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From the Institute for Ageing and Health (B.K.S., F.H., I.G.M., G.A.F.), University of Newcastle, Newcastle upon Tyne; and Cognitive Drug Research Ltd. (B.K.S., K.A.W.), Goring-on-Thames, UK.
Address correspondence and reprint requests to Professor Gary A. Ford, Clinical Research Centre, 4th Floor Leazes Wing, Royal Victoria Infirmary, Newcastle upon Tyne, UK, NE1 4LP g.a.ford{at}ncl.ac.uk.
Background: Hypertension is associated with impaired cognitive function but the effect of antihypertensive treatment on cognitive function is unclear.
Methods: We investigated the effect of treatment of hypertension on cognition with the angiotensin-receptor-blocker, candesartan, in a placebo-controlled, double-blind, randomized controlled trial at one center participating in the Study on Cognition and Prognosis in the Elderly. A total of 257 older adults with hypertension (mean age 76 years, blood pressure 165 ± 8/88 ± 7 mm Hg) were recruited from general practice and treated with 8–16 mg candesartan or placebo once daily, for a mean follow-up period of 44 months. Additional antihypertensive therapy was permitted in both groups to achieve treatment targets. Cognitive function was measured using the Cognitive Drug Research computerized assessment battery, trail-making tests, and verbal fluency. Data from annual assessments were used to calculate individual coefficients of decline by regressing composite test scores over time for five cognitive domains.
Results: The blood pressure difference between groups at study close was 8/3 mm Hg. The candesartan group showed less decline in attention (0.004 vs –0.036, p = 0.04) and episodic memory (0.14 vs –0.22, p = 0.04) compared to placebo, a similar trend for speed of cognition (–2.3 vs –17.4, p = 0.15), but no differences in working memory (0.0014 vs 0.0010, p = 0.90) or executive function (–0.0031 vs –0.0023, p = 0.95). Effect sizes were in the small-to-moderate range.
Conclusions: The potential for blood pressure–lowering with angiotensin-receptor-blockers to reduce the rate of decline of specific areas of cognitive function in older patients with hypertension warrants further investigation to determine clinical efficacy.
Abbreviations: ARB = angiotensin-receptor-blocker; BHS = British Hypertension Society; BP = blood pressure; CDR = Cognitive Drug Research; DBP = diastolic BP; HCTZ = hydrochlorothiazide; MMSE = Mini-Mental State Examination; NART = New Adult Reading Test; SBP = systolic BP; SCOPE = Study on Cognition and Prognosis in the Elderly; SHEP = Systolic Hypertension in the Elderly Program; Syst-Eur = Systolic Hypertension in Europe.
Financial support of the cognitive substudy was provided by the Astra Research Foundation UK and AstraZeneca International. The main SCOPE trial was supported by AstraZeneca International.
Disclosure: This study was sponsored by AstraZeneca. The sponsor designed the main SCOPE study, but played no role in the design and conduct of the cognitive substudy reported in this article and no role in the collection of data. The sponsor was responsible for data monitoring and management of the main SCOPE study (including randomization). The sponsor played no role in the analysis and interpretation of the data, and no role in the preparation, review, or approval of the manuscript. Keith A. Wesnes is sole shareholder of Cognitive Drug Research Ltd., which owns the computerized cognitive assessment system used in this study. Cognitive Drug Research Ltd. has over 50 clients, one of whom is AstraZeneca. Brian K. Saxby is an employee of Cognitive Drug Research Ltd. Gary A. Ford has acted as a paid consultant for AstraZeneca.
Received April 25, 2007. Accepted in final form November 8, 2007.
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