The association of blood‐based biomarkers of neuropathology with cognitive performance and dementia in a diverse, population‐based sample of US adults.

Background: The association of blood‐based biomarkers of neuropathology with cognition and dementia, including potential variation by race/ethnicity (whites, blacks and Hispanics), has not been examined in large, diverse, population‐based samples of adults. Method: The sample included Health and Retirement Study (HRS) respondents over age 50 with blood‐based neuropathology biomarker, demographic, and cognitive data (n = 4,214). A훃‐40, A훃‐42, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were measured in plasma (Quanterix Neurology 4‐Plex E kit), and phosphorylated tau (pTau‐181) was measured in serum (Quanterix Advantage V2.0 kit). Cognitive tests included immediate and delayed word recall, serial 7s, and backward counting (total score 0‐27). Dementia classification relied on a diagnostic algorithm previously validated in HRS. Linear and unconditional logistic regressions were weighted to account for sample design and used to model associations between the biomarkers and the cognitive score/dementia classification after controlling for age, sex, and batch effects. Result: About 80% of the sample was white, 10% black, and 10% Hispanic. Correlations were modest among pTau‐181, NfL, and GFAP (r = 0.29‐0.46). When the biomarkers were analyzed individually, higher A훃‐42/A훃‐40 ratio was associated with higher cognitive score among whites. Higher NfL was associated with lower cognitive score in the total sample and in each race/ethnic group (whites, blacks and Hispanics). Higher pTau‐181 was associated with lower cognitive score in the total and white sample. Higher GFAP was related to lower cognitive score in the total, white, and Hispanic samples. In a model that included all four biomarkers, GFAP remained significantly related to cognitive performance in the total sample, and NfL remained significantly related to cognitive performance in the total sample and in each race/ethnic group. When the biomarkers were analyzed individually, higher NfL was associated with higher likelihood of dementia in the total sample. Higher pTau‐181 was associated with higher likelihood of dementia among whites. Higher GFAP was associated with dementia in the total and white samples, alone and in the fully adjusted model with all four biomarkers. Conclusion: These results show the importance of examining blood‐based biomarkers of neuropathology as predictors of cognitive performance and dementia in diverse, population‐based samples. [ABSTRACT FROM AUTHOR]