Increased brain iron deposition in the basial ganglia is associated with cognitive and motor dysfunction in type 2 diabetes mellitus.

Objective: Compared with those in type 2 diabetes mellitus (T2DM) patients without diabetic peripheral neuropathy (DPN), alterations in brain iron levels in the basal ganglia (an iron-rich region) and motor and cognitive dysfunction in T2DM patients with DPN have not been fully elucidated. We aimed to explore changes in brain iron levels in the basal ganglia in T2DM patients with DPN using quantitative susceptibility mapping (QSM).

Methods: Thirty-four patients with DPN, fifty-five patients with diabetes without DPN (non-DPN, NDPN), and fifty-one healthy controls (HCs) were recruited and underwent cognitive and motor assessments, blood biochemical tests, and brain QSM imaging. One-way ANOVA was applied to evaluate the variations in cognitive, motor and blood biochemical indicators across the three groups. Then, we performed multiple linear regression analysis to identify the possible factors associated with the significant differences in susceptibility values of the basal ganglia subregions between the two T2DM groups.

Results: Susceptibility values in the putamen and the caudate nucleus were greater in the T2DM patients than in the HCs (DPN patients vs. HCs, p < 0.05; NDPN patients vs. HCs, p < 0.05, FDR correction), and there were no significant differences between the DPN patients and NDPN patients. Multiple linear regression analysis revealed that age and history of diabetes played crucialroles in brain iron deposition in the putamen and the caudate nucleus. Notably, DPN in T2DM patients had no effect on brain iron deposition in the putamen or the caudate nucleus. The susceptibility values of the putamen was positively correlated with the Timed Up and Go test score and negatively correlated with gait speed, the Montreal Cognitive Assessment score, and the Symbol Digit Modalities Test score in T2DM patients.

Conclusions: Iron-based susceptibility in the putamen, measured by QSM, can reflect motor function in T2DM patients and might indicate micropathological changes in brain tissue in T2DM patients.