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Research

Use of angiotensin receptor blockers and risk of dementia in a predominantly male population: prospective cohort analysis

BMJ 2010; 340 doi: https://doi.org/10.1136/bmj.b5465 (Published 13 January 2010) Cite this as: BMJ 2010;340:b5465
  1. Nien-Chen Li, statistician12,
  2. Austin Lee, senior statistician23,
  3. Rachel A Whitmer, research epidemiologist4,
  4. Miia Kivipelto, associate professor5,
  5. Elizabeth Lawler, epidemiologist6,
  6. Lewis E Kazis, professor12,
  7. Benjamin Wolozin, professor27
  1. 1Center for the Assessment of Pharmaceutical Practices and Pharmaceutical Assessment, Management and Policy Program, Department of Health Policy and Management, Boston University School of Public Health, Boston, MA, USA
  2. 2Center for Health Quality Outcomes and Economic Research, Veteran Affairs Medical Center, Bedford, MA
  3. 3Department of Surgery, Massachusetts General Hospital, Boston, MA
  4. 4Division of Research, Epidemiology, Etiology and Prevention, Kaiser Permanente, Oakland, CA, USA
  5. 5Aging Research Center, Karolinska Institute, Stockholm, Sweden
  6. 6MAVERIC, VA Cooperative Studies Program, Boston, MA
  7. 7Department of Pharmacology and Department of Neurology, Boston University School of Medicine, Boston, MA 02118-2526, USA
  1. Correspondence to: bwolozin{at}bu.edu
  • Accepted 26 October 2009

Abstract

Objective To investigate whether angiotensin receptor blockers protect against Alzheimer’s disease and dementia or reduce the progression of both diseases.

Design Prospective cohort analysis.

Setting Administrative database of the US Veteran Affairs, 2002-6.

Population 819 491 predominantly male participants (98%) aged 65 or more with cardiovascular disease.

Main outcome measures Time to incident Alzheimer’s disease or dementia in three cohorts (angiotensin receptor blockers, lisinopril, and other cardiovascular drugs, the “cardiovascular comparator”) over a four year period (fiscal years 2003-6) using Cox proportional hazard models with adjustments for age, diabetes, stroke, and cardiovascular disease. Disease progression was the time to admission to a nursing home or death among participants with pre-existing Alzheimer’s disease or dementia.

Results Hazard rates for incident dementia in the angiotensin receptor blocker group were 0.76 (95% confidence interval 0.69 to 0.84) compared with the cardiovascular comparator and 0.81 (0.73 to 0.90) compared with the lisinopril group. Compared with the cardiovascular comparator, angiotensin receptor blockers in patients with pre-existing Alzheimer’s disease were associated with a significantly lower risk of admission to a nursing home (0.51, 0.36 to 0.72) and death (0.83, 0.71 to 0.97). Angiotensin receptor blockers exhibited a dose-response as well as additive effects in combination with angiotensin converting enzyme inhibitors. This combination compared with angiotensin converting enzyme inhibitors alone was associated with a reduced risk of incident dementia (0.54, 0.51 to 0.57) and admission to a nursing home (0.33, 0.22 to 0.49). Minor differences were shown in mean systolic and diastolic blood pressures between the groups. Similar results were observed for Alzheimer’s disease.

Conclusions Angiotensin receptor blockers are associated with a significant reduction in the incidence and progression of Alzheimer’s disease and dementia compared with angiotensin converting enzyme inhibitors or other cardiovascular drugs in a predominantly male population.

Footnotes

  • Contributors: N-CL acquired and analysed the data, critically revised the manuscript, and provided technical support. AL and EL designed the study, acquired the data, did the statistical analysis, and critically revised the manuscript. RAW and MK interpreted the data and critically revised the manuscript for important intellectual content. LEK designed the study, analysed and interpreted the data, obtained funding, and critically revised the manuscript. BW conceived, designed, and supervised the study, analysed and interpreted the data, drafted the manuscript, and obtained funding. He is guarantor.

  • Funding: This work was supported by a grant award to BW from the Retirement Research Foundation and a donation from the Casten Foundation. The researchers operate independently of the funders of the study.

  • Competing interests: BW and RAW received a grant award from the Retirement Research Foundation to fund this research. BW received a donation from the Casten Foundation to fund this research.

  • Ethical approval: This study was approved by internal review boards of the Boston University School of Medicine, the Bedford Veterans Affairs Medical Center, and Jamaica Plains Veterans Affairs Medical Center. The study was based on administrative datasets and the participants were not identifiable to the authors.

  • Data sharing: No additional data available.

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