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Title: Tau PET and multimodal brain imaging in patients at risk for chronic traumatic encephalopathy

Abstract

OBJECTIVE: To characterize individual and group-level neuroimaging findings in patients at risk for Chronic Traumatic Encephalopathy (CTE). METHODS: Eleven male patients meeting criteria for Traumatic Encephalopathy Syndrome (TES, median age: 64) underwent neurologic evaluation, 3-Tesla MRI, and PET with [18F]-Flortaucipir (FTP, tau-PET) and [11C]-Pittsburgh compound B (PIB, amyloid-PET). Six patients underwent [18F]-Fluorodeoxyglucose-PET (FDG, glucose metabolism). We assessed imaging findings at the individual patient level, and in group-level comparisons with modality-specific groups of cognitively normal older adults (CN). Tau-PET findings in patients with TES were also compared to a matched group of patients with mild cognitive impairment or dementia due to Alzheimer's disease (AD). RESULTS: All patients with TES sustained repetitive head injury participating in impact sports, ten in American football. Three patients met criteria for dementia and eight had mild cognitive impairment. Two patients were amyloid-PET positive and harbored the most severe MRI atrophy, FDG hypometabolism, and FTP-tau PET binding. Among the nine amyloid-negative patients, tau-PET showed either mildly elevated frontotemporal binding, a "dot-like" pattern, or no elevated binding. Medial temporal FTP was mildly elevated in a subset of amyloid-negative patients, but values were considerably lower than in AD. Voxelwise analyses revealed a convergence of imaging abnormalities (higher FTP binding,more » lower FDG, lower gray matter volumes) in frontotemporal areas in TES compared to controls. CONCLUSIONS: Mildly elevated tau-PET binding was observed in a subset of amyloid-negative patients at risk for CTE, in a distribution consistent with CTE pathology stages III-IV. FTP-PET may be useful as a biomarker of tau pathology in CTE but is unlikely to be sensitive to early disease stages.« less

Authors:
 [1];  [1];  [1]; ORCiD logo [2];  [1];  [1];  [1];  [1];  [2];  [2];  [3];  [2];  [1];  [1];  [1];  [1];  [4];  [5]
  1. Univ. of California, San Francisco, CA (United States)
  2. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
  3. Univ. of California, San Francisco, CA (United States); San Francisco Veterans Affair Medical Center, CA (United States)
  4. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Univ. of California, Berkeley, CA (United States)
  5. Univ. of California, San Francisco, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Univ. of California, Berkeley, CA (United States)
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC); National Institute on Aging; Alzheimer's Association
OSTI Identifier:
1599790
Grant/Contract Number:  
AC02-05CH11231; R01-AG045611; R01-AG034570; P50-AG023501; AARF-16-443577
Resource Type:
Accepted Manuscript
Journal Name:
NeuroImage: Clinical
Additional Journal Information:
Journal Volume: 24; Journal Issue: C; Journal ID: ISSN 2213-1582
Publisher:
Elsevier
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; chronic traumatic encephalopathy (CTE); imaging; positron emission tomography (PET); tau; amyloid; magnetic resonance imaging (MRI)

Citation Formats

Lesman-Segev, Orit H., La Joie, Renaud, Stephens, Melanie L., Sonni, Ida, Tsai, Richard, Bourakova, Viktoriya, Visani, Adrienne V., Edwards, Lauren, O'Neil, James P., Baker, Suzanne L, Gardner, Raquel C., Janabi, Mustafa, Chaudhary, Kiran, Perry, David C., Kramer, Joel H., Miller, Bruce L., Jagust, William J., and Rabinovici, Gil D. Tau PET and multimodal brain imaging in patients at risk for chronic traumatic encephalopathy. United States: N. p., 2019. Web. doi:10.1016/j.nicl.2019.102025.
Lesman-Segev, Orit H., La Joie, Renaud, Stephens, Melanie L., Sonni, Ida, Tsai, Richard, Bourakova, Viktoriya, Visani, Adrienne V., Edwards, Lauren, O'Neil, James P., Baker, Suzanne L, Gardner, Raquel C., Janabi, Mustafa, Chaudhary, Kiran, Perry, David C., Kramer, Joel H., Miller, Bruce L., Jagust, William J., & Rabinovici, Gil D. Tau PET and multimodal brain imaging in patients at risk for chronic traumatic encephalopathy. United States. doi:10.1016/j.nicl.2019.102025.
Lesman-Segev, Orit H., La Joie, Renaud, Stephens, Melanie L., Sonni, Ida, Tsai, Richard, Bourakova, Viktoriya, Visani, Adrienne V., Edwards, Lauren, O'Neil, James P., Baker, Suzanne L, Gardner, Raquel C., Janabi, Mustafa, Chaudhary, Kiran, Perry, David C., Kramer, Joel H., Miller, Bruce L., Jagust, William J., and Rabinovici, Gil D. Thu . "Tau PET and multimodal brain imaging in patients at risk for chronic traumatic encephalopathy". United States. doi:10.1016/j.nicl.2019.102025. https://www.osti.gov/servlets/purl/1599790.
@article{osti_1599790,
title = {Tau PET and multimodal brain imaging in patients at risk for chronic traumatic encephalopathy},
author = {Lesman-Segev, Orit H. and La Joie, Renaud and Stephens, Melanie L. and Sonni, Ida and Tsai, Richard and Bourakova, Viktoriya and Visani, Adrienne V. and Edwards, Lauren and O'Neil, James P. and Baker, Suzanne L and Gardner, Raquel C. and Janabi, Mustafa and Chaudhary, Kiran and Perry, David C. and Kramer, Joel H. and Miller, Bruce L. and Jagust, William J. and Rabinovici, Gil D.},
abstractNote = {OBJECTIVE: To characterize individual and group-level neuroimaging findings in patients at risk for Chronic Traumatic Encephalopathy (CTE). METHODS: Eleven male patients meeting criteria for Traumatic Encephalopathy Syndrome (TES, median age: 64) underwent neurologic evaluation, 3-Tesla MRI, and PET with [18F]-Flortaucipir (FTP, tau-PET) and [11C]-Pittsburgh compound B (PIB, amyloid-PET). Six patients underwent [18F]-Fluorodeoxyglucose-PET (FDG, glucose metabolism). We assessed imaging findings at the individual patient level, and in group-level comparisons with modality-specific groups of cognitively normal older adults (CN). Tau-PET findings in patients with TES were also compared to a matched group of patients with mild cognitive impairment or dementia due to Alzheimer's disease (AD). RESULTS: All patients with TES sustained repetitive head injury participating in impact sports, ten in American football. Three patients met criteria for dementia and eight had mild cognitive impairment. Two patients were amyloid-PET positive and harbored the most severe MRI atrophy, FDG hypometabolism, and FTP-tau PET binding. Among the nine amyloid-negative patients, tau-PET showed either mildly elevated frontotemporal binding, a "dot-like" pattern, or no elevated binding. Medial temporal FTP was mildly elevated in a subset of amyloid-negative patients, but values were considerably lower than in AD. Voxelwise analyses revealed a convergence of imaging abnormalities (higher FTP binding, lower FDG, lower gray matter volumes) in frontotemporal areas in TES compared to controls. CONCLUSIONS: Mildly elevated tau-PET binding was observed in a subset of amyloid-negative patients at risk for CTE, in a distribution consistent with CTE pathology stages III-IV. FTP-PET may be useful as a biomarker of tau pathology in CTE but is unlikely to be sensitive to early disease stages.},
doi = {10.1016/j.nicl.2019.102025},
journal = {NeuroImage: Clinical},
number = C,
volume = 24,
place = {United States},
year = {2019},
month = {10}
}

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