A major challenge to developing therapeutic interventions for cognitive loss and dementia in aging individuals with Down syndrome (DS) is the selection of appropriate outcome measures. This report describes the adaptation of the Brief Praxis Test (a nonverbal cognitive test) as a primary outcome measure, as well as the selection of secondary outcome measures for a multicenter clinical trial of vitamin E in aging individuals with DS. Instruments were chosen to assess cognition, behavior, and clinical global function based on previous work in DS and in Alzheimer's disease. Measures of cognition included verbal and nonverbal memory, vocabulary, and orientation. An informant-based measure of behavior and function was adapted from several existing rating scales, and the Clinical Global Impression was adapted for use with this group. This report also describes initial experiences using these measures with the participants who were enrolled in the clinical trial. As in other populations of persons with dementia, verbal learning, memory, and delayed recall proved to be highly associated with the presence of dementia in our study participants. With the exception of visual memory and orientation measures (which proved too difficult to use with portions of this cohort), the tests employed proved useful in the assessment of individuals across a range of premorbid levels of intellectual disability. The authors conclude that the measures chosen for the assessment of behavior and functional ability and the use of the Clinical Global Impression appear to be appropriate for this population and comparable to instruments that have captured pharmacological benefits in other disease groups.