血浆proBDNF、mBDNF与t-PA水平对脑小血管病认知障碍的预测价值及机制探讨OA

Objective To explore the predictive value and underlying mechanisms of plasma precursor of brain-derived neurotrophic factor(proBDNF),mature brain-derived neurotrophic factor(mBDNF),and tissue-type plasminogen activator(t-PA)levels for cognitive impairment in cerebral small vessel disease(CSVD). Methods A cross-sectional case-control study was conducted to enroll CSVD patients admitted to the Department of Neurology,the Second Affiliated Hospital of Kunming Medical University from November 2021 to November 2022.The patients were classified into a CSVD with normal cognition group and a CSVD with cognitive impairment group based on their educational level and MoCA score.Meanwhile,eligible healthy volunteers receiving physical examination,as well as family members and caregivers of CSVD patients during the same period,were selected as the control group.Enzyme linked immunosorbent assay was used to detect plasma concentrations of proBDNF,mBDNF,and t-PA.The total CSVD burden was assessed by the total CSVD burden score(0-4 points),and cognitive function was evaluated by the MoCA.Analysis of covariance was performed to adjust for confounding factors and compare the differences in plasma biomarker levels among the three groups.Partial correlation analysis was applied to explore the correlations between plasma biomarker levels and MoCA scores.ROC curves were used to evaluate the discriminatory efficacy of plasma biomarker levels and the combined model in distinguishing CSVD with cognitive impairment from CSVD with normal cognition. Results A total of 131 subjects were enrolled,including 32 in the control group,38 in the CSVD with normal cognition group,and 61 in the CSVD with cognitive impairment group.After adjusting for confounding factors,plasma proBDNF level in the CSVD with cognitive impairment group was lower than that in the CSVD with normal cognition group and the control group,and plasma mBDNF level was lower than that in the control group,whereas plasma t-PA level was higher than that in the control group(all P＜0.05).Partial correlation analysis showed that plasma proBDNF and mBDNF levels were positively correlated with total MoCA scores(r=0.439,P＜0.001;r=0.269,P=0.007),while plasma t-PA level was negatively correlated with total MoCA scores(r=—0.270,P=0.007).ROC curve analysis indicated that plasma proBDNF and t-PA levels had moderate predictive value in distinguishing CSVD with cognitive impairment from CSVD with normal cognition(AUC 0.709,P＜0.001;AUC 0.684,P＜0.001).The combined model constructed based on plasma levels of proBDNF,mBDNF,and t-PA,and the total CSVD burden score had the optimal predictive efficacy(AUC 0.844,95％CI 0.779-0.908). Conclusions Reduced plasma proBDNF and mBDNF levels and elevated t-PA level were observed in CSVD patients with cognitive impairment,and the changes were associated with the severity of cognitive impairment.Plasma proBDNF and t-PA levels have moderate predictive value for cognitive impairment in CSVD,and the combined model incorporating the total CSVD burden score can effectively improve the predictive efficacy.