Effects of blood pressure lowering for the prevention of dementia: meta‐analysis of individual patient data from five seminal randomised controlled trials involving 28008 participants

Background Observational studies indicate U‐shaped associations of blood pressure (BP) and incident dementia in older age, but randomised controlled trials of BP lowering treatment show mixed results on this outcome in hypertensive patients. We undertook a pooled individual participant data analysis of five seminal double‐blind placebo‐controlled randomised trials to better define the effects of BP lowering treatment for the prevention of dementia and cognitive decline. Methods Multilevel logistic regression was used to evaluate the treatment effect on incident dementia. Effect modification was assessed for key population characteristics including age, baseline systolic BP, sex, and presence of prior stroke. Mediation analysis was used to quantify the contribution of trial medication and changes in systolic and diastolic BP on risk of dementia. Results The total sample included 28,008 individuals recruited from 20 countries. After a median follow‐up of 4.3 years, there were 861 cases of incident dementia. Multilevel logistic regression reported an adjusted odds ratio 0.87 (95% confidence interval 0.75, 0.99) in favour of antihypertensive treatment reducing risk of incident dementia with a mean BP lowering of 10/4mmHg. Further multinomial regression taking account of death as a competing risk found similar results. There was no effect modification by age or sex. Mediation analysis confirmed the greater fall in BP in the actively treated group was associated with a greater reduction in dementia risk. Conclusion Using data from double‐blind placebo‐controlled clinical trials, we provide evidence in the first single‐stage individual participant meta‐analysis to support benefits of antihypertensive treatment in late‐mid and later life to lower the risk of dementia. Questions remain as to the potential for additional BP lowering in those with already well‐controlled hypertension and of antihypertensive treatment commenced earlier in the life‐course to reduce the long‐term risk of dementia.