Developing methods to detect and diagnose chronic traumatic encephalopathy during life: rationale, design, and methodology for the DIAGNOSE CTE Research Project

Authors

Michael L. Alosco, Boston University Alzheimer's Disease Research Center, Boston University CTE Center, Department of Neurology, Boston University School of Medicine, Boston, MA, USA.
Megan L. Mariani, Boston University CTE Center, Boston University School of Medicine, Boston, MA, USA.
Charles H. Adler, Department of Neurology, Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale, AZ, USA.
Laura J. Balcer, Departments of Neurology, Population Health and Ophthalmology, NYU Grossman School of Medicine, New York, NY, USA.
Charles Bernick, Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, USA.
Rhoda Au, Boston University Alzheimer's Disease Research Center, Boston University CTE Center, Framingham Heart Study, and Slone Epidemiology Center, Boston, MA, USA.
Sarah J. Banks, Departments of Neuroscience and Psychiatry, University of California, San Diego, CA, USA.
William B. Barr, Department of Neurology, NYU Grossman School of Medicine, New York, NY, USA.
Sylvain Bouix, Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Robert C. Cantu, Boston University Alzheimer's Disease Research Center, Departments of Neurology and Neurosurgery, Boston University School of Medicine, Boston, MA, USA.
Michael J. Coleman, Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Boston, MA, USA.Follow
David W. Dodick, Department of Neurology, Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale, AZ, USA.
Lindsay A. Farrer, Departments of Medicine (Biomedical Genetics), Neurology, Ophthalmology, Epidemiology, and Biostatistics, BU Schools of Medicine and Public Health, Boston, MA, USA.
Yonas E. Geda, Alzheimer's Disease and Memory Disorders Program, Department of Neurology, Barrow Neurological Institute, Phoenix, AZ, USA.Follow
Douglas I. Katz, Department of Neurology, Boston University School of Medicine, Boston, MA, USA.
Inga K. Koerte, Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Neil W. Kowall, Boston University Alzheimer's Disease Research Center, Departments of Neurology and Neurosurgery, Boston University School of Medicine, Boston, MA, USA.
Alexander P. Lin, Center for Clinical Spectroscopy, Department of Radiology, Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Daniel S. Marcus, Department of Radiology, Washington University School of Medicine, St. Louis, MO, USA.
Kenneth L. Marek, Institute for Neurodegenerative Disorders, Invicro, LLC, New Haven, CT, USA.
Michael D. McClean, Department of Environmental Health, Boston University School of Public Health, Boston, MA, USA.
Ann C. McKee, Boston University Alzheimer's Disease Research Center, Boston University CTE Center, Department of Neurology, Boston University School of Medicine, Boston, MA, USA.
Jesse Mez, Boston University Alzheimer's Disease Research Center, Boston University CTE Center, Framingham Heart Study, Department of Neurology, Boston University School of Medicine, Boston, MA, USA.
Joseph N. Palmisano, Biostatistics and Epidemiology Data Analytics Center (BEDAC), Boston University School of Public Health, Boston, MA, USA.
Elaine R. Peskind, VA Northwest Mental Illness Research, Education, and Clinical Center, VA Puget Sound Health Care System, Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA, USA.
Yorghos Tripodis, Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
Robert W. Turner, Department of Clinical Research & Leadership, The George Washington University School of Medicine & Health Sciences, Washington, DC, USA.
Jennifer V. Wethe, Department of Psychiatry and Psychology, Mayo Clinic School of Medicine, Mayo Clinic Arizona, Scottsdale, AZ, USA.
Jeffrey L. Cummings, Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, University of Nevada Las Vegas, Las Vegas, NV, USA.
Eric M. Reiman, Banner Alzheimer's Institute, University of Arizona, Arizona State University, Translational Genomics Research Institute, and Arizona Alzheimer's Consortium, Phoenix, AZ, USA.
Martha E. Shenton, Psychiatry Neuroimaging Laboratory, Departments of Psychiatry and Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Robert A. Stern, Boston University Alzheimer's Disease Research Center, Boston University CTE Center, Departments of Neurology, Neurosurgery, and Anatomy & Neurobiology, Boston University School of Medicine, Boston, MA, USA. bobstern@bu.edu.

Document Type

Article

Abstract

BACKGROUND: Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease that has been neuropathologically diagnosed in brain donors exposed to repetitive head impacts, including boxers and American football, soccer, ice hockey, and rugby players. CTE cannot yet be diagnosed during life. In December 2015, the National Institute of Neurological Disorders and Stroke awarded a seven-year grant (U01NS093334) to fund the "Diagnostics, Imaging, and Genetics Network for the Objective Study and Evaluation of Chronic Traumatic Encephalopathy (DIAGNOSE CTE) Research Project." The objectives of this multicenter project are to: develop in vivo fluid and neuroimaging biomarkers for CTE; characterize its clinical presentation; refine and validate clinical research diagnostic criteria (i.e., traumatic encephalopathy syndrome [TES]); examine repetitive head impact exposure, genetic, and other risk factors; and provide shared resources of anonymized data and biological samples to the research community. In this paper, we provide a detailed overview of the rationale, design, and methods for the DIAGNOSE CTE Research Project. METHODS: The targeted sample and sample size was 240 male participants, ages 45-74, including 120 former professional football players, 60 former collegiate football players, and 60 asymptomatic participants without a history of head trauma or participation in organized contact sports. Participants were evaluated at one of four U.S. sites and underwent the following baseline procedures: neurological and neuropsychological examinations; tau and amyloid positron emission tomography; magnetic resonance imaging and spectroscopy; lumbar puncture; blood and saliva collection; and standardized self-report measures of neuropsychiatric, cognitive, and daily functioning. Study partners completed similar informant-report measures. Follow-up evaluations were intended to be in-person and at 3 years post-baseline. Multidisciplinary diagnostic consensus conferences are held, and the reliability and validity of TES diagnostic criteria are examined. RESULTS: Participant enrollment and all baseline evaluations were completed in February 2020. Three-year follow-up evaluations began in October 2019. However, in-person evaluation ceased with the COVID-19 pandemic, and resumed as remote, 4-year follow-up evaluations (including telephone-, online-, and videoconference-based cognitive, neuropsychiatric, and neurologic examinations, as well as in-home blood draw) in February 2021. CONCLUSIONS: Findings from the DIAGNOSE CTE Research Project should facilitate detection and diagnosis of CTE during life, and thereby accelerate research on risk factors, mechanisms, epidemiology, treatment, and prevention of CTE. TRIAL REGISTRATION: NCT02798185.

Medical Subject Headings

Aged; COVID-19; Chronic Traumatic Encephalopathy (diagnosis); Humans; Male; Middle Aged; Neurodegenerative Diseases; Pandemics; Reproducibility of Results; SARS-CoV-2

Publication Date

8-12-2021

Publication Title

Alzheimer's research & therapy

E-ISSN

1758-9193

Volume

13

Issue

1

First Page

136

PubMed ID

34384490

Digital Object Identifier (DOI)

10.1186/s13195-021-00872-x

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