DEFINING COGNITIVE DECLINE IN ADULTS WITH DOWN SYNDROME

Abstract

Down syndrome (DS) is associated with a specific mechanism for Alzheimer's disease related to overproduction of amyloid due to APP gene triplication on chromosome 21. DS is therefore an important population in which to consider amyloid targeting treatments to prevent or delay onset of clinical symptoms. Although amyloid pathology suggestive of Alzheimer's disease (AD) are present in the brains of nearly all individuals with Down syndrome (DS) after the age of 30, there is considerable variability in age of onset of clinical symptoms. We need a better understanding of the natural history of AD in DS and clinical progression as well as associated biomarkers in order to conduct such trials. The London Down syndrome consortium has been conducting an in-depth longitudinal cognitive phenotyping study of >400 adults with DS using a variety of cognitive tasks including tests of memory and executive functions (using CANTAB computer tasks and table-top tasks) and symptoms of dementia (using CAMDEX-DS). All participants donated blood or sputum for DNA and genetic analysis. We will present data on the sequence of cognitive decline with aging in DS, clinical predictors of decline, and clinical differences associated with APOE and other genetic markers. Such data may be used to develop reliable cognitive outcome measures and to stratify and plan clinical trials to prevent or delay AD in the DS population. Some of the issues related to conducting clinical trials in this population will be highlighted alongside potential solutions.