Core D: Cognition, Exposure, and Covariates (CEC) Data Core

COGNITION, EXPOSURE, AND COVARIATES DATA CORE REVISED SUMMARY The TIME-AD project will use multiple data sources to enhance understanding of how AD/ADRD risk is affected by four high priority risk factor categories: alcohol use; depression and anti-depressant medications; prevention and treatment of hearing and vision impairments; and social isolation. The Cognition, Exposure, and Covariates (CEC) Data Core is an essential component of TIME-AD and creates critical synergies to make this highly ambitious project feasible. The CEC will provide analytic data sets to each of the four projects, taking advantage of shared resources for the intensive data cleaning, wrangling, and data set construction efforts required, bringing together broad expertise to guide decisions about how to code AD/ADRD-related outcomes, and minimizing the need for each research team to revisit decisions about coding outcomes or covariates. Two major methodologic challenges shared across projects will be tackled within the CEC core. The first is identifying optimal measures of cognitive outcomes and evaluating tradeoffs between measures grounded in clinical diagnoses versus measures based on repeated cognitive assessments in a research setting. Within clinical diagnostic categories, additional nuance is involved in handling dementia etiology (e.g., AD, cerebrovascular) versus all-cause dementia, given the high preponderance of multiple copathologies and limitations of clinical measures to differentiate specific pathologies. The second major methodologic challenge is identifying appropriate covariate sets for time-varying exposures and survival models, to maximize control of confounding, and address selective survival, while avoiding controlling for mediators. Researchers conducting analyses for the four projects will consult with the CEC to ensure analytic data sets reflect topical expertise and are appropriate for each project. The CEC Core team includes experts on each of the data sets, investigators with expertise in methodologic considerations that will guide data set construction (e.g., for emulated trial designs, clinical and neuropsychological outcomes), and leaders who will ensure cross-project compatibility and documentation. The CEC will work in close contact with each of the projects (to ensure the data sets meet the research needs of each project), the Genetic and Policy Data Core (to incorporate the IV measures into the project data sets), the Analytics Core (to ensure the data set structures match the needs of the proposed analyses, e.g., for survival models), and the Maximizing Population Impact Core (to communicate our findings to a range of stakeholders).