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Despite the fact that Parkinson's disease is the second most common neurodegenerative disease, little is known about risk factors for the disease. Laboratory experiments indicate that physical activity may have a neuroprotective effect; however, there are few data on whether physical activity is associated with decreased risk of Parkinson's disease.To investigate the relationship between physical activity and Parkinson's disease in 10,714 men (mean age, 67.6 years) from the Harvard Alumni Health Study, who were diagnosed as free of self-reported Parkinson's disease in 1988.Physical activity was assessed in 1988 by asking about the daily number of blocks walked and stairs climbed, and participation in sports and recreational activities in the past week. Energy expenditure was then estimated and men were categorised into four groups:1000, 1000-1999, 2000-2999 oror = 3000 kcal/week. In addition, physical activity data were available for three past time points: during college, 1962 or 1966, and 1977. Incident cases of Parkinson's disease occurring after 1988 (n = 101) were identified through a follow-up health questionnaire in 1993 and death certificates obtained until 1997.In multivariate analyses, the relative risks (RR) for Parkinson's disease associated with1000, 1000-1999, 2000-2999 andor = 3000 kcal/week of physical activity were 1 (referent), 1.15 (95% confidence interval (95% CI) 0.71 to 1.88), 0.92 (0.50 to 1.71) and 0.63 (0.36 to 1.12), respectively; p for trend was 0.12. When walking was examined separately, somewhat lower, but not significant, risks were observed for Parkinson's disease. The multivariate RRs (95% CI) for walking5, 5-10, 10-20 and20 km/week were 1 (referent), 0.67 (0.37 to 1.23), 0.81 (0.50 to 1.31) and 0.72 (0.39 to 1.34), respectively; p for trend was 0.26. Analyses that considered physical activity at other time points before 1988 did not show any significant associations.These data do not strongly support the hypothesis that physical activity lowers the risk of Parkinson's disease. However, as the number of patients with Parkinson's disease in this study was not large, statistical power may have been limited and further large studies are needed to provide additional data.