Clinical Core – Project Summary The Clinical Core (CC) is the centerpiece of the Wake Forest Alzheimer’s Disease Research Center (WF ADRC), providing rigorously collected and innovative resources to advance the ADRC themes: to elucidate the factors influencing the transitions from normal aging to MCI and dementia, with special emphasis on understanding the role of vascular and metabolic conditions and health disparities in these transitions. Although in existence for only four years, the CC has surpassed its original enrollment target of 500 participants. As of August 2020, we enrolled 583 participants (20% from underrepresented groups), contributed 1135 UDS3 evaluations and 555 MRI images to NACC, and 295 samples to NCRAD. The CC has also contributed 256 well-characterized participants to clinical studies. Consonant with the WF ADRC focus on early transitions, the cohort is weighted toward cognitively normal adults and participants with MCI, with a smaller number of participants with AD, mixed AD/vascular or other dementias. All participants have been carefully characterized with the UDS3 and MRI, and with specialized metabolic and vascular measures. Many participants have also undergone lumbar puncture, amyloid or tau PET, and mitochondrial analysis. In the coming cycle, we will increase the CC cohort size to follow 600 participants and will introduce a panel of innovative biometric measures relating to sleep, physical activity, glucose metabolism, and vascular function. The CC cohort is well-suited to address WF ADRC themes and provide resources that will contribute to greater understanding of the influence of metabolic/vascular factors and health disparities on ADRD risk. Approximately 70% of CC participants have glucose intolerance or hypertension, as expected given high regional prevalence of these disorders. To facilitate research on the role of health disparities in AD risk, we will work with the Outreach, Recruitment and Engagement Core to maximize engagement with underrepresented groups. Our CC will also align with the WF Older Adults Independence Center (OAIC) to facilitate studies on the role of aging in AD. Further, CC investigators will participate in an innovative program to foster alignment of large cohort studies with ADRC practices through the Clinical HArmonization and IMPlementation Service (CHAMPS). WF CHAMPS led the development and piloting of the UDS3 Telephone/Video Cognitive Battery provided to ADRCs when in-person research was restricted due to the COVID-19 pandemic. In summary, our CC has made exceptional progress in its first 4 years; it has enrolled 583 participants, contributed copious resources to the ADRC network, and provided a foundation for the explosive growth of ADRD research at Wake Forest. In the next cycle, we will leverage this success to further promote high-impact research on strategies for prevention and treatment of AD and related disorders.