| BackgroundAlzheimer’s disease(AD)is the most common of all dementia diseases,accounting for 60% of all dementia patients.In the early stage of AD,the quality of life and social skills decline,and there is a high disability rate in the late stage,resulting in patients losing the ability to live independently and completely in need of care.Currently,there is no effective treatment for AD.With the development of neuroimaging,people’s understanding of AD is no longer limited to the atrophy of hippocampal volume in structural magnetic resonance imaging.Molecular imaging of amyloid and Tau proteins in the brain further enables us to recognize the continuous pathological spectrum that has existed in the pre-clinical stage of AD,providing clues of time target for the prevention of AD.In AD,there are not only cortical degeneration and atrophy,but also changes in white matter.More and more studies have shown that the change of white matter in AD occurs at an early stage,and the change does not depend on the atrophy of gray matter in the projection area.The change of white matter is closely related to AD specific biomarkers and cognitive function level,and white matter damage is also considered as an important part of AD pathology.Diffusion tensor imaging(DTI),which is widely used clinically to assess changes in the microstructure of white matter,provides information on the orientation and voluntary movement of water molecules in brain tissue to evaluate the integrity of white matter,which is helpful to explore the role of white matter change in cognitive impairment and its influencing factors in AD.PurposeExploring the correlation between white matter integrity and cognitive function level and the influencing factors of white matter integrity provides valuable clues for the targets of prevention and treatment of AD.MethodsFrom January 2019 to December 2019,38 AD patients who visited the outpatient department of neurology or were hospitalized in the department of Neurology of the First Affiliated Hospital of Zhengzhou University were selected.Clinical data such as age,sex,disease course,years of education,height and quality index,history of hypertension,and history of diabetes were collected for all enrolled subjects.Cognitive function level was assessed by the Mini-Mental State Examination,Auditory-Verbal Learning Test,Clock Drawing Test,Digit Span Test and Trail Making Test A.Fasting peripheral venous blood was extracted to detect apolipoprotein E genotype and serum nerve filament protein light chain level.The Fazekas scale was used to score the severity of white matter hyperintensities based on T2-FLAIR sequence imaging.Fractional anisotropy(FA)and mean diffusivity(MD)of brain DTI were used to assess the integrity of white matter.Patients with AD were divided into ApoE ε4 carrier group and ApoE ε4 non-carrier group according to whether they carried ApoE ε4 or not.The differences in the integrity of white matter fiber tracts between the two groups were compared using tract-based spatial statistics(TBSS).Furthermore,20 regions of interest were established by JHU White-matter Tractography Atlas of Johns Hopkins University,and FA and MD values were extracted to analyze the correlation between the integrity of white matter fiber tracts and the level of cognitive function,as well as the effects of ApoE ε4 carrying status and white matter hyperintensities on the integrity of white matter fiber tracts.Results1.FA values of bilateral cingulum(cingulate gyrus)and right uncinate fasciculus were positively correlated with the MMSE score(P<0.05).FA values of forceps minor,left inferior longitudinal fasciculus and bilateral uncinate fasciculus were positively correlated with the Aditory-Verbal Learning Test(immediate recall)score(P<0.05).FA value of right uncinate fasciculus was positively correlated with the Clock Drawing Test and Digit Span Test scores(P<0.05).Fazekas score was positively correlated with completion time of Trail Making Test A(P<0.05).There was no significant correlation between Fazekas score and MMSE score,Clock Drawing Test score,or Digit Span Test score.2.According to whether ApoE ε4 was present or not,patients with AD were divided into ApoE ε4 carrying group and ApoE ε4 non-carrying group.There were no statistically significant differences in age,sex,disease duration,years of education,history of hypertension,history of diabetes,BMI,and Fazekas scores between the two groups.The MMSE score of patients with AD in the ApoE ε4 carrier group was lower than that of the ApoE ε4 carrier group(14.09 vs 20.33,P<0.05).3.Compared with the group without ApoE ε4,FA value of the left cingulum(cingulate gyrus)was lower in the group with ApoE ε4.Age,sex,years of education,Fazekas score,and carrier status of ApoE ε4 were included in multiple linear regression models to investigate the factors influencing FA values of white matter fiber tracts.,and the analytic outcome indicated that ApoE ε4 was significantly correlated with FA values of bilateral uncinate fasciculus(P<0.05),WMH was significantly correlated with FA values of the widespread white matter(P<0.05),years of education was significantly correlated with FA values of left anterior thalamic radiation,forceps minor,and right inferior frontal-occipital tract(P<0.05).Stratification analysis of gender showed that ApoE ε4 was significantly correlated with FA values of left cingulum(cingulate gyrus),left hippocampal cingulum and right uncinate fasciculus in the female AD group(P<0.05).There was no significant correlation between ApoE ε4 and FA values of white matter tracts mentioned above in the male AD group.4.There was no significant correlation between serum NFL level and Fazekas score(r = 0.263,P = 0.325).5.Serum NFL level was significantly correlated with FA values of bilateral cingulum(cingulate gyrus),bilateral hippocampal cingulum,and bilateral superior longitudinal fasciculus(temporal part),and right uncinate fasciculus(P<0.05).The serum NFL level was significantly correlated with MD values of bilateral cingulum(cingulate gyrus),left hippocampal cingulum,left superior longitudinal fasciculus(temporal part),and bilateral uncinate fasciculus(P<0.05).Conclusions1.Impairment of brain white matter integrity in AD is one of the important pathological changes.FA value of white matter tracts is significantly correlated with the overall cognitive function level,as well as memory,visuospatial structure ability,and attention domains in AD patients.2.In sporadic AD,ApoE ε4 and WMH are risk factors for white matter integrity,and the correlation between ApoE ε4 and the integrity of left cingulum(cingulate gyrus),left hippocampal cingulum,and right uncinate fasciculus was more significant in female AD patients.Education level is a protective factor for the integrity of white matter,and increasing education experience may help to slow down the progression of cognitive impairment in the context of brain Tau pathology.3.There was no significant correlation between serum NFL level and white matter hyperintensities.Serum NFL level was significantly correlated with white matter integrity of susceptible brain regions of AD,which may reflect a higher level of Tau pathology in the corresponding brain.regions. |
PDF Full Text Request