Insulin resistance, cognition, and functional brain network topology in older adults with obesity.

Objective: Cross-sectional data from a sample of older adults with obesity was used to determine how peripheral and neuronal insulin resistance (IR) relate to executive function and functional brain network topology. Methods: Older adults (n=71) with obesity but without type 2 diabetes were included. Peripheral IR was quantified by HOMA2-IR. Neuronal IR was quantified according to a proposed neuron-derived exosome-based method (NDE-IR). An executive function composite score, summed scores to the Auditory Verbal Learning Test (AVLT) trials 1-5, and functional brain networks generated from resting-state functional magnetic resonance imaging were outcomes in analyses. We used general linear models and a novel regression framework for brain network analysis to identify relationships between IR measures and brain-related outcomes. Results: HOMA2-IR, but not NDE-IR, was negatively associated with executive function. Neither IR measure was associated with AVLT score. Peripheral IR was also related to hippocampal network topology in participants who had undergone functional neuroimaging. Neither peripheral nor neuronal IR were significantly related to network topology of the central executive network. Conclusions: Cognitive and functional imaging effects were observed from HOMA2-IR, but not NDE-IR. The hippocampus may be particularly vulnerable to effects of peripheral IR.