Study On Clinical Efficacy And Mechanism Of "Sancai Yizhi Moxibustion" Combined With "Simultaneous Multi-Task" In The Intervention Of Mild Cognitive Impairment

Objective1.To observe the clinical effect and safety of the intervention mode of moxibustion combined with cognitive rehabilitation training,which is called the “San Cai of Health of Brain” moxibustion and “Simultaneous multitasking” cognitive rehabilitation training on the cognitive function of elderly patients with mild cognitive impairment（MCI）,and to provide an advantageous solution for the early intervention of MCI.2.To observe the effect on serum protein markers Aβ1-42、Tau and p-tau of the intervention mode of "San Cai of Health of Brain" moxibustion combined with "Simultaneous multitasking" cognitive rehabilitation training in the early intervention of mild cognitive impairment（MCI）.To analyze the correlation with the cognitive function of MCI patients,and to clarify the mechanism of the effect of moxibustion combined with cognitive rehabilitation training on the cognitive function of MCI patients from the perspective of serum biochemistry.3.Using functional magnetic resonance multimodal imaging techniques,through the analysis method of graph theory,discuss the effect of central neutral system caused by the brain functional network damage mode of MCI patients.To study the regulatory effect of "San Cai of Health of Brain" moxibustion combined with "Simultaneous multitasking" intervention program on the brain functional network of MCI patients,and preliminaries to elaborate the mechanism of moxibustion combined with cognitive training therapy in shaping brain network topology,so as to provide objectified theoretical basis for clinical treatment.By analyzing the topological characteristics of the functional brain network of MCI patients before and after the intervention of “San cai of Health of Brain” Moxibustion combined with “Simultaneous Multitasking” cognitive rehabilitation training,the central effects of the brain function damage in MCI patients were investigated through graphical analysis.This study investigates the effect of “San cai of Health of Brain”Moxibustion combined with "Simultaneous Multi-tasking" cognitive rehabilitation training on the regulation of the functional brain network of MCI patients and provides a theoretical basis for the clinical treatment of MCI.Methods1.A total of 232 patients with MCI were included in this study and randomly divided into moxibustion group,training group,moxibustion plus training group and drug group.The patients in the moxibustion group were given moxibustion at Baihui（GV20）,Shenque（CV8）,and Yongquan（KI1）once every other day,20 minutes each time,for a total of 8 weeks.The patients in the training group were given cognitive rehabilitation training every other day,20 minutes each time,for a total of 8 weeks.The moxibustion plus training group add cognitive rehabilitation training into the treatment plan on the basis of the moxibustion group,and the treatment frequency is the same as that of the moxibustion group.In the drug group,the donepezil was taken orally for 5mg once a day for 8 weeks.The Monterey Cognitive Assessment（Mo CA）scale,mini-mental Status Examination（MMSE）scale scores and event-related potential p300 latency were evaluated before treatment,after 8 weeks of treatment,and at 12 weeks after treatment,and the safety of treatment was analyzed for four groups.The correlations between the Mo CA scale score and MMSE score and eventrelated potential p300 before and after treatment were analyzed.2.According to the result of the clinical trial,32 patients with MCI from each of the four groups（moxibustion group,training group,moxibustion plus training group and drug group）were included in this study,and a total of 128 patients with MCI were included.Enzyme-Linked Immunosorbent Assay（ELISA）was used to detect the changes in serum protein marker levels of Aβ1-42,Tau and p-tau before and after treatment.The correlations between the Mo CA scale score,MMSE score,event-related potential p300 and serum protein markers Aβ1-42,Tau and p-tau before and after treatment were analyzed.3.25 elderly patients with MCI who were eligible for MRI scanning were randomly selected from the moxibustion plus training group of the clinical trial,and 20 healthy subjects were recruited.Functional magnetic resonance imaging（f MRI）technology was used to collect the resting-state data of healthy subjects and MCI patients before and after moxibustion combined with functional training intervention.The whole brain functional network of subjects was constructed.Based on graph theory analysis,the topological properties of the whole brain network and local topological properties were calculated.To evaluate the correlation between significantly different imaging indicators and cognitive impairment in MCI patients.Results（1）Four groups had significant increases in Mo CA score after treatment and during follow-up（P<0.01,P<0.05）.Compared with the moxibustion group,the training group and the drug group,the moxibustion plus training group had a significant increase in Mo CA score after treatment（P<0.01）.Compared with the training group,the moxibustion group and the drug group had a significant increase in Mo CA score after treatment（P<0.01）.Compared with the moxibustion group and the training group,the moxibustion plus training group had a significant increase in Mo CA score during follow-up（P<0.01）.Compared with the training group,the moxibustion group and the drug group had a significant increase in Mo CA score during follow-up（P<0.01）.（2）Four groups had significant increases in MMSE score after treatment and during follow-up（P<0.01）.Compared with the training group,the moxibustion plus training group had a significant increase in MMSE score after treatment（P<0.01）.Compared with the other three groups,the moxibustion plus training group had a significant increase in MMSE score during follow-up（P<0.01）.（3）Four groups had significant reduction in p300 latency after treatment and during follow-up（P<0.01）.Compared with the other three groups,the moxibustion plus training group had a significant reduction in p300 latency after treatment（P<0.01）.（4）The total score of Mo CA and MMSE had significantly negatively correlated with the p300 latency（P<0.05）.2.Four groups had significant differences in the level of serum Aβ1-42,Tau and p-tau（P<0.05）.Compared with the other three groups,moxibustion plus training group had a significant difference in the level of serum Tau（P<0.05）.the other groups were no statistically significant differences（P>0.05）.The total score of the Mo CA and MMSE had significantly negatively correlated with the serum Aβ1-42,Tau and p-tau（P<0.05）.（1）MCI group and HC group functional network topology attribute results（1）Small world attributes and global attributes: MCI group and HC group functional network all accord with "small world attribute".The characteristic pathlength（Lp）,normalized clustering coefficient（γ）,network global efficiency（Eg）,local efficiency（Eloc）between the two groups had significant differences,P<0.05.（2）Node attributes of the local network: Compared to HC group,MCI group significantly reduced nodal efficiency in the bilateral hippocampus（HIP.L/R）,bilateral fusiformgyrus（FFG.L/R）,right temporal pole（TPOsup.R）and vermis3,vermis7 were significantly decreased,P<0.05.The local efficiency of right occipital_Mid（MOG.R）,right heschl（HES.R）and vermis3 were significantly decreased,P<0.05.（3）Node centrality and core nodes of the local network: Compared to HC group,in the MCI group,the left rolandic_Oper（ROL.L）,bilateral supplementary motor area（SM A.L/R）,right hippocampus（HIp.R）,right occipital_Mid（MOG.R）,right fusiform（FFG.R）,right frontal_Mid_Orb（ORBmid.R）,Cerebelum_Crus1,Cerebelum_Crus2,Cerebelum₇b_Lnode centrality decreased significantly,P<0.05.（4）The correlation between functional network topology and cognition: The Mo CA score and MMSE score of the MCI group was significantly negatively correlated with the characteristic pathlength（Lp）of the functional network of patients,P<0.05.The MCOA score of the MCI group was significantly negatively correlated with the network global efficiency（Eg）and local efficiency（Eloc）of the functional network of patients,P<0.05.The total score of the Mo CA scale in the MCI group was significantly negatively correlated with the bilateral right fusiform（FFG.R）（P<0.05）;and the scores of each sub-item（such as short-latency memory,execution factor,etc.）and left supplementary motor area（SMA.L）,left hippocampus（HIP.R）,right temporal pole（TPOsup.R）have significant correlations with node topology changes,P<0.05.（2）MCI group functional network topology attribute results（1）Small world attributes and global attributes: MCI group and treat group functional network all accord with “small world attribute”.The characteristic pathlength（Lp）,normalized clustering coefficient（γ）,network global efficiency（Eg）,local efficiency（Eloc）between the two groups have significant differences,P<0.05.（2）Node attributes of the local network: after treatment the MCI patients significantly induced nodal efficiency in the left precuneus（PCUN.R）were significantly increased,P<0.05.The local efficiency of left temporal_pole_Sup（TPOsup.L）and Cerebellum Inferior Cerebelum_9R were significantly increased,P<0.05.（3）Node centrality and core nodes of the local network: after treatment the MCI patients the right supplementary motor area（SMA.R）,right frontal_Sup_Orb（ORBmid.R）,right frontal_Sup（SFGmed.L）,right frontal_Inf_Orb（ORBinf.R）,left temporal_pole_Mid（TPOmid.L）node centrality increased significantly,P<0.05.Conclusions1.After treatment,the comprehensive cognitive ability of MCI patients in the moxibustion group,training group,moxibustion plus training group and drug group were significantly improved.In terms of improving cognitive function,moxibustion plus training group is better than the other three groups.2.Compared with before treatment,serum Aβ1-42,Tau and p-tau levels of MCI patients in the moxibustion group,training group,moxibustion plus training group and drug group decreased,and the moxibustion plus training group can significantly reduce serum Aβ1-42 levels compared with the other three groups.3.The changes in local topological indexes of brain functional networks in MCI patients can reflect the cognitive impairment of MCI patients to a certain extent.The different brain regions mainly involve the Default Mode Network（DMN）.The spontaneous neural activity changes in DMN-related brain regions may be an important functional activity characteristic of MCI patients and can be used as specific imaging indicators of MCI.It provides an objective basis for early clinical diagnosis,dynamic observation of disease course and prognosis evaluation." San Cai of Health of Brain " moxibustion combined with "Simultaneous multitasking" intervention program can change the pathological state of the small-world network in patients with MCI,and the improvement of local efficiency of nodes in the brain functional network may be one of the main mechanisms of "San Cai of Health of Brain " moxibustion combined with " Simultaneous multitasking " intervention program in the treatment of MCI.4.Both moxibustion and functional training can improve cognitive function,and the intervention mode of " San Cai of Health of Brain " moxibustion combined with "Simultaneous multitasking" intervention program is more superior and effective,which can be promoted as an advantageous scheme for early screening and intervention of MCI in the clinical.