Cognitive markers of preclinical and prodromal Alzheimer's disease in Down syndrome

Introduction: Down syndrome (DS) is associated with an almost universal development of Alzheimer's disease. Individuals with DS are therefore an important population for randomized controlled trials to prevent or delay cognitive decline, though it is essential to understand the time course of early cognitive changes. Methods: We conducted the largest cognitive study to date with 312 adults with DS to assess age-related and Alzheimer's disease-related cognitive changes during progression from preclinical to prodromal dementia, and prodromal to clinical dementia. Results: Changes in memory and attention measures were most sensitive to early decline. Resulting sample size calculations for randomized controlled trials to detect significant treatment effects to delay decline were modest. Discussion: Our findings address uncertainties around the development of randomized controlled trials to delay cognitive decline in DS. Such trials are essential to reduce the high burden of dementia in people with DS and could serve as proof-of-principle trials for some drug targets. (C) 2018 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association.