Living in Disadvantaged Neighborhoods Linked to Brain Atrophy

Damian McNamara

January 15, 2020

There is a "robust" link between living in a disadvantaged neighborhood and developing brain atrophy over time, a finding that carries potential implications for cognitive function as individuals age, new research suggests.

In a study of almost 1000 participants, those who lived in the most disadvantaged neighborhoods were more likely to have significantly smaller hippocampal and total brain tissue volume vs other middle-aged and older adults who lived in areas with the least disadvantage. Living in the most disadvantaged neighborhood was equivalent to a mean of 7 years of age-related hippocampal atrophy.

This is the first study to show a "robust association" between neighborhood-level disadvantage and hippocampal volume, the investigators note. Interestingly, men living in this kind of environment were at higher risk for this type of atrophy compared with women.

"Neighborhood disadvantage — a fundamental social determinant of health reflecting education, income, employment, and housing quality within a precise geographic area — was found to be associated with cerebral and hippocampal volume," study author Amy J.H. Kind, MD, PhD, Medicine Health Services and Care Research Program, Wisconsin Alzheimer's Disease Research Center, University of Wisconsin, Madison, told Medscape Medical News.

The results "may point to important population markers that can be leveraged in future research studies focusing on brain health," Kind added.

The findings were published online January 6 in JAMA Neurology.

You Are Where You Live?

The hippocampus may be one of the brain regions particularly vulnerable to neighborhood disadvantages, the researchers write. Such conditions can drive daily changes in cortisol patterns and the way individuals respond to stressors. Previous research has also linked chronic stress to changes in hippocampal structure and function.

Prior studies have examined how individual socioeconomic status (SES) might contribute to neurodegeneration risk. However, the current investigators chose to examine neighborhood-level associations because they include more potential contributors.

"The association of an individual's neighborhood context with health and disease is distinct from — and sometimes greater than — the association of individual SES with health and disease," they write.

The analysis included 951 cognitively unimpaired, community-dwelling adults. The investigators assessed T1-weighted structural MRI scans from two longitudinal studies: the Wisconsin Registry for Alzheimer's Prevention and the Wisconsin Alzheimer's Disease Research Center cohorts.

Total hippocampal volume was calculated by combining both left and right measures, as well a total brain tissue volume based on total white and gray matter. These outcomes were chosen "based on their previously reported associations with Alzheimer disease and related dementias," the researchers report.

They also compared participants living in the most and least disadvantaged neighborhoods using 17 US census factors in the Area Deprivation Index (ADI). The ADI takes poverty, education, employment status, and physical environment into account.

For example, those living in the most disadvantaged neighborhoods reported significantly less education than those in the least disadvantaged area (mean of 15 years vs 16.4 years, respectively). In addition, a lower proportion of the most disadvantaged group identified as white (66% vs 90%) and fewer were black/African American (34% vs. 7%).

Age, sex, parental dementia history, and APOE-ε4 allele status did not differ significantly between these cohorts.

Residential Revelations

Compared with living in the least disadvantaged areas, living in the most disadvantaged neighborhoods was associated with a 4.1% lower hippocampal volume (β = −317.44; 95% confidence interval [CI], −543.32 to −91.56; P = .006). However, after adjusting for total brain volume, the decrease in hippocampal volume was 3%.

Total brain volume was 2% less among residents of the most disadvantaged communities (β = −20,959.67; 95% CI, −37,611.92 to −4307.43; P = .01).

Overall, men and older participants were more likely to have lower hippocampal and total brain volumes. Higher educational levels were protective in terms of higher total brain volume only.

The researchers also evaluated any contribution to the associations they found from cardiovascular disease risk.

Although they uncovered no link between cardiovascular risk and hippocampal volume, they did find "significant negative associations" between how participants scored on the atherosclerotic cardiovascular disease (ASCVD) measure and total brain volume.

Furthermore, the 10-year ASCVD score of participants living in the most disadvantaged neighborhoods was 3.9% higher than for other areas, which was a significant difference.

Another Step Forward

One of the study's potential limitations was that the investigators "enriched" their study cohort for Alzheimer disease risk by including older participants and those with a parental history of dementia.

This group "might be particularly vulnerable to the deleterious effects of neighborhood-level disadvantage on the hippocampus," they write. In addition, the findings reflect associations and not causality because the study was cross-sectional and observational in design.

The mechanism behind the associations in the study also remains an unanswered question. In other words, does the neighborhood-level disadvantage reflect accelerated age-related cerebral atrophy, pathologic neurodegenerative processes, or both?

Regardless, "this new research takes another step toward better understanding of social-biological mechanisms," Kind said.

Going forward, neighborhood-level disadvantage could be considered in clinical decision-making or guide public health initiatives that promote healthy brain aging in at-risk neighborhoods, the researchers write.

"There is much yet to be learned," Kind said. "We look forward to expanding these investigations in the coming years to offer additional data on these factors within different populations and for varying points across the life course."

Robust Racial Link

Commenting on the findings for Medscape Medical News, Jennifer Manly, PhD, professor at the Taub Institute for Research on Alzheimer's Disease at Columbia University Irving Medical Center in New York City, said the study is an important addition to the literature because of the associations shown between social forces and brain health.

"This study is unable to make causal conclusions but is consistent with prior work on neighborhood and health," said Manly, who was not involved with the research.

She added that the study's link between neighborhood disadvantage and race was "very strong." Black participants accounted for 34% of the study population living in the most disadvantaged neighborhoods but only 7% of the least disadvantaged areas, Manly noted.

Raising awareness "that social inequalities limit individual health behaviors and increase exposure to potential harms," is one of the research implications of the study, she said.

Manly added that some neighborhood risk factors could be mitigated. For example, many disadvantaged neighborhoods have less green space, fewer places to walk or exercise, more noise and pollution, and less access to healthcare, she said.

As reported by Medscape Medical News, Manly was the senior author of a recent study showing that illiteracy was associated with a threefold increase in dementia risk.

Going forward, more research is warranted, including studies that evaluate larger and more representative population samples; consider other social factors that could influence brain health over a lifetime, such as childhood poverty; and are designed longitudinally "where cause and effect can be properly examined," Manly said.

Also commenting on the findings for Medscape Medical News, Robbert Gobbens, PhD, Inholland University of Applied Sciences in Amsterdam, the Netherlands, applauded the researchers for using ADI.

ADI's four individual components — poverty, education, employment, and physical environment — and their association with brain volumes could be helpful, added Gobbens, who is lead author of a previous study assessing the link between environmental factors and quality of iife in older adults.

However, he noted that the study's cross-sectional design was a limitation, explaining that a longitudinal study would be useful in confirming the link between living in disadvantaged neighborhoods and brain atrophy

The study was supported by the National Institute on Aging, the National Institute on Minority Health and Health Disparities, and the UW Institute for Clinical and Translational Research. Kind reports receiving grants from these two NIH institutes and the NIH in general during the conduct of the study. Gobbens has disclosed no relevant financial relationships.

JAMA Neurol. Published online January 6, 2020. Abstract

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