Diuretic antihypertensive drugs and incident dementia risk: a systematic review, meta-analysis and meta-regression of prospective studies.

OBJECTIVE

Diuretic drugs have been a mainstay of hypertension treatment in the elderly however their dementia sparing effects are under-reported. The objective was to quantify dementia risk in relation to diuretic antihypertensive drugs.

METHODS

Electronic databases were searched until June 2015.

ELIGIBILITY CRITERIA

population, adults without dementia from primary care, community cohort, residential/institutionalized, or randomized controlled trial; exposure, diuretic antihypertensive drug; comparison, no diuretic drug, other or no antihypertensive drug, placebo-control; outcome, incident dementia diagnosed by standardized criteria. Adjusted hazard ratios (HR) with 95% confidence intervals (CI) were pooled in fixed-effects models with RevMan 5.3 (The Nordic Cochrane Centre, Copenhagen, Denmark) and the findings rated according to The Grading of Recommendations Assessment, Development and Evaluation criteria.

RESULTS

A total of 15 articles were included (52 599 persons, 3444 dementia cases, median age 76.1 years) and median follow-up was 6.1 years. Diuretics were associated with reduced dementia risk (HR 0.83; 95% CI 0.76-0.91, P < 0.0001, I = 0) and Alzheimer's disease risk (HR 0.82; 95% CI 0.71-0.94, P = 0.004, I = 0). Stratified analysis indicated a difference between potassium sparing, thiazide and loop diuretics (P = 0.01). Risk estimates were generally consistent comparing monotherapy vs. combination therapy, study design and follow-up. Meta-regression showed that demographics, stroke, heart failure, diabetes, liver disease, attrition, mortality rate, cognitive function, and apolipoprotein E allele did not moderate the results.

CONCLUSION

Diuretic antihypertensive drugs were associated with a consistent reduction in dementia risk without heterogeneity, pointing to generalizability of these findings.

REGISTRATION

PROSPERO [CRD42015023428].