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. 2024 Mar 1;81(3):233-239.
doi: 10.1001/jamaneurol.2023.5491.

Healthy Lifestyle and Cognition in Older Adults With Common Neuropathologies of Dementia

Klodian Dhana  1   2 , Puja Agarwal  2   3 , Bryan D James  2   3 , Sue E Leurgans  3   4 , Kumar B Rajan  1   2 , Neelum T Aggarwal  3   4 , Lisa L Barnes  3   4 , David A Bennett  3   4 , Julie A Schneider  3   4   5
Affiliations

Healthy Lifestyle and Cognition in Older Adults With Common Neuropathologies of Dementia

Klodian Dhana et al. JAMA Neurol. .

Abstract

Importance: A healthy lifestyle is associated with better cognitive functioning in older adults, but whether this association is independent of the accumulation of dementia-related pathologies in the brain is uncertain.

Objective: To determine the role of postmortem brain pathology, including β-amyloid load, phosphorylated tau tangles, cerebrovascular pathology, and other brain pathologies, in the association between lifestyle and cognition proximate to death.

Design, setting, and participants: This cohort study used data from the Rush Memory and Aging Project, a longitudinal clinical-pathologic study with autopsy data from 1997 to 2022 and up to 24 years of follow-up. Participants included 754 deceased individuals with data on lifestyle factors, cognitive testing proximate to death, and a complete neuropathologic evaluation at the time of these analyses. Data were analyzed from January 2023 to June 2023.

Exposures: A healthy lifestyle score was developed based on self-reported factors, including noncurrent smoking, at least 150 minutes of physical activity per week, limiting alcohol consumption, a Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet score higher than 7.5, and a late-life cognitive activity score higher than 3.2. The lifestyle score ranges from 0 to 5, with higher scores reflecting a healthier lifestyle.

Main outcomes and measures: The global cognitive score was derived from a battery of nineteen standardized tests. Brain pathology measures included β-amyloid load, phosphorylated tau tangles, global Alzheimer disease pathology, vascular brain pathologies, Lewy body, hippocampal sclerosis, and TAR DNA-binding protein 43.

Results: Of 586 included decedents, 415 (70.8%) were female, 171 (29.2%) were male, and the mean (SD) age at death was 90.9 (6.0) years. Higher lifestyle score was associated with better global cognitive functioning proximate to death. In the multivariable-adjusted model, a 1-point increase in lifestyle score was associated with 0.216 (SE = 0.036, P < .001) units higher in global cognitive scores. Neither the strength nor the significance of the association changed substantially when common dementia-related brain pathologies were included in the multivariable-adjusted models. The β estimate after controlling for the β-amyloid load was 0.191 (SE = 0.035; P < .001). A higher lifestyle score was associated with lower β-amyloid load in the brain (β = -0.120; SE = 0.041; P = .003), and 11.6% of the lifestyle-cognition association was estimated through β-amyloid load.

Conclusions and relevance: This study found that in older adults, a healthy lifestyle may provide a cognitive reserve to maintain cognitive abilities independently of common neuropathologies of dementia.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Dhana reported grants paid to their institution from the Alzheimer’s Association outside the submitted work. Dr Agarwal reported grants from the Alzheimer’s Association and Michael J. Fox Foundation for Parkinson’s Research outside the submitted work. Dr James reported drafting a report for the Alzheimer’s Association and serving on a drug advisory committee for Eisai outside the submitted work. Dr Barnes reported serving as deputy editor for Alzheimer’s and Dementia outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Interaction Between Common Alzheimer Disease (AD) Brain Pathologies and Lifestyle Score in Association With Global Cognitive Function Proximate to Death
β-Amyloid load, phosphorylated tau tangle, and global AD pathology were square root–transformed. Models A, B, and C included an interaction term between lifestyle score and brain pathology (eg, β-amyloid load) and were adjusted for age at death, sex, education, APOE e4, and time intervals from the last assessment to death (in years) and from death to autopsy (in hours). Shading indicates SD. P > .30 for interactions for each of the studied pathologies. One individual did not have data on phosphorylated tau tangle, so the statistical model with phosphorylated tau tangle (B) included 585 individuals.
Figure 2.
Figure 2.. Pathway Analysis Using Structural Equation Modeling to Determine the Direct and Indirect Associations of Lifestyle Score With Global Cognition
Models A, B, and C were adjusted by age at death, sex, education, APOE e4, and time intervals from the last assessment to death (in years) and from death to autopsy (in hours). β-Amyloid load was square root–transformed. Of the association between lifestyle score and global cognition proximate to death, 11.6% (indirect ÷ total = 0.025 ÷ 0.216) was through the β-amyloid pathway. The direct effect was 88.4% (direct ÷ total = 0.191 ÷ 0.216).
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