Research Project
10274393
PROJECT ABSTRACT Down syndrome (DS), a trisomy of chromosome 21 and the most common genetic cause of intellectual disability, was once a condition in which children would rarely see adulthood. In 1950, the estimated mean life expectancy for a person with DS was 26 years and median age at death was 4 years. With improvements in recognition and treatment of co-occurring conditions of DS, such as congenital heart defects, the estimated median life expectancy in 2010 was 53 years (median age at death was 58). There is now a large and diverse population with DS across all ages who are in dire need of solutions and treatments for medical issues that were inconceivable 60 years ago. Two conditions of high interest that often presage other morbidity, greatly harm quality of life, and lead to premature mortality are obstructive sleep apnea (OSA) and dementia. OSA is an episodic sleep-state collapse of the upper airway which results in reduction or lack of ventilation during sleep and is prevalent in more than half of people with DS. The triplication of chromosome 21 in DS is associated with an overproduction of the amyloid precursor protein and is pivotal to the accelerated development of dementia and Alzheimer's disease. Even when not the proximal cause of death, in post-mortem autopsy nearly all older adults with DS have beta amyloid plaques and neurofibrillary tangles that signify Alzheimer's disease. More needs to be known about causes, course, and the impact of social determinants on these conditions and resulting premature mortality, especially as clinical DS samples are often under powered and often lack participants of color. To meet the directives of the National Institutes of Health's Investigation of Co-occurring conditions across the lifespan in Down syndrome project and the National Institute on Aging's priorities we propose to create Down Syndrome: Towards Optimal Trajectories and Health Equity using Medicaid Analytic eXtract (DS-TO-THE-MAX). DS-TO-THE-MAX will identify a retrospective longitudinal cohort of >100,000 adults with DS and >4,000,000 adults without DS from 10 years of Medicaid Analytic eXtract data plus additional Medicare data for dual enrollees. Our innovation lies in a DS sample orders of magnitude larger than past work, a social determinants of health framework, and novel machine learning and quantitative bias analysis methods. We will complete two aims: 1) Assess epidemiology and social determinants of obstructive sleep apnea, dementia, and mortality 2) Use machine learning to identify risk algorithms for obstructive sleep apnea, dementia, and mortality. The results of this project will strengthen the epidemiologic and public health basis for DS research and population level intervention. In building the DS-TO THE MAX cohort and assessing risk, resilience, social determinants we will have a vital big data set to complement clinical research and work toward the population with DS living long, healthy, and self-determined lives.
