title: Assessing clinicopathological correlation in chronic traumatic encephalopathy: rationale and methods for the UNITE study.
abstract: BACKGROUND
  Chronic traumatic encephalopathy (CTE) is a progressive neurodegeneration associated with repetitive head impacts. Understanding Neurologic Injury and Traumatic Encephalopathy (UNITE) is a U01 project recently funded by the National Institute of Neurological Disorders and Stroke and the National Institute of Biomedical Imaging and Bioengineering. The goal of the UNITE project is to examine the neuropathology and clinical presentation of brain donors designated as "at risk" for the development of CTE based on prior athletic or military exposure. Here, we present the rationale and methodology for UNITE.
  
  
  METHODS
  Over the course of 4 years, we will analyze the brains and spinal cords of 300 deceased subjects who had a history of repetitive head impacts sustained during participation in contact sports at the professional or collegiate level or during military service. Clinical data are collected through medical record review and retrospective structured and unstructured family interviews conducted by a behavioral neurologist or neuropsychologist. Blinded to the clinical data, a neuropathologist conducts a comprehensive assessment for neurodegenerative disease, including CTE, using published criteria. At a clinicopathological conference, a panel of physicians and neuropsychologists, blinded to the neuropathological data, reaches a clinical consensus diagnosis using published criteria, including proposed clinical research criteria for CTE.
  
  
  RESULTS
  We will investigate the validity of these clinical criteria and sources of error by using recently validated neuropathological criteria as a gold standard for CTE diagnosis. We also will use statistical modeling to identify diagnostic features that best predict CTE pathology.
  
  
  CONCLUSIONS
  The UNITE study is a novel and methodologically rigorous means of assessing clinicopathological correlation in CTE. Our findings will be critical for developing future iterations of CTE clinical diagnostic criteria.
authors.affiliation: Alzheimer's Disease Center, Boston University School of Medicine, 72 East Concord Street, B-7800, Boston, MA, 02118, USA. jessemez@bu.edu.|Department of Neurology, Boston University School of Medicine, 72 East Concord Street, Boston, MA, 02118, USA. jessemez@bu.edu.
authors.forename: Jesse
authors.initials: J
authors.lastname: Mez
authors.affiliation: Alzheimer's Disease Center, Boston University School of Medicine, 72 East Concord Street, B-7800, Boston, MA, 02118, USA. tsolom@bu.edu.
authors.forename: Todd M
authors.initials: TM
authors.lastname: Solomon
authors.affiliation: Alzheimer's Disease Center, Boston University School of Medicine, 72 East Concord Street, B-7800, Boston, MA, 02118, USA. ddanesh@bu.edu.|Sports Legacy Institute, 230 Second Avenue, Waltham, MA, 02451, USA. ddanesh@bu.edu.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Daneshvar
authors.affiliation: Alzheimer's Disease Center, Boston University School of Medicine, 72 East Concord Street, B-7800, Boston, MA, 02118, USA. lmurphy2@bu.edu.|Department of Neurology, Boston University School of Medicine, 72 East Concord Street, Boston, MA, 02118, USA. lmurphy2@bu.edu.
authors.forename: Lauren
authors.initials: L
authors.lastname: Murphy
authors.affiliation: Alzheimer's Disease Center, Boston University School of Medicine, 72 East Concord Street, B-7800, Boston, MA, 02118, USA. pkiernan@bu.edu.|Department of Neurology, Boston University School of Medicine, 72 East Concord Street, Boston, MA, 02118, USA. pkiernan@bu.edu.
authors.forename: Patrick T
authors.initials: PT
authors.lastname: Kiernan
authors.affiliation: Alzheimer's Disease Center, Boston University School of Medicine, 72 East Concord Street, B-7800, Boston, MA, 02118, USA. valmont@bu.edu.|Department of Anatomy and Neurobiology, Boston University School of Medicine, 72 East Concord Street, Boston, MA, 02118, USA. valmont@bu.edu.
authors.forename: Philip H
authors.initials: PH
authors.lastname: Montenigro
authors.affiliation: Alzheimer's Disease Center, Boston University School of Medicine, 72 East Concord Street, B-7800, Boston, MA, 02118, USA. jkriegel@bu.edu.|Department of Neurology, Boston University School of Medicine, 72 East Concord Street, Boston, MA, 02118, USA. jkriegel@bu.edu.
authors.forename: Joshua
authors.initials: J
authors.lastname: Kriegel
authors.affiliation: Alzheimer's Disease Center, Boston University School of Medicine, 72 East Concord Street, B-7800, Boston, MA, 02118, USA. babdolmo@bu.edu.|Department of Neurology, Boston University School of Medicine, 72 East Concord Street, Boston, MA, 02118, USA. babdolmo@bu.edu.
authors.forename: Bobak
authors.initials: B
authors.lastname: Abdolmohammadi
authors.affiliation: Alzheimer's Disease Center, Boston University School of Medicine, 72 East Concord Street, B-7800, Boston, MA, 02118, USA. bfry@bu.edu.|Department of Neurology, Boston University School of Medicine, 72 East Concord Street, Boston, MA, 02118, USA. bfry@bu.edu.
authors.forename: Brian
authors.initials: B
authors.lastname: Fry
authors.affiliation: Alzheimer's Disease Center, Boston University School of Medicine, 72 East Concord Street, B-7800, Boston, MA, 02118, USA. kbabcock@bu.edu.|Department of Neurology, Boston University School of Medicine, 72 East Concord Street, Boston, MA, 02118, USA. kbabcock@bu.edu.
authors.forename: Katharine J
authors.initials: KJ
authors.lastname: Babcock
authors.affiliation: Alzheimer's Disease Center, Boston University School of Medicine, 72 East Concord Street, B-7800, Boston, MA, 02118, USA. jadams2@bu.edu.|Department of Neurology, Boston University School of Medicine, 72 East Concord Street, Boston, MA, 02118, USA. jadams2@bu.edu.
authors.forename: Jason W
authors.initials: JW
authors.lastname: Adams
authors.affiliation: Alzheimer's Disease Center, Boston University School of Medicine, 72 East Concord Street, B-7800, Boston, MA, 02118, USA. abourlas@bu.edu.|Department of Neurology, Boston University School of Medicine, 72 East Concord Street, Boston, MA, 02118, USA. abourlas@bu.edu.
authors.forename: Alexandra P
authors.initials: AP
authors.lastname: Bourlas
authors.affiliation: Alzheimer's Disease Center, Boston University School of Medicine, 72 East Concord Street, B-7800, Boston, MA, 02118, USA. zpapadopoulos@colgate.edu.|Department of Neurology, Boston University School of Medicine, 72 East Concord Street, Boston, MA, 02118, USA. zpapadopoulos@colgate.edu.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Papadopoulos
authors.affiliation: Sports Legacy Institute, 230 Second Avenue, Waltham, MA, 02451, USA. lmchale@sportslegacy.org.
authors.forename: Lisa
authors.initials: L
authors.lastname: McHale
authors.affiliation: Data Coordinating Center, Boston University School of Public Health, 715 Albany Street, Boston, MA, 02118, USA. ardaugh@bu.edu.
authors.forename: Brent M
authors.initials: BM
authors.lastname: Ardaugh
authors.affiliation: Data Coordinating Center, Boston University School of Public Health, 715 Albany Street, Boston, MA, 02118, USA. brmartin@bu.edu.
authors.forename: Brett R
authors.initials: BR
authors.lastname: Martin
authors.affiliation: Data Coordinating Center, Boston University School of Public Health, 715 Albany Street, Boston, MA, 02118, USA. dixon@bu.edu.
authors.forename: Diane
authors.initials: D
authors.lastname: Dixon
authors.affiliation: Sports Legacy Institute, 230 Second Avenue, Waltham, MA, 02451, USA. nowinski@sportslegacy.org.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Nowinski
authors.affiliation: Data Coordinating Center, Boston University School of Public Health, 715 Albany Street, Boston, MA, 02118, USA. chaisson@bu.edu.
authors.forename: Christine
authors.initials: C
authors.lastname: Chaisson
authors.affiliation: Alzheimer's Disease Center, Boston University School of Medicine, 72 East Concord Street, B-7800, Boston, MA, 02118, USA. valvarez@bu.edu.|VA Boston Healthcare System, U.S. Department of Veterans Affairs, 150 South Huntington Street, Jamaica Plain, MA, 02130, USA. valvarez@bu.edu.|Department of Veterans Affairs Medical Center, 200 Springs Road, Bedford, MA, 01730, USA. valvarez@bu.edu.|Department of Pathology, Boston University School of Medicine, 72 East Concord Street, Boston, MA, 02118, USA. valvarez@bu.edu.
authors.forename: Victor E
authors.initials: VE
authors.lastname: Alvarez
authors.affiliation: Department of Biostatistics, Boston University School of Public Health, 72 East Concord Street, Boston, MA, 02118, USA. yorghos@bu.edu.
authors.forename: Yorghos
authors.initials: Y
authors.lastname: Tripodis
authors.affiliation: Alzheimer's Disease Center, Boston University School of Medicine, 72 East Concord Street, B-7800, Boston, MA, 02118, USA. tdstein@bu.edu.|VA Boston Healthcare System, U.S. Department of Veterans Affairs, 150 South Huntington Street, Jamaica Plain, MA, 02130, USA. tdstein@bu.edu.|Department of Veterans Affairs Medical Center, 200 Springs Road, Bedford, MA, 01730, USA. tdstein@bu.edu.|Department of Pathology, Boston University School of Medicine, 72 East Concord Street, Boston, MA, 02118, USA. tdstein@bu.edu.
authors.forename: Thor D
authors.initials: TD
authors.lastname: Stein
authors.affiliation: Alzheimer's Disease Center, Boston University School of Medicine, 72 East Concord Street, B-7800, Boston, MA, 02118, USA. lgold@bu.edu.|Department of Neurology, Boston University School of Medicine, 72 East Concord Street, Boston, MA, 02118, USA. lgold@bu.edu.
authors.forename: Lee E
authors.initials: LE
authors.lastname: Goldstein
authors.affiliation: Department of Neurology, Boston University School of Medicine, 72 East Concord Street, Boston, MA, 02118, USA. dkatz@bu.edu.|Braintree Rehabilitation Hospital, 250 Pond Street, Braintree, MA, 02184, USA. dkatz@bu.edu.
authors.forename: Douglas I
authors.initials: DI
authors.lastname: Katz
authors.affiliation: Alzheimer's Disease Center, Boston University School of Medicine, 72 East Concord Street, B-7800, Boston, MA, 02118, USA. nkowall@bu.edu.|VA Boston Healthcare System, U.S. Department of Veterans Affairs, 150 South Huntington Street, Jamaica Plain, MA, 02130, USA. nkowall@bu.edu.|Department of Pathology, Boston University School of Medicine, 72 East Concord Street, Boston, MA, 02118, USA. nkowall@bu.edu.|Department of Pathology and Laboratory Medicine, Boston University School of Medicine, 72 East Concord Street, Boston, MA, 02118, USA. nkowall@bu.edu.
authors.forename: Neil W
authors.initials: NW
authors.lastname: Kowall
authors.affiliation: Alzheimer's Disease Center, Boston University School of Medicine, 72 East Concord Street, B-7800, Boston, MA, 02118, USA. rcantu@emersonhosp.org.|Department of Neurology, Boston University School of Medicine, 72 East Concord Street, Boston, MA, 02118, USA. rcantu@emersonhosp.org.|Sports Legacy Institute, 230 Second Avenue, Waltham, MA, 02451, USA. rcantu@emersonhosp.org.|Department of Neurosurgery, Boston University School of Medicine, 72 East Concord Street, Boston, MA, 02118, USA. rcantu@emersonhosp.org.|Department of Neurosurgery, Emerson Hospital, 133 Old Road to Nine Acre Corner, Concord, MA, 01742, USA. rcantu@emersonhosp.org.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Cantu
authors.affiliation: Alzheimer's Disease Center, Boston University School of Medicine, 72 East Concord Street, B-7800, Boston, MA, 02118, USA. bobstern@bu.edu.|Department of Neurology, Boston University School of Medicine, 72 East Concord Street, Boston, MA, 02118, USA. bobstern@bu.edu.|Department of Anatomy and Neurobiology, Boston University School of Medicine, 72 East Concord Street, Boston, MA, 02118, USA. bobstern@bu.edu.|Department of Neurosurgery, Boston University School of Medicine, 72 East Concord Street, Boston, MA, 02118, USA. bobstern@bu.edu.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Stern
authors.affiliation: Alzheimer's Disease Center, Boston University School of Medicine, 72 East Concord Street, B-7800, Boston, MA, 02118, USA. amckee@bu.edu.|Department of Neurology, Boston University School of Medicine, 72 East Concord Street, Boston, MA, 02118, USA. amckee@bu.edu.|VA Boston Healthcare System, U.S. Department of Veterans Affairs, 150 South Huntington Street, Jamaica Plain, MA, 02130, USA. amckee@bu.edu.|Department of Veterans Affairs Medical Center, 200 Springs Road, Bedford, MA, 01730, USA. amckee@bu.edu.|Department of Pathology, Boston University School of Medicine, 72 East Concord Street, Boston, MA, 02118, USA. amckee@bu.edu.|Department of Pathology and Laboratory Medicine, Boston University School of Medicine, 72 East Concord Street, Boston, MA, 02118, USA. amckee@bu.edu.
authors.forename: Ann C
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authors.lastname: McKee
mesh_terms: D056352:Athletes; D001265:Athletic Injuries / Q000150:complications; D001921:Brain / Q000473:pathology*; D020208:Brain Injury, Chronic / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D032921:Consensus; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007407:Interviews as Topic; D008297:Male; D008889:Military Personnel; D019636:Neurodegenerative Diseases / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D012189:Retrospective Studies; D013116:Spinal Cord / Q000473:pathology*; D000067398:War-Related Injuries / Q000150:complications