This study aimed to examine the associations between sleep traits, physical activity, and the risk of Amyotrophic Lateral Sclerosis (ALS)

Sleep behavior and physical activity are closely linked to neurodegenerative diseases. However, compared with Alzheimer’s disease, research on ALS is limited and findings remain inconsistent.

A total of 502,279 participants aged 37–73 years were enrolled in a large-scale prospective cohort from 2006 to 2010. ALS incidence was identified using the International Classification of Diseases, 10th Revision (ICD-10). Baseline sleep traits and physical activity were assessed via standardized questionnaires. Cox proportional hazards models and restricted cubic spline analyses were performed.

A total of 502,279 participants were included, with a mean baseline age of 56.5 years, 45.6% of men, and 94.5% of white. After a median follow-up of 13.74 years, 675(0.14%) incident ALS events were documented. In sleep traits, a U-shaped association was observed between sleep duration and ALS risk (P for non-linearity = 0.002). An early chronotype was associated with reduced ALS risk after adjusting for age, sex, BMI, and other covariates (HR = 0.80, 95% CI: 0.67–0.96, p = 0.018). In physical activity, higher exercise (≥600 MET-min/week) was inversely associated with ALS (HR = 0.74, 95% CI: 0.59–0.93, p = 0.011). Additionally, a higher healthy activity score served as a protective factor (HR = 0.83, 95% CI: 0.71–0.96, p = 0.015). These associations remained robust in sensitivity analyses.

Early chronotype and higher levels of physical activity were associated with a lower risk of ALS. Promoting healthy lifestyle behaviors may represent a potential strategy to mitigate ALS risk.