ABSTRACT Most adults with Down syndrome (DS) will develop pathology associated with Alzheimer's disease (AD) beginning at ~ age 40. By age 65 the cumulative incidence of dementia exceeds 90% and is the leading cause of death in people with DS. However, individuals with DS have traditionally been left out of many of the national ADRCs clinical cohorts and are not included in state-of-the-art trials developed to prevent, delay, or treat AD. This administrative supplement will support the University of Kansas Alzheimer’s Disease Research Center’s (KU ADRC) clinical core to develop a Down Syndrome (DS) Cohort, which will increase opportunities for the study of DS and AD at KU and beyond. Additionally, to advance the KU ADRCs scientific theme of the role of altered energy metabolism in brain aging and AD, the development of this cohort will allow us to measure metabolic outcomes (e.g. physical activity, aerobic fitness, body composition, and dietary assessment) in individuals with DS and support clinical trials testing the therapeutic potential of manipulating energy metabolism to enable new avenues of research in AD prevention and treatment in individuals with DS. Specifically, we will recruit a well characterized sample of 40 adults with DS for enrollment into collaborating studies. All participants will undergo clinical testing by our clinical core using the NACC DS module which will allow them to be enrolled in a DS registry and available for enrollment in both national cohorts and investigator-initiated trials. Secondarily, to prepare for collaboration with national cohorts and future investigator-initiated trials we will recruit 20 participants from our DS cohort to participate in a trial readiness cohort where we will collect an expanded cognitive battery, blood sample, and neuroimaging assessments (MRI, amyloid PET, and tau PET) harmonized to the methods employed in the Alzheimer’s Biomarker Consortium- Down Syndrome (ABC-DS). Additionally, we will collect metabolic factors such as physical activity, aerobic fitness, body composition, and dietary intake. Creating a dedicated infrastructure and refining our data collection capabilities will enable the KU ADRC to advance local and national studies in DS and dementia and accelerate new avenues of research into the role of metabolism in brain aging and AD in the DS patient.

PROJECT NARRATIVE Most adults with Down syndrome (DS) will develop pathology associated with Alzheimer's disease (AD). However, people with DS have traditionally been left out of many of the national Alzheimer’s Disease Research Centers (ADRCs) clinical cohorts and are not included in state-of-the-art trials developed to prevent, delay, or treat AD. Support through this Administrative Supplement will allow us to develop a Down Syndrome cohort within the clinical core at the KU ADRC, which will provide the infrastructure to study AD in people with DS.