Peters R, Yasar S, Anderson CS, et al. Investigation of antihypertensive class, dementia, and cognitive decline: A meta-analysis. Neurology. 2020 Jan 21;94(3):e267-e281. doi: 10.1212/WNL.0000000000008732. Epub 2019 Dec 11. (Systematic review)

OBJECTIVE: High blood pressure is one of the main modifiable risk factors for dementia. However, there is conflicting evidence regarding the best antihypertensive class for optimizing cognition. Our objective was to determine whether any particular antihypertensive class was associated with a reduced risk of cognitive decline or dementia using comprehensive meta-analysis including reanalysis of original participant data.

METHODS: To identify suitable studies, MEDLINE, Embase, and PsycINFO and preexisting study consortia were searched from inception to December 2017. Authors of prospective longitudinal human studies or trials of antihypertensives were contacted for data sharing and collaboration. Outcome measures were incident dementia or incident cognitive decline (classified using the reliable change index method). Data were separated into mid and late-life (>65 years) and each antihypertensive class was compared to no treatment and to treatment with other antihypertensives. Meta-analysis was used to synthesize data.

RESULTS: Over 50,000 participants from 27 studies were included. Among those aged >65 years, with the exception of diuretics, we found no relationship by class with incident cognitive decline or dementia. Diuretic use was suggestive of benefit in some analyses but results were not consistent across follow-up time, comparator group, and outcome. Limited data precluded meaningful analyses in those =65 years of age.

CONCLUSION: Our findings, drawn from the current evidence base, support clinical freedom in the selection of antihypertensive regimens to achieve blood pressure goals.

CLINICAL TRIALS REGISTRATION: The review was registered with the international prospective register of systematic reviews (PROSPERO), registration number CRD42016045454.

Discipline Area Score
Family Medicine (FM)/General Practice (GP) 6 / 7
General Internal Medicine-Primary Care(US) 6 / 7
Internal Medicine 6 / 7
Geriatrics 5 / 7
Neurology 5 / 7
Comments from MORE raters

Geriatrics rater

I had never wondered before if different antihypertensive treatments could have a different preventive effect on cognitive impairment according to the pleiotropic neuroprotective effect beyond the decrease in blood pressure. The general opinion is that the treatment of hypertension and other cardiovascular risk factors (CVRF) in the average age of life has positive effects in reducing dementia in old age due exclusively to the reduction in the number of CVRF and, in In this sense, this document corroborates this assertion.

Internal Medicine rater

This is a very interesting and worthwhile question but the analysis is disappointing in a number of ways: They pool observational studies rather than RCTs. They take no account of time, pooling OR rather than HR despite different lengths of follow-up. There does not appear to be any accounting for competing risks, e.g. those who died during follow-up do not have a chance to develop dementia. It is not clear that studies are adjusted for the same set of covariates. There is moderate to high heterogeneity for most of the pooled estimates.

Internal Medicine rater

Although this is a 'negative' study, it is reassuring to know that selection of antihypertensive therapy has little impact on dementia.
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