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

Educational Objective
To review the effect of blood pressure lowering for the prevention of dementia or cognitive impairment.
1 Credit CME
Key Points

Question  Is there an association between blood pressure lowering with antihypertensive therapy and the incidence of dementia or cognitive impairment?

Findings  In this meta-analysis that included 12 trials with 92 135 participants for the primary outcome measure, blood pressure lowering with antihypertensive agents, compared with control, was associated with the development of a composite dementia or cognitive impairment outcome in 7.0% vs 7.5% of patients over a mean trial follow-up of 4.1 years, a difference that was statistically significant.

Meaning  Lowering blood pressure may be associated with a lower risk of dementia or cognitive impairment.

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.

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Article Information

Corresponding Author: Michelle Canavan, PhD, HRB Clinical Research Facility, Galway University Hospital, Newcastle Road, Galway, Ireland, H91YR7 (michelle.canavan@hse.ie).

Accepted for Publication: March 13, 2020.

Author Contributions: Drs Hughes and Judge had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis as co–first authors.

Concept and design: Hughes, Judge, Murphy, Loughlin, O'Donnell, Canavan.

Acquisition, analysis, or interpretation of data: Hughes, Judge, Murphy, Costello, Whiteley, Bosch, O'Donnell, Canavan.

Drafting of the manuscript: Hughes, Judge, Murphy, Loughlin, Costello, O'Donnell, Canavan.

Critical revision of the manuscript for important intellectual content: Hughes, Judge, Murphy, Whiteley, Bosch, O'Donnell, Canavan.

Statistical analysis: Hughes, Judge, Costello, Canavan.

Obtained funding: Judge.

Administrative, technical, or material support: Murphy, Loughlin, Canavan.

Supervision: Murphy, Loughlin, O'Donnell, Canavan.

Conflict of Interest Disclosures: Dr Judge reported receiving grants from the Wellcome Trust and the Health Research Board during the conduct of the study. Dr Whiteley reported receiving grants from the Chief Scientist Office outside the submitted work. Dr Bosch reported receiving personal fees from Bayer AG outside the submitted work. No other disclosures were reported.

Funding/Support: Dr Judge was supported by the Irish Clinical Academic Training Programme, the Wellcome Trust, the Health Research Board (grant number 203930/B/16/Z), the Health Service Executive, National Doctors Training and Planning, and the Health and Social Care Research and Development Division Northern Ireland. Dr O’Donnell was supported by the European Research Council (COSIP grant 640580).

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: John Ferguson, PhD (HRB Clinical Research Facility, Galway), contributed to the updated analysis (bootstrapping method for applying relative risk reduction to baseline risk of dementia). He did not receive compensation for his contribution.

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