Central Obesity Disrupts Brain Network Organization in Aging via Metabolic and Structural Pathways
Marina Fernandez-Alvarez1,2, Karel M Lopez-Vilaret1,3, Jose L Cantero1,2
1Laboratory of Functional Neuroscience, Pablo de Olavide University, Seville, Spain.
Aging and Disease
|November 10, 2025
Summary
Central obesity, not overall obesity, is linked to reduced brain network segregation. Abdominal fat accumulation may drive cognitive decline through insulin resistance and brain changes.
Area of Science:
- Neuroscience
- Metabolic Health
- Aging Research
Background:
- Obesity is a known risk factor for age-related cognitive decline.
- Central (abdominal) obesity poses a significant threat to brain health.
Purpose of the Study:
- To investigate the distinct effects of central versus overall obesity on brain connectivity.
- To explore the underlying mechanisms linking central obesity to cognitive decline.
Main Methods:
- Cross-sectional study of 89 cognitively healthy adults (52-79 years).
- Resting-state fMRI to measure brain network segregation.
- Multimodal neuroimaging (structural MRI, T1w/T2w MRI, FDG-PET, FBB-PET) and insulin resistance index (HOMA-IR).
Main Results:
- Central obesity, not overall obesity, was associated with reduced network segregation in key brain networks.
- Central obesity linked to insulin resistance, impacting intracortical myelin, glucose metabolism, and amyloid-beta (Aβ) load.
- Metabolic and structural brain changes mediated the link between central obesity and reduced network segregation.
Conclusions:
- Central obesity is associated with brain network disruptions via metabolic pathways.
- Targeting abdominal fat and metabolic factors may preserve brain health and reduce cognitive vulnerability in aging.
- Findings highlight the detrimental impact of abdominal fat on brain functional integrity.
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