PROJECT SUMMARY/ABSTRACT CLINICAL CORE There is now abundant evidence that the pathology of Alzheimer's disease and related disorders (collectively referred to as AD) begins decades before the onset of clinical symptoms. This prodromal, preclinical period, while appearing cognitively and functionally silent is in fact associated with robust changes that may be detected by biomarkers and presents an ideal opportunity for early detection and intervention. To do this, we have taken the lead in developing and validating novel and innovative clinical-cognitive-behavioral measurements to identify individuals at-risk and combine these findings with state-of-art biomarker studies. The NYU ADC current research focus is on individuals with NIA-AA Stages 1 to 3 (particular focus on subjective memory complaints, CSF and imaging biomarkers, and physical functionality): preclinical disease, MCI, and mild AD compared with healthy aging (NIA-AA preclinical stage 0). The overall goal of the Clinical Core is to provide accurate research diagnoses for a cohort of longitudinally followed older adults to autopsy to provide appropriate subjects and subject-derived materials for research projects conducted by ADC investigators and collaborating scientists. This focus directly serves the primary research theme of the NYU ADC: the characterization of preclinical AD and its transition to MCI and early AD. We propose 8 Specific Aims: (1) Maintain and characterize an active UDS cohort of ~400 individuals (Clinical Dementia Rating [CDR] 0 50% of cohort), MCI (CDR 0.5 30% of cohort), or mild AD (CDR 0.5 or 1 20% of cohort); (2) Recruit, assess, and retain new participants (~45) from diverse backgrounds to replenish the cohort in proportion to attritional losses; (3) Provide culturally-sensitive recruitment strategies and longitudinal research assessments; (4) Collect, store, and distribute CSF, blood, and DNA biospecimens; (5) Obtain consent for brain donations; (6) Provide appropriate subjects, data, and biospecimens for research studies; (7) Integrate data collection and quality control procedures; and (8) provide infrastructure, resources, and coordinate contribution to NACC and other national and international collaborations. By providing a wealth of standardized longitudinal clinical, cognitive, biomarker, and neuroimaging data to investigators, the NYU ADC Clinical Core is poised to play a significant role in providing the infrastructure and resources necessary to advance our understanding of preclinical AD and its transition to the symptomatic stages of MCI and mild AD.