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ArticleBrain imaging and behavior2025

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

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

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Article in Brain imaging and behavior, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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6 authors.

Xiuhang Ruan *First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China.
Mengfan Wang *Department of Radiology, School of Medicine, Guangzhou First People's Hospital, South China University of Technology, Guangzhou, Guangdong, China.
Xiaofei HuangDepartment of Radiology, School of Medicine, Guangzhou First People's Hospital, South China University of Technology, Guangzhou, Guangdong, China.
Ting WangDepartment of Neurology, School of Medicine, Guangzhou First People's Hospital, South China University of Technology, Guangzhou, Guangdong, China.
Mengyan LiDepartment of Neurology, School of Medicine, Guangzhou First People's Hospital, South China University of Technology, Guangzhou, Guangdong, China.
Xinhua WeiFirst Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China. eyxinhuawei@scut.edu.cn.

Funding

Guangdong Basic and Applied Basic Research Foundation 2023A1515010606Guangzhou Health Science and Technology Project 20251A011014Guangzhou Key Research and Development Program 2024C-GX16Guangzhou Science and Technology Projects 202201010610National Natural Science Foundation of China 82101430
6 · The paper itself

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.

Indexed as

Cognitive DysfunctionGait Disorders, NeurologicGlymphatic SystemParkinson DiseaseAgedCross-Sectional StudiesDisease ProgressionFemaleHumansLongitudinal StudiesMagnetic Resonance ImagingMaleMiddle AgedCognitive declineFreezing of gaitGlymphatic systemMultimodal MRIParkinson's disease

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.