Limbic-Predominant Cortical Magnetic Susceptibility Alterations Are Associated With Glycemic Dysregulation and Cognitive Performance in Type 2 Diabetes.

AIMS: To characterize the spatial pattern of cortical magnetic susceptibility alterations in Type 2 diabetes mellitus (T2DM) and to determine whether hyperglycemia moderates the association between regional cortical QSM values and cognitive performance. METHODS: In this cross-sectional study, 145 patients with T2DM and 182 healthy controls underwent 3 T MRI. Cortical gray matter magnetic susceptibility was quantified using quantitative susceptibility mapping (QSM). Cognitive function was assessed with a multidomain neuropsychological battery. Partial correlation, general linear models, and moderation analyses examined associations among cortical susceptibility, glycemic indices, and cognitive performance. Support vector regression (SVR) with nested cross-validation evaluated the predictive value of limbic subregional QSM values for information processing speed. RESULTS: Whole-cortex analyses showed nominally higher QSM values in the bilateral limbic cortices of patients with T2DM, while post hoc analyses identified significantly higher QSM values in the left cingulate cortex and right parahippocampal gyrus after FDR correction. QSM values in selected limbic cortical regions at both the lobar and subregional levels were positively correlated with FPG and HbA1c. Covariate-adjusted analyses further indicated associations between higher QSM values in frontal, parietal, and limbic regions and poorer episodic memory and executive function. Moderation analyses suggested that higher HbA1c levels strengthened the inverse associations between QSM values in selected limbic cortical regions and cognitive performance on the MMSE, MoCA, and CDT. Within the T2DM group, SVR models based on limbic subregional QSM values showed cross-validated predictive performance for TMT-A scores. CONCLUSIONS: Patients with T2DM showed a limbic-predominant pattern of cortical magnetic susceptibility alterations, with higher QSM values in selected regions associated with poorer performance across multiple cognitive domains. HbA1c moderated the associations between regional QSM values and cognitive performance. These findings suggest that limbic cortical susceptibility alterations may be relevant to metabolic dysregulation and cognitive vulnerability in T2DM.