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From the Department of Neurology of the Rudolf Magnus Institute of Neuroscience (Drs. Veldink, Kalmijn, Groeneveld, Titulaer, Wokke, and van den Berg); and Julius Center for Health Sciences and Primary Care (Dr. Kalmijn), University Medical Center Utrecht, The Netherlands.
Address correspondence and reprint requests to Dr. L.H. van den Berg, Department of Neurology, G.03.228, University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands; e-mail: l.h.vandenberg{at}neuro.azu.nl
Objective: To assess whether lifetime physical activity during work and leisure time is associated with an increased risk of developing ALS and to determine the association between physical activity and duration or age at onset of disease.
Methods: Patients referred to our clinic during the 1-year period 2001 to 2002 who had definite, probable, or possible ALS according to El Escorial criteria, without a familial history of ALS, were asked to participate in the study. A case-control study was performed taking into account all occupational and leisure time activities of patients (n = 219) and controls (n = 254). Multivariate analysis included confounding factors (sex, age, level of education, body mass index, alcohol use, and smoking). Three quantitative measures of cumulative physical activity were calculated: until 1 year before the onset of disease (total physical activity), the last 10 years before the onset of disease (late physical activity), and until the age of 25 (early physical activity). In addition, a systematic review of all published data is presented.
Results: Smoking and alcohol use were independently associated with ALS (current smoking increased risk, OR = 1.8, 95% CI = 1.0 to 3.0, p = 0.03, ever/current alcohol use decreased risk, OR = 0.6, 95% CI = 0.3 to 0.9, p = 0.04). No significant association with occupational or leisure time physical activity was found (all ORs 
1.7), which was in agreement with most studies with the highest level of evidence in the systematic review. Higher leisure time activities were associated with an earlier age at onset: activity levels before age of 25 (p < 0.001, 7 years earlier), and activity during the last 10 years (p < 0.001, 3 years earlier).
Conclusions: There is no association between physical activity and the risk of developing ALS.
Supported by a grant from ZonMw, The Netherlands Organization for Health Research and Development.
Received February 5, 2004. Accepted in final form October 5, 2004.
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