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

Abstract

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 years), living in the 20% most disadvantaged neighborhoods (n = 19) relative to state of residence was associated with cortical thinning in Alzheimer signature regions (p = 0.002) and decline in the Preclinical Alzheimer's Disease Cognitive Composite (p = 0.04), particularly the Trail-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 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.

Figure 1. Association Between Neighborhood-Level Disadvantage and Per-Year Change in Cortical Thickness in Alzheimer Disease (AD) Signature Regions

Plot depicts per-year change in cortical thickness in AD signature meta–regions of interest (ROIs) and individual component ROIs (middle temporal, fusiform, entorhinal, precuneus, inferior temporal, and inferior parietal). Colors of ROIs on cortical surface displayed above plot correspond to ROI label colors on plot. Estimated annual change in ROI thickness and 95% confidence intervals are displayed for participants with the 20% most relative neighborhood-level disadvantage (red lines) and those with the 80% least disadvantage (blue lines), adjusted for baseline age, sex, and years of education. Participants living in the most relatively disadvantaged neighborhoods exhibited significant cortical thinning in AD signature meta-ROI and middle temporal, entorhinal, and inferior parietal subregions compared with those living in the least disadvantaged neighborhoods. Unadjusted p values from regression model neighborhood-level disadvantage terms are displayed for each ROI: ns p > 0.1, #p < 0.1, *p < 0.05, **p < 0.01.

Figure 2. Association Between Neighborhood-Level Disadvantage and Longitudinal Cognitive Trajectories

Plots depict performance on Preclinical Alzheimer's Cognitive Composite–Revised (PACC-R) composite (A) and component subtests (B–D) on the y-axis and age on the x-axis. Higher scores equate to better performance on cognitive test (Trail-Making Test, part B [TMT-B] scores are multiplied by −1 for graphical consistency). Cognitive test scores are adjusted for sex, years of education, practice effects, and individual-level intercepts and slopes. Small lines (spaghetti plot) depict individual trajectories; large lines depict estimated quadratic slopes for participants with the 80% least neighborhood-level disadvantage (blue lines, n = 582) and 20% most disadvantage (red lines, n = 19). Participants from the most highly disadvantaged neighborhoods exhibited significantly steeper decline in PACC-R and TMT-B than participants from less disadvantaged neighborhoods, but showed no difference in decline of Story Memory Delayed Recall (SM-D) or Rey Auditory Verbal Learning Test, total trials 1–5 (RAVLT-L). Unadjusted p values for age2:neighborhood disadvantage interaction terms are displayed on plots for each cognitive test: ns p > 0.05, *p < 0.05, ***p < 0.001.

Figure 3. Mediation Testing of the Association Between Neighborhood-Level Disadvantage and Per-Year Change in Cognitive Performance via Per-Year Change in Cortical Thickness

(A) A hypothetical model for mediation of the effect of neighborhood-level disadvantage on cognitive decline via thinning in Alzheimer disease (AD) signature cortical regions. Separate mediation models were tested for the Preclinical Alzheimer's Cognitive Composite–Revised (PACC-R) (B) and for component subtests Trail-Making Test, part B (TMT-B) (C), Story Memory Delayed Recall (SM-D) (D), and Rey Auditory Verbal Learning Test, total trials 1–5 (RAVLT-L) (E). For each mediation model, parameter estimates for total (blue), direct (red), and indirect (green) are displayed. 95% Confidence intervals were constructed using nonparametric percentile bootstrapping (10,000 iterations). The loss of cortical thickness in AD signature regions significantly mediated the effect of neighborhood-level disadvantage on the declining performance on PACC-R, subtests TMT-B and RAVLT-L, but not subtest SM-D. Significance testing of mediation model parameters: ns p > 0.1, #p < 0.1; *p < 0.05; **p < 0.01.