Digital Evaluations and Technologies Enabling Clinical Translation for AD

To achieve this objective, we propose the DETECT-AD (Digital Evaluations and Technologies Enabling Clinical Translation for AD) Study. DETECT-AD is a prospective trial simulation study using a current, extensible, sharable, technology agnostic, and home-based assessment platform that continuously generates DBs and metrics of everyday cognition and function (or Daily Indicators of Active Life - 'DIALS'). The platform also allows for remote capture of conventional clinical assessments as well. A simulated trial study design is used, as there are no current established therapies that will reliably improve meaningful function in stage 1-3 AD10 patients to a degree that one can directly test the sensitivity of DBs or DIALS to treatment mediated change. In short, if there is no change over time in the proposed measure, one would not know if it was a failure of the measure or the treatment. Hence, the use of the simulation paradigm. In this trial, participants with known CNS amyloid (Aβ) status (SUVR-based PET "positive" or "negative") will be enrolled. In the simulation, Aβ "positive" (higher amyloid burden) patients will predictably progress, as if they were receiving placebo; those with less amyloid (Aβ "negative") will have less progression, simulating effective treatment. Primary outcomes will be the change in DBs and DIALS composed of measures in 4 key domains: mobility, cognition, sleep, and socialization. Exploratory analyses of the relationship of the DBs with contemporary imaging (MRI) and blood-based biomarkers related to inflammation, neurodegeneration, vascular risk or injury, and nutritional health will also be conducted. Impact: Successful completion of this study will provide foundational validated DB and DIALS data improving treatment response readout sensitivity, thus advancing AD clinical trial capability and capacity. The intent is to not only validate a single app or device, but to advance ecologically valid multi-domain assessment, as well as an entire trials-environment specific, DB-facilitated protocol that could be adapted and shared for use by any clinical trial or related study going forward.