Study On The Correlation Between Brain Microstructure Changes And Cognitive Dysfunction In Patients With Type 2 Diabetes

ObjectiveDiabetes mellitus（DM）is a chronic,progressive metabolic disease characterized by persistent hyperglycemia.Its etiology is complicated.It can cause insulin resistance and（or）hypofunction of islets due to infection,immune dysfunction,genetics,mental factors and other factors,causing abnormal metabolism of carbohydrates,lipids and proteins,which can cause long-term Multiple organ diseases throughout the body,including damage to the heart,brain,kidney,and retina.It has been confirmed that T2DM can increase the risk of cerebrovascular disease,cause severe damage to cognition,and even develop into Alzheimer’s Disease（AD）^[1,2].Epidemiological data statistics show that the risk of mild cognitive impairment in T2DM（Type 2 Diabetes Mellitus,T2DM）patients is 1.4 to 1.8times higher than that of the general population,and the risk of dementia is 1.5 to 2.5 times higher^[3].Cognitive dysfunction caused by T2DM brain damage mainly includes:memory function,attention,visual space,executive function and information processing speed^[4-7].Type 2 Diabetes Mellitus-Mild cognitive impairment（T2DM-MCI）is an irreversible degenerative disease of the central nervous system.Its pathogenesis is not yet clear,and there are no clinical indicators for early clinical diagnosis.,Routine imaging examination has limited effect on its diagnosis.It has an insidious onset and can have no symptoms in the early stage.As the disease progresses,the symptoms become increasingly obvious.It often progresses to the extent that it significantly affects the patient’s quality of life before it attracts attention,causing a great burden on the patient’s family and society.Early diagnosis and identification and early intervention in the development of T2DM-MCI can significantly delay the brain damage of T2DM,prevent the occurrence of dementia and AD,and are of great significance for improving the quality of life of patients and exploring specific pathogenesis^[8,9].In recent years,with the development of science and technology,brain imaging technology has provided new ideas for the research of T2DM-MCI.It reflects the subtle changes in brain function and structure,reveals the underlying mechanism of the disease,and provides new possibilities for early diagnosis and evaluation of the condition of T2DM-MCI.This study uses new technologies such as voxel-based morphometry（VBM）and voxel-mirrored homotopic connectivity（VMHC）to explore the neural basis of cognitive impairment in T2DM patients,and analyze the cognition of T2DM patients The correlation between ability decline and neuropathy is to explore sensitive indicators for identifying early cognitive decline in T2DM patients from the imaging technology level,and provide new clinical indicators for early identification of T2DM-MCI,early intervention,judgment of the disease,and prognosis.Methods1.Collect data of 50 T2DM patients and 46 healthy subjects matching age,gender and education level,and perform VBM analysis based on MRI brain gray matter data.The Mo CA（Montreal Cognitive Assessment）scale was used to assess the cognitive performance of the two groups of subjects.2.The study included 50 T2DM patients and 46 normal control groups.Free Surfer software was used to automatically segment the 7 deep subcortical gray matter structures of the subjects and assess their volumes.The Mo CA scale was used to score the cognitive scores of the subjects in each group.In patients with T2DM,partial correlation analysis was used to evaluate the correlation between the level of glycosylated hemoglobin and the volume of deep subcortical gray matter and the subject’s neuropsychological tests.3.Include 50 T2DM patients and 46 normal control subjects,and use the VMHC method to analyze the resting MRI data of all subjects.Partial correlation score is used to study the correlation between VMHC value of brain area and neuropsychological test.Result:1.Compared with the normal control group,the cognitive ability,memory,attention,visual space ability and execution ability of T2DM patients were significantly reduced,and the overall cognitive ability was worse than that of the normal population（P<0.05）.The total gray matter volume of patients in the T2DM group（558.42±30.75ml）was significantly lower than that of normal healthy persons（618.12±46.62ml）.Compared with the normal control group,the T2DM group showed a significant decrease in the gray matter volume in the cerebellum,fusiform gyrus,frontal lobe,occipital lobe,and temporal lobe regions;while the inter-hemispheric and inferior frontal gyrus gray matter volume was significantly higher than that in the control group（P<0.05）.The volume of brain gray matter was correlated with Moc A patients and memory score（P<0.05）.2.Compared with the normal healthy group,the bilateral hippocampus,caudate nucleus and thalamus volume of T2DM patients were significantly reduced.Partial correlation analysis showed that the level of glycosylated hemoglobin in T2DM patients had a significant negative correlation with hippocampal volume（r=-0.367,P=0.025）,and a significant positive correlation with putamen（r=-0.342,P=0.032）.There is no significant correlation between the Mo CA score of T2DM patients and the amygdala,caudate nucleus,hippocampus,globus pallidus,parahippocampal gyrus,putamen,and thalamus,but the auditory vocabulary learning test（AVLT）and other scales related to memory loss The gray matter volume of bilateral hippocampus,amygdala,and parahippocampal gyrus were all significantly positively correlated（P<0.05）.In addition,in patients with type 2 diabetes,higher Hb A1c levels were significantly associated with poor memory and hippocampal atrophy（P<0.05）.3.There are differences in VMHC between the T2DM group and the normal control group.Compared with the normal healthy group,the VMHC of T2DM patients in the default network brain areas such as the middle temporal gyrus and brain areas such as cerebellum＿10 and posterior cerebellum significantly decreased（P<0.05）.In individual brain areas,such as the talus sulcus brain area,VMHC showed a significant upward trend（P<0.05）.This difference may provide clues for early detection of cognitive impairment related to T2DM.In addition,there was a significant positive correlation between the VMHC values of cerebellum＿10,posterior cerebellar lobe,and talus sulcus and Mo CA scores in T2DM patients.Conclusion1.T2DM patients and the normal control group have a significant decrease in the overall gray matter volume of the brain and the gray matter volume of the local brain regions,including the temporal lobe,frontal lobe and occipital lobe,which involve cognitive,memory and speech functions.In addition,T2DM patients show significant cognitive impairment,which indicates that cognitive dysfunction in T2DM is related to the damage of the temporal lobe,frontal lobe,occipital lobe,parietal lobe,lingual gyrus,cerebellum and other brain structures.Among them,the brain microstructure changes in the frontal and temporal lobes play an important role in the cognitive impairment of patients with T2DM.2.In the deep subcortical gray matter structure,bilateral hippocampus,caudate nucleus,and thalamus may be the main affected areas of T2DM.Hyperglycemia and insulin resistance may be the main potential neurobiological pathological mechanisms of hippocampal dysfunction.3.T2DM patients mainly have abnormal changes in mirror homotopy connection in the default network brain areas such as the middle temporal gyrus and multiple cerebellar areas,suggesting that damage to the default network area of the brain in T2DM patients is an important pathological basis for cognitive dysfunction.