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      Duration of American Football Play and Chronic Traumatic Encephalopathy

      research-article
      , MD, MS 1 , 2 , 3 , , MD, PhD 1 , 4 , , BA 1 , 2 , , MS 1 , 5 , , PhD 1 , 2 , , BA 1 , 2 , 6 , , BA 1 , 2 , , BA 1 , 2 , , MS 1 , 7 , , MS 1 , 7 , , PhD 1 , 8 , , PhD 1 , 2 , , PhD 1 , 9 , 10 , , MD 1 , 9 , 10 , , MD 2 , 11 , , MD, PhD 1 , 2 , 9 , 10 , , MD, PhD 1 , 3 , 9 , 10 , 12 , , MD, PhD 1 , 2 , 12 , 13 , 14 , , MD 2 , 11 , , MD 1 , 2 , 8 , 15 , 16 , , PhD 1 , 3 , 17 , 18 , , MD 1 , 2 , 9 , 12 , , PhD 1 , 2 , 15 , 17 , , MS, ScD 19 , , MPH, ScD 18 , , PhD 1 , 5 , , MD 1 , 2 , 3 , 9 , 10 , 12 ,
      Annals of Neurology
      John Wiley & Sons, Inc.

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          Abstract

          Objective

          Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with exposure to contact and collision sports, including American football. We hypothesized a dose–response relationship between duration of football played and CTE risk and severity.

          Methods

          In a convenience sample of 266 deceased American football players from the Veterans Affairs–Boston University–Concussion Legacy Foundation and Framingham Heart Study Brain Banks, we estimated the association of years of football played with CTE pathological status and severity. We evaluated the ability of years played to classify CTE status using receiver operating characteristic curve analysis. Simulation analyses quantified conditions that might lead to selection bias.

          Results

          In total, 223 of 266 participants met neuropathological diagnostic criteria for CTE. More years of football played were associated with having CTE (odds ratio [OR] = 1.30 per year played, 95% confidence interval [CI] = 1.19–1.41; p = 3.8 × 10 −9) and with CTE severity (severe vs mild; OR = 1.14 per year played, 95% CI = 1.07–1.22; p = 3.1 × 10 −4). Participants with CTE were 1/10th as likely to have played <4.5 years (negative likelihood ratio [LR] = 0.102, 95% CI = 0.100–0.105) and were 10 times as likely to have played >14.5 years (positive LR = 10.2, 95% CI = 9.8–10.7) compared with participants without CTE. Sensitivity and specificity were maximized at 11 years played. Simulation demonstrated that years played remained adversely associated with CTE status when years played and CTE status were both related to brain bank selection across widely ranging scenarios.

          Interpretation

          The odds of CTE double every 2.6 years of football played. After accounting for brain bank selection, the magnitude of the relationship between years played and CTE status remained consistent. ANN NEUROL 2020;87:116–131

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          Most cited references25

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          National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease: a practical approach.

          We present a practical guide for the implementation of recently revised National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease (AD). Major revisions from previous consensus criteria are: (1) recognition that AD neuropathologic changes may occur in the apparent absence of cognitive impairment, (2) an "ABC" score for AD neuropathologic change that incorporates histopathologic assessments of amyloid β deposits (A), staging of neurofibrillary tangles (B), and scoring of neuritic plaques (C), and (3) more detailed approaches for assessing commonly co-morbid conditions such as Lewy body disease, vascular brain injury, hippocampal sclerosis, and TAR DNA binding protein (TDP)-43 immunoreactive inclusions. Recommendations also are made for the minimum sampling of brain, preferred staining methods with acceptable alternatives, reporting of results, and clinico-pathologic correlations.
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            Chronic traumatic encephalopathy in athletes: progressive tauopathy after repetitive head injury.

            Since the 1920s, it has been known that the repetitive brain trauma associated with boxing may produce a progressive neurological deterioration, originally termed dementia pugilistica, and more recently, chronic traumatic encephalopathy (CTE). We review 48 cases of neuropathologically verified CTE recorded in the literature and document the detailed findings of CTE in 3 profession althletes, 1 football player and 2 boxers. Clinically, CTE is associated with memory disturbances, behavioral and personality changes, parkinsonism, and speech and gait abnormalities. Neuropathologically, CTE is characterized by atrophy of the cerebral hemispheres, medial temporal lobe, thalamus, mammillary bodies, and brainstem, with ventricular dilatation and a fenestrated cavum septum pellucidum. Microscopically, there are extensive tau-immunoreactive neurofibrillary tangles, astrocytic tangles, and spindle-shaped and threadlike neurites throughout the brain. The neurofibrillary degeneration of CTE is distinguished from other tauopathies by preferential involvement of the superficial cortical layers, irregular patchy distribution in the frontal and temporal cortices, propensity for sulcal depths, prominent perivascular, periventricular, and subpial distribution, and marked accumulation of tau-immunoreactive astrocytes. Deposition of beta-amyloid, most commonly as diffuse plaques, occurs in fewer than half the cases. Chronic traumatic encephalopathy is a neuropathologically distinct slowly progressive tauopathy with a clear environmental etiology.
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              Clinicopathological Evaluation of Chronic Traumatic Encephalopathy in Players of American Football.

              Players of American football may be at increased risk of long-term neurological conditions, particularly chronic traumatic encephalopathy (CTE).
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                Author and article information

                Contributors
                amckee@bu.edu
                Journal
                Ann Neurol
                Ann. Neurol
                10.1002/(ISSN)1531-8249
                ANA
                Annals of Neurology
                John Wiley & Sons, Inc. (Hoboken, USA )
                0364-5134
                1531-8249
                23 November 2019
                January 2020
                : 87
                : 1 ( doiID: 10.1002/ana.v87.1 )
                : 116-131
                Affiliations
                [ 1 ] Boston University Alzheimer's Disease and Chronic Traumatic Encephalopathy Center Boston University School of Medicine Boston MA
                [ 2 ] Department of Neurology Boston University School of Medicine Boston MA
                [ 3 ] Framingham Heart Study Boston University School of Medicine Boston MA
                [ 4 ] Department of Rehabilitation Medicine Stanford University School of Medicine Stanford CA
                [ 5 ] Department of Biostatistics Boston University School of Public Health Boston MA
                [ 6 ] Midwestern University Arizona College of Osteopathic Medicine Glendale AZ
                [ 7 ] Data Coordinating Center Boston University School of Public Health Boston MA
                [ 8 ] Concussion Legacy Foundation Boston MA
                [ 9 ] VA Boston Healthcare System, US Department of Veteran Affairs Boston MA
                [ 10 ] Department of Veterans Affairs Medical Center Bedford MA
                [ 11 ] Braintree Rehabilitation Hospital Braintree MA
                [ 12 ] Department of Pathology and Laboratory Medicine Boston University School of Medicine Boston MA
                [ 13 ] Department of Psychiatry Boston University School of Medicine Boston MA
                [ 14 ] Department of Biomedical Engineering Boston University College of Engineering Boston MA
                [ 15 ] Department of Neurosurgery Boston University School of Medicine Boston MA
                [ 16 ] Department of Neurosurgery Emerson Hospital Concord MA
                [ 17 ] Department of Anatomy & Neurobiology Boston University School of Medicine Boston MA
                [ 18 ] Department of Epidemiology Boston University School of Public Health Boston MA
                [ 19 ] Department of Environmental Health Boston University School of Public Health Boston MA
                Author notes
                [*] [* ] Address correspondence to

                Dr McKee, Boston University AD and CTE Center, 72 E Concord Street, Robinson Suite 7800, Boston, MA 02118.

                E‐mail: amckee@ 123456bu.edu

                Author information
                https://orcid.org/0000-0003-1438-5442
                Article
                ANA25611
                10.1002/ana.25611
                6973077
                31589352
                1c07b128-d816-4786-a194-f613af11fde2
                © 2019 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 06 February 2019
                : 27 August 2019
                : 23 September 2019
                Page count
                Figures: 5, Tables: 5, Pages: 16, Words: 9843
                Funding
                Funded by: Alzheimer's Association , open-funder-registry 10.13039/100000957;
                Award ID: NIRG‐15‐362697
                Award ID: NIRG‐305779
                Funded by: Andlinger Foundation
                Funded by: Concussion Legacy Foundation
                Funded by: National Football League , open-funder-registry 10.13039/100006425;
                Funded by: National Institute of Neurological Disorders and Stroke , open-funder-registry 10.13039/100000065;
                Award ID: K23NS102399
                Award ID: R01NS07833
                Award ID: R56NS078337
                Award ID: U01NS086659
                Award ID: U01NS093334
                Funded by: National Institute on Aging , open-funder-registry 10.13039/100000049;
                Award ID: F32NS096803
                Award ID: K23AG046377
                Award ID: P30AG13846
                Award ID: R01AG057902
                Award ID: R01AG061028
                Award ID: R01AG1649
                Award ID: R21HD089088
                Award ID: supplement 0572063345
                Funded by: Nick and Lynn Buoniconti Foundation
                Funded by: the National Operating Committee on Standards for Athletic Equipment (NOCSAE) , open-funder-registry 10.13039/100005636;
                Funded by: U.S. Department of Defense , open-funder-registry 10.13039/100000005;
                Award ID: PRARP‐13267017
                Award ID: W81XWH‐13‐2‐0064
                Award ID: W81XWH‐13‐2‐0095
                Award ID: W81XWH1810580
                Funded by: U.S. Department of Veterans Affairs , open-funder-registry 10.13039/100000738;
                Award ID: B6796‐C
                Award ID: CSP 501
                Award ID: I01 CX001135
                Funded by: World Wrestling Entertainment (WWE)
                Categories
                Research Article
                Research Articles
                Custom metadata
                2.0
                January 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.7.5 mode:remove_FC converted:21.01.2020

                Neurology
                Neurology

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