| Objective: Vascular cognitive impairment(VCI)refers to cognitive dysfunction syndrome caused by cerebrovascular diseases such as ischemic stroke,hemorrhagic stroke and low perfusion in memory,cognition and behavior brain regions.The morbidity of vascular dementia(VD)in China is 1.1% ? 3.0% but not all patients with cerebrovascular diseases have cognitive impairment.Therefore,it is of clinical value to accurately identify high-risk patients and carrying out intervention with nootropic agents early.In this study,the presence or absence of cognitive impairment and obvious aggravation of mild cognitive impairment,the relationship between cognitive impairment and substances detected in early stage are assessed through early monitoring of plasma markers beta-amyloid(A?),Tau protein and serum thyroid hormone levels in the process of ischemic stroke so as to determine the potential application value of blood biomarkers in predicting post-stroke cognitive impairment(PSCI).Methods: A total of 278 patients with acute ischemic stroke who were admitted to the Neurology Department,Baoshan Branch,Shanghai First People's Hospital between January 2016 and January 2018 were selected.Their clinical baseline data,including demographic data,life history and health status,were collected in 3 ? 5 days after admission.The infarct sites were recorded by Siemens MAGNETOM Skyra 3.0T smart magnetic resonance imager,and TOAST grading was performed.The patients' fasting venous blood was collected in the morning within 24 hours after admission to detect biochemical indexes such as total cholesterol(TC),triglyceride(TG),low-density lipoprotein(LDL),high-density lipoprotein(HDL),high-sensitivity C-reactive protein(hs-CRP)and homocysteine(Hcy)with AU-400 automatic biochemical analyzer.The levels of A?1-42 and total Tau protein were determined by ELISA.The levels of thyroid hormones [triiodothyronine(T3),thyroxin(T4),free triiodothyronine(FT3),free thyroxin(FT4),thyrotropin(TSH)] were detected by chemiluminescence immunoassay.The cognitive function was evaluated with Mo CA within 1 week after the onset of the disease.The Mo CA score lower than 26 points indicates cognitive impairment,while Mo CA score not lower than 26 points indicates normal cognitive function.Patients with MMSE scores not higher than 21 points were excluded.Patients were given routine treatment,and they were followed up at 1 week,3 months,6 months and 1 year after onset.Patients with cognitive impairment or cognitive function significantly lower than baseline were screened.Outcome events were defined as Mo CA score lower than 26 points(the score was increased by 1 point if the patient's education level not higher than 12 years).Besides,patients with Mo CA score lower than 26 points were included in PSCI group,while those with Mo CA score not lower than 26 points were included in the normal group.The progress of the patient's condition was assessed: the Mo CA score decreasing by 4 points or more from the baseline value indicated aggravation,the score lower than 3 points indicated stable condition,and the score higher than 4 points indicated improvement.SPSS16.0 statistical software was used for data analysis,t test was used for measurement data comparison,and Chi-square test was used for counting data.Spearman correlation analysis was performed to analyze the relationship between A 1-42,Tau protein,thyroxine levels and disease progression,and Cox regression analysis was performed to analyze the influencing factors of PSCI.The receiver operating characteristic(ROC)curve was used to analyze the value of each index and combination of all indexes in predicting the development of PSCI.Significant level ?=0.05.Results:(1)At the end of follow-up,14 of the 278 patients were lost to follow-up,and the follow-up data of 264 patients were complete.According to the follow-up Mo CA scores,92 patients were included in PSCI group,and 172 patients were included in the normal group.The analysis results of baseline data showed that the proportions of females,patients with education level ?12 years,patients with history of stroke/TIA,and those with atrial fibrillation in PSCI group were significantly higher than those in the normal group(P<0.05).The age of patients,levels of TG,LDL and total Tau protein,and NIHSS score at admission in PSCI group were significantly higher than those in the normal group(P<0.05).The levels of A?1-42,T3 and FT4 in PSCI group were significantly lower than those in the normal group(P<0.05).(2)There was no significant difference between PSCI group and the normal group in the total Mo CA score or each subscale score at 1 week after admission.However,the above scores of PSCI group were significantly lower than those of the normal group at 6 months after admission(P<0.05).(3)The A?1-42 and T3 levels in both groups were decreased at 1 week ? 3 months after onset,and reached the lowest level and became stable at 3 months after onset.Then,the levels gradually increased within 3 months ? 1 year,close to those at onset.The Tau protein reached the highest level within 1 week after onset,and then gradually decreased,showing a stable trend.A?1-42 and T3 levels in PSCI group were significantly lower than those in the normal group at 1 week,3 months,6 months and 1 year after onset,while the Tau protein level was significantly higher than the normal group(P<0.05).FT4 levels in both groups increased with time at 1 week ? 1 year after onset,and the levels in PSCI group were significantly lower than those in the normal group at 1 week,3 months,6 months and 1 year after onset(P<0.05).(4)Spearman correlation analysis showed that A?1-42,T3 and FT4 were negatively correlated with the progression of PSCI(P<0.05),and the levels decreased with severity.The content of Tau protein was positively correlated with the progression(P<0.05),and it increased with severity.(5)Univariate Cox regression analysis showed that A?1-42,Tau protein,T3 and FT4 were independent factors affecting PSCI in patients,with A?1-42,T3 and FT4 as protective factors and Tau protein as risk factors.After adjusting for age and gender,the above indexes are still important factors affecting the occurrence of diseases.A?1-42,Tau protein and T3 had A regression relationship with patients' cognitive function.After further adjustment for NIHSS score,LDL,TG and other factors,it was found that elevated A?1-42 and T3 could reduce the risk of PSCI in patients(P<0.05).(6)ROC curve analysis showed that the areas under the curves of A?1-42,Tau protein,T3 and FT4 for predicting PSCI were 0.753,0.813,0.589,and 0.754,respectively.The sensitivities were 71.9%,81.8%,60.9%,and 56.8%,respectively.The specificities were 75.0%,66.7%,56.9%,and 90.3%,respectively.The area under the curve of combined prediction was 0.897.The sensitivity and specificity were 74.0% and 91.7%.The value of combined prediction was significantly greater than that of single prediction.Conclusion:(1)The incidence rate of PSCI is high after ischemic stroke.(2)Patients with PSCI are relatively older.Most of them are female,those with lower education level and those with history of atrial fibrillation.(3)The levels of plasma A?1-42,serum T3 and FT4 in patients with PSCI were significantly lower than those in the normal group,while the content of Tau protein was significantly higher than the normal group.(4)A?1-42,T3 and FT4 are negatively correlated with the progression of PSCI,and the levels decrease with severity.The Tau protein content was positively correlated with the progression,and it increases with severity.(5)A?1-42,T3 and FT4 are independent protective factors while Tau protein is an in dependent risk factor for the occurrence of PSCI.(6)The combination of A?1-42,Tau protein,T3 and FT4 can better predict and evaluate the occurrence and severity of PSCI.Combined detection of plasma A?1-42,Tau protein,serum T3 and FT4 levels can reduce the incidence of PSCI,improve the quality of life of patients,and provide an effective basis for clinical diagnosis and disease assessment. |
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