Associations of Adiposity With Cortical Atrophy and Network Dyssynchrony in Type 2 Diabetes: A Multimodal MRI Study

While Type 2 diabetes mellitus (T2DM) is a known risk factor for cognitive decline, it remains unclear whether comorbid obesity merely parallels or synergistically correlates with this trajectory. We aimed to disentangle the specific neurotoxic impacts of adiposity from chronic hyperglycemia on cortical structure and function.

In this cross-sectional study, 102 matched participants (obese T2DM [n = 31], normal-weight T2DM [n = 40] and healthy controls [n = 31]) underwent high-resolution multimodal MRI, specifically Surface-Based Morphometry (SBM) and 2D-Regional Homogeneity (ReHo), to evaluate cortical thickness, area, and network synchronization.

Our analyses revealed that the obese T2DM cohort exhibited profound structural and functional vulnerability compared to normal-weight peers. High body mass index (BMI) robustly predicted severe cortical thinning in frontal-reward circuits and widespread functional dyssynchrony within the default mode network. Furthermore, SBM captured localized morphometric increases in the fusiform gyrus unique to obese T2DM patients, which we hypothesize may reflect an early, reactive phase of neuroinflammation. Crucially, chronological disease duration showed no significant correlation with these metrics.

Adiposity is profoundly associated with structural and functional neural disruption in T2DM. Comorbid obesity represents a prominent risk factor associated with brain morphometric patterns resembling advanced aging, highlighting the potential clinical importance of early weight management for neuroprotection.