SUMMARY/ABSTRACT: Project 4 Precision Methods for Assessing Brain Health and Age-related Cognitive Impairment and AD Combatting the growing public health and societal burdens associated with age-related cognitive impairment (ARCI) and cognitive decline will not be easy. What is needed are reliable risk assessment, early detection, and ultimately, intervention strategies for maintaining cognitive health at older ages. The development and implementation of such strategies are complicated by the number, complexity, and heterogeneous nature of the factors that contribute to ARCI. To understand this complexity, it will be necessary to collect and integrate different sources of information. These data will come from large samples of longitudinally characterized individuals through the use of assays designed to interrogate phenomena such as molecular, genetic, physiological, biometric, clinical, psychometric, social, lifestyle, and environmental factors. In addition, appropriate methods for integrating the data obtained from these assays and drawing comprehensive yet compelling inferences are essential. The research to be pursued in the proposed Precision Aging Network (PAN) will involve collecting comprehensive data on 1,620 older individuals face-to-face and over 50,000 individuals tracked longitudinally who are cognitively characterized based on a set of validated online tests. PAN Project 4 “Precision methods for assessing brain health and age-related cognitive impairment” is devoted to integrating these data, along with complementary data from the public domain, using a suite of techniques designed to identify factors contributing to the maintenance or vulnerability of cognitive function in the face of aging, Alzheimer’s disease (AD), and AD-related dementias (ADRD). Project 4 will work with Project 2 to explore predictive models of cognitive decline, as well as Project 3 to identify preventive and therapeutic targets. Data are to be generated as part of the Molecular Profiling (MP) Core, Cognitive Assessment and Neuroimaging (CAN) Core, and the Non-Invasive Technology (NIT) Core – all in the service of the large-scale human cohort studies to be pursued in Projects 1 - 3 of the proposed research. Project 4 will work closely with members of the Data Science (DS) Core to ensure that all data collected and analyzed across all Projects and Cores funnel seamlessly into a pipeline that will allow for reliable model building. Project 4 deliverables, which are meant to seed potential products to be used to combat ARCI and age-related cognitive decline, include prediction models to classify individuals into subgroups more amenable to possible interventional strategies; long-term prognostic models that suggest activities or daily living strategies to maintain cognitive health; monitoring strategies for individuals exhibiting cognitive changes that could be implemented on a mobile device; markers for intervention efficacy as well as potential drug targets and...