Project Summary The theme of the Cleveland Alzheimer's Disease Center (CADRC) is focused on understanding the clinical and pathologic heterogeneity observed in Alzheimer's disease (AD) and the AD-related dementias (ADRD), which is in alignment with the broader goal of the National Alzheimer's Plan Act (NAPA). The Clinical Core (CC) and Clinical Core Registry (CCR), a key resource of the CADRC, focus on several populations that can provide special insights into this broad goal. The process of meeting this goal encompasses the major activities of the CC, which include enrolling, characterizing, and following longitudinally a diverse population of older individuals in the CCR (Specific Aims 1,2). Extensive interactions of the CC with other cores are essential for the function of the CADRC and to meet this important goal. The diverse populations targeted for furthering this goal include participants with Mild Cognitive Impairment/AD, dementia with Lewy bodies, Atypical AD dementias (Rapidly progressive/Cortical Variant AD), and a cohort of cognitively normal controls with a large proportion having at least one APOE e4 allele. A strong minority recruitment effort spanning multiple community- and clinic-based approaches is outlined and builds upon the experience of the investigators working with this community, and across cores, especially the Outreach, Recruitment, and Engagement Core (Specific Aim 6). The CC team works with the Data Management and Statistics Core to store data to facilitate future research and to share data with the National Alzheimer's Coordinating Center in a timely manner (Specific Aim 5). The CC is the starting point for collection of biomarker, imaging and post-mortem autopsies to advance our understanding of brain-behavior relationships by coordination with the Neuroimaging, Biomarker and Neuropathology Cores. This involves the collection from CCR participants of blood and cerebral spinal fluid biomarkers, 3T and 7T brain MRI and Amyloid PET imaging, and obtaining consent for post-mortem neuropathology examination with brain autopsy across all of these diverse cohorts in a culturally sensitive and efficient manner (Specific Aims 3,4). The CC is committed to support future Administrative Core development projects and the Translational Therapeutics Core and the Research Education Component in their mission to support basic scientist investigators both locally, nationally, and internationally, and training the next generation of basic and clinical science researchers (Specific Aims 7,8). Overall, the CC contributes to understanding AD in its fullest extent across cultures and its varied clinical forms, while providing vital infrastructure for the basic, social, and clinical researchers in our larger medical community.