Life course neighborhood conditions and change: a 20-year examination of neighborhood context and associations with Alzheimer's disease biomarkers in late life.

INTRODUCTION: Life course models of Alzheimer's disease (AD) suggest that both long-term exposure to neighborhood conditions and changes in neighborhood context may shape dementia risk. This study examined the impact of mid- and late-life levels of neighborhood segregation, as well as longitudinal change in segregation, on plasma AD biomarkers. METHODS: Participants were 119 racially/ethnically diverse (60% Black/Latino) adults. Residential addresses were geocoded to temporally harmonized US Census tracts, and the dissimilarity index quantified segregation. Plasma neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and amyloid beta (Aβ) 42/40 were measured. RESULTS: Generalized estimating equations adjusting for individual-level sociodemographic and health characteristics revealed mid-life, but not late-life, levels of segregation were significantly associated with NfL. Increasing segregation across 10- and 20-year periods was associated with higher levels of GFAP and NfL, respectively. DISCUSSION: Mid-life levels of segregation and longitudinal change in segregation were linked to plasma markers of neurodegeneration and astroglial activation.