Global Alzheimer's Platform Trial-Ready Cohort For Preclinical/Prodromal Alzheimer's Disease: Infrastructure

GAP/TRC-PAD Overarching Aim: The goal of the Global Alzheimer’s Platform (GAP) Trial Ready Cohort for Prevention of Alzheimer’s Disease (TRC-PAD) initiative is to accelerate drug development for AD through establishment of an infrastructure to ensure timely recruitment of targeted individuals into optimally-designed trials. The specific goal is to establish a trial-ready cohort (initial n=2000, 1000 preclinical and 1000 prodromal) at ~35 sites across the US, to facilitate recruitment into preclinical and prodromal AD cognitive-endpoint trials Operational aims: 1. Establish feeder registries connected (with transfer of data) to GAP registry; web-based consent 2. Optimize transition from GAP registry to GAP cohort, with validation of web-based consent and cognitive testing 3. Optimize and implement site characteristics 4. Optimize and implement network characteristics 5. Achieve timeline goals: shorten time to site activation for trials, markedly accelerate recruitment 6. Reduce expense and reduce screen failures; improve retention in clinical trials 7. Reduce unexplained variance in cognitive testing through optimal training, certification, informatics and monitoring Scientific Aims and hypotheses: 1. Web-based mechanisms feeding an in-person trial-ready cohort can attract and maintain potential participants for preclinical and prodromal AD trials, accelerating the drug development process. 2. Assessment of e-consent: in-person validation will confirm the reliability of an con-based remote informed consent process 3. Validation of web-based cognitive assessment: of episodic memory and executive function correlates closely with standard in-person cognitive assessment 4. Utility of longitudinal remote cognitive assessment: web-based cognitive performance and self-reported symptom trajectories predict subsequent decline in cognition and self-reported outcomes 5. Evaluation of adaptive risk scoring: analysis of remotely-collected demographic, lifestyle, cognitive and genetic factors increases prevalence of amyloid positivity in risk-identified older, non-demented individuals, reducing costly screen failures. Future Aims: 1. Design and implement proof of concept and confirmatory trial designs that take full advantage of the TRC-PAD infrastructure 2. Establish a business model for long-term sustainability based on dual mechanisms of financial support from pharmaceutical companies: upfront investment in the infrastructure plus trial enrollment-based reimbursement