Alzheimer's disease (AD) currently affects over 4 million Americans, and these numbers are expected to increase three-fold over the next 50 years. Worldwide prevalence is estimated to be between 18 and 34 million individuals. Though the etiologies of AD continue to remain elusive, the prevention of AD is becoming a critical focus for treatment. The PREADVISE study is investigating the long-term use of antioxidant supplements vitamin E and selenium for the prevention of AD. Further, PREADVISE is utilizing an innovative sub-study model in cooperation with the SELECT prostate cancer trial and has thus far accrued over 5,100 participants. This article introduces the PREADVISE/SELECT ancillary study model and discusses its potential benefits for conducting large-scale, longitudinal, clinical trials in dementia research.