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

J Hypertens. 2016 Jun;34(6):1027-35. doi: 10.1097/HJH.0000000000000868.


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].

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Alzheimer Disease / epidemiology
  • Antihypertensive Agents / therapeutic use*
  • Dementia / epidemiology*
  • Diuretics / therapeutic use*
  • Diuretics, Potassium Sparing / therapeutic use
  • Drug Therapy, Combination
  • Humans
  • Hypertension / drug therapy
  • Prospective Studies
  • Protective Factors
  • Sodium Potassium Chloride Symporter Inhibitors / therapeutic use


  • Antihypertensive Agents
  • Diuretics
  • Diuretics, Potassium Sparing
  • Sodium Potassium Chloride Symporter Inhibitors