3 Area Deprivation Index Interacts with Sex to Predict Atrophy and Cognitive Trajectory Over a 5-Year Follow-Up Period

Objective:Area Deprivation Index (ADI) is a measurement of neighborhood disadvantage. Evidence suggests that living in a disadvantaged neighborhood has a negative impact on health outcomes independent of socioeconomic status, including increased risk for Alzheimer's disease (AD). However, less is known about the biological mechanisms that drive these associations. We examined how ADI influences structural imaging variables and cognitive performance in community-dwelling older adults. We hypothesized that greater neighborhood disadvantage would predict atrophy and worse cognitive trajectory over time.Participants and Methods:Participants included the legacy cohort from the Vanderbilt Memory and Aging Project (n=295, 73±7 years of age, 16±3 years of education, 42% female, 85% non-Hispanic White) who lived in the state of Tennessee. T1-weighted and T2-weighted fluid-attenuated inversion recovery brain MRIs and a comprehensive neuropsychological assessment were acquired at baseline, 18-month, 3-year, 5-year and 7-year follow-up time (mean follow-up time=5.2 years). Annual change scores were calculated for all neuropsychological and structural MRI outcome variables. Baseline state ADI was calculated using the University of Wisconsin School of Medicine and Public Health Neighborhood Atlas (Kind & Buckingham, 2018) and was based on deciles where 1 represents the least deprived area and 10 represents the most. Mixed effects regression models related baseline ADI to longitudinal brain structure (volume, thickness, white matter hyperintensities) and neuropsychological trajectory (one test per model). Analyses adjusted for age, sex, race/ethnicity, education, Framingham Stroke Risk Profile score, (apolipoprotein) APOE-e4 status, cognitive status, and intracranial volume (for MRI outcomes). Models were repeated testing interactions with APOE-e4 status, sex, and cognitive status. A false discovery rate (FDR) correction for multiple comparisons was performed.Results:On average, the sample was from relatively less disadvantaged neighborhoods in Tennessee (ADI state decile=2.4±1.8). Greater neighborhood disadvantage at study entry predicted more thinning of an AD-signature composite over time (ß=-0.002, p=0.005, pFDR=0.06); however, all other models testing MRI and neuropsychological outcomes were null (p-values>0.05, pFDR-values>0.51). Baseline ADI interacted with sex on longitudinal cortical thinning captured on the AD-signature composite (ß=0.004, p=0.006, pFDR=0.08) as well as several longitudinal cognitive outcomes including an executive function composite score (ß=0.033, p<0.001, pFDR=0.01), naming (ß=0.10, p=0.01, pFDR=0.12), visuospatial functioning (ß=0.083, p=0.02, pFDR=0.09), and an episodic memory composite score (ß=0.021, p=0.02, pFDR=0.07). In stratified models by sex, greater ADI predicted greater cortical thinning over time and worse longitudinal neuropsychological performance among men only. All stratified models in women were null except for executive function composite score, which did not survive correction for multiple comparisons (ß=-0.013, p=0.03, pFDR=0.61). Interactions by APOE-e4 and cognitive status were null (p-values>0.06, pFDR-values>0.61).Conclusions:Among community-dwelling older adults, greater neighborhood disadvantage predicted greater cortical thinning over the mean 5-year follow-up in anatomical regions susceptible to AD-related neurodegeneration. Neighborhood disadvantage also interacted with sex on cortical thickness and several cognitive domains, with stronger effects found among men versus women. By contrast, there were no interactions between neighborhood disadvantage and genetic risk for AD or cognitive status. This study provides valuable evidence for sociobiological mechanisms that may underlie health disparities in aging adults whereby neighborhood deprivation is linked with neurodegeneration over time.