Physical Activity, Fitness, and Long-Term Risk of Amyotrophic Lateral Sclerosis

Abstract

Background and ObjectivesObservational studies have demonstrated an increased amyotrophic lateral sclerosis (ALS) risk among professional athletes in various sports. For moderately increased levels of physical activity and fitness, the results are diverging. Through a cohort study, we aimed to assess the relationship between indicators of physical activity and fitness (self-reported physical activity and resting heart rate) and long-term ALS risk. MethodsFrom a large Norwegian cardiovascular health survey (1985)(1986)(1987)(1988)(1989)(1990)(1991)(1992)(1993)(1994)(1995)(1996)(1997)(1998)(1999), we collected information on self-reported physical activity in leisure time, resting heart rate, and other cardiovascular risk factors. Patients with ALS were identified through health registries covering the whole population. We fitted Cox proportional hazard models to assess the risk of ALS according to levels of self-reported physical activity in 3 categories (1: sedentary; 2: minimum 4 hours per week of walking or cycling; 3: minimum 4 hours per week of recreational sports or hard training), and resting heart rate modeled both on the continuous scale and as quartiles of distribution. ResultsOut of 373,696 study participants (mean 40.9 [SD 1.1] years at inclusion), 504 (41.2% women) developed ALS during a mean follow-up time of 27.2 (SD 5.0) years. Compared with participants with the lowest level of physical activity, the hazard ratio was 0.71 (95% CI 0.53-0.95) for those with the highest level. There were no clear associations between resting heart rate and ALS in the total sample. In men, the hazard ratio of ALS was 0.71 (95% CI 0.53-0.95) for those reporting moderate levels of physical activity and 0.59 (95% CI 0.42-0.84) for those reporting high levels, compared with those reporting low levels. Men with resting heart rate in the lowest quartile had 32% reduced risk of ALS (hazard ratio 0.68, 95% CI 0.49-0.94) compared with those in the second highest quartile. In women, no association was detected between neither self-reported levels of physical activity nor resting heart rate and ALS risk. DiscussionIndicators of high levels of physical activity and fitness are associated with a reduced risk of ALS more than 30 years later in men, but not in women.

Physical Activity as a Risk Factor for Amyotrophic Lateral Sclerosis

“…An alternative explanation might be that there is a detrimental effect of exercise in women that is not present in men. 1 We note that there is good evidence for a neuroprotective effect of estrogen in the pathogenesis of ALS 8,9 and that physical activity induces a reduction in circulating sex hormones in women. 8-10…”

“…An alternative explanation might be that there is a detrimental effect of exercise in women that is not present in men. 1 We note that there is good evidence for a neuroprotective effect of estrogen in the pathogenesis of ALS 8,9 and that physical activity induces a reduction in circulating sex hormones in women. [8][9][10] Overall, this study is a valuable contribution to the field and potentially provides some reassurance that mild/moderate levels of physical activity in middle age do not increase the risk of ALS but may instead have a beneficial protective effect.…”

“…One methodologic strength was that the authors considered whether their findings could be explained by a prodrome, that is, could higher levels of PA be protective because those individuals performing lower levels of physical exercise were in fact reducing their activity because of early stages of disease? 1 To test this possibility, the authors performed a sensitivity analysis in which they excluded individuals who developed ALS within 10 years of the baseline survey. This did not alter their result, and the authors concluded that a mild motor impairment 5 prodrome did not affect their overall findings.…”

“…In this issue of Neurology ®, Vaage et al 1 publish a study in which they used a prospective analysis to address the role of physical activity (PA) and fitness in the later development of amyotrophic lateral sclerosis (ALS). This is a controversial area that has been the subject of significant interest in the field, 1 especially given the number of high-profile athletes who have been reported to develop ALS.…”

“…Impressively, the authors supported this with an objective measure of physical fitness—resting heart rate—where a lower heart rate at this time point was associated with a lower future risk of ALS. 1…”