{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T22:29:06Z","timestamp":1790461746797,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,12,28]],"date-time":"2023-12-28T00:00:00Z","timestamp":1703721600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000050","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":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>INTRODUCTION<\/jats:title><jats:p>We examined midlife (1990\u20131992, mean age 57) and late\u2010life (2011\u20132013, mean age 75) nonalcoholic fatty liver disease (NAFLD) and aminotransferase with incident dementia risk through 2019 in the Atherosclerosis Risk in Communities (ARIC) Study.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>We characterized NAFLD using the fatty liver index and fibrosis\u20104, and we categorized aminotransferase using the optimal equal\u2010hazard ratio (HR) approach. We estimated HRs for incident dementia ascertained from multiple data sources.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Adjusted for demographics, alcohol consumption, and kidney function, individuals with low, intermediate, and high liver fibrosis in midlife (HRs: 1.45, 1.40, and 2.25, respectively), but not at older age, had higher dementia risks than individuals without fatty liver. A U\u2010shaped association was observed for alanine aminotransferase with dementia risk, which was more pronounced in late\u2010life assessment.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>Our findings highlight dementia burden in high\u2010prevalent NAFLD and the important feature of late\u2010life aminotransaminase as a surrogate biomarker linking liver hypometabolism to dementia.<\/jats:p><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Although evidence of liver involvement in dementia development has been documented in animal studies, the evidence in humans is limited.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Midlife NAFLD raised dementia risk proportionate to severity.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Late\u2010life NAFLD was not associated with a high risk of dementia.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Low alanine aminotransferase was associated with an elevated dementia risk, especially when measured in late life.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><\/jats:sec>","DOI":"10.1002\/alz.13601","type":"journal-article","created":{"date-parts":[[2023,12,28]],"date-time":"2023-12-28T09:24:35Z","timestamp":1703755475000},"page":"1913-1922","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Liver integrity and the risk of Alzheimer's disease and related dementias"],"prefix":"10.1002","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8907-4898","authenticated-orcid":false,"given":"Yifei","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Epidemiology, Gillings School of Global Public Health University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James 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