Glymphatic dysfunction is related to motor disability fully mediated by gray matter degeneration in early-stage Parkinson's disease

IF 5.6 2区 医学 Q1 NEUROSCIENCES
Zihao Zhu , Xiaojie Duanmu , Cheng Zhou , Jiaqi Wen , Jianmei Qin , Qianshi Zheng , Weijin Yuan , Tao Guo , Haoting Wu , Chenqing Wu , Jingwen Chen , Jingjing Wu , Yingni Jin , Nan Lu , Lu Wang , Bingting Zhu , Yuelin Fang , Lifang Wang , Ziyi Zhu , Yaping Yan , Xiaojun Xu
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Abstract

Background

Glymphatic dysfunction plays a critical role in Parkinson's disease (PD), but its impact on neurodegeneration and clinical symptoms in the early-stage remains unclear. This study investigates the relationship between glymphatic dysfunction, gray matter (GM) degeneration, and clinical deterioration in early-stage PD.

Methods

A total of 249 early-stage PD patients and 114 healthy controls (HC) underwent T1-weighted and DTI scans, along with clinical assessments. Among them, 83 patients and 32 HC were longitudinally re-visited. The diffusion tensor imaging along the perivascular space (DTI-ALPS) index was used to estimate glymphatic function. Linear mixed model was performed to identify longitudinal GM degeneration and clinical deterioration; partial correlation analysis was applied to explore GM degeneration associated with glymphatic dysfunction; while mediation analysis was conducted to investigate the mediation role of GM degeneration in the relationship between glymphatic dysfunction and clinical deterioration.

Results

Significantly lower DTI-ALPS index was observed in PD patients, which correlated with reduced cortical thickness in the bilateral posterior cingulate and left lingual gyrus at baseline, and faster atrophy in the left rostral anterior cingulate during follow-up. The relationship between DTI-ALPS index and baseline motor disability was fully mediated by the degeneration of the left posterior cingulate.

Conclusion

Glymphatic dysfunction in early-stage PD correlates with GM degeneration and motor decline. Left posterior cingulate degeneration fully mediates the impact of glymphatic dysfunction on motor disability. These findings deepen the understanding of the clinical relevance of glymphatic dysfunction and provide further insights into the regulatory mechanisms underlying PD-related neurodegenerative circuits.
脑淋巴功能障碍与早期帕金森病灰质变性完全介导的运动障碍相关
背景:淋巴功能障碍在帕金森病(PD)中起关键作用,但其对早期神经变性和临床症状的影响尚不清楚。本研究探讨早期PD患者淋巴功能障碍、灰质(GM)变性与临床恶化的关系。方法249例早期PD患者和114例健康对照(HC)进行t1加权扫描和DTI扫描,并进行临床评估。其中83例患者和32例HC进行了纵向复诊。采用沿血管周围间隙弥散张量成像(DTI-ALPS)指数评估淋巴功能。采用线性混合模型识别纵向GM变性和临床恶化;应用偏相关分析探讨GM变性与淋巴功能障碍的相关性;同时进行中介分析,探讨GM变性在淋巴功能障碍与临床恶化关系中的中介作用。结果PD患者DTI-ALPS指数明显降低,与基线时双侧后扣带和左侧舌回皮质厚度减小、随访期间左吻侧前扣带萎缩加快有关。DTI-ALPS指数与基线运动障碍之间的关系完全由左侧后扣带退变介导。结论早期PD患者淋巴功能障碍与GM变性和运动能力下降有关。左扣带后变性完全介导了淋巴功能障碍对运动障碍的影响。这些发现加深了对淋巴功能障碍临床相关性的理解,并为pd相关神经退行性回路的调节机制提供了进一步的见解。
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来源期刊
Neurobiology of Disease
Neurobiology of Disease 医学-神经科学
CiteScore
11.20
自引率
3.30%
发文量
270
审稿时长
76 days
期刊介绍: Neurobiology of Disease is a major international journal at the interface between basic and clinical neuroscience. The journal provides a forum for the publication of top quality research papers on: molecular and cellular definitions of disease mechanisms, the neural systems and underpinning behavioral disorders, the genetics of inherited neurological and psychiatric diseases, nervous system aging, and findings relevant to the development of new therapies.
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