{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T01:15:55Z","timestamp":1793495755479,"version":"4.5.0"},"reference-count":54,"publisher":"American Medical Association (AMA)","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Neurol"],"published-print":{"date-parts":[[2025,8,1]]},"abstract":"\n Importance<\/jats:title>\n Older individuals without dementia often have amyloid-beta (A\u03b2) Thal phases similar to patients with Alzheimer disease (AD), suggesting that A\u03b2 pathology may be a benign consequence of aging.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To explore whether A\u03b2 pathology in centenarians is associated with cognitive performance.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This longitudinal cohort study used cross-sectional data on antemortem cognitive performance and postmortem neuropathology of participants in the Dutch 100-plus Study. Cognitive performance was measured a median of 10 (IQR, 3-13) months before postmortem brain donation. From January 2013 to July 2022, 1187 centenarians who self-reported being cognitively healthy, confirmed by proxy, were approached: 406 were included and 95 donated their brain. Centenarians were compared with patients with clinicopathologically confirmed AD from the Netherlands Brain Bank. Data were analyzed from June 2022 to October 2024.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n A\u03b2 pathology was assessed with the Thal phase for A\u03b2 progression and by determining quantitative A\u03b2 loads (percentage positive area) in the frontal, parietal, temporal, and occipital neocortices, 3 parahippocampal, and 5 hippocampal subregions. A\u03b2 pathology was associated with performance on 13 neuropsychological tests assessing memory, fluency, attention\/processing speed, and executive functioning, as well as 4 measures of global cognition.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n This study evaluated A\u03b2 pathology in 95 centenarians (median age at brain donation, 103.5 [IQR, 102.3-104.7] years; 71 female [75%] and 24 male [25%]) and 38 patients with AD (median age, 84 [IQR, 78-90] years; 18 female [47%] and 20 male [53%]). Global cognition parameters were available for all 95 centenarians and complete cognitive assessment for 72 centenarians (76%). A fraction of the centenarians had no A\u03b2 load (9 of 95 [9%]), most had low A\u03b2 load (53 of 95 [56%]) and, despite high Thal phases, about one-third (33 of 95 [35%]) had high A\u03b2 load comparable with patients with AD. Centenarians with no or low A\u03b2 load had significantly higher cognitive performance than centenarians with high A\u03b2 loads. Higher A\u03b2 loads across all 4 neocortical regions, cornu ammonis 3, cornu ammonis 1\/subiculum, and the entorhinal cortex specifically affected executive functioning. Interestingly, 5 resilient centenarians maintained high cognitive performance despite having high A\u03b2 loads; they had significantly less tau pathology compared with centenarians with high A\u03b2 loads and low cognitive performance.<\/jats:p>\n <\/jats:sec>\n \n Conclusions and relevance<\/jats:title>\n These results indicate that A\u03b2 pathology is not a benign consequence of aging. Even in the oldest individuals, A\u03b2 and tau pathology interaction was consistent with the amyloid cascade hypothesis.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamaneurol.2025.1734","type":"journal-article","created":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T11:00:37Z","timestamp":1751281237000},"page":"837","source":"Crossref","is-referenced-by-count":28,"title":["Amyloid-Beta Pathology and Cognitive Performance in Centenarians"],"prefix":"10.1001","volume":"82","author":[{"given":"Susan K.","family":"Rohde","sequence":"first","affiliation":[{"name":"Department of Human Genetics, Genomics of Neurodegenerative Diseases and Aging, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands"},{"name":"Department of Neurology and Alzheimer Center Amsterdam, Amsterdam UMC location VUmc, Amsterdam, the Netherlands"},{"name":"Department of Pathology, Amsterdam UMC location VUmc, Amsterdam, the Netherlands"},{"name":"Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maruelle C.","family":"Luimes","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Genomics of Neurodegenerative Diseases and Aging, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands"},{"name":"Department of Neurology and Alzheimer Center Amsterdam, Amsterdam UMC location VUmc, Amsterdam, the Netherlands"},{"name":"Department of Pathology, Amsterdam UMC location VUmc, Amsterdam, the Netherlands"},{"name":"Amsterdam Neuroscience, Neurodegeneration, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda M. C.","family":"Lorenz","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Genomics of Neurodegenerative Diseases and Aging, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands"},{"name":"Department of Neurology and Alzheimer Center Amsterdam, Amsterdam UMC location VUmc, Amsterdam, the Netherlands"},{"name":"Amsterdam Neuroscience, Neurodegeneration, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Fierro-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Genomics of Neurodegenerative Diseases and Aging, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands"},{"name":"Department of Pathology, Amsterdam UMC location VUmc, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemieke J. M.","family":"Rozemuller","sequence":"additional","affiliation":[{"name":"Department of Pathology, Amsterdam UMC location VUmc, Amsterdam, the Netherlands"},{"name":"Netherlands Institute for Neuroscience, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Hulsman","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Genomics of Neurodegenerative Diseases and Aging, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands"},{"name":"Department of Neurology and Alzheimer Center Amsterdam, Amsterdam UMC location VUmc, Amsterdam, the Netherlands"},{"name":"Delft Bioinformatics Lab, Delft Technical University, Delft, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Genomics of Neurodegenerative Diseases and Aging, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands"},{"name":"Delft Bioinformatics Lab, Delft Technical University, Delft, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marieke J. I.","family":"Graat","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Genomics of Neurodegenerative Diseases and Aging, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands"},{"name":"Department of Neurology and Alzheimer Center Amsterdam, Amsterdam UMC location VUmc, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myke E.","family":"van der Hoorn","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Genomics of Neurodegenerative Diseases and Aging, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands"},{"name":"Department of Neurology and Alzheimer Center Amsterdam, Amsterdam UMC location VUmc, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique A. H.","family":"Daatselaar","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Genomics of Neurodegenerative Diseases and Aging, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands"},{"name":"Department of Neurology and Alzheimer Center Amsterdam, Amsterdam UMC location VUmc, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Scheltens","sequence":"additional","affiliation":[{"name":"Department of Neurology and Alzheimer Center Amsterdam, Amsterdam UMC location VUmc, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy E.","family":"Richardson","sequence":"additional","affiliation":[{"name":"Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie M.","family":"Walker","sequence":"additional","affiliation":[{"name":"Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sietske A. M.","family":"Sikkes","sequence":"additional","affiliation":[{"name":"Department of Neurology and Alzheimer Center Amsterdam, Amsterdam UMC location VUmc, Amsterdam, the Netherlands"},{"name":"Amsterdam Neuroscience, Neurodegeneration, Amsterdam, the Netherlands"},{"name":"Faculty of Behavioral and Movement Sciences, Clinical Developmental Psychology and Clinical Neuropsychology, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeroen J. 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