{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T06:52:24Z","timestamp":1789627944599,"version":"build-2803163510"},"reference-count":56,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2020,11,5]],"date-time":"2020-11-05T00:00:00Z","timestamp":1604534400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Even though there is a clear link between Alzheimer\u2019s Disease (AD) related neuropathology and cognitive decline, numerous studies have observed that healthy cognition can exist in the presence of extensive AD pathology, a phenomenon sometimes called Cognitive Resilience (CR). To better understand and study CR, we develop the Alzheimer\u2019s Disease Cognitive Resilience Score (AD-CR Score), which we define as the difference between the observed and expected cognition given the observed level of AD pathology. Unlike other definitions of CR, our AD-CR Score is a fully non-parametric, stand-alone, individual-level quantification of CR that is derived independently of other factors or proxy variables. Using data from two ongoing, longitudinal cohort studies of aging, the Religious Orders Study (ROS) and the Rush Memory and Aging Project (MAP), we validate our AD-CR Score by showing strong associations with known factors related to CR such as baseline and longitudinal cognition, non AD-related pathology, education, personality, APOE, parkinsonism, depression, and life activities. Even though the proposed AD-CR Score cannot be directly calculated during an individual\u2019s lifetime because it uses postmortem pathology, we also develop a machine learning framework that achieves promising results in terms of predicting whether an individual will have an extremely high or low AD-CR Score using only measures available during the lifetime. Given this, our AD-CR Score can be used for further investigations into mechanisms of CR, and potentially for subject stratification prior to clinical trials of personalized therapies.<\/jats:p>","DOI":"10.1371\/journal.pone.0241707","type":"journal-article","created":{"date-parts":[[2020,11,5]],"date-time":"2020-11-05T18:30:00Z","timestamp":1604601000000},"page":"e0241707","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":25,"title":["Quantifying cognitive resilience in Alzheimer\u2019s Disease: The Alzheimer\u2019s Disease Cognitive Resilience Score"],"prefix":"10.1371","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8380-2866","authenticated-orcid":true,"given":"Tianyi","family":"Yao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Sweeney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Nagorski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua M.","family":"Shulman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genevera I.","family":"Allen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2020,11,5]]},"reference":[{"issue":"8","key":"pone.0241707.ref001","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1016\/S1474-4422(07)70178-3","article-title":"Research criteria for the diagnosis of Alzheimer\u2019s disease: revising the NINCDS\u2013ADRDA criteria","volume":"6","author":"B Dubois","year":"2007","journal-title":"The Lancet Neurology"},{"issue":"4","key":"pone.0241707.ref002","doi-asserted-by":"crossref","first-page":"336","DOI":"10.2174\/156720511795745302","article-title":"Cognition and neuropathology in aging: multidimensional perspectives from the Rush Religious Orders Study and Rush Memory and Aging Project","volume":"8","author":"S Negash","year":"2011","journal-title":"Current Alzheimer Research"},{"issue":"3","key":"pone.0241707.ref003","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1002\/ana.23964","article-title":"Much of late life cognitive decline is not due to common neurodegenerative pathologies","volume":"74","author":"PA Boyle","year":"2013","journal-title":"Annals of neurology"},{"issue":"12","key":"pone.0241707.ref004","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1212\/01.wnl.0000219668.47116.e6","article-title":"Neuropathology of older persons without cognitive impairment from two community-based studies","volume":"66","author":"DA Bennett","year":"2006","journal-title":"Neurology"},{"issue":"3","key":"pone.0241707.ref005","doi-asserted-by":"crossref","first-page":"665","DOI":"10.3233\/JAD-2009-1179","article-title":"Neuropathologic studies of the Baltimore longitudinal study of aging (BLSA)","volume":"18","author":"RJ O\u2019Brien","year":"2009","journal-title":"Journal of Alzheimer\u2019s Disease"},{"issue":"3","key":"pone.0241707.ref006","doi-asserted-by":"crossref","first-page":"713","DOI":"10.3233\/JAD-2009-1178","article-title":"Brain lesions at autopsy in older Japanese-American men as related to cognitive impairment and dementia in the final years of life: a summary report from the Honolulu-Asia aging study","volume":"18","author":"L White","year":"2009","journal-title":"Journal of Alzheimer\u2019s Disease"},{"issue":"1","key":"pone.0241707.ref007","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.jns.2007.01.045","article-title":"Neuropathological evaluation of mixed dementia","volume":"257","author":"KA Jellinger","year":"2007","journal-title":"Journal of the neurological sciences"},{"issue":"11","key":"pone.0241707.ref008","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1016\/S1474-4422(12)70191-6","article-title":"Cognitive reserve in ageing and Alzheimer\u2019s disease","volume":"11","author":"Y Stern","year":"2012","journal-title":"The Lancet Neurology"},{"issue":"04","key":"pone.0241707.ref009","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1017\/S1355617710001748","article-title":"Conceptual and measurement challenges in research on cognitive reserve","volume":"17","author":"RN Jones","year":"2011","journal-title":"Journal of the International Neuropsychological Society"},{"issue":"03","key":"pone.0241707.ref010","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1017\/S1355617702813248","article-title":"What is cognitive reserve? 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