Cognitive and clinical outcome measures for Alzheimer's disease prevention trials in adults with Down syndrome

Abstract

AbstractBackgroundAdults with Down syndrome (DS) are at ultra‐high risk for developing Alzheimer’s disease (AD) due to APP gene triplication on chromosome 21. There is interest in conducting trials of treatment that can delay or prevent onset of disease in at‐risk individuals with DS. Reliable outcome measures are required to demonstrate clinical benefit of treatment in a population with premorbid cognitive impairments that affect their performance on cognitive outcome measures. We aimed to identify the most efficient clinical and cognitive outcomes for prevention trials of AD in DS.MethodsAnalysis of cognitive data based on different test batteries from several recent longitudinal cohort studies of AD in DS in Europe and the US (n >300 with 2 years of follow‐up data), using staging and E‐Max models and other statistical methods.ResultsThe age range within which cognitive decline can be first reliably observed in DS adults who do not yet have dementia is around age 45; this varies by outcome measure, with memory, attention, orientation and some verbal tasks being the most feasible and reliable tests for prevention trials. We will report effect sizes for these outcome measures to inform trial design.ConclusionsTrials of treatment to prevent or delay AD in DS individuals using cognitive measures as primary outcomes are feasible if targeted at individuals within age ranges where decline can be first observed, but effect sizes (and sample sizes) vary by outcome measures selected.