Independent associations of phosphorylated tau181 and neurofilament light with cognitive outcomes in the Health and Aging Brain Study–Health Disparities (HABS-HD)

BackgroundThe extent to which plasma biomarkers of Alzheimer's disease and neurodegeneration capture domain-specific cognitive performance across diverse populations remains unclear.ObjectiveTo determine whether plasma phosphorylated tau181 (p-tau181) and neurofilament light (NfL) are independently associated with cognitive domains, and whether associations differ across non-Hispanic White (NHW), non-Hispanic Black (NHB), and Hispanic participants.MethodsWe analyzed 3023 community-dwelling older adults from the Health and Aging Brain Study-Health Disparities (38.4% NHW, 22.6% NHW, 38.9% Hispanic). We used linear regressions to test associations between plasma biomarkers and cognitive domains (memory, executive function, processing speed, language), adjusting for age, sex, education, and apolipoprotein ε4 carriership. We fit models including both p-tau181 and NfL to assess their independent associations, evaluate biomarker × racial/ethnic interactions, and test p-tau181 × NfL interactions within each racial/ethnic group.ResultsAmong NHW participants, higher p-tau181 and NfL were associated with poorer memory, executive function, processing speed, and language. In NHB participants, p-tau181 was associated with memory, showed attenuated associations for language, and demonstrated similar associations with executive function and processing speed as observed in NHW participants. In Hispanic participants, p-tau181 was associated with memory and processing speed but was nonsignificant for executive function and language, and NfL showed significant but attenuated associations across all domains. Higher p-tau181 and NfL were jointly associated with slower processing speed only in NHW and NHB participants.ConclusionsPlasma p-tau181 and NfL were associated with multiple cognitive domains, with the strongest effects in NHW participants and attenuated associations in NHB and Hispanic individuals.