HIGHER device-measured physical activity has been associated with a lower risk of amyotrophic lateral sclerosis (ALS), according to a large UK Biobank analysis, while self-reported activity has shown a non-linear pattern, with ALS risk lowest at mid-range levels.
The role of physical activity in ALS risk has remained debated. Strenuous exercise has been linked to higher ALS risk in selected athlete groups, whereas several population-based studies found no positive association. Moreover, whether the relationship differs in people at high genetic risk of ALS is unclear.
In this study, researchers analysed UK Biobank data on self-reported and device-measured physical activity and incident ALS diagnosis. Among 384,836 participants with valid questionnaire data, median age was 57.0 years (interquartile range: 50.0–63.0) and median follow-up was 14.0 years (interquartile range: 13.3–14.6), with 541 incident ALS diagnoses. The device-measured analysis included 96,570 participants with 98 ALS events.
Higher device-measured physical activity was associated with a lower risk of ALS (hazard ratio per 1 standard deviation: 0.75; 95% CI: 0.58-0.97), with a linear dose-response relationship. Higher self-reported activity was also associated with a lower risk of ALS (hazard ratio for high versus low activity: 0.77; 95% CI: 0.61-0.96), with a non-linear relationship and the lowest risk at mid-range activity. The overall association was more prominent in women and related to moderate rather than vigorous activity or walking.
In analyses restricted to participants with increased genetic risk, the association was similar to that of the overall cohort in individuals with C-allele homozygosity at rs12608932 in UNC13A, and directionally consistent but not statistically significant in C9ORF72 expansion carriers (n=535; 56 ALS events).
These findings are consistent with the wide-ranging benefits of physical activity, including in individuals at higher genetic risk of ALS. Further research is needed to clarify why the dose-response relationship differed by measurement method and to confirm the findings in C9ORF72 expansion carriers. As an observational study, it cannot establish causation.
Reference
Gao J et al. Associations of self-reported and objectively measured physical activity and amyotrophic lateral sclerosis risk. Journal of Neurology, Neurosurgery & Psychiatry. 2026;97(11):958-64.
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