European Primary Care Cardiovascular Society

Antihypertensive treatment associated with lower risk of dementia

Blood pressure lowering and prevention of dementia: an individual patient data meta-analysis

Literature - Peters R, Xu Y, Fitzgerald O, et al. - Eur Heart J. 2022 Oct 25;ehac584. doi: 10.1093/eurheartj/ehac584

Introduction and methods


Previous observational studies have demonstrated a strong association between elevated blood pressure (BP) and increased risk of dementia and cognitive decline, particularly in individuals aged 40–65 years [1]. However, RCTs have shown mixed results regarding the effects of antihypertensive treatment on the prevention of dementia [2]. Possibly, a meta-analysis can solve this issue. Yet, prior meta-analyses in this area were at risk of bias in their estimates because, for example, analysis and data handling could not be standardized. This limitation can be overcome with a patient-level meta-analysis in which data from sufficiently similar studies are combined and analyzed as a single dataset.

Aim of the study

The aim was to better analyze the effects of antihypertensive treatment on the prevention of dementia by performing a single-stage individual participant data meta-analysis of 5 randomized double-blind placebo-controlled trials.


For the current metanalysis, individual participant data of the following 5 double-blind placebo-controlled RCTs (>2000 participants each) that compared the effect of antihypertensive medication with that of placebo only in participants with increased vascular risk and that included incident dementia as the endpoint were pooled:

The total sample consisted of 28,008 individuals (mean age: 69.1 years; SD: 9.3), who had been recruited from 20 countries. The primary endpoint of the current meta-analysis was incident all-cause dementia. Incident cognitive decline, based on Mini-Mental State Examination (MMSE) scores, was also assessed.

The a priori statistical analysis plan included multilevel logistic regression to evaluate the treatment effect on incident dementia; multilevel multinomial logistic regression to account for death as a competing risk; effect modification by age, sex, baseline systolic BP, prior stroke, or baseline MMSE score; and mediation analysis to quantify the contribution of trial medication and changes in the systolic and diastolic BP to incident dementia.

Main results

Effect of antihypertensive treatment on incident dementia

Effect of antihypertensive treatment on incident cognitive decline

Classification of evidence


In this patient-level meta-analysis of pooled raw data from 5 large double-blind placebo-controlled RCTs, antihypertensive treatment was associated with a reduction of incident dementia compared with placebo. A previous meta-analysis of 7 population-based cohorts showed a U-shaped relationship between BP and dementia risk in participants over 80 years of age [13]. The authors of the current meta-analysis emphasized that in their study, “[t]here was no evidence of a U-shaped relation of the effect at any age , nor any increase in risk of dementia with treatment in the oldest age” group (>80 years).


Show references

Find this article online at Eur Heart J.

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