Study On The Relationship Between Serum Aβ_1-42、Orexin-a、Tau Protein Levels And Ischemic Post-stroke Cognitive Impairment

Objective:To investigate the relationship between the expression of Amyloid beta_1-42(Aβ_1-42),Orexin-A（OX-A）,Tau protein and and ischemic post-stroke cognitive impairment（PSCI）and its value in early diagnosis of ischemic PSCI,and to understand the effect of other risk factors on ischemic PSCI.Methods:Choose between April 2018 and January 2019 in the first affiliated hospital of hainan medical college neurology treated 117 cases of patients with acute cerebral infarction and in the same period 65 cases of healthy physical examination as the research object,and record the subjects’demographic data（age,gender,level of education）,past medical history（high blood pressure,diabetes,coronary heart disease）,personal history,history of smoking,drinking)and blood biochemical general project（total cholesterol,triglycerides,high-density lipoprotein cholesterol,low density lipoprotein cholesterol,hypersensitive c-reactive protein and homocysteine）and other information,and to return their fasting venous blood samples,The expression of Aβ_1-42,Orexin-A,Tau protein was detected by ELISA.Three months later,the patients in the cerebral infarction group were followed up.After completing the（MMSE）score of Montreal Cognitive Assessment scale（MoCA）and Mini Mental State examination scale（MMSE）,according to the MoCA evaluation results,the patients were divided into cognitive impairment group 1（PSCI group 1）after cerebral infarction and cognitive normal group 1（non-psci group 1）after cerebral infarction,according to the MMSE evaluation results,the patients were divided into cognitive impairment group 2（PSCI group 2）after cerebral infarction and cognitive normal group 2（non-psci group 2）after cerebral infarction.Serum Aβ_1-42,Orexin-A and Tau protein concentrations in PSCI group 1 and non-psci group 1,PSCI group 2 and non-psci group 2 were compared respectively,to analyze the correlation between serum Aβ_1-42,Orexin-A and p-tau concentrations and cognitive dysfunction after ischemic stroke and its value in early diagnosis of ischemic PSCI.Results:1、The level of serum Aβ_1-42（138.77±90.54）pg/m L in cerebral infarction group was significantly higher than that in healthy control group（101.39±76.01）pg/m L,P<0.05;The serum Orexin-A concentration（1000.67±1182.23）pg/m L in cerebral infarction group was significantly higher than that in healthy control group（450.02±268.93）pg/m L,P<0.001;The level of serum P-tau in cerebral infarction group（234.20±320.27）pg/m L was lower than that in healthy control group（257.96±328.18）pg/m L,P>0.05;2、The level of serum Aβ_1-42in PSCI grou 1（114.06±80.14）pg/m L was significantly lower than that in non-PSCI group 1（171.87±93.83）pg/m L,P<0.001;The levels of serum P-tau（184.25±252.69）pg/m L and Orexin-A（880.33±1112.40）pg/m L in PSCI group1 were significantly lower than those in non-PSCI group1（301.13±385.79）pg/m L.There was no significant difference in Orexin-A level（1161.93±1263.21）pg/m L,P>0.05;The level of serum Aβ_1-42in PSCI group2（91.38±72.92）pg/m L was significantly lower than that in non-PSCI group2（178.01±85.16）pg/m L,P<0.001;The levels of serum P-tau（176.30±243.93）pg/m L and Orexin-A（804.27±1075.29）pg/m L in PSCI group 2 were significantly lower than those in non-PSCI group 2（282.15±366.87）pg/m L and Orexin-A（1163.32±1248.92）pg/m L.There was no significant difference between the two groups,P>0.05.3、The results of binary Logistic regression analysis showed that under the MoCA scoring system,low years of education（OR=0.705,P<0.000）,hypertension（OR=2.889,P=0.011）,high TG（OR=1.890,P=0.032）and high HCY（OR=1.145,P=0.000）,high Hs-CRP（OR=1.124,P=0.015）and ischemic PSCI existed regression analysis.Low serum Aβ_1-42concentration（OR=0.985,P=0.000）,low education years（OR=0.618,P=0.00）,high HCY（OR=1.145,P=0.015）and ischemic PSCI were correlated with MMSE score.4、In MoCA assessment,there were significant differences in visual spatial executive function,naming,attention,language,delayed memory and orientation in patients with post-stroke cognitive impairment（P<0.05）.In MMSE assessment,there were significant differences in orientation,attention and calculation,recall,comprehension and painting among patients with cognitive impairment after stroke（P<0.05）.5、Spearman correlation analysis showed that there was a significant positive correlation between MoCA score and serum Aβ_1-42level after 3 months of cerebral infarction（r=0.537,P<0.001）,and a significant positive correlation between MoCA score and serum Orexin-A level（r=0.339,P<0.001）.There was a significant positive correlation between MMSE scores and serum Aβ_1-42levels in patients with cerebral infarction 3 months later（r=0.555,P<0.001）and serum Orexin-A levels（r=0.336,P<0.001）,and in patients with cerebral infarction,there was a significant positive correlation between them（r=0.336,P<0.001）and serum Aβ_1-42levels（r=0.555,P<0.001）.There was no correlation between MoCA score and MMSE score and Tau protein level（P>0.05）.There was a positive correlation between serum OX and Aβ_1-42（r=0.555,P<0.01）;No correlation between OX and Tau protein in serum（P>0.05）.6、The results of ROC curve showed that:（1）the results of MoCA after 3 months of cerebral infarction were used as the criteria for the diagnosis of cognitive impairment.According to the Joden index,the optimal critical value of Aβ_1-42for diagnosis of ischemic PSCI was 120.96 PG/ml,and the area under the curve was AUC 0.68.The sensitivity and specificity were 76%and 58%respectively.The optimal critical value for diagnosis of ischemic PSCI by Orexin-A was 445.62 PG/ml,the area under the curve was 0.61,the sensitivity was 78%,and the specificity was 42%for diagnosis of ischemic PSCI.The AUC under the curve was 0.57,the sensitivity was 32%and the specificity was 87%.（2）According to the MMSE results of 3 months after cerebral infarction as the criteria for the diagnosis of cognitive impairment,the optimal critical value of Aβ_1-42for diagnosis of ischemic PSCI was 120.96 pg/m L,the area under the curve AUC was 0.80 and the sensitivity was 81%,according to the Joden index,the optimal threshold for the diagnosis of ischemic PSCI was 120.96 PG/ml,and the sensitivity was 81%.The specificity was 74%;The optimal critical value for diagnosis of ischemic PSCI by Orexin-A was 445.62 pg/m L,the area under the curve was 0.66,the sensitivity was 81%,and the specificity was 146.58 PG/ml for the diagnosis of ischemic PSCI.The area under the curve was 57%AUC,47%sensitivity and 72%specificity.（3）The sensitivity and specificity of combining Aβ_1-42,Tau protein,Orexin-A to predict the occurrence of PSCI in the MoCA standard were 0.76 and 0.58respectively,and the area under the ROC curve（AUC）of the combined effect of the three indexes was 0.68.The sensitivity and specificity of combining Aβ_1-42,Tau protein,Orexin-A to predict the occurrence of PSCI in the MMSE standard were 0.77 and 0.75,respectively,and the area under the ROC curve（AUC）of the combined effect of the three indexes was 0.78.Conclusions:1.The levels of serum Aβ_1-42and Orexin-A were correlated with ischemic PSCI,and the levels of serum Aβ_1-42and Orexin-A were positively correlated with the scores of MoCA and MMSE 3 months after cerebral infarction.There was no correlation between serum Tau protein level and ischemic PSCI.There was a positive correlation between serum orexin-a and Aβ_1-42;There was no correlation between OX and Tau protein in serum2.Low education years,hypertension,high TG,and high HCY,and high Hs-CRP were independent risk factors for ischemic PSCI under MoCA scoring system.Low serum Aβ_1-42concentration,low education years and high HCY were independent risk factors for ischemic PSCI under MMSE scoring system.3.Serum Aβ_1-42may be used as a relative biomarker to predict ischemic PSCI in patients with cerebral infarction,and the serum Orexin-A in patients with cerebral infarction has certain value in the clinical evaluation of ischemic PSCI;Serum Tau protein level can not be used as a clinical index to predict ischemic PSCI.