Abstract
BACKGROUND: Social determinants of health (SDOH) are increasingly recognized as contributors to Alzheimer disease (AD) risk, yet the impact of multidimensional social disadvantage early AD-related pathophysiology remains poorly understood. METHODS: We studied 1,466 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) cohort with SDOH assessed in early midlife (mean age 40 ± 3.6 years) and plasma AD biomarkers measured 20 years later. A comprehensive SDOH index was constructed from 12 indicators spanning five domains (economic stability, education, neighborhood and physical environment, community and social context, and health care access). We examined associations between SDOH quartile and log-transformed, standardized plasma phosphorylated tau 217 (p-tau217), neurofilament light chain (NfL), and amyloid-β42/40 (Aβ42/40) using linear regression adjusted for age, sex, race, and estimated glomerular filtration rate. Linear trends across SDOH quartile were also evaluated. RESULTS: Participants in the most disadvantaged SDOH quartile had higher p-tau217, higher NfL and lower Aβ42/40 level compared with those in the least disadvantaged quartile (p-tau 217: β = 0.12, 95% CI 0.03-0.21, p = 0.008; NfL: β = 0.20, 95% CI 0.05-0.35, p = 0.009; Aβ42/40: β = -0.15, 95% CI -0.30-0.00, p=0.05). There was also a significant trend across quartile (p-tau 217: p for trend = 0.012; NfL: p for trend =0.001). Analyses of individual SDOH domains indicated that lower economic stability, poorer health care access, and lower education were associated with higher NfL, and poorer health care access was associated with higher p-tau217. CONCLUSIONS: Greater SDOH disadvantage in early midlife was associated with higher levels of plasma AD biomarkers reflecting AD pathology and neurodegeneration decades later. These findings suggest that social disadvantage during midlife may contribute to early AD-related biological changes and highlight potentially modifiable social factors relevant for dementia prevention.