帕金森病步态冻结中脑淋巴系统功能与认知衰退的关联:横断面和纵向研究的多模态磁共振成像证据

The association of glymphatic system function with cognitive decline in PD-FOG: multimodal MRI evidence from cross-sectional and longitudinal studies.

作者信息

Ruan Xiuhang, Wang Mengfan, Huang Xiaofei, Wang Ting, Li Mengyan, Wei Xinhua

机构信息

First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China.

Department of Radiology, School of Medicine, Guangzhou First People's Hospital, South China University of Technology, Guangzhou, Guangdong, China.

出版信息

Brain Imaging Behav. 2025 Aug 11. doi: 10.1007/s11682-025-01044-3.

Abstract

This study aims to investigate glymphatic system dysfunction in idiopathic Parkinson's disease (PD) using a dual-cohort design, focusing on its associations with freezing of gait (FOG) and cognitive decline. A cross-sectional analysis was conducted on 43 PD patients with FOG, 106 without FOG, and 46 healthy controls. A longitudinal study followed 146 early-stage PD patients from the Parkinson's Progression Markers Initiative database over five years, with 65 developing FOG. Covariate analysis was performed, controlling for variables like gender, age, and education. Survival analysis compared cognitive decline between FOG and stable groups. Random forest analysis identified key predictors of FOG development. The cross-sectional study demonstrated significantly enlarged normalized choroid plexus volume in PD patients with FOG compared to healthy controls. Both FOG and non-FOG groups showed increased perivascular space enlargement in the basal ganglia and centrum semiovale, as well as reduced average analysis along the perivascular space index compared to healthy controls. PD patients with FOG exhibited more pronounced disease progression and cognitive decline than those without FOG. Glymphatic markers were associated with age, cognitive scores, and gait performance. The longitudinal study showed slightly more severe motor symptoms and accelerated cognitive decline in the FOG group during follow-up. Random forest analysis identified age, cognitive scales, and glymphatic function metrics as robust predictors of FOG development. These findings highlight the potential significance of brain glymphatic system function in the development of freezing of gait and cognitive decline in PD patients, offering novel neuroimaging biomarkers for early detection. These authors have contributed equally to this work and share first authorship.

摘要

本研究旨在采用双队列设计调查特发性帕金森病(PD)中的类淋巴系统功能障碍,重点关注其与步态冻结(FOG)和认知衰退的关联。对43例有FOG的PD患者、106例无FOG的PD患者和46名健康对照进行了横断面分析。一项纵向研究跟踪了帕金森病进展标志物倡议数据库中的146例早期PD患者,为期五年,其中65例出现了FOG。进行了协变量分析,控制了性别、年龄和教育程度等变量。生存分析比较了FOG组和稳定组之间的认知衰退情况。随机森林分析确定了FOG发生的关键预测因素。横断面研究表明,与健康对照相比,有FOG的PD患者的标准化脉络丛体积显著增大。与健康对照相比,FOG组和非FOG组在基底神经节和半卵圆中心的血管周围间隙均增大,且沿血管周围间隙指数的平均分析值降低。有FOG的PD患者比无FOG的患者表现出更明显的疾病进展和认知衰退。类淋巴标志物与年龄、认知评分和步态表现相关。纵向研究表明,在随访期间,FOG组的运动症状略更严重,认知衰退加速。随机森林分析确定年龄、认知量表和类淋巴功能指标是FOG发生的有力预测因素。这些发现突出了脑类淋巴系统功能在PD患者步态冻结和认知衰退发生中的潜在重要性,为早期检测提供了新的神经影像学生物标志物。这些作者对这项工作贡献相同,共同担任第一作者。

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