PROJECT SUMMARY/ABSTRACT The 75-90% lifetime risk of Alzheimer’s disease (AD) in Down syndrome (DS) is a significant health concern for the DS community. Despite the progress of large international consortiums preparing the field for upcoming clinical trials, there are currently no validated remote assessment options for tracking AD-related cognitive decline for adults with DS. Remote assessment offers numerous benefits to participants and researchers and will support recruitment and retention in AD clinical trials, which involve many study visits to assess cognitive and behavioral changes throughout a pharmaceutical or behavioral intervention. Additionally, remote assessment will enhance the accuracy of longitudinal research studies by allowing more frequent data collection without significantly increasing participant burden. Using remote assessments will open participation to those in rural communities, those with low economic statuses, and racial/ethnic groups who may not have the time or resources for the travel and cost that in-person participation requires. This study will focus on the life stage when AD pathology is beginning (22 – 55 years old) to ensure that those in beginning stages of disease progression are included in the study sample. All cognitive measures selected to transition from in- person to remote administration have been shown to be promising for tracking early AD. The K99 phase of the study will focus on the feasibility and modification of remote administration to ensure families are satisfied with remote assessment procedures. The R00 phase will focus on evaluating the reliability and validity of remote measures by comparing performance to in-person assessments, investigating test-retest performance, and measuring change over 16 months. The R00 phase will also include a blood draw to examine associations between cognitive measures and plasma AD biomarkers. Methodology is innovative in that it involves a new frontier of remote assessment tools and incorporates plasma biomarkers of AD to compare remote and in- person cognitive performance to AD pathology. There are three primary aims of the proposed study (1) Develop and test the feasibility and acceptability of remote assessments to measure AD-related cognitive decline in adults with DS, (2) Evaluate the reliability of each remote AD cognitive assessment and construct validity with in-person cognitive assessments, and (3) Determine sensitivity of remote and in-person AD cognitive assessments to plasma biomarkers of AD pathology. This project’s goals are aligned with the NIH INCLUDE (INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE) initiative and will serve to increase measurement options for treatment studies in AD and DS and subsequently improve reach and representation of diverse individuals in clinical trials and DS research.