Evaluation of Intensive vs Standard Blood Pressure Reduction and Association With Cognitive Decline and Dementia: A Systematic Review and Meta-analysis.

Importance: Optimal blood pressure (BP) targets for the prevention of cognitive impairment remain uncertain. Objective: 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. Data Sources and Study Selection: 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 Extraction and Synthesis: 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. Main Outcomes and Measures: 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. Results: 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. Conclusions and Relevance: 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.