PROJECT SUMMARY – CLINICAL CORE The Mayo ADRC is comprised of two sites: Mayo Clinic Rochester (MCR) and Mayo Clinic Florida (MCF) that have collaborated closely for the past 30 years. Following the theme of expanded phenotyping to characterize multi-etiology contributions to later life cognitive impairment, the Mayo ADRC will take advantage of our long- standing interests and involvement in Alzheimer Disease (AD), frontotemporal lobar degeneration (FTLD), and Lewy Body Disease (LBD) spectrum disorders to provide the clinical and logistical infrastructure needed to support the many clinical projects in which Mayo investigators are involved. We have expanded our characterization of the cerebrovascular contribution to cognitive impairment (VCID). Each of these disease entities are represented in joint engagement by the Clinical Core of the ADRC and separate NIH-funded multi- center investigations (ADNI, DLB-U01, NAPS, LEADS, ALLFTD, Mark-VCID2). The Clinical Core also works closely with the ORE Core, with the MCF Clinical Core unit will continue its very successful focus on enrolling cognitively unimpaired African American/Black participants and, more recently, Hispanic/Latino participants, as well as individuals from those communities with AD/ADRD. The MCR Clinical Core along with the ORE Core will continue to focus on recruitment of persons from rural areas, an effort that has long been a strength of the MCR site of this ADRC. The Clinical Core behavioral neurologists perform full clinical evaluations, while study coordinators perform detailed interviews with knowledgeable informants that include functional assessments, review of medical history and medications and assessments of structural and social determinants of health. All participants undergo neuropsychological testing with trained psychometric technicians that is reviewed by ADRC neuropsychologists. The Clinical Core operates in close coordination with the Neuroimaging Core to obtain and interpret MRI, amyloid PET, tau PET, FDG PET and DAT scans in a large proportion of our participants. With the rapid developments in plasma biomarkers, the Clinical Core will also be operating in close collaboration the Genomics and Biomarker Cores for obtaining blood and CSF and performing biomarker assays including expansion of our multiomics capabilities. We will phenotype all participants and render diagnoses that are reviewed at our regular consensus conferences at each site. Several times a year, joint MCR and MCF consensus conferences are held to standardize our approach across sites and ensure data harmonization. Clinical Core physicians are primarily responsible for presenting the case to participants to allow post-mortem neuropathological examinations. The Clinical Core clinicians and the Neuropathology Core physicians meet biweekly to conduct clinico-pathological conferences. At those conferences, clinical, imaging, and more recently biofluid studies are reviewed and compared to neuropatholo...