Alzheimer Biomarker Consortium - Down Syndrome (ABC-DS) - Supplement

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Abstract Alzheimer disease (AD) is the most common cause of dementia in the general population and the number of people living with AD is increasing rapidly. As the focus of pharmacologic treatment of AD has shifted toward prevention trials, there has been increased interest in individuals who have biomarkers (e.g., the ApoE4 allele) that place them at greater risk for dementia. One group of particular interest is adults with Down syndrome (DS), almost all of whom will be diagnosed with AD by the age of 70. Virtually all people with DS develop significant AD neuropathology, especially amyloid plaques by middle age. Early accumulation of amyloid plaques is thought to arise from overproduction of AE, which is derived from the E-amyloid precursor protein; the gene for E-amyloid precursor protein (APP) is located on the trisomic chromosome 21. While the mean age for developing AD among adults with DS is approximately 53 years, there is considerable variability in the age of onset, ranging from prior to age 40 to over age 70. Therefore, other factors such as genetics, lifestyle, and comorbid health issues likely contribute to the age of individual AD onset. In this supplement, “The ABC-DS: Administrative Supplement on Gait,” we propose to leverage the currently funded Alzheimer's Biomarker Consortium – Down Syndrome study (ABC-DS) to pilot a project focusing on gait as a possible clinical biomarker for dementia in the DS population. We propose to conduct a cross-sectional study using state-of-the-art assessment of dual-task gait measures among a cohort of 140 individuals with DS who are serving as participants in the ABC-DS. The ABC-DS has been following over 400 adults with DS since 2015 and was recently re-funded to increase this cohort to 550 individuals. Results will demonstrate the feasibility of conducting gait assessments across ABC-DS sites and to compare the findings with other AD biomarkers. In addition, this will provide the opportunity to assess additional dual-tasks that may be more sensitive across the entire IQ range (i.e., borderline to severe ID) and to provide the necessary pilot data to conduct a power analysis for a future R01 submission. Finally, the pilot will provide a rich dataset that can be shared and made available to other researchers and permit the testing of hypotheses related to the Projects in U19AG068054.