| Objective: Type 2 diabetes mellitus with a long course of disease is prone to cause cognitive impairment,resulting in impaired learning,memory,or executive functions.In this study,patients with type 2 diabetes mellitus complicated with cognitive impairment were selected as research object,and “Adjust Zang-fu and Arouse Spirit”electroacupuncture(EA)was used as the intervention method.The resting-state functional magnetic resonance imaging(rs-f MRI)and magnetic resonance spectroscopy(MRS)were used to reveal the brain central pathogenesis of type 2 diabetes mellitus complicated with cognitive impairment patients,clarify the central effector mechanism of “Adjust Zang-fu and Arouse Spirit” EA on improving cognitive dysfunction of type 2 diabetes mellitus complicated with cognitive impairment patients,and analyze the relationship between clinical characteristics and brain function characteristics of patients.Methods:1.Healthy subjects(HC group),type 2 diabetes mellitus without cognitive impairment patients(T2DM group)and type 2 diabetes mellitus with cognitive impairment(DCI group)were included.On the one hand,the clinical indicators of the subjects were tested,including blood glucose and blood lipids;on the other hand,the cognitive function of the subjects were evaluated,including the overall cognitive function evaluation using the Montreal Cognitive Assessment(Mo CA)Scale and the Clinical Dementia Rating(CDR)Scale,and the specific cognitive function evaluation using the lateral inhibition task(Flanker paradigm),the cognitive conflict task(Stroop paradigm),the working memory task(Nback paradigm)and the scene recognition task(Scene＿Recognition paradigm).The resting-state functional magnetic resonance(f MRI)and magnetic resonance spectroscopy(MRS)were used to analyze the changes of brain function and brain metabolites in the three groups of subjects.The hippocampal subregion and the default mode network(DMN)subregion were used as the regions of interest for resting-state functional connectivity,and the basal ganglia region was used as the brain region for magnetic resonance spectroscopy.The correlation between brain function and clinical cognitive function was analyzed.2.The DCI group was intervened by “Adjust Zang-fu and Arouse Spirit” EA.Acupoint selection were GV20,DU24,BL13(bilateral),BL20(bilateral),BL23(bilateral),LI4(bilateral),ST36(bilateral),SP6(bilateral),LR3(bilateral).After acupuncture Deqi,unilateral GV20-DU24,BL20-BL23,ST36-SP6 were used as electroacupuncture connecting points.EA stimulation was performed,30 min/time/d,5 times as a course of treatment.The course of treatment rested for 2 days,and eight courses of treatment were continuously intervened.After the intervention,the blood glucose and blood lipid of the subjects were detected,and the improvement of clinical indicators in DCI patients was evaluated.Hippocampal subregion and DMN subregion were used as the regions of interest for resting-state functional connectivity,and basal ganglia region was used as the detection brain region of magnetic resonance spectroscopy.The improvement of brain network and brain metabolites on DCI by “Adjust Zang-fu and Arouse Spirit” EA was analyzed,and the correlation analysis was performed with clinical cognitive function indexes.Results:1.Comparison of clinical indicators,cognitive assessment indicators,brain function and metabolites among HC group,T2 DM group and DCI group(1)Clinical indicators: The fasting plasma glucose(FPG)and glycated hemoglobin glycosylated hemoglobin(Hb A1c)in the T2 DM group and the DCI group were significantly higher than the HC group,and the difference was statistically significant(p<0.05,p<0.001).There was no significant difference in the general demographic data and blood lipid test among the three groups,such as age,gender and education years.(2)Cognitive assessment indicators: Mo CA score of DCI group was significantly lower than HC group and T2 DM group,CDR score of DCI group was significantly higher than HC group and T2 DM group.The ability to complete the corresponding experimental paradigm of lateral inhibition task,cognitive conflict task and working memory task(only1-back)in the DCI group was significantly lower than the HC group,and the difference was statistically significant(p<0.05,p<0.01,p<0.001).(3)Results of rs-f MRI:The difference in resting-state functional connectivity with hippocampal subregion as ROI is as follows.Compared with the HC group,the functional connection between the left anterior hippocampus and the left anterior central gyrus was enhanced,and the functional connection between the left anterior hippocampus and the left angular gyrus was reduced in the DCI group.Compared with the HC group,the functional connection between the left middle hippocampus and the right medial frontal gyrus,the right middle hippocampus and the left anterior wedge lobe,the right anterior hippocampus and the left anterior wedge lobe were enhanced,and the functional connection between the left anterior hippocampus and the right anterior wedge lobe,and the right posterior middle temporal gyrus were reduced in the T2 DM group.Compared with the T2 DM group,the functional connection between the left posterior hippocampus and the left precuneus was enhanced in the DCI group,and the functional connection between the central right hippocampus and the left precuneus was reduced in the DCI group.The functional connectivity between left posterior hippocampus and left precuneus in DCI group was positively correlated with Stroop conflict condition response time(r=0.536,p=0.048).The difference in resting-state functional connectivity with DMN subregion as ROI is as follows.Compared with the HC group,the functional connection between the left middle temporal gyrus and the right middle frontal gyrus and the left inferior parietal gyrus were enhanced,and the functional connection between the right middle temporal gyrus and the left angular gyrus was reduced in the DCI group.Compared with the HC group,the functional connections between the right anterior cingulate gyrus and the left superior margin gyrus or the right anterior wedge lobe,the right posterior cingulate gyrus and the left superior margin gyrus or the left inferior parietal gyrus were enhanced,and the functional connections between the left middle temporal gyrus and the bilateral angular gyrus,the right middle temporal gyrus and the right posterior cingulate gyrus or the bilateral angular gyrus,the left anterior cingulate gyrus and the left middle hippocampus,the right anterior cingulate gyrus and the left medial frontal gyrus,the left posterior cingulate gyrus and the posterior part of the bilateral middle temporal gyrus,and the right posterior cingulate gyrus and the posterior part of the bilateral middle temporal gyrus were reduced in the T2 DM group.Compared with the T2 DM group,the functional connection between the bilateral anterior cingulate gyrus and the right middle frontal gyrus was reduced in the DCI group.The functional connectivity between left middle temporal gyrus and left inferior parietal gyrus in DCI patients was positively correlated with Stroop neutral condition response time(r=0.620,p=0.018).Functional connectivity between left middle temporal gyrus and left inferior parietal gyrus in DCI patients was positively correlated with Stroop conflict condition response time(r=0.682,p=0.007).(4)Results of MRS: The NAA/Cr ratio in the left basal ganglia of DCI patients was significantly lower than the HC group and T2 DM group,and the difference was statistically significant(p<0.001).The right m I/Cr ratio was significantly higher than the HC group,and the difference was statistically significant(p<0.05).The right m I/Cr ratio in basal ganglia of DCI patients was significantly positively correlated with the reaction time under Stroop consistency condition(r=0.671,p=0.012),and the right m I/Cr ratio was significantly positively correlated with the reaction time under Stroop conflict condition(r=0.576,p=0.039).2.Comparison of clinical indexes,cognitive evaluation indexes,brain function and metabolites before and after intervention of“Adjust Zang-fu and Arouse Spirit” EA in DCI group(1)Clinical indicators: After intervention of“Adjust Zang-fu and Arouse Spirit” EA,Hb A1 c in DCI patients was significantly different from that before treatment(p=0.074).(2)Cognitive assessment indicators: The Mo CA score of DCI patients after treatment was significantly higher than that before treatment,and the CDR score was significantly lower than before treatment,and the difference was statistically significant(p<0.05,p<0.001).The ability of lateral inhibition task(Flanker conflict),cognitive conflict task(Stroop conflict condition)and working memory task(1-back)in DCI group was significantly higher than before treatment,and the difference was statistically significant(p<0.05,p<0.01,p<0.001).(3)Results of rs-f MRI:After intervention of “Adjust Zang-fu and Arouse Spirit” EA,the difference in resting-state functional connectivity with hippocampal subregion as ROI is as follows.Compared with before treatment,the functional connection between the left anterior hippocampus and the left angular gyrus,the left posterior hippocampus and the right inferior parietal angular gyrus were enhanced,and the functional connection between the left posterior hippocampus and the right middle occipital gyrus was reduced in the DCI group.After intervention,the difference of functional connectivity between left anterior hippocampus and left angular gyrus in DCI patients was negatively correlated with the difference of Stroop conflict condition response time(r=-0.608,p=0.027).The difference in resting-state functional connectivity with DMN subregion as ROI is as follows.Compared with before treatment,the functional connections between the right middle temporal gyrus and the left anterior wedge,the left posterior cingulate gyrus and the left inferior orbital frontal gyrus,and the right posterior cingulate gyrus and the left superior orbital medial frontal gyrus were reduced in the DCI group.(4)Results of MRS: After intervention of “Adjust Zang-fu and Arouse Spirit” EA,the NAA/Cr ratio on the left side of basal ganglia was significantly higher than that before treatment,the m I/Cr ratio on the right side was significantly lower that before treatment,and the GABA/Cr ratio on the right side was significantly higher than before treatment,and the difference was statistically significant(p<0.05).After intervention,the left NAA/Cr difference was negatively correlated with Flanker conflict response time improvement(r=-0.633,p=0.020).Conclusion:1.The overall cognitive function of DCI patients decreased,attentional inhibition and working memory decreased in the meantime.The disorder of cognitive function network in the brain of DCI patients is characterized by abnormal functional connectivity between hippocampus and DMN or DMN subregion.Among them,the functional connectivity enhancement of the left posterior hippocampus-left precuneus and left middle temporal gyrus-left inferior parietal gyrus may be the potential central mechanism of cognitive control decline in DCI patients.There was no obvious clinical cognitive dysfunction in patients with T2 DM,but the functional connectivity has been more extensive abnormalities,which further indicated that T2 DM was an important risk factor for mild cognitive dysfunction and Alzheimer ’s disease.Left precuneus and right middle frontal gyrus may be the key brain regions of T2 DM converting to DCI.In addition,DCI patients may have decreased number of neurons and glial cell proliferation in basal ganglia.The increase of m I/Cr ratio in the right basal ganglia may reflect the decrease of inhibitory control ability of DCI patients.2.“Adjust Zang-fu and Arouse Spirit” EA can improve the overall cognitive function of patients with DCI,and has a certain improvement effect on attention control and working memory ability.It may take effect by improving the functional connectivity abnormality between hippocampal subregion and DMN or DMN subregions,and regulating the number or functional abnormality of neurons in basal ganglia.The enhanced of functional connectivity between left anterior hippocampus and left angular gyrus,the increase of NAA/Cr ratio in left basal ganglia may be the potential mechanism of “Adjust Zang-fu and Arouse Spirit” EA regulating attention control ability in DCI patients. |
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