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Diuretic antihypertensive drugs and incident dementia risk

a systematic review, meta-analysis and meta-regression of prospective studies

Tully, Phillip J.; Hanon, Olivier; Cosh, Suzanne; Tzourio, Christophe

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, I2 = 0) and Alzheimer's disease risk (HR 0.82; 95% CI 0.71–0.94, P = 0.004, I2 = 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].

aUniversity Bordeaux, Neuroepidemiology, UMR, Bordeaux, France

bFreemasons Foundation Centre for Men's Health, Discipline of Medicine, School of Medicine, The University of Adelaide, Adelaide, Australia

cINSERM, Service de Gériatrie, Université Paris Descartes, Hôspital Broca, Paris, France

dSchool of Psychology, The University of Adelaide, Adelaide, Australia

eINSERM, Neuroepidemiology, UMR, Bordeaux, France

Correspondence to Phillip J. Tully, Freemasons Foundation Centre for Men's Health, Discipline of Medicine, School of Medicine, The University of Adelaide, Adelaide, SA 5005, Australia. Tel: +618 8313 0514; fax: +618 8313 0355; e-mail:

Received 13 October, 2015

Revised 18 December, 2015

Accepted 23 December, 2015

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