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The published effects of Vitamin E (VitE) in treating mild cognitive impairment (MCI) or dementia due to Alzheimer's disease (AD) have been inconsistent. Possible explanations include severity differences, different underlying MCI etiologies, insensitive outcome measures or analytical methods. Previously, we have shown that advanced analytical methods detected a treatment effect in the Myriad, FDA phase III clinical trial that was not detected with traditional methods. Here, we applied Hierarchical Markov models to the item responses of the ADAS-Cog 10-word recall task from the ADCS MCI Donepezil/VitE/Placebo trial. The Markov model assumed that in the ADAS-Cog 10-word memory task (three study and one no-study recall trials), each word resides in one of three cognitive states - Unlearned, Working or Short-Term Memory. The model measured the effect of a word's list position, in each study-recall trial, on the probabilities of being stored and retrieved into Working or Short-Term Memory as well as probabilities of recalling a word from Working and Short-Term Memory.The changes in storage and retrieval parameters from baseline to defined end points were compared among the placebo (N=143), donepezil (N=132), and VitE (N=139) treatment groups. Analysis of variance was then used to test for treatment effects on each of the storage and retrieval parameters. Bonferroni correction was used to adjust for multiple comparisons. Statistically significant treatment group differences were detected between Vitamin E vs. placebo (p<0.01), and donepezil vs. placebo (p<0.01), for the working memory retrieval parameter, plus short-term memory storage and retrieval parameters. Vitamin E vs. donepezil treatments did not significantly differ. The Hierarchical Markov model detected treatment effects missed by standard analyses, plus specified the cognitive processes affected by these treatments in amnestic MCI patients. These findings parallel the delayed functional decline recently reported in AD patients treated with Vitamin E.