PROJECT SUMMARY People with Down syndrome (DS) evidence an overproduction of amyloid-beta (Aβ), due to having three copies of chromosome 21. With age, Aβ aggregates into extracellular brain plaques, which is a hallmark feature of Alzheimer’s disease (AD); however, there is variability in the age at which this AD pathology begins and how clinical AD symptomology unfolds in DS. Stressful life experiences, both in childhood and in adulthood, are associated with aging-related cognitive decline and risk of sporadic late onset AD outside of DS. Stressful life experiences may exacerbate AD pathology and/or its effects on cognition through inflammation, and/or by contributing to conditions (e.g., obesity, cardiovascular disease, depression, sleep disorders) that are known risk factors for AD. The goal of the Administrative Supplement, “Life Stressors and Alzheimer’s Disease in Down syndrome,” is to expand on the R01AG70028 “Lifestyle Risk and Resiliency Factors and Alzheimer’s Disease in Down syndrome” project to examine the effect of adverse childhood events (e.g., parent divorce, abuse/neglect, poverty) and recent life stressors (e.g., job termination, new staff, death of family member) on the timing of AD pathology and symptomology in people with Down syndrome. Specifically, this supplement will: 1) include a new measure into the Lifestyle R01 protocol to capture adverse childhood experiences (ACEs); 2) use a new coding technique to capture stressful life events in adulthood; and 3) conduct new analyses to determine the association between stressful childhood and adult life experiences and AD imaging and biofluid biomarkers and cognitive impairments. The parent R01 follows 180 adults with DS who are co-enrolled in the NIH-funded Alzheimer’s Biomarker Consortium in DS (ABC-DS), in which AD biomarkers (e.g., PET Aβ, and tau, CSF Aβ42, and plasma p-tau 217), cognitive functioning, and dementia status are collected. The parent Lifestyle R01 collects three time points of data, aligning with ABC-DS cycles, and focuses on four modifiable lifestyle factors – physical activity, sleep, cognitive stimulation, and social engagement. The “Life Stressors and Alzheimer’s Disease in Down syndrome” Administrative Supplement will build on these aims by generating novel and significant information on the effect of life stressors on AD in DS that can drive social policy and interventions in the future.

PROJECT NARRATIVE The goal of this Administrative Supplement is to expand on the parent R01AG70028 “Lifestyle Risk and Resiliency Factors and Alzheimer’s Disease in Down syndrome” project by examining the effect of adverse childhood events (e.g., parent divorce, abuse/neglect, poverty) and recent life stressors (e.g., job termination, new staff, death of family member) on the timing of Alzheimer’s disease pathology and symptomology in people with Down syndrome. To accomplish this goal, the current project will include a new measure into the Lifestyle R01 protocol to capture adverse childhood experiences (ACEs); 2) use a new coding technique to capture stressful life events in adulthood; and 3) conduct new analyses to determine the association between stressful childhood and adult life experiences and Alzheimer’s disease imaging and biofluid biomarkers and cognitive performance measures. These analyses will investigate the direct effect of stressful life experiences on biomarkers of Alzheimer’s disease and cognitive impairments and the indirect effects through inflammation (e.g., plasma IL-6) and co-occurring health conditions (e.g., obesity, depression, cardiovascular disease, and disordered sleep).