There is controversy as to whether vitamin E is beneficial in Alzheimer's disease (AD). In this study, we tested if vitamin E prevents oxidative stress and loss of cognition in AD. Fifty-seven AD patients were recruited and divided in two groups: placebo or treated with 800 IU of vitamin E per day for six months. Of these 57 patients, only 33 finished the study. We measured blood oxidized glutathione (GSSG) and used the following cognitive tests: Mini-Mental State Examination, Blessed-Dementia Scale, and Clock Drawing Test. Of those patients treated with vitaimin E, we found two groups. In the first group,“respondents” to vitamin E, GSSG levels were lower after the treatment and scores on the cognitive tests were maintained. The second group,“non-respondents”, consisted of patients in which vitamin E was not effective in preventing oxidative stress. In these patients, cognition decreased sharply, to levels even lower than those of patients taking placebo. Based on our findings, it appears that vitamin E lowers oxidative stress in some AD patients and maintains cognitive status, however, in those in which vitamin E does not prevent oxidative stress, it is detrimental in terms of cognition. Therefore, supplementation of AD patients with vitamin E cannot be recommended without determination of its antioxidant effect in each patient.