Alzheimer's Disease (AD), the most common late-onset dementing disorder, affects approximately four million individuals in the USA and is projected to affect 14 to 16 million individuals by the year 2050. Prevention may be the key to eliminate AD. It is clear that oxidative damage plays a role in the pathogenesis of AD, and our studies show that it is present in mild cognitive impairment (MCI), the earliest phase of AD, and thus, preventive measures should be initiated in the presymptomatic stages. This research project is an add-on study to the Selenium (Se) and Vitamin E Prostate Cancer Prevention Trial (SELECT). The SELECT study is funded by the NCI to assess the effect of Se and vitamin E, alone and in combination, on the reduction of incidence of prostate cancer in 35,534 healthy men age 55 or older (50 or older if African American). The Prevention of Alzheimer's Disease by Vitamin E and Selenium (PREADVISE) evaluates the effectiveness of these supplements on reducing incident AD and other dementias in a group of more than 6,100 men (17% of whom are minorities, recruited from the SELECT Study). The study duration is 12 years. While SELECT has reached its recruitment goal, PREADVISE has permission to continue recruiting to exceed 6,500 participants. This is the first randomized controlled trial to evaluate the effect of antioxidants (vitamin E and Se) on preventing dementia in the elderly. The specific aims are:1) To define the effect of Se and vitamin E, in combination and alone, in the reduction of the incidence of AD, as determined by the clinical evaluation, in a population of men age 62 or older (60 if minority) participating in SELECT; 2) To assess the effect of Se and vitamin E on the reduction of other neurodegenerative dementing diseases while also ascertaining the effect of the supplements on transition from normal to MCI and from MCI to AD and dementia;. 3) To validate the two-stage screening methodology with in-depth longitudinal cognitive assessments in a subset of 500 subjects who "pass" their initial screen; 4) To increase the number of subjects in PREADVISE to 6,504 or more; and 5) To emphasize retention of subjects in PREADVISE and SELECT. [unreadable] [unreadable] [unreadable] [unreadable]