Study On The Correlation Between APOE Epsilon 4 Gene Carrying,Blood Brain Barrier Permeability And Cognitive Impairment In Patients With Small Vascular Disease

Objective:Cerebral small vascular disease is one of the main causes of cognitive impairment,but its mechanism remains unclear.Previous studies have shown that APOEε4 gene and BBB damage are involved in the cognitive impairment of various neurodegenerative diseases(PD,AD,etc.),but the role of APOEε4 gene in the cognitive impairment of cerebral small vascular disease(CSVD)remains unclear.The purpose of this study was to investigate:1)whether APOEε4 gene carrier mediated cognitive impairment in patients with CSVD;2)Whether the change of periventricular BBB permeability is involved in the cognitive impairment of CSVD patients;3)Peripheral blood biomarkers(Aβ42,P-tau,CYPA,MMP-9,PFGFR-β,ICAM-1)were detected to screen peripheral blood biomarkers associated with cognitive impairment and BBB impairment in patients with CSVD.Methods:This study is divided into two parts.Part I:A total of 303 subjects who met the inclusion/exclusion criteria admitted to the Department of Neurology of our Hospital from February 2021 to October 2022 were collected and divided into two groups according to APOE genotype:75 APOE ε4(+)and 228 APOE ε4(-).Baseline data(general clinical data,serum lipid,creatinine,uric acid,serum homocysteine and other biochemical indicators)were collected,and cognitive scales such as the Chinese version of the Montreal Cognitive Assessment Scale(MoCA)and the Simple Mental State Examination Scale(MMSE)were evaluated.Cranial magnetic resonance imaging(MRI)was performed(T1,T2,T2 Flair)and graded according to the Fazekas scale for periventricular white matter lesions.Part Two:Forty-eight of these patients underwent dynamic enhanced magnetic resonance imaging(DCE-MRI)to measure the BBB Ktrans value of the periventricular white matter,and collected fasting peripheral blood in the morning to detect the biological indicators(Aβ42,P-tau,CYPA,MMP-9,PFGFR-β,ICAM-1)related to cognition and BBB destruction.Results:Part Ⅰ:Among the 303 subjects who met the inclusion/exclusion criteria,there were no statistically significant differences in baseline data such as sex,age,hypertension,diabetes,coronary heart disease history,blood lipid,creatinine,uric acid,and homocysteine between the APOEε4 carriers and non-carriers(p>0.05).There were also no significant differences in MMSE and MoCA scores between the two groups(p>0.05).Part Ⅱ:The results showed that Ktrans value of the lateral ventricular white matter blood-brain barrier was significantly correlated with MoCA score(r=0.306,p=0.036),and was significantly correlated with naming,speech and orientation in each individual cognitive domain(p<0.05),after adjusting for age,gender,hypertension and other common vascular risk factors,were still significantly correlated(p=0.01 8).In the analysis of correlation between BBB permeability markers(CYPA,MMP-9,PFGFR-β,ICAM-1)and cognition,each marker was negatively correlated with the overall cognitive score,but there was no statistical significance(p>0.05),in the scores of each individual cognitive domain,each marker was significantly correlated with multiple individual cognitive domains;There was no significant correlation between the cognitive pathologic pathogens(Aβ42,P-tau)and the overall or individual cognitive domains.Only the correlation between ICAM-1 and ktrans was statistically significant(r=0.461,p=0.001).Conclusion:1.No correlation was found between APOE Epsilon 4 gene carrying and cognitive scores in CSVD patients.2.Lateral ventricular votor BBB damage is associated with cognitive impairment of CSVD.3.Markers associated with BBB destruction are associated with cognitive impairment of CSVD,suggesting that endothelial cell dysfunction has a greater influence on the changes of BBB permeability in CSVD patients.