The DIAGNOSE CTE Research Project-II

The aims of the DIAGNOSE CTE Research Project-II are to: * retain and grow DIAGNOSE-I and examine the clinical and biomarker course of Traumatic Encephalopathy Syndrome (TES); * investigate risk and resilience factors of TES; and * compare biomarkers of amyloid (Aβ), p-tau, neurodegeneration, neuroinflammation, and white matter (WM) injury between TES and AD. The investigators hypothesize that TES has unique clinical and biomarker profiles, and RHI and non-RHI risk factors influence the development of TES. There will be 3 study groups: 1. Retention, 150 former football players and 50 controls retained from DIAGNOSE-I; 2. Expansion, the investigators will grow DIAGNOSE-I by newly recruiting 75 former college and professional football players and 25 controls; 3. AD, 50 Aβ+ participants with cognitive impairment. In total, the investigators will study 225 former football players, 75 controls, and 50 AD. Participants will complete a single visit, including clinical exams, social determinants of health (SDOH) measures, MRI, blood draw, and tau PET, at 1 of 5 P30 AD Research Centers (ADRCs): Boston University (BU), University of California, San Francisco (UCSF), Arizona/Banner Alzheimer's Institute (BAI), University of Florida (1Florida), and University of Texas Health Science Center at San Antonio (South Texas). The Retention Cohort will have 18F-Flortaucipir (18F-AV-1451, Tauvid (FTP)) PET to study its longitudinal value. The Expansion Cohort will have 18F-MK-6240 (MK-6240) PET to build on the investigators' preliminary data. A subset of the Retention Cohort (n=20) will have FTP and MK-6240 for tracer comparison. Blood will be analyzed for 6 p-tau epitopes, Aβ40/42, neuroinflammation, and WM injury. DIAGNOSE-I participants were asked to pledge to donate their brain. This study will permit continued brain donation and clinical-pathological validation studies. Results will provide insight into the detection, diagnosis, and prognosis for people living with CTE, paving the way for treatment trials.