Tau positron-emission tomography in former national football league players

Robert A. Stern, Charles H. Adler, Kewei Chen, Michael Navitsky, Ji Luo, David W. Dodick, Michael L. Alosco, Yorghos Tripodis, Dhruman D. Goradia, Brett Martin, Diego Mastroeni, Nathan G. Fritts, Johnny Jarnagin, Michael D. Devous, Mark A. Mintun, Michael J. Pontecorvo, Martha E. Shenton, Eric M. Reiman

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease that has been associated with a history of repetitive head impacts. The neuropathological diagnosis is based on a specific pattern of tau deposition with minimal amyloid-beta deposition that differs from other disorders, including Alzheimer’s disease. The feasibility of detecting tau and amyloid deposition in the brains of living persons at risk for CTE has not been well studied. METHODS We used flortaucipir positron-emission tomography (PET) and florbetapir PET to measure deposition of tau and amyloid-beta, respectively, in the brains of former National Football League (NFL) players with cognitive and neuropsychiatric symptoms and in asymptomatic men with no history of traumatic brain injury. Automated image-analysis algorithms were used to compare the regional tau standardized uptake value ratio (SUVR, the ratio of radioactivity in a cerebral region to that in the cerebellum as a reference) between the two groups and to explore the associations of SUVR with symptom severity and with years of football play in the former-player group. RESULTS A total of 26 former players and 31 controls were included in the analysis. The mean flortaucipir SUVR was higher among former players than among controls in three regions of the brain: bilateral superior frontal (1.09 vs. 0.98; adjusted mean difference, 0.13; 95% confidence interval [CI], 0.06 to 0.20; P<0.001), bilateral medial temporal (1.23 vs. 1.12; adjusted mean difference, 0.13; 95% CI, 0.05 to 0.21; P<0.001), and left parietal (1.12 vs. 1.01; adjusted mean difference, 0.12; 95% CI, 0.05 to 0.20; P=0.002). In exploratory analyses, the correlation coefficients in these three regions between the SUVRs and years of play were 0.58 (95% CI, 0.25 to 0.79), 0.45 (95% CI, 0.07 to 0.71), and 0.50 (95% CI, 0.14 to 0.74), respectively. There was no association between tau deposition and scores on cognitive and neuropsychiatric tests. Only one former player had levels of amyloid-beta deposition similar to those in persons with Alzheimer’s disease. CONCLUSIONS A group of living former NFL players with cognitive and neuropsychiatric symptoms had higher tau levels measured by PET than controls in brain regions that are affected by CTE and did not have elevated amyloid-beta levels. Further studies are needed to determine whether elevated CTE-associated tau can be detected in individual persons.

Original languageEnglish (US)
Pages (from-to)1716-1725
Number of pages10
JournalNew England Journal of Medicine
Volume380
Issue number18
DOIs
StatePublished - May 2 2019

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Football
Positron-Emission Tomography
Amyloid
Confidence Intervals
Neurobehavioral Manifestations
Brain
Alzheimer Disease
Neurodegenerative Diseases
Cerebellum
Radioactivity
Head
Chronic Traumatic Encephalopathy

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Stern, R. A., Adler, C. H., Chen, K., Navitsky, M., Luo, J., Dodick, D. W., ... Reiman, E. M. (2019). Tau positron-emission tomography in former national football league players. New England Journal of Medicine, 380(18), 1716-1725. https://doi.org/10.1056/NEJMoa1900757

Tau positron-emission tomography in former national football league players. / Stern, Robert A.; Adler, Charles H.; Chen, Kewei; Navitsky, Michael; Luo, Ji; Dodick, David W.; Alosco, Michael L.; Tripodis, Yorghos; Goradia, Dhruman D.; Martin, Brett; Mastroeni, Diego; Fritts, Nathan G.; Jarnagin, Johnny; Devous, Michael D.; Mintun, Mark A.; Pontecorvo, Michael J.; Shenton, Martha E.; Reiman, Eric M.

In: New England Journal of Medicine, Vol. 380, No. 18, 02.05.2019, p. 1716-1725.

Research output: Contribution to journalArticle

Stern, RA, Adler, CH, Chen, K, Navitsky, M, Luo, J, Dodick, DW, Alosco, ML, Tripodis, Y, Goradia, DD, Martin, B, Mastroeni, D, Fritts, NG, Jarnagin, J, Devous, MD, Mintun, MA, Pontecorvo, MJ, Shenton, ME & Reiman, EM 2019, 'Tau positron-emission tomography in former national football league players', New England Journal of Medicine, vol. 380, no. 18, pp. 1716-1725. https://doi.org/10.1056/NEJMoa1900757
Stern RA, Adler CH, Chen K, Navitsky M, Luo J, Dodick DW et al. Tau positron-emission tomography in former national football league players. New England Journal of Medicine. 2019 May 2;380(18):1716-1725. https://doi.org/10.1056/NEJMoa1900757
Stern, Robert A. ; Adler, Charles H. ; Chen, Kewei ; Navitsky, Michael ; Luo, Ji ; Dodick, David W. ; Alosco, Michael L. ; Tripodis, Yorghos ; Goradia, Dhruman D. ; Martin, Brett ; Mastroeni, Diego ; Fritts, Nathan G. ; Jarnagin, Johnny ; Devous, Michael D. ; Mintun, Mark A. ; Pontecorvo, Michael J. ; Shenton, Martha E. ; Reiman, Eric M. / Tau positron-emission tomography in former national football league players. In: New England Journal of Medicine. 2019 ; Vol. 380, No. 18. pp. 1716-1725.
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abstract = "Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease that has been associated with a history of repetitive head impacts. The neuropathological diagnosis is based on a specific pattern of tau deposition with minimal amyloid-beta deposition that differs from other disorders, including Alzheimer’s disease. The feasibility of detecting tau and amyloid deposition in the brains of living persons at risk for CTE has not been well studied. METHODS We used flortaucipir positron-emission tomography (PET) and florbetapir PET to measure deposition of tau and amyloid-beta, respectively, in the brains of former National Football League (NFL) players with cognitive and neuropsychiatric symptoms and in asymptomatic men with no history of traumatic brain injury. Automated image-analysis algorithms were used to compare the regional tau standardized uptake value ratio (SUVR, the ratio of radioactivity in a cerebral region to that in the cerebellum as a reference) between the two groups and to explore the associations of SUVR with symptom severity and with years of football play in the former-player group. RESULTS A total of 26 former players and 31 controls were included in the analysis. The mean flortaucipir SUVR was higher among former players than among controls in three regions of the brain: bilateral superior frontal (1.09 vs. 0.98; adjusted mean difference, 0.13; 95{\%} confidence interval [CI], 0.06 to 0.20; P<0.001), bilateral medial temporal (1.23 vs. 1.12; adjusted mean difference, 0.13; 95{\%} CI, 0.05 to 0.21; P<0.001), and left parietal (1.12 vs. 1.01; adjusted mean difference, 0.12; 95{\%} CI, 0.05 to 0.20; P=0.002). In exploratory analyses, the correlation coefficients in these three regions between the SUVRs and years of play were 0.58 (95{\%} CI, 0.25 to 0.79), 0.45 (95{\%} CI, 0.07 to 0.71), and 0.50 (95{\%} CI, 0.14 to 0.74), respectively. There was no association between tau deposition and scores on cognitive and neuropsychiatric tests. Only one former player had levels of amyloid-beta deposition similar to those in persons with Alzheimer’s disease. CONCLUSIONS A group of living former NFL players with cognitive and neuropsychiatric symptoms had higher tau levels measured by PET than controls in brain regions that are affected by CTE and did not have elevated amyloid-beta levels. Further studies are needed to determine whether elevated CTE-associated tau can be detected in individual persons.",
author = "Stern, {Robert A.} and Adler, {Charles H.} and Kewei Chen and Michael Navitsky and Ji Luo and Dodick, {David W.} and Alosco, {Michael L.} and Yorghos Tripodis and Goradia, {Dhruman D.} and Brett Martin and Diego Mastroeni and Fritts, {Nathan G.} and Johnny Jarnagin and Devous, {Michael D.} and Mintun, {Mark A.} and Pontecorvo, {Michael J.} and Shenton, {Martha E.} and Reiman, {Eric M.}",
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TY - JOUR

T1 - Tau positron-emission tomography in former national football league players

AU - Stern, Robert A.

AU - Adler, Charles H.

AU - Chen, Kewei

AU - Navitsky, Michael

AU - Luo, Ji

AU - Dodick, David W.

AU - Alosco, Michael L.

AU - Tripodis, Yorghos

AU - Goradia, Dhruman D.

AU - Martin, Brett

AU - Mastroeni, Diego

AU - Fritts, Nathan G.

AU - Jarnagin, Johnny

AU - Devous, Michael D.

AU - Mintun, Mark A.

AU - Pontecorvo, Michael J.

AU - Shenton, Martha E.

AU - Reiman, Eric M.

PY - 2019/5/2

Y1 - 2019/5/2

N2 - Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease that has been associated with a history of repetitive head impacts. The neuropathological diagnosis is based on a specific pattern of tau deposition with minimal amyloid-beta deposition that differs from other disorders, including Alzheimer’s disease. The feasibility of detecting tau and amyloid deposition in the brains of living persons at risk for CTE has not been well studied. METHODS We used flortaucipir positron-emission tomography (PET) and florbetapir PET to measure deposition of tau and amyloid-beta, respectively, in the brains of former National Football League (NFL) players with cognitive and neuropsychiatric symptoms and in asymptomatic men with no history of traumatic brain injury. Automated image-analysis algorithms were used to compare the regional tau standardized uptake value ratio (SUVR, the ratio of radioactivity in a cerebral region to that in the cerebellum as a reference) between the two groups and to explore the associations of SUVR with symptom severity and with years of football play in the former-player group. RESULTS A total of 26 former players and 31 controls were included in the analysis. The mean flortaucipir SUVR was higher among former players than among controls in three regions of the brain: bilateral superior frontal (1.09 vs. 0.98; adjusted mean difference, 0.13; 95% confidence interval [CI], 0.06 to 0.20; P<0.001), bilateral medial temporal (1.23 vs. 1.12; adjusted mean difference, 0.13; 95% CI, 0.05 to 0.21; P<0.001), and left parietal (1.12 vs. 1.01; adjusted mean difference, 0.12; 95% CI, 0.05 to 0.20; P=0.002). In exploratory analyses, the correlation coefficients in these three regions between the SUVRs and years of play were 0.58 (95% CI, 0.25 to 0.79), 0.45 (95% CI, 0.07 to 0.71), and 0.50 (95% CI, 0.14 to 0.74), respectively. There was no association between tau deposition and scores on cognitive and neuropsychiatric tests. Only one former player had levels of amyloid-beta deposition similar to those in persons with Alzheimer’s disease. CONCLUSIONS A group of living former NFL players with cognitive and neuropsychiatric symptoms had higher tau levels measured by PET than controls in brain regions that are affected by CTE and did not have elevated amyloid-beta levels. Further studies are needed to determine whether elevated CTE-associated tau can be detected in individual persons.

AB - Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease that has been associated with a history of repetitive head impacts. The neuropathological diagnosis is based on a specific pattern of tau deposition with minimal amyloid-beta deposition that differs from other disorders, including Alzheimer’s disease. The feasibility of detecting tau and amyloid deposition in the brains of living persons at risk for CTE has not been well studied. METHODS We used flortaucipir positron-emission tomography (PET) and florbetapir PET to measure deposition of tau and amyloid-beta, respectively, in the brains of former National Football League (NFL) players with cognitive and neuropsychiatric symptoms and in asymptomatic men with no history of traumatic brain injury. Automated image-analysis algorithms were used to compare the regional tau standardized uptake value ratio (SUVR, the ratio of radioactivity in a cerebral region to that in the cerebellum as a reference) between the two groups and to explore the associations of SUVR with symptom severity and with years of football play in the former-player group. RESULTS A total of 26 former players and 31 controls were included in the analysis. The mean flortaucipir SUVR was higher among former players than among controls in three regions of the brain: bilateral superior frontal (1.09 vs. 0.98; adjusted mean difference, 0.13; 95% confidence interval [CI], 0.06 to 0.20; P<0.001), bilateral medial temporal (1.23 vs. 1.12; adjusted mean difference, 0.13; 95% CI, 0.05 to 0.21; P<0.001), and left parietal (1.12 vs. 1.01; adjusted mean difference, 0.12; 95% CI, 0.05 to 0.20; P=0.002). In exploratory analyses, the correlation coefficients in these three regions between the SUVRs and years of play were 0.58 (95% CI, 0.25 to 0.79), 0.45 (95% CI, 0.07 to 0.71), and 0.50 (95% CI, 0.14 to 0.74), respectively. There was no association between tau deposition and scores on cognitive and neuropsychiatric tests. Only one former player had levels of amyloid-beta deposition similar to those in persons with Alzheimer’s disease. CONCLUSIONS A group of living former NFL players with cognitive and neuropsychiatric symptoms had higher tau levels measured by PET than controls in brain regions that are affected by CTE and did not have elevated amyloid-beta levels. Further studies are needed to determine whether elevated CTE-associated tau can be detected in individual persons.

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