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How and Why Living in Disadvantaged Communities Contributes to Neurodegeneration

Article In Brief

Older residents who live in a neighborhood considered disadvantaged based on income, housing, and other indicators of poverty experienced more hippocampal volume loss than those who lived in more advantaged neighborhoods.

Where a person lives may be one of the social factors that can influence their brain health, suggests a new imaging study of older residents from urban and rural neighborhoods in Wisconsin. The neighborhoods were considered socioeconomically disadvantaged based on a measure that factors in income, education, employment, and housing quality in characterizing a neighborhood.

The paper, published January 6 online in JAMA Neurology, found older residents of the most disadvantaged neighborhoods had smaller hippocampal areas and total brain volume than their peers in less disadvantaged neighborhoods. However, the study authors acknowledged that the presence of cardiovascular disease factors such as obesity, hypertension, and cholesterol played a role in driving the loss of total brain volume.

Hippocampal and cortical volume loss precedes clinically-identifiable cognitive deficits, said study author Barbara Bendlin, PhD, associate professor at the University of Wisconsin-Madison School of Medicine and Public Health and Wisconsin Alzheimer's Disease Research Center (ADRC).

“We are seeing an effect of neighborhood disadvantage on the brain, which may translate to increased risk for developing dementia in the future,” said Dr. Bendlin, who co-led the study with Amy Kind, MD, PhD, associate professor in the division of geriatrics at the UW-Madison's School of Medicine and Public Health.

“This is the first study to show a robust association between hippocampal volume and disadvantaged neighborhoods,” she said.

The impact of neighborhood disadvantage on hippocampal volume was equivalent to the loss expected to be seen with an additional seven years of aging, said Dr. Bendlin.

The study is part of a larger research program that is examining a wide-range of factors that contribute to aging brain health or pathology being conducted at the Bendlin Laboratory at the University of Wisconsin and funded by the National Institute on Aging.

Study Design, Findings

For the current study, the researchers conducted a cross-sectional analysis of 951 cognitively unimpaired adults who underwent structural MRIs from January 6, 2010 to January 17, 2019. “These volumetric scans tell us something about the total size of the brain and brain structures,” said Dr. Bendlin.

The study volunteers were enrolled in the Wisconsin ADRC Clinical Core and the Wisconsin Registry for Alzheimer's Prevention study. The majority of participants were women (67 percent) with a mean age of 63.9 years. The vast majority were white (88.9 percent) and the remainder were black or African-American (8.2 percent), American Indian or Alaska Native (2.4 percent), Hispanic (0.85 percent) or other (0.5 percent). Sixty-five percent had a parental history of dementia.

The researchers used the Area Deprivation Index (ADI), a composite measure of neighborhood disadvantage based on 17 area-level US Census indicators of poverty, education, employment, and housing quality from the 2013 American Community Survey data. The ADI metrics are available through the Neighborhood Atlas, a geospatial tool developed by Dr. Kind, that is publicly available. The most disadvantaged neighborhoods made up 20 percent of all the neighborhoods studied.


“We are seeing an effect of neighborhood disadvantage on the brain, which may translate to increased risk for developing dementia in the future.”—DR. BARBARA BENDLIN

The participants in the most disadvantaged neighborhoods—in rural and urban areas—showed a significantly lower hippocampal volume (4.1 percent) and total brain tissue volume (2 percent) than participants in more advantaged neighborhoods, after controlling for intracranial volume, individual-level educational attainment, age, and sex.

“We determined from our follow-up analysis that the differences between the most and least disadvantaged groups were not due to racial/ethnic or demographic characteristics,” said Dr. Bendlin.

The researchers also estimated the hippocampal volume loss from living in the most disadvantaged neighborhood for the average study participant (a 64-year-old woman in the 50th percentile for hippocampal volume) was equivalent to a mean of seven years (95% CI, 2.5-12 years) of age-associated hippocampal atrophy.

The study was limited by having only 41 participants from the most disadvantaged neighborhoods compared with 910 participants from the least disadvantaged neighborhoods. In addition, the neighborhoods were only in Wisconsin.

“We need to broaden our research participation to other states and increase the ethno-racial and socioeconomic diversity of the sample. That's absolutely necessary if we are going to design interventions that benefit cognitive aging for all individuals,” said Dr. Bendlin.

She envisions clinical uses of the Neighborhood Atlas tool. “A physician could determine whether a patient resides in an area with an increased risk for poorer health outcomes. In forward-thinking personalized medicine, doctors should be aware of how contextual factors can affect disease risk and medical progress, including factors such as access to healthy foods, transportation to receive services, and factors that affect compliance with medication schedules.”

The researchers will continue to mine the cohort database to better understand the salient factors of neighborhood disadvantage that relate to brain aging such as the presence of co-morbidities and chronic stress and how that relates to where participants live over the years. They will also follow participants over time to see who develops dementia.

Expert Commentary

This study adds to the research literature showing associations between socioeconomic status and individual brain health, said Jennifer J. Manly, PhD, professor of neuropsychology in neurology at the Taub Institute for Research in Aging and Alzheimer's disease and the department of neurology at Columbia University in New York, who was not involved in the study.

Dr. Manly noted that previous studies looking at these associations have had mixed results. A common dilemma in research on brain health and the impact of where people live is that participants are not randomly sampled by neighborhood—in this study they were volunteers for a brain-imaging study. As a result, only 41 of the 951 total participants were in the group “exposed” to disadvantaged neighborhoods, said Dr. Manly.

Of the 41 participants in the exposed group, 34 percent were African-American compared with only 7 percent in more advantaged neighborhoods, noted Dr. Manly.

“That's a huge racial disparity and reflects how neighborhoods are segregated in Wisconsin and all over the country. There is a profound racial bias in housing opportunities and income barriers,” said Dr. Manly.

Major possible confounders in this study are racism, wealth, childhood socioeconomic status, and family resources. “It isn't clear whether these factors are contributing to neurodegeneration or whether the neighborhood is causing it,” she said.

Nonetheless, “it's clear that people living in neighborhoods that lack resources such as public spaces in good condition and proximity to public transit have fewer opportunities to age in a healthy way,” said Dr. Manly.

People living in more under-resourced neighborhoods may face increased stress and barriers to physical activity, she said. These barriers include a lack of safety, higher pollution and noise levels, and less green space. They may also have less access to health care, fewer transportation options, and may be under- or uninsured. If diseases including diabetes and hypertension are untreated, that can also increase the risk of neurodegeneration.

“We have a moral imperative to reduce social inequalities by improving neighborhood resources. We know social inequality is bad for a person's health. There is now growing evidence that inequality is also bad for someone's brain and cognition as they age,” said Dr. Manly.

She suggested that rather than using the Neighborhood Atlas tool to flag patients from lower socioeconomic neighborhoods, clinicians ask patients directly about their living situation and their neighborhood, such as whether it's noisy, has sidewalks, and whether they feel safe, and inquire about whether they experience issues with access to care such as transportation and insurance.

“This would help clinicians better understand the context in which patients live, and tailor treatment plans or disease prevention.”

However, clinicians have on average seven minutes to spend with patients per visit so “a medical care system that's interested in reducing disparities would reimburse doctors for spending more time with these patients,” said Dr. Manly.

“What is interesting and important about this study is that it shows the effects of socioeconomic disparities on the brains of healthy people,” said Martha J. Farah, PhD, director of the Center for Neuroscience and Society at the University of Pennsylvania, in an email.

“Recent studies of child development have shown that a child's home address is a significant predictor of their later life success. And, here we see that for healthy elders, residential neighborhood is also important in that it predicts brain atrophy.”

The findings also provide a new insight about the mechanisms linking neighborhood and brain health, in that cardiovascular risk factors accounted for the association between deprivation and overall brain size. However, the association between deprivation and hippocampal size appears to require a different explanation.

“We don't know what that is, but by raising the question the authors have taken us one step closer to knowing the answer,” said Dr. Farah.

A finding she considered particularly striking was the translation of the volume findings into equivalent years of aging. “Most of us don't really care about the size of particular brain structures in the abstract. But the idea that people living in a poor neighborhood have, on average, the hippocampal volume of better-off people who are seven years older, that puts the inequality in terms that we can all understand.”

Link Up for More Information

• Hunt JFV, Buckingham W, Kim AJ, et al. Association of neighborhood-level disadvantage with cerebral and hippocampal volume JAMA Neurol 2020; Epub 2020 Jan 6.