{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T14:43:33Z","timestamp":1791816213618,"version":"4.3.4"},"reference-count":40,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T00:00:00Z","timestamp":1744243200000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG089445"],"award-info":[{"award-number":["R01AG089445"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG076234"],"award-info":[{"award-number":["R01AG076234"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01DK133465"],"award-info":[{"award-number":["R01DK133465"]}],"id":[{"id":"10.13039\/100000062","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":[[2025,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>INTRODUCTION<\/jats:title><jats:p>Whether reductions in glycated hemoglobin (HbA1c) levels and body mass index (BMI) mediate the association between glucagon\u2010like peptide\u20101 receptor agonists (GLP\u20101RAs) and Alzheimer's disease and related dementias (ADRD) risk is unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>This cohort study included 22,908 patients aged \u2265 50 years with type 2 diabetes (T2D) newly prescribed GLP\u20101RA or other second\u2010line glucose\u2010lowering drugs (GLDs). Causal mediation analysis was used to estimate to what extent the effect of GLP\u20101RAs on ADRD risk was attributable to lowering HbA1c or BMI.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Compared to other GLD users, GLP\u20101RA users had significant reductions in HbA1c levels by 0.16% and BMI by 0.23\u00a0kg\/m<jats:sup>2<\/jats:sup>, along with a 26% lower ADRD risk. The direct protective effect of GLP\u20101RAs on ADRD risk persisted even after accounting for HbA1c and BMI reductions, with minimal mediation effects observed through these factors.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>GLP\u20101RAs reduce ADRD risk, largely independent of their effects on HbA1c and BMI.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Glucagon\u2010like peptide\u20101 receptor agonists (GLP\u20101RAs) were associated with reductions in glycated hemoglobin (HbA1c) and body mass index (BMI) compared to other second\u2010line glucose\u2010lowering drugs(GLDs).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>GLP\u20101RA users were associated with a 26% lower risk of Alzheimer's disease and related dementias (ADRD) than other GLD users.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The protective effect of GLP\u20101RAs against ADRD in adults with type 2 diabetes (T2D) is largely independent of their effects on HbA1c and BMI.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.70161","type":"journal-article","created":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T04:59:01Z","timestamp":1744261141000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Glycated hemoglobin and body mass index as mediators of GLP\u20101RAs and Alzheimer's disease and related dementias in patients with type 2 diabetes"],"prefix":"10.1002","volume":"21","author":[{"given":"Huilin","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Outcomes and Policy University of Florida College of Pharmacy  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William T","family":"Donahoo","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Florida College of Medicine  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven T.","family":"DeKosky","sequence":"additional","affiliation":[{"name":"Department of Neurology and McKnight Brain Institute University of Florida College of Medicine  Gainesville Florida USA"},{"name":"Florida Alzheimer's Disease Research Center (ADRC) University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao An","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Outcomes and Policy University of Florida College of Pharmacy  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikael","family":"Svensson","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Outcomes and Policy University of Florida College of Pharmacy  Gainesville Florida USA"},{"name":"Center for Drug Evaluation and Safety University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang","family":"Bian","sequence":"additional","affiliation":[{"name":"Department of Health Outcomes and Biomedical Informatics College of Medicine University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingchuan","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Outcomes and Policy University of Florida College of Pharmacy  Gainesville Florida USA"},{"name":"Center for Drug Evaluation and Safety University of Florida  Gainesville Florida 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