Investigation of neighborhood disadvantage in the context of APOE‐associated amyloid onset age risk

Abstract

AbstractBackgroundExposome social determinants of health (SDoH), such as neighborhood disadvantage, have shown associations with accelerated cognitive decline, brain volume loss, and postmortem AD pathology. However, associations between neighborhood disadvantage and amyloid biomarker positivity (A+) onset remain understudied. This study uses estimated A+ onset age (EAOA) and the Area Deprivation Index (ADI; an exposome SDoH) to investigate associations between neighborhood disadvantage and A+ risk.MethodsParticipants (n = 599, Table 1) from the Wisconsin Registry for Alzheimer’s Prevention (WRAP) and the Wisconsin Alzheimer’s Disease Research Center (WADRC) with available amyloid PET, address, and APOE genotype were included. EAOA was estimated using sampled iterative local approximation. Neighborhood disadvantage was categorized by national‐rank 2020 ADI (most disadvantaged ≥80th percentile; least disadvantaged <80th percentile). APOE groups were established based on the number of e4 alleles. Cox proportional hazard models assessed A+ risk associated with APOE, ADI, and their interaction. Secondary Cox models used continuous ADI and a lower 70th ADI percentile for neighborhood groups. Kaplan‐Meier curves were generated to depict A‐ probability vs. age for combinations of APOE and ADI groups. A‐ were right censored.ResultsA significant interaction (p = 0.015) between ADI and APOE groups was observed such that APOE‐e4 homozygotes who resided within a highly disadvantaged neighborhood had higher risk of becoming A+, but this group was limited to two participants. Secondary analyses indicated no significant effect of ADI or interaction with APOE on A+ risk (p>0.49). Plots of A+/‐ and EAOA by ADI and APOE group (Figure 1) and Kaplan‐Meier EAOA curves indicated EAOA overlap of ADI groups within APOE strata. A+ risk was significantly higher for APOE‐e4 homozygotes, followed by APOE‐e4 heterozygotes, and then APOE‐e4 non‐carriers.ConclusionsIn this mostly unimpaired, highly educated sample, higher number of APOE‐e4 alleles was associated with higher A+ risk and earlier A+ onset. APOE‐associated A+ risk was similar for all ADI groups, but representation across APOE genotypes for individuals residing within highly disadvantaged neighborhoods was limited. Further work is needed in more diverse samples to investigate the possible influence of ADI and other exposome SDoH factors on AD biomarker timing and trajectories.