Cholinergic nucleus degeneration and its association with gait impairment in Parkinson's disease.

IF 5.2 2区 医学 Q1 ENGINEERING, BIOMEDICAL
Xiaodan Zhang, Mateng Wang, Shi Yeow Lee, Yumei Yue, Zhaoying Chen, Yilin Zhang, Lulu Wang, Qiongfeng Guan, Weinv Fan, Ting Shen
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Abstract

Background: The contribution of cholinergic degeneration to gait disturbance in Parkinson's disease (PD) is increasingly recognized, yet its relationship with dopaminergic-resistant gait parameters has been poorly investigated. We investigated the association between comprehensive gait parameters and cholinergic nucleus degeneration in PD.

Methods: This cross-sectional study enrolled 84 PD patients and 69 controls. All subjects underwent brain structural magnetic resonance imaging to assess the gray matter density (GMD) and volume (GMV) of the cholinergic nuclei (Ch123/Ch4). Gait parameters under single-task (ST) and dual-task (DT) walking tests were acquired using sensor wearables in PD group. We compared cholinergic nucleus morphology and gait performance between groups and examined their association.

Results: PD patients exhibited significantly decreased GMD and GMV of the left Ch4 compared to controls after reaching HY stage > 2. Significant correlations were observed between multiple gait parameters and bilateral Ch123/Ch4. After multiple testing correction, the Ch123/Ch4 degeneration was significantly associated with shorter stride length, lower gait velocity, longer stance phase, smaller ankle toe-off and heel-strike angles under both ST and DT condition. For PD patients with HY stage 1-2, there were no significant degeneration of Ch123/4, and only right side Ch123/Ch4 were corrected with the gait parameters. However, as the disease progressed to HY stage > 2, bilateral Ch123/Ch4 nuclei showed correlations with gait performance, with more extensive significant correlations were observed in the right side.

Conclusions: Our study demonstrated the progressive association between cholinergic nuclei degeneration and gait impairment across different stages of PD, and highlighting the potential lateralization of the cholinergic nuclei's impact on gait impairment. These findings offer insights for the design and implementation of future clinical trials investigating cholinergic treatments as a promising approach to address gait impairments in PD.

帕金森病患者胆碱能核变性及其与步态障碍的关系
背景:人们越来越认识到胆碱能变性对帕金森病(PD)步态障碍的影响,但其与多巴胺能耐受步态参数的关系却鲜有研究。我们研究了帕金森病综合步态参数与胆碱能核变性之间的关系:这项横断面研究共纳入 84 名帕金森病患者和 69 名对照组。所有受试者均接受了脑结构磁共振成像,以评估胆碱能核(Ch123/Ch4)的灰质密度(GMD)和体积(GMV)。使用传感器可穿戴设备采集了PD组在单任务(ST)和双任务(DT)步行测试中的步态参数。我们比较了组间胆碱能核形态和步态表现,并研究了它们之间的关联:结果:与对照组相比,PD 患者在达到 HY 阶段 > 2 后,左侧 Ch4 的 GMD 和 GMV 明显降低。多个步态参数与双侧 Ch123/Ch4 之间存在显著相关性。经多重测试校正后,在ST和DT条件下,Ch123/Ch4退化与步长变短、步速降低、步态阶段变长、踝关节趾离地角度和足跟打击角度变小显著相关。对于 HY 1-2 期的帕金森病患者,Ch123/4 没有明显退化,只有右侧 Ch123/Ch4 与步态参数相关。然而,当病情发展到HY>2期时,双侧Ch123/Ch4核与步态表现出现相关性,其中右侧的相关性更为显著:我们的研究表明,在帕金森病的不同阶段,胆碱能核变性与步态障碍之间存在渐进关系,并强调了胆碱能核对步态障碍影响的潜在侧向性。这些发现为未来临床试验的设计和实施提供了启示,研究胆碱能治疗是解决帕金森病步态障碍的一种很有前景的方法。
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来源期刊
Journal of NeuroEngineering and Rehabilitation
Journal of NeuroEngineering and Rehabilitation 工程技术-工程:生物医学
CiteScore
9.60
自引率
3.90%
发文量
122
审稿时长
24 months
期刊介绍: Journal of NeuroEngineering and Rehabilitation considers manuscripts on all aspects of research that result from cross-fertilization of the fields of neuroscience, biomedical engineering, and physical medicine & rehabilitation.
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