This review found that antihypertensive medication use could decrease the risk of the development of vascular dementia and any dementia, but not the risk of new onset Alzheimer's disease, cognitive impairment or decline. Methodological flaws and the potential for bias mean that the results should be interpreted with caution and the reliability of the authors' conclusions is unclear.

To evaluate the association of antihypertensive medication treatment with the development of dementia or mild cognitive decline.

MEDLINE and EMBASE were searched up to February 2011 for published studies in English or Chinese; search terms were reported. Bibliographies of relevant studies were checked.

Prospective longitudinal studies that compared the incidence of Alzheimer's disease, vascular dementia or any dementia or cognitive impairment in patients with versus without antihypertensive medication treatment were eligible for inclusion. Studies were excluded in which participants presented with dementia or mild cognitive impairment at baseline, or where participant recruitment was by convenience sampling in retrospective studies. Studies that attained quality scores less than 5 points were excluded from the review.

In included studies, the antihypertensive medications given were atenolol; indapamide; enalapril; hydrochlorothiazide; nitrendipine; perindopril; reserpine; telmisartan; angiotensin-converting enzyme inhibitors; calcium channel blockers; and/or diuretics (where stated). The age of included patients at baseline ranged from 50 to 89 years. The methods used to measure cognition included the Mini-Mental State Examination, the National Institute of Neurological and Communicative Disease and Stroke/Alzheimer's Disease and related Disorders Association, the Diagnostic and Statistical Manual of Mental Disorders, and the Metro-Hartford Information Service.

The authors did not state how many reviewers performed the study selection.

Two reviewers assessed methodological quality for external validity (recruitment, participation at follow-up), internal validity (duration of follow-up, exposure assessment, outcome status and co-variates, analytical approach), and descriptive issues. Any discrepancies between the reviewers were resolved by discussion.

Two reviewers independently extracted data to calculate relative risks (RR) and 95% confidence intervals (CI) for the outcomes on incidence of dementia or cognitive decline with the use of anti-hypertensive medication. Any discrepancies between the reviewers were resolved by discussion.

Pooled relative risks and 95% confidence intervals were calculated using Mantel-Haenszel fixed-effect and DerSimonian and Laird random-effects models. Studies were also analysed grouped by design and results reported. Statistical heterogeneity was evaluated using the Χ² test and Ι²; where heterogeneity was present, a random-effects model was used. The authors assessed publication bias by visual appraisals of funnel plots.

Fourteen studies (70,851 patients) were included in the review, comprising eight randomised controlled trials (RCTs) and six cohort studies. Five RCTs scored of 6 points for quality, one RCT scored 7 points, and two RCTs scored 8 points. One cohort study scored 5 points for quality, one study scored 6 points, three studies scored 8 points, and one study scored 9 points. Follow-up ranged from 2.2 years to 32 years.

There was a trend towards a decreased incidence of vascular dementia associated with the use of antihypertensive medication (RR 0.76, 95% CI 0.57 to 1.00) in three RCTs (11,840 patients), which reached statistical significance when combined with the results of one cohort study (RR 0.67, 95% CI 0.52 to 0.87; Ι²=47.7%; 18,812 patients).

The results of three RCTs showed no difference between patients who received antihypertensive medication and patients who received placebo in the incidence of any dementia (11,850 patients); the inclusion of the results from four cohort studies showed a decreased incidence of any dementia with anti-hypertensive treatment (RR 0.86, 95% CI 0.77 to 0.96; Ι²=0%; 21,665 patients).

There were no significant differences observed in the risk of Alzheimer's disease (two RCTs and five cohort studies; 21,744 patients), risk of cognitive impairment (eight RCTs and one cohort study; 53,582 patient), and risk of cognitive decline (six RCTs; 46,214 patients) in patients who received antihypertensive treatment compared with those without.

There was no statistically significant heterogeneity observed for any outcome across the included studies.

There was no evidence of publication bias found across the outcomes.

The use of antihypertensive medication could decrease the risk of new onset of vascular dementia and any dementia, but could not decrease the risk of new onset of Alzheimer's disease, cognitive impairment or decline.

The review addressed a clear question. Some criteria for the inclusion of studies in the review were outlined and were generally reproducible. Two appropriate databases were searched for relevant studies. The restriction of the review to studies published in particular languages meant there was some risk of language bias and studies may have been missed. The reviewers evaluated the potential for publication bias using validated methods. Steps were taken to minimise errors and bias for the assessment of methodological quality and for data extraction, but were not reported for study selection.

The results of the quality assessment of included studies were also used as inclusion criterion. However, the results of the quality assessment were not reported in detail, apart from the summary scores. Although the authors conducted separate analyses for the controlled trials and the cohort studies, the results from these different study designs were combined in a meta-analysis. The results from cohort studies were vulnerable to a number of potential biases, so the pooling of the studies in this way may have led to an over-estimation of treatment effect.

Some methodological flaws and the potential for a number of biases mean that the results of the review should be interpreted with some caution and the reliability of the authors' conclusions is unclear.

Practice: The authors stated that in the general population of elderly people, blood pressure should be examined and hypertension should be diagnosed and treated with antihypertensive medication in hypertension patients.

Research: The authors did not state any implications for research.

National Basic Research program of China; Government of SiChuan province of China; Health Department in SiChuan province; Government of MianYang City; Third hospital of MianYang.

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.