Multicentre, cross-cultural, population-based, case-control study of physical activity as risk factor for amyotrophic lateral sclerosis.

Objective: To investigate the association between physical activity (PA) and amyotrophic lateral sclerosis (ALS) in population-based case-control studies in three European countries using a validated and harmonised questionnaire.
Methods: Patients with incident ALS and controls were recruited from five population-based registers in The Netherlands, Ireland and Italy. Demographic and data regarding educational level, smoking, alcohol habits and lifetime PA levels in both leisure and work time were gathered by questionnaire, and quantified using metabolic equivalent of task scores. Logistic regression models adjusting for PA-related factors were used to determine the association between PA and ALS risk, and forest plots were used to visualise heterogeneity between regions.
Results: 1557 patients and 2922 controls were included. We found a linear association between ALS and PA in leisure time (OR 1.07, P=0.01) and occupational activities (OR 1.06, P<0.001), and all activities combined (OR 1.06, P<0.001), with some heterogeneity between regions: the most evident association was seen in the Irish and Italian cohorts. After adjustment for other occupational exposures or exclusion of patients with a C9orf72 mutation, the ORs remained similar.
Conclusion: We provide new class I evidence for a positive association between PA and risk of ALS in a large multicentre study using harmonised methodology to objectively quantify PA levels, with some suggestions for population differences.
Competing Interests: Competing interests: AEV, FD, HJW, RCHV and GL report no disclosures. JPKR reports grants from health research board, during the conduct of the study. EB reports grants from UCB-Pharma, grants from Shire, grants from EISAI, personal fees from Viropharma, grants from Italian Ministry of Health, grants from European Union, grants from Fondazione Borgonovo, grants from Associazione IDIC 15, outside the submitted work. AC reports personal fees from Biogen Idec, personal fees from Cytokinetics, grants from Italfarmaco, personal fees from Mitsubishi, outside the submitted work. OH reports grants from framework 7 EUROMOTOR project, grants from Health Research Board Ireland, grants from Science Foundation Ireland, during the conduct of the study; personal fees from ALS FTD Journal, outside the submitted work. JHV reports other from Vertex Pharmaceuticals, outside the submitted work. LHvdB reports grants from Netherlands ALS Foundation, grants from The Netherlands Organisation for Health Research and Development, during the conduct of the study; grants from Baxalta, grants from Prinses Beatrix Spierfonds, grants from European Community’s Health Seventh Framework Programme, outside the submitted work; LHvdB serves on scientific advisory boards for the Prinses Beatrix Spierfonds, Thierry Latran Foundation, Biogen and Cytokinetics and serves on the editorial board of amyotrophic lateral sclerosis and frontotemporal degeneration and the journal of neurology, neurosurgery and psychiatry.
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