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

Do Angiotensin Receptor Blockers Really Hold Promise for the Improvement of Cognitive... In reply We appreciate the interest by Drs Andrade and Fernandes in our recent report.1 As noted, this is a small pilot study intended to provide preliminary data in a randomized setting. Nonetheless, correcting for multiple testing (8 cognitive tests) using the False Discovery Rate method,2 a P value less than .01 would be significant. Therefore, our findings for Trails B and Trails B-A remain significant with adjustment for multiple comparisons. After 1 year of treatment, the lisinopril group showed a worsening of 14.44 seconds, while the candesartan and hydrochlorothiazide groups showed improvements of 17.11 seconds and 4.24 seconds, respectively. These correspond to improvements in the candesartan group of 31.55 seconds relative to the lisinopril group and 12.87 seconds relative to the hydrochlorothiazide group (effect sizes [difference in group means divided by pooled standard deviation] of 1.05 for the candesartan vs lisinopril groups and 0.43 for the candesartan vs hydrochlorothiazide groups). These are medium to large effects.3 We did not include a cross-over or a discontinuation phase because these approaches were not included in the study protocol and were beyond the scope of this study. Finally, as shown in Figure 1 in our report,1 the effects of angiotensin receptor blockers on Trails B and Trails B-A were progressive at the 6- and 12-month assessments. These data suggest an increasing effect over the 1-year period. However, we cannot rule out a ceiling or nonenduring effect beyond this time frame. Back to top Article Information Correspondence: Dr Hajjar, Department of Medicine, University of Southern California, 2020 Zonal Ave, IRD 320, Los Angeles, California 90033 (ihajjar@usc.edu). Financial Disclosure: None reported. Additional Contributions: Dr Hajjar and the AVEC trial are supported by grant 1 K23 AG030057 from the National Institute on Aging (NIA). This work is also supported by grants P01-AG004390 and R37-AG025037 from the NIA to Dr Lipsitz, the Irving and Edyth S. Usen and Family Chair in Geriatric Medicine at Hebrew SeniorLife, and the generous donation by Hinda Marcus to the Cardiovascular Research Laboratory at Hebrew SeniorLife and Harvard Medical School. References 1. Hajjar I, Hart M, Chen YL, 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. Benjamini Y, Drai D, Elmer G, Kafkafi N, Golani I. Controlling the false discovery rate in behavior genetics research. Behav Brain Res. 2001;125(1-2):279-28411682119PubMedGoogle ScholarCrossref 3. Cohen J. Statistical Power Analysis for the Behavioral Sciences. 2nd ed. Hillsdale, NJ: L Erlbaum Associates; 1988 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?—Reply

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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.2012.3885
Publisher site
See Article on Publisher Site

Abstract

In reply We appreciate the interest by Drs Andrade and Fernandes in our recent report.1 As noted, this is a small pilot study intended to provide preliminary data in a randomized setting. Nonetheless, correcting for multiple testing (8 cognitive tests) using the False Discovery Rate method,2 a P value less than .01 would be significant. Therefore, our findings for Trails B and Trails B-A remain significant with adjustment for multiple comparisons. After 1 year of treatment, the lisinopril group showed a worsening of 14.44 seconds, while the candesartan and hydrochlorothiazide groups showed improvements of 17.11 seconds and 4.24 seconds, respectively. These correspond to improvements in the candesartan group of 31.55 seconds relative to the lisinopril group and 12.87 seconds relative to the hydrochlorothiazide group (effect sizes [difference in group means divided by pooled standard deviation] of 1.05 for the candesartan vs lisinopril groups and 0.43 for the candesartan vs hydrochlorothiazide groups). These are medium to large effects.3 We did not include a cross-over or a discontinuation phase because these approaches were not included in the study protocol and were beyond the scope of this study. Finally, as shown in Figure 1 in our report,1 the effects of angiotensin receptor blockers on Trails B and Trails B-A were progressive at the 6- and 12-month assessments. These data suggest an increasing effect over the 1-year period. However, we cannot rule out a ceiling or nonenduring effect beyond this time frame. Back to top Article Information Correspondence: Dr Hajjar, Department of Medicine, University of Southern California, 2020 Zonal Ave, IRD 320, Los Angeles, California 90033 (ihajjar@usc.edu). Financial Disclosure: None reported. Additional Contributions: Dr Hajjar and the AVEC trial are supported by grant 1 K23 AG030057 from the National Institute on Aging (NIA). This work is also supported by grants P01-AG004390 and R37-AG025037 from the NIA to Dr Lipsitz, the Irving and Edyth S. Usen and Family Chair in Geriatric Medicine at Hebrew SeniorLife, and the generous donation by Hinda Marcus to the Cardiovascular Research Laboratory at Hebrew SeniorLife and Harvard Medical School. References 1. Hajjar I, Hart M, Chen YL, 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. Benjamini Y, Drai D, Elmer G, Kafkafi N, Golani I. Controlling the false discovery rate in behavior genetics research. Behav Brain Res. 2001;125(1-2):279-28411682119PubMedGoogle ScholarCrossref 3. Cohen J. Statistical Power Analysis for the Behavioral Sciences. 2nd ed. Hillsdale, NJ: L Erlbaum Associates; 1988

Journal

Archives of Internal MedicineAmerican Medical Association

Published: Aug 13, 2012

Keywords: angiotensin receptor antagonists,mental processes,cognitive ability

References