Multimodal neuroimaging of brain microstructure and hippocampal morphology alterations in type 2 diabetes mellitus

Type 2 diabetes affects the central nervous system, yet the role of glymphatic dysfunction remains unclear. This study investigated alterations in the DTI-ALPS index in T2DM patients and its associations with cognitive function, white matter integrity, and hippocampal morphology. 74 T2DM patients and 32 healthy controls underwent brain T1-weighted and diffusion tensor imaging. The DTI-ALPS index, white matter microstructure, and hippocampal subregion volumes were quantified. Correlation and mediation analyses assessed relationships between the DTI-ALPS index and cognitive assessments, clinical indicators, white matter microstructures, and hippocampus subregions. T2DM patients exhibited reduced DTI-ALPS index and fractional anisotropy, increased axial diffusivity, and decreased global network efficiency. Furthermore, both betweenness centrality and degree centrality in the right superior frontal gyrus were significantly reduced. Hippocampal subfield volumes were significantly reduced. The DTI-ALPS index correlated positively with HDL and MMSE scores, but negatively with fasting blood glucose (FBG). Mediation analysis showed that the DTI-ALPS index partially mediated the relationship between fasting glucose and cognition. T2DM is linked to glymphatic dysfunction, white matter damage, and hippocampal atrophy, contributing to cognitive decline. The DTI-ALPS index may serve as a sensitive biomarker for early glymphatic impairment, emphasizing the role of metabolic clearance dysfunction in diabetes-related cognitive deterioration. Trial registration Chinese Clinical Trial Registry (ChiCTR1900024109) on June 26, 2019.