Association of Blood Pressure Lowering With Incident Dementia or Cognitive Impairment: A Systematic Review and Meta-analysis

Abstract

Importance: The benefit of blood pressure lowering for the prevention of dementia or cognitive impairment is unclear.

Objective: To determine the association of blood pressure lowering with dementia or cognitive impairment.

Data sources and study selection: Search of PubMed, EMBASE, and CENTRAL for randomized clinical trials published from database inception through December 31, 2019, that evaluated the association of blood pressure lowering on cognitive outcomes. The control groups consisted of either placebo, alternative antihypertensive agents, or higher blood pressure targets.

Data extraction and synthesis: Data were screened and extracted independently by 2 authors. Random-effects meta-analysis models were used to report pooled treatment effects and CIs.

Main outcomes and measures: The primary outcome was dementia or cognitive impairment. The secondary outcomes were cognitive decline and changes in cognitive test scores.

Results: Fourteen randomized clinical trials were eligible for inclusion (96 158 participants), of which 12 reported the incidence of dementia (or composite of dementia and cognitive impairment [3 trials]) on follow-up and were included in the primary meta-analysis, 8 reported cognitive decline, and 8 reported changes in cognitive test scores. The mean (SD) age of trial participants was 69 (5.4) years and 40 617 (42.2%) were women. The mean systolic baseline blood pressure was 154 (14.9) mm Hg and the mean diastolic blood pressure was 83.3 (9.9) mm Hg. The mean duration of follow-up was 49.2 months. Blood pressure lowering with antihypertensive agents compared with control was significantly associated with a reduced risk of dementia or cognitive impairment (12 trials; 92 135 participants) (7.0% vs 7.5% of patients over a mean trial follow-up of 4.1 years; odds ratio [OR], 0.93 [95% CI, 0.88-0.98]; absolute risk reduction, 0.39% [95% CI, 0.09%-0.68%]; I2 = 0.0%) and cognitive decline (8 trials) (20.2% vs 21.1% of participants over a mean trial follow-up of 4.1 years; OR, 0.93 [95% CI, 0.88-0.99]; absolute risk reduction, 0.71% [95% CI, 0.19%-1.2%]; I2 = 36.1%). Blood pressure lowering was not significantly associated with a change in cognitive test scores.

Conclusions and relevance: In this meta-analysis of randomized clinical trials, blood pressure lowering with antihypertensive agents compared with control was significantly associated with a lower risk of incident dementia or cognitive impairment.

Figure 1.. Association of Blood Pressure Lowering With Dementia or Cognitive Impairment

The squares and bars represent the mean values and 95% CIs of the effect sizes and the area of the squares reflects the weight of the studies. Diamonds represent the combined effects and the vertical dotted line represents the line of no association. ^aComposite of dementia and cognitive impairment.

Figure 2.. Association of Blood Pressure Lowering With Dementia or Cognitive Impairment/Decline by Cumulative Systolic Blood Pressure Change and Baseline Systolic Blood Pressure

The squares and bars represent the mean values and 95% CIs of the effect sizes and the area of the squares reflects the weight of the studies. The vertical dotted line represents the line of no association.

Figure 3.. Association of Blood Pressure Lowering and Cognitive Decline

The squares and bars represent the mean values and 95% CIs of the effect sizes and the area of the squares reflects the weight of the studies. The diamond represents the combined effect and the vertical dotted line represents the line of no association.