Exercise: A potential contributing factor to the relationship between folate and dementia

OBJECTIVES: To investigate whether exercise confounds the relationship between folate and cerebrovascular events, all-cause dementia, and Alzheimer's disease. DESIGN: Prospective cohort study. SETTING: Multiple centers in Canada. PARTICIPANTS: In the Canadian Study of Health and Aging, 466 people reported exercise levels, had folate measurements, and were not demented at baseline. After 5 years, 194 had adverse cerebrovascular events, and 65 had dementia (Alzheimer's disease in 47). MEASUREMENTS: Associations between folate and cerebrovascular outcomes were examined using logistic regression in the presence and absence of exercise and other confounders. RESULTS: Folate was associated with greater risk of Alzheimer's disease (odds ratio (OR)=2.12, 95% confidence interval (CI)=1.01-4.54) and cerebrovascular outcomes (OR=2.05, 95% CI=1.11-3.78) in adjusted analyses before the inclusion of exercise and neared significance with all-cause dementia (OR=1.80, 95% CI=0.94-3.45). After the inclusion of exercise, the association between folate and dementia and Alzheimer's disease was 29% and 25% lower, respectively, and neither association was any longer significant (Alzheimer's disease: OR=1.91, 95% CI=0.89-4.11; all-cause dementia: OR=1.62, 95% CI=0.84-3.15). Exercise was a significant confounder in the relationship between folate and Alzheimer's disease (P=.03) and dementia (P=.003) but not cerebrovascular outcomes (P=.64). Unlike folate, exercise was significantly associated with Alzheimer's disease (OR=0.43, 95% CI=0.19-0.98) and dementia (OR=0.35, 95% CI=0.17-0.72) in adjusted analyses. CONCLUSION: Exercise seems to account for much of the relationship between folate and incident dementia and Alzheimer's disease.