Journal of neurology, neurosurgery, and psychiatry
August 13, 2026 · via Europe PMC
Associations of self-reported and objectively measured physical activity and amyotrophic lateral sclerosis risk.
Gao J, Chalitsios CV, Bennett D, Doherty A, Turner MR, Thompson AG.
AI summary — for doctors, generated from the abstract only
In a large UK Biobank cohort, both higher self-reported and device-measured physical activity were associated with a lower risk of later being diagnosed with amyotrophic lateral sclerosis (ALS), though the self-reported relationship appeared non-linear with lowest risk at mid-range activity levels.
What was studied
A prospective cohort analysis using the UK Biobank examined associations between self-reported and accelerometer (device)-measured physical activity and incident ALS diagnosis using Cox regression with cubic splines to assess non-linearity, in the overall cohort (384,836 participants with questionnaire data, 541 incident ALS cases) and in subgroups with increased genetic ALS risk (C9ORF72 expansion carriers or UNC13A rs12608932 C-allele homozygotes).
Key findings
- Higher self-reported physical activity was associated with lower ALS risk (hazard ratio for high vs low activity 0.77, 95% CI 0.61-0.96), with a non-linear relationship showing lowest risk at mid-range self-reported activity
- Higher device-measured overall activity was also associated with lower ALS risk (HR per 1 SD increase 0.75, 95% CI 0.58-0.97, n=96,570 with 98 ALS events), with a linear dose-response relationship
- The association was similar in people with increased genetic risk via UNC13A C-allele homozygosity
- The association was directionally consistent but not statistically significant in the smaller C9ORF72 expansion carrier subgroup (n=535, 56 ALS events)
Clinical relevance
The findings suggest a modest inverse association between physical activity and ALS risk in the general population, which may be relevant to discussions about lifestyle factors and neurodegenerative disease risk, though the authors note the non-linear self-reported relationship and limited statistical power in the genetic-risk subgroups. This is observational association data and does not establish that increasing physical activity prevents ALS.
Who should care
Limitations
As an observational cohort study, reverse causation is a concern (reduced activity could reflect early, undiagnosed ALS-related motor decline rather than cause future risk), and the genetic-risk subgroup analyses, particularly for C9ORF72 carriers, had limited statistical power (only 56 ALS events).
Higher physical activity, whether self-reported or device-measured, was linked to lower subsequent ALS risk in this large UK Biobank study, though reverse causation and limited power in genetic-risk subgroups temper the interpretation.
This is an AI-generated summary of the published abstract, not a clinical recommendation. It may not reflect the full text or subsequent updates — verify against the original source before acting on it.
Abstract
Background
The role of physical activity in the risk of amyotrophic lateral sclerosis (ALS) is debated. It is also unclear whether the association differs in people at high genetic risk of ALS.
Methods
The strength and shape of the association between self-reported and device-measured physical activity and incident diagnosis of ALS in the UK Biobank cohort was analysed using Cox regression, adjusting for potential confounders. Cubic splines were used to assess non-linearity. Analyses were performed in the entire cohort and restricted to those with increased genetic risk due to C9ORF72 expansion carriage or C-allele homozygosity at rs12608932 in UNC13A.
Results
Among 384 836 participants with valid questionnaire data, the median age at recruitment was 57.0 years (IQR 50.0-63.0) and median follow-up was for 14.0 years (IQR 13.3-14.6), with 541 incident diagnoses of ALS. Higher self-reported physical activity was associated with a lower risk of ALS (HRhigh vs low=0.77, 95% CI 0.61 to 0.96). The relationship was non-linear, with lowest risk in those in the mid-range self-reported activity. Higher overall device-measured activity was also associated with a lower risk of ALS (HRper 1SD = 0.75, 95% CI 0.58 to 0.97, n=96 570, 98 ALS events) but with a linear dose-response relationship. The association of physical activity with ALS was similar in individuals with C-allele homozygosity at rs12608932 in UNC13A and directionally consistent but not statistically significant in C9ORF72-HRE carriers (n=535, 56 ALS events).
Conclusion
Higher self-reported and device-measured overall physical activity were associated with a lower risk of ALS overall, but with a potentially non-linear dose-response relationship.
DOI
10.1136/jnnp-2026-339165
PMID
42595352
Research metadata (titles, abstracts, authors, publication dates) is sourced from Europe PMC, which aggregates content from PubMed/MEDLINE, PubMed Central, and other providers under the U.S. National Library of Medicine (NLM/NCBI). NLM does not claim copyright on abstracts; the original journal publishers or authors may hold rights to the full articles. AI-generated summaries are derived only from the abstract, never the full text, and are always labeled as AI-generated.
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