ABSTRACT - Clinical Core The Clinical Core is critical to the mission of the Duke/UNC Alzheimer’s Disease Research Center, given its role in recruiting, clinically characterizing, and following a diverse group of individuals that will provide participants, biomarker data and brain tissue to investigators working on Alzheimer’s disease (AD) at Duke and UNC. Although we support investigators pursuing any research on AD or Alzheimer’s disease-related dementias (AD+ADRD), the particular focus of the Core relates to the Center’s theme of identifying changes across the lifespan, including the onset of comorbidities and cellular and molecular changes associated with aging, that influence the development, progression, or experience of AD. A related goal is to assist national efforts to understand the increased prevalence of memory disorders in minority and rural populations. The Clinical Core will develop and maintain a prospectively followed cohort of 420 research participants, ages 45 to 80, supplemented with a one-time evaluation of 120 younger participants, allowing our center to investigate age- related drivers of AD (Aim 1); the cohort will have substantial rural and African-American enrollment, allowing us to address known disparities related to AD. The Longitudinal Cohort (n=420) will consist of 320 participants who are cognitively normal at entry and roughly equal in distribution between ages 45 to 80, and with at least 100 participants symptomatic at entry (MCI or dementia). This cohort will enable us to observe key transition periods related to AD risk, including menopause, onset of comorbidities, and the transition to MCI and dementia. This cohort design will also allow us to supply Duke and UNC investigators with symptomatic and normal participants from the outset of the study. The second, Young Cohort (n=120) will consist of participants ages 25-44 who will undergo a one-time evaluation and biomarker collection. The availability of this unique comparison group, which is supported almost entirely by institutional funding, will enable investigators to evaluate the degree to which novel biomarkers or signatures associated with AD in older cohorts are linked to other contributing factors, such as age or genetic risk. The Clinical Core will perform UDS-based medical, neurologic, psychiatric, and neuropsychological evaluations (Aim 2). In addition, working with the Biomarker Core, the Clinical Core will facilitate the collection of blood and cerebrospinal fluid specimens, brain MRI and PET scans, and motor-sensory assessments including retinal imaging to enable discovery of novel biomarkers (Aim 3). The Core will also develop and utilize novel and portable testing modalities. The Clinical Core, with the assistance of the Outreach, Recruitment, and Engagement Core (autopsy consent) and Neuropathology Core (brain recovery), will facilitate collection of brain tissue obtained at the time of death (Aim 4). The Core will interact with the Data Managem...