Altered cerebellar activity and cognitive deficits in Type 2 diabetes: Insights from resting-state fMRI

To investigate alterations in brain activity in patients with Type 2 Diabetes and explore the relationship between altered regions and neuropsychological performances.

A total of 36 patients with Type 2 Diabetes and 40 age- and education-matched healthy controls were recruited for this case-control study. All participants underwent resting-state functional magnetic resonance imaging (Resting-state fMRI) and neuropsychological tests. The neuropsychological scales included the Auditory Verbal Learning Test (AVLT), Shape Trajectory Test B (STT-B), Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), and Boston Naming Test (BNT), Symbol Digit Modality Test (SDMT), Regional homogeneity (ReHo) and the amplitude of low-frequency fluctuations (ALFF) were used to assess differences in spontaneous regional brain activity. For functional connectivity (FC) analyses, the differences identified among the groups were selected as seed regions. Then, the correlations between neuropsychological scale scores (AVLT, HAMA, HAMD, STT-B, BNT, and SDMT) and ALFF/ReHo values were specifically analyzed in the focal regions that exhibited significant alterations between the T2DM and control groups, as detailed in Tables 2 and 3.

Patients with Type 2 Diabetes exhibited significantly higher ALFF values in the superior lobe of the cerebellum, specifically in the left cerebellar crus I (Cerebellum_Crus I_L), left cerebellar lobule VI (Cerebellum_6_L), and left cerebellar lobule IV-V (Cerebellum_4_5_L). Additionally, they exhibited elevated ReHo values in the Cerebellum_Crus I_L and Cerebellum_6_L. The findings were statistically significant with a family-wise error-corrected, cluster-level p-value of less than 0.05. However, the FC analysis was not significant. AVLT scores were significantly lower in the diabetes group. The correlation analysis demonstrated a negative association between ALFF values of the Cerebellum_6_L and AVLT scores (R² = 0.1375, P < 0.001). The ReHo values within the Cerebellum_6_L also exhibited a negative association with AVLT scores (R² = 0.0937, P = 0.007).

Patients with Type 2 Diabetes showed abnormal neural activities in diverse cerebellar regions mainly related to cognitive functions. This provides supplementary information to deepen our insight into the neural mechanisms by which Type 2 Diabetes affects the functional activity of the brain's posterior circulation, as well as the potential association of these changes with cognitive impairment.