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The Association Between Blood Pressure and Incident Alzheimer Disease: A Systematic Review and Meta-analysis

Power, Melinda C.a,b; Weuve, Jenniferb,c; Gagne, Joshua J.a,d; McQueen, Matthew B.e; Viswanathan, Anandf; Blacker, Deboraha,g

doi: 10.1097/EDE.0b013e31822708b5
Neurologic

Background: Many epidemiologic studies have considered the association between blood pressure (BP) and Alzheimer disease, yet the relationship remains poorly understood.

Methods: In parallel with work on the AlzRisk online database (www.alzrisk.org), we conducted a systematic review to identify all epidemiologic studies meeting prespecified criteria reporting on the association between hypertension, systolic BP, or diastolic BP and incident Alzheimer disease. When possible, we computed summary measures using random-effects models and explored potential heterogeneity related to age at BP assessment.

Results: Eighteen studies reporting on 19 populations met the eligibility criteria. We computed summary relative risks (RRΣ) for 3 measures of BP: hypertension (RRΣ = 0.97 [95% confidence interval = 0.80–1.16]); a 10-mm Hg increase in systolic BP (RRΣ = 0.95 [0.91–1.00]); and a 10-mm Hg increase in diastolic BP (RRΣ = 0.94 [0.85–1.04]). We were unable to compute summary estimates for the association between categories of systolic or diastolic BP and Alzheimer disease; however, there did not appear to be a consistent pattern across studies. After stratifying on age at BP assessment, we found a suggestion of an inverse association between late-life hypertension and Alzheimer disease and a suggestion of an adverse association between midlife diastolic hypertension and Alzheimer disease.

Conclusions: Based on existing epidemiologic research, we cannot determine whether there is a causal association between BP and Alzheimer disease. Selection bias and reverse causation may account for the suggested inverse association between late-life hypertension on Alzheimer disease, but, given the expected direction of these biases, they are less likely to account for the suggestion that midlife hypertension increases risk. We advocate continuing systematic review; the AlzRisk database entry on this topic (www.alzrisk.org), which was completed in parallel with this work, will be updated as new studies are published.

From the Departments of aEpidemiology and bEnvironmental Health, Harvard School of Public Health, Boston, MA; cInstitute for Healthy Aging and Department of Internal Medicine, Rush University Medical Center, Chicago, IL; dDivision of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; eDepartment of Psychology and Institute for Behavioral Genetics, University of Colorado at Boulder, Boulder, CO; fHemorrhagic Stroke Research Program, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA; and gGerontology Research Unit, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA.

Submitted 11 October 2010; accepted 29 March 2011; posted 24 June 2011.

Supported by a grant from an anonymous foundation. Supported by a National Institute of Environmental Health Sciences training grant (T32 ES007069) (to M.C.P.).

Supplemental digital content is available through direct URL citations in the HTML and PDF versions of this article (www.epidem.com).

Correspondence: Melinda C. Power, Harvard School of Public Health, 3rd Floor East, Landmark Center, PO BOX 15697, Boston, MA 02215. E-mail: mcpower@hsph.harvard.edu.

© 2011 Lippincott Williams & Wilkins, Inc.