Healthier Lifestyle Associated With Better Cognitive Function, Independent of Alzheimer Disease Pathology


Key Takeaways:

  1. Healthy Lifestyle Correlates and Stronger Cognition: The study highlights that adopting a healthier lifestyle— characterized by factors including diet quality, cognitive activities, physical exercise, and moderate alcohol consumption—is associated with better cognitive function prior to death, independent of Alzheimer disease pathology burden.
  2. Cognition and Lifestyle Association Independent from Brain Pathology: Despite the presence of Alzheimer disease-related brain pathologies, the association between lifestyle and cognitive function remained significant, indicating that lifestyle factors might contribute to cognitive reserve, enabling better cognitive performance despite potential neuropathological changes.
  3. Potential Mechanisms and Implications for Alzheimer Prevention: The findings suggest that lifestyle modifications may lower the risk of Alzheimer disease by reducing vascular disease burden, likely through antioxidant, anti-inflammatory effects, and cognitive reserve; however, further research is needed to understand the specific mechanisms and to establish causality between lifestyle factors and cognitive outcomes.

The prevention of Alzheimer disease through adjustments and modifications in lifestyle is a topic of interest among researchers, and it is estimated that approximately 40% of worldwide dementia could theoretically be prevented if individuals adapt a healthier lifestyle. Investigators of a study published in JAMA Neurology investigated the impact of lifestyle interventions on cognition in older adults as a preventative measure. Further, the authors specifically looked at individuals who had died and had an autopsy to evaluate whether lifestyle factors had an influence on cognition prior to death.

This cohort study utilized data from the Rush Memory and Aging Project (Rush MAP), a longitudinal clinical-pathologic study with autopsy data from 1997 to 2022 with up to 24 years of follow-up. The investigators analyzed 754 deceased individuals and their individual data on lifestyle factors, cognitive testing close to death, as well as a complete neuropathologic evaluation at the time of the analyses. Of the included 754 individuals, 586 had valid dietary and lifestyle data in addition to cognitive testing and complete autopsy data at the time of analyses. The authors also compared the participants demographics (eg, age, sex, and education) as well as genetic characteristics of MAP eligible for the study.

Dietary intake was assessed with a 144-item food frequency questionnaire (FFQ) in which participants reported their usual frequency of consumption of food items over the previous 12 months. Overall diet quality was calculated by a diet score that did not take alcohol intake into consideration. In addition to diet, cognitive activities were assessed using a questionnaire that measures participation in 7 cognitively stimulating activities within the previous year (eg, reading; visiting a museum; and playing cards, checkers, crosswords, or puzzles). Further, physical activity was assessed by a survey adapted specifically for older adults. Participants were to self-report the amount of time spent completing activities that were moderate to vigorous in intensity, and included walking, gardening or yard work, swimming, bike riding, and calisthenics. Finally, mean consumption of alcohol was obtained through self-reported surveys.

Using these factors, participants were categorized as low-risk or “healthy” if a participant was in the healthiest 40% of the total analyzed population (equivalent to a diet score higher than 7.5 and cognitive activities score higher than 3.20). Further, a healthy lifestyle score had also included the performance of moderate or vigorous activities for at least 150 minutes weekly, light to moderate alcohol consumption (up to 15 g/d for women and up to 30 g/d for men), as well as no smoking at the time of self-report.

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Once the patients were deceased, the brain was removed examined to determine cognition or the presence of Alzheimer disease. Procedures for quantifying β-amyloid deposition, phosphorylated tau tangles, neuritic and diffuse plaques, neurofibrillary tangles, and other pathologies were performed. Further, immunohistochemistry and staining techniques across specific brain regions were performed to generate composite measures of Alzheimer disease pathology as well as assess for related conditions (eg, atherosclerosis, Lewy body disease, and hippocampal sclerosis). Cognitive function was evaluated annually with 19 tests, and each score was standardized to the mean at baseline, of which a standardized cognitive score for the 19 tests was utilized to create a composite score for the overall global cognitive function. Positive scores demonstrated stronger cognitive performance, and negative scores indicated poor cognitive performance.

The analysis results indicated that a higher lifestyle score—or healthier lifestyle—was associated with better cognitive function prior to death. In addition, the lifestyle-cognition association was independent of Alzheimer disease pathology burden, indicating that strength of significance of the lifestyle-cognition association changed significantly when β-amyloid load, phosphorylated tau tangle, or other memory-related brain pathologies were included in the regression tool.

Further, the study determined that the correlation of lifestyle with cognition is independent of brain pathology, although approximately 12% was through β-amyloid. The authors note that this finding supports the role of lifestyle in providing cognitive reserve to maintain cognitive function in older adults despite the accumulation of common brain pathologies related to dementia. In addition, the investigators suggest that further research should analyze the role of duration and lifestyle changes during the study period and how that influences cognition, or if it is independent of pathology.

In addition, the analysis suggests that lifestyle may lower the risk of Alzheimer disease by reducing vascular disease burden. This supports prior findings, which demonstrated that both diet and physical activity are associated with cognitive abilities independently from vascular disease burden. The link between lifestyle and cognition, according to the study authors, may be a result of the antioxidant and anti-inflammatory capacities of each lifestyle factor (eg, nutrition and physical activity) as well as cognitive reserve (eg, cognition-based activities) that can contribute to reductions in inflammation and oxidative stress. The study authors note that further research on the specific associations of lifestyle factors and inflammatory markers in the brain are necessary to better understand the mechanisms of how lifestyle and cognitive scores prior to death are correlated.

Limitations of the study include the reliance on self-reported lifestyle factors which can lead to inaccurate results, the potential that cognitive abilities may impact the ability to adhere to certain lifestyle factors (eg, physical activity), and the limited demographics of the patient population. The study authors also emphasize that due to the observational design of the study, causality of reported associations cannot be assumed.


Dhana K, Agarwal P, James BD, et al. Healthy Lifestyle and Cognition in Older Adults With Common Neuropathologies of Dementia. JAMA Neurol. Published online February 05, 2024. doi:10.1001/jamaneurol.2023.5491


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