RT Journal A1 Hajjar I, Mack W, Lipsitz L T1 DO angiotensin receptor blockers really hold promise for the improvement of cognitive functioning?—reply JF Archives of Internal Medicine JO Archives of Internal Medicine YR 2012 FD August 13 VO 172 IS 15 SP 1191 OP 1192 DO 10.1001/archinternmed.2012.3885 UL http://dx.doi.org/10.1001/archinternmed.2012.3885 AB 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.