{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T03:06:05Z","timestamp":1792206365068,"version":"4.4.0"},"reference-count":60,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T00:00:00Z","timestamp":1751587200000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100010969","name":"Alzheimer Nederland","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010969","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's & Dementia"],"published-print":{"date-parts":[[2025,7]]},"abstract":"Abstract<\/jats:title>\n \n INTRODUCTION<\/jats:title>\n Cognitive resilience refers to maintaining cognitive function despite Alzheimer's disease (AD) pathophysiology.<\/jats:p>\n <\/jats:sec>\n \n METHODS<\/jats:title>\n \n We analyzed amyloid\u2010positive individuals across clinical stages of AD in two cohorts: the Amsterdam Dementia Cohort (ADC,\n N<\/jats:italic>\n \u00a0=\u00a01036) and Alzheimer's Disease Neuroimaging Initiative (ADNI,\n N<\/jats:italic>\n \u00a0=\u00a0685). Cognitive resilience was conceptualized from a canonical correlation analysis of magnetic resonance imaging and neuropsychological data in each cohort separately. Model validation involved education as a resilience proxy and key genetic factors (apolipoprotein E [\n APOE<\/jats:italic>\n ] \u03b54 and\n APOE<\/jats:italic>\n \u03b52) of AD. We explored associations between 83 AD risk loci and cognitive resilience.\n <\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n \n Resilience was correlated with education (ADC: \u03b2\u00a0=\u00a00.144,\n p<\/jats:italic>\n \u00a0<\u00a00.001; ADNI: \u03b2\u00a0=\u00a00.149,\n p<\/jats:italic>\n \u00a0<\u00a00.001) and\n APOE<\/jats:italic>\n \u03b54 (\u03b2\n meta\u2010analysis\u00a0<\/jats:sub>\n =\u00a0\u20130.052,\n p<\/jats:italic>\n \u00a0=\u00a00.014). Exploratory single nucleotide polymorphism meta\u2010analysis identified potential involvement of genetic variants around genes\n UNC5CL<\/jats:italic>\n ,\n USP6NL<\/jats:italic>\n , and\n TPCN1<\/jats:italic>\n in lower, and genes\n COX7C<\/jats:italic>\n and\n MINDY2<\/jats:italic>\n in higher resilience.\n <\/jats:p>\n <\/jats:sec>\n \n DISCUSSION<\/jats:title>\n Our novel resilience approach showed conceptual validity and potential for future discovery of resilience\u2010related genetic variants.<\/jats:p>\n <\/jats:sec>\n \n Highlights<\/jats:title>\n \n \n \n We define a novel approach to resilience using canonical correlation analysis (CCA).<\/jats:p>\n <\/jats:list-item>\n \n Apolipoprotein E \u03b54 is linked to lower resilience, suggesting increased vulnerability.<\/jats:p>\n <\/jats:list-item>\n \n \n Genetic loci around\n COX7C<\/jats:italic>\n and\n MINDY2<\/jats:italic>\n are potentially involved in higher resilience.\n <\/jats:p>\n <\/jats:list-item>\n \n This novel approach may be used for multi\u2010cohort studies such as genome\u2010wide association studies in the future.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/alz.70379","type":"journal-article","created":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T07:17:03Z","timestamp":1751613423000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["A novel approach to resilience and its links with education and Alzheimer's disease genetics"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-3506-9708","authenticated-orcid":false,"given":"Maria","family":"Carrigan","sequence":"first","affiliation":[{"name":"Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam Amsterdam UMC location VUmc Amsterdam the Netherlands"},{"name":"Amsterdam Neuroscience, Neurodegeneration Amsterdam the Netherlands"},{"name":"Faculty of Science Swammerdam Institute for Life Sciences University of Amsterdam Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana I.","family":"Bocancea","sequence":"additional","affiliation":[{"name":"Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam Amsterdam UMC location VUmc Amsterdam the Netherlands"},{"name":"Amsterdam Neuroscience, Neurodegeneration Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Vogel","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences Malm\u00f6 Faculty of Medicine SciLifLab, Lund University Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna C.","family":"van Loenhoud","sequence":"additional","affiliation":[{"name":"Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam Amsterdam UMC location VUmc Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niccol\u00f3","family":"Tesi","sequence":"additional","affiliation":[{"name":"Section Genomics of Neurodegenerative Diseases and Aging, Department of Clinical Genetics Vrije Universiteit Amsterdam, Amsterdam UMC Amsterdam the Netherlands"},{"name":"Delft Bioinformatics Lab Delft University of Technology Delft the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederik","family":"Barkhof","sequence":"additional","affiliation":[{"name":"Queen Square Institute of Neurology and Centre for Medical Image Computing University College London Queen Square London UK"},{"name":"Department of Radiology & Nuclear Medicine Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.","family":"Lucassen","sequence":"additional","affiliation":[{"name":"Faculty of Science Swammerdam Institute for Life Sciences University of Amsterdam Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wiesje M.","family":"van der Flier","sequence":"additional","affiliation":[{"name":"Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam Amsterdam UMC location VUmc Amsterdam the Netherlands"},{"name":"Department of Epidemiology & Data Science Amsterdam UMC location Vrije Universiteit Amsterdam Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harm J.","family":"Krugers","sequence":"additional","affiliation":[{"name":"Faculty of Science Swammerdam Institute for Life Sciences University of Amsterdam Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven J.","family":"Van der Lee","sequence":"additional","affiliation":[{"name":"Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam Amsterdam UMC location VUmc Amsterdam the Netherlands"},{"name":"Section Genomics of Neurodegenerative Diseases and Aging, Department of Clinical Genetics Vrije Universiteit Amsterdam, Amsterdam UMC Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rik","family":"Ossenkoppele","sequence":"additional","affiliation":[{"name":"Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam Amsterdam UMC location VUmc Amsterdam the Netherlands"},{"name":"Department of Clinical Sciences Malm\u00f6 Faculty of Medicine SciLifLab, Lund University Lund 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