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.)

Researchers say this discovery points to several possible ways the drug supports heart health, suggesting that its protective effects go beyond weight loss alone.

Large Study Confirms Broad Heart Benefits

Published in The Lancet and funded by Novo Nordisk, the study analyzed data from 17,604 adults aged 45 and older who were overweight and had cardiovascular disease. Participants were randomly assigned to receive either weekly semaglutide injections or a placebo.

Earlier results from the same international research team showed that semaglutide lowered the risk of heart attacks, strokes, and other major cardiac events by 20%.

In the new analysis, scientists found that these heart benefits occurred across all body types. People who were only slightly overweight, with a body mass index (BMI) of 27 (the average BMI among UK adults), experienced similar protection as participants with obesity and much higher BMIs.

Waist Size Plays a Role but Not the Whole Story

The reduction in cardiovascular risk remained largely the same no matter how much weight participants lost during the first four and a half months of treatment. However, a decrease in waist size (waist circumference) was linked to about one-third of the heart protection seen after two years on semaglutide.

Professor John Deanfield (UCL Institute of Cardiovascular Science), who led the study, explained: "Abdominal fat is more dangerous for our cardiovascular health than overall weight and therefore it is not surprising to see a link between reduction in waist size and cardiovascular benefit. However, this still leaves two thirds of the heart benefits of semaglutide unexplained."

He added, "These findings reframe what we think this medication is doing. It is labelled as a weight loss jab but its benefits for the heart are not directly related to the amount of weight lost. In fact it is a drug that directly affects heart disease and other diseases of aging."

Implications for How the Drug Is Used

According to Professor Deanfield, the research could change how semaglutide and similar drugs are prescribed. "You don't have to lose a lot of weight and you don't need a high BMI to gain cardiovascular benefit. If your aim is to reduce cardiovascular disease, restricting its use to a limited time only and for those with the highest BMIs doesn't make sense."

He cautioned that benefits should always be balanced with safety considerations: "The benefits need to be weighed against potential side effects. Investigations of side effects become especially important given the broad range of people this medicine and others like it could help."

A Broader Class of Heart-Helping Drugs

Although this study focused on semaglutide, researchers believe the same results may apply to other medications that act on the same hormone system (glucagon-like peptide-1, or GLP-1).

GLP-1 drugs may improve cardiovascular health by enhancing the function of blood vessel linings, reducing inflammation, improving blood pressure regulation, and lowering cholesterol and other fats in the bloodstream.

The analysis drew on data from the landmark SELECT trial, which is the largest and longest clinical trial to date investigating semaglutide's effects on weight in people who were overweight or obese but did not have diabetes. The trial included more than 17,000 participants worldwide and was co-led by Professor Deanfield.

Semaglutide, a GLP-1 receptor agonist, mimics the body's natural incretin hormones that help control blood sugar after meals. It was first approved for managing type 2 diabetes.

From Diabetes Treatment to Heart Protection

Semaglutide is the active ingredient in the medications Wegovy and Ozempic. Following evidence from the SELECT trial, the UK's medicines regulator approved Wegovy for use in patients with cardiovascular disease, allowing it to be prescribed privately.

On the NHS, Wegovy is available through specialist weight management clinics for weight loss. Another GLP-1 drug, Mounjaro, can be prescribed by general practitioners in England for people with a BMI of 40 or above (or 37.5 for those from minority ethnic backgrounds) and at least four of five conditions (type 2 diabetes, high blood pressure, heart and vascular disease, high cholesterol and obstructive sleep apnea).

The study authors noted that most participants were male and white. They recommended that future research on GLP-1 receptor agonists include broader representation across sex and ethnicity to better understand how different populations respond to these medications.

A preliminary analysis of the SELECT data that laid the groundwork for this research was presented by Professor Deanfield and his co-authors at the European Congress on Obesity (ECO) last year.