The goal of this project is to examine the clinical presentation and biomarkers that accompany chronic traumatic encephalopathy (CTE;also known as dementia pugilistica), a preventable cause of dementia. Although concussive and/or subconcussive brain trauma appears to be a necessary factor in the development of CTE, it is not sufficient. The specific additional risk factors (e.g., genetics), and possible preventive strategies (e.g., concussion management, limiting overall subconcussive trauma) for this condition remain unknown. Moreover, although case studies have suggested that the pre-dementia clinical presentation includes cognitive deficits, depression, suicidal behavior, and problems with impulse control, there have been no systematic studies to support these observations. The research team has conducted neuropathological studies demonstrating that CTE is a tauopathy with a unique profile of neurodegeneration that is distinct from Alzheimer's and other neurodegenerative diseases of aging. To date, the only means of diagnosing CTE is post-mortem brain examination. In order to conduct prospective research into the epidemiology, early detection, risk factors, clinical course, and, ultimately, treatment and prevention of CTE, objective biomarkers for the disease must first be discovered. This project involves a cross-sectional examination of the biomarkers and clinical presentation of CTE. This initial study will focus on a sample of subjects who are at high risk of developing CTE: a randomly selected group of 150 retired NFL athletes, ages 40-69, all with high head trauma exposure (load) based on a combination of the total years played and positions played, incorporating helmet sensor data to determine the relative risk of various positions. We will also select a control group of same-age male athletes, with exclusion criteria based on a history of brain trauma or any participation in organized sports or military that may have caused exposure to even subconcussive brain trauma. In addition, APOE genotype will be examined as a potential moderating variable, based on our neuropathological findings and other data reported in the literature, both of which suggest that the APOE 54 allele may increase disease susceptibility. We will compare the high exposure group to the control group on several potential biomarkers, selected based on our previous neuropathological studies of CTE, our pilot neuroimaging data, and other findings by our team and in the literature regarding the long-term effects of repetitive brain trauma. We will then compare the groups on pertinent clinical variables, including neurologic, motor, neuropsychological, and psychiatric evaluations, and examine the relationship between the clinical variables and biomarkers in the high exposure group. Results of this initial investigation will help guide future longitudinal studies into the epidemiology, risk factors, and clinical presentation of CTE, and may provide additional knowledge relevant to the pathogenesis, detection, and eventual treatment of other neurodegenerative diseases such as AD.

Public Health Relevance

Chronic Traumatic Encephalopathy (CTE) is a degenerative disease of the brain resulting from repetitive head injuries, such as those experienced by athletes involved in football and other contact sports. Given the millions of Americans who participate in these sports at all levels of play, including youth, high school, college, and professional, it is imperative to be able to detect, diagnose, and eventually treat this preventable, progressive brain disease. This study will be the first to address these issues and may, therefore, have a tremendous impact on public health.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS078337-03
Application #
8466390
Study Section
Clinical Neuroscience and Neurodegeneration Study Section (CNN)
Program Officer
Hicks, Ramona R
Project Start
2011-08-01
Project End
2014-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
3
Fiscal Year
2013
Total Cost
$627,421
Indirect Cost
$132,906
Name
Boston University
Department
Neurology
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
Alosco, M L; Kasimis, A B; Stamm, J M et al. (2017) Age of first exposure to American football and long-term neuropsychiatric and cognitive outcomes. Transl Psychiatry 7:e1236
Alosco, Michael L; Mez, Jesse; Kowall, Neil W et al. (2017) Cognitive Reserve as a Modifier of Clinical Expression in Chronic Traumatic Encephalopathy: A Preliminary Examination. J Neuropsychiatry Clin Neurosci 29:6-12
Alosco, Michael L; Jarnagin, Johnny; Tripodis, Yorghos et al. (2017) Olfactory Function and Associated Clinical Correlates in Former National Football League Players. J Neurotrauma 34:772-780
Mez, Jesse; Daneshvar, Daniel H; Kiernan, Patrick T et al. (2017) Clinicopathological Evaluation of Chronic Traumatic Encephalopathy in Players of American Football. JAMA 318:360-370
Alosco, Michael L; Duskin, Jonathan; Besser, Lilah M et al. (2017) Modeling the Relationships Among Late-Life Body Mass Index, Cerebrovascular Disease, and Alzheimer's Disease Neuropathology in an Autopsy Sample of 1,421 Subjects from the National Alzheimer's Coordinating Center Data Set. J Alzheimers Dis 57:953-968
Shaker, Matineh; Erdogmus, Deniz; Dy, Jennifer et al. (2017) Subject-specific abnormal region detection in traumatic brain injury using sparse model selection on high dimensional diffusion data. Med Image Anal 37:56-65
Alosco, Michael L; Jarnagin, Johnny; Tripodis, Yorghos et al. (2017) Utility of providing a concussion definition in the assessment of concussion history in former NFL players. Brain Inj 31:1116-1123
Alosco, Michael L; Tripodis, Yorghos; Jarnagin, Johnny et al. (2017) Repetitive head impact exposure and later-life plasma total tau in former National Football League players. Alzheimers Dement (Amst) 7:33-40
McKee, Ann C; Cairns, Nigel J; Dickson, Dennis W et al. (2016) The first NINDS/NIBIB consensus meeting to define neuropathological criteria for the diagnosis of chronic traumatic encephalopathy. Acta Neuropathol 131:75-86
Koerte, Inga K; Hufschmidt, Jakob; Muehlmann, Marc et al. (2016) Cavum Septi Pellucidi in Symptomatic Former Professional Football Players. J Neurotrauma 33:346-53

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