Moderating Effect of Insulin Resistance on the Relationship between Gray Matter Volumes and Cognitive Function

Background: It is controversial whether exposure to insulin resistance accelerates cognitive deterioration. The present study aimed to investigate the association between insulin resistance and gray matter volume loss to predict the cognitive decline. Methods: We recruited 160 participants (78 with Alzheimer’s disease and 82 without Alzheimer’s disease). Insulin resistance, regional gray matter volume, and cognitive function were assessed. A hierarchical moderated multiple regression (MMR) model was used to determine any associations among insulin resistance, structural changes in the brain, and cognitive decline. Results: The volumes of 7 regions in the gray matter were negatively related to insulin resistance in Alzheimer’s disease (p =0.032). Hierarchical MMR analysis indicated that insulin resistance did not directly affect the cognitive decline but moderated the cognitive decline through the decrease in gray matter volume in the key brain regions, i.e., inferior orbitofrontal gyrus (left), middle cingulate gyrus (right), hippocampus (right), and precuneus (right) (p < 0.05 in each case). Conclusion: Insulin resistance appears to exacerbate the cognitive decline associated with several gray matter volume loss.