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Published online before print February 18, 2009, doi:10.1212/01.wnl.0000345062.86148.3f)
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 Volume 72, Number 20, May 19, 2009
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Received October 10, 2008
Accepted January 9, 2009

Duration of antihypertensive drug use and risk of dementia. A prospective cohort study

M. D.M. Haag PharmD, A. Hofman PhD, P. J. Koudstaal PhD, M. M.B. Breteler PhD, and B. H.C. Stricker PhD*

From the Departments of Epidemiology (M.D.M.H., A.H., M.M.B.B., B.H.C.S.), Neurology (P.J.K.), and Internal Medicine (B.H.C.S.), Erasmus Medical Center, Rotterdam; and Inspectorate for Health Care (B.H.C.S.), The Hague, The Netherlands.


* To whom correspondence should be addressed. E-mail: b.stricker{at}erasmusmc.nl.

Background: The evidence from prospective observational research for a protective effect of antihypertensive drug use on the risk of dementia is far from uniform. Duration of follow-up was limited and relied mainly on baseline drug exposure data without information on duration of use. We investigated the association between the duration of antihypertensive use and risk of dementia.

Methods: We followed 6,249 participants (mean 68.4 years, 60% women) of a prospective, population-based cohort from baseline (1990–1993) until 2005 for incident dementia. Continuous data on filled prescriptions came from pharmacy records. Total cumulative duration of antihypertensive use was expressed in years. We subtracted a latent 4-year period before the date of dementia diagnosis in the quantification of exposure duration to avoid potential bias in antihypertensive prescription due to prodromal changes in blood pressure or cognition. With Cox regression models, we calculated crude and adjusted hazard ratios (HRs) of all dementia and Alzheimer disease (AD) with antihypertensive use vs never used.

Results: Compared to never used, antihypertensive use was associated with a reduced risk of all dementia (adjusted HR per year of use 0.95; 95% confidence interval [CI] 0.91–0.99). We observed an 8% (95% CI -15% to -1%) risk reduction per year of use for persons ≤75 years, whereas for persons >75 years this was 4% (95% CI -11% to 4%). Equivalent estimates were observed for AD. No apparent differences were observed among different types of antihypertensive drugs.

Conclusions: Antihypertensive drug use was associated with 8% risk reduction of dementia per year of use for persons ≤75 years.


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