Abstract
Optimal blood pressure (BP) targets for the prevention of cognitive impairment remain uncertain. To explore the association of intensive (ie, lower than usual) BP reduction vs standard BP management with the incidence of cognitive decline and dementia in adults with hypertension. A systematic review and meta-analysis of randomized clinical trials that evaluated the association of intensive systolic BP lowering on cognitive outcomes by searching MEDLINE, Embase, CENTRAL, Web of Science, CINAHL, PsycINFO, the International Clinical Trials Registry Platform, and ClinicalTrials.gov from database inception to October 27, 2020. Data screening and extraction were performed independently by 2 reviewers based on Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. The risk of bias was assessed using the Cochrane risk of bias 2 tool. Random-effects models with the inverse variance method were used for pooled analyses. The presence of potential heterogeneity was evaluated with the I2 index. The primary outcome was cognitive decline. Secondary outcomes included the incidence of dementia, mild cognitive impairment (MCI), cerebrovascular events, serious adverse events, and all-cause mortality. From 7755 citations, we identified 16 publications from 5 trials with 17 396 participants (mean age, 65.7 years [range, 63.0-80.5 years]; 10 562 [60.5%] men) and 2 additional ongoing trials. All 5 concluded trials included in quantitative analyses were considered at unclear to high risk of bias. The mean follow-up duration was 3.3 years (range, 2.0 to 4.7 years). Intensive BP reduction was not significantly associated with global cognitive performance (standardized mean difference, 0.01; 95% CI, -0.04 to 0.06; I2 = 0%; 4 trials; 5246 patients), incidence of dementia (risk ratio [RR], 1.09; 95% CI, 0.32 to 3.67; I2 = 27%; 2 trials; 9444 patients) or incidence of MCI (RR, 0.91; 95% CI, 0.73 to 1.14; I2 = 74%; 2 trials; 10 774 patients) when compared with standard treatment. However, a reduction of cerebrovascular events in the intensive group was found (RR, 0.79; 95% CI, 0.67 to 0.93; I2 = 0%; 5 trials; 17 396 patients) without an increased risk of serious adverse events or mortality. In this study, there was no significant association between BP reduction and lower risk of cognitive decline, dementia, or MCI. The certainty of this evidence was rated low because of the limited sample size, the risk of bias of included trials, and the observed statistical heterogeneity. Therefore, current available evidence does not justify the use of lower BP targets for the prevention of cognitive decline and dementia.
Highlights
Dementia was declared a world health priority by the World Health Organization (WHO),[1] with intense global research efforts dedicated toward the design of interventions to prevent, delay, or treat etiologies leading to cognitive impairment and dementia
Intensive blood pressure (BP) reduction was not significantly associated with global cognitive performance, incidence of dementia or incidence of mild cognitive impairment (MCI) (RR, 0.91; 95% CI, 0.73 to 1.14; I2 = 74%; 2 trials; 10 774 patients) when compared with standard treatment
In this study, there was no significant association between BP reduction and lower risk of cognitive decline, dementia, or MCI
Summary
Dementia was declared a world health priority by the World Health Organization (WHO),[1] with intense global research efforts dedicated toward the design of interventions to prevent, delay, or treat etiologies leading to cognitive impairment and dementia. Cerebrovascular disease (CVD) is a major contributor.[2] an important overlap exists between CVD and neurodegenerative conditions, especially Alzheimer disease (AD), with more than half of autopsied cases being of mixed etiologies.[3] CVD, AD, and mixed CVD/AD are associated with as many as 80% of all dementia cases in community-dwelling older persons.[4,5]. A recent systematic review of randomized clinical trials[10] found an association between BP reduction and reduced risk of cognitive decline. The WHO 2019 guidelines[11] recommend that standard hypertension management be offered to adults with hypertension to reduce the risk of cognitive decline and/or dementia (very low quality of evidence, conditional strength of the recommendation)
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