Study On The Risk Factors Of TCM Syndromes, Imaging Features And Outcome Of Amnestic Mild Cognitive Impairment

Objective:This study aimed to study the TCM syndromes,neuropsychological and structural imaging features of patients with amnestic mild cognitive impairment(aMCI),to find the risk factors of aMCI and Alzheimer’s disease(AD),to explore the relationship between TCM syndrome and cognitive function and to evaluate the influence of demographic factors,clinical information,TCM syndromes and cognitive function on the conversion of aMCI.Methods:Study 1:275 subjects were enrolled and divided into normal control group(NC,n=40),aMCI group(n=147),and AD group(n=29).After the general data and clinical information collection,neuropsychological test,TCM syndromes evaluation were completed,the above items of the three groups were compared and the correlation between TCM syndromes and cognitive function in patients with aMCI was analyzed.The risk factors of aMCI and AD were evaluated by logistic regression.Study 2:119 subjects were enrolled and divided into normal control group(n=45),aMCI group(n=60),and AD group(n=14).Thin layer brain magnetic resonance image(MRI)scanning was performed.The cortical thickness,hippocampal volume(HV),and amygdala volume(AV)were segmented and measured with FreeSurfer 6.0,and the volume of the above region of interest(ROI)was corrected.The mean cortical thickness,hippocampal volume and amygdala volume in the three groups were compared and the correlation between the ROI and cognitive function was analyzed.Receiver operating characteristic(ROC)curve was used to evaluate the diagnostic accuracy of cortical thickness,hippocampal volume and amygdala volume in distinguishing NC from aMCI and aMCI from AD.Study 3:142 aMCI subjects were followed up for 24 months.The observation time points were baseline,6 months,12 months,and 24 months,at each of which neuropsychological tests and TCM syndromes evaluation was performed.The correlation between TCM syndrome changes and cognitive function changes in the aMCI subjects was analyzed.At the end of the 12-month and 24-month follow-up,the aMCI subjects were divided into three groups according to the outcome:the stable cognition group(stable group),the reversal to normal cognition group(reversal group),and the progression to dementia group(progressive group).The difference in demographic factors,clinical information,cognitive function and TCM syndromes of the three groups was compared,and logistic regression was used to find the risk factors for the conversion of aMCI.Results:1.(1)The age of AD group is higher than that of NC group(P=0.037);the years of education in aMCI group(P=0.001)and AD group(P=0.009)are lower than that of NC group;the proportion of smokers in aMCI group is higher than that of NC group and AD group(P<0.05);the proportion of people interested in hobbies in NC group and aMCI group is higher than that of AD group(P<0.05).(2)With the exception of MCI-ADL,there were significant differences in the scores of all scales among the three groups(P<0.001).(3)As to the aMCI group,the MMSE score is negatively correlated with kidney deficiency(b=-0.135,P=0.031),Qi deficiency(b=-0.106,P=0.036);The language score in the MMSE scale is negatively correlated with spleen deficiency(b=-0.037,P=0.009);The completion time of the Trail Making Test-A(TMT-A)is positively correlated with yang hyperactivity(b=1.862,P=0.034),and the and the MCI-ADL score is negatively correlated with Qi deficiency(b=-0.573,P=0.029).As to the AD group,the score of Clock Drawing Test is negatively correlated with marrow deficiency(b=-0.213,P=0.047);The completion time of TMT-A is positively correlated with marrow deficiency(b=7.371,P=0.015);The Activities of Daily Living score is positively correlated with spleen deficiency(b=2.010,P=0.006)and endogenous heat(b=3.689,P=0.007).(4)Taking "NC group" and "aMCI group" as dependent variables,logistic regression shows that,age(OR=1.054,95%Cl 1.016-1.093,P=0.005),years of education(OR = 0.831,95%CI 0.758-0.911,P<0.001),smoking(OR=2.343,95%CI 1.157-4.746,P=0.018),and marrow deficiency(OR=1.090,95%CI 1.002-1.186,P=0.046)are significantly correlated with aMCI,while age(OR=1.080,95%CI 1.011-1.156,P=0.022);marrow deficiency(OR=1.392,95%CI 1.163-1.667,P=0.000);phlegm turbidity(OR=0.698,95%CI 0.569-0.857,P=0.001)and blood stasis(OR=0.702,95%CI 0.518-0.951.P=0.023)are significantly correlated with AD when taking "NC group" and "AD group" as dependent variables.2.(1)Left HV,right HV,total HV,left AV,right AV,total AV,and cortical thickness gradually decrease among the NC group,aMCI group,and AD group(P<0.01).(2)In aMCI group,the MMSE score are positively correlated with total hippocampal volume(b=0.001,P=0.005),but not with total amygdala volume and cortical thickness;Delayed Story Recall(DSR)score are positively correlated with total hippocampal volume(b=0.003,P=0.000),but not with total amygdala volume and cortical thickness;Boston Naming Test-30(BNT-30)are positively correlated with cortical thickness(b=18.99,P=0.005),but not with total hippocampal volume and total amygdala volume;There is a negative correlation between the completion time of TMT-A and the total amygdala volume(b=-0.035,P=0.025).(3)Cortical thicknss distinguishes NC from aMCI with an area under curve(AUC)of 0.652,while the sensitivity and specificity are 0.622 and 0.683 respectively;the AUC for distinguishing between aMCI and AD is 0.774,and the sensitivity and specificity are respectively 0.683,0.857.When distinguishing NC from aMCI,the AUC of left HV,right HV and total HV is 0.731,0.727.0.728,respectively,the sensitivity 0.432,0.727,0.682,and the specificity 0.915,0.661,0.729,respectively.When distinguishing aMCI from AD,the AUC of left HV,right HV and total HV is 0.821,0.872,0.854,the sensitivity 0.898,0.780,0.797,the specificity 0.714,0.929,0.857,respectively.The left AV,rightAV and total AV distinguish NC from aMCI with the AUC of 0.710,0.683,0.688,specificity of 0.831,0.864,0.932,and sensitivity of 0.523,0.500,0.386,respectively.When distinguishing aMCI from AD,the AUC of left AV,righr AV and total AV is 0.850,0.840,0.849,sensitivity 0.797,0.712,0.695,and specificity 0.857,0.929,0.929,respectively.3.(1)80 subjects with aMCI completed the 12-month follow-up trial,and 49 of them completed the 24-month follow-up trial.In the 12-month follow-up trial,13 cases(16.25%)progressed to dementia(progressive group),11 cases(13.75%)reverted to normal(reversal group),and 56 cases remained stable(70.00%)(stable group).In the 24-month follow-up trial,17 cases(34.69%)progressed to dementia(progressive group),10 cases(20.41%)reverted to normal(reversal group),and 22 cases(44.90%)remained stable(stable group).(2)Logistic regression shows that,DSR score(OR=0.680,95%CI 0.506-0.914,P=0.011),ADL score(OR=0.680,95%CI 0.506-0.914,P=0.011),ADL(OR=33.132,95%CI 1.844-595.313,P=0.018),and blood deficiency(OR=0.509,95%CI 0.262-0.989,P=0.046)are significantly correlated with aMCI progression to dementia within 12 months.There is no significant correlation between gender,occupation,arrhythmia,DSR score,endogenous heat and aMCI reversion to normal cognition within 12 monthsConclusion:1.Age,low education,smoking and marrow deficiency may be independent risk factors for aMCI,while age and marrow deficiency may be independent risk factors for AD.For aMCI patients,the more serious the kidney deficiency and Qi deficiency are,the worse the general cognitive function is;The more serious the spleen deficiency is,the worse the language function is;The more severe yang hyperactivity,the worse executive function;The more serious the Qi deficiency,the worse the ability of daily life.For AD patients,the more severe the marrow deficiency,the worse the visual spatial function and executive function;The more severe the spleen deficiency and endogenous heat,the worse the ability of daily life.2.Hippocampal volume,amygdala volume and cortical thickness are related to the degree of cognitive decline in AD patients.The decline of cognitive function and episodic memory function in aMCI may be related to hippocampal atrophy,but not to amygdala and cortical atrophy;The decreased naming function of aMCI may be related to the atrophy of cortex,but not to the atrophy of hippocampus and amygdala;The decreased executive function of aMCI may be related to amygdala atrophy;but not to hippocampus and cortex atrophy.Cortical thickness cannot be used as a diagnostic marker of aMCI;Hippocampal volume and amygdala volume cannot be used as diagnostic markers to distinguish aMCI from NC;Hippocampus volume and amygdala volume can be used as diagnostic markers to distinguish aMCI from AD dementia3.The changes of yin deficiency,marrow deficiency,spleen deficiency,Qi deficiency,blood deficiency,yang deficiency and phlegm turbidity reflect the changes of cognitive function in patients with aMCI.DSR score and ADL score may be independent risk factors for aMCI progression to dementia within 12 months.