Healthy lifestyle, brain pathology, and cognition in community‐dwelling older adults

Abstract

AbstractBackgroundLifestyle interventions for primary prevention of Alzheimer’s dementia recruit people at advanced ages who are at high risk of cognitive decline in the timeline of the trial. Given that Alzheimer’s disease and other dementia‐causing pathologies may accumulate in the brain years or even decades before older adults begin to show cognitive deficits, it is important to determine the association of lifestyle factors, cognition, and the role of dementia‐related brain pathologies.MethodUtilizing data from the Rush Memory and Aging Project, a longitudinal clinical‐pathologic study, we studied 566 decedents with lifestyle, cognitive testing proximate to death, and complete autopsy data at the time of these analyses. A healthy lifestyle score included being a non‐smoker, ≥150 min/week moderate/vigorous‐intensity physical activity, light‐to‐moderate alcohol consumption, MIND diet score >7.5, and late‐life cognitive activity score >3.2. Brain pathology included measures of beta‐amyloid, neuronal neurofibrillary tangles, Lewy body disease, hippocampal sclerosis, TDP‐43, cerebral infarcts, cerebral amyloid angiopathy, and arteriolosclerosis and atherosclerotic disease. The global cognitive score was derived from a comprehensive battery of nineteen standardized tests.ResultA higher healthy lifestyle score was associated with better global cognitive functioning proximate to death (beta=0.149, SE=0.036, p<0.001) and slower annual cognitive decline (beta=0.014 units/year, SE=0.004, p<0.001). A higher healthy lifestyle score was associated with less beta‐amyloid accumulation (beta=‐0.087, SE=0.041, p=0.034), but not with tangles, other neurodegenerative pathology, or indices of vascular pathology. Pathway analysis using structural equation modeling examined whether beta‐amyloid mediated the relationships between healthy lifestyle score and global cognition. Lifestyle score had a significant positive direct effect (beta=0.130, SE=0.035, p<0.001) on global cognition. The indirect effect of lifestyle score on cognition through the pathway of beta‐amyloid load was also significant but had a relatively small effect size (beta=0.019, SE=0.009, p=0.045)ConclusionA healthy lifestyle was associated with better cognitive functioning even after accounting for dementia‐related brain pathologies, suggesting that lifestyle intervention may have cognitive benefits. Moreover, given that beta‐amyloid accumulates years to decades prior to the onset of cognitive decline, the indirect effect of lifestyle on cognition through beta‐amyloid may indicate that a healthy lifestyle could additionally provide primary prevention of Alzheimer’s disease and dementia.