Neighborhood disadvantage is associated with changes in cerebrovascular function among older adults over a 9 year follow‐up period

Background Stressful social environments exert a strong influence on unhealthy aging, both in greater magnitude and independent of individual socioeconomic and lifestyle factors. Neighborhood disadvantage specifically has been linked to accelerated biological aging, cognitive decline, and core Alzheimer’s disease (AD) neuropathology, but little is known about whether neighborhood disadvantage contributes to cerebrovascular dysfunction commonly observed in aging and AD. We examine whether neighborhood disadvantage relates to changes in cerebrovascular outcomes over time, including blood‐brain barrier (BBB) integrity, cerebral blood flow (CBF), and small vessel disease (SVD) biomarkers. Methods Vanderbilt Memory and Aging Project participants (n = 296, 73±7 years, 40% female) underwent fasting blood and cerebrospinal fluid (CSF) acquisition serially over a 9‐year follow‐up period (mean follow‐up = 5.5 years). Area Deprivation Index (ADI), representing neighborhood disadvantage, was quantified at baseline based on 17 components [e.g., housing, income, education, and household characteristics (Kind & Buckingham, 2018)]. BBB markers (MMP‐2, MMP‐3, MMP‐9, TIMP‐1, TIMP‐2, PDGFRβ) were quantified from CSF and CSF/plasma albumin ratio was quantified from both CSF and plasma. 3T multimodal MRI images were used to quantify grey matter CBF and SVD markers, including white matter hyperintensities (WMHs), perivascular spaces (PVS), and lacunes. Linear mixed effects regression models related time x ADI to longitudinal BBB, CBF, and SVD outcomes adjusting for age, sex, race/ethnicity, education, cognitive status, Framingham Stroke Risk Profile (minus age), apolipoprotein ε4 status, and follow‐up time. CBF models additionally adjusted for corresponding grey matter volume while SVD models adjusted for T1‐weighted intracranial volume. Results Baseline ADI related to increased MMP‐9 (β = 0.03, p‐value = 0.01) and decreased PDGFRβ (β = ‐0.1407, p‐value0.35), SVD (p‐values>0.36), or other BBB outcomes (p‐values>0.07). Conclusions Neighborhood socioeconomic disadvantage relates to changes in BBB integrity among older adults over time, particularly molecular markers of barrier disruption and pericyte damage. Findings support the hypothesis that adverse environmental conditions, including low quality housing and community‐wide resource constraints, may contribute to early‐stage cerebrovascular dysfunction beyo