OBJECTIVE: The aim of our present systematic review and meta-analysis was to roundly evaluate the association between AD and its modifiable risk factors. BACKGROUND: The prevalence of Alzheimer's disease is increasing but that there is currently no cure solution for the disease. Recent studies showed that improved physical and cognitive functioning may contribute to decline of the dementia prevalence. These findings are suggestive of critical roles of adjusting modifiable risk factors in preventing AD incidence. DESIGN/METHODS: We systematically searched the PubMed, the Cochrane Database of Systematic Reviews from inception to July, 2014, and references of retrieved relevant articles. We included prospective cohort studies and retrospective case-control studies. RESULTS: 16906 articles were identified of which 323 with 93 factors met the inclusion criteria for meta-analysis. Among factors with relatively strong evidence (pooled population>5000) in our meta-analysis, we found grade I evidence for four medical exposures (estrogen, statin, anti-hypertensive medications and NSAIDs therapy) as well as four dietary exposures (folate, Vitamin E/C and coffee) as protective factors of AD. We found grade I evidence showing that one biochemical exposure (hyperhomocysteine) and one psychological condition (depression) significantly increase risk of developing AD. Grade I evidence also indicated complex roles of pre-existing disease (frailty, carotid atherosclerosis, hypertension, low DBP, DM-2 (Asian population) increasing risk whereas history of arthritis, heart disease, metabolic syndrome and cancer decreasing risk) and lifestyle (low education, high BMI in mid-life and low BMI increasing the risk whereas cognitive activity, current smoking (Western population), light-to-moderate drinking, stress, high BMI in late-life decreasing the risk) in influencing AD risk. We identified no evidence suggestive of significant association with occupational exposures. CONCLUSIONS: Effective interventions in diet, medications, biochemical exposures, psychological condition, pre-existing disease, and lifestyle may decrease new incidence of AD.
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