{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T22:38:32Z","timestamp":1791499112352,"version":"4.3.4"},"reference-count":22,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T00:00:00Z","timestamp":1745798400000},"content-version":"vor","delay-in-days":27,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["320030_220269"],"award-info":[{"award-number":["320030_220269"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>INTRODUCTION<\/jats:title><jats:p>Resilience, the ability to maintain cognition or brain integrity despite Alzheimer's disease (AD) pathology, is often quantified using the residual approach. However, the variability in methodology and correction methods for this approach raises concerns about the interpretability of findings across studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>We assessed brain resilience (BR) and cognitive resilience (CR) in a memory clinic population using the residual approach. We compared non\u2010corrected and corrected residuals\u2019 associations with risk factors using linear regression models, and their impact on longitudinal cognition using linear mixed\u2010effects models.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Corrected versus non\u2010corrected BR yielded distinct, often opposing, associations. For example, glial fibrillary acidic protein (GFAP) was negatively associated with non\u2010corrected BR (\u03b2\u00a0=\u00a0\u20130.33; <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.01) but positively with corrected BR (\u03b2\u00a0=\u00a00.5, <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.001). Only corrected CR measures yielded significant associations. Only corrected residuals predicted cognitive decline.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>The observed discrepancies raise questions about the reliability of the residual approach in accurately capturing resilience.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Corrected and non\u2010corrected residuals show distinct associations with risk factors.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Corrected and non\u2010corrected residuals show different predictions of cognitive decline.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These approaches may reflect general brain health rather than true resilience mechanisms.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.70185","type":"journal-article","created":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T05:06:36Z","timestamp":1745816796000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Resilience in Alzheimer's disease: Impact of operationalization and methodological choices"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2683-2465","authenticated-orcid":false,"given":"Sophie","family":"Mutel","sequence":"first","affiliation":[{"name":"Laboratory of Neuroimaging of Aging (LANVIE) University of Geneva  Geneva Switzerland"},{"name":"Geneva Memory Centre Department of Rehabilitation and Geriatrics Geneva University Hospitals  Geneva 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Geneva University Hospitals  Geneva Switzerland"},{"name":"Center for Interdisciplinary Study of Gerontology and Vulnerability (CIGEV) University of Geneva  Carouge Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max","family":"Scheffler","sequence":"additional","affiliation":[{"name":"Division of Radiology Geneva University Hospitals  Thonex Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl\u2010Olof","family":"L\u00f6vblad","sequence":"additional","affiliation":[{"name":"Neurodiagnostic and Neurointerventional Division Diagnostic Department Geneva University Hospitals  Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaj","family":"Blennow","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology The Sahlgrenska Academy at the University of Gothenburg  G\u00f6teborg Sweden"},{"name":"Clinical Neurochemistry Laboratory Sahlgrenska University Hospital  M\u00f6lndal Sweden"},{"name":"Paris Brain Institute ICM Piti\u00e9 Salp\u00eatri\u00e8re Hospital Sorbonne University  Paris France"},{"name":"Neurodegenerative Disorder Research Centre Division of Life Sciences and Medicine and Department of Neurology Institute on Aging and Brain Disorders University of Science and Technology of China and First Affiliated Hospital of USTC  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J.","family":"Ashton","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology The Sahlgrenska Academy at the University of Gothenburg  G\u00f6teborg Sweden"},{"name":"Centre for Age\u2010Related Medicine Stavanger University Hospital  Stavanger Norway"},{"name":"King's College London Institute of Psychiatry Psychology &amp; Neuroscience Maurice Wohl Clinical Neuroscience Institute  London UK"},{"name":"NIHR 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