| Objective: Type 2 diabetes mellitus(T2DM)is associated with cognitive function impairment,structure and function changes in brain.Previous studies have shown that T2DM is an important risk factor for mild cognitive impairment(MCI),Alzheimer’s disease(AD)and other brain diseases.Neurovascular coupling changes play an important role in cognitive function impairment of T2DM patients.In this study,regional homogeneity(Re Ho)and functional connectivity strength(FCS)were used to represent the neural activity of the local and whole brain,respectively.To investigate the relationship between neurovascular coupling and cognitive impairment in T2DM patients without complications,we used neuronal activity and CBF to conduct cross-voxel coupling analysis and ratio analysis in the whole brain gray matter.Methods: In our study,a total of 135 T2DM patients(70 males and 65 females,with an average age of 59.48 ± 7.34 years)were recruited,and 134 healthy controls(HCs)(58 males and 76 females,with an average age of 58.01±8.12 years)were collected in the meantime.GE Discovery MR750 3.0T magnetic resonance scanner was used to execute magnetic resonance scanning on total subjects,mainly including resting functional magnetic resonance and 3D pseudo-continuous arterial spin labeling sequence collection.The data were preprocessed to obtain the whole brain Re Ho,FCS and CBF maps of the two groups of subjects.At the same time,the subjects were assessed in behavioral and neuropsychological tests,including episodic memory,learning ability,attention and information processing ability,and fasting venous blood was collected.First,SPSS 25.0 software was used for statistical analysis.Demographic information,clinical laboratory indicators and behavioral indicators of the two groups were compared to find the difference indicators.To evaluate the coupling relationship between local and whole brain neural activity and CBF,the correlation between Re Ho-CBF and FCS-CBF in the gray matter template of all subjects was calculated and compared between groups.Then,the ratio of each voxel Re Ho/CBF and FCS/CBF in the gray matter template of all subjects was calculated,and the two sample t-test was performed based on SPM12 software.To conduct comparison among groups,age,gender and years of education were used as control covariates,and the differences between the groups of Re Ho,FCS and CBF were evaluated based on voxel-based levels.Finally,the mean values of Re Ho/CBF and FCS/CBF in the brain areas with between-group variance were extracted.The correlation analysis was made between the clinical and behavioral indicators and imaging indicators with statistical differences.To ensure reproducibility of the results,the above operations were repeated for all subjects with FCS thresholds of 0.1,0.2,and 0.3,respectively,to observe the neurovascular coupling of whole brain activity under different thresholds.In addition,since the influence of whole brain gray matter volume(GMV)on neurovascular coupling has not been determined,GMV of each subject was used as a control covariates to repeat the above steps to remove the influence of GMV on neurovascular coupling.Results: 1.There were no statistically significant differences in gender,age,years of education,blood pressure and total cholesterol between the T2DM group and the HCs group(P > 0.05).Compared with HCs group,T2DM group fasting blood glucose(FBG),glycosylated hemoglobin(Hb A1c)were significantly increased(P < 0.001),HOMA-β were significantly reduced(P<0.001).Compared to the HCs group,RAVLT-immediate recall(RAVLT-IR)、 delayed recall(RAVLT-DR)and ReyOsterrieth complex figure(ROCF)in the immediate recall(ROCF-immediate recall,ROCF-IR)and delayed recall(ROCF-delay recall,ROCF-DR)and Symbol Digit Modalities Test(SDMT)were significantly lower(P < 0.05).2.There was no statistically significant difference in the whole gray matter coupling between the T2DM group and the HCs group(P > 0.05).3.Compared with HCs group,T2DM group’s part of the brain regions exist change of Re Ho/CBF and FCS/CBF ratio,including the ratio of Re Ho/CBF in the right inferior parietal lobule and superior temporal gyrus decreased significantly,bilateral orbitofrontal region,left medial frontal gyrus,right superior frontal gyrus and medial frontal gyrus of Re Ho/CBF ratio increased significantly,and the ratio of FCS/CBF in bilateral orbitofrontal area,middle frontal gyrus and inferior frontal gyrus increased significantly(P < 0.05,FDR correction).4.The ratio of Re Ho/CBF in the right frontal lobe of the T2DM group was positively correlated with ROCF-IR and ROF-DR scores(r = 0.195,P = 0.024;r = 0.176,P = 0.043),FCS/CBF ratio of right frontal lobe was positively correlated with SDMT score(r = 0.215,P = 0.013),and was positively correlated with ROCF-IR and ROCF-DR scores(r = 0.177,P = 0.042;r = 0.178,P = 0.041).5.After GMV adjustment,there was no statistically significant coupling difference between Re Ho-CBF and FCS-CBF in the whole brain gray matter of T2DM patients compared with the HCs group(P > 0.05).The changes in Re Ho/CBF and FCS/CBF ratios between the two groups were basically consistent with the results of unadjusted GMV,indicating that GMV changes had little effect on neurovascular coupling.Under different FCS thresholds,the results of FCS-CBF coupling and FCS/CBF ratio between the two groups were basically the same.Conclusions: In our study,local and whole brain neurovascular coupling of T2DM patients without complications was analyzed,and it was found that Re Ho/CBF and FCS/CBF ratios in some brain regions of T2DM patients were changed,which was related to cognitive impairment in T2DM patients.This study suggests that the change of neurovascular coupling state is a potential neuroimaging mechanism for early cognitive impairment in T2DM patients,and provides early imaging marker for cognitive impairment in T2DM patients. |
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