{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:10:00Z","timestamp":1785409800650,"version":"3.56.0"},"posted":{"date-parts":[[2026,5,27]]},"group-title":"Neurology","reference-count":28,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T00:00:00Z","timestamp":1779840000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["1K12TR004555"],"award-info":[{"award-number":["1K12TR004555"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R61NS135587"],"award-info":[{"award-number":["R61NS135587"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["U01AG009740"],"award-info":[{"award-number":["U01AG009740"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["U01AG058499"],"award-info":[{"award-number":["U01AG058499"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["RC2AG036495"],"award-info":[{"award-number":["RC2AG036495"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["RC4AG039029"],"award-info":[{"award-number":["RC4AG039029"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,28]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>INTRODUCTION<\/jats:title>\n                  <jats:p>MethylCog is a 29-CpG blood DNA methylation (DNAm) proxy for general cognitive ability (g). Its incremental association with blood biomarkers of Alzheimer\u2019s disease and related dementias (ADRD) and prospective cognitive ability remains unclear.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>METHODS<\/jats:title>\n                  <jats:p>\n                    In the held-out test set from the original MethylCog study, we tested whether MethylCog explained baseline\n                    <jats:italic>g<\/jats:italic>\n                    beyond four ADRD blood biomarkers, and whether it predicted six-year follow-up g beyond baseline\n                    <jats:italic>g<\/jats:italic>\n                    and biomarkers.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>\n                    MethylCog showed a stronger age-adjusted association with baseline\n                    <jats:italic>g<\/jats:italic>\n                    than individual biomarkers (r=.368 vs absolute r=.083\u2013.162). MethylCog added 10.0% variance beyond all four biomarkers cross-sectionally (p&lt;.001) and predicted six-year follow-up g in the biomarker-adjusted model (\u03b2=.108, p=.002). No individual ADRD biomarker independently predicted follow-up g.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>DISCUSSION<\/jats:title>\n                  <jats:p>MethylCog may provide cognition-related DNAm information complementary to blood-based ADRD biomarkers.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.05.26.26354133","type":"posted-content","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T02:30:18Z","timestamp":1779935418000},"source":"Crossref","is-referenced-by-count":0,"title":["MethylCog predicts six-year cognitive ability beyond blood-based ADRD biomarkers"],"prefix":"10.64898","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, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lily","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Biostatistics, Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Lukacsovich","sequence":"additional","affiliation":[{"name":"Division of Biostatistics, Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Biostatistics, Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E.","family":"Galvin","sequence":"additional","affiliation":[{"name":"Comprehensive Center for Brain Health, Department of Neurology, University of Miami Miller School of Medicine, Boca Raton, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026060100050652000_2026.05.26.26354133v2.1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12724"},{"key":"2026060100050652000_2026.05.26.26354133v2.2","doi-asserted-by":"publisher","DOI":"10.1002\/dad2.12375"},{"key":"2026060100050652000_2026.05.26.26354133v2.3","doi-asserted-by":"publisher","DOI":"10.1002\/alz.70948"},{"key":"2026060100050652000_2026.05.26.26354133v2.4","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-025-03166-y"},{"key":"2026060100050652000_2026.05.26.26354133v2.5","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-025-03605-x"},{"key":"2026060100050652000_2026.05.26.26354133v2.6","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwaf179"},{"key":"2026060100050652000_2026.05.26.26354133v2.7","doi-asserted-by":"publisher","DOI":"10.3233\/jad-221145"},{"key":"2026060100050652000_2026.05.26.26354133v2.8","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyr147"},{"key":"2026060100050652000_2026.05.26.26354133v2.9","doi-asserted-by":"publisher","DOI":"10.2217\/epi-2018-0042"},{"issue":"1","key":"2026060100050652000_2026.05.26.26354133v2.10","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/s41539-018-0020-2","article-title":"DNA methylation signatures of educational attainment","volume":"3","year":"2018","journal-title":"npj Science of Learning"},{"key":"2026060100050652000_2026.05.26.26354133v2.11","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-025-01733-7"},{"key":"2026060100050652000_2026.05.26.26354133v2.12","doi-asserted-by":"publisher","DOI":"10.1002\/alz.71421"},{"key":"2026060100050652000_2026.05.26.26354133v2.13","doi-asserted-by":"publisher","DOI":"10.1159\/000503004"},{"issue":"5","key":"2026060100050652000_2026.05.26.26354133v2.14","first-page":"741","article-title":"GrimAge outperforms other epigenetic clocks in the prediction of age-related clinical phenotypes and all-cause mortality","volume":"76","year":"2021","journal-title":"The Journals of Gerontology: Series A"},{"key":"2026060100050652000_2026.05.26.26354133v2.15","doi-asserted-by":"publisher","DOI":"10.1186\/s13148-026-02142-9"},{"key":"2026060100050652000_2026.05.26.26354133v2.16","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-021-02596-5"},{"key":"2026060100050652000_2026.05.26.26354133v2.17","doi-asserted-by":"crossref","unstructured":"Juster FT , Suzman R . 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