PROJECT SUMMARY Alzheimer’s disease and related dementias (ADRD) are a leading cause of neurological disability, causing devastating impairments in cognition and functional capacity . Although there has been considerable progress in identifying mechanisms underlying ADRD, and symptomatic treatment is available for some ADRD, there is urgent need for greater understanding of the mechanisms underlying these dementias to identify potential treatment targets and to contribute to successful treatment trials. Because of its ability to resolve brain structure and function noninvasively, neuroimaging has become a leading strategy used for translational research in ADRD and a prominent biomarker strategy for clinical differential diagnosis of ADRD, for defining preclinical stages of ADRD, and for evaluating for target engagement and therapeutic responses in trials. Modern neuroimaging is an inherently interdisciplinary field combining expertise in physics, chemistry, engineering, computer science, neuroscience, and statistics to localize and quantify a large array of metrics reflecting the molecular, cellular, structural, functional, and physiological properties of the central nervous system. Additional expertise in topics such as genomics, proteomics, metabolomics, neuropharmacology, psychology, and neuromodulation are also required to optimally combine or apply neuroimaging with other key areas in ADRD research. Finally, because of its multidimensional nature, neuroimaging is a “big data” field requiring expertise in informatics and data management. The University of Pennsylvania has a longstanding track record of innovation and translation in biomedical neuroimaging in ADRD, and supports state-of-the-art instrumentation for in vivo MRI, PET, CT, and optical imaging in both humans and preclinical models as well as extensive expertise and resources in image processing and spatiotemporal statistics. In response to PAR-21-112 the proposed “Cross-disciplinary training program in translational neuroimaging of ADRD” will draw predoctoral and postdoctoral trainees from both biological and quantitative science backgrounds who are seeking a research career focusing on neuroimaging in ADRD. A core curriculum covering neuroimaging methods will be combined with specializations in 1) imaging studies of disease mechanism, 2) imaging biomarkers and neuroimaging trials, or 3) statistical and computational approaches to neuroimaging data. A diverse faculty with outstanding track records of research and mentoring in neuroimaging and related fields will participate, with each trainee receiving dual mentorship from faculty with complementary expertise. The aims of the proposed training program are 1) to train the next generation of ADRD neuroimaging researchers, 2) to increase diversity in neuroimaging research through efforts to increase diversity in both program trainees and program faculty, 3) to expand local ADRD neuroimaging research through participation of training ...