{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T06:40:56Z","timestamp":1785393656994,"version":"3.55.0"},"posted":{"date-parts":[[2025,11,13]]},"group-title":"Epidemiology","reference-count":63,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T00:00:00Z","timestamp":1762992000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,11,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>BACKGROUND<\/jats:title>\n                  <jats:p>Peripheral blood DNA methylation may have utility as an early dementia risk biomarker.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>METHODS<\/jats:title>\n                  <jats:p>We analyzed DNA methylation (blood collected 2016) and cognitive impairment in the Health and Retirement Study, a longitudinal study representative of US adults over age 50 (3,921 individuals and 585,356 CpG sites). We analyzed methylation associations with cognitive status both cross-sectionally and prospectively among participants with normal cognition at baseline with four years follow-up.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>\n                    Cross-sectionally, 5,322 CpGs were associated (p-value&lt;0.01) with cognitive impairment non-dementia, and 14,366 (166 genome-wide FDR&lt;0.05) with dementia. Prospectively, 4,898 CpGs were associated with any-impairment. Enriched biologic pathways include ion transport, ligand-gated channel, and neuron differentiation. Nine CpGs overlapped all analyses including cg02583484 (\n                    <jats:italic>HNRNPA1<\/jats:italic>\n                    ), cg15266133 (\n                    <jats:italic>LOC102724084<\/jats:italic>\n                    ), cg24287460 (\n                    <jats:italic>CCDC48<\/jats:italic>\n                    ), cg17124509 (\n                    <jats:italic>C17orf57<\/jats:italic>\n                    ), and cg02553054 (\n                    <jats:italic>SMARCD1<\/jats:italic>\n                    ).\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>DISCUSSION<\/jats:title>\n                  <jats:p>CpGs identified were enriched in pathways related to Alzheimer\u2019s disease pathology and provide promising grounds for non-invasive blood biomarkers. Future studies for replication and with longer follow-up are needed.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.11.10.25339919","type":"posted-content","created":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T02:55:16Z","timestamp":1763088916000},"source":"Crossref","is-referenced-by-count":1,"title":["DNA methylation-wide association study of prevalent and incident dementia in the US Health and Retirement Study"],"prefix":"10.64898","author":[{"given":"John","family":"Dou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scarlet","family":"Cockell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Hemenway","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay","family":"Ryan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matt","family":"Zawistowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin B.","family":"Ware","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9605-6337","authenticated-orcid":false,"given":"Kelly M.","family":"Bakulski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025111505000858000_2025.11.10.25339919v1.1","unstructured":"National Insitutes of Health. What Is Dementia? Symptoms, Types, and Diagnosis. Dec 8 2022. Published online June 20, 2024. https:\/\/www.nia.nih.gov\/health\/alzheimers-and-dementia\/what-dementia-symptoms-types-and-diagnosis"},{"key":"2025111505000858000_2025.11.10.25339919v1.2","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13809"},{"key":"2025111505000858000_2025.11.10.25339919v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30367-6"},{"key":"2025111505000858000_2025.11.10.25339919v1.4","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12822"},{"key":"2025111505000858000_2025.11.10.25339919v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.06.3063"},{"key":"2025111505000858000_2025.11.10.25339919v1.6","doi-asserted-by":"publisher","DOI":"10.3390\/genes13081308"},{"key":"2025111505000858000_2025.11.10.25339919v1.7","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-017-0283-5"},{"key":"2025111505000858000_2025.11.10.25339919v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.tjpad.2024.100056"},{"key":"2025111505000858000_2025.11.10.25339919v1.9","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-023-01216-7"},{"key":"2025111505000858000_2025.11.10.25339919v1.10","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw967"},{"key":"2025111505000858000_2025.11.10.25339919v1.11","doi-asserted-by":"publisher","DOI":"10.1007\/s40572-020-00287-0"},{"key":"2025111505000858000_2025.11.10.25339919v1.12","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-021-02347-6"},{"key":"2025111505000858000_2025.11.10.25339919v1.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioana.2024.05.005"},{"key":"2025111505000858000_2025.11.10.25339919v1.14","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-32475-x"},{"key":"2025111505000858000_2025.11.10.25339919v1.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.003"},{"key":"2025111505000858000_2025.11.10.25339919v1.16","doi-asserted-by":"publisher","DOI":"10.1007\/s40142-020-00190-y"},{"key":"2025111505000858000_2025.11.10.25339919v1.17","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyu067"},{"key":"2025111505000858000_2025.11.10.25339919v1.18","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-016-1066-1"},{"key":"2025111505000858000_2025.11.10.25339919v1.19","doi-asserted-by":"publisher","DOI":"10.1186\/s13148-018-0504-1"},{"key":"2025111505000858000_2025.11.10.25339919v1.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.envres.2024.118956"},{"key":"2025111505000858000_2025.11.10.25339919v1.21","doi-asserted-by":"publisher","DOI":"10.1186\/s13148-023-01459-z"},{"key":"2025111505000858000_2025.11.10.25339919v1.22","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt090"},{"key":"2025111505000858000_2025.11.10.25339919v1.23","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts680"},{"key":"2025111505000858000_2025.11.10.25339919v1.24","doi-asserted-by":"publisher","DOI":"10.1093\/geronb\/gbr048"},{"key":"2025111505000858000_2025.11.10.25339919v1.25","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2016.6807"},{"key":"2025111505000858000_2025.11.10.25339919v1.26","doi-asserted-by":"publisher","DOI":"10.1093\/gpbjnl\/qzae044"},{"key":"2025111505000858000_2025.11.10.25339919v1.27","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-018-1448-7"},{"key":"2025111505000858000_2025.11.10.25339919v1.28","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-13-86"},{"key":"2025111505000858000_2025.11.10.25339919v1.29","unstructured":"R Core Team. R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing; 2024. https:\/\/www.R-project.org\/"},{"key":"2025111505000858000_2025.11.10.25339919v1.30","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv007"},{"key":"2025111505000858000_2025.11.10.25339919v1.31","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1995.tb02031.x"},{"key":"2025111505000858000_2025.11.10.25339919v1.32","doi-asserted-by":"publisher","DOI":"10.1109\/TVCG.2014.2346248"},{"key":"2025111505000858000_2025.11.10.25339919v1.33","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty892"},{"key":"2025111505000858000_2025.11.10.25339919v1.34","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btz456"},{"key":"2025111505000858000_2025.11.10.25339919v1.35","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2020.06.023"},{"key":"2025111505000858000_2025.11.10.25339919v1.36","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10112798"},{"key":"2025111505000858000_2025.11.10.25339919v1.37","doi-asserted-by":"publisher","DOI":"10.3390\/cimb46080508"},{"key":"2025111505000858000_2025.11.10.25339919v1.38","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-019-1091-5"},{"key":"2025111505000858000_2025.11.10.25339919v1.39","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13153869"},{"key":"2025111505000858000_2025.11.10.25339919v1.40","doi-asserted-by":"publisher","DOI":"10.1177\/1533033820921248"},{"key":"2025111505000858000_2025.11.10.25339919v1.41","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-022-01492-z"},{"key":"2025111505000858000_2025.11.10.25339919v1.42","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4562-11.2012"},{"key":"2025111505000858000_2025.11.10.25339919v1.43","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2017.09.008"},{"key":"2025111505000858000_2025.11.10.25339919v1.44","doi-asserted-by":"crossref","first-page":"26","DOI":"10.20517\/2574-1209.2020.18","article-title":"SNRK: a metabolic regulator with multifaceted role in development and disease","volume":"4","year":"2020","journal-title":"Vessel Plus"},{"key":"2025111505000858000_2025.11.10.25339919v1.45","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-06-162180"},{"key":"2025111505000858000_2025.11.10.25339919v1.46","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.12.032"},{"key":"2025111505000858000_2025.11.10.25339919v1.47","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-016-1683-5"},{"key":"2025111505000858000_2025.11.10.25339919v1.48","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-020-02203-0"},{"key":"2025111505000858000_2025.11.10.25339919v1.49","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3002028"},{"key":"2025111505000858000_2025.11.10.25339919v1.50","unstructured":"EFCC1 EF-hand and coiled-coil domain containing 1 [Homo sapiens (human)] - Gene - NCBI. Accessed March 14, 2025. https:\/\/www.ncbi.nlm.nih.gov\/gene\/79825"},{"key":"2025111505000858000_2025.11.10.25339919v1.51","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1326-4-20"},{"key":"2025111505000858000_2025.11.10.25339919v1.52","unstructured":"EFCAB13 EF-hand calcium binding domain 13 [Homo sapiens (human)] - Gene - NCBI. Accessed March 14, 2025. https:\/\/www.ncbi.nlm.nih.gov\/gene\/124989"},{"key":"2025111505000858000_2025.11.10.25339919v1.53","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2015.06.548"},{"key":"2025111505000858000_2025.11.10.25339919v1.54","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.15517"},{"key":"2025111505000858000_2025.11.10.25339919v1.55","unstructured":"SMARCD1 SWI\/SNF related BAF chromatin remodeling complex subunit D1 [Homo sapiens (human)] - Gene - NCBI. Accessed March 14, 2025. https:\/\/www.ncbi.nlm.nih.gov\/gene\/6602"},{"key":"2025111505000858000_2025.11.10.25339919v1.56","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-020-02190-z"},{"key":"2025111505000858000_2025.11.10.25339919v1.57","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2019.02.001"},{"key":"2025111505000858000_2025.11.10.25339919v1.58","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3359"},{"key":"2025111505000858000_2025.11.10.25339919v1.59","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2017.00243"},{"key":"2025111505000858000_2025.11.10.25339919v1.60","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21073"},{"key":"2025111505000858000_2025.11.10.25339919v1.61","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.113171"},{"key":"2025111505000858000_2025.11.10.25339919v1.62","doi-asserted-by":"publisher","DOI":"10.1002\/alz.14496"},{"key":"2025111505000858000_2025.11.10.25339919v1.63","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2012-111592"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.11.10.25339919","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:50:58Z","timestamp":1768510258000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.1101\/2025.11.10.25339919"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,13]]},"references-count":63,"URL":"https:\/\/doi.org\/10.1101\/2025.11.10.25339919","relation":{},"subject":[],"published":{"date-parts":[[2025,11,13]]},"subtype":"preprint"}}