ABSTRACT Down syndrome (DS) is the most common genetically defined cause of intellectual disability and a major cause of early-onset Alzheimer’s disease (AD)-type dementia. Recently, we concluded and published the results of a randomized phase II trial of 16-week treatment with the AD drug memantine (the follow-up memantine trial) in which we investigated the safety and efficacy of this drug on cognitive and adaptive test results in adolescents and young adults with DS. This study was performed between May 13, 2015 and July 22, 2020. In total, 185 participants with Down syndrome were assessed for eligibility and 160 (86%) were randomly assigned either memantine (n=81) or placebo (n=79), which makes it one of the largest clinical trials in the field of DS to date. Participants (aged 15–32 years) with either trisomy 21 or complete unbalanced translocation of chromosome 21 and in general good health were recruited from the community at one site in Cleveland, Ohio, and another in São Paulo, Brazil. Although the trial found no evidence of cognitive-enhancing effects of the standard dose of memantine treatment in the study participants, hypothesis-generating, exploratory analysis in that work pointed toward the need of memantine doses higher than those typically used in patients with AD to produce significant cognitive-enhancing effects in healthy adolescents and young adults with DS. In addition to information on drug effects, this study generated a comprehensive array of neuropsychological and clinical data in a large and diverse set of individuals with DS. The trial protocol also included (as exploratory parallel experiments) collection of evoked electroencephalographic (EEG) data to test auditory brainstem responses and mismatch negativity before and after memantine treatment and quantification of plasma biomarkers of AD at the final visit of the study. Here, we propose to perform analyses on the relationships between scores in the various neuropsychological measures and the EEG and AD biomarker assessments and to share the de- identified data with the community. Accordingly, this project has three specific aims: (1) Analyze the EEG and plasma AD biomarker data generated in the follow-up memantine trial and study their relationship with scores of neuropsychological assessments; (2) Build a comprehensive database of all clinical, neuropsychological, electrophysiological, and biomarker data from the follow-up memantine trial; and (3) Contribute the database to the NIH-funded INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE (INCLUDE) Project through the INCLUDE Data Coordinating Center (DCC). Transferring all the data collected from the follow-up memantine trial will represent a significant contribution to Component 2 of the INCLUDE project, which involves the “Assembly of a large cohort of individuals with Down syndrome across the lifespan to perform deep phenotyping and study co-existing conditions.”