Structural And Functional Change Of Cerebellum And Cerebellar-cerebral Circuit In T2DM:A Multimodal MR Imaging Study

Background and Objective: Type 2 diabetes increased the risk of cognitive impairment and dementia.T2 DM patients with cognitive dysfunction also showed neuroimaging changes in cerebral structure and function.The cerebellum widely communicates with the cerebral cortex through the input and output neural circuits of multiple synapses,which play an important role in human cognition.As a vulnerable region of glucose metabolism disorders,whether the cerebellar structure and the cerebellar-cerebral circuit are impaired in T2 DM and its relationship with cognitive dysfunction is still unclear.Therefore,the purpose of this study is to evaluate the cerebellar gray matter structure,related white matter fiber tracts microstructure,and cerebellar-cerebral circuit connection in patients with T2 DM using multimodal MRI,and to explore its relationship with diabetes clinic characteristics and cognitive performance.Methods: A total of 47 patients with T2 DM and 35 Age and Gender matched normal controls were included in this study.Montreal cognitive assessment(Mo CA)was used to evaluate the global cognitive,visuospatial,executive,naming,attention,language,abstraction,delayed recall,and orientation ability of all subjects.Magnetic resonance conventional sequence images of the head,high-resolution 3D T1 weighted structural images of the whole brain,diffusion tensor images,and resting-state functional images were acquired.The gray matter volume(GMV)of the cerebellar cortex and cerebellar dentate nucleus(DN)was assessed using voxel-based morphometry(VBM)combined with a spatially unbiased atlas template of the human cerebellum(SUIT);The microstructure of the cerebellar white matter channel fiber tracts(cerebellar peduncles)was assessed using the Tract-Based Spatial Statistical(TBSS)tool;Alterations in the functional connectivity(FC)of the cerebellar-cerebral circuit was assessed by seed-based FC analysis.These alterations were simultaneously analyzed for association with diabetes clinical variables and cognitive performance.Results:(1)Cognitive assessment demonstrated a global cognitive decline in patients with T2 DM,with significant reductions in visuospatial,executive,and language performance.(2)Cerebellar cortex GMV assessment demonstrated that,compared with healthy controls,T2 DM patients showed a decrease in local GMV in the left Crus II/I,right IX,and right Crus I in the posterior lobe of the cerebellum;the degree of GMV reduction was negatively correlated with fasting blood glucose(FPG)and insulin resistance index(HOMA-IR).The GMV of right cerebellar Crus I was positively correlated with the visuospatial and executive performance.(3)In the assessment of FC in regions of reduced GMV in cerebellar cortex,it was shown that increased FC of left cerebellar Crus II/I,right cerebellar IX,and right cerebellar Crus I with multiple DMN regions in T2 DM patients,including the medial prefrontal lobe,superior frontal gyrus,inferior frontal gyrus,middle temporal gyrus,angle gyrus,and posterior cingulate/precuneus.FC between right cerebellar IX and pons,inferior temporal gyrus(ITG),and FC between right Crus I and ITG were also enhanced in T2 DM patients.The correlated analysis found that partial FC was negatively correlated with diabetes duration and positively correlated with reduced cognition(total Mo CA score,visuospatial,executive,and language performance).The GMV of right cerebellar IX was negatively correlated with the FC between the cerebellum and medial prefrontal lobes.(4)In the structural evaluation of cerebellar output channel(DN),it was shown that the microstructure of DN related fiber tracts(cerebellar peduncle)in T2 DM patients was damaged(specifically,the decrease of local FA value and increase of RD value in bilateral superior cerebellar peduncle,bilateral middle cerebellar peduncle and left inferior cerebellar peduncle).In the functional evaluation of the cerebellar output channel(DN),it was shown that FCs between DN and visual network(middle occipital gyrus)and language-related brain areas(ITG and hippocampus)were increased in T2 DM patients compared with healthy controls.These alterations were negatively correlated with FPG and Hb A1 c and positively correlated with diabetes duration and language performance.In addition,it was also found that increased RD in bilateral superior cerebellar peduncle was negatively correlated with increased DN related functional connectivity.Conclusions:(1)T2DM impaired the local GMV of the posterior cerebellum and damage the microstructure of cerebellar white matter pathways,leading altered to the integrity of the cerebellar-cerebral circuit connection.The influence is manifested as increased FC between the cerebellum and default mode network,visual network,and language related cerebral regions in T2 DM patients.(2)Abnormal cerebellar structure and increased cerebellar-cerebral circuit connection were associated with visuospatial,executive,and language performance in patients with T2 DM.(3)The clinical variables of T2DM(fasting plasm glucose,insulin resistance,and diabetes duration)were associated with the damage to the cerebellar structure and the abnormal enhanced cerebellar-cerebral circuit in patients with T2 DM.