Altered Cerebellar-Cerebral Circuits in Patients With Type 2 Diabetes Mellitus

Abstract

The role of the cerebellum in type 2 diabetes mellitus (T2DM) has been receiving increased attention. However, the functional connectivity (FC) between the cerebellar subregions and the cerebral cortex has not been investigated in T2DM. Therefore, the purpose of this study was to investigate cerebellar-cerebral FC and the relationship between FC and clinical/cognitive variables in patients with T2DM. A total of 34 patients with T2DM and 30 healthy controls were recruited for this study to receive a neuropsychological assessment and undergo resting-state FC. We selected four subregions of the cerebellum (bilateral lobules IX, right and left Crus I/II, and left lobule VI) as regions of interest (ROIs) to examine the differences in cerebellar-cerebral circuits in patients with T2DM compared to healthy controls. Correlation analysis was performed to examine the relationship between FC and clinical/cognitive variables in the patients. Compared to healthy controls, patients with T2DM showed significantly decreased cerebellar-cerebral FC in the default-mode network (DMN), executive control network (ECN), and visuospatial network (VSN). In the T2DM group, the FC between the left cerebellar lobule VI and the right precuneus was negatively correlated with the Trail Making Test A (TMT-A) score (r = −0.430, P = 0.013), after a Bonferroni correction. In conclusion, patients with T2DM have altered FC between the cerebellar subregions and the cerebral networks involved in cognitive and emotional processing. This suggests that a range of cerebellar-cerebral circuits may be involved in the neuropathology of T2DM cognitive dysfunction.

Regional Spontaneous Neural Activity Alterations in Type 2 Diabetes Mellitus: A Meta-Analysis of Resting-State Functional MRI Studies

“…Previous laboratory studies found the association between motor deficits and the cerebellar damage in diabetic rats (Sherin et al, 2010;Nagayach et al, 2014). The cerebellum dysfunctions also related to impaired cognition in patients with T2DM as structural and functional connectivity alterations were found in the cerebellar and cerebrocerebellar circuits (Fang et al, 2017;Zhang D. et al, 2020). The hyperactivity in the cerebellum might be a recruitment of additional neural resources to compensate for loss of cognitive function in the cerebral regions (Xia et al, 2013).…”

Brain Structural Alterations, Diabetes Biomarkers, and Cognitive Performance in Older Adults With Dysglycemia

“…The cerebellum is connected to the prefrontal cortex and other non-motor cortical regions via projecting fibers and synapses (29). In a recent functional neuroimaging study, patients with type 2 diabetes showed decreased functional connectivity between the cerebellum and dorsolateral prefrontal cortex compared to normal controls (42). Atrophic changes of related structures in diabetes are linked to gait disturbance even in patients without diabetic peripheral neuropathy (36).…”

Altered Functional Network Connectivity of Precuneus and Executive Control Networks in Type 2 Diabetes Mellitus Without Cognitive Impairment

“…Previous cross-sectional magnetic resonance imaging (MRI) studies have consistently reported associations between T2DM and reduced global brain volume ( Wardlaw et al, 2013 ; Weinstein et al, 2015 ; Zhang et al, 2020 ; Adachi et al, 2021 ; Hyung et al, 2021 ). In addition, microvascular lesions and neurodegeneration markers related to Alzheimer’s disease (AD) have been associated with T2DM ( Tan et al, 2019 ; Zhang et al, 2019 ; Wu et al, 2020 ).…”