| Objective:To investigate brain function changes in patients with Type 2 diabetes mellitus(T2DM)and its relationship with Mild cognitive impairment(MCI),and to search for potential early neuroimaging markers of T2 DM cognitive impairment Method:Gender and education matched T2 DM patients with MCI(n=21),T2 DM patients without MCI(n=18)and healthy volunteers(n=20)were collected.Cognitive score,blood biochemical examination,peripheral blood cell marker PDGFRβ examination and multimodal MR Scanning(including MPRAGE,DCE,DSI and QSM sequences)were performed.Mo CA scale and MMSE scale were used to evaluate the cognitive score of each group.PDGFRβ concentration was detected by ELISA.The volume of each brain region was evaluated by artificial intelligence brain segmentation technology.Tissue4 D,DSI Studio and MEDI software processed DCE,DSI and QSM data to obtain Ktrans,GFA,QA,MD values and magnetic sensitivity values.The differences between groups were evaluated by single factor analysis.Receiver operating characteristic curve(ROC)was further used to analyze diagnostic efficacy of statistically significant parameters in different brain regions.Pearson correlation analysis was used to evaluate the correlation between Ktrans value and GFA,QA,MD value and magnetic sensitivity value,respectively.To study the abnormal brain changes in T2 DM patients from clinical,cytokine,brain structure and function.All data were analyzed by IBM SPSS 26.0 software,P<0.05 was statistically significant.Results:1.Comparison of clinical data: Age,fasting blood glucose,two hours postprandial blood glucose and glycosylated hemoglobin in T2DM-MCI group and T2DM-n MCI group were higher than control group,and the differences between the two groups were statistically significant(P < 0.05).The age of the three groups were72.43±9.01,65.61±10.26 and 61.90±8.81.Fasting blood glucose was 7.02±1.91,8.09±2.99,5.11±0.68.Two hours after meal blood glucose was 12.56±0.75,9.40±0.53,7.20±0.21.Hba1 c was 7.23±1.50,6.96±1.42 and 5.55±0.46.2.Pericellular marker PDGFRβ: PDGFRβ concentration in T2DM-MCI was higher than that in control group,and the difference was statistically significant(P<0.05).The concentrations of PDGFRβ in the three groups were 57.18±36.60、41.08±20.73 and 24.16±16.58.3.Brain structure changes: The volume of bilateral hippocampus,basal ganglia and brain white matter in T2DM-MCI group and T2DM-n MCI group was lower than that in control group,and the difference between the two groups was statistically significant(P<0.05);the volume of bilateral hippocampus and basal ganglia in T2DM-MCI group was lower than that in T2DM-n MCI group(P<0.05).The hippocampal volumes of the three groups were 6.52±2.44,8.10±1.35 and 8.38±1.67.The volume of basal ganglia was 20.53±3.49,23.31±2.77 and 24.35±3.3.The white matter volumes were 390.30±64.54,391.03±60.01 and 437.08±43.42.4.Multi-modal MRI changes:(1)DCE-MRI: Ktrans values in frontal lobe and basal ganglia of T2DM-MCI group were higher than those of control group,and Ktrans values in frontal lobe,temporal lobe,basal ganglia region,thalamus and hippocampus of T2DM-MCI group were higher than those of control group(P<0.05).The basal ganglia and hippocampal Ktrans values of T2DM-MCI were higher than those of T2DM-n MCI(P< 0.05).(2)DSI: The GFA values of the left uncinus tract,bilateral hippocampal tract,left upper longitudinal tract and right corticospinal tract in T2DM-MCI group,the QA values of the bilateral uncinus tract and bilateral upper longitudinal tract were lower than those in control group,and the MD values of the right uncinus tract,bilateral upper longitudinal tract,bilateral hippocampus and bilateral corticospinal tract were higher than those in control group(P<0.05).The GFA value of the right corticospinal tract and the QA value of bilateral corticospinal tract in T2DM-n MCI were lower than those in control group,and the MD value of the right corticospinal tract was higher than that in control group(P<0.05).The GFA values of the right uncinated tract,bilateral hippocampus and left upper longitudinal tract in T2DM-MCI group,the QA values of the bilateral hippocampus and bilateral corticospinal tract were lower than those in T2DM-n MCI group,and the MD values of the right uncinated tract,right hippocampus and right upper longitudinal tract in T2DM-MCI group were higher than those in T2DM-n MCI group(P< 0.05).(3)QSM: The magnetic sensitivity values of bilateral red nuclei in T2DM-n MCI group were higher than control group,and the magnetic sensitivity values of the right thalamus,bilateral putamen,bilateral pallidus,bilateral substantia nigra,bilateral red nuclei and bilateral hippocampus in T2DM-MCI group were higher than those in control group(P< 0.05).Compared with T2DM-n MCI group,T2DM-MCI group had higher magnetic sensitivity values in bilateral putamen,bilateral hippocampus,right substantia nigra and left red nucleus(P < 0.05).(4)ROC curve analysis: the AUC of basal ganglia region and hippocampus Ktrans value were 0.697 and 0.877,the sensitivity and specificity were 71.4% and66.7%.76.2%,88.9%.The GFA values of the left and right hippocampus were 0.854 and 0.878,the sensitivity and specificity were 76.2% and 85.7%.77.8%,90.5%.The AUC values of the left and right hippocampus were 0.733 and 0.743 The sensitivity and specificity were 71.4% and 66.7%,71.4% and 66.7%.The AUC of MD in the left and right hippocampus were 0.706 and 0.664,and the sensitivity and specificity were57.1% and 83.3%,90.5% and 38.9%.The AUC of the left and right hippocampus were 0.881 and 0.845.The sensitivity and specificity were 66.7% and 94.4%,66.7%and 94.4%(P < 0.05).(5)Correlation between Ktrans value and GFA,QA,MD and magnetic sensitivity values: The correlation coefficients r of Ktrans value in hippocampus with GFA,QA,MD and magnetic sensitivity values were-0.736,-0.629,0.535 and 0.664,respectively(P < 0.05).Conclusion:In T2 DM patients with MCI,hippocampal and basal ganglia atrophy,blood-brain barrier damage,white matter fiber bundle integrity damage and intracranial iron deposition are present.Blood-brain barrier injury may play an early and critical role in the pathophysiological process of white matter microstructure damage and iron deposition in T2 DM patients with MCI.Ktrans value,GFA value and magnetic sensitivity value of hippocampus have high specificity and sensitivity,and are sensitive neuroimaging markers in the assessment of cognitive dysfunction in T2 DM. |
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