MRI Markers of Perivascular Fluid Dynamics in Type 2 Diabetes and Their Associations with Glycemic Control

Backgrounds: Perivascular fluid dynamics support brain-wide solute transport and have been described to be perturbed in type 2 diabetes mellitus (T2DM) models. In this study, we aimed to evaluate T2DM-related alterations in MRI perivascular markers and their associations with glycemic control and cognitive performances. Methods: Thirty-four T2DM patients and 34 age- and sex-matched controls underwent multimodal MRI to quantify perivascular metrics: the diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index reflects perivenous diffusion anisotropy, white matter free water (WM-FW) indicates CSF-interstitial fluid exchange, and perivascular space volume fraction (PVSVF) indexes perivascular conduits burden. Cognitive function and metabolic indicators were evaluated. Group comparisons and associations were tested with multivariable linear regression adjusting for key demographic and intracranial covariates. Results: Compared with controls, T2DM showed a lower ALPS index (adjusted β = -0.091, 95% CI -0.155 to -0.027, p = 0.006; FDR-adjusted p = 0.025). The group differences were more prominent among male and older patients, although formal interactions were not significant. WM-FW and PVSVF showed no group difference after adjusting covariates. Within T2DM, lower ALPS was associated with higher postprandial glucose (partial r = -0.46) and HbA1c (partial r = -0.37) (all p ≤0.05, FDR-adjusted p = 0.11). Multivariable linear regression including all MRI markers showed that ALPS was the only imaging metric that remained independently associated with glycemic measures. Conclusions: T2DM is associated with altered perivascular diffusion anisotropy on MRI, indicating perivascular dysfunction. Associations with glycemic profile suggest these modifiable factors may influence perivascular health in T2DM and merit prospective evaluation.