Study On The Correlation Between White Matter Hypersignal And Cognitive Impairment And Cerebrospinal Fluid Iomarkers In Patients With Alzheimer’s Disease

Objective:A large amount of epidemiological,genetic and clinical evidence indicates that Alzheimer’s disease(AD)is associated with cerebrovascular disease(CSVD).CSVD may lead to cognitive impairment through the accumulation of brain Aβ,which may play an important role in the development of AD,but its specific mechanism remains to be further studied.The purpose of this research was to preliminarily explore the correlation between white matter hypersignaling(WMH)load and the degree of cognitive impairment,hippocampus atrophy,vascular risk factors and cerebrospinal fluid core biomarkers in AD patients.This research may lay a preliminary foundation for further exploring the possible mechanism of the occurrence and development of white matter lesions in AD patients,which may provide a new way for further searching for the mechanism and treatment of its comorbidities.Method:86 AD patients and 43 cognitive normal controls enrolled from September 2018 to October 2021 were random selected from the First Affiliated Hospital of University of Science and Technology of China.The baseline data such as sex,age,education level,hypertension and diabetes were collected.All research subjects were assessed by the Intelligent Status Check Scale(MMSE).All patients were tested by head MRI scans,including T1,T2,and FLAIR.All patients were evaluated by blinded assessment of brain atrophy and white matter lesions by two experienced imaging physicians.The degree of hippocampal atrophy of the included subjects was assessed by the MTA score.All white matter lesions were scored as judged by cranial MRI-T2/FLAIR sequence.The whole blood and CSF from the patients were collected for AOPE genotype testing,Aβ1-40,ELISA),Aβ1-42 assay,P-tau181,and T-tau.All data were analysed using SPSS 22.0.All data were analysed using SPSS 22.0.Independent sample t-test,and Mann Whitney U non-parametric test were used.The grade data were compared between groups by chi-square test..Multivariate Logistic regression analysis was used to explore the effects of WMH with AD biomarkers,cognitive impairment,hippocampal atrophy,and vascular risk factors.The ROC analysis was used to test the accuracy of the markers distinguishing the different clinical groups.Result:1.There was no statistical difference in gender,education level in AD group and control group(P=0.106 and P=0.780).The difference in the age distribution between the two groups(P=0.005).There was no significant difference in the proportion of hypertension and diabetes(P=0.523,P=0.571).In terms of APOE ε 4 genotype expression,APOEε4 in AD group was significantly higher than that in the control group(P<0.001).In terms of cognitive function,the MMSE score in AD group was significantly lower than that in cognitively normal control group(P<0.001).2.There was no significant differenc in the content of Aβ1-40 in AD group and control group(P=0.703).Aβ1-42 and Aβ1-42/Aβ1-40 in AD group were significantly lower than that in control group(P<0.001).CSF P-tau181 and T-tau in AD group were significantly higher than that in control group(P<0.001).3.After adjusting for age and sex,the AD group was significantly more atrophy than that in control group(P<0.001).57 AD cases(66.28%)had white matter hyperintensity,which was significantly higher than that in control group 9 cases(22.93%).According to the Fazekas scale,after adjusting for age,sex,hypertension and diabetes,the AD group had significantly higher WMH total scores(P<0.001),DWMH(P<0.001)and PVWMH(P<0.001)compared with the control group.4.The age in AD group with white matter lesions(WMH≧1)was significantly higher than that in the group with no white matter lesions(WMH=0)(P<0.0001),and the education level was higher(P=0.004).In addition,AD patients without white matter lesions had lower CSF levels of Aβ1-42(P=0.007).There were no significant differences in gender(P=0.308),hypertension(P=0.829),diabetes(P=0.428),APOEε4 carriage(P=0.099),MMSE score(P=0.694),CSF Aβ1-40(P=0.244),P-tau181(P=0.123),T-tau(P=0.164).A higher MTA grade within the AD group was accompanied by a higher WMH score(P=0.004).In AD group,after adjusting for age,sex,hypertension,diabetes,and APOE genotype,the level of cerebrospinal fluid Aβ1-42 was higher in WMH(grade 1-2)and lower in grade 5-6 under different WMH grades in AD group(P=0.024),and the level of cerebrospinal fluid P-tau181 was lower in grade 5-6 under different grades of WMH,DWMH,and PVWMH(P=0.008).5.WMH score alone and traditional CSF biomarker diagnosis were not dominant in different clinical groups(AUC=0.7489,P<0.0001),but the WMH score combined with MTA score can significantly distinguished the AD group and control group(AUC=0.9654,P<0.0001).Conclusion:The study found that under the framework of ATN study,the degree of cerebral white matter lesions in AD patients has different grades of hippocampal atrophy,the more severe the hippocampal atrophy,the more severe the cerebral white matter lesions,further indicating that the cerebral white matter lesions in AD patients are associated with the disease process of AD.