A Multimodal MRI Study of the White Matter Microstructural and Hemodynamic Underpinnings of Cognitive Decline in Type 2 Diabetes Mellitus.

To explore the relationship between alterations in cerebral white matter microstructure and cerebral blood perfusion underlying cognitive decline in patients with type 2 diabetes mellitus (T2DM). This cross-sectional study enrolled 47 T2DM patients (26 with mild cognitive impairment [T2DM-MCI] and 21 without [T2DM-nMCI]) and 23 healthy controls. All participants underwent multi-post-labeling delay arterial spin labeling and diffusion tensor imaging to assess cerebral blood flow (CBF) and white matter integrity. Group differences in imaging parameters and their correlations with cognitive scores were analyzed. Mediation analysis explored pathways between fractional anisotropy (FA), CBF, and cognition. The T2DM-MCI group showed significantly reduced CBF in the bilateral frontal lobes and lower FA in multiple tracts (e.g., superior/inferior longitudinal fasciculus, cingulum, corpus callosum) compared to both control groups (all P < 0.05). MoCA scores positively correlated with FA in several tracts and right frontal CBF. Crucially, mediation analysis revealed that cerebral hypoperfusion accounted for 24.83% of the effect of white matter damage on MCI (β = 0.016, 95% CI: 0.000-0.040). T2DM-MCI is characterized by co-occurring white matter microstructural damage and cerebral hypoperfusion. Our findings identify cerebral hypoperfusion as a significant mediator linking white matter injury to cognitive impairment, providing new mechanistic insights into diabetic cognitive decline.