Developing methods to detect and diagnose chronic traumatic encephalopathy during life: rationale, design, and methodology for the DIAGNOSE CTE Research Project
Authors: Alosco Michael L. , Mariani Megan L. , Adler Charles H. , Balcer Laura J. , Bernick Charles , Au Rhoda , Banks Sarah J. , Barr William B. , Bouix Sylvain , Cantu Robert C. , Coleman Michael J. , Dodick David W. , Farrer Lindsay A. , Geda Yonas E. , Katz Douglas I. , Koerte Inga K. , Kowall Neil W. , Lin Alexander P. , Marcus Daniel S. , Marek Kenneth L. , McClean Michael D. , McKee Ann C. , Mez Jesse , Palmisano Joseph N. , Peskind Elaine R. , Tripodis Yorghos , Turner Robert W. , Wethe Jennifer V. , Cummings Jeffrey L. , Reiman Eric M. , Shenton Martha E. , Stern Robert A. ,   for the DIAGNOSE CTE Research Project Investigators, Adler Charles H. , Alosco Michael L. , Au Rhoda , Balcer Laura , Banks Sarah , Barr William , Bernick Charles , Bouix Sylvain , Cantu Robert C. , Chen Kewei , Coleman Michael J. , Cummings Jeffrey L. , Dodick David W. , Farrer Lindsay , Fitzsimmons Jennifer , Geda Yonas , Goldberg Judith , Helm Robert , Johnson Keith A. , Katz Douglas I. , Kirov Ivan , Koerte Inga K. , Kowall Neil , Lin Alexander P. , Lui Yvonne , Marcus Daniel S. , Marek Kenneth L. , Mariani Megan , Marmar Charles , McClean Michael , McKee Ann C. , Mez Jesse , Miller Jason , Palmisano Joseph N. , Pasternak Ofer , Peskind Elaine R. , Protas Hillary , Reiman Eric , Ritter Aaron , Shenton Martha E. , Stern Robert A. , Su Yi , Tripodis Yorghos , Turner Robert W. , Weller Jason , Wethe Jennifer V. 
Published: August 2021

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