University of Pittsburgh Brain Health Initiative

Study Overview
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Brief Summary
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This project will define the prevalence of brain health (i.e., normal cognitive, neuromotor, behavioral function) in living professional football retirees and group-matched controls through a comprehensive assessment of clinical, neuroimaging, and biomarker measures.

Official Title
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Prevalence of Brain Health Versus Neurodegeneration in Former Professional Football Players

Conditions
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Traumatic Brain Injury

Intervention / Treatment
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* Diagnostic Test: Cognitive/Neuropsychological Testing
* Diagnostic Test: Vestibular/Ocular-Motor Testing
* Diagnostic Test: Sleep Evaluation
* Diagnostic Test: MRI, High-Resolution
* Diagnostic Test: Health & Physical Exam
* Diagnostic Test: Physical Function
* Diagnostic Test: Blood Testing and Biomarker Analysis
* Diagnostic Test: Applanation Tonometry
* Diagnostic Test: PET brain imaging
* Drug: [C-11]6-OH-BTA-1
* Drug: [F-18]AV-1451


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Former professional football player/exposed group: Professional football retiree aged 29-59 Played a minimum of 3 professional football seasons, with a minimum of 3 games in each season Fluent in English (translations are not available/validated for most neuropsychological tests) Control/unexposed group: Age 29-59 male High school education or beyond Fluent in English (translations are not available/validated for most neuropsychological tests) Exclusion criteria: Control/unexposed group: Played organized football beyond high school History of severe TBI Current unstable cardiovascular disorder For both groups: Prior history of psychosis (such as schizophrenia), or other major neurological disorder that would interfere with testing, in the opinion of the primary investigator. Contraindication to MR imaging, such as ferrous metal, pacemakers, or concerns about claustrophobia

Ages Eligible for Study
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Minimum Age: 29 Years
Maximum Age: 59 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Former Professional Football Players<br>Former professional football players who played in at least 3 professional seasons, with at least 3 games each season. | Diagnostic Test: Cognitive/Neuropsychological Testing<br>* Comprehensive testing of cognitive function and brain health.<br>Diagnostic Test: Vestibular/Ocular-Motor Testing<br>* A series of tests and questionnaires that asses vestibular function, balance, ocular-motor coordination, and reflexes.<br>Diagnostic Test: Sleep Evaluation<br>* A full assessment of sleep health, including insomnia (duration, frequency, daytime consequences) and other sleep disorders such as obstructive sleep apnea. Overnight sleep study is included.<br>Diagnostic Test: MRI, High-Resolution<br>* A high-resolution MRI to provide qualitative and quantitative assessments of brain structure.<br>Diagnostic Test: Health & Physical Exam<br>* Participants will undergo an executive history and physical exam of all body systems.<br>Diagnostic Test: Physical Function<br>* These assessments will involve a series of tests and questionnaires that focus on physical function.<br>Diagnostic Test: Blood Testing and Biomarker Analysis<br>* A blood draw will be performed to measure standard clinical labs as part of a full history and physical, as well as additional analysis of biomarkers indicative of brain health. An optional lumbar puncture will be performed and CSF samples (20-30 mL) stored in the NCTC Biorepository until shipment to the CLIA-certified laboratory. Both CSF and blood samples will be analyzed for t-tau, p-tau, and Aβ42 and stored for future testing,<br>Diagnostic Test: Applanation Tonometry<br>* Hearth health is evaluated through testing of arterial stiffness and pulse wave reflections using a high fidelity applanation tonometer.<br>* Other names: Continuous arterial pressure;Diagnostic Test: PET brain imaging<br>* PET imaging of the brain using tau and amyloid ligands.<br>Drug: [C-11]6-OH-BTA-1<br>* PET imaging of the brain using an amyloid ligand.<br>* Other names: Pittsburgh Compound B;Drug: [F-18]AV-1451<br>* PET imaging of the brain using a tau ligand.<br>* Other names: [F-18]T807, LY3191748;|
| Control Groups<br>Friends and brothers of the Former Professional Football Player group. | Diagnostic Test: Cognitive/Neuropsychological Testing<br>* Comprehensive testing of cognitive function and brain health.<br>Diagnostic Test: Vestibular/Ocular-Motor Testing<br>* A series of tests and questionnaires that asses vestibular function, balance, ocular-motor coordination, and reflexes.<br>Diagnostic Test: Sleep Evaluation<br>* A full assessment of sleep health, including insomnia (duration, frequency, daytime consequences) and other sleep disorders such as obstructive sleep apnea. Overnight sleep study is included.<br>Diagnostic Test: MRI, High-Resolution<br>* A high-resolution MRI to provide qualitative and quantitative assessments of brain structure.<br>Diagnostic Test: Health & Physical Exam<br>* Participants will undergo an executive history and physical exam of all body systems.<br>Diagnostic Test: Physical Function<br>* These assessments will involve a series of tests and questionnaires that focus on physical function.<br>Diagnostic Test: Blood Testing and Biomarker Analysis<br>* A blood draw will be performed to measure standard clinical labs as part of a full history and physical, as well as additional analysis of biomarkers indicative of brain health. An optional lumbar puncture will be performed and CSF samples (20-30 mL) stored in the NCTC Biorepository until shipment to the CLIA-certified laboratory. Both CSF and blood samples will be analyzed for t-tau, p-tau, and Aβ42 and stored for future testing,<br>Diagnostic Test: Applanation Tonometry<br>* Hearth health is evaluated through testing of arterial stiffness and pulse wave reflections using a high fidelity applanation tonometer.<br>* Other names: Continuous arterial pressure;Diagnostic Test: PET brain imaging<br>* PET imaging of the brain using tau and amyloid ligands.<br>Drug: [C-11]6-OH-BTA-1<br>* PET imaging of the brain using an amyloid ligand.<br>* Other names: Pittsburgh Compound B;Drug: [F-18]AV-1451<br>* PET imaging of the brain using a tau ligand.<br>* Other names: [F-18]T807, LY3191748;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rates of Brain Health versus Cognitive Impairment | The diagnosis of cognitive impairment is based on the ADRC National Alzheimer's Coordinating Center (NACC) criteria for mild cognitive impairment. This criteria is adjudicated following a comprehensive neuropsychological exam, and includes: (1) Self- or informant-reported cognitive complaint, (2) Objective cognitive impairment, (3) Preserved independence in functional abilities, and (4) No dementia. | 1-week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Syndromes of Neurodegeneration | The determination of trauma-related neurodegeneration will be based on: 1) presence of cognitive deficits, and/or neuromotor manifestations, and/or behavioral/mood-related symptoms; 2) PET scans demonstrating abnormal amyloid and/or tau deposition; 3) quantitative MR evidence of cortical volume loss and/or white matter injury; and 4) elevated CSF tau/Aβ42 ratio. These multiple measures will be combined to arrive at a single overall outcome measure. This will be adjudicated at a blinded Diagnostic Consensus Conference comprised of experts from each field. | 1-week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Brain Health, Football, Contact Sport, Concussion