Area Deprivation Index is associated with biomarkers of inflammation cross‐sectionally and longitudinally over a 9‐year follow‐up period

Background

Living in a socioeconomically disadvantaged neighborhood has a negative impact on health outcomes, including increased risk for Alzheimer’s disease (AD). The biological mechanisms underlying this risk are poorly understood. We examined how neighborhood disadvantage relates to core AD pathology, neurodegeneration, and inflammatory biomarkers in community‐dwelling older adults

Method

Vanderbilt Memory and Aging Project participants (n = 327, 73±8 years, 41% female) underwent fasting blood and cerebrospinal fluid (CSF) acquisition serially over a 9‐year follow‐up period (mean follow‐up = 5.8 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)]. Ordinary least squares regressions cross‐sectionally related ADI to plasma and CSF biomarkers adjusting for age, sex, race/ethnicity, education, modified Framingham Stroke Risk Profile score, apolipoprotein E‐e4 status, and cognitive status. Linear mixed‐effects regression models related baseline ADI to longitudinal biomarkers with identical baseline covariates plus follow‐up time. Outcomes included CSF chitinase‐3‐like protein 1 (YKL‐40), CSF soluble triggering receptor expressed on myeloid cells 2 (sTREM2), CSF amyloid‐b₄₀ (Ab₄₀), CSF amyloid‐b₄₂ (Ab₄₂), CSF Ab₄₀/Ab₄₂ ratio, CSF tau, CSF phosphorylated tau (ptau), plasma high sensitivity C‐reactive protein (CRP), and plasma and CSF neurofilament light chain (NfL).

Result

On average, the sample was from relatively less disadvantaged neighborhoods (ADI national decile = 35.4±25.0, range = 1‐98). Greater neighborhood disadvantage at study entry was cross‐sectionally associated with elevated CSF YKL‐40 (β = ‐0.733, p = 0.003), sTREM2 (β = 19.74, p = 0.04), Aβ₄₀ (β = 35.96, p = 0.01), tau (β = 2.31, p = 0.02), and ptau (β = 0.33, p = 0.03). Greater neighborhood disadvantage at study entry related to longitudinal increases in CRP (β = 0.012, p<0.001) and decreases in plasma NfL (β = ‐0.025, p = 0.04) over the follow‐up period.

Conclusion

Among community‐dwelling older adults, greater neighborhood disadvantage was associated with elevated inflammatory and AD CSF biomarkers cross‐sectionally, and longitudinal increases in a non‐specific inflammatory blood biomarker. Collectively, findings suggest that neighborhood disadvantage confers immediate risk for systemic neuroinflammation and AD and future risk for non‐specific inflammation, providing valuable evidence of a sociobiological mechanism underlying health disparities in aging adults based on geographic location.

Funding. R01‐AG034962, K24‐AG046373, T32‐AG058524, P20‐AG068082