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Blood levels of GFAP have been associated with cognitive decline and dementia status. However, further examinations at a population\u2010based level are necessary to broaden generalizability to community settings.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Circulating GFAP levels were assayed using a Simoa HD\u20101 analyzer in 4338 adults without prevalent dementia from four longitudinal community\u2010based cohort studies. The associations between GFAP levels with general cognition, total brain volume, and hippocampal volume were evaluated with separate linear regression models in each cohort with adjustment for age, sex, education, race, diabetes, systolic blood pressure, antihypertensive medication, body mass index, apolipoprotein E \u03b54 status, site, and time between GFAP blood draw and the outcome. Associations with incident all\u2010cause and Alzheimer's disease dementia were evaluated with adjusted Cox proportional hazard models. Meta\u2010analysis was performed on the estimates derived from each cohort using random\u2010effects models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Meta\u2010analyses indicated that higher circulating GFAP associated with lower general cognition (<jats:italic>\u00df<\/jats:italic>\u2009=\u2009\u22120.09, [95% confidence interval [CI]: \u22120.15 to \u22120.03], <jats:italic>p<\/jats:italic>\u2009=\u20090.005), but not with total brain or hippocampal volume (<jats:italic>p<\/jats:italic>\u2009&gt;\u20090.05). However, each standard deviation unit increase in log\u2010transformed GFAP levels was significantly associated with a 2.5\u2010fold higher risk of incident all\u2010cause dementia (Hazard Ratio [HR]: 2.47 (95% CI: 1.52\u20134.01)) and Alzheimer's disease dementia (HR: 2.54 [95% CI: 1.42\u20134.53]) over up to 15\u2010years of follow\u2010up.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Results support the potential role of circulating GFAP levels for aiding dementia risk prediction and improving clinical trial stratification in community settings.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.51652","type":"journal-article","created":{"date-parts":[[2022,9,3]],"date-time":"2022-09-03T07:39:09Z","timestamp":1662190749000},"page":"1574-1585","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["A <scp>population\u2010based meta\u2010analysis<\/scp> of circulating <scp>GFAP<\/scp> for cognition and dementia risk"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8467-0938","authenticated-orcid":false,"given":"Mitzi M.","family":"Gonzales","sequence":"first","affiliation":[{"name":"Glenn Biggs Institute for Alzheimer's &amp; 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