Adverse Social Exposome During the Life Course and Vascular Brain Injury.

Importance: The adverse social exposome, the entirety of harmful lifetime social-environmental exposures, is associated with Alzheimer disease and related dementias (ADRD) risk and may be key to informing modifiable systemic and behavioral risk interventions. With increasing emphasis to understand lifetime risk, methods are needed to measure and study social exposome relative to ADRD-related biological processes, including cerebrovascular disease. Objective: To evaluate the association between adverse social exposome and the burden of vascular brain injury (VBI) post mortem. Design, Setting, and Participants: This retrospective cohort study analyzed brain bank donors from 2 Alzheimer Disease Research Centers. Donations occurred between January 5, 2000, and August 5, 2018. Analysis was performed between January 13 and July 20, 2023. Exposures: Adverse social exposome, via geo-linked, time-concordant Area Deprivation Index (ADI) rankings for each year of a donor's lifetime. Main Outcomes and Measures: The main outcome consisted of the presence or absence of VBI indicators: infarcts, microinfarcts, hemorrhages, and white matter rarefaction. Association between cumulative or change in life-course ADI and VBI burden was evaluated using multivariate logistic regression models adjusted for sex and age at death. Results: The sample included 740 donors (417 female [56.4%]; mean [SD] age at death, 81.5 [10.3] years; mean [SD] VBI score, 0.7 [1.0]; and median life course ADI, 7.08 [IQR, 4.33-9.83]), with residential years spanning 1905 to 2018. In adjusted models, living more years in a county with an ADI ranked above the study population median was associated with increased VBI odds (adjusted odds ratio [AOR], 1.04; 95% CI, 1.03-1.05). Greater odds of VBI were identified in those with increasing ADI between youth and adulthood (AOR, 3.67; 95% CI, 3.65-3.70) and youth and older adulthood (AOR, 12.02; 95% CI, 7.87-18.35). Increased odds were found in groups with stable high median ADI from youth to adulthood (AOR, 3.08; 95% CI, 3.01-3.14) and youth to older adulthood (AOR, 8.46; 95% CI, 8.04-8.90). Conclusions and Relevance: In this cohort study of 740 brain bank donors, an association between ADI and the presence of VBI was indicated, when considering the full life course as well as specific life course periods. These results show promise for identifying geographic areas in need of targeted interventions to reduce cerebrovascular disease and ADRD risk factors.