{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:17:04Z","timestamp":1792790224709,"version":"4.5.0"},"reference-count":31,"publisher":"American Medical Association (AMA)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Neurol"],"published-print":{"date-parts":[[2024,3,1]]},"abstract":"Importance<\/jats:title>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.<\/jats:p><\/jats:sec>Objective<\/jats:title>To determine the role of postmortem brain pathology, including \u03b2-amyloid load, phosphorylated tau tangles, cerebrovascular pathology, and other brain pathologies, in the association between lifestyle and cognition proximate to death.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>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.<\/jats:p><\/jats:sec>Exposures<\/jats:title>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.<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>The global cognitive score was derived from a battery of nineteen standardized tests. Brain pathology measures included \u03b2-amyloid load, phosphorylated tau tangles, global Alzheimer disease pathology, vascular brain pathologies, Lewy body, hippocampal sclerosis, and TAR DNA-binding protein 43.<\/jats:p><\/jats:sec>Results<\/jats:title>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\u2009=\u20090.036,P<\/jats:italic>\u2009&amp;lt;\u2009.001) 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 \u03b2 estimate after controlling for the \u03b2-amyloid load was 0.191 (SE\u2009=\u20090.035;P<\/jats:italic>\u2009&amp;lt;\u2009.001). A higher lifestyle score was associated with lower \u03b2-amyloid load in the brain (\u03b2\u2009=\u2009\u22120.120; SE\u2009=\u20090.041;P<\/jats:italic>\u2009=\u2009.003), and 11.6% of the lifestyle-cognition association was estimated through \u03b2-amyloid load.<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>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.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamaneurol.2023.5491","type":"journal-article","created":{"date-parts":[[2024,2,5]],"date-time":"2024-02-05T16:01:09Z","timestamp":1707148869000},"page":"233","source":"Crossref","is-referenced-by-count":60,"title":["Healthy Lifestyle and Cognition in Older Adults With Common Neuropathologies of Dementia"],"prefix":"10.1001","volume":"81","author":[{"given":"Klodian","family":"Dhana","sequence":"first","affiliation":[{"name":"Rush Institute for Healthy 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Illinois"},{"name":"Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Bennett","sequence":"additional","affiliation":[{"name":"Rush Alzheimer\u2019s Disease Center, Rush University Medical Center, Chicago, Illinois"},{"name":"Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie A.","family":"Schneider","sequence":"additional","affiliation":[{"name":"Rush Alzheimer\u2019s Disease Center, Rush University Medical Center, Chicago, Illinois"},{"name":"Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois"},{"name":"Department of Pathology, Rush University Medical Center, Chicago, 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