Clinical Core: Summary/Abstract The Clinical Core serves two primary functions for the ADNI project: day-to-day coordination of all clinical activities at the ADNI sites, and oversight of the scientific clinical aims. Project management, regulatory oversight, site management and monitoring, clinical data collection and management and site contracting are managed at the USC Alzheimer’s Therapeutic Research Center (ATRI), which also coordinates the NIA Alzheimer’s Clinical Trials Consortium; ADNI procedures mirror the ATRI clinical trials procedures. Overall direction to the scientific aims of the Clinical Core, focused on the study of relationships among the cognitive, clinical, biofluid and imaging markers of AD to inform therapeutic trial design are jointly led by Drs. Ron Petersen at the Mayo Clinic and Paul Aisen at USC. To maintain the value of the longstanding ADNI cohorts, the Clinical Core will focus on retention and continued follow-up of the ADNI3 cognitively normal (CN) participants and those with mild cognitive impairment (MCI) or dementia. New participants will be recruited from a web-based cohort utilizing plasma assays of AD neurobiology. The Clinical Core will collaborate closely with the new Engagement Core to assure that 50-60% of new participants will be from under-represented populations (URPs; e.g., Black, Latinx; low socioeconomic status). Almost all ADNI3 assessments will be continued in ADNI4 to preserve the rich longitudinal dataset, but novel web-based unsupervised computerized cognitive assessments and new sociocultural measures will be added in ADNI4. The scientific aims of the Clinical Core include continued characterization of the cross-sectional features and longitudinal trajectories of CN and MCI participants, including those who progress to dementia; assessment of the cross-sectional and predictive value of remote and in-person cognitive assessments along with plasma amyloid, phosphorylated tau and neurodegeneration assays; and application of these findings to optimal clinical trial designs.