Adults with Down syndrome in randomized clinical trials targeting prevention of Alzheimer's disease

Introduction Adults with Down syndrome, the largest population genetically predisposed to high risk for Alzheimer's disease (AD), are ideally suited participants for clinical trials targeting prevention. Critically important considerations for the design of such trials include appropriate selection of participants, outcome measures, and duration of follow-up. Methods Archived data for 12 measures of performance over a 3-year period were analyzed for 185 adults with Down syndrome 36 years of age and older with presumptive preclinical AD. Results Declines over 3 years were not observed prior to 46 years of age. However, declines were observed at older ages, increasing monotonically for groups aged 46-49, 50-55, and >55, as did incidence of prodromal AD and dementia. Discussion Significant decline over a 2- to 3-year period for a prospective placebo group of adults with Down syndrome enrolled in clinical prevention trials can only be expected when inclusion is limited to adults older than 45 years of age.

Automated summary

Adults with Down syndrome do not show declines over a 3-year period before the age of 46, but declines are observed at older ages, along with an increase in prodromal AD and dementia incidence. It is expected that significant decline in a 2- to 3-year period for a placebo group in clinical prevention trials will only occur if the group is limited to adults over the age of 45.