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      Cumulative Effects of Prior Concussion and Primary Sport Participation on Brain Morphometry in Collegiate Athletes: A Study From the NCAA–DoD CARE Consortium

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          Abstract

          Prior studies have reported long-term differences in brain structure (brain morphometry) as being associated with cumulative concussion and contact sport participation. There is emerging evidence to suggest that similar effects of prior concussion and contact sport participation on brain morphometry may be present in younger cohorts of active athletes. We investigated the relationship between prior concussion and primary sport participation with subcortical and cortical structures in active collegiate contact sport and non-contact sport athletes. Contact sport athletes (CS; N = 190) and matched non-contact sport athletes (NCS; N = 95) completed baseline clinical testing and participated in up to four serial neuroimaging sessions across a 6-months period. Subcortical and cortical structural metrics were derived using FreeSurfer. Linear mixed-effects (LME) models examined the effects of years of primary sport participation and prior concussion (0, 1+) on brain structure and baseline clinical variables. Athletes with prior concussion across both groups reported significantly more baseline concussion and psychological symptoms (all ps < 0.05). The relationship between years of primary sport participation and thalamic volume differed between CS and NCS ( p = 0.015), driven by a significant inverse association between primary years of participation and thalamic volume in CS ( p = 0.007). Additional analyses limited to CS alone showed that the relationship between years of primary sport participation and dorsal striatal volume was moderated by concussion history ( p = 0.042). Finally, CS with prior concussion had larger hippocampal volumes than CS without prior concussion ( p = 0.015). Years of contact sport exposure and prior concussion(s) are associated with differences in subcortical volumes in young-adult, active collegiate athletes, consistent with prior literature in retired, primarily symptomatic contact sport athletes. Longitudinal follow-up studies in these athletes are needed to determine clinical significance of current findings.

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          Recurrent concussion and risk of depression in retired professional football players.

          The purpose of our study was to investigate the association between prior head injury and the likelihood of being diagnosed with clinical depression among retired professional football players with prior head injury exposure. A general health questionnaire, including information about prior injuries, the SF-36 (Short Form 36), and other markers for depression, was completed by 2552 retired professional football players with an average age of 53.8 (+/-13.4) yr and an average professional football-playing career of 6.6 (+/-3.6) yr. A second questionnaire focusing on mild cognitive impairment (MCI)-related issues was completed by a subset of 758 retired professional football players (50 yr and older). Two hundred sixty-nine (11.1%) of all respondents reported having prior or current diagnosis of clinical depression. There was an association between recurrent concussion and diagnosis of lifetime depression (chi2=71.21, df=2, P<0.005), suggesting that the prevalence increases with increasing concussion history. Compared with retired players with no history of concussion, retired players reporting three or more previous concussions (24.4%) were three times more likely to be diagnosed with depression; those with a history of one or two previous concussions (36.3%) were 1.5 times more likely to be diagnosed with depression. The analyses controlled for age, number of years since retirement, number of years played, physical component score on the SF-36, and diagnosed comorbidities such as osteoarthritis, coronary heart disease, stroke, cancer, and diabetes. Our findings suggest a possible link between recurrent sport-related concussion and increased risk of clinical depression. The findings emphasize the importance of understanding potential neurological consequences of recurrent concussion.
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            Cumulative Head Impact Exposure Predicts Later-Life Depression, Apathy, Executive Dysfunction, and Cognitive Impairment in Former High School and College Football Players

            The term "repetitive head impacts" (RHI) refers to the cumulative exposure to concussive and subconcussive events. Although RHI are believed to increase risk for later-life neurological consequences (including chronic traumatic encephalopathy), quantitative analysis of this relationship has not yet been examined because of the lack of validated tools to quantify lifetime RHI exposure. The objectives of this study were: 1) to develop a metric to quantify cumulative RHI exposure from football, which we term the "cumulative head impact index" (CHII); 2) to use the CHII to examine the association between RHI exposure and long-term clinical outcomes; and 3) to evaluate its predictive properties relative to other exposure metrics (i.e., duration of play, age of first exposure, concussion history). Participants included 93 former high school and collegiate football players who completed objective cognitive and self-reported behavioral/mood tests as part of a larger ongoing longitudinal study. Using established cutoff scores, we transformed continuous outcomes into dichotomous variables (normal vs. impaired). The CHII was computed for each participant and derived from a combination of self-reported athletic history (i.e., number of seasons, position[s], levels played), and impact frequencies reported in helmet accelerometer studies. A bivariate probit, instrumental variable model revealed a threshold dose-response relationship between the CHII and risk for later-life cognitive impairment (p < 0.0001), self-reported executive dysfunction (p < 0.0001), depression (p < 0.0001), apathy (p = 0.0161), and behavioral dysregulation (p < 0.0001). Ultimately, the CHII demonstrated greater predictive validity than other individual exposure metrics.
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              A proposed injury threshold for mild traumatic brain injury.

              Traumatic brain injuries constitute a significant portion of injury resulting from automotive collisions, motorcycle crashes, and sports collisions. Brain injuries not only represent a serious trauma for those involved but also place an enormous burden on society, often exacting a heavy economical, social, and emotional price. Development of intervention strategies to prevent or minimize these injuries requires a complete understanding of injury mechanisms, response and tolerance level. In this study, an attempt is made to delineate actual injury causation and establish a meaningful injury criterion through the use of the actual field accident data. Twenty-four head-to-head field collisions that occurred in professional football games were duplicated using a validated finite element human head model. The injury predictors and injury levels were analyzed based on resulting brain tissue responses and were correlated with the site and occurrence of mild traumatic brain injury (MTBI). Predictions indicated that the shear stress around the brainstem region could be an injury predictor for concussion. Statistical analyses were performed to establish the new brain injury tolerance level.
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                Author and article information

                Contributors
                Journal
                Front Neurol
                Front Neurol
                Front. Neurol.
                Frontiers in Neurology
                Frontiers Media S.A.
                1664-2295
                28 July 2020
                2020
                : 11
                : 673
                Affiliations
                [1] 1Department of Neurosurgery, Medical College of Wisconsin , Milwaukee, WI, United States
                [2] 2Department of Neurology, Medical College of Wisconsin , Milwaukee, WI, United States
                [3] 3The Mind Research Network/Lovelace Biomedical and Environmental Research Institute , Albuquerque, NM, United States
                [4] 4Neurology and Psychiatry Departments, University of New Mexico School of Medicine , Albuquerque, NM, United States
                [5] 5Department of Psychology, University of New Mexico , Albuquerque, NM, United States
                [6] 6Department of Epidemiology and Biostatistics, Indiana University , Bloomington, IN, United States
                [7] 7School of Kinesiology and Michigan Concussion Center, University of Michigan , Ann Arbor, MI, United States
                [8] 8Department of Psychiatry, Indiana University School of Medicine , Bloomington, IN, United States
                [9] 9Department of Biomedical Engineering, Medical College of Wisconsin , Milwaukee, WI, United States
                [10] 10Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin , Milwaukee, WI, United States
                Author notes

                Edited by: Thor Stein, Boston University, United States

                Reviewed by: Charles Bernick, University of Washington, United States; Breton Michael Asken, University of California, San Francisco, United States

                *Correspondence: Timothy B. Meier tmeier@ 123456mcw.edu

                This article was submitted to Dementia and Neurodegenerative Diseases, a section of the journal Frontiers in Neurology

                †CARE Consortium Investigators are listed alphabetically by institution: John P. DiFiori, MD (Hospital for Special Surgery); Andrew J. Saykin, PsyD Yu-Chien Wu, MD, PhD (Indiana University School of Medicine); Andrew S. Nencka PhD, (Medical College of Wisconsin); Christopher C. Giza, MD and Joshua Goldman, MD, MBA (University of California Los Angeles); Jason P. Mihalik, PhD, CAT(C), ATC (University of North Carolina at Chapel Hill); Alison Brooks, MD (University of Wisconsin-Madison); Stefan M. Duma, PhD and Steven Rowson, PhD (Virginia Tech)

                Article
                10.3389/fneur.2020.00673
                7399344
                32849177
                b0b03da7-86be-4475-940d-ebb82b655bfe
                Copyright © 2020 Brett, Bobholz, España, Huber, Mayer, Harezlak, Broglio, McAllister, McCrea, Meier and CARE Consortium Investigators.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 25 February 2020
                : 05 June 2020
                Page count
                Figures: 4, Tables: 3, Equations: 0, References: 55, Pages: 12, Words: 8471
                Funding
                Funded by: National Collegiate Athletic Association 10.13039/100012676
                Funded by: U.S. Department of Defense 10.13039/100000005
                Funded by: Office of the Assistant Secretary for Health 10.13039/100006438
                Funded by: National Institute of Neurological Disorders and Stroke 10.13039/100000065
                Categories
                Neurology
                Original Research

                Neurology
                concussion and sports,traumatic brain injury,care consortium,brain morphometry,contact sport exposure,grey matter (gm)

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