Accelerating real-world prediction and research in Alzheimer's: The M3AD study

Chronic diseases, including Alzheimer's disease (AD) and related dementia (ADRD), do not exist solely as isolated entities. Instead, they weave concomitant trajectories of multiple diseases, conditions, behaviors, and risks, mutually influencing each other's course and natural history, in ways yet unexplored. Electronic health records (EHRs) provide us with a unique opportunity to look at related and unrelated clinical trajectories over time, thus potentially providing insight into unrecognized prodromes, while incorporating the complexities of patients' lives. We harmonize and federate a three-city EHR metaplatform of nearly 10 million patients (∼60,000 with AD/ADRD), which we further embed within census tracts, to contextualize these health trajectories. Our multidisciplinary approach ambitions a unique dynamic platform to inform strategies to tailor risk prediction, complex clinical management, and real-world evaluation of future treatments of AD/ADRD. We present the rationale for and design of the Multimorbidity Three-City Alzheimer's Disease EHR (M3AD) Study and real-world data metaplatform, progress and demonstration of feasibility, its expected singular and complementary contributions to the field. HIGHLIGHTS: Our success in living longer lives often brings chronic conditions and multimorbidity. Alzheimer's research should comprise life trajectories' complexity in multimorbidity. New real-world analytical approaches allow integrated prediction of Alzheimer's disease. We are building a three-city electronic health record (EHR) metaplatform for prediction, prevention, and impact We further embed EHR within census tracts to contextualize Alzheimer's trajectories.