An exploratory goal of this study was to estimate treatment effect size for pioglitazone. Sample size analyses were conducted to determine the number of subjects needed to detect significant differences between the pioglitazone and control group on 2 outcome measures typically used for regulatory approval, ADAS-COG and CDR-SB. We used Optimal Design software (J. Spybrook, S. W. Raudenbush, R. Congdon, A. Martinez, “Optimal Design for Longitudinal and Multilevel Research,” University of Michigan: Institute of Social Research, 2009) to compute the sample size needed to detect a significant difference of the magnitude of the regression coefficient for pioglitazone estimated in Table 4 (−0.746 for ADAS-COG and −0.354 for CDR-SB). For α = .05 and power = 0.80, a sample size of 340 (170 pioglitazone, 170 placebo) would be needed to find the estimated effect (−0.746) of pioglitazone on ADAS-COG to be significant. For α = .05 and power = 0.80, a sample size of 155 (78 pioglitazone, 77 placebo) would be needed to find the estimated effect (−0.354) of pioglitazone on CDR-SB to be significant. The needed sample size for CDR-SB is slightly less than half the needed sample size for ADAS-COG. Pivotal trials leading to Food and Drug Administration approval of currently available drugs typically enrolled 250 to 500 patients. Several ongoing clinical trials for disease-modifying agents will enroll more than 1000 subjects to test their hypotheses. These figures suggest that further studies to assess the clinical efficacy of pioglitazone or similar PPARγ agents would be feasible.