Mechanism Of Acupuncture On Amnestic Mild Cognitive Impairment Revealed By Multi-modal Magnetic Resonance Imaging

Objective:To explore the central pathological mechanism of patients with amnestic mild cognitive impairment(aMCI)based on multi-modal magnetic resonance imaging,and the central response mechanism of acupuncture in improving symptoms of patients with aMCI.Methods:Part Ⅰ clinical study:A case-control study was performed,46 patients with amnestic mild cognitive impairment(aMCI)who met the inclusion criteria and 28 healthy subjects matched for gender,age and education were recruited from the Department of Acupuncture and Moxibustion and the Department of Brain Diseases and Psychology of Shenzhen Traditional Chinese Medicine Hospital.The structural and functional image data scans,including threedimensional T1-weighted images(3DT1WI),resting-state functional magnetic resonance imaging(BOLD-fMRI),diffusion tensor imaging(DTI),magnetic susceptibility weighted imaging and Flair sequences,were completed at the Imaging Department of Shenzhen Traditional Chinese Medicine Hospital,as well as the Simple Mental State Examination Scale(MMSE),Montreal Cognitive Assessment Scale-Beijing version(MoCA),Chinese Huashan Auditory Language Learning Test(AVLT-H),Hamilton Depression Scale(HAMD),Activity of Daily Living(ADL)scale and Clinical Dementia Rating(CDR).In terms of statistical analyses,the clinical data were analyzed using IBM SPSS Statistics 23,the imaging data were pre-processed and analysed in Matlab 2013b and using SPM12 and DPARSF v6.0 software,where the structural indexs included grey matter volume(GMV),fractional anisotropy(FA)and mean diffusivity(MD),and the functional indexs included amplitude of low frequency fluctuation(ALFF),fractional amplitude of low frequency fluctuation(fALFF)and regional homogeneity(ReHo).The correlation between abnormal brain regions of aMCI and clinical scales was analyzed using Pearson correlation.Part Ⅱ clinical study:A randomized,controlled,single-blind research was used.The 46 aMCI patients who met the inclusion criteria were randomly divided into verum acupuncture group and sham acupuncture group according to a randomised numerical table with a blinded triple separation of patients,statisticians and scale evaluators.The subjects received verum acupuncture or sham acupuncture,respectively,3 times/week,8 weeks,for a total of 24 times.Clinical scale evaluation of MoCA,MMSE,AVLT-H,HAMD and multi-modal magnetic resonance image scanning were performed at baseline and after treatment.Clinical data were analyzed using IBM SPSS Statistics 23 The imaging data was pre-processed and analysed using SPM12 and DPARSF v6.0 software in a Matlab 2013b based environment,with the same index data analysed as in Part 1.A mixedeffects model analysis was also used to understand the interaction and between-group effects of true and sham acupuncture,then correlation between clinical improvement and neuroimaging changes before and after verum acupuncture treatment was analyzed by Pearson correlation.Finally,the imaging results of the first part were combined to understand the trends of changes in statistically different brain areas before and after acupuncture and in healthy subjects.Results:Part Ⅰ clinical study:Compared with the healthy group,aMCI patients showed no significant differences in gender,age and years of education(P>0.05),whereas showed significant differences in MMSE,MoCA,HAMD,AVLT immediate memory,AVLT short delay and long delay memory,and AVLT recognition(P<0.05).Compared with the healthy group,the aMCI group exhibited increased FA in left upper cerebellum,right lingual gyrus,and right lower cerebellum,decreased MD in the left orbital superior frontal gyrus,decreased ALFF in the left middle frontal gyrus and left precuneus,and increased ALFF in the right postcentral gyrus,increased fALFF in the right precentral gyrus,increased ReHo in the left postcentral gyrus and the right postcentral gyrus,and decreased ReHo in the left middle temporal gyrus.In terms of correlation analysis,the MoCA score of aMCI patients was negatively correlated with the mean ALFF in the left precuneus(P<0.05),and positively correlated with the mean ReHo in the left middle temporal gyrus(P<0.05).There was a significantly positive correlation between MoCA score and mean ReHo in the left middle temporal gyrus,between the HAMD scores and the mean ALFF in the right postcentral gyrus,between the AVLT immediate memory scores and the mean ReHo in the left middle temporal gyrus(P<0.05).Part Ⅱ clinical study:A total of 46 patients with aMCI were collected,with 20 cases of true acupuncture and 20 cases of sham acupuncture completed in the end.There were no significant differences in age,sex,years of education,MMSE,MoCA,HAMD,AVLT immediate memory,AVLT short and long delayed memory,and AVLT recognition between the verum acupuncture group and sham acupuncture group at baseline(P>0.05).After 8 weeks of treatment,both verum acupuncture group and sham acupuncture treatment group showed significant difference in MMSE,MoCA,AVLT immediate memory,AVLT short and long delayed memory(P<0.05).We further compared the difference between verum acupuncture and sham acupuncture before and after treatment,and found that there were significant differences in MMSE,MoCA,AVLT immediate memory,AVLT short and long delay memory before and after verum acupuncture compared with sham acupuncture(P<0.05).There was a significant interaction effect between treatment and time in FA,after treatment,the FA in the inferior cerebellum was decreased in verum acupuncture group,whereas sham acupuncture group showed opposite results;The between-group effect showed that both verum acupuncture and sham acupuncture group exhibited reduced FA in the left middle temporal pole,right superior cerebellum,and right inferior temporal gyrus;Compared with before verum acupuncture treatment,the aMCI patients showed decreased FA in the inferior cerebellum.There was a significant interaction effect between treatment and time in MD,after treatment,verum acupuncture group showed increased MD values in the left lingual gyrus,left middle occipital gyrus and left inferior parietal lobule,whereas sham acupuncture group showed opposite results;No significant between-group effect was found;Compared with before verum acupuncture treatment,aMCI patients showed increased MD in the right middle cingulate.There was a significant interaction effect between treatment and time in ALFF,after treatment,the verum acupuncture group showed decreased ALFF in the right caudate nucleus,and increased ALFF in the left cuneus and left superior parietal gyrus,whereas the sham acupuncture group showed opposite results;The between-group effect showed that ALFF values in the right posterior central gyrus and left anterior central gyrus was increased,and the ALFF values in the right anterior cingulate and paracingulate gyrus were decreased in both verum acupuncture and sham acupuncture group;Compared with before verum acupuncture treatment,aMCI patients showed decreased ALFF in the right fusiform gyrus,and increased ALFF in the left cuneus and left precentral gyrus.There was a significant interaction effect between treatment and time in fALFF,after treatment,the verum acupuncture group showed increased fALFF value in the right orbital superior frontal gyrus and left precentral gyrus,and decreased fALFF value in the left middle temporal gyrus and right middle frontal gyrus,whereas the sham acupuncture group showed opposite results;The between-group effect showed that the fALFF values in the right insula,left thalamus,right postcentral gyrus,and left postcentral gyrus were increased in both verum acupuncture and sham acupuncture groups;Compared with before verum acupuncture treatment,aMCI showed increased fALFF values in right middle temporal gyrus and left postcentral gyrus.There was a significant interaction effect between treatment and time in ReHo,after treatment,the verum acupuncture group showed increased ReHo in the left dorsolateral superior frontal gyrus,whereas the sham acupuncture group showed opposite results.The between-group effect that ReHo value in the bilateral postcentral gyrus was increased in both verum acupuncture and sham acupuncture;Compared with before verum acupuncture treatment,aMCI patients showed increased ReHo value in right inferior temporal gyrus.In terms of correlation analysis,the changed MMSE before and after treatment in aMCI patients was negatively correlated with changed ALFF in the left cuneus(P<0.05),and the changed HAMD was positively correlated with changed ALFF in the left precentral gyrus(P<0.05).Compared to the healthy control group,patients with aMCI before true acupuncture treatment had higher FA values in the right inferior cerebellar gyrus,lower ALFF values in the left superior frontal gyrus,left precuneus,left cuneus and left superior parietal gyrus,higher ALFF values in the right caudate nucleus and lower ReHo values in the left middle temporal gyrus,while after true acupuncture treatment,all these abnormal brain areas tended to improve towards the healthy control group.Conclusions:1.The structural and functional impairment of aMCI patients may reflect the central pathological mechanism of their cognitive impairment.In addition,the functional characteristics of the precuneus and middle temporal gyrus could indicate the severity of cognitive impairment in patients with aMCI.This provides not only imaging markers for the diagnosis of aMCI,but also brain regions for its treatment.2.Acupuncture not only significantly improved the cognitive function of patients with aMCI,but also significantly remodeled its brain structure and function.In addition,functional indicators can predict the clinical efficacy of acupuncture.This not only provides an objective theoretical basis for the acupuncture treatment of aMCI,but also provides a possibility to predict the efficacy of acupuncture in patients with aMCI.