| Objectives:In this study,we evaluated the total burden of magnetic resonance imaging(Magnetic resonance imaging,MRI)in patients with cerebral small vessel disease(CSVD),and measured the levels of two brain-derived neurotrophic factors(Brain-derived neurotrophic factor,BDNF),BDNF precursor(pro-brain-derived neurotrophic factor,proBDNF)and mature BDNF(Mature brain-derived neurotrophic factor,mBDNF),and tissue plasminogen activator(Tissue plasmin-ogen activator,tPA)in plasma.The purpose of this study is to explore To explore the correlation between total MRI burden,plasma levels of proBDNF,mBDNF,tPA and cognitive impairment in patients with CSVD,and try to find possible biomarkers of CSVD cognitive impairment.Methods:This study included patients who were hospitalized and signed informed consent in the Department of Neurology of the Second Affiliated Hospital of Kunming Medical University from October 2021 to October 2022.All enrolled patients completed skull MRI examination,biochemical index testing,and baseline data collection.Patients with CSVD were included with reference to the diagnostic criteria in the "Consensus of Chinese Experts on the Diagnosis and Treatment of Cerebrovascular Diseases 2021".The MRI total burden score method was used to assess the overall MRI imaging characteristics of patients with CSVD.Enzyme-linked immunosorbent assay(ELISA)was used to measure the levels of proBDNF,mBDNF,and tPA in plasma.The Montreal Cognitive Assessment(Mo CA),Wechsler Memory Scale,Connection Tests A,B,and Stroop Color Word Test were used to assess cognitive function.Subjects with normal MRI and Mo CA scores were included as the control group.According to the MRI total burden score,CSVD patients were divided into 0-2 groups and 3-4 groups.The overall cognitive function,various cognitive domain involvement,and plasma levels of proBDNF,mBDNF,and tPA in the control group,0-2 groups,and 3-4 groups were compared.Then,CSVD patients were divided into CSVD cognitive normal group and CSVD cognitive impairment group based on their education level and total Mo CA score(illiteracy ≤ 13 points,education years1-6 years ≤ 19 points,education years 7 years and above Mo CA score ≤ 24points).The changes in plasma proBDNF,mBDNF,and tPA levels in the control group,CSVD cognitive normal group,and CSVD cognitive impairment group were compared.And then this study analyzed the correlation between the levels of proBDNF,mBDNF,and tPA and cognitive function,and evaluated the combined diagnostic effect of MRI total burden,plasma proBDNF,mBDNF,and tPA levels on cognitive impairment in CSVD.Results:1 Cognitive assessment results of different MRI total burden groups1.1 Mo CA scale: Compared with the control group,the scores of Mo CA total score,visual space and executive function,naming and orientation of CSVDMRI total burden 0-2 group were significantly lower than those of the control group.Compared with the control group,the scores of Mo CA total score,visual space and executive function,naming,attention,language(repetition + comprehension),abstraction,delayed recall and orientation in the 3-4 CSVDMRI total burden group were significantly lower than those in the control group.The language ability score of 3-4group was worse than that of 0-2 group(P <0.05).There was no statistical difference in computing power among the three groups.1.2 Wechsler Memory Scale: The scores of picture recall,visual recognition,visual regeneration,associative learning,tactile memory,understanding memory and inverted number in MRI total burden group 3-4 were significantly lower than those in control group and total burden group 0-2(P <0.05)..1.3 Connection A and B test: compared with the control group,the connection A time,connection B time and connection time of 3-4 groups were prolonged(P <0.05),and the scores of connection An and B test were decreased(P <0.05).Compared with the 0-2 group of MRI total burden,the total burden of 3-4 group An and B were longer,and the scores of An and B were lower(P<0.05).1.4 Stroop color word test: compared with the control group,the number of correct part C of the total burden 0-2 group decreased,the number of errors increased,and the value of reaction interference increased(P <0.05).Compared with the control group,the time of part A,part B and part C of the total burden group 3-4 was prolonged,the number of correct part B and part C decreased,the number of errors increased,and the time-consuming interference and reaction interference increased(P<0.05).The time of A part,B part and C part of 3-4 group was longer than that of 0-2group,the correct number of B part was less than that of 0-2 group,and the value of time-consuming interference was higher than that of 0-2 group(P <0.05).2 Detection results of plasma proBDNF,mBDNF and tPA levels in different MRI total burden groupsThe levels of plasma proBDNF,mBDNF and tPA in different MRI total burden groups were lower than those in the control group(302.00(172.00-410.00)pg/ml vs422.59(251.10-599.00)pg/ml,and the plasma mBDNF level(1726.29(1213.94-2291.20)pg/ml)was also lower than that in the control group 2903.13(1450.18-4316.19)pg/ml.The plasma tPA level of 4347.00(3525.33-5717.00)pg/ml was significantly higher than that of 3578.55(2802.00-4587.93)pg/ml in the control group(P <0.05).The plasma mBDNF level of 1780.32(1059.97-12370.39)pg/ml in the total burden 0-2 group was significantly lower than that of 2903.13(1450.18-4316.19)pg/ml in the control group(P<0.05).3 Results of plasma proBDNF,mBDNF and tPA levels in different cognitive function groups of CSVDThe plasma proBDNF level of CSVD cognitive impairment group was274.00(154.50-373.67)pg/ml lower than that of control group 422.59(251.10-599.00)pg/ml and CSVD cognitive normal group 425.0(330.47-495.64)pg/ml(P < 0.05).The plasma mBDNF level of CSVD cognitive impairment group was1627.05(1090.91-2189.81)pg/ml,and that of CSVD cognitive normal group was1983.08(1181.98-2604.57)pg/ml,which was significantly lower than that of control group(2903.13.1450.18-4316.19)pg/ml(P< 0.05).The plasma tPA level of CSVD cognitive impairment group was 4432.00(3878.67-5518.67)pg/ml,which was higher than that of control group 3578.55(2802.00-4587.93)pg/ml and CSVD cognitive normal group 3773.43(3085.75-4923.78)pg/ml(P < 0.05).4 Analysis of the relationship between plasma levels of proBDNF,mBDNF,tPA and cognitive function4.1 Analysis of the relationship between plasma levels of proBDNF,mBDNF,tPA and cognitive function :Plasma pro BDN level was positively correlated with the total score of Mo CA,visual space and executive function,naming,attention,computational ability,language,abstraction,delayed recall and orientation(P <0.05).The level of plasma mBDNF was positively correlated with the total score of Mo CA,visual space and executive function,computational power,abstraction and delayed recall(P <0.05).The level of plasma tPA was negatively correlated with the total score of Mo CA,visual space and executive function,attention,language,abstraction,delayed recall and orientation(P <0.05).4.2 Correlation with Wechsler memory scale :The level of plasma pro BDN was positively correlated with the scores of picture recall,visual recognition,visual regeneration,associative learning,understanding and memory,forward back,forward back + inversion(P <0.05).The level of plasma mBDNF was positively correlated with the scores of picture recall,visual recognition,visual regeneration and associative learning(P <0.05).The level of plasma tPA was negatively correlated with the scores of picture recall,visual regeneration and tactile memory(P <0.05).4.3 Correlation with connection An and B test: The level of plasma pro BDN was negatively correlated with the time of connection An and B test,and positively correlated with the score of connection B test(P<0.05).The level of plasma mBDNF was negatively correlated with the time of connection An and B test(P<0.05).The level of plasma tPA was positively correlated with the time of connection B test(P<0.05).4.4 Correlation with Stroop Color words Test: The plasma pro BDN level was negatively correlated with the time consuming of part A,B and C of Stroop test,and positively correlated with the number of correct parts A,B and C,and negatively correlated with the number of errors in part A,B and C(P<0.05).The level of plasma mBDNF was negatively correlated with the time spent in part B and C of Stroop test(P <0.05).The plasma tPA level was positively correlated with the time consuming of part A,B,C,the number of errors in part An and the amount of time-consuming interference in part An of Stroop test,and negatively correlated with the number of correct parts in part A(P <0.05).5 Multivariate Logistic regression analysis of cognitive impairment caused by CSVDWith or without cognitive impairment as dependent variables,MRI total burden and plasma levels of proBDNF,mBDNF and tPA as independent variables,binary Logistic regression analysis showed that MRI total burden score was its influencing factor(P <0.05).6 Diagnostic value of total MRI burden and plasma levels of proBDNF,mBDNF and tPA in cognitive impairmentWhen diagnosed alone,the diagnostic value of MRI total burden,plasma proBDNF,mBDNF and tPA levels were statistically different(P <0.05).The diagnostic value of MRI total burden for the diagnosis of CSVD cognitive impairment was the highest(AUC0.809,sensitivity 95.1%,specificity 54.0%).The AUC of plasma proBDNF,mBDNF and tPA levels for the diagnosis of CSVD cognitive impairment was 0.709,0.633 and 0.684,respectively.The diagnostic value of the combined detection of the above indexes was significantly improved(AUC reached0.844,sensitivity 75.4%,specificity 79.0%).Conclusions:1 CSVD patients have a wide range of cognitive impairment areas,including overall cognitive function and specific cognitive level,including spatial structure ability,executive ability(attention and anti-interference ability),naming,language(repetition + comprehension),memory(short-term memory,instantaneous memory,understanding memory,situational memory)and directional ability,which have significant differences.The higher the total burden score of MRI in CSVD patients,the more severe the cognitive impairment.The main areas of impairment are memory,attention and executive function.2 The higher the total MRI burden,the lower the plasma levels of proBDNF and mBDNF,and the higher level of the tPA.CSVD is easy to be complicated with extensive cognitive impairment,which may be related to the decrease of plasma proBDNF,mBDNF and the increase of tPA levels.3 The total burden of MRI,plasma proBDNF,mBDNF,tPA have a good sensitivity for the diagnosis of CSVD cognitive impairment,and the diagnostic predictive value of combined predictive diagnosis is significantly improved. |
PDF Full Text Request