Long-term brain health profiles following exposure to repetitive head impacts and/or concussions in contact sports are a public health focus and the subject of a national debate. The true prevalence rates of mild cognitive impairment (MCI) or neurobehavioural dysregulation are unknown in the nearly 20 000 current/living former professional football players. Here, we describe the procedures and methodology of the prevalence study of cognitive function in former professional football players from the Brain Health Initiative at the University of Pittsburgh. The objective is to define the prevalence of normal cognitive function versus neurodegeneration in former professional football players through clinical, neuroimaging and biomarker assessments.

Participants include former professional football players aged 29–59 years at study onset who played a minimum of three professional football games in three professional seasons and non-exposed controls. Participants are recruited by two mechanisms, a random and non-random sample. The full study protocol includes a 3–4-day, multidomain assessment (eg, neurological, neurocognitive, psychiatric, sleep, vestibular, orthopaedic and cardiovascular) for neurodegenerative disease and overall health and function, including MRI, positron emission tomography scans, analysis of blood plasma and cerebrospinal fluid, neurocognitive assessments, applanation tonometry, overnight sleep study and informant interview. A multidisciplinary clinical panel conducts a blinded diagnostic consensus conference to adjudicate the presence of MCI and/or traumatic encephalopathy syndrome, which serve as the study’s primary and secondary outcomes, respectively. Point prevalence of these for both the exposed and unexposed cohorts will be calculated as the primary statistical analysis.

The University of Pittsburgh Institutional Review Board approved the study prior to recruiting human subjects (protocol numbers STUDY19010008: sIRB - Brain Health Initiative (Part 1) and STUDY19030211: sIRB - Brain Health Initiative (Part 2)). The results will be disseminated in peer-reviewed journals and as presentations at national and international scientific conferences.