Abstract
Objectives: To conduct a geographically defined, UK-based case-control study, to examine any association between physical activity (PA) and amyotrophic lateral sclerosis (ALS). Methods: A novel historical PA questionnaire was designed, validated, and subsequently administered in individual face-to-face interviews of 175 newly diagnosed sporadic ALS cases and 317 age- and sex-matched community controls. Historical PA energy expenditure and time spent in vigorous-intensity PA were derived from questionnaire data and compared between cases and controls. Results: Participation in an extra 10kJ/kg/day of PA (equivalent to approximately 45minutes brisk walking) was consistently associated with an increased risk of ALS, with the strongest association observed for adulthood exercise-related PA (OR 1.47, 95% CI 1.10-1.97). An extra 10mins/day of vigorous PA was also associated with the odds of ALS (OR 1.03, 95% CI 1·01-1·05). Results were slightly attenuated following adjustment for smoking and educational attainment. Conclusions: To our knowledge this is the first study to demonstrate a positive association between ALS and PA participation using a specifically designed and validated historical PA questionnaire. Despite the well-established health benefits of PA, a high activity lifestyle may also be associated with elevated risk of ALS. Large-scale prospective studies in the future may help to confirm this association.
Highlights
Amyotrophic lateral sclerosis (ALS) is a disabling, terminal neurodegenerative condition characterised by progressive paralysis and atrophy of limb, bulbar and respiratory muscles
To the best of our knowledge, this is the first study to use a designed and validated physical activity (PA) questionnaire to demonstrate a positive association between PA and the development of sporadic amyotrophic lateral sclerosis (ALS)
Positive associations were reported for all domains of PA and both time periods, and remained following adjustment for potential confounders, with the strongest associations for those reporting higher levels of exercise-related PA throughout adulthood
Summary
Amyotrophic lateral sclerosis (ALS) is a disabling, terminal neurodegenerative condition characterised by progressive paralysis and atrophy of limb, bulbar and respiratory muscles. Epidemiological, biological and genetic research suggests a complex pathogenic interaction between genetic and environmental exposures [4]. The strongest evidence relates to smoking, which was associated with incident ALS in a recent meta-analysis of prospective studies including over 1 million participants [5]. Following proposals of an association between physical activity (PA) and the development of ALS [6], several observational studies have examined this hypothesis, with inconsistent results [7,8,9,10,11]. Reports of elevated ALS incidence in Italian professional footballers stimulated further epidemiological research [12,13,14]. Methodological challenges when examining exogenous associations with (Received 6 December 2015; revised 10 January 2016; accepted 17 January 2016)
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