{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:05:07Z","timestamp":1792785907660,"version":"4.5.0"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T00:00:00Z","timestamp":1788566400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"University of Miami Clinical and Translational Science Institute","award":["1K12TR004555"],"award-info":[{"award-number":["1K12TR004555"]}]},{"name":"National Institute on Aging and the National Institute of Neurological Disorders and Stroke","award":["R61NS135587"],"award-info":[{"award-number":["R61NS135587"]}],"id":[{"id":"https:\/\/ror.org\/01s5ya894","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>MethylCog is a 29-CpG blood DNA methylation (DNAm) score developed to index general cognitive ability (g). Whether it captures cognition-related information associated with later cognitive performance that is not fully represented by blood-based biomarkers of Alzheimer\u2019s disease and related dementias (ADRD) remains unclear. Using the held-out Health and Retirement Study Harmonized Cognitive Assessment Protocol (HRS-HCAP) test set from the original MethylCog study (N\u2009=\u2009605), we examined associations with baseline g after adjustment for age, sex, education, apolipoprotein E (APOE) \u03b54 carrier status, neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), phosphorylated tau 181 (p-tau181), and amyloid-\u03b2 42\/40 ratio (A\u03b242\/40). Prospective associations with six-year follow-up g were examined after adjustment for baseline g, age, sex, education, and APOE \u03b54 carrier status, with additional adjustment for the ADRD biomarker panel. MethylCog remained associated with baseline g in the fully adjusted cross-sectional model (standardized \u03b2 = .178, 95% CI: .111-.244, p &amp;lt; .001; \u0394AdjR\u00b2 = .025). MethylCog was also associated with six-year follow-up g after adjustment for baseline g and all covariates and biomarkers (standardized \u03b2 = .101, 95% CI: .033-.170, p = .004; N\u2009=\u2009331; \u0394AdjR\u00b2 = .007). Findings were similar among participants without baseline cognitive impairment. These findings provide preliminary evidence that a cognition-trained DNAm signature captures variation in later cognitive performance not fully represented by baseline cognition or available ADRD blood biomarkers.<\/jats:p>","DOI":"10.1093\/gerona\/glag222","type":"journal-article","created":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T13:52:06Z","timestamp":1788616326000},"source":"Crossref","is-referenced-by-count":0,"title":["A blood DNA methylation marker of cognitive ability is associated with six-year cognitive performance independent of blood Alzheimer\u2019s disease biomarkers"],"prefix":"10.1093","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3313-7655","authenticated-orcid":false,"given":"Deirdre M","family":"O\u2019Shea","sequence":"first","affiliation":[{"name":"Comprehensive Center for Brain Health, Department of Neurology, University of Miami Miller School of Medicine , Boca Raton, Florida,","place":["United 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E","family":"Galvin","sequence":"additional","affiliation":[{"name":"Comprehensive Center for Brain Health, Department of Neurology, University of Miami Miller School of Medicine , Boca Raton, Florida,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"key":"2026100601011933100_glag222-B1","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1016\/j.jalz.2018.07.219","article-title":"Whitepaper: defining and investigating cognitive reserve, brain reserve, and brain maintenance","volume":"16","author":"Stern","year":"2020","journal-title":"Alzheimers Dement"},{"key":"2026100601011933100_glag222-B2","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1001\/jamaneurol.2019.5154","article-title":"Assessment of demographic, genetic, and imaging variables associated with brain resilience and cognitive resilience to pathological tau in patients with Alzheimer 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