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We therefore sought to review evidence from prospective epidemiological studies of physical activity and neurodegenerative disease risk.We limited the current systematic review to prospective cohort epidemiological studies in an attempt to eliminate selection and recall bias.Criteria for inclusion were as follows: prospective cohort studies in nondemented men and women at baseline, with a diagnosis of Amiodarone hydrochloride dementia or cognitive impairment at followup; and at baseline.Information on participants and study characteristics, measurement of exposure and outcome, adjustment for potential confounders, and hazard ratio and veried by another. Assessment of quality was made based on the validity and accuracy of the physical activity exposure measure and adjustment for potential confounding.Quality and validity were assessed independently by both reviewers and any discrepancies were resolved by discussion.HR or RR was used as a measure of the association between physical activity and risk of neurodegenerative disease.In each case we extracted a RR for the highest versus the lowest reported physical activity group. If HR or RR was not presented we calculated RR and CI from the study data with the use of the number of participants and unexposed groups. We also performed sensitivity analyses based on gender and quality of studies.The included studies incorporated participants with cases at followup.Two studies were performed in men only, whereas the remainder were mixed cohorts.To further explore the heterogeneity issue we performed sensitivity analyses based on gender and study quality.In studies that presented separate gender eects, the RR was more robust for men than for women in relation to risk of dementia.Physical activity was not associated with a signicant reduction in risk of M.There was a large amount of heterogeneity in our ndings that was possibly due to dierent gender eects although there were limited studies to specically examine this issue.Possible gender eects might reect dierences in biological responses to exercise in men and women that have relevance for cognitive health, although future studies should be conducted to conrm this nding.The higher quality studies demonstrated more robust eects and this may have been partly due to more precise categorization of physical activity exposure.A substantial proportion of the included studies did not accurately dene physical activity levels in terms of frequency, duration and intensity, which may be important in relation to risk of neurodegenerative disease.Nevertheless, in studies that examined relative risk of dementia across welldened physical activity quintiles, a linear doseresponse relationship was not consistently demonstrated.The optimal dose of physical activity for risk reduction therefore remains to be accurately dened.One important factor that is likely to bias the association between physical activity and neurodegenerative disease risk is the presence of Imiquimod subtle cognitive changes at baseline that may inuence physical activity and other lifestyle behaviours.Thus studies with short followups and a lack of adjustment for cognitive function at baseline may be particularly vulnerable to such biases.In addition, the timing of physical activity assessment in relation to neurodegeneration might be crucial.For example, it is not clear at what stage in an individuals life physical activity is most important for future protection.Physical activity may be protective against cognitive decline and neurodegenerative diseases through a number of possible mechanisms.

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