Study On White Matter Fiber Bundle Damage In Mild Cognitive Impairment Due To Different Etiology Based On Atlas-based Analysis

Background:In recent years,the focus of dementia has shifted to the stage of mild cognitive impairment(MCI).Alzheimer’s disease(AD)and small vessel disease(SVD)are the two main diseases leading to dementia,and the preclinical stages of the two diseases are AD-MCI and SVD-MCI.The differential diagnosis of AD-MCI and SVD-MCI is still difficult because neuropsychological features and conventional neuroimaging findings often overlap.Here is no specific identification marker between the two MCI subtypes.White matter hyperintensity is one of the typical imaging manifestations of SVD-MCI and has been proved to exist in AD-MCI.Magnetic resonance diffusion tensor imaging(DTI)has been proved to be a sensitive imaging tool for identifying the changes of white matter microstructure.Objective:To compare the characteristics of cognitive and white matter microstructure damage in AD-MCI and SVD-MCI patients,and explored the correlation between white matter microstructure and cognitive of different MCI subtypes.To understand the neuropsychological characteristics and neuropathological mechanisms of two MCI subtypes in order to provide more reliable indicators for differential diagnosis of AD-MCI and SVDMCI patients.Methods:33 AD-MCI patients and 25 SVD-MCI patients have been selected in Memory Disorder Clinic of our hospital from January 2019 to August 2020,20 volunteers matched with sex,age and education level were recruited at the same time.The demographic and clinical data of all subjects were collected,and all subjects underwent a series of neuropsychological assessment including general cognition,memory,language,attention,visuospatial function,executive function,daily life ability,depression and anxiety emotion and cranial magnetic resonance scanning.Diffusion tensor parameters including fractional anisotropy(FA)and mean diffusivity(MD)of 20 major white matter tracts corresponding to DTI images were obtained by atlas-based analysis(ABA).The neuropsychological tests scores and diffusion tensor parameters of the three groups were compared.The receiver operating characteristic(ROC)curve have been used to calculate the diagnostic efficacy of neuropsychological tests and diffusion tensor parameters which had significant differences between the two MCI subgroups.Spearman partial correlation method was used to analyze the correlation between cognitive function which had significant difference among groups and white matter tracts in two groups of MCI.Results:(1)General information analysis:There was no significant difference in age,sex,education,diabetes mellitus,hyperlipidemia,smoking,drinking,activity of daily living scale(ADL),Hamilton depression rating scale(HAMD),Hamilton anxiety rating scale(HAMA)between the three groups.The proportion of hypertension in the SVD-MCI group were significantly higher than the NC group and the AD-MCI group(p<0.05).(2)The results of neuropsychological assessment:There were significant differences in mini mental state examination(MMSE),Montreal cognitive assessment scale(MoCA),Rey auditory verbal learning test-immediate recall(RAVLT-IR),Rey auditory verbal learning test-delayed recall(RAVLT-DR),and verbal fluency test(VFT)(p<0.05)between the NC and AD-MCI groups.There were significant differences in MMSE、MoCA、RAVLT-IR、RAVLT-DR、VFT、digit span test(DST),Stroop’s color word test(SCWT)text time,SCWT dot time,SCWT color time,SCWT text errors,and SCWT color errors(p<0.05)between the NC and SVDMCI groups.There were significant differences in SCWT color time and SCWT color errors between the AD-MCI and SVD-MCI groups.(3)Characteristics of fiber bundle damage:Compared with the controls,AD-MCI group had significantly decreased FA values of cingulum(cingulate gyrus),cingulum(hippocampus),occipital region of corpus callosum,frontal part of the corpus callosum,left inferior fronto-occipital fasciculus,inferior longitudinal fasciculus,superior longitudinal fasciculus,uncinate fasciculus and increased MD values of cingulum(cingulate gyrus),cingulum(hippocampus),occipital region of corpus callosum,frontal part of the corpus callosum,left inferior longitudinal fasciculus,superior longitudinal fasciculus,uncinate fasciculus.Compared with the controls,SVD-MCI group had significantly decreased FA values of anterior thalamic radiation,left cingulum(cingulate gyrus),cingulum(hippocampus),occipital region of corpus callosum,frontal part of the corpus callosum,inferior frontooccipital fasciculus,inferior longitudinal fasciculus,superior longitudinal fasciculus,uncinate fasciculus and increased MD values of anterior thalamic radiation,cingulum(cingulate gyrus),cingulum(hippocampus),occipital region of corpus callosum,frontal part of the corpus callosum,left inferior longitudinal fasciculus,superior longitudinal fasciculus,uncinate fasciculus.The fiber bundles with significant difference in FA values between AD-MCI and SVDMCI groups included the bilateral anterior thalamic radiation,frontal part of the corpus callosum and right inferior longitudinal fasciculus.The statistically different MD values of fiber tracts included the occipital region of corpus callosum and frontal part of the corpus callosum.(4)Identification of two MCI subgroups:ROC analysis indicated that the MD value of frontal part of the corpus callosum had a higher ability to identify the two MCI subgroups(The area under the curve was 0.815;specificity was 72.7%;sensitivity was 88.0%;p<0.0001;95%CI 0.698-0.932).SCWT color errors also had moderate discrimination potential(The area under the curve was 0.747;specificity was 63.6%;sensitivity was 76.0%;95%CI 0.617-0.877).The combined predictors of the two indicators had the best diagnostic efficacy(The area under the curve was 0.822;specificity was 69.7%;sensitivity was 92.0%;p<0.0001;95%CI 0.707-0.937).(5)Correlation analysis between executive function and white matter tracts of two MCI subgroups showed that executive function in the AD-MCI group was associated with anterior thalamic radiation,corticospinal tract,cingulum(hippocampus),inferior frontooccipital fasciculus,inferior longitudinal fasciculus,superior longitudinal fasciculus,uncinate fasciculus and superior longitudinal fasciculus-temporal part.Executive function in the SVD-MCI group was associated anterior thalamic radiation,corticospinal tract,cingulum(cingulate gyrus),cingulum(hippocampus),occipital region of corpus callosum,frontal part of the corpus callosum,inferior fronto-occipital fasciculus,inferior longitudinal fasciculus,superior longitudinal fasciculus,uncinate fasciculus and superior longitudinal fasciculus-temporal part.Conclusion:(1)AD-MCI was manifested as the impairment of memory and language function,while SVD-MCI was manifested as the impairment of multi-recognition domain of memory,language,attention and executive function.There was difference in executive function between the two MCI groups.(2)There was a large amount of white matter tracts damaged in both AD-MCI and S VDMCI,and the damage of white matter tracts in SVD-MCI was more extensive and serious.There were differences in the anterior thalamic radiation,occipital region of corpus callosum,frontal part of the corpus callosum,right inferior longitudinal fasciculus between two MCI groups,which were related to executive function.(3)SCWT color errors and the MD value of frontal part of the corpus callosum can be used to identify different MCI patients due to AD and SVD,the combination of the two index has better diagnostic efficacy,DTI is a useful neuroimaging tool for MCI etiology diagnosis.(4)The differential relationship between executive function of AD-MCI and SVD-MCI and white matter tracts indicated the independent neuropathology of executive function damage in different diseases of dementia.In clinical work,it is of great significance to make clear the etiological diagnosis of MCI for early intervention and treatment.