at baseline in 1970-1971 and followed them until they turned 60. After adjustment, participants with high occupational PA had a 55% greater risk of developing dementia compared with those doing sedentary work.
 

Good vs. bad PA

“[T]he WHO [World Health Organization] guide to preventing dementia and disease on the whole mentions physical activity as an important factor. But our study suggests that it must be a ‘good’ form of physical activity, which hard physical work is not,” said Kirsten Nabe-Nielsen, PhD, lead author of this study

Beyond dementia, another recent study adds to a wealth of data on associations between occupational PA and cardiovascular risks. The cross-sectional analysis of U.S. data from the National Institute for Occupational Safety and Health showed that odds of CVD were higher when participants were “always” performing total occupational activity (odds ratio [OR], 1.99), occupational exertion (OR, 2.15), or occupational standing and walking around (OR, 1.84) compared with “never” engaging in these activities.

The contrasting effects of leisure-time vs. occupational PA constitute the “physical activity paradox” hypothesis. Starting in 2011, multiple studies by Andreas Holtermann, PhD, of the National Research Centre for the Working Environment lend support to the PA paradox theory, as do subsequent studies by others.

Although only “marginally considered” until a few years ago, recent large cohort studies seem to confirm the paradox, Pier Luigi Temporelli, MD wrote in a recent editorial.

In separate interviews, Dr. Skirbekk and lead author Tyler Quinn, PhD, MS, West Virginia University, Morgantown, pointed to the PA paradox as an explanation for their own recent findings, suggesting that the mechanisms that underlie it probably are responsible for the associated deleterious effects of occupational PA on the brain and heart, and even mortality.

“It’s well established that PA in your leisure time can be positive, but in the workplace, the results are quite the opposite,” Dr. Skirbekk said. “The specific mechanisms for why occupational PA is associated with elevated dementia risk are still not well understood and we need more knowledge. But we know that higher occupational physical demands have been linked to smaller hippocampal volume and poorer memory performance.”

Furthermore, he said, individuals working in jobs with high demands, both psychological and physical, combined with low job control perform more poorly on cognitive testing later in life.

“We looked mainly at professions where people have heavy workloads and you have much less autonomy, such as nursing assistants, office cleaners, childcare workers, and other personal care workers,” he said. “You cannot sit. You have somebody relying on you. It’s not all pleasure, and it can be very hard. That’s where we find the associations.”
 

Lack of autonomy

Specific characteristics indirectly associated with high occupational PA jobs – low cognitive stimuli, lifestyle factors, and socioeconomic influences – as well as factors directly related to high occupational PA, such as long hours, repetitive tasks, low levels of control, and stress, could also adversely affect cognitive trajectories, Dr. Skirbekk explained.

“By contrast, leisure-time physical activities tend to be of much shorter duration; are associated with socialization, play, [and] positive emotions; and [include] the opportunity to take breaks or shift to other types of activities if one prefers,” he said. “It may also be that too little or too much PA could be adversely related to cognitive outcomes – hence moderate activity levels, for example 10,000 steps a day, are still likely beneficial for cognitive functioning.”

Dr. Quinn said most of the CVD risk linked to occupational PA has to do with long periods of exertion such as lifting and carrying objects. While occupational standing and walking all day are also linked to CVD risk, they’re not as risky as lifting and carrying, he said.

Like Dr. Skirbekk, Dr. Quinn noted that individuals can take a break from leisure-time PA when they are tired, but occupational PA doesn’t have that same autonomy to allow for recovery.

“So, in many cases, individuals are not getting the recovery their body needs to actually experience PA benefits, because those benefits come during rest,” Dr. Quinn said.

“We’ve shown that PA at work raises acute cardiovascular responses, which are related to cardiovascular risk. For example, 24-hour and waking heart rate and diastolic blood pressure, as well as nonwork diastolic blood pressure, all were significantly higher on workdays versus non-workdays,” he said.

Dr. Quinn also said that psychological stress at work amplifies risk. “A person who does PA at work and is stressed is likely to be at greater risk than someone who has a physically active job but doesn’t have psychological stress combined with it.”
 

Research gaps

However, Dr. Skirbekk noted that there are strategies that can reduce the risk for MCI and dementia despite high levels of occupational PA. “It is often difficult to change professions, and even if you do, it won’t immediately affect cognition. But altering one’s lifestyle is likely to have effects on cognitive development across the life cycle.

“Many clinicians say they always advise lifestyle changes, but nothing happens. But it makes sense to emphasize that these changes – stopping smoking, eating well, getting proper sleep, etc. – affect not only cardiovascular risk but also cognition. And I think clinicians should also take a patient’s occupation into account during any evaluation,” Dr. Skirbekk noted.

Dr. Quinn said it isn’t realistic to expect workers to come up with solutions to the PA paradox because many don’t have the autonomy to be able to mitigate their occupational risk.

“I think administrative controls and policy changes eventually will be the levers of change. We’re not quite there yet, but those are the types of things we should do when we’re trying to reduce loads in some way, or reduce the time that people spend doing certain tasks we know are potentially bad,” he said.

However, not everyone agrees that occupational PA doesn’t confer the same benefits of leisure-time PA, at least with respect to cardiovascular risk. For example, the Prospective Urban Rural Epidemiology (PURE) study, which includes a cohort of 130,000 people from 17 high-income, middle-income, and low-income countries, concluded that both higher recreational and nonrecreational PA were associated with a lower risk for mortality and CVD events.

What additional research is needed to clarify the effects of occupational and leisure-time activity and to address conflicting findings?

“Even studies coming out now regarding the effects of occupational PA have mainly used older data,” Dr. Skirbekk noted. “Labor markets and job demands have changed over time. There are different types of tasks and skills required now than there were 20 or 40 years ago. And of course, working from home is a recent phenomenon that’s happened on a large scale and might affect daily routines, sleep patterns, and also cognition. We need a better understanding of what the consequences might be.”
 

Health inequity issue

More research is also necessary to understand the social determinants of cognitive decline, impairment, and dementia, he said. “Many of the studies we see today are based on self-report of what someone has done in the past, which is particularly problematic for individuals who are impaired or who give interviews with others, which can induce biases.”

Dr. Quinn suggests that PA guidelines may need to differentiate between occupational and leisure-time PA to better reflect current research findings.

Meanwhile, Dr. Skirbekk and Dr. Quinn both point to the toll that occupational PA takes on the brain and body in lower-income workers as an important health equity issue.

“Our national guidelines for PA include occupational activity,” said Dr. Quinn. “But it’s clear that a lot of people who are getting a lot of occupational PA, particularly socioeconomic and racial/ethnic minorities, are not benefiting from it.”

Dr. Holtermann, who has arguably done the most research to date on the PA paradox, noted in a recent editorial that the majority of workers with high occupational PA have a low socioeconomic position and therefore “improving our understanding of the underlying mechanisms behind the PA health paradox and identifying new intervention targets along those pathways will be an important step to reduce socioeconomic health inequalities across the globe.”
 

A version of this article first appeared on Medscape.com.

Leading UK Alzheimer’s organizations have launched an ambitious plan to have a diagnostic Alzheimer’s disease (AD) blood test widely available within the next 5 years.

Alzheimer’s Research UK, the Alzheimer’s Society, and the National Institute for Health and Care Research (NIHR) are collaborating and leading AD researchers to bring a diagnostic blood test to the UK’s National Health Service (NHS).

“Dementia affects around 900,000 people in the UK today, and that number is expected to rise to 1.4 million by 2040. It is the UK’s biggest killer,” Fiona Carragher, with the Alzheimer’s Society, said during a media briefing announcing the project.

Yet, many people face a very long wait of up to 2-4 years to get a dementia diagnosis, and many cases remain undiagnosed, she noted.

A chief reason is lack of access to specialized diagnostic testing. Currently, only 2% of people in the United Kingdom have access to advanced diagnostic tests such as PET scans and lumbar punctures owing to limited availability.

“Getting an early and accurate diagnosis is the pivotal first step to getting help today and unlocking hope for the future” and blood biomarkers provide a “real opportunity to disrupt the diagnostic paradigm,” Ms. Carragher said. It also offers greater opportunities to participate in research and clinical trials, she added.
 

Attitude shift

Susan Kohlhaas, PhD, with Alzheimer’s Research UK, noted that attitudes toward dementia diagnosis have changed in the past few years. The days when people may have not wanted to know if they have dementia are gone.

Data from the latest wave of the Alzheimer’s Research UK Dementia Attitudes Monitor survey show that 9 in 10 people would seek a diagnosis from their provider. “That’s been driven by awareness of treatments and things that people can proactively do to try and slow disease progression,” Dr. Kohlhaas said.

“As new treatments for dementia become available there will to be a surge in people seeking a diagnosis. At the moment, we don’t have adequate infrastructure to cope with that demand,” Dr. Kohlhaas added.

She noted that blood tests are starting to show their potential as an effective part of the diagnosis and are widely used in research.

“In some cases, they are similar in sensitivity to gold-standard PET scans and lumbar punctures, and they’re less expensive and potentially more scalable on the NHS. What we need to do over the next several years is to understand how they fit into the clinical pathway,” Dr. Kohlhaas said.

The project will involve working with leading dementia researchers to pilot the implementation of potential blood tests in the NHS that can give an early and accurate diagnose of dementia.

The project, which kicks off in January 2024, will receive £5 million ($6.13 million) awarded by the UK Postcode Dream Fund. Specific details regarding the leadership team, participating centers, and specific blood biomarker tests to be trialed will be announced then.

Ms. Carragher and Dr. Kohlhaas reported no relevant financial conflicts of interest.
 

A version of this article appeared on Medscape.com.

Leading UK Alzheimer’s organizations have launched an ambitious plan to have a diagnostic Alzheimer’s disease (AD) blood test widely available within the next 5 years.

Alzheimer’s Research UK, the Alzheimer’s Society, and the National Institute for Health and Care Research (NIHR) are collaborating and leading AD researchers to bring a diagnostic blood test to the UK’s National Health Service (NHS).

“Dementia affects around 900,000 people in the UK today, and that number is expected to rise to 1.4 million by 2040. It is the UK’s biggest killer,” Fiona Carragher, with the Alzheimer’s Society, said during a media briefing announcing the project.

Yet, many people face a very long wait of up to 2-4 years to get a dementia diagnosis, and many cases remain undiagnosed, she noted.

A chief reason is lack of access to specialized diagnostic testing. Currently, only 2% of people in the United Kingdom have access to advanced diagnostic tests such as PET scans and lumbar punctures owing to limited availability.

“Getting an early and accurate diagnosis is the pivotal first step to getting help today and unlocking hope for the future” and blood biomarkers provide a “real opportunity to disrupt the diagnostic paradigm,” Ms. Carragher said. It also offers greater opportunities to participate in research and clinical trials, she added.
 

Attitude shift

Susan Kohlhaas, PhD, with Alzheimer’s Research UK, noted that attitudes toward dementia diagnosis have changed in the past few years. The days when people may have not wanted to know if they have dementia are gone.

Data from the latest wave of the Alzheimer’s Research UK Dementia Attitudes Monitor survey show that 9 in 10 people would seek a diagnosis from their provider. “That’s been driven by awareness of treatments and things that people can proactively do to try and slow disease progression,” Dr. Kohlhaas said.

“As new treatments for dementia become available there will to be a surge in people seeking a diagnosis. At the moment, we don’t have adequate infrastructure to cope with that demand,” Dr. Kohlhaas added.

She noted that blood tests are starting to show their potential as an effective part of the diagnosis and are widely used in research.

“In some cases, they are similar in sensitivity to gold-standard PET scans and lumbar punctures, and they’re less expensive and potentially more scalable on the NHS. What we need to do over the next several years is to understand how they fit into the clinical pathway,” Dr. Kohlhaas said.

The project will involve working with leading dementia researchers to pilot the implementation of potential blood tests in the NHS that can give an early and accurate diagnose of dementia.

The project, which kicks off in January 2024, will receive £5 million ($6.13 million) awarded by the UK Postcode Dream Fund. Specific details regarding the leadership team, participating centers, and specific blood biomarker tests to be trialed will be announced then.

Ms. Carragher and Dr. Kohlhaas reported no relevant financial conflicts of interest.
 

A version of this article appeared on Medscape.com.

Leading UK Alzheimer’s organizations have launched an ambitious plan to have a diagnostic Alzheimer’s disease (AD) blood test widely available within the next 5 years.

Alzheimer’s Research UK, the Alzheimer’s Society, and the National Institute for Health and Care Research (NIHR) are collaborating and leading AD researchers to bring a diagnostic blood test to the UK’s National Health Service (NHS).

“Dementia affects around 900,000 people in the UK today, and that number is expected to rise to 1.4 million by 2040. It is the UK’s biggest killer,” Fiona Carragher, with the Alzheimer’s Society, said during a media briefing announcing the project.

Yet, many people face a very long wait of up to 2-4 years to get a dementia diagnosis, and many cases remain undiagnosed, she noted.

A chief reason is lack of access to specialized diagnostic testing. Currently, only 2% of people in the United Kingdom have access to advanced diagnostic tests such as PET scans and lumbar punctures owing to limited availability.

“Getting an early and accurate diagnosis is the pivotal first step to getting help today and unlocking hope for the future” and blood biomarkers provide a “real opportunity to disrupt the diagnostic paradigm,” Ms. Carragher said. It also offers greater opportunities to participate in research and clinical trials, she added.
 

Attitude shift

Susan Kohlhaas, PhD, with Alzheimer’s Research UK, noted that attitudes toward dementia diagnosis have changed in the past few years. The days when people may have not wanted to know if they have dementia are gone.

Data from the latest wave of the Alzheimer’s Research UK Dementia Attitudes Monitor survey show that 9 in 10 people would seek a diagnosis from their provider. “That’s been driven by awareness of treatments and things that people can proactively do to try and slow disease progression,” Dr. Kohlhaas said.

“As new treatments for dementia become available there will to be a surge in people seeking a diagnosis. At the moment, we don’t have adequate infrastructure to cope with that demand,” Dr. Kohlhaas added.

She noted that blood tests are starting to show their potential as an effective part of the diagnosis and are widely used in research.

“In some cases, they are similar in sensitivity to gold-standard PET scans and lumbar punctures, and they’re less expensive and potentially more scalable on the NHS. What we need to do over the next several years is to understand how they fit into the clinical pathway,” Dr. Kohlhaas said.

The project will involve working with leading dementia researchers to pilot the implementation of potential blood tests in the NHS that can give an early and accurate diagnose of dementia.

The project, which kicks off in January 2024, will receive £5 million ($6.13 million) awarded by the UK Postcode Dream Fund. Specific details regarding the leadership team, participating centers, and specific blood biomarker tests to be trialed will be announced then.

Ms. Carragher and Dr. Kohlhaas reported no relevant financial conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

A history of military service is associated with a 26% increased risk for amyloid plaque and 10% increased risk for elevated tau tangle levels, underscoring the urgent need for amyloid screening among veterans.

METHODOLOGY:

• The study included 597 male decedents who donated their brains to one of two Alzheimer’s Disease Research Center (ADRC) brain bank programs between 1986 and 2018.
• Researchers conducted public data tracing for historical information on military history, which included searching online commercial genealogical databases and paper archives.
• They evaluated tau tangles (using a B score of neurofibrillary tangle deposition in four stages: B0 [not present], B1 [transentorhinal stages], B2 [limbic stages], and B3 [isocortical stages]) and amyloid plaque pathology (using a C score that classifies neuritic amyloid plaque into four categories: no plaques, sparse, moderate, or frequent).
• The study involved three B score comparisons (1, 2, 3 vs. 0; 2, 3 vs. 0, 1; and 3 vs. 0, 1, 2) and two C score comparisons (sparse, moderate, or frequent vs. no plaques, and moderate or frequent vs. no plaque or sparse).

TAKEAWAY:

• Public record tracing determined that 60% of the sample of male decedents had a history of military service; the median year of birth was 1923 and the median year of death was 2007.
• After adjustment for age and year of death, those with a military service history had a 26% increased risk for a higher neuritic amyloid plaque C score compared with those without such history (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.06-1.49), an increase that applied for both relevant comparisons.
• A history of military service was also associated with a 10% greater adjusted odds of a higher neurofibrillary tangle B score (OR, 1.10; 95% CI, 1.08-1.12), with the increase applying to all three comparisons.
• A sensitivity analysis that included both the male decedents and 556 female decedents (increasing the overall sample to 1,153) and was adjusted for sex in addition to age and year of death showed similar results to the male-only sample estimations for both B and C score comparisons.

IN PRACTICE:

Understanding how military service affects AD biological processes is “essential” from a research perspective, the investigators noted. These new findings “emphasize that targeted AD therapies in the veteran population are urgently needed.”

SOURCE:

The study was conducted by W. Ryan Powell, Center for Health Disparities Research and Department of Medicine, Geriatrics Division, University of Wisconsin School of Medicine and Public Health, and colleagues. It was published online in Alzheimer’s & Dementia.

LIMITATIONS:

Selection bias in brain donation is likely because ADRC cohorts are recruitment based. The study was unable to rigorously identify factors that may explain why individuals with military service are at greater risk of having amyloid and tau neuropathology (including the interplay between environmental and genetic risk factors such as apolipoprotein E status).

DISCLOSURES:

The study was supported by the National Institute on Aging. The authors reported no disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

A history of military service is associated with a 26% increased risk for amyloid plaque and 10% increased risk for elevated tau tangle levels, underscoring the urgent need for amyloid screening among veterans.

METHODOLOGY:

• The study included 597 male decedents who donated their brains to one of two Alzheimer’s Disease Research Center (ADRC) brain bank programs between 1986 and 2018.
• Researchers conducted public data tracing for historical information on military history, which included searching online commercial genealogical databases and paper archives.
• They evaluated tau tangles (using a B score of neurofibrillary tangle deposition in four stages: B0 [not present], B1 [transentorhinal stages], B2 [limbic stages], and B3 [isocortical stages]) and amyloid plaque pathology (using a C score that classifies neuritic amyloid plaque into four categories: no plaques, sparse, moderate, or frequent).
• The study involved three B score comparisons (1, 2, 3 vs. 0; 2, 3 vs. 0, 1; and 3 vs. 0, 1, 2) and two C score comparisons (sparse, moderate, or frequent vs. no plaques, and moderate or frequent vs. no plaque or sparse).

TAKEAWAY:

• Public record tracing determined that 60% of the sample of male decedents had a history of military service; the median year of birth was 1923 and the median year of death was 2007.
• After adjustment for age and year of death, those with a military service history had a 26% increased risk for a higher neuritic amyloid plaque C score compared with those without such history (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.06-1.49), an increase that applied for both relevant comparisons.
• A history of military service was also associated with a 10% greater adjusted odds of a higher neurofibrillary tangle B score (OR, 1.10; 95% CI, 1.08-1.12), with the increase applying to all three comparisons.
• A sensitivity analysis that included both the male decedents and 556 female decedents (increasing the overall sample to 1,153) and was adjusted for sex in addition to age and year of death showed similar results to the male-only sample estimations for both B and C score comparisons.

IN PRACTICE:

Understanding how military service affects AD biological processes is “essential” from a research perspective, the investigators noted. These new findings “emphasize that targeted AD therapies in the veteran population are urgently needed.”

SOURCE:

The study was conducted by W. Ryan Powell, Center for Health Disparities Research and Department of Medicine, Geriatrics Division, University of Wisconsin School of Medicine and Public Health, and colleagues. It was published online in Alzheimer’s & Dementia.

LIMITATIONS:

Selection bias in brain donation is likely because ADRC cohorts are recruitment based. The study was unable to rigorously identify factors that may explain why individuals with military service are at greater risk of having amyloid and tau neuropathology (including the interplay between environmental and genetic risk factors such as apolipoprotein E status).

DISCLOSURES:

The study was supported by the National Institute on Aging. The authors reported no disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

A history of military service is associated with a 26% increased risk for amyloid plaque and 10% increased risk for elevated tau tangle levels, underscoring the urgent need for amyloid screening among veterans.

METHODOLOGY:

• The study included 597 male decedents who donated their brains to one of two Alzheimer’s Disease Research Center (ADRC) brain bank programs between 1986 and 2018.
• Researchers conducted public data tracing for historical information on military history, which included searching online commercial genealogical databases and paper archives.
• They evaluated tau tangles (using a B score of neurofibrillary tangle deposition in four stages: B0 [not present], B1 [transentorhinal stages], B2 [limbic stages], and B3 [isocortical stages]) and amyloid plaque pathology (using a C score that classifies neuritic amyloid plaque into four categories: no plaques, sparse, moderate, or frequent).
• The study involved three B score comparisons (1, 2, 3 vs. 0; 2, 3 vs. 0, 1; and 3 vs. 0, 1, 2) and two C score comparisons (sparse, moderate, or frequent vs. no plaques, and moderate or frequent vs. no plaque or sparse).

TAKEAWAY:

• Public record tracing determined that 60% of the sample of male decedents had a history of military service; the median year of birth was 1923 and the median year of death was 2007.
• After adjustment for age and year of death, those with a military service history had a 26% increased risk for a higher neuritic amyloid plaque C score compared with those without such history (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.06-1.49), an increase that applied for both relevant comparisons.
• A history of military service was also associated with a 10% greater adjusted odds of a higher neurofibrillary tangle B score (OR, 1.10; 95% CI, 1.08-1.12), with the increase applying to all three comparisons.
• A sensitivity analysis that included both the male decedents and 556 female decedents (increasing the overall sample to 1,153) and was adjusted for sex in addition to age and year of death showed similar results to the male-only sample estimations for both B and C score comparisons.

IN PRACTICE:

Understanding how military service affects AD biological processes is “essential” from a research perspective, the investigators noted. These new findings “emphasize that targeted AD therapies in the veteran population are urgently needed.”

SOURCE:

The study was conducted by W. Ryan Powell, Center for Health Disparities Research and Department of Medicine, Geriatrics Division, University of Wisconsin School of Medicine and Public Health, and colleagues. It was published online in Alzheimer’s & Dementia.

LIMITATIONS:

Selection bias in brain donation is likely because ADRC cohorts are recruitment based. The study was unable to rigorously identify factors that may explain why individuals with military service are at greater risk of having amyloid and tau neuropathology (including the interplay between environmental and genetic risk factors such as apolipoprotein E status).

DISCLOSURES:

The study was supported by the National Institute on Aging. The authors reported no disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

In the first year of the COVID-19 pandemic, there was a significant drop in working memory and executive function in older individuals. This was attributed to an increase in known dementia risk factors, including increased alcohol use and a more sedentary lifestyle. This trend persisted into the second year of the pandemic, after social restrictions had eased.

METHODOLOGY:

• In total, 3,140 participants (54% women; mean age, 68 years) in the PROTECT study, a longitudinal aging study in the United Kingdom, completed annual cognitive assessments and self-reported questionnaires related to mental health and lifestyle.
• Investigators analyzed cognition across three time periods: during the year before the pandemic (March 2019 to February 2020), during pandemic year 1 (March 2020 to February 2021), and pandemic year 2 (March 2021 to February 2022).
• Investigators conducted a subanalysis on those with mild cognitive impairment and those with a history of COVID-19 (n = 752).

TAKEAWAY:

• During the first year of the pandemic, when there were societal lockdowns totaling 6 months, significant worsening of executive function and working memory was seen across the entire cohort (effect sizes, 0.15 and 0.51, respectively), in people with mild cognitive impairment (effect sizes, 0.13 and 0.40, respectively), and in those with a previous history of COVID-19 (effect sizes, 0.24 and 0.46, respectively).
• Worsening of working memory was sustained across the whole cohort in the second year of the pandemic after lockdowns were lifted (effect size, 0.47).
• Even after investigators removed data on people with mild cognitive impairment and COVID-19, the decline in executive function (effect size, 0.15; P < .0001) and working memory (effect size, 0.53; P < .0001) persisted.
• Cognitive decline was significantly associated with known risk factors for dementia, such as reduced exercise (P = .0049) and increased alcohol use (P = .049), across the whole cohort, as well as depression (P = .011) in those with a history of COVID-19 and loneliness (P = .0038) in those with mild cognitive impairment.

IN PRACTICE:

Investigators noted that these data add to existing knowledge of long-standing health consequences of COVID-19, especially for older people with memory problems. “On the positive note, there is evidence that lifestyle changes and improved health management can positively influence mental functioning,” study coauthor Dag Aarsland, MD, PhD, professor of old age psychiatry at the Institute of Psychiatry, Psychology & Neuroscience of King’s College London, said in a press release. “The current study underlines the importance of careful monitoring of people at risk during major events such as the pandemic.”

SOURCE:

The study was led by Anne Corbett, PhD, of University of Exeter, and was published online in The Lancet Healthy Longevity. The research was funded by the National Institute for Health and Care Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London and the NIHR Exeter Biomedical Research Centre.

LIMITATIONS:

The study relied on self-reported data. In addition, the PROTECT cohort is self-selected and may skew toward participants with higher education levels.

DISCLOSURES:

Dr. Corbett reported receiving funding from the NIHR and grants from Synexus, reMYND, and Novo Nordisk. Other disclosures are noted in the original article.
 

A version of this article appeared on Medscape.com.

TOPLINE:

In the first year of the COVID-19 pandemic, there was a significant drop in working memory and executive function in older individuals. This was attributed to an increase in known dementia risk factors, including increased alcohol use and a more sedentary lifestyle. This trend persisted into the second year of the pandemic, after social restrictions had eased.

METHODOLOGY:

• In total, 3,140 participants (54% women; mean age, 68 years) in the PROTECT study, a longitudinal aging study in the United Kingdom, completed annual cognitive assessments and self-reported questionnaires related to mental health and lifestyle.
• Investigators analyzed cognition across three time periods: during the year before the pandemic (March 2019 to February 2020), during pandemic year 1 (March 2020 to February 2021), and pandemic year 2 (March 2021 to February 2022).
• Investigators conducted a subanalysis on those with mild cognitive impairment and those with a history of COVID-19 (n = 752).

TAKEAWAY:

• During the first year of the pandemic, when there were societal lockdowns totaling 6 months, significant worsening of executive function and working memory was seen across the entire cohort (effect sizes, 0.15 and 0.51, respectively), in people with mild cognitive impairment (effect sizes, 0.13 and 0.40, respectively), and in those with a previous history of COVID-19 (effect sizes, 0.24 and 0.46, respectively).
• Worsening of working memory was sustained across the whole cohort in the second year of the pandemic after lockdowns were lifted (effect size, 0.47).
• Even after investigators removed data on people with mild cognitive impairment and COVID-19, the decline in executive function (effect size, 0.15; P < .0001) and working memory (effect size, 0.53; P < .0001) persisted.
• Cognitive decline was significantly associated with known risk factors for dementia, such as reduced exercise (P = .0049) and increased alcohol use (P = .049), across the whole cohort, as well as depression (P = .011) in those with a history of COVID-19 and loneliness (P = .0038) in those with mild cognitive impairment.

IN PRACTICE:

Investigators noted that these data add to existing knowledge of long-standing health consequences of COVID-19, especially for older people with memory problems. “On the positive note, there is evidence that lifestyle changes and improved health management can positively influence mental functioning,” study coauthor Dag Aarsland, MD, PhD, professor of old age psychiatry at the Institute of Psychiatry, Psychology & Neuroscience of King’s College London, said in a press release. “The current study underlines the importance of careful monitoring of people at risk during major events such as the pandemic.”

SOURCE:

The study was led by Anne Corbett, PhD, of University of Exeter, and was published online in The Lancet Healthy Longevity. The research was funded by the National Institute for Health and Care Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London and the NIHR Exeter Biomedical Research Centre.

LIMITATIONS:

The study relied on self-reported data. In addition, the PROTECT cohort is self-selected and may skew toward participants with higher education levels.

DISCLOSURES:

Dr. Corbett reported receiving funding from the NIHR and grants from Synexus, reMYND, and Novo Nordisk. Other disclosures are noted in the original article.
 

A version of this article appeared on Medscape.com.

TOPLINE:

In the first year of the COVID-19 pandemic, there was a significant drop in working memory and executive function in older individuals. This was attributed to an increase in known dementia risk factors, including increased alcohol use and a more sedentary lifestyle. This trend persisted into the second year of the pandemic, after social restrictions had eased.

METHODOLOGY:

• In total, 3,140 participants (54% women; mean age, 68 years) in the PROTECT study, a longitudinal aging study in the United Kingdom, completed annual cognitive assessments and self-reported questionnaires related to mental health and lifestyle.
• Investigators analyzed cognition across three time periods: during the year before the pandemic (March 2019 to February 2020), during pandemic year 1 (March 2020 to February 2021), and pandemic year 2 (March 2021 to February 2022).
• Investigators conducted a subanalysis on those with mild cognitive impairment and those with a history of COVID-19 (n = 752).

TAKEAWAY:

• During the first year of the pandemic, when there were societal lockdowns totaling 6 months, significant worsening of executive function and working memory was seen across the entire cohort (effect sizes, 0.15 and 0.51, respectively), in people with mild cognitive impairment (effect sizes, 0.13 and 0.40, respectively), and in those with a previous history of COVID-19 (effect sizes, 0.24 and 0.46, respectively).
• Worsening of working memory was sustained across the whole cohort in the second year of the pandemic after lockdowns were lifted (effect size, 0.47).
• Even after investigators removed data on people with mild cognitive impairment and COVID-19, the decline in executive function (effect size, 0.15; P < .0001) and working memory (effect size, 0.53; P < .0001) persisted.
• Cognitive decline was significantly associated with known risk factors for dementia, such as reduced exercise (P = .0049) and increased alcohol use (P = .049), across the whole cohort, as well as depression (P = .011) in those with a history of COVID-19 and loneliness (P = .0038) in those with mild cognitive impairment.

IN PRACTICE:

Investigators noted that these data add to existing knowledge of long-standing health consequences of COVID-19, especially for older people with memory problems. “On the positive note, there is evidence that lifestyle changes and improved health management can positively influence mental functioning,” study coauthor Dag Aarsland, MD, PhD, professor of old age psychiatry at the Institute of Psychiatry, Psychology & Neuroscience of King’s College London, said in a press release. “The current study underlines the importance of careful monitoring of people at risk during major events such as the pandemic.”

SOURCE:

The study was led by Anne Corbett, PhD, of University of Exeter, and was published online in The Lancet Healthy Longevity. The research was funded by the National Institute for Health and Care Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London and the NIHR Exeter Biomedical Research Centre.

LIMITATIONS:

The study relied on self-reported data. In addition, the PROTECT cohort is self-selected and may skew toward participants with higher education levels.

DISCLOSURES:

Dr. Corbett reported receiving funding from the NIHR and grants from Synexus, reMYND, and Novo Nordisk. Other disclosures are noted in the original article.
 

A version of this article appeared on Medscape.com.

Recorded October 13, 2023. This transcript has been edited for clarity.

Kathrin LaFaver, MD: I’ll be talking today with Dr. Meredith Wicklund, senior associate consultant and behavioral neurologist specialist at Mayo Clinic in Arizona. Welcome, Meredith.

Meredith Wicklund, MD: Thank you.
 

Lecanemab data

Dr. LaFaver: I’m very excited about our topic. We’ll be talking about monoclonal antibody therapy against amyloid in Alzheimer’s disease – which has really been a hot topic, especially this year with the FDA approval of lecanemab – and associated questions. Could you give us a brief overview of why there has been so much research interest in this topic of anti-amyloid antibodies?

Dr. Wicklund: The pathologic component of what defines something as Alzheimer’s disease is, by definition, presence of amyloid plaques and tau tangles. When it was first discovered in the 1980s that the component of the plaques was actually the amyloid protein – beta amyloid specifically – interest went right from there to developing therapies to directly target the pathology that is Alzheimer’s disease.

Dr. LaFaver: Lecanemab is the first FDA-approved disease-modifying antibody in that realm. Could you review the study data, especially as it applies to both of us in daily neurology clinic?

Dr. Wicklund: The study data from a phase 3 trial did show, for the primary outcome, that there was a 27% slowing of decline compared with individuals on placebo. It’s important to point out that this was slowing of decline. It was not stabilizing decline. It was not improving decline.

I think it’s important that we inform our patients that really, even with this therapy, there’s no prospect of stabilizing or restoring cognition or function. We do progress at a slower rate compared with individuals not on this treatment, which, given that this medication is for individuals in mild disease who have relatively preserved functional status, that can be potentially very meaningful to families.

The overall benefit was small. It essentially amounts to half a point on an 18-point scale, which is statistically significant. How much clinical meaningfulness that actually leads to is unclear. Finding clinical meaningfulness cannot be defined by a particular test. It really can only be defined on the individual level, what is meaningful to them.
 

Recommended tests

Dr. LaFaver: It is my understanding that, to qualify for lecanemab use, one needs to have a biomarker-supported diagnosis of Alzheimer’s disease, either via an amyloid PET scan or CSF biomarkers. What would your recommendation be for a neurologist in practice to go about these requirements?

Dr. Wicklund: Since this medication is directly targeting the amyloid pathology, and it does convey a potential risk, we want to make sure that the actual pathology is present in the individuals before we treat them and potentially expose them to risk. The best way of doing that is through either an amyloid PET scan or spinal fluid testing of beta amyloid and tau.

There are several plasma-based biomarkers in development. However, I would avoid using those currently. There are still many unknowns in terms of what exactly is the right species of tau that we should be looking at, the right mechanism of the lab test, how minority status may influence it, and how different comorbidities may influence it.

I would recommend, at this time, sticking with amyloid PET or CSF testing. Given that amyloid PET is not widely available in many community practices, generally only available at academic centers, and is quite costly, many insurances do not cover it – although Medicare has a proposal to potentially start covering it – I generally go with spinal fluid testing, which is more widely available. There are several labs across the country that can process that testing in a reliable way.
 

Amyloid-related imaging abnormalities

Dr. LaFaver: That’s very helpful to know. There’s been a large amount of buzz just these past couple of weeks about the blood biomarker coming up. I think, as you point out, this wasn’t the marker used in the clinical studies and there are still unknowns. Maybe it’s not quite time for clinical use, unfortunately.

We also have learned that there are significant potential risks involved. One issue that’s really been a focus is ARIA – amyloid-related imaging abnormalities. Could you speak a bit about that and requirements for monitoring?

Dr. Wicklund: ARIA essentially amounts to either vasogenic edema, microhemorrhages, or superficial siderosis that develops as a result of treatment. It relates to activation of the immune system with these passive monoclonal antibodies that’s going to occur with targeting against the plaques. In the parenchyma, it will cause edema. If you have amyloid in the walls of the blood vessels, it can cause microhemorrhages.

While the term “ARIA” implies an imaging-related abnormality, and it largely is purely an imaging finding, it’s not solely an imaging-related finding. It can cause symptoms, including very serious symptoms.

Overall, with lecanemab, the incidence of ARIA within the treatment group in the phase 3 study, combined between both ARIA-E (edema/effusion) and ARIA-H (hemorrhage), was 21.5%, with about 17% being ARIA-H and about 12.5% being ARIA-E. Of course, they can occur at the same time.

Overall, in terms of people in the clinical trials, for most it was purely an imaging-related finding. About 3% developed symptomatic ARIA. Some of those were very serious symptoms, including things like seizures and need to be hospitalized. A couple of deaths have been attributed to ARIA as well.

Patients on anticoagulation

Dr. LaFaver: Along those lines, any additional words to say for people who might be on anticoagulation or might require medications for a stroke, for example?

Dr. Wicklund: While individuals on anticoagulation were allowed in the clinical trials, the current, published appropriate-use guideline is recommending against its use, as several of the serious adverse effects, including the deaths, were for the most part attributed to anticoagulation use.

When it comes to acute stroke treatment, one must carefully consider use of tPA, as two of the three deaths were tPA associated in the clinical trials. It shouldn’t necessarily be an absolute contraindication, but it can make the clinical picture very muddy. If an individual is on lecanemab and comes to the ER with acute stroke-like symptoms, it’s more likely that they’re going to be having an ARIA side effect rather than an acute stroke.

A general recommendation would be to obtain an acute head CT with a CTA, and if there is a large vessel occlusion, proceed to thrombectomy. However, if there isn’t a large vessel occlusion, if you have the ability to get a rapid MRI with diffusion-weighted imaging to screen for acute stroke changes or tissue flair with acute edema changes suggestive of ARIA, that would be preferred before proceeding with thrombolysis. These are all relative contraindications and are going to depend on what’s available near you.
 

Donanemab approval pending

Dr. LaFaver: This will be an issue because the population we’re talking about is definitely at risk for stroke as well as Alzheimer’s disease. Where do you see this field going as far as amyloid antibody therapy is concerned, with another agent, donanemab, possibly getting FDA approval later this year as well?

Dr. Wicklund: We’re anticipating that donanemab will get FDA approval in the next coming months. Donanemab also targets the amyloid in the brain, although lecanemab and donanemab target different aspects of the production of the amyloid plaque. They were both shown to have roughly equal efficacy in their phase 3 clinical trials. Donanemab has the benefit of being a once-monthly infusion as opposed to twice-monthly infusions with lecanemab. It does have a slightly higher risk for ARIA compared with lecanemab.

Those are just some things to take into consideration when talking with your patients. In terms of where we’re going from here, we’re moving even earlier in terms of disease state. The lecanemab and donanemab phase 3 trials were done in individuals with mild cognitive impairment or mild dementia due to Alzheimer’s disease. They should not be used in individuals with moderate or more advanced Alzheimer’s disease.

There are ongoing, large, national, multicenter clinical trials of both lecanemab and donanemab in a preclinical state of Alzheimer’s disease. These individuals have evidence of amyloidosis, either through PET imaging or through CSF, but are clinically asymptomatic and do not yet have any signs of cognitive impairment or functional decline. We look forward to those results in the next few years. Hopefully, they’ll be able to show even greater benefit when moving into these early disease states in terms of delaying or even preventing cognitive decline.

Dr. LaFaver: That’s definitely very interesting to hear about. Where can people go for more information?

Dr. Wicklund: There’s a guideline on the use of lecanemab through the American Academy of Neurology. I encourage you to look at that. Also, look at the appropriate-use recommendations that were published this year in The Journal of Prevention of Alzheimer’s Disease.

Dr. LaFaver: Wonderful. With that being said, thank you so much for talking to me. I learned a lot. Thanks, everyone, for listening.
 

Dr. LaFaver is a neurologist at Saratoga Hospital Medical Group, Saratoga Springs, N.Y. She disclosed having no relevant financial relationships. Dr. Wicklund is senior associate consultant in the department of Neurology at Mayo Clinic, Phoenix, Ariz. She disclosed having no relevant financial relationships.

A version of this article appeared on Medscape.com.

Recorded October 13, 2023. This transcript has been edited for clarity.

Kathrin LaFaver, MD: I’ll be talking today with Dr. Meredith Wicklund, senior associate consultant and behavioral neurologist specialist at Mayo Clinic in Arizona. Welcome, Meredith.

Meredith Wicklund, MD: Thank you.
 

Lecanemab data

Dr. LaFaver: I’m very excited about our topic. We’ll be talking about monoclonal antibody therapy against amyloid in Alzheimer’s disease – which has really been a hot topic, especially this year with the FDA approval of lecanemab – and associated questions. Could you give us a brief overview of why there has been so much research interest in this topic of anti-amyloid antibodies?

Dr. Wicklund: The pathologic component of what defines something as Alzheimer’s disease is, by definition, presence of amyloid plaques and tau tangles. When it was first discovered in the 1980s that the component of the plaques was actually the amyloid protein – beta amyloid specifically – interest went right from there to developing therapies to directly target the pathology that is Alzheimer’s disease.

Dr. LaFaver: Lecanemab is the first FDA-approved disease-modifying antibody in that realm. Could you review the study data, especially as it applies to both of us in daily neurology clinic?

Dr. Wicklund: The study data from a phase 3 trial did show, for the primary outcome, that there was a 27% slowing of decline compared with individuals on placebo. It’s important to point out that this was slowing of decline. It was not stabilizing decline. It was not improving decline.

I think it’s important that we inform our patients that really, even with this therapy, there’s no prospect of stabilizing or restoring cognition or function. We do progress at a slower rate compared with individuals not on this treatment, which, given that this medication is for individuals in mild disease who have relatively preserved functional status, that can be potentially very meaningful to families.

The overall benefit was small. It essentially amounts to half a point on an 18-point scale, which is statistically significant. How much clinical meaningfulness that actually leads to is unclear. Finding clinical meaningfulness cannot be defined by a particular test. It really can only be defined on the individual level, what is meaningful to them.
 

Recommended tests

Dr. LaFaver: It is my understanding that, to qualify for lecanemab use, one needs to have a biomarker-supported diagnosis of Alzheimer’s disease, either via an amyloid PET scan or CSF biomarkers. What would your recommendation be for a neurologist in practice to go about these requirements?

Dr. Wicklund: Since this medication is directly targeting the amyloid pathology, and it does convey a potential risk, we want to make sure that the actual pathology is present in the individuals before we treat them and potentially expose them to risk. The best way of doing that is through either an amyloid PET scan or spinal fluid testing of beta amyloid and tau.

There are several plasma-based biomarkers in development. However, I would avoid using those currently. There are still many unknowns in terms of what exactly is the right species of tau that we should be looking at, the right mechanism of the lab test, how minority status may influence it, and how different comorbidities may influence it.

I would recommend, at this time, sticking with amyloid PET or CSF testing. Given that amyloid PET is not widely available in many community practices, generally only available at academic centers, and is quite costly, many insurances do not cover it – although Medicare has a proposal to potentially start covering it – I generally go with spinal fluid testing, which is more widely available. There are several labs across the country that can process that testing in a reliable way.
 

Amyloid-related imaging abnormalities

Dr. LaFaver: That’s very helpful to know. There’s been a large amount of buzz just these past couple of weeks about the blood biomarker coming up. I think, as you point out, this wasn’t the marker used in the clinical studies and there are still unknowns. Maybe it’s not quite time for clinical use, unfortunately.

We also have learned that there are significant potential risks involved. One issue that’s really been a focus is ARIA – amyloid-related imaging abnormalities. Could you speak a bit about that and requirements for monitoring?

Dr. Wicklund: ARIA essentially amounts to either vasogenic edema, microhemorrhages, or superficial siderosis that develops as a result of treatment. It relates to activation of the immune system with these passive monoclonal antibodies that’s going to occur with targeting against the plaques. In the parenchyma, it will cause edema. If you have amyloid in the walls of the blood vessels, it can cause microhemorrhages.

While the term “ARIA” implies an imaging-related abnormality, and it largely is purely an imaging finding, it’s not solely an imaging-related finding. It can cause symptoms, including very serious symptoms.

Overall, with lecanemab, the incidence of ARIA within the treatment group in the phase 3 study, combined between both ARIA-E (edema/effusion) and ARIA-H (hemorrhage), was 21.5%, with about 17% being ARIA-H and about 12.5% being ARIA-E. Of course, they can occur at the same time.

Overall, in terms of people in the clinical trials, for most it was purely an imaging-related finding. About 3% developed symptomatic ARIA. Some of those were very serious symptoms, including things like seizures and need to be hospitalized. A couple of deaths have been attributed to ARIA as well.

Patients on anticoagulation

Dr. LaFaver: Along those lines, any additional words to say for people who might be on anticoagulation or might require medications for a stroke, for example?

Dr. Wicklund: While individuals on anticoagulation were allowed in the clinical trials, the current, published appropriate-use guideline is recommending against its use, as several of the serious adverse effects, including the deaths, were for the most part attributed to anticoagulation use.

When it comes to acute stroke treatment, one must carefully consider use of tPA, as two of the three deaths were tPA associated in the clinical trials. It shouldn’t necessarily be an absolute contraindication, but it can make the clinical picture very muddy. If an individual is on lecanemab and comes to the ER with acute stroke-like symptoms, it’s more likely that they’re going to be having an ARIA side effect rather than an acute stroke.

A general recommendation would be to obtain an acute head CT with a CTA, and if there is a large vessel occlusion, proceed to thrombectomy. However, if there isn’t a large vessel occlusion, if you have the ability to get a rapid MRI with diffusion-weighted imaging to screen for acute stroke changes or tissue flair with acute edema changes suggestive of ARIA, that would be preferred before proceeding with thrombolysis. These are all relative contraindications and are going to depend on what’s available near you.
 

Donanemab approval pending

Dr. LaFaver: This will be an issue because the population we’re talking about is definitely at risk for stroke as well as Alzheimer’s disease. Where do you see this field going as far as amyloid antibody therapy is concerned, with another agent, donanemab, possibly getting FDA approval later this year as well?

Dr. Wicklund: We’re anticipating that donanemab will get FDA approval in the next coming months. Donanemab also targets the amyloid in the brain, although lecanemab and donanemab target different aspects of the production of the amyloid plaque. They were both shown to have roughly equal efficacy in their phase 3 clinical trials. Donanemab has the benefit of being a once-monthly infusion as opposed to twice-monthly infusions with lecanemab. It does have a slightly higher risk for ARIA compared with lecanemab.

Those are just some things to take into consideration when talking with your patients. In terms of where we’re going from here, we’re moving even earlier in terms of disease state. The lecanemab and donanemab phase 3 trials were done in individuals with mild cognitive impairment or mild dementia due to Alzheimer’s disease. They should not be used in individuals with moderate or more advanced Alzheimer’s disease.

There are ongoing, large, national, multicenter clinical trials of both lecanemab and donanemab in a preclinical state of Alzheimer’s disease. These individuals have evidence of amyloidosis, either through PET imaging or through CSF, but are clinically asymptomatic and do not yet have any signs of cognitive impairment or functional decline. We look forward to those results in the next few years. Hopefully, they’ll be able to show even greater benefit when moving into these early disease states in terms of delaying or even preventing cognitive decline.

Dr. LaFaver: That’s definitely very interesting to hear about. Where can people go for more information?

Dr. Wicklund: There’s a guideline on the use of lecanemab through the American Academy of Neurology. I encourage you to look at that. Also, look at the appropriate-use recommendations that were published this year in The Journal of Prevention of Alzheimer’s Disease.

Dr. LaFaver: Wonderful. With that being said, thank you so much for talking to me. I learned a lot. Thanks, everyone, for listening.
 

Dr. LaFaver is a neurologist at Saratoga Hospital Medical Group, Saratoga Springs, N.Y. She disclosed having no relevant financial relationships. Dr. Wicklund is senior associate consultant in the department of Neurology at Mayo Clinic, Phoenix, Ariz. She disclosed having no relevant financial relationships.

A version of this article appeared on Medscape.com.

Recorded October 13, 2023. This transcript has been edited for clarity.

Kathrin LaFaver, MD: I’ll be talking today with Dr. Meredith Wicklund, senior associate consultant and behavioral neurologist specialist at Mayo Clinic in Arizona. Welcome, Meredith.

Meredith Wicklund, MD: Thank you.
 

Lecanemab data

Dr. LaFaver: I’m very excited about our topic. We’ll be talking about monoclonal antibody therapy against amyloid in Alzheimer’s disease – which has really been a hot topic, especially this year with the FDA approval of lecanemab – and associated questions. Could you give us a brief overview of why there has been so much research interest in this topic of anti-amyloid antibodies?

Dr. Wicklund: The pathologic component of what defines something as Alzheimer’s disease is, by definition, presence of amyloid plaques and tau tangles. When it was first discovered in the 1980s that the component of the plaques was actually the amyloid protein – beta amyloid specifically – interest went right from there to developing therapies to directly target the pathology that is Alzheimer’s disease.

Dr. LaFaver: Lecanemab is the first FDA-approved disease-modifying antibody in that realm. Could you review the study data, especially as it applies to both of us in daily neurology clinic?

Dr. Wicklund: The study data from a phase 3 trial did show, for the primary outcome, that there was a 27% slowing of decline compared with individuals on placebo. It’s important to point out that this was slowing of decline. It was not stabilizing decline. It was not improving decline.

I think it’s important that we inform our patients that really, even with this therapy, there’s no prospect of stabilizing or restoring cognition or function. We do progress at a slower rate compared with individuals not on this treatment, which, given that this medication is for individuals in mild disease who have relatively preserved functional status, that can be potentially very meaningful to families.

The overall benefit was small. It essentially amounts to half a point on an 18-point scale, which is statistically significant. How much clinical meaningfulness that actually leads to is unclear. Finding clinical meaningfulness cannot be defined by a particular test. It really can only be defined on the individual level, what is meaningful to them.
 

Recommended tests

Dr. LaFaver: It is my understanding that, to qualify for lecanemab use, one needs to have a biomarker-supported diagnosis of Alzheimer’s disease, either via an amyloid PET scan or CSF biomarkers. What would your recommendation be for a neurologist in practice to go about these requirements?

Dr. Wicklund: Since this medication is directly targeting the amyloid pathology, and it does convey a potential risk, we want to make sure that the actual pathology is present in the individuals before we treat them and potentially expose them to risk. The best way of doing that is through either an amyloid PET scan or spinal fluid testing of beta amyloid and tau.

There are several plasma-based biomarkers in development. However, I would avoid using those currently. There are still many unknowns in terms of what exactly is the right species of tau that we should be looking at, the right mechanism of the lab test, how minority status may influence it, and how different comorbidities may influence it.

I would recommend, at this time, sticking with amyloid PET or CSF testing. Given that amyloid PET is not widely available in many community practices, generally only available at academic centers, and is quite costly, many insurances do not cover it – although Medicare has a proposal to potentially start covering it – I generally go with spinal fluid testing, which is more widely available. There are several labs across the country that can process that testing in a reliable way.
 

Amyloid-related imaging abnormalities

Dr. LaFaver: That’s very helpful to know. There’s been a large amount of buzz just these past couple of weeks about the blood biomarker coming up. I think, as you point out, this wasn’t the marker used in the clinical studies and there are still unknowns. Maybe it’s not quite time for clinical use, unfortunately.

We also have learned that there are significant potential risks involved. One issue that’s really been a focus is ARIA – amyloid-related imaging abnormalities. Could you speak a bit about that and requirements for monitoring?

Dr. Wicklund: ARIA essentially amounts to either vasogenic edema, microhemorrhages, or superficial siderosis that develops as a result of treatment. It relates to activation of the immune system with these passive monoclonal antibodies that’s going to occur with targeting against the plaques. In the parenchyma, it will cause edema. If you have amyloid in the walls of the blood vessels, it can cause microhemorrhages.

While the term “ARIA” implies an imaging-related abnormality, and it largely is purely an imaging finding, it’s not solely an imaging-related finding. It can cause symptoms, including very serious symptoms.

Overall, with lecanemab, the incidence of ARIA within the treatment group in the phase 3 study, combined between both ARIA-E (edema/effusion) and ARIA-H (hemorrhage), was 21.5%, with about 17% being ARIA-H and about 12.5% being ARIA-E. Of course, they can occur at the same time.

Overall, in terms of people in the clinical trials, for most it was purely an imaging-related finding. About 3% developed symptomatic ARIA. Some of those were very serious symptoms, including things like seizures and need to be hospitalized. A couple of deaths have been attributed to ARIA as well.

Patients on anticoagulation

Dr. LaFaver: Along those lines, any additional words to say for people who might be on anticoagulation or might require medications for a stroke, for example?

Dr. Wicklund: While individuals on anticoagulation were allowed in the clinical trials, the current, published appropriate-use guideline is recommending against its use, as several of the serious adverse effects, including the deaths, were for the most part attributed to anticoagulation use.

When it comes to acute stroke treatment, one must carefully consider use of tPA, as two of the three deaths were tPA associated in the clinical trials. It shouldn’t necessarily be an absolute contraindication, but it can make the clinical picture very muddy. If an individual is on lecanemab and comes to the ER with acute stroke-like symptoms, it’s more likely that they’re going to be having an ARIA side effect rather than an acute stroke.

A general recommendation would be to obtain an acute head CT with a CTA, and if there is a large vessel occlusion, proceed to thrombectomy. However, if there isn’t a large vessel occlusion, if you have the ability to get a rapid MRI with diffusion-weighted imaging to screen for acute stroke changes or tissue flair with acute edema changes suggestive of ARIA, that would be preferred before proceeding with thrombolysis. These are all relative contraindications and are going to depend on what’s available near you.
 

Donanemab approval pending

Dr. LaFaver: This will be an issue because the population we’re talking about is definitely at risk for stroke as well as Alzheimer’s disease. Where do you see this field going as far as amyloid antibody therapy is concerned, with another agent, donanemab, possibly getting FDA approval later this year as well?

Dr. Wicklund: We’re anticipating that donanemab will get FDA approval in the next coming months. Donanemab also targets the amyloid in the brain, although lecanemab and donanemab target different aspects of the production of the amyloid plaque. They were both shown to have roughly equal efficacy in their phase 3 clinical trials. Donanemab has the benefit of being a once-monthly infusion as opposed to twice-monthly infusions with lecanemab. It does have a slightly higher risk for ARIA compared with lecanemab.

Those are just some things to take into consideration when talking with your patients. In terms of where we’re going from here, we’re moving even earlier in terms of disease state. The lecanemab and donanemab phase 3 trials were done in individuals with mild cognitive impairment or mild dementia due to Alzheimer’s disease. They should not be used in individuals with moderate or more advanced Alzheimer’s disease.

There are ongoing, large, national, multicenter clinical trials of both lecanemab and donanemab in a preclinical state of Alzheimer’s disease. These individuals have evidence of amyloidosis, either through PET imaging or through CSF, but are clinically asymptomatic and do not yet have any signs of cognitive impairment or functional decline. We look forward to those results in the next few years. Hopefully, they’ll be able to show even greater benefit when moving into these early disease states in terms of delaying or even preventing cognitive decline.

Dr. LaFaver: That’s definitely very interesting to hear about. Where can people go for more information?

Dr. Wicklund: There’s a guideline on the use of lecanemab through the American Academy of Neurology. I encourage you to look at that. Also, look at the appropriate-use recommendations that were published this year in The Journal of Prevention of Alzheimer’s Disease.

Dr. LaFaver: Wonderful. With that being said, thank you so much for talking to me. I learned a lot. Thanks, everyone, for listening.
 

Dr. LaFaver is a neurologist at Saratoga Hospital Medical Group, Saratoga Springs, N.Y. She disclosed having no relevant financial relationships. Dr. Wicklund is senior associate consultant in the department of Neurology at Mayo Clinic, Phoenix, Ariz. She disclosed having no relevant financial relationships.

A version of this article appeared on Medscape.com.