Abstract
AbstractBackgroundExpression of glial fibrillary acidic protein (GFAP), a marker of reactive astrocytosis, co‐localizes with neuropathology in the brain. Blood‐derived levels of GFAP have been associated with cognitive decline and dementia status. However, further examinations at a population‐based level are necessary to broaden generalizability and assess the biomarker’s potential efficacy in community settings.MethodPlasma GFAP levels were assayed using a Simoa HD‐1 analyzer in 4,338 adults without prevalent dementia from four longitudinal cohort studies, the Framingham Heart Study (FHS), the Cardiovascular Health Study (CHS), the Age, Gene/Environment Susceptibility – Reykjavik Study (AGES), and the Coronary Artery Risk Development in Young Adults Study (CARDIA). The associations between plasma GFAP levels with a general cognition score derived from multiple cognitive tests, 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 ε4 status, site, and time between GFAP blood draw and the outcome. Associations with incident all‐cause and Alzheimer’s disease dementia were evaluated with adjusted Cox proportional hazard models. Meta‐analysis was performed on the estimates derived from each cohort using random effects models with inverse variance weighting. The Sidik‐Jonkman estimator was used to report overall associations across studies.ResultMeta‐analysis indicated that higher plasma GFAP associated with lower general cognition (ß=‐0.09, [95% confidence interval [CI]: ‐0.15 to ‐0.03], p=0.005), but not with total brain or hippocampal volume (p>0.05 for all). However, higher GFAP was significantly associated with a 2.5‐fold higher risk of incident all‐cause (Hazard Ratio [HR]: 2.47 (95% CI: 1.52‐4.01)) and Alzheimer’s disease dementia (HR: 2.54 (95% CI: 1.42‐4.53) per standard deviation increase over up to 15‐years of follow‐up.ConclusionThe findings suggest that elevations in plasma GFAP may be detectable several years prior to a clinical diagnosis, highlighting the potential value of the biomarker for aiding dementia risk prediction at a population‐based level
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