The MRI Study Of Brain Structure And Hippocampal Functional Connectivity In Type 2 Diabetes Mellitus

Part 1: Research on brain microstructure alteration in type 2 diabetes mellitus without hypertension by VBM and TBSS analysisAims: Type 2 diabetes mellitus(T2DM)is a systemic metabolic disease that can cause multiple organ complications.The central nervous system(CNS)can be damaged in T2 DM patients,causing cognitive impairment which may progress to dementia in some patients eventually.Therefore,it is important to explore the neuroimaging characteristics of CNS changes in T2 DM patients.Current studies have found that T2 DM can cause CNS abnormalities,influencing brain volume,white matter,and cerebral blood flow,which were significantly associated with cognitive impairment.However,the blood pressures of T2 DM patients and healthy controls were not unified in most of domestic and international studies,which could not exclude the effects of hypertension on brain.The prevalence of hypertension in T2DMpatients was double that in normal subjects and the onset age of the former was ten years younger.In addition,hypertension would aggravate cerebral vascular injury in patients with T2 DM,and the structural and functional damages of CNS among T2 DM patients with hypertension were more severe and cognitive dysfunction occurred more often.Therefore,we need to recruit the T2 DM patients without hypertension,and explore the damages of hyperglycemia on the brain.Methods: Twenty T2 DM patients without hypertension and twenty age-,gender-,and education-matched healthy controls were recruited in this study.Structural image and DTI data were acquired by 3.0T MR scanner.Voxel-based morphometry(VBM)and tract-based spatial statistics(TBSS)analysis were used to investigate the changes of brain volume,white matter fractional anisotropy(FA)and mean diffusivity(MD)values in T2 DM patients compared with control groups;and to investigate the difference of DTI ratio between left and right hemisphere.Results: Compared with healthy controls,there was no significant decrease of brain volume in T2 DM patients without hypertension(P > 0.05).However,significant changes of FA and MD value were found in genu and body of corpus callosum,left anterior limb of internal capsule,anterior and superior corona radiate,cingulum and superior fronto-occipital fasciculus(P < 0.05).There was a significant increase of MD value in bilateral superior corona radiate,especially in left hemisphere(P < 0.05).Conclusions: Widespread disruptions of white matter microstructure were found in T2 DM patients without hypertension,especially in the left hemisphere.The damage of white matter integrity in the corresponding brain regions may be the basis of the cognitive impairment caused by T2 DM.Part 2:Alterations of white matter integrity and hippocampal functional connectivity in type 2 diabetes without mild cognitive impairmentAims: T2 DM affects the central nervous system,resulting in mild cognitive impairment(MCI),which would progress to dementia in some patients eventually.Therefore,it is of great significance to reveal the neural mechanisms of T2 DM in patients with MCI,which contribute to delay the progression of MCI to dementia.Previous studies have shown that there was a wide range of changes in brain among T2 DM patients with MCI.However,once MCI was found in T2 DM patients,which were irreversible generally,dementia would occur within five years among one in three patients.Although the cognitive function was normal in the early stage of T2 DM,the long-term effects of hyperglycemia would result in subtle changes in the structure and function of the brain regions associated with cognitive function.The detection of these subtle changes could help us turn the intervention time forward.Therefore,we study the potential changes of function connection in the hippocampus and white matter fibers in T2 DM patients with normal cognitive function by TBSS and resting-state functional connectivity analysis and explore the relationship between alterations of white matter and that of function connection in the hippocampus.Methods: Sixteen T2 DM patients without MCI and twenty-four age-,sex-,and educationmatched healthy controls(HC)were recruited in this study.DTI and rs-f MRI data were subsequently acquired on a 3.0T MR scanner.Tract-based spatial statistics(TBSS)combining region of interest(ROI)analysis was used to investigate the alterations of DTImetrics(FA and MD)and FC measurement was performed to calculate hippocampal FC with other brain regions,respectively.Cognitive function was evaluated with Mini-Mental State Examination(MMSE)and Montreal Cognitive Assessment(Mo CA).Brain volumes were also evaluated among these participants.Results: There was no difference of MMSE and Mo CA scores between two groups.Neither whole brain nor regional brain atrophy was revealed in T2 DM patients.DTI analysis revealed WM disruptions,especially in the whole corpus callosum.Significant decreases of hippocampal FC with other brain region were revealed,especially with the bilateral frontal gyri.Furthermore,the decreased FA in left posterior thalamic radiation and increased MD in the splenium of corpus callosum were closely related with the decreased hippocampal FC to caudate and frontal gyri.Conclusions: The integrity of the white matter was impaired in T2 DM patients without MCI,especially in the whole corpus callosum;The FC of bilateral hippocampus and frontal cortex was decreased,and the decrease of hippocampal FC was significantly correlated with the damage of white matter integrity.The decreased of the integrity of corpus callosum and the hippocampal FC with frontal cortex may be the early signs of MCI.