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Do Angiotensin Receptor Blockers Really Hold Promise for the Improvement of Cognitive Functioning?

Do Angiotensin Receptor Blockers Really Hold Promise for the Improvement of Cognitive Functioning? In a small (n = 53), 12-month, randomized controlled trial, Hajjar et al1 found that elderly hypertensive subjects with impaired executive functioning showed greater executive improvements with candesartan (an angiotensin receptor blocker [ARB]) therapy than with lisinopril or hydrochlorothiazide. They concluded that cognitive protection may arise through selectivity of angiotensin receptor blockade with ARBs. Some questions spring to mind; these address the study by Hajjar et al1 as well as future research: The study1 reported benefits on only some of several neuropsychological outcomes; was correction applied against a type I statistical error? What were the effect sizes for the significant findings? Neuropsychological tests can identify subtle differences, and unless the separation between groups is considerable, the number-needed-to-treat statistic will be large when outcomes are categorized for real-world relevance. Are the benefits with ARBs limited to the duration of therapy or are they enduring? This can be determined through drug discontinuation or crossover studies. Obviously, nonenduring benefits will have little to no practical value. Do the benefits with ARBs increase with time or do they reach a ceiling? This is important because only a progressively widening advantage will eventually assume clinical significance for disorders such as mild cognitive impairment and Alzheimer disease. If benefits were obtained on only some cognitive outcomes, if effect sizes were small, and if the benefits did not survive correction against a type I error, the cognitive promise of ARBs may be small and clinically irrelevant. Consider that previous studies found inconsistent cognitive benefits in elderly subjects receiving ARBs, with low to moderate effect sizes when soft end points were addressed2 and no benefits for hard end points.3,4 Back to top Article Information Correspondence: Dr Andrade, Department of Psychopharmacology, National Institute of Mental Health and Neurosciences, Hosur Road, Bangalore 560029, India (andradec@gmail.com). Financial Disclosure: None reported. References 1. Hajjar I, Hart M, Chen Y-L, et al. Effect of antihypertensive therapy on cognitive function in early executive cognitive impairment: a double-blind randomized clinical trial. Arch Intern Med. 2012;172(5):442-44422412114PubMedGoogle ScholarCrossref 2. Saxby BK, Harrington F, Wesnes KA, McKeith IG, Ford GA. Candesartan and cognitive decline in older patients with hypertension: a substudy of the SCOPE trial. Neurology. 2008;70(19 Pt 2):1858-186618458219PubMedGoogle Scholar 3. Lithell H, Hansson L, Skoog I, et al; SCOPE Study Group. The Study on Cognition and Prognosis in the Elderly (SCOPE): principal results of a randomized double-blind intervention trial. J Hypertens. 2003;21(5):875-88612714861PubMedGoogle ScholarCrossref 4. Anderson C, Teo K, Gao P, et al; ONTARGET and TRANSCEND Investigators. Renin-angiotensin system blockade and cognitive function in patients at high risk of cardiovascular disease: analysis of data from the ONTARGET and TRANSCEND studies. Lancet Neurol. 2011;10(1):43-5320980201PubMedGoogle ScholarCrossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Internal Medicine American Medical Association

Do Angiotensin Receptor Blockers Really Hold Promise for the Improvement of Cognitive Functioning?

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Publisher
American Medical Association
Copyright
Copyright © 2012 American Medical Association. All Rights Reserved.
ISSN
0003-9926
eISSN
1538-3679
DOI
10.1001/archinternmed.2012.2091
Publisher site
See Article on Publisher Site

Abstract

In a small (n = 53), 12-month, randomized controlled trial, Hajjar et al1 found that elderly hypertensive subjects with impaired executive functioning showed greater executive improvements with candesartan (an angiotensin receptor blocker [ARB]) therapy than with lisinopril or hydrochlorothiazide. They concluded that cognitive protection may arise through selectivity of angiotensin receptor blockade with ARBs. Some questions spring to mind; these address the study by Hajjar et al1 as well as future research: The study1 reported benefits on only some of several neuropsychological outcomes; was correction applied against a type I statistical error? What were the effect sizes for the significant findings? Neuropsychological tests can identify subtle differences, and unless the separation between groups is considerable, the number-needed-to-treat statistic will be large when outcomes are categorized for real-world relevance. Are the benefits with ARBs limited to the duration of therapy or are they enduring? This can be determined through drug discontinuation or crossover studies. Obviously, nonenduring benefits will have little to no practical value. Do the benefits with ARBs increase with time or do they reach a ceiling? This is important because only a progressively widening advantage will eventually assume clinical significance for disorders such as mild cognitive impairment and Alzheimer disease. If benefits were obtained on only some cognitive outcomes, if effect sizes were small, and if the benefits did not survive correction against a type I error, the cognitive promise of ARBs may be small and clinically irrelevant. Consider that previous studies found inconsistent cognitive benefits in elderly subjects receiving ARBs, with low to moderate effect sizes when soft end points were addressed2 and no benefits for hard end points.3,4 Back to top Article Information Correspondence: Dr Andrade, Department of Psychopharmacology, National Institute of Mental Health and Neurosciences, Hosur Road, Bangalore 560029, India (andradec@gmail.com). Financial Disclosure: None reported. References 1. Hajjar I, Hart M, Chen Y-L, et al. Effect of antihypertensive therapy on cognitive function in early executive cognitive impairment: a double-blind randomized clinical trial. Arch Intern Med. 2012;172(5):442-44422412114PubMedGoogle ScholarCrossref 2. Saxby BK, Harrington F, Wesnes KA, McKeith IG, Ford GA. Candesartan and cognitive decline in older patients with hypertension: a substudy of the SCOPE trial. Neurology. 2008;70(19 Pt 2):1858-186618458219PubMedGoogle Scholar 3. Lithell H, Hansson L, Skoog I, et al; SCOPE Study Group. The Study on Cognition and Prognosis in the Elderly (SCOPE): principal results of a randomized double-blind intervention trial. J Hypertens. 2003;21(5):875-88612714861PubMedGoogle ScholarCrossref 4. Anderson C, Teo K, Gao P, et al; ONTARGET and TRANSCEND Investigators. Renin-angiotensin system blockade and cognitive function in patients at high risk of cardiovascular disease: analysis of data from the ONTARGET and TRANSCEND studies. Lancet Neurol. 2011;10(1):43-5320980201PubMedGoogle ScholarCrossref

Journal

Archives of Internal MedicineAmerican Medical Association

Published: Aug 13, 2012

Keywords: angiotensin receptor antagonists,mental processes,cognitive ability

References