血管周围间隙扩大与帕金森病患者认知和运动纵向变化的关系

Relationship between perivascular space enlargement and cognitive and motor longitudinal changes in patients with Parkinson′s disease

目的探讨基底神经节(BG)血管周围间隙扩大(EPVS;BG-EPVS)与初诊帕金森病及其不同运动亚型[震颤优势型(TD)、姿势不稳和步态障碍型(PIGD)]患者认知和运动纵向变化的相关性。方法从帕金森进展标志物倡议(PPMI)数据库中筛选131例帕金森病患者,分别收集其基线和随访1、2年的数据,通过患者头颅影像学资料,在轴位T2加权像上评估不同脑区的EPVS数量,并根据EPVS程度将其分为BG-EPVS-和BG-EPVS+组。将帕金森病患者通过国际运动障碍协会帕金森病统一评定量表(MDS-UPDRS)评分分为TD和PIGD组,比较两组的EPVS数量和临床数据,并分析基线时BG-EPVS数量和程度与帕金森病及其不同运动亚型(TD、PIGD)临床结局指标纵向变化的相关性。结果在所有帕金森病患者中,BG-EPVS与年龄(r=0.32,P<0.01)、Hoehn和Yahr分级(r=0.21,P<0.05)、血清神经丝轻链(r=0.18,P<0.05)和Epworth嗜睡量表评分(r=0.20,P<0.05)呈正相关。在基线及第2年时,PIGD组的BG-EPVS数量多于TD组(11.0±4.2比9.0±3.8,t=2.18,P=0.03;16.3±6.7比12.6±4.6,t=2.71,P=0.007;校正后)。在基线时,帕金森病及其运动亚型(TD、PIGD)组患者中较多的BG-EPVS数量与基线运动结局显著相关(β=0.66,P=0.01;β=0.64,P=0.008;β=0.91,P=0.009),与认知结局不相关。通过线性混合效应模型分析,在帕金森病及其运动亚型(TD、PIGD)组患者中,BG-EPVS数量与运动结局随时间变化呈正相关(β=0.51,P=0.008;β=0.59,P=0.025;β=0.80,P=0.038);将帕金森病患者的BG-EPVS分为不同程度后,BG-EPVS中重度与运动结局随时间变化呈正相关(β=3.30,P=0.031)。结论在这项纵向研究中,较高基线BG-EPVS数量与帕金森病患者运动障碍严重程度纵向变化呈正相关,与认知变化不相关,且能够在2年随访期间预测运动功能的下降。

Objective To investigate the correlation between basal ganglia(BG)enlarged perivascular space(EPVS;BG-EPVS)and cognitive and motor longitudinal changes in patients with newly diagnosed Parkinson′s disease and its different motor subtypes[tremor dominant(TD),postural instability and gait disorder(PIGD)].Methods A total of 131 Parkinson′s disease patients from the Parkinson Progression Markers Initiative(PPMI)database were screened and their clinical data were collected at baseline,1 year and 2 years of follow-up.The number of EPVS in different brain regions was assessed on axial T2-weighted images by cranial imaging data,and they were divided into two groups according to the degree of EPVS:BG-EPVS-and BG-EPVS+.Parkinson′s disease patients were divided into TD and PIGD groups by Movement Disorder Society Unified Parkinson′s Disease Rating Scale(MDS-UPDRS)score,and the number and clinical data of EPVS were compared between the two groups,and the correlation between the number and degree of BG-EPVS at baseline and longitudinal changes in clinical outcome measures of Parkinson′s disease and its different motor subtypes(TD,PIGD)was analyzed.Results BG-EPVS was positively correlated with age(r=0.32,P<0.01),Hoehn&Yahr stage(r=0.21,P<0.05),serum neurofilament light chain(r=0.18,P<0.05)and Epworth Sleepiness Scale score(r=0.20,P<0.05)in all Parkinson′s disease patients.At baseline and 2 years,the number of BG-EPVS was more in the PIGD group than in the TD group(11.0±4.2 vs 9.0±3.8,t=2.18,P=0.03;16.3±6.7 vs 12.6±4.6,t=2.71,P=0.007;after correction).At baseline,more BG-EPVS in patients with Parkinson′s disease and its motor subtypes(TD,PIGD)was significantly associated with baseline motor outcomes(β=0.66,P=0.01;β=0.64,P=0.008;β=0.91,P=0.009),but not with cognitive outcomes.By linear mixed effects model analysis,BG-EPVS numbers and moderate to severe BG-EPVS were positively correlated with motor outcomes over time in patients with Parkinson′s disease and its motor subtypes(TD,PIGD)(β=0.51,P=0.008;β=0.59,P=0.025;β=0.80,P=0.038).After dividing BG-EPVS in Parkinson′s disease patients into different degrees,moderate to severe BG-EPVS was positively correlated with motor outcomes over time(β=3.30,P=0.031).Conclusion In this longitudinal study,bigger baseline BG-EPVS numbers were found to be positively associated with longitudinal changes in dyskinesia severity in Parkinson′s disease patients,not with cognitive changes,and be able to predict decline in motor function over a 2-year follow-up period.