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Funded Projects

Investigating Associations between Neighborhood-Level Disadvantage and Microstructural Neurodegeneration Across the Alzheimer’s Disease Continuum

Outcome Report
Awarded in 2024
Postdoctoral Grant
Updated Aug 3, 2026

At a Glance

Aging brains follow different paths, with some individuals maintaining cognitive health while others progress to Alzheimer’s disease (AD) and related dementias. This project combined advanced diffusion-weighted MRI with fluid biomarkers to examine how living in disadvantaged neighborhoods relates to microstructural brain changes across the AD continuum. Findings show lower neurite density in people from highly disadvantaged neighborhoods, particularly in regions of the brain vulnerable to AD. The study also found high biomarkers of axonal degeneration and glial activation in those who resided in the most disadvantaged neighborhoods in the first 18 years of life. This project helped elucidate the significance of residing in a socioeconomically-disadvantaged neighborhood throughout the lifetime as a modifiable risk factor for AD development.

The Challenge

A growing body of literature suggests that socioeconomic risk factors are implicated in the development and progression of Alzheimer’s disease and related dementias. For example, higher income and education level have been linked to a decreased risk of mild cognitive impairment and AD. There is some evidence that neighborhood-level disadvantage, which reflects the relative socioeconomic status of a geographic region, may provide a more generalizable, population-level representation of the social factors that increase the risk of pathological aging compared to individual-level variables.

Project Goals

The goals of this project were to:

  1. Determine the impact of neighborhood-level disadvantage in aging adults across the Alzheimer’s disease continuum.
  2. Use cerebrospinal fluid and plasma biomarkers to determine the influences of area-level disadvantage on axonal degeneration and glial activation in aging adults across the Alzheimer’s disease continuum.

Results

Dr. Moody conducted a mixed-longitudinal analysis of 539 late-middle-aged participants within the Wisconsin Registry for Alzheimer’s Prevention and the Wisconsin Alzheimer’s Disease Research Center to assess the extent to which the Area Deprivation Index, as a proxy for neighborhood-level disadvantage, is associated with brain microstructure. The researcher used diffusion-weighted imaging, a non-invasive MRI technique, to assess microstructure. Participants residing in the 20% most disadvantaged neighborhoods had a significantly lower neurite density index compared to those residing in the 80% least disadvantaged neighborhoods. The loss of neurites is an indication of neurodegeneration and a critical factor in Alzheimer’s disease. Additionally, Dr. Moody analyzed cerebrospinal fluid and plasma markers of axonal degeneration and glial activation, which are significant indicators of AD progression, in 1,099 aging adults. Participants who resided in the most disadvantaged third of counties within the first 18 years of life exhibited significantly more axonal degeneration, glial activation and downstream neuroinflammation later in life compared to those who resided in counties within the least disadvantaged third.

More Funded Projects

research icon: microscope and stethoscope
Postdoctoral Grant

Preconception Weight Loss Strategy Impact on Gestational Glycemia, Milk Lipids and Offspring Islet Health

Outcome Report
Awarded in 2024
In Wisconsin, nearly 30 percent of those giving birth have obesity, which increases the risk of adverse outcomes for both parent and child. There is an urgent need for evidence on safe, effective weight loss recommendations before pregnancy to help reduce the intergenerational risk of diabetes and improve maternal-child health outcomes. This project compared four preconception weight loss strategies using mouse models. Both dietary change and bariatric surgery were sufficient for inducing weight loss and improving body composition before pregnancy, but breeding difficulties and loss of pups hindered the ability to assess how the different weight loss methods affect milk fat production and offspring pancreatic health. The project has been proven viable and is well-positioned for further work.
research icon: microscope and stethoscope
Postdoctoral Grant

Signal Transducers Regulating Dietary and Pharmacological BCAA Restriction in Obesity and Type II Diabetes: The Role of Mitochondrial BCAA Carrier Slc25a44

Awarded in 2024
Obesity and type 2 diabetes (T2D) are major public health challenges, with impaired branched-chain amino acid (BCAA) metabolism playing a key role. Restricting dietary BCAAs or using the FDA-approved drug 4-PBA improves body composition, glucose control and lifespan in animal models. Exercise is also critical for weigh loss and maintaining muscle mass, but its interaction with BCAA-targeted interventions is unknown. This project will test whether dietary BCAA restriction, 4-PBA, and exercise—alone or in combination—reverse obesity and improve metabolic health in mice. Using genetic knockout models, it will also determine whether these benefits depend on the mitochondrial BCAA carrier Slc25a44. Findings will provide insights into diet- and drug-based strategies that can be paired with exercise to combat obesity and T2D. By focusing on accessible interventions, the study has the potential to promote health equity in communities disproportionately affected by metabolic disease.