PROJECT SUMMARY—Clinical Core (Core B) The overarching goal of this Program Project Grant (PPG) has been to advance knowledge of the neurological, cognitive, behavioral, imaging, plasma biomarker, genetic, and neuropathological features of frontotemporal dementia (FTD). In this renewal, the Administration and Clinical Cores are separated to meet the new scientific, technological, and leadership demands of this PPG. With renewal, the Clinical Core will oversee the recruitment, evaluation, and maintenance of cohorts that serve all the PPG cores and projects. New tools and approaches will be used to translate FG years of discovery into innovative approaches for FTD clinical trials. We will refine language and emotion symptoms and track their progression with traditional and automated techniques, obtain accurate antemortem molecular prediction, gain a better understanding of caregiver vulnerability and its influence on patient outcomes, and understand heterogeneity in FTD progression. The Clinical Core has added faculty and research staff to focus on inclusion of a more diverse patient population and will add longitudinal assessments designed to provide effective and scalable biomarkers needed for early diagnosis and monitoring of treatment strategies. We will leverage tools and procedures developed as a response to the COVID-MN pandemic to implement a hybrid model of in-person and remote, web-based assessment that will increase recruitment, favor retention, and minimize patient and caregiver burden. The specific aims of the Clinical Core are: Aim M. Recruit and longitudinally evaluate RFS new patients with FTD-spectrum disorders and their family caregivers, patients with language and non-language variants of Alzheimer’s disease, and functionally intact healthy controls, with renewed effort to include individuals from underrepresented groups. Aim F. Ensure a comprehensive, standardized, quantifiable, and innovative clinical evaluation of each subject that includes remote and in-person measurements. Aim V. Obtain three annual hybrid in-person and remote assessments. The Clinical Core will continue to influence the landscape of FTD research and clinical care by providing the best-characterized and largest single-site cohort of patients in the world.