Do lifestyle factors affect late-life cognition and dementia pathology impact?


In a recent study published in the journal JAMA Neurology, scientists from the Rush University Medical Center in Chicago, United States, investigated whether brain pathology related to dementia, such as cerebrovascular pathology, phosphorylated tau fibril tangles, and β-amyloid accumulation, modify the association between healthy lifestyle choices and cognition during the later years in life.


Increasing research in the field of dementia and Alzheimer’s disease report that a shift towards healthy lifestyle choices can decrease the risk of these diseases, and approximately 40% of dementia cases across the world could theoretically be prevented if the global population makes significant changes towards a healthier lifestyle. Previous research by the same team of scientists has also reported that healthier lifestyles are associated not only with longer life expectancies but also with longer lives without Alzheimer’s disease.

Based on these findings, various clinical trials across the world are investigating the effectiveness of lifestyle alterations among middle-aged to older individuals in cognitive decline prevention. However, brain pathologies related to dementia, such as phosphorylated tau fibril tangles and β-amyloid load, are believed to accumulate with age well before the onset of dementia. Whether this age-associated accumulation of brain pathologies modifies the impact of healthy lifestyles in preventing dementia remains unknown.

About the study

In the present study, the researchers conducted a cohort study using autopsy data from a longitudinal study on clinical pathology, along with 24-year follow-up information such as neuropathologic evaluation, cognitive testing, and lifestyle factors such as cognitive and physical exercise, diet, smoking behavior, and alcohol intake.

They aimed to evaluate how these lifestyle factors were associated with cognitive abilities closer to death and whether postmortem findings on brain pathologies related to dementia influenced this association. Additionally, the role of vascular diseases such as arteriosclerosis, infarctions, and cerebral atherosclerosis in modifying the association between lifestyle factors and cognition was also explored.

The association between lifestyle choices and cognition in older adults was also evaluated while accounting for pathologies related to Alzheimer’s disease, as well as trans-activation response element (TAR) deoxyribonucleic acid (DNA) binding protein 43 (TDP-43), hippocampal sclerosis, and Lewy body.

Self-reported lifestyle factors such as current non-smoking behavior, meeting the recommended levels of exercise, limited consumption of alcohol, and higher than the stipulated cut-off scores for targeted diet to decrease the risk of cognitive decline and cognitive activity scores were used to develop a healthy lifestyle score.

The Mediterranean-Dietary Approaches to Stop Hypertension (DASH) Intervention for Neurodegenerative Delay (MIND) diet, as the name suggests, is a combination of the Mediterranean diet and the hypertension diet aimed at lowering the risk of dementia and cognitive decline. Food frequency questionnaires were used to assess dietary intake, while other structured questionnaires were used to evaluate cognitive and physical activity levels.

While the healthy lifestyle score was the exposure, the major measured outcome was the global cognitive score, which was calculated based on a battery of 19 standardized cognitive tests. Measures of brain pathology included the detection of phosphorylated tau fibril tangles, β-amyloid load, disease pathologies related to Alzheimer’s disease, vascular pathologies in the brain, hippocampal sclerosis, TDP-43, and Lewy body.


The results suggested that independent of brain pathologies related to Alzheimer’s disease or dementia, healthy lifestyles were associated with lower cognitive decline proximate to death. The inclusion of brain pathologies related to dementia in the multivariable models evaluating the association between healthy lifestyles and cognitive activity scores did not impact the significance or strength of the association.

Although the researchers concluded that the association between lifestyle factors and cognition is largely independent of brain pathologies related to Alzheimer’s disease or dementia, the findings did indicate a 12% influence of β-amyloid load. However, the researchers believe that while these results should be interpreted with caution, largely, the results support the positive influence of healthy lifestyle choices in improving cognitive abilities in older adults.

The study also found that lifestyle factors such as physical activity and diet are associated with lower cognitive decline independent of the influence of vascular disease. However, these findings could be a result of the study population consisting of substantially older adults, for whom vascular pathologies in the brain were a consequence of age.


Overall, the findings indicated that healthy lifestyle factors could contribute significantly to lowering age-associated cognitive decline in older adults, independent of neuropathologies related to dementia or Alzheimer’s disease.

Journal reference:

  • Dhana, K., Agarwal, P., James, B. D., Leurgans, S. E., Rajan, K. B., Aggarwal, N. T., Barnes, L. L., Bennett, D. A., & Schneider, J. A. (2024). Healthy Lifestyle and Cognition in Older Adults With Common Neuropathologies of Dementia. JAMA Neurology. doi:


Jose Reber

Jose Reber is a professional writer based in Wisconsin. He guides editorial teams consisting of writers across the US to help them become more skilled and diverse writers. In his free time he enjoys spending time with his wife and children.

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