Charles Tator

Charles Tator
University of Toronto | U of T · Department of Surgery

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531
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Publications

Publications (531)
Article
At the Canadian Concussion Centre, we treated 136 patients from 2000 to 2020 who sustained concussion plus persisting concussion symptoms (C+PCS) as motor vehicle occupants involved in motor vehicle crashes (MVCs). This center specializes in the treatment of patients with C+PCS. The objective of the present study was to identify strategies for prev...
Article
Falls in older adults and those with neurodegenerative disease (ND) are a current public health hazard and the primary cause of sustaining a mild traumatic brain injury (mTBI)/concussion. Little is known regarding how post-concussion symptoms present in older adults and patients with ND, even though they are the demographic at highest risk. A combi...
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Background The long-term consequences of concussions may include pathological neurodegeneration as seen in Alzheimer’s disease (AD) and chronic traumatic encephalopathy (CTE). Tau-PET showed promise as a method to detect tau pathology of CTE, but more studies are needed Objective This study aimed (1) to assess the association of imaging evidence o...
Article
Background: The drivers that activate endogenous ependymal-derived neural stem/progenitor cells (epNSPCs) remain unknown. Understanding the mechanisms that govern the biology of these cells is critical in developing a therapeutic strategy to harness their regenerative potential after injury. Methods: FoxJ1-CreER-tdTomato reporter mice were used for...
Article
Aims Hirano bodies (HBs) are eosinophilic pathological structures with two morphological phenotypes commonly found in the hippocampal CA1 region in Alzheimer's disease (AD). This study evaluated the prevalence and distribution of HBs in AD and other neurodegenerative diseases. Methods This cross‐sectional study systematically evaluated HBs in a co...
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The most frequent neurodegenerative proteinopathies include diseases with deposition of misfolded tau or α-synuclein in the brain. Pathological protein aggregates in the peripheral nervous system (PNS) are well-recognized in α-synucleinopathies and have recently attracted attention as a diagnostic biomarker. However, there is a paucity of observati...
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Background Misfolded α‐synuclein in Parkinson's disease (PD) and dementia with Lewy bodies (DLB) can be detected using the real‐time quaking‐induced conversion (RT‐QuIC) technique in cerebrospinal fluid (CSF). Objectives The objectives are (1) to examine misfolded CSF α‐synuclein incidence, and (2) to compare clinical presentation, sports history,...
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Repulsive guidance molecule A (RGMa) is an inhibitor of neuronal growth and survival which is upregulated in the damaged central nervous system following acute spinal cord injury (SCI), traumatic brain injury, acute ischemic stroke (AIS), and other neuropathological conditions. Neutralization of RGMa is neuroprotective and promotes neuroplasticity...
Article
Background Long term effects of concussions and sub‐concussions in athletes can include delayed neurodegeneration as seen in Alzheimer’s disease (AD) and chronic traumatic encephalopathy (CTE). The PET tracer [18F]AV1451 has high affinity and selectivity for paired helical filament‐tau in vivo, the pathological form of tau in CTE and AD. The aim of...
Article
Objective Concern exists about possible problems with later-in-life brain health, such as cognitive impairment, mental health problems and neurological diseases, in former athletes. We examined the future risk for adverse health effects associated with sport-related concussion, or exposure to repetitive head impacts, in former athletes. Design Sys...
Article
Background: The adult spinal cord contains a population of ependymal-derived neural stem/progenitor cells (epNSPCs) with the potential to enhance endogenous regeneration. However, little is known about the mechanisms that regulate the activation of these cells after injury. Recently, we discovered that glutamate excitotoxicity, a hallmark in the pa...
Article
The North America Clinical Trials Network (NACTN) for Spinal Cord Injury (SCI) is a consortium of tertiary medical centers that has maintained a prospective SCI registry since 2004, and has espoused that early surgical intervention is associated with improved outcome. It has previously been shown that initial presentation to a lower acuity center a...
Article
The bulbocavernosus reflex (BCR) has been used during the initial evaluation of a spinal cord injury patient as a metric to determine prognosis and whether the patient is in "spinal shock". This reflex has been less utilized over the last decade and therefore, a review was performed to assess the value of BCR in patient prognosis. The North America...
Article
There is a paucity of data comparing the demographics, mechanism of injury, and outcomes of upper versus lower cervical spinal cord injuries (cSCI). The study objective was to define different clinical manifestations of cSCI. Data were collected prospectively through centers of the North American Clinical Trials Network (NACTN). Data was collected...
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Full-text available
The adult spinal cord contains a population of ependymal-derived neural stem/progenitor cells (epNSPCs) that are normally quiescent, but are activated to proliferate, differentiate, and migrate after spinal cord injury. The mechanisms that regulate their response to injury cues, however, remain unknown. Here, we demonstrate that excitotoxic levels...
Article
Only 100 years ago, traumatic spinal cord injury (SCI) was commonly lethal. Today, most people who sustain SCI survive with continual efforts to improve their quality of life and neurological outcomes. SCI epidemiology is changing as preventative interventions reduce injuries in younger individuals, and there is an increased incidence of incomplete...
Article
This is a historical account of the origin and accomplishments of the North American Clinical Trials Network (NACTN) for traumatic spinal cord injury (SCI), which was established in 2004 by Christopher Reeve and Dr. Robert Grossman. Christopher Reeve was an actor who became quadriplegic and started the Christopher and Dana Reeve Foundation, while R...
Article
Mild traumatic brain injury (mTBI) in former contact sports athletes is a risk factor for dementia. However, it is unknown why only some individuals with mTBI develop dementia, suggesting that head injury exposure alone is not sufficient to produce the condition. We hypothesize that mTBI could be associated with neurodegenerative processes that tar...
Article
Changes in demography and injury patterns have altered the profile and outcome of acute SCI over time. This study sought to describe recent trends in epidemiology and early clinical outcomes using the multi-center North American Clinical Trial Network (NACTN) for Spinal Cord Injury Registry. All participants with blunt acute traumatic SCI (n=782) w...
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Background: Concussion public policies have been developed to address the burden of concussions. The aim of the present study was to examine implementation compliance, barriers, and facilitators of Canada's first concussion public policy, Ontario's Policy/Program Memorandum 158: School Board Policies on Concussion (PPM158). Methods: An electroni...
Article
Spinal cord injury (SCI) elicits a cascade of degenerative events including cell death, axonal degeneration, and the upregulation of inhibitory molecules which limit repair. Repulsive guidance molecule A (RGMa) is an axon growth inhibitor which is also involved in neuronal cell death and differentiation. SCI causes upregulation of RGMa in the injur...
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Background Considering the wide range of outcomes following sport-related concussions, biomarkers are needed to detect underlying pathological changes. The objective was to analyze the use of plasma phosphorylated tau 181 (pTau181) as a non-invasive measure of underlying brain changes in a cohort of retired contact sports athletes at risk of neurod...
Article
Objectives Concussions are a major public health concern, and, thus, specific policies have been developed for implementation targeting vulnerable populations such as school-aged children and youth in the school setting, in whom the majority of concussions are sports related. Currently, concussion policies exist in various jurisdictions, including...
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Background Neuro-axonal brain damage releases neurofilament light chain (NfL) proteins, which enter the blood. Serum NfL has recently emerged as a promising biomarker for grading axonal damage, monitoring treatment responses, and prognosis in neurological diseases. Importantly, serum NfL levels also increase with aging, and the interpretation of se...
Article
Background: Post-concussion syndrome (PCS) or persistent symptoms of concussion refers to a constellation of symptoms that persist for weeks and months after a concussion. To better capture the heterogeneity of the symptoms of patients with post-concussion syndrome, we aimed to separate patients into clinical subtypes based on brain connectivity c...
Article
Background: Evidence suggests that cerebrovascular reactivity (CVR) increases within the first week after the incidence of concussion, indicating a disruption of normal autoregulation. We sought to extend these findings by investigating the effects of acute concussion on the speed of CVR response and by visualizing global and regional impairments...
Article
Spinal cord injury (SCI) is a devastating condition characterized by loss of function, secondary to damaged spinal neurons, disrupted axonal connections, and myelin loss. Spontaneous recovery is limited, and there are no approved pharmaceutical treatments to reduce ongoing damage or promote repair. Repulsive guidance molecule A (RGMa) is upregulate...
Article
BACKGROUND Sport-related structural brain injury (SRSBI) is intracranial pathology incurred during sport. Management mirrors that of non-sport-related brain injury. An empirical vacuum exists regarding return to play (RTP) following SRSBI. OBJECTIVE To provide key insight for operative management and RTP following SRSBI using a (1) focused systema...
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Objective: To determine whether an association exists between career duration or position played and the presence of chronic traumatic encephalopathy (CTE) at autopsy in a series of elite football and hockey players. Methods: This retrospective cohort study analyzed post-mortem brains of 35 former football or hockey players (29 professional, 6 u...
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Concussions are associated with a range of cognitive, neuropsychological and behavioral sequelae that, at times, persist beyond typical recovery times and are referred to as postconcussion syndrome (PCS). There is growing support that concussion can disrupt network-based connectivity post-injury. To date, a significant knowledge gap remains regardi...
Article
Concussions are associated with a range of cognitive, neuropsychological and behavioral sequelae that, at times, persist beyond typical recovery times and are referred to as postconcussion syndrome (PCS). There is growing support that concussion can disrupt network-based connectivity post-injury. To date, a significant knowledge gap remains regardi...
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Concussion imaging research has primarily focused on neuronal disruption with lesser emphasis directed toward vascular dysfunction. However, blood flow metrics may be more sensitive than measures of neuronal integrity. Vascular dysfunction can be assessed by measuring cerebrovascular reactivity (CVR), the change in cerebral blood flow per unit chan...
Article
Persisting concussion symptoms (PCS) can last for months, years, or indefinitely and affect a considerable number of concussion patients. The objectives of this study were to evaluate the prevalence of clinical symptoms of anxiety and depression and the relationship between PCS and quality of life in patients examined at the Canadian Concussion Cen...
Article
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Spinal cord injury (SCI) often results in permanent functional loss due to a series of degenerative events including cell death, axonal damage, and the upregulation of inhibitory proteins that impede regeneration. Repulsive Guidance Molecule A (RGMa) is a potent inhibitor of axonal growth that is rapidly upregulated following injury in both the rod...
Article
Background/Objective This study aimed to evaluate serum neurofilament light chain (NF‐L) levels in former professional contact sports athletes with multiple concussions (ExPro) as a potential biomarker of neurodegeneration and predictor of white‐matter (WM) abnormality progression. Methods Concentrations of NF‐L in the serum of fifty‐two cognitive...
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Background Concussions among adult bicyclists are common, but little is known about the long-term effects of the consequences of these concussions such as postconcussion syndrome (PCS) including its occurrence, clinical features and recovery potential. Indeed, our study is the first to examine PCS due to bicycling in any age group. Objectives We e...
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Background: Genetic polymorphisms like apolipoprotein E (APOE) and microtubule-associated protein tau (MAPT) genes increase the risk of neurodegeneration. Methods: 38 former players (age 52.63±14.02) of contact sports underwent neuroimaging, biofluid collection, and comprehensive neuropsychological assessment. The [F-18]AV-1451 tracer signal was...
Article
The purpose of this study was to assess the frequency of structural lesions on conventional MRI of the brain in a large prospective cohort of post-concussion syndrome (PCS) patients. Conventional 3T MRI was used to evaluate 127 prospectively enrolled PCS patients and 29 controls for non-specific white matter hyperintensities (WMH) and traumatic str...
Article
Nearly a century ago, the concept of the secondary injury in spinal cord trauma was first proposed to explain the complex cascade of molecular and cellular events leading to widespread neuronal and glial cell death after trauma. In recent years, it has been established that the ependymal region of the adult mammalian spinal cord contains a populati...
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Objectives: To identify novel targets for neurorehabilitation of people with a remote history of multiple concussions by: (1) comprehensively characterizing neuropsychiatric and cognitive functioning in former professional football players, with a focus on executive functions; (2) distinguishing concussion-related findings from pre-morbid/cohort ch...
Chapter
In human spinal cord injury, the most common mechanism is the combination of acute impact and continuing compression. To simulate combined impact-compression, we developed in the 1970s the acute clip impact-compression model, one of the first non-transection models in the rodent. Subsequently, we characterized the relationships between clip strengt...
Article
Objective: To identify CSF biomarkers that are related to decreased white matter (WM) integrity and poor cognitive performance in former professional athletes with a history of multiple concussions. Methods: Concentrations of phosphorylated tau181, total tau (t-tau), and β-amyloid in the CSF were measured in 3 groups: 22 former professional athl...
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Rowan’s Rugby Fatality Prompts Canada’s First Concussion Legislation - Volume 46 Issue 3 - Charles Tator, Jill Starkes, Gillian Dolansky, Julie Quet, Jean Michaud, Michael Vassilyadi
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Second impact syndrome (SIS) is associated with malignant brain swelling and usually occurs in young athletes with one or more prior, recent concussions. SIS is rare and some dispute its existence. We report a case of SIS in Rowan Stringer, age 17, a rugby player who sustained a fatal brain injury despite prompt medical therapy including decompress...
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Mild traumatic brain injury (mTBI) is common in many populations, including athletes, veterans, and domestic abuse victims. mTBI can cause chronic symptoms, including depression, irritability, memory problems, and attention deficits. A history of repetitive mTBI has been epidemiologically associated with developing early-onset dementia and neurodeg...
Article
Concussion has emerged as an important public health issue affecting thousands of Canadians annually. Health care providers including paediatricians, family and emergency medicine physicians, nurses, and nurse practitioners are commonly tasked with the responsibility of providing primary care to patients with acute concussion and those with persist...
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Background Despite concussion now being recognized as a public health priority in Canada, recent studies—including our 2012 survey of Canadian medical schools—have revealed major gaps in concussion education at the undergraduate medical school level. Methods We re-surveyed all 17 Canadian medical schools using a questionnaire divided in two catego...
Chapter
Improvements have been made in the management of concussions, and this includes the methods for advising concussed patients about the processes to be followed for return to play (RTP) in sports, return to learn (RTL) in schools, and return to work (RTW) on the job. The aim of management is to facilitate return by a graduated process of steps during...
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Background Certain factors such as age and gender seem to affect the risk of developing post-concussion syndrome (PCS). We assessed the interactions between age, gender, concussion history and mechanism of injury in PCS patients so that a better understanding could guide the development of targeted prevention strategies. Methods Demographic data i...
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Liquid crystal display (LCD) screens refresh at a rate of 60 times per second, which can be perceived by concussed individuals who have photosensitivity, leading to computer intolerance. A non-LCD computer screen that refreshes at a much lower rate could relieve this photosensitivity and computer screen intolerance in patients with post-concussion...
Article
Background: Transplantation of neural stem/progenitor cells (NSPCs) following spinal cord injury (SCI) is a promising strategy to enhance regeneration but is limited by poor survival of grafted cells. Recently, we demonstrated for the first time that the excitatory neurotransmitter glutamate, which is released after SCI, promotes survival/prolifera...
Article
Full-text available
Multiple concussions, particularly in contact sports, have been associated with cognitive deficits, psychiatric impairment and neurodegenerative diseases like chronic traumatic encephalopathy. We used volumetric and deformation-based morphometric analyses to test the hypothesis that repeated concussions may be associated with smaller regional brain...
Article
Current biomarker research in spinal cord injury (SCI) and traumatic brain injury has focused on a number of structural protein candidates, including the microtubule-associated protein tau. Evidence from models of traumatic brain injury has demonstrated that hyperphosphorylation of tau (p-tau) occurs within injured axons and provides evidence of it...
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Background: Epidemiologic studies have suggested that concussion, or mild traumatic brain injury (mTBI), is associated with a twofold or greater increase in relative risk for the development of post-traumatic epilepsy. To assess the clinical validity of these findings, we analyzed the incidence of epilepsy in a large cohort of post-concussion pati...
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The lack of tissue regeneration after traumatic spinal cord injury (SCI) in animal models is largely attributed to the local inhibitory microenvironment. To overcome this inhibitory environment while promoting tissue regeneration, we investigated the combined delivery of chondroitinase ABC (chABC) with human induced pluripotent stem cell-derived ne...
Preprint
Full-text available
Multiple concussions, particularly in contact sports, have been associated with cognitive deficits, psychiatric impairment and neurodegenerative diseases like chronic traumatic encephalopathy. We used volumetric and deformation-based morphometric analyses to test the hypothesis that repeated concussions may be associated with smaller regional brain...
Article
The objective of this study was to assess the incidence of motor impairment in former professional Canadian Football League (ex-CFL) players with multiple concussions. We investigated motor symptoms and signs in 45 ex-CFL players with multiple concussions and 25 age-and education matched healthy controls with no history of concussion. Neurological...
Article
The aim of this study was to examine the potential utility of a self-paced saccadic eye movement as a marker of post-concussion syndrome (PCS) and monitoring the recovery from PCS. Fifty-nine persistently symptomatic participants with at least two concussions performed the self-paced saccade (SPS) task. We evaluated the relationships between the nu...
Article
Full-text available
Traumatic spinal cord injury (SCI) causes a cascade of degenerative events including cell death, axonal damage, and the upregulation of inhibitory molecules which prevent regeneration and limit recovery. Repulsive guidance molecule A (RGMa) is a potent neurite growth inhibitor in the central nervous system, exerting its repulsive activity by bindin...
Article
Full-text available
The ideal biomarker for central nervous system (CNS) trauma in patients would be a molecular marker specific for injured nervous tissue that would provide a consistent and reliable assessment of the presence and severity of injury and the prognosis for recovery. One candidate biomarker is the protein tau, a microtubule-associated protein abundant i...
Article
Transplantation of neural stem/progenitor cells (NSPCs) following spinal cord injury (SCI) is a promising strategy to enhance regeneration but is limited by poor survival of grafted cells. Determining methods to enhance survival of NSPCs is therefore essential. Positive modulation of AMPA receptors has been shown to enhance neurogenesis in various...
Article
OBJECTIVE A surgical series of 201 benign and malignant peripheral nerve sheath tumors (PNSTs) was assessed to characterize the anatomical and clinical presentation of tumors and identify predictors of neurological outcome, recurrence, and extent of resection. METHODS All surgically treated PNSTs from the Division of Neurosurgery at Toronto West...
Article
The Fifth International Conference on Concussion in Sport was held in Berlin in October 2016. A series of 12 questions and subquestions was developed and the expert panel members were required to perform a systematic review to answer each question. Following presentation at the Berlin meeting of the systematic review, poster abstracts and audience...
Article
Objective: To assess the knowledge of, attitudes toward, and learning needs for concussion diagnosis and management among family medicine residents. Design: E-mail survey. Setting: University of Toronto in Ontario. Participants: Family medicine residents (N = 348). Main outcome measures: To describe relationships between awareness of concu...
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Full-text available
Objective It has been stated that concussion is a risk factor for the development of post-traumatic epilepsy, but few data exist to support or refute this statement. We analysed the incidence and prevalence of epilepsy in a large cohort of post-concussion patients. Design Retrospective cohort study. Setting Academic tertiary care centre. Partici...
Article
Objective Ontario is the first province in Canada to implement a school-based concussion policy, Policy/Program Memorandum (PPM) 158. It requires all public school boards to develop a concussion strategy. The aim of this research was to conduct a pilot assessment of PPM 158 implementation in one large school board, and then to develop a novel polic...
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Objective To assess eye movements in patients with post-concussion syndrome (PCS) and use diffusion tensor imaging (DTI) to determine relationship between eye movements and white matter integrity. Design cross-sectional study. Intervention Attention and executive function were tested using Visual Attention Scanning Technology (VAST) [EL-MAR Inc.,...
Article
Objective To assess knowledge, attitude and learning needs about concussion among family medicine residents Design A web-based prospective survey Setting Toronto, Canada. Participants Family medicine residents at the University of Toronto. Intervention A link to the survey was disseminated via e-mail by the Department of Family and Community Me...
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Objective: Systematic review of possible long-term effects of sports-related concussion in retired athletes. Data sources: Ten electronic databases. Study selection: Original research; incidence, risk factors or causation related to long-term mental health or neurological problems; individuals who have suffered a concussion; retired athletes a...
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The 2017 Concussion in Sport Group (CISG) consensus statement is designed to build on the principles outlined in the previous statements1–4 and to develop further conceptual understanding of sport-related concussion (SRC) using an expert consensus-based approach. This document is developed for physicians and healthcare providers who are involved in...
Article
Traumatic spinal cord injury (SCI) is a devastating event for which functional recovery remains elusive. Due to the complex nature of SCI pathology, a combination treatment strategy will likely be required for success. We hypothesized that tissue and functional repair would be achieved in a rat model of impact-compression SCI by combining degradati...
Article
Aim or objective To examine the effectiveness of concussion prevention strategies in reducing concussion risk in sport. Design Systematic review according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines. Data sources Eleven electronic databases searched and hand-search of references from selected stud...
Article
In this article, we conduct a review of introduced and enacted youth concussion legislation in Canada and present a conceptual framework and recommendations for future youth sport concussion laws. We conducted online searches of federal, provincial, and territorial legislatures to identify youth concussion bills that were introduced or successfully...
Article
We examined recovery from postconcussion syndrome (PCS) in a series of 285 patients, diagnosed with concussion based on international sport concussion criteria, who received a questionnaire regarding recovery . Of 141 respondents, those with postconcussion symptoms lasting less than 3 months, a positive CT and/or MRI, litigants, and known Test of M...
Article
The immune system plays a critical and complex role in the pathobiology of spinal cord injury (SCI), exerting both beneficial and detrimental effects. Increasing evidence suggests that there are injury level-dependent differences in the immune response to SCI. Patients with traumatic SCI have elevated levels of circulating autoantibodies against co...
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Aim Several high-profile professional hockey players have retired due to career-ending concussions sustained in the National Hockey League (NHL). We sought to determine the salary cost of career-ending concussions in the NHL. Methods Concussion-induced retirements from 1995 to 2015 were identified using public media sources. The number of missed g...
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Retired professional athletes, who have suffered repetitive concussions, report symptoms of depression, anxiety, and memory impairment over time. Moreover, recent imaging data suggest chronic white-matter tract deterioration in sport-related concussion. The aim of this study is to evaluate the impact of repetitive concussions in retired professiona...