title: Mixed pathologies including chronic traumatic encephalopathy account for dementia in retired association football (soccer) players.
abstract: In retired professional association football (soccer) players with a past history of repetitive head impacts, chronic traumatic encephalopathy (CTE) is a potential neurodegenerative cause of dementia and motor impairments. From 1980 to 2010, 14 retired footballers with dementia were followed up regularly until death. Their clinical data, playing career, and concussion history were prospectively collected. Next-of-kin provided consent for six to have post-mortem brain examination. Of the 14 male participants, 13 were professional and 1 was a committed amateur. All were skilled headers of the ball and had played football for an average of 26 years. Concussion rate was limited in six cases to one episode each during their careers. All cases developed progressive cognitive impairment with an average age at onset of 63.6 years and disease duration of 10 years. Neuropathological examination revealed septal abnormalities in all six post-mortem cases, supportive of a history of chronic repetitive head impacts. Four cases had pathologically confirmed CTE; concomitant pathologies included Alzheimer's disease (N = 6), TDP-43 (N = 6), cerebral amyloid angiopathy (N = 5), hippocampal sclerosis (N = 2), corticobasal degeneration (N = 1), dementia with Lewy bodies (N = 1), and vascular pathology (N = 1); and all would have contributed synergistically to the clinical manifestations. The pathological diagnosis of CTE was established in four individuals according to the latest consensus diagnostic criteria. This finding is probably related to their past prolonged exposure to repetitive head impacts from head-to-player collisions and heading the ball thousands of time throughout their careers. Alzheimer's disease and TDP-43 pathologies are common concomitant findings in CTE, both of which are increasingly considered as part of the CTE pathological entity in older individuals. Association football is the most popular sport in the world and the potential link between repetitive head impacts from playing football and CTE as indicated from our findings is of considerable public health interest. Clearly, a definitive link cannot be established in this clinico-pathological series, but our findings support the need for further systematic investigation, including large-scale case-control studies to identify at risk groups of footballers which will justify for the implementation of protective strategies.
authors.affiliation: Queen Square Brain Bank for Neurological Disorders, UCL Institute of Neurology, University College London, London, UK.|Reta Lila Weston Institute for Neurological Studies, UCL Institute of Neurology, 1 Wakefield Street, WC1N 1PJ, London, UK.|Department of Molecular Neuroscience, UCL Institute of Neurology, University College London, London, UK.
authors.forename: Helen
authors.initials: H
authors.lastname: Ling
authors.affiliation: Department of Clinical Neuroscience, UCL Institute of Neurology, London, UK.
authors.forename: Huw R
authors.initials: HR
authors.lastname: Morris
authors.affiliation: Department of Cellular Pathology, Cardiff University, Cardiff, Wales, UK.
authors.forename: James W
authors.initials: JW
authors.lastname: Neal
authors.affiliation: Queen Square Brain Bank for Neurological Disorders, UCL Institute of Neurology, University College London, London, UK.|Reta Lila Weston Institute for Neurological Studies, UCL Institute of Neurology, 1 Wakefield Street, WC1N 1PJ, London, UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Lees
authors.affiliation: Queen Square Brain Bank for Neurological Disorders, UCL Institute of Neurology, University College London, London, UK.|Reta Lila Weston Institute for Neurological Studies, UCL Institute of Neurology, 1 Wakefield Street, WC1N 1PJ, London, UK.|Department of Molecular Neuroscience, UCL Institute of Neurology, University College London, London, UK.
authors.forename: John
authors.initials: J
authors.lastname: Hardy
authors.affiliation: Queen Square Brain Bank for Neurological Disorders, UCL Institute of Neurology, University College London, London, UK. janice.holton@ucl.ac.uk.|Reta Lila Weston Institute for Neurological Studies, UCL Institute of Neurology, 1 Wakefield Street, WC1N 1PJ, London, UK. janice.holton@ucl.ac.uk.|Department of Molecular Neuroscience, UCL Institute of Neurology, University College London, London, UK. janice.holton@ucl.ac.uk.
authors.forename: Janice L
authors.initials: JL
authors.lastname: Holton
authors.affiliation: Queen Square Brain Bank for Neurological Disorders, UCL Institute of Neurology, University College London, London, UK. t.revesz@ucl.ac.uk.|Reta Lila Weston Institute for Neurological Studies, UCL Institute of Neurology, 1 Wakefield Street, WC1N 1PJ, London, UK. t.revesz@ucl.ac.uk.|Department of Molecular Neuroscience, UCL Institute of Neurology, University College London, London, UK. t.revesz@ucl.ac.uk.
authors.forename: Tamas
authors.initials: T
authors.lastname: Revesz
authors.affiliation: Cefn Coed Hospital, Swansea, Wales, UK.
authors.forename: David D R
authors.initials: DD
authors.lastname: Williams
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001344:Autopsy; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D002135:Calcium-Binding Proteins; D000070627:Chronic Traumatic Encephalopathy / Q000150:complications*; D004268:DNA-Binding Proteins / Q000378:metabolism; D003704:Dementia / Q000209:etiology* / Q000473:pathology*; D006801:Humans; D008297:Male; D008840:Microfilament Proteins; D008875:Middle Aged; D012179:Retirement; D012189:Retrospective Studies; D000071456:Sequestosome-1 Protein / Q000378:metabolism; D012916:Soccer; D051844:alpha-Synuclein / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
chemical_list: C112986:AIF1 protein, human; D016229:Amyloid beta-Peptides; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D008840:Microfilament Proteins; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; C000598624:TARDBP protein, human; D051844:alpha-Synuclein; D016875:tau Proteins
keywords: Chronic traumatic encephalopathy; Concussion; Football; Heading; Soccer; Tauopathy; Traumatic brain injury