What do we still need to know about antihypertensives and dementia prevention?

Abstract

AbstractThere is a substantial evidence base linking higher blood pressures to an increased risk of cognitive decline and dementia and an increasingly strong evidence base showing reduced dementia risk with blood pressure lowering. Several clinical trials including SPRINT‐MIND have strongly suggested that antihypertensive treatment to lower blood pressure reduces dementia risk. Furthermore, a recent individual participant data meta‐analysis combining data from 5 large double‐blind placebo‐controlled trials of antihypertensives in a late‐mid to early‐late life population (N = 28008) found a 13% reduction in incident dementia cases (OR0.87 (95%CI: 0.75,0.99))(1). The blood pressure difference between the two combined trial arms was ∼10mmHg in systolic blood pressure and there was no clear U shape indicating no increase in risk at lower pressures. This is supported by numerous earlier meta‐analyses of published trial and epidemiological data. Blood pressure lowering is acknowledged as one of the most promising ways in which we might reduce the risk of dementia and cognitive decline.Despite this substantial progress and although we are arguably closer than ever before to answering the question of whether blood pressure lowering reduces dementia risk, there have been no double‐blind placebo‐controlled trials that have definitively shown dementia risk reduction with antihypertensive use. In the absence of strong results, recommendations for antihypertensive use inevitably remain cautious. Furthermore, not only do we still lack a definitive blood pressure dementia risk reduction trial, such a trial would need to be large and complex. Uncertainties also exist about how to deliver treatment against the backdrop of widespread antihypertensive use to reduce cardiovascular risks such as stroke or heart attack. Research is also still progressing on key practical questions. For example, whether we should have a goal blood pressure for brain health, how far we should lower blood pressure to reduce dementia risk, what is the ideal treatment package and how much do factors such as age and frailty matter? We present the key evidence so far and an ongoing pilot trial designed to answer the leading questions in the field.(1)Peters et al Eur Heart J 2022