Holdom Cory J, Pilkar Rakesh, Guo Christine C, Eijk Ruben P A van, Sethi Nadia, Henderson Robert D, Ngo Shyuan T, Steyn Frederik J
Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Australia.
ActiGraph, LLC, Pensacola, FL, USA.
EBioMedicine. 2025 May 29;117:105779. doi: 10.1016/j.ebiom.2025.105779.
Motor neuron disease (MND) leads to progressive functional decline, making reliable measures of disease progression critical for patient care and clinical trials. Current clinical outcome measures lack the ability to continuously and objectively track functional decline in daily life of patients with MND. This study assessed and validated wrist-worn accelerometry outcome measures for continuous monitoring in MND, with the potential to refine clinical trial outcomes.
This longitudinal study included 95 patients with MND who wore an ActiGraph GT9X Link device on their non-dominant wrist for 8 days, with follow-up every 3-4 months. Accelerometer data were processed using ActiLife and GGIR. Joint models were used to simultaneously investigate the longitudinal change in ALS Functional Rating Scale-Revised (ALSFRS-R) scores and accelerometer-derived outcomes alongside their relationship with overall survival. Sample size estimates for clinical trials were generated using both accelerometer- and ALSFRS-R-based outcomes, and principal component analysis (PCA) explored outcome relationships.
Accelerometer outcomes showed a slower rate of decline (-0.03 to -0.07 SD/month) compared to ALSFRS-R (-0.10 SD/month) and had stronger correlations with ALSFRS-R motor subdomains (partial r: 0.60-0.73). PCA revealed that longitudinal measures of accelerometry were distinct from the ALSFRS-R, highlighting the complementary nature of these measures. Peak 6-min activity predicted smaller clinical trial sample sizes for studies over 12 months. Accelerometer-derived outcomes were not significantly associated with survival.
Wrist-worn accelerometry offers a practical solution for continuous monitoring in MND, complementing ALSFRS-R. Measures of peak performance, and specifically peak 6-min activity shows promise, potentially reducing sample sizes and improving disease tracking over longer duration studies. Further refinement and validation are needed to adopt actigraphy measures as clinical assessment outcomes.
This study was supported by Wesley Medical Research (2016-32), the Honda Foundation, Motor Neurone Disease Research Australia, and FightMND. CJH received a Higher Degree Research Scholarship from UQ. STN received support from the Scott Sullivan Fellowship (MND and Me Foundation/RBWH Foundation), a FightMND Mid-Career Fellowship, and the AIBN.
运动神经元病（MND）会导致功能逐渐衰退，因此，对于患者护理和临床试验而言，可靠的疾病进展测量方法至关重要。当前的临床结局测量方法缺乏持续、客观地追踪MND患者日常生活中功能衰退情况的能力。本研究评估并验证了腕部佩戴式加速度计测量结果用于MND患者的连续监测，有望优化临床试验结局。
这项纵向研究纳入了95例MND患者，他们在非优势手腕佩戴ActiGraph GT9X Link设备8天，并每3 - 4个月进行一次随访。加速度计数据使用ActiLife和GGIR进行处理。联合模型用于同时研究修订的肌萎缩侧索硬化功能评定量表（ALSFRS - R）评分的纵向变化以及加速度计得出的测量结果，以及它们与总生存期的关系。使用基于加速度计和ALSFRS - R的测量结果生成临床试验的样本量估计值，主成分分析（PCA）探索测量结果之间的关系。
与ALSFRS - R（每月下降0.10标准差）相比，加速度计测量结果显示出较慢的下降速度（每月下降 - 0.03至 - 0.07标准差），并且与ALSFRS - R运动子领域的相关性更强（偏相关系数r：0.60 - 0.73）。主成分分析表明，加速度计的纵向测量结果与ALSFRS - R不同，突出了这些测量方法的互补性。6分钟峰值活动预测了超过12个月研究的较小临床试验样本量。加速度计得出的测量结果与生存期无显著关联。
腕部佩戴式加速度计为MND的连续监测提供了一种实用的解决方案，可补充ALSFRS - R。峰值性能测量，特别是6分钟峰值活动显示出前景，有可能减少样本量并在更长时间的研究中改善疾病追踪。需要进一步完善和验证，以便将活动记录仪测量结果用作临床评估结局。
本研究由卫斯理医学研究（2016 - 32）、本田基金会、澳大利亚运动神经元病研究协会和抗击运动神经元病协会资助。CJH获得了昆士兰大学的高等学位研究奖学金。STN获得了斯科特·沙利文奖学金（运动神经元病与我基金会/皇家布里斯班妇女医院基金会）、抗击运动神经元病中期职业奖学金以及澳大利亚生物工程与纳米技术研究所的支持。
