Diuretic medication use reduces incident dementia risk: A meta-analysis of prospective studies

Introduction: Numerous observational studies suggest that blood pressure management with antihypertensive drugs may be effective in reducing dementia risk. Objective: To quantify dementia risk in relation to diuretic medication use. Methods: Electronic databases were searched until June 2015. Eligibility criteria: population, adults without dementia at baseline from primary care, community cohort, residential/institutionalized or randomized controlled trial (RCT); exposure, diuretic medication; comparison, no diuretic medication, other or no antihypertensive medication, placebo-control; outcome, incident dementia in accordance with standardized criteria. Adjusted hazard ratios (HR) with 95% confidence intervals (CI) were pooled in fixed-effects models with RevMan 5.3. The overall quality and strength of evidence was rated with GRADE criteria. Results: Fifteen articles were eligible comprising a pooled sample of 52,599 persons and 3444 incident dementia cases (median age 76.1 years, 40% male) with a median follow-up of 6.1 years. Diuretic use was associated with 17% reduction in dementia risk (HR 0.83; 95% CI 0.75 to 0.90) and a 21% reduction in Alzheimer's disease risk (HR 0.79; 95% CI 0.68 to 0.93). GRADE was rated as moderate. Risk estimates were consistent comparing monotherapy versus combination therapy, study design and follow-up. Meta-regression did not suggest that age, gender, systolic blood pressure, attrition, mortality rate, education, cognitive function, stroke, Apolipoprotein E allele, heart failure or diabetes altered the primary results. Conclusions: Diuretic medication was associated with a consistent reduction in dementia and Alzheimer's disease risk and the absence of heterogeneity points to the generalizability of these findings.