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Research Highlights

Excess belly fat in midlife may be associated with early markers of Alzheimer’s

Some early Alzheimer’s disease-related brain changes, including beta-amyloid buildup and lower cortical thickness, were greater among middle-aged adults with abdominal obesity. Findings from the NIA-funded pilot study were published in Aging and Disease.

Close up of person in purple shirt measuring own belly with tape measure

Although midlife obesity is considered an Alzheimer’s risk factor, some studies suggest that high body mass index (BMI) — a measure of body fat based on height and weight — is not always associated with increased likelihood of developing the disease. In this study, researchers from Washington University in St. Louis explored whether abdominal obesity could be used to assess Alzheimer’s risk. Abdominal obesity occurs when more fat is stored deep in the belly compared to under the skin.

The research team analyzed BMI, insulin resistance, and brain scans from 32 cognitively normal, midlife adults (ages 40-60 years). They also used MRI to measure abdominal fat. This provided them with an alternative to using the BMI scale to assess obesity.

The researchers found that men had higher levels of abdominal obesity than women. However, they found no gender differences in BMI or insulin resistance, another obesity-related risk that may contribute to Alzheimer’s.

Analysis of brain scan data showed that higher BMI, abdominal obesity, and insulin resistance scores were associated with lower cortical thicknesses in the temporal lobe and other regions that are often damaged by Alzheimer’s.

In men, abdominal obesity was linked to higher levels of the hallmark protein beta-amyloid in the precuneus cortex, an area affected early by Alzheimer’s.

BMI, abdominal obesity, and insulin resistance were not found to be associated with tau buildup or brain volume, another key marker of Alzheimer’s. This may suggest that the association of abdominal obesity with beta-amyloid buildup and lower cortical thickness in midlife are early biomarkers, occurring before tau buildup and cognitive decline.

The findings of this pilot study support the idea that abdominal obesity may be used to assess Alzheimer’s risk. The researchers plan to recruit 20 participants for the next phase of research.

This research was supported by NIA grants 1RF1AG072637-01, P30AG066444, P01AG026276, and P01AG003991.

These activities relate to NIH’s Alzheimer’s and Related Dementias Research Implementation Milestones:

  • 1.F, “Support the inclusion of measures of AD-related phenotypes and environmental exposures in non-AD cohorts to enable new discovery research and to accelerate cross-validation of discoveries made in AD cohorts.”
  • 2.B, “Establish new research programs that employ data-driven, systems-based approaches to understand the interaction between peripheral systems (in particular: immune, metabolic, microbiome) and the brain and the impact of this interaction on brain aging and neurodegeneration.”

Reference: Dolatshahi M, et al. Alzheimer disease pathology and neurodegeneration in midlife obesity: A pilot study. Aging and Disease. 2023. Epub Aug. 3. doi: 10.14336/AD.2023.0707.

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