TY - JOUR
T1 - Developing methods to detect and diagnose chronic traumatic encephalopathy during life
T2 - rationale, design, and methodology for the DIAGNOSE CTE Research Project
AU - for the DIAGNOSE CTE Research Project Investigators
AU - Alosco, Michael L.
AU - Mariani, Megan L.
AU - Adler, Charles H.
AU - Balcer, Laura J.
AU - Bernick, Charles
AU - Au, Rhoda
AU - Banks, Sarah J.
AU - Barr, William B.
AU - Bouix, Sylvain
AU - Cantu, Robert C.
AU - Coleman, Michael J.
AU - Dodick, David W.
AU - Farrer, Lindsay A.
AU - Geda, Yonas E.
AU - Katz, Douglas I.
AU - Koerte, Inga K.
AU - Kowall, Neil W.
AU - Lin, Alexander P.
AU - Marcus, Daniel S.
AU - Marek, Kenneth L.
AU - McClean, Michael D.
AU - McKee, Ann C.
AU - Mez, Jesse
AU - Palmisano, Joseph N.
AU - Peskind, Elaine R.
AU - Tripodis, Yorghos
AU - Turner, Robert W.
AU - Wethe, Jennifer V.
AU - Cummings, Jeffrey L.
AU - Reiman, Eric M.
AU - Shenton, Martha E.
AU - Stern, Robert A.
AU - Banks, Sarah
AU - Barr, William
AU - Chen, Kewei
AU - Farrer, Lindsay
AU - Fitzsimmons, Jennifer
AU - Geda, Yonas
AU - Goldberg, Judith
AU - Helm, Robert
AU - Johnson, Keith A.
AU - Kirov, Ivan
AU - Kowall, Neil
AU - Lui, Yvonne
AU - Mariani, Megan
AU - Marmar, Charles
AU - McClean, Michael
AU - Miller, Jason
AU - Pasternak, Ofer
AU - Protas, Hillary
AU - Reiman, Eric
AU - Ritter, Aaron
AU - Stern, Robert A.
AU - Su, Yi
AU - Turner, Robert W.
AU - Weller, Jason
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
KW - Biomarkers
KW - Chronic traumatic encephalopathy
KW - Cognitive function
KW - College football
KW - Concussion
KW - Football
KW - Head trauma
KW - MRI
KW - MRS
KW - National Football League
KW - Neurodegenerative disease
KW - Neuroimaging
KW - Positron emission tomography
KW - Remote assessment
KW - Repetitive head impacts
KW - Subconcussion
KW - Tau
KW - Traumatic brain injury
KW - Traumatic encephalopathy syndrome
UR - http://www.scopus.com/inward/record.url?scp=85112678073&partnerID=8YFLogxK
U2 - 10.1186/s13195-021-00872-x
DO - 10.1186/s13195-021-00872-x
M3 - Article
C2 - 34384490
AN - SCOPUS:85112678073
SN - 1758-9193
VL - 13
JO - Alzheimer's Research and Therapy
JF - Alzheimer's Research and Therapy
IS - 1
M1 - 136
ER -