Recurrent concussions are a major concern at every competitive level of contact sports. The long-term effects of concussion are poorly understood and need further investigation. The results of recent studies indicate that retired athletes with history of multiple concussions are at increased risk for depression, cognitive impairment, early onset Alzheimer's disease, and chronic traumatic encephalopathy (CTE). The proposed study aims will elucidate the relationship between repetitive head trauma and early cognitive decline, a possible prodrome of CTE.
In Aim 1, we propose to identify cases of mild cognitive impairment in a cohort of retired professional football players with history of multiple concussions and compare the severity and nature of clinical impairment to a cohort of mild cognitively impaired, matched controls without concussion history. Based on many previous studies and our own preliminary data, we predict that the retired athletes will have similar cognitive impairments, but worse neuropsychiatric symptomatology. We hypothesize that these symptoms are mediated by fronto-limbic dysfunction. Accordingly, Aim 2 entails functional neuroimaging to assess connectivity within the fronto-limbic emotional processing network. We will utilize a task paradigm that places a high cognitive load on this network to compare functional connectivity between the retired athletes and controls. We predict athletes will have altered fronto-limbic functional connectivity relative to controls. Overall, this project will provide critical insight ito the role of repetitive head trauma on cognitive decline and neurodegenerative disease. Furthermore, it will advance clinical practice by characterizing the presentation of early cognitiv decline secondary to head trauma and probing underlying neural network dysfunctions related to this unique decline. This information could be used to improve screening, prognosis, and patient counseling and may even provide a surrogate marker (fronto-limbic connectivity) for treatment efficacy in clinical trials in this population.

Public Health Relevance

The long-term effects of recurrent sport-related concussions are a major concern for athletes, but as yet, are poorly understood. This study will examine cognitive impairment and neurodegenerative disease in a sample of retired football players and a clinical comparison cohort using clinical assessments and advanced neuroimaging. The results of this work will improve our understanding of the association between repetitive head trauma and the development of neurodegenerative disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
1F30NS090816-01A1
Application #
8983258
Study Section
NST-2 Subcommittee (NST)
Program Officer
Bellgowan, Patrick S F
Project Start
2015-08-15
Project End
2019-08-14
Budget Start
2015-08-15
Budget End
2016-08-14
Support Year
1
Fiscal Year
2015
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Other Health Professions
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Clark, Michael D; Varangis, Eleanna M L; Champagne, Allen A et al. (2018) Effects of Career Duration, Concussion History, and Playing Position on White Matter Microstructure and Functional Neural Recruitment in Former College and Professional Football Athletes. Radiology 286:967-977
Kuzminski, S J; Clark, M D; Fraser, M A et al. (2018) White Matter Changes Related to Subconcussive Impact Frequency during a Single Season of High School Football. AJNR Am J Neuroradiol 39:245-251
Powierza, Camilla S; Clark, Michael D; Hughes, Jaime M et al. (2017) Validation of a Self-Monitoring Tool for Use in Exercise Therapy. PM R 9:1077-1084