{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T19:54:22Z","timestamp":1773690862802,"version":"3.50.1"},"posted":{"date-parts":[[2026,1,26]]},"group-title":"Epidemiology","reference-count":0,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T00:00:00Z","timestamp":1769385600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,1,26]]},"abstract":"<jats:p>Epigenetic clocks of biological aging have been associated with cognitive impairment and dementia. Less is known about whether they are associated with an older-appearing brain or with an atrophy pattern associated with dementia. We examined associations of five epigenetic clocks measured at baseline with the Spatial Pattern of Atrophy for Recognition of Brain Aging (SPARE-BA) and the Alzheimer's Disease Pattern Similarity Score (AD-PS) derived from structural MRIs obtained an average of 8 years later among 1,196 older women. Using linear regression models adjusting for relevant covariates, we observed no associations between any epigenetic clock and accelerated brain aging based on SPARE-BA. We observed a significant association between AgeAccelGrim2 and AD-PS (\u03b2 = 0.015; 95% CI 0.004 to 0.027; p = 0.01). This association appeared to be primarily driven by the association of a DNA methylation marker of smoking pack years with frontal and temporal lobe volumes. AgeAccelGrim2 was not associated with volumes in regions implicated in early AD (hippocampus and entorhinal cortex). Taken together with prior findings, these results suggest that measures of epigenetic and brain age acceleration capture different aspects of biological aging, and that AgeAccelGrim2 is predictive of neurodegenerative changes associated with smoking that increase risk of dementia.<\/jats:p>","DOI":"10.64898\/2026.01.23.26344650","type":"posted-content","created":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T21:25:10Z","timestamp":1769462710000},"source":"Crossref","is-referenced-by-count":1,"title":["Association of epigenetic age acceleration with MRI biomarkers of aging and Alzheimer's disease neurodegeneration"],"prefix":"10.64898","author":[{"given":"Linda K.","family":"McEvoy","sequence":"first","affiliation":[{"name":"Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9686-0897","authenticated-orcid":false,"given":"Bowei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA, USA;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5193-7042","authenticated-orcid":false,"given":"Steve","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA, USA;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam X.","family":"Maihofer","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA, USA;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline M.","family":"Nievergelt","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA, USA;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Casanova","family":"Ramon","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Data Science, Wake University School of Medicine, Winston-Salem, NC;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4110-3589","authenticated-orcid":false,"given":"Steve","family":"Horvath","sequence":"additional","affiliation":[{"name":"Altos Labs Cambridge Institute of Science, Cambridge, UK;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ake T.","family":"Lu","sequence":"additional","affiliation":[{"name":"Altos Labs, San Diego, CA;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christos","family":"Davatzikos","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Pennsylvania School of Medicine, Philadelphia, PA;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6633-4861","authenticated-orcid":false,"given":"Guray","family":"Erus","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Pennsylvania School of Medicine, Philadelphia, PA;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan M","family":"Resnick","sequence":"additional","affiliation":[{"name":"Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark A.","family":"Espeland","sequence":"additional","affiliation":[{"name":"Division of Gerontology and Geriatric Medicine, School of Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen R","family":"Rapp","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth","family":"Beckman","sequence":"additional","affiliation":[{"name":"Genomics Center, University of Minnesota, Minneapolis, MN, USA;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luigi","family":"Ferrucci","sequence":"additional","affiliation":[{"name":"Longitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, Baltimore, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea Z.","family":"LaCroix","sequence":"additional","affiliation":[{"name":"Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA, USA;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aladdin H","family":"Shadyab","sequence":"additional","affiliation":[{"name":"Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA, USA;"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.01.23.26344650","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T21:25:10Z","timestamp":1769462710000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.64898\/2026.01.23.26344650"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,26]]},"references-count":0,"URL":"https:\/\/doi.org\/10.64898\/2026.01.23.26344650","relation":{},"subject":[],"published":{"date-parts":[[2026,1,26]]},"subtype":"preprint"}}