PDF(Pubmed)
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.
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.
摘要：
背景：越来越认识到胆碱能变性对帕金森病（PD）步态障碍的影响，然而，它与多巴胺抵抗步态参数的关系研究甚少。我们研究了PD中综合步态参数与胆碱能核变性之间的关系。
方法：这项横断面研究纳入了84名PD患者和69名对照。所有受试者均接受了脑结构磁共振成像，以评估胆碱能核的灰质密度（GMD）和体积（GMV）（Ch123/Ch4）。使用PD组的传感器可穿戴设备获取单任务（ST）和双任务（DT）步行测试下的步态参数。我们比较了各组之间的胆碱能核形态和步态表现，并检查了它们的关联。
结果：PD患者在达到HY阶段>2后，与对照组相比，左侧Ch4的GMD和GMV显着降低。在多个步态参数与双侧Ch123/Ch4之间观察到显着相关性。经过多次测试校正后，Ch123/Ch4变性与较短的步幅显著相关，较低的步态速度，更长的站立阶段，在ST和DT条件下，较小的脚踝脚趾和脚跟撞击角度。对于HY1-2期的PD患者，Ch123/4无明显变性，仅右侧Ch123/Ch4用步态参数校正。然而,随着疾病进展到HY阶段>2，双侧Ch123/Ch4核显示与步态表现相关，在右侧观察到更广泛的显著相关性。
结论：我们的研究表明，在PD的不同阶段，胆碱能核变性与步态损害之间存在进行性关联，并强调胆碱能核对步态损害的影响的潜在侧化。这些发现为研究胆碱能治疗作为解决PD步态障碍的有希望的方法的未来临床试验的设计和实施提供了见解。
方法：这项横断面研究纳入了84名PD患者和69名对照。所有受试者均接受了脑结构磁共振成像，以评估胆碱能核的灰质密度（GMD）和体积（GMV）（Ch123/Ch4）。使用PD组的传感器可穿戴设备获取单任务（ST）和双任务（DT）步行测试下的步态参数。我们比较了各组之间的胆碱能核形态和步态表现，并检查了它们的关联。
结果：PD患者在达到HY阶段>2后，与对照组相比，左侧Ch4的GMD和GMV显着降低。在多个步态参数与双侧Ch123/Ch4之间观察到显着相关性。经过多次测试校正后，Ch123/Ch4变性与较短的步幅显著相关，较低的步态速度，更长的站立阶段，在ST和DT条件下，较小的脚踝脚趾和脚跟撞击角度。对于HY1-2期的PD患者，Ch123/4无明显变性，仅右侧Ch123/Ch4用步态参数校正。然而,随着疾病进展到HY阶段>2，双侧Ch123/Ch4核显示与步态表现相关，在右侧观察到更广泛的显著相关性。
结论：我们的研究表明，在PD的不同阶段，胆碱能核变性与步态损害之间存在进行性关联，并强调胆碱能核对步态损害的影响的潜在侧化。这些发现为研究胆碱能治疗作为解决PD步态障碍的有希望的方法的未来临床试验的设计和实施提供了见解。
