The Alzheimer's Prevention Initiative (API) Colombia Trial is a collaborative project involving the Neurosciences Group of Antioquia (GNA), Genentech/Roche, and the Banner Alzheimer's Institute studying whether crenezumab can delay or prevent the clinical onset of Alzheimer's disease in asymptomatic individuals who carry the PSEN1 E280A mutation. In an effort to optimize participant compliance and adherence, and maintain interest in the trial for its duration, the GNA developed an “Adherence/Retention Plan.” This Plan identifies potential barriers related to characteristic of participants and study partners, protocol design, sponsors, investigators, contextual and environment factors, and characteristics of this population in general. GNA designed and implemented a number of strategies including: a carefully designed schedule of visits and assessments, appointment reminders, reimbursement for transportation and missed work, meals during study procedures, birthday cards, quarterly newsletters, annual in-person feedback meetings, provision of a health plan to participants and a social plan to family members. In the context of health care in Colombia, we determined that a study-related health plan was needed to ensure timely evaluation, treatment and follow up of adverse events, conduct additional testing if needed, offer contraception, and provide gynecological and other specialist evaluations for participants in instances where their standard medical care could not address health concerns in a timely way or at all. The social plan consists of programs/workshops to assist affected individuals and their families, provide coping strategies, support their participation in relevant research, and improve the quality of their lives. The social plan does not benefit trial participants directly and all services are provided whether or not family members participate in GNA research. All strategies are approved by a local Ethics Committee, reevaluated using an annual survey and adjusted according to the needs of participants, investigators and to the experience gained during the study. By the end of third year, the trial, retention of participants is 96.6% and 80.3% of participants report feeling “very satisfied” with their experience. The Adherence/Retention Plan plays a crucial role in maintaining adherence and compliance needed to achieve the ambitious goals of the Colombian API Autosomal Dominant Alzheimer's Disease Trial.