Association of Neighborhood Context, Cognitive Decline, and Cortical Change in an Unimpaired Cohort.

OBJECTIVE To test the hypothesis that neighborhood-level disadvantage is associated with longitudinal measures of neurodegeneration and cognitive decline in an unimpaired cohort. METHODS Longitudinal MRI and cognitive testing data were collected from 601 cognitively unimpaired participants in the Wisconsin Registry for Alzheimer's Prevention study and the Wisconsin Alzheimer's Disease Research Center clinical cohort. Area Deprivation Index was geospatially determined based on participant residence geocode and ranked relative to state of residence. Linear regression models were fitted to test associations between neighborhood-level disadvantage and longitudinal change in cortical thickness and cognitive test performance. Mediation tests were used to assess whether neurodegeneration and cognitive decline were associated with neighborhood-level disadvantage along the same theoretical causal path. RESULTS In our middle to older aged study population (mean baseline age=59), living in the 20% most disadvantaged neighborhoods (N=19) relative to state of residence was associated with cortical thinning in Alzheimer's signature regions (p=0.002) and decline in the Preclinical Alzheimer's disease Cognitive Composite (p=0.04), particularly the Trails-Making Test Part B (p<0.001), but not Rey Auditory Verbal Learning Test (p=0.77) or Story Memory Delayed Recall (p=0.49) subtests. Associations were attenuated but remained significant after controlling for racial and demographic differences between neighborhood-level disadvantage groups. Cortical thinning partially mediated the association between neighborhood-level disadvantage and cognitive decline. CONCLUSIONS In this longitudinal study of cognitively unimpaired adults, living in the most highly disadvantaged neighborhoods was associated with accelerated degeneration in Alzheimer's signature regions and cognitive decline. This study provides further evidence for neighborhood-level disadvantage as a risk factor for preclinical neurodegeneration and cognitive decline in certain populations. Limitations of the present study, including a small number of participants from highly disadvantaged neighborhoods and a circumscribed geographic setting, should be explored in larger and more diverse study cohorts.