Upper limb movements as digital biomarkers in people with ALSResearch in context

Summary: Background: Objective evaluation of people with amyotrophic lateral sclerosis (PALS) in free-living settings is challenging. The introduction of portable digital devices, such as wearables and smartphones, may improve quantifying disease progression and hasten therapeutic development. However, there is a need for tools to characterize upper limb movements in neurologic disease and disability. Methods: Twenty PALS wore a wearable accelerometer, ActiGraph Insight Watch, on their wrist for six months. They also used Beiwe, a smartphone application that collected self-entry ALS Functional Rating Scale—Revised (ALSFRS-RSE) survey responses every 1–4 weeks. We developed several measures that quantify count and duration of upper limb movements: flexion, extension, supination, and pronation. New measures were compared against ALSFRS-RSE total score (Q1–12), and individual responses to specific questions related to handwriting (Q4), cutting food (Q5), dressing and performing hygiene (Q6), and turning in bed and adjusting bed clothes (Q7). Additional analysis considered adjusting for total activity counts (TAC). Findings: At baseline, PALS with higher Q1–12 performed more upper limb movements, and these movements were faster compared to individuals with more advanced disease. Most upper limb movement metrics had statistically significant change over time, indicating declining function either by decreasing count metrics or by increasing duration metric. All count and duration metrics were significantly associated with Q1–12, flexion and extension counts were significantly associated with Q6 and Q7, supination and pronation counts were also associated with Q4. All duration metrics were associated with Q6 and Q7. All duration metrics retained their statistical significance after adjusting for TAC. Interpretation: Wearable accelerometer data can be used to generate digital biomarkers on upper limb movements and facilitate patient monitoring in free-living environments. The presented method offers interpretable monitoring of patients’ functioning and versatile tracking of disease progression in the limb of interest. Funding: Mitsubishi-Tanabe Pharma Holdings America, Inc.