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We examined whether lifelong CR accumulation is associated with disability\u2010free survival and explored the extent to which cognitive function mediates this association.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Within the Rush Memory and Aging Project, 1633 dementia\u2010 and disability\u2010free participants were followed annually for up to 22 years. Lifelong CR including education, early\u2010\/mid\u2010\/late\u2010life cognitive activities, and late\u2010life social activity was assessed and tertiled.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>CR score was dose\u2010dependently associated with disability\/death (hazard ratio [HR] 0.96, 95% confidence interval [CI] 0.93\u20130.99). Compared to low CR, the HR (95% CI) of disability\/death was 0.82 (0.70\u20130.95) for high CR. The median disability\u2010free survival time was prolonged by 0.99 (95% CI 0.28\u20131.71) years for participants with high CR. Cognitive function mediated 35.7% of the association between CR and disability\u2010free survival.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>High lifelong CR was associated with prolonged disability\u2010free survival. Cognitive function mediates about one\u2010third of this association. Our findings underscore the importance of CR for healthy aging.<\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.12670","type":"journal-article","created":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T02:23:52Z","timestamp":1648520632000},"page":"208-216","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["High lifelong cognitive reserve prolongs disability\u2010free survival: The role of cognitive function"],"prefix":"10.1002","volume":"19","author":[{"given":"Xuerui","family":"Li","sequence":"first","affiliation":[{"name":"Department of Epidemiology and Biostatistics School of Public Health Tianjin Medical University  Tianjin China"},{"name":"Tianjin Key Laboratory of Environment, Nutrition and Public Health  Tianjin China"},{"name":"Center for International Collaborative Research on Environment Nutrition and Public Health  Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenzhe","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics School of Public Health Tianjin Medical University  Tianjin China"},{"name":"Tianjin Key Laboratory of Environment, Nutrition and Public Health  Tianjin China"},{"name":"Center for International Collaborative Research on Environment Nutrition and Public Health  Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics School of Public Health Tianjin Medical University  Tianjin China"},{"name":"Tianjin Key Laboratory of Environment, Nutrition and Public Health  Tianjin China"},{"name":"Center for International Collaborative Research on Environment Nutrition and Public Health  Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abigail","family":"Dove","sequence":"additional","affiliation":[{"name":"Aging Research Center, Department of Neurobiology, Care Sciences and Society Karolinska Institutet  Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiuying","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics School of Public Health Tianjin Medical University  Tianjin China"},{"name":"Tianjin Key Laboratory of Environment, Nutrition and Public Health  Tianjin China"},{"name":"Center for International Collaborative Research on Environment Nutrition and Public Health  Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A.","family":"Bennett","sequence":"additional","affiliation":[{"name":"Rush Alzheimer's Disease Center Rush University Medical Center  Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weili","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics School of Public Health Tianjin Medical University  Tianjin China"},{"name":"Tianjin Key Laboratory of Environment, Nutrition and Public Health  Tianjin China"},{"name":"Center for International Collaborative Research on Environment Nutrition and Public Health  Tianjin China"},{"name":"Aging Research Center, Department of Neurobiology, Care Sciences and Society Karolinska Institutet  Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,3,28]]},"reference":[{"key":"e_1_2_8_2_1","unstructured":"NationsU.World population ageing 2020 highlights. 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