AbstractBackgroundChronic traumatic encephalopathy (CTE) is neurodegenerative disease associated with a history of repetitive head impacts (RHI). The majority of CTE cases have been reported in former contact sport athletes, including American football players. In 2017, a case series from the Understanding Neurologic Injury and Traumatic Encephalopathy (UNITE) Brain Bank reported that 48 of the first 53 donors with college football as their highest level of play had CTE. Here we present updated numbers of former college football players with CTE in the UNITE Brain Bank and compare them to former college football players without CTE. We hypothesized that increasing CTE stage would be associated with dementia and increasing scores on clinical scales of informant reported symptoms.MethodBrain donors from the UNITE Brain Bank with college football as their highest level of play were included. CTE neuropathological diagnosis and staging (0‐IV; 0 = no CTE, IV = most severe) were assessed using validated criteria. Informants completed standardized scales of cognition (Cognitive Difficulties Scale, CDS), activities of daily living (Functional Activities Questionnaire, FAQ), and neurobehavioral dysregulation (BRIEF‐A Behavioral Regulation Index, BRI). Consensus dementia diagnoses were made by expert clinicians. Multivariable regression models examined associations between CTE stage, dementia, and each clinical scale, controlling for age at death, racial identity, education, and duration of football play in years.ResultAmong 319 donors with college football as their highest level of play (median age at death = 64.0; IQR = 47‐77), 222 (69.5%) had CTE. Among those with CTE, 44 (19.8%) were stage I, 47 (21.2%) were stage II, 79 (35.6%) were stage III and 52 (23.4%) were stage IV. Among those with CTE, 122 (55.0%) were demented and 123 (61.5%) and 131 (70.8%) had clinically meaningful elevations on the FAQ and BRI respectively. CTE stage was significantly associated with having dementia (OR = 1.37; 95%CI:1.08‐1.72) and with more symptoms on the CDS (beta = 5.04; 95%CI:1.41‐8.66) and FAQ (beta = 1.12; 95%CI:0.38‐1.86), but not the BRI. Effect estimates were larger after removing donors with non‐CTE neurodegenerative pathology.ConclusionAmong former college football playing brain donors, CTE pathology was very common. CTE stage was significant associated with dementia history and symptoms on clinical scales.