The study, recently featured in Alzheimer's & Dementia: Behavior & Socioeconomics of Aging (a journal of the Alzheimer's Association), found that people residing in neighborhoods marked by greater social vulnerability, environmental inequities, and economic hardship showed measurable differences in both brain structure and activity.

"This study is consistent with other research showing that the state of the social environment in which people live can shape their brain health in profound ways," said Timothy Hughes, Ph.D., associate professor of gerontology and geriatric medicine at Wake Forest University School of Medicine and senior author.

How the Study Was Conducted

The researchers examined data from 679 adults participating in the Healthy Brain Study at the Wake Forest Alzheimer's Disease Research Center. Each volunteer received brain imaging and blood testing designed to detect early indicators of Alzheimer's disease and related forms of dementia.

Those biological results were then compared with three national tools that measure neighborhood conditions by zip code: the Area Deprivation Index, the Social Vulnerability Index, and the Environmental Justice Index. These indices assess factors such as income, housing quality, pollution exposure, and community resilience.

Clear Links Between Neighborhood Stress and Brain Changes

Participants living in areas with higher scores on these indices -- indicating more social and environmental disadvantages -- showed greater evidence of brain changes tied to dementia risk. These effects were most pronounced among Black participants, whose communities often face higher levels of environmental and socioeconomic strain.

The brain-related markers included a thinner cerebral cortex, white matter changes linked to vascular disease, and reduced or uneven blood flow. Such biological differences may contribute to memory problems and cognitive decline as people age.

Environment's Lasting Impact on the Brain

"This study is one of the first to connect a variety of place-based social factors with advanced biological markers of dementia," said Sudarshan Krishnamurthy, a sixth-year M.D.-Ph.D. candidate and the study's lead author. "It shows that the conditions and environment in which people live -- such as access to clean air, safe housing, nutritious food and economic opportunity -- may leave a lasting imprint on brain health.

The findings add to growing scientific evidence that where people live and the resources available to them are not just background influences but critical factors in understanding and addressing Alzheimer's disease and related disorders.

A Call for Broader Policy Action

Krishnamurthy noted that these results highlight the need for systemic change.

"If we truly want to improve brain health across all communities, we must look beyond individual choices and hone in on the broader systems and structures that shape health at the neighborhood level."

The study was supported by the National Institutes of Health (grants F30 AG085932 and P30 AG07294) and the American Heart Association (grant 24PRE1200264).

Aging affects every part of the body, inside and out. The wrinkles and gray hair that appear on the surface often mirror similar changes happening deep within our organs. This connection suggests that aging does not occur in isolation but instead spreads throughout the body in a coordinated way. In other words, when one system begins to age, others may follow.

A research team at the University of Tsukuba turned its attention to a molecule called CtBP2 while studying the biological links between obesity and metabolism. CtBP2 acts as a sensor that responds to metabolic changes, and earlier research had shown that its activity declines in people with obesity, which can contribute to metabolic syndrome. Interestingly, stimulating or activating CtBP2 has been shown to produce therapeutic effects that improve metabolism.

The Tsukuba scientists explored CtBP2 in greater depth to understand its molecular behavior. They discovered that this molecule, once believed to function only inside cells, is actually released outside the cell when activated. When CtBP2 is active and present in the bloodstream, it helps maintain healthy metabolism across the body. However, when its activity is disrupted, it can trigger systemic aging and an increase in health-related issues. This finding supports the idea that aging occurs as an interconnected, body-wide process rather than a series of isolated events.

After developing a method to measure CtBP2 levels in blood samples, the researchers observed that these levels tend to decline with age. People from long-lived families, however, consistently showed higher concentrations of CtBP2 in their blood. In contrast, individuals with advanced diabetes complications had notably lower levels. These results suggest that measuring CtBP2 in the blood could serve as a useful biomarker for assessing both biological aging and overall health.

The researchers believe their discovery could pave the way for new ways to monitor and promote healthy aging. By using CtBP2 as an indicator, doctors and scientists may one day be able to estimate a person’s aging status and develop personalized health strategies. Future research could also explore how to safely boost CtBP2 secretion in the bloodstream to slow age-related decline and improve overall well-being.

This research was supported by the Japan Promotion of Science (Grant Numbers 20K08855 and 23K18270 to M.S.), the Japan Agency for Medical Research and Development (AMED) under Grant Numbers JP18gm5910007, JP25gm6710004 and JP22ek0210175, Takeda Science Foundation, Ono Medical Research Foundation, Manpei Suzuki Diabetes Foundation and Japan Diabetes Foundation (to M.S.)