Project Summary/Abstract: Clinical Core The Clinical Core of the UK-ADRC maintains a well-characterized, community-based cohort focused on normal aging and early transitional disease states and follows individuals longitudinally until brain autopsy. We maintain a mandatory autopsy requirement for all subjects (with the exception of our Minority Gateway Clinic, where autopsy is promoted but not required), allowing major contributions in the area of clinical- pathological correlative studies, and definition of early preclinical and pre-dementia disease states. These efforts have been a driving force in our recognition of the heterogeneity of community-acquired dementia, including major contributions to the field in regard to LATE, PART, VCID, and the role these pathologic states play in conjunction with traditional AD, LBD, and FTLD disease states. A major focus of our work has also been on defining early clinical transitions involving the interplay of these disease states that has driven the widespread exploration of late-life multi-etiology dementia syndromes. To further such advances, the UK-ADRC Clinical Core emphasizes deep clinical, biomarker, genetic, and post-mortem phenotyping of a diverse cohort of elderly subjects at high risk for multi-etiology dementia. Major initiatives in the area of AD mimics and transitions from normal to late-life multi-etiology dementia are well-poised to continue to move the field forward in the areas of both diagnosis and translational interventional discoveries. We have introduced exciting new initiatives in our expansion of antemortem biomarker research allowing an even deeper clinical phenotyping of our participants as we work towards translational discoveries for multi-etiology dementia. The UK-ADRC will continue to constantly evolve in dynamic ways through our proposed specific aims. Aim 1: Maintain & longitudinally characterize a central longitudinal cohort enrolling cognitively normal subjects to facilitate our understanding of preclinical disease and early cognitive transitions to multi-etiology MCI & dementia. Aim 2: Maintain and expand our successful Minority Gateway Clinics to maintain and grow our (significantly) above-parity for population minority engagement. Aim 3: Further develop and maintain an infrastructure to support translational therapeutic development through all clinical trial phases in support of NIH, ADCS, ACTC initiatives, industry-sponsored drug trials, and investigator-initiated projects. Aim 4: Foster education and support of research participants and families to ensure that our efforts are clinically meaningful, both in novel prevention studies as well as treatment in established disease Overall, the Clinical Core will continue to provide an infrastructure and environment that will continue to contribute to our success in advancing multidisciplinary, innovative AD research supporting our center theme of Transitions from Normal to Late-Life Multi-Etiology Dementia.