Abstract The Clinical Core serves the USC ADRC’s themes, cerebrovascular and metabolic contributions to cognitive impairment; vascular and metabolic risk factors in cognitive decline; Alzheimer pathogenesis; and the prevention and treatment of Alzheimer-related disorders. The Core’s three overarching objectives are to: 1) develop and maintain a vascular risk factors cohort; 2) catalyze local, clinical and translational research, including early phase clinical trials; 3) provide expertise in vascular disease, biomarkers, and imaging to national collaborative initiatives. The Core addresses many important goals of the 2011 National Alzheimer Project Act (NAPA): translational tools, infrastructure, trial design and conduct, novel drug targets, research on caregiver support, recruitment and citizen engagement, biomarkers, health disparities, data sharing, and enabling technologies. The Core enrolls and retains the primary ADRC cohorts, i.e., the Vascular Cohort Study, Brain Research (autopsy) Study, and participants co-enrolled in Affiliated-Studies. The core performs standard evaluations and diagnoses, oversees neuroimaging and blood and CSF biomarker collection. For this renewal, the core plans to increase the vascular cohort, enrollment for autopsy, and Latinx participation; and continue to provide infrastructure for over 25 ADRC-affiliated, independently-funded research studies including USC Investigator- initiated NIH-funded clinical studies. The core is an integrated, collaborative team, including physicians (Lon Schneider, Helena Chui, John Ringman, Elizabeth Joe, Sonia Pawluczyk), neuropsychologists (Lina D’Orazio, Carol McCleary), and other investigators (Hussein Yassine, Judy Pa, Michael Harrington). Its specific aims are to: 1) collaborate with the other ADRC cores to support the ADRC’s central theme by recruiting and maintaining the vascular risk cohort; 2) recruit and maintain an ethnically diverse cohort focusing on Latinx individuals and emphasizing vascular and metabolic risk, ADRC participation, and affiliated funded studies; 3) recruit and maintain a the Brain Research Study cohort and work with other cores to share specimens; 4) perform annual NACC Uniform Data Set (UDS) evaluations, submit data to NACC, promote an integrated national database, facilitate collaborative research and data sharing; 5) advance USC’s participation and leadership in national collaborative studies by recruiting, retaining participants in ADRC-affiliated national and multicenter projects; 6) enhance recruitment and promote dementia prevention efforts and translational research opportunities in collaboration with the ORE core that particularly includes participants from Latinx and underrepresented groups, and from the USC California-funded Alzheimer’s Disease Centers (CADC), and Roybal Comprehensive Healthcare Clinic; and 7) support neuroimaging and biofluid biomarker studies.