Correlation between enlarged perivascular spaces and glymphatic system function with cognitive function in patients with recent subcortical small infarction
10.3969/j.issn.1672-5921.2025.07.002
- VernacularTitle:近期皮质下小梗死患者血管周围间隙扩大与脑类淋巴系统功能及认知功能的相关性研究
- Author:
Xue ZHANG
1
;
Min ZHANG
1
;
Wenwei YUN
1
Author Information
1. 213000 江苏省常州市,南京医科大学第三附属医院(常州市第二人民医院)神经内科
- Publication Type:Journal Article
- Keywords:
Recent subcortical small infarct;
Enlarged perivascular spaces;
Glymphatic system;
Diffusion tensor imaging analysis along the perivascular space;
Cognitive function
- From:
Chinese Journal of Cerebrovascular Diseases
2025;22(7):453-464
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the correlation between enlarged perivascular spaces(EPVS)in different regions and glymphatic system(GS)function with cognitive function in patients with recent subcortical small infarction(RSSI).Methods A retrospective study was conducted by consecutively enrolling patients with RSSI who were hospitalized in the Department of Neurology at the Third Affiliated Hospital of Nanjing Medical University(Changzhou Second People's Hospital)from December 2023 to December 2024.Baseline and clinical data were collected,including age,sex,body mass index(BMI),history of smoking and alcohol consumption,hypertension,diabetes mellitus,atrial fibrillation,coronary heart disease,and laboratory indicators(including homocysteine,total cholesterol,triglycerides,low-density lipoprotein cholesterol,high-density lipoprotein cholesterol,glycated hemoglobin,uric acid,and creatinine).Cognitive function was assessed within 7 d of onset using the mini-mental state examination(MMSE)and Montreal cognitive assessment(MoCA)scale,which covers seven cognitive domains:visuospatial and executive functioning,naming,attention,language,abstraction,memory,and orientation.All patients underwent brain MRI within 3 d of admission,including diffusion tensor imaging(DTI)sequences.The DTI along the perivascular space(DTI-ALPS)post-processing tool was used to calculate the DTI-ALPS index on both sides,and the mean value was taken as an indicator to evaluate overall GS function.The volumes of EPVS in the basal ganglia(BG)and centrum semiovale(CSO)were measured.EPVS severity was visually rated based on Potter's method(on a scale range from 0 to 4)and categorized into a none-to-mild(grades 0-1)and a moderate-to-severe(grades 2-4)group.Patients were further classified by region into a BG-EPVS and a CSO-EPVS subgroups under each severity group.(1)Univariate analyses were performed to compare baseline characteristics,DTI-ALPS index,and cognitive assessment scores between groups.Variables with P＜0.05 in univariate analyses were tested for multicollinearity using variance inflation factor.Variables without multicollinearity were included in multivariate Logistic regression to identify independent factors associated with BG-EPVS.To assess the robustness of the predictive value of the DTI-ALPS index,outlier diagnostics and exclusion were performed,followed by re-estimation of the Logistic regression model.Spearman's correlation analysis was used to examine the associations of BG-EPVS volume with the DTI-ALPS index,MMSE scale score,MoCA scale score,and each cognitive domain score.Mediation analysis was conducted to evaluate whether the DTI-ALPS index mediated the relationship between BG-EPVS volume and MoCA scale score.Results A total of 65 RSSI patients were included in the study,comprising 34 males and 3 1 females,aged 37 to 78 years,with a mean age of(53±15)years.Among them,30 patients were classified into the none-to-mild EPVS group and 35 into the moderate-to-severe EPVS group.For regional classification,34 were in the none-to-mild BG-EPVS group and 31 in the moderate-to-severe BG-EPVS group;36 were in the none-to-mild CSO-EPVS group and 29 in the moderate-to-severe CSO-EPVS group.(1)Univariate analysis showed,in both overall EPVS and BG-EPVS subgroup,the none-to-mild groups had lower age,lower proportions of male and hypertensive patients,and higher DTI-ALPS indices,MMSE scale scores,and MoCA scale scores than the moderate-to-severe groups(all P＜0.05).No significant differences were found in other baseline or clinical characteristics(all P＞0.05).In the CSO-EPVS subgroup,age was the only variable differed significantly between the none-to-mild group(significantly younger)and the moderate-to-severe group(P＜0.05),no other variables showed significant differences between the groups(all P＞0.05).(2)No multicollinearity was found among age,sex,hypertension,and the DTI-ALPS index through the multicollinearity analysis.Multivariate Logistic regression identified older age(OR,4.410,95％CI 1.211-16.025,P=0.024),male(OR,1.076,95％CI 1.001-1.156,P=0.048),and hypertension(OR,6.287,95％CI 1.635-24.167,P=0.007)as independent risk factors for moderate-to-severe BG-EPVS in RSSI patients,while a higher DTI-ALPS index was an independent protective factor(OR,0.002,95％CI 0.000-0.904,P=0.046).To assess the robustness of this model,six outlier cases were identified and excluded.After reanalysis,the negative association between the DTI-ALPS index and BG-EPVS risk remained significant(OR,0.050,95％CI 0.003-0.974,P=0.048).(3)Spearman correlation analysis revealed that the BG-EPVS volume in RSSI patients was negatively correlated with the DTI-ALPS index(rs=-0.842,P=0.007),MMSE scale score(rs=-0.491,P=0.033),MoCA scale score(rs=-0.563,P=0.018),and visuospatial/executive function score(rs=-0.596,P=0.001).No significant correlations were found between BG-EPVS volume and other cognitive domains,including naming,attention,language,abstraction,memory,and orientation(all P＞0.05).(4)Mediation analysis showed that the total effect size of BG-EPVS volume on MoCA scale score was-0.673,with a direct effect size of-0.537(account for 79.79％of the total effect size)and an indirect effect size via the DTI-ALPS index of-0.136(account for 20.21％).Conclusions In RSSI patients,age,sex,hypertension,and the DTI-ALPS index were identified as independent factors associated with the severity of BG-EPVS.BG-EPVS volume was negatively correlated with the DTI-ALPS index and cognitive function scores in RSSI patients.Moreover,the DTI-ALPS index mediated the relationship between BG-EPVS volume and cognitive function in RSSI patients.
