Association of Neighborhood-Level Disadvantage With Cerebral and Hippocampal Volume

Abstract

Importance: Identifying risk factors for brain atrophy during the aging process can help direct new preventive approaches for dementia and cognitive decline. The association of neighborhood socioeconomic disadvantage with brain volume in this context is not well known.

Objective: To test whether neighborhood-level socioeconomic disadvantage is associated with decreased brain volume in a cognitively unimpaired population enriched for Alzheimer disease risk.

Design, setting, and participants: This study, conducted from January 6, 2010, to January 17, 2019, at an academic research neuroimaging center, used cross-sectional data on 951 participants from 2 large, ongoing cohort studies of Alzheimer disease (Wisconsin Registry for Alzheimer's Prevention and Wisconsin Alzheimer's Disease Research Center clinical cohort). Participants were cognitively unimpaired based on National Institute on Aging-Alzheimer's Association workgroup diagnostic criteria for mild cognitive impairment and Alzheimer disease, confirmed through a consensus diagnosis panel. The cohort was enriched for Alzheimer disease risk based on family history of dementia. Statistical analysis was performed from April 3 to September 27, 2019.

Main outcomes and measures: The Area Deprivation Index, a geospatially determined index of neighborhood-level disadvantage, and cardiovascular disease risk indices were calculated for each participant. Linear regression models were fitted to test associations between relative neighborhood-level disadvantage (highest 20% based on state of residence) and hippocampal and total brain tissue volume, as assessed by magnetic resonance imaging.

Results: In the primary analysis of 951 participants (637 women [67.0%]; mean [SD] age, 63.9 [8.1] years), living in the 20% most disadvantaged neighborhoods was associated with 4.1% lower hippocampal volume (β = -317.44; 95% CI, -543.32 to -91.56; P = .006) and 2.0% lower total brain tissue volume (β = -20 959.67; 95% CI, -37 611.92 to -4307.43; P = .01), after controlling for intracranial volume, individual-level educational attainment, age, and sex. Robust propensity score-matched analyses determined that this association was not due to racial/ethnic or demographic characteristics. Cardiovascular risk score, examined in a subsample of 893 participants, mediated this association for total brain tissue but not for hippocampal volume.

Conclusions and relevance: For cognitively unimpaired individuals, living in the most disadvantaged neighborhoods was associated with significantly lower cerebral volumes, after controlling for maximal premorbid (total intracranial) volume. This finding suggests an association of community socioeconomic context, distinct from individual-level socioeconomic status, with brain volume during aging. Cardiovascular risk mediated this association for total brain tissue volume but not for hippocampal volume, suggesting that neighborhood-level disadvantage may be associated with these 2 outcomes via distinct biological pathways.

Figure 1.. Mapping Neighborhood Socioeconomic Disadvantage Onto the Study Population

A, Area disadvantage (ADI) scores are calculated for every census block group in each state and converted to relative deciles based on statewide norms. The state of Wisconsin is shown as an illustrative example. B, Study population residential zip codes +4 (neighborhoods) are geocoded and mapped to nearest block group. C, ADI deciles from matching block groups are mapped onto participant neighborhood. Pop-out highlights the increased density of block groups characteristic of urban areas. Gray areas indicate no study participants residing in corresponding block group.

Figure 2.. Association of Neighborhood-Level Disadvantage With Lower Total Brain Tissue Volume and Hippocampal Volume

A, Total brain tissue volume. B, Total brain tissue volume by sex. C, Hippocampal volume. D, Hippocampal volume by sex. Total brain tissue and hippocampal volume were significantly lower in participants living in the most disadvantaged neighborhoods. Male participants living in the most disadvantaged neighborhoods had significantly lower mean hippocampal volume than female participants living in the most disadvantaged neighborhoods. There was no significant difference in total brain tissue volume between male and female participants living in the most disadvantaged neighborhoods. All volumetric values are adjusted for intracranial volume, age, sex, educational level, and magnetic resonance imaging scanner variables and are standardized (z score) for direct comparison between brain volume outcomes. Box plots show means with 95% CIs estimated by bootstrapping with 1000 iterations.

Figure 3.. Cardiovascular Risk Mediation of Association Between Neighborhood-Level Disadvantage and Global Brain Volume

A, Conceptual model for path analysis and mediation model parameters. B, Results of cardiovascular risk mediation of neighborhood-level disadvantage on total hippocampal volume. C, Results of cardiovascular risk mediation of neighborhood-level disadvantage on total brain tissue volume. z-Score–scaled β coefficients (Cohen d statistic) for relevant variables are shown for stepwise multiple regression models in path analysis (X → M and M → Y), Cohen d and 95% CIs are shown for estimation of indirect, direct and total effects using quasi-bayesian Monte Carlo simulation mediation modeling. Effect sizes can be directly compared between the 2 outcomes. Cardiovascular risk significantly mediated the association between neighborhood disadvantage and total brain tissue volume, but not for hippocampal volume. All models control for intracranial volume, age, sex, educational level, and magnetic resonance imaging scanner variables. ^aP < .001. ^bP < .10. ^cP < .01. ^dP > .10. ^eP < .05.