{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T13:24:31Z","timestamp":1791897871886,"version":"4.3.4"},"reference-count":63,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T00:00:00Z","timestamp":1775433600000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82171582"],"award-info":[{"award-number":["82171582"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Hyperhomocysteinemia represents a modifiable risk factor for cognitive decline and dementia, yet the role of epigenetic aging mechanisms in mediating this association remain poorly characterized, limiting development of targeted interventions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We analyzed 1343 National Health and Nutrition Examination Survey participants aged \u2265 60 years using weighted regression, cubic splines, and mediation analyses. An independent cohort of 2073 participants validated findings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Elevated homocysteine concentrations were significantly associated with reduced cognitive processing speed. GrimAge2 epigenetic age acceleration significantly mediated this association, accounting for 33.3% of the total effect. \u03b22\u2010microglobulin emerged as the strongest mediating component, explaining 38.8% of the homocysteine\u2013cognition relationship. Folate demonstrated cognitive protection through homocysteine reduction (18.7% of total effect) without modulating downstream pathological cascades.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Epigenetic aging\u2010associated neuroinflammation serves as a key mechanistic link between hyperhomocysteinemia and cognitive decline. The neuroprotective effects of folate are mediated specifically through homocysteine reduction, providing novel mechanistic insights for precision prevention strategies in cognitive aging.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71349","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T06:08:26Z","timestamp":1775542106000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Accelerated epigenetic aging as a modifier of homocysteine\u2010associated cognitive decline: Findings from NHANES"],"prefix":"10.1002","volume":"22","author":[{"given":"Haoxuan","family":"Li","sequence":"first","affiliation":[{"name":"Grade 2023 Clinical Medicine Hebei Medical University  Shijiazhuang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy Neuroscience Research Center Hebei Medical University  Shijiazhuang China"},{"name":"Hebei Key Laboratory of Neurodegenerative Disease Mechanism  Shijiazhuang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Wang","sequence":"additional","affiliation":[{"name":"Grade 2024 Clinical Medicine Hebei Medical University  Shijiazhuang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yankun","family":"Wang","sequence":"additional","affiliation":[{"name":"Grade 2024 Clinical Medicine Hebei Medical University  Shijiazhuang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Bi","sequence":"additional","affiliation":[{"name":"Grade 2024 Integrated Traditional Chinese and Western Medicine Hebei Medical University  Shijiazhuang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayu","family":"Hou","sequence":"additional","affiliation":[{"name":"Grade 2023 Clinical Medicine Hebei Medical University  Shijiazhuang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy Neuroscience Research Center Hebei Medical University  Shijiazhuang China"},{"name":"Hebei Key Laboratory of Neurodegenerative Disease Mechanism  Shijiazhuang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy Neuroscience Research Center Hebei Medical University  Shijiazhuang China"},{"name":"Hebei Key Laboratory of Neurodegenerative Disease Mechanism  Shijiazhuang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenhao","family":"Guo","sequence":"additional","affiliation":[{"name":"Grade 2022 Basic Medicine Hebei Medical University  Shijiazhuang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuo","family":"Chen","sequence":"additional","affiliation":[{"name":"Grade 2023 Clinical Medicine Hebei Medical University  Shijiazhuang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huixian","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy Neuroscience Research Center Hebei Medical University  Shijiazhuang China"},{"name":"Hebei Key Laboratory of Neurodegenerative Disease Mechanism  Shijiazhuang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sha","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy Neuroscience Research Center Hebei Medical University  Shijiazhuang China"},{"name":"Hebei Key Laboratory of Neurodegenerative Disease Mechanism  Shijiazhuang China"},{"name":"The Key Laboratory of Neural and Vascular Biology of Ministry of Education  Shijiazhuang China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,6]]},"reference":[{"key":"e_1_2_11_2_1","volume-title":"World Alzheimer Report 2023: Reducing Dementia Risk: Never Too Early, Never Too Late","author":"Long S","year":"2023"},{"key":"e_1_2_11_3_1","unstructured":"World Health Organization.Dementia2023. 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