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Published in: Sports Medicine 3/2024

06-10-2023 | Sleep Apnea | Original Research Article

Interaction of Medical Conditions and Football Exposures Associated with Premortem Chronic Traumatic Encephalopathy Diagnosis in Former Professional American Football Players

Authors: Shawn R. Eagle, Rachel Grashow, Heather DiGregorio, Douglas P. Terry, Aaron Baggish, Marc G. Weisskopf, David O. Okonkwo, Ross Zafonte

Published in: Sports Medicine | Issue 3/2024

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Abstract

Background and Objective

Despite being a postmortem diagnosis, former professional American-style football players report receiving chronic traumatic encephalopathy (CTE) diagnoses from medical care providers. However, many players also report other health conditions that manifest with cognitive and psychological symptoms. The purpose of this study was to identify how medical conditions, psychological disorders, and football exposure combinations are associated with former athletes reporting a premortem CTE diagnosis.

Methods

This study was a cross-sectional cohort survey from 2015 to 2019 of 4033 former professional American-style football players. Demographics (age, race, domestic status, primary care recipient), football-related factors (position, years of professional play, burden of symptoms following head impacts, performance-enhancing drug use), and comorbidities (sleep apnea, psychological disorder status [depression and anxiety; either depression or anxiety; neither depression nor anxiety], diabetes mellitus, attention-deficit/hyperactivity disorder, hypertension, heart conditions, high cholesterol, stroke, cancer, low testosterone, chronic pain, current and maximum body mass index) were recorded. A Chi-square automatic interaction detection (CHAID) decision tree model identified interactive effects between demographics, health conditions, and football exposures on the CTE diagnosis.

Results

Depression showed the strongest univariate association with premortem CTE diagnoses (odds ratio [OR] = 9.5, 95% confidence interval [CI] 6.0–15.3). CHAID differentiated participants with premortem CTE diagnoses with 98.2% accuracy and area under the curve = 0.81. Participants reporting both depression and anxiety were more likely to have a CTE diagnosis compared with participants who reported no psychological disorders (OR = 12.2; 95% CI 7.3–21.1) or one psychological disorder (OR = 4.5; 95% CI 1.9–13.0). Sleep apnea was also associated with a CTE diagnosis amongst those with both depression and anxiety (OR = 2.7; 95% CI 1.4–5.2).

Conclusions

Clinical phenotypes including psychological disorders and sleep apnea were strongly associated with an increased likelihood of having received a pre-mortem CTE diagnosis in former professional football players. Depression, anxiety, and sleep apnea produce cognitive symptoms, are treatable conditions, and should be distinguished from neurodegenerative disease.
Literature
1.
go back to reference Katz DI, Bernick C, Dodick DW, Mez J, Mariani ML, Adler CH, et al. National Institute of Neurological Disorders and Stroke consensus diagnostic criteria for traumatic encephalopathy syndrome. Neurology. 2021;96(18):848–63.CrossRefPubMedPubMedCentral Katz DI, Bernick C, Dodick DW, Mez J, Mariani ML, Adler CH, et al. National Institute of Neurological Disorders and Stroke consensus diagnostic criteria for traumatic encephalopathy syndrome. Neurology. 2021;96(18):848–63.CrossRefPubMedPubMedCentral
2.
go back to reference McKee AC, Stein TD, Nowinski CJ, Stern RA, Daneshvar DH, Alvarez VE, et al. The spectrum of disease in chronic traumatic encephalopathy. Brain. 2013;136(1):43–64.CrossRefPubMed McKee AC, Stein TD, Nowinski CJ, Stern RA, Daneshvar DH, Alvarez VE, et al. The spectrum of disease in chronic traumatic encephalopathy. Brain. 2013;136(1):43–64.CrossRefPubMed
3.
go back to reference Grashow R, Weisskopf MG, Baggish A, Speizer FE, Whittington AJ, Nadler L, et al. Premortem chronic traumatic encephalopathy diagnoses in professional football. Ann Neurol. 2020;88(1):106–12.CrossRefPubMedPubMedCentral Grashow R, Weisskopf MG, Baggish A, Speizer FE, Whittington AJ, Nadler L, et al. Premortem chronic traumatic encephalopathy diagnoses in professional football. Ann Neurol. 2020;88(1):106–12.CrossRefPubMedPubMedCentral
4.
go back to reference Farr SA, Yamada KA, Butterfield DA, Abdul HM, Xu L, Miller NE, et al. Obesity and hypertriglyceridemia produce cognitive impairment. Endocrinology. 2008;149(5):2628–36.CrossRefPubMedPubMedCentral Farr SA, Yamada KA, Butterfield DA, Abdul HM, Xu L, Miller NE, et al. Obesity and hypertriglyceridemia produce cognitive impairment. Endocrinology. 2008;149(5):2628–36.CrossRefPubMedPubMedCentral
5.
go back to reference Gualtieri CT, Morgan DW. The frequency of cognitive impairment in patients with anxiety, depression, and bipolar disorder: an unaccounted source of variance in clinical trials. J Clin Psychiatry. 2008;69(7):7441.CrossRef Gualtieri CT, Morgan DW. The frequency of cognitive impairment in patients with anxiety, depression, and bipolar disorder: an unaccounted source of variance in clinical trials. J Clin Psychiatry. 2008;69(7):7441.CrossRef
6.
7.
go back to reference Tenforde AS, Cortez B, Coughlan-Gifford E, Grashow R, Baker J, Baggish AL, et al. Individual and cumulative health afflictions are associated with greater impairment in physical and mental function in former professional American style football players. PM R. 2022;14(1):30–9.CrossRefPubMed Tenforde AS, Cortez B, Coughlan-Gifford E, Grashow R, Baker J, Baggish AL, et al. Individual and cumulative health afflictions are associated with greater impairment in physical and mental function in former professional American style football players. PM R. 2022;14(1):30–9.CrossRefPubMed
8.
go back to reference Cherrier M, Asthana S, Plymate S, Baker L, Matsumoto A, Peskind E, et al. Testosterone supplementation improves spatial and verbal memory in healthy older men. Neurology. 2001;57(1):80–8.CrossRefPubMed Cherrier M, Asthana S, Plymate S, Baker L, Matsumoto A, Peskind E, et al. Testosterone supplementation improves spatial and verbal memory in healthy older men. Neurology. 2001;57(1):80–8.CrossRefPubMed
9.
go back to reference Stewart W, Allinson K, Al-Sarraj S, Bachmeier C, Barlow K, Belli A, et al. Primum non nocere: a call for balance when reporting on CTE. Lancet Neurol. 2019;18(3):231–3.CrossRefPubMedPubMedCentral Stewart W, Allinson K, Al-Sarraj S, Bachmeier C, Barlow K, Belli A, et al. Primum non nocere: a call for balance when reporting on CTE. Lancet Neurol. 2019;18(3):231–3.CrossRefPubMedPubMedCentral
10.
go back to reference Larson DC, Bobeuf F, Bergeron H, et al. Impact of aerobic exercise on attention and visual memory in an ageing mild traumatic brain injury population. Brain Inj. 2017;31(6–7):821. Larson DC, Bobeuf F, Bergeron H, et al. Impact of aerobic exercise on attention and visual memory in an ageing mild traumatic brain injury population. Brain Inj. 2017;31(6–7):821.
11.
go back to reference Chen JM, Pauker K, Gaitherd SE, Hamilton DL, Sherman JW. Black + White = not White: a minority bias in categorizations of Black-White multiracials. J Exp Soc Psychol. 2018;78:43–54.CrossRef Chen JM, Pauker K, Gaitherd SE, Hamilton DL, Sherman JW. Black + White = not White: a minority bias in categorizations of Black-White multiracials. J Exp Soc Psychol. 2018;78:43–54.CrossRef
12.
go back to reference Ho AK, Sidanius J, Levin DT, Banaji MR. Evidence for hypodescent and racial hierarchy in the categorization and perception of biracial individuals. J Pers Soc Psychol. 2011;100(3):492–506.CrossRefPubMed Ho AK, Sidanius J, Levin DT, Banaji MR. Evidence for hypodescent and racial hierarchy in the categorization and perception of biracial individuals. J Pers Soc Psychol. 2011;100(3):492–506.CrossRefPubMed
13.
go back to reference Krosch AR, Berntsen L, Amodio DM, Jost JT, Van Bavel JJ. On the ideology of hypodescent: political conservatism predicts categorization of racially ambiguous faces as Black. J Exp Soc Psychol. 2013;49:1196–203.CrossRef Krosch AR, Berntsen L, Amodio DM, Jost JT, Van Bavel JJ. On the ideology of hypodescent: political conservatism predicts categorization of racially ambiguous faces as Black. J Exp Soc Psychol. 2013;49:1196–203.CrossRef
14.
go back to reference Grashow R, Weisskopf MG, Miller KK, Nathan DM, Zafonte R, Speizer FE, et al. Association of concussion symptoms with testosterone levels and erectile dysfunction in former professional US-style football players. JAMA Neurol. 2019;76(12):1428–38.CrossRefPubMedPubMedCentral Grashow R, Weisskopf MG, Miller KK, Nathan DM, Zafonte R, Speizer FE, et al. Association of concussion symptoms with testosterone levels and erectile dysfunction in former professional US-style football players. JAMA Neurol. 2019;76(12):1428–38.CrossRefPubMedPubMedCentral
15.
go back to reference Roberts AL, Pascual-Leone A, Speizer FE, Zafonte RD, Baggish AL, Taylor H Jr, et al. Exposure to American football and neuropsychiatric health in former National Football League players: findings from the Football Players Health Study. Am J Sports Med. 2019;47(12):2871–80.CrossRefPubMedPubMedCentral Roberts AL, Pascual-Leone A, Speizer FE, Zafonte RD, Baggish AL, Taylor H Jr, et al. Exposure to American football and neuropsychiatric health in former National Football League players: findings from the Football Players Health Study. Am J Sports Med. 2019;47(12):2871–80.CrossRefPubMedPubMedCentral
16.
go back to reference Roberts AL, Zafonte RD, Speizer FE, Baggish A, Taylor HA, Nadler L, et al. Modifiable risk factors for poor cognitive function in former American-style football players: findings from the Harvard Football Players Health Study. J Neurotrauma. 2021;38(2):189–95.PubMed Roberts AL, Zafonte RD, Speizer FE, Baggish A, Taylor HA, Nadler L, et al. Modifiable risk factors for poor cognitive function in former American-style football players: findings from the Harvard Football Players Health Study. J Neurotrauma. 2021;38(2):189–95.PubMed
17.
go back to reference Eagle SR, Brent D, Covassin T, Elbin RJ, Wallace J, Ortega J, et al. Exploration of race and ethnicity, sex, sport-related concussion, depression history, and suicide attempts in US youth. JAMA Netw Open. 2022;5(7): e2219934.CrossRefPubMedPubMedCentral Eagle SR, Brent D, Covassin T, Elbin RJ, Wallace J, Ortega J, et al. Exploration of race and ethnicity, sex, sport-related concussion, depression history, and suicide attempts in US youth. JAMA Netw Open. 2022;5(7): e2219934.CrossRefPubMedPubMedCentral
18.
go back to reference Eagle SR, Kontos AP, Mi QI, Flanagan SD, Nindl BC, Beals K, et al. Shared neuromuscular performance traits in military personnel with prior concussion. Med Sci Sports Exerc. 2019;51(8):1619–25.CrossRefPubMed Eagle SR, Kontos AP, Mi QI, Flanagan SD, Nindl BC, Beals K, et al. Shared neuromuscular performance traits in military personnel with prior concussion. Med Sci Sports Exerc. 2019;51(8):1619–25.CrossRefPubMed
19.
go back to reference Connaboy C, Eagle SR, Johnson CD, Flanagan SD, Mi QI, Nindl BC. Using machine learning to predict lower-extremity injury in US Special Forces. Med Sci Sports Exerc. 2019;51(5):1073–9.CrossRefPubMed Connaboy C, Eagle SR, Johnson CD, Flanagan SD, Mi QI, Nindl BC. Using machine learning to predict lower-extremity injury in US Special Forces. Med Sci Sports Exerc. 2019;51(5):1073–9.CrossRefPubMed
20.
go back to reference McCarty JA, Hastak M. Segmentation approaches in data-mining: a comparison of RFM, CHAID, and logistic regression. J Business Res. 2007;60(6):656–62.CrossRef McCarty JA, Hastak M. Segmentation approaches in data-mining: a comparison of RFM, CHAID, and logistic regression. J Business Res. 2007;60(6):656–62.CrossRef
21.
go back to reference Kelly JP, Priemer DS, Perl DP, Filley CM. Sports concussion and chronic traumatic encephalopathy: finding a path forward. Ann Neurol. 2023;93(2):222–5.CrossRefPubMedPubMedCentral Kelly JP, Priemer DS, Perl DP, Filley CM. Sports concussion and chronic traumatic encephalopathy: finding a path forward. Ann Neurol. 2023;93(2):222–5.CrossRefPubMedPubMedCentral
22.
23.
go back to reference Iverson GL, Gardner AJ. Risk of misdiagnosing chronic traumatic encephalopathy in men with depression. J Neuropsychiatry Clin Neurosci. 2020;32(2):139–46.CrossRefPubMed Iverson GL, Gardner AJ. Risk of misdiagnosing chronic traumatic encephalopathy in men with depression. J Neuropsychiatry Clin Neurosci. 2020;32(2):139–46.CrossRefPubMed
24.
go back to reference Iverson GL, Merz ZC, Terry DP. Examining the research criteria for traumatic encephalopathy syndrome in middle-aged men from the general population who played contact sports in high school. Front Neurol. 2021;12: 632618.CrossRefPubMedPubMedCentral Iverson GL, Merz ZC, Terry DP. Examining the research criteria for traumatic encephalopathy syndrome in middle-aged men from the general population who played contact sports in high school. Front Neurol. 2021;12: 632618.CrossRefPubMedPubMedCentral
25.
go back to reference Asken BM, Tanner JA, VandeVrede L, Casaletto KB, Staffaroni AM, Mundada N, et al. Multi-modal biomarkers of repetitive head impacts and traumatic encephalopathy syndrome: a clinicopathological case series. J Neurotrauma. 2022;39(17–18):1195–213.CrossRefPubMedPubMedCentral Asken BM, Tanner JA, VandeVrede L, Casaletto KB, Staffaroni AM, Mundada N, et al. Multi-modal biomarkers of repetitive head impacts and traumatic encephalopathy syndrome: a clinicopathological case series. J Neurotrauma. 2022;39(17–18):1195–213.CrossRefPubMedPubMedCentral
26.
go back to reference Ritter A, Shan G, Montes A, Randall R, Bernick C. Traumatic encephalopathy syndrome: application of new criteria to a cohort exposed to repetitive head impacts. Br J Sports Med. 2023;57(7):389–94.CrossRefPubMed Ritter A, Shan G, Montes A, Randall R, Bernick C. Traumatic encephalopathy syndrome: application of new criteria to a cohort exposed to repetitive head impacts. Br J Sports Med. 2023;57(7):389–94.CrossRefPubMed
27.
go back to reference Hazrati LN, Schwab N. Embracing the unknown in the diagnosis of traumatic encephalopathy syndrome. Neurology. 2021;96(18):835–6.CrossRefPubMed Hazrati LN, Schwab N. Embracing the unknown in the diagnosis of traumatic encephalopathy syndrome. Neurology. 2021;96(18):835–6.CrossRefPubMed
28.
go back to reference Schwab N, Hazrati LN. Assessing the limitations and biases in the current understanding of chronic traumatic encephalopathy. J Alzheimers Dis. 2018;64(4):1067–76.CrossRefPubMed Schwab N, Hazrati LN. Assessing the limitations and biases in the current understanding of chronic traumatic encephalopathy. J Alzheimers Dis. 2018;64(4):1067–76.CrossRefPubMed
29.
go back to reference Van Ommeren R, Hazrati LN. Pathological assessment of chronic traumatic encephalopathy: review of concepts and methodology. Acad Forensic Pathol. 2018;8(3):555–64.CrossRefPubMedPubMedCentral Van Ommeren R, Hazrati LN. Pathological assessment of chronic traumatic encephalopathy: review of concepts and methodology. Acad Forensic Pathol. 2018;8(3):555–64.CrossRefPubMedPubMedCentral
30.
go back to reference Iverson GL, Luoto TM, Karhunen PJ, Castellani RJ. Mild chronic traumatic encephalopathy neuropathology in people with no known participation in contact sports or history of repetitive neurotrauma. J Neuropathol Exp Neurol. 2019;78(7):615–25.CrossRefPubMedPubMedCentral Iverson GL, Luoto TM, Karhunen PJ, Castellani RJ. Mild chronic traumatic encephalopathy neuropathology in people with no known participation in contact sports or history of repetitive neurotrauma. J Neuropathol Exp Neurol. 2019;78(7):615–25.CrossRefPubMedPubMedCentral
31.
go back to reference Postupna N, Rose SE, Gibbons LE, Coleman NM, Hellstern LL, Ritchie K, et al. The delayed neuropathological consequences of traumatic brain injury in a community-based sample. Front Neurol. 2021;12: 624696.CrossRefPubMedPubMedCentral Postupna N, Rose SE, Gibbons LE, Coleman NM, Hellstern LL, Ritchie K, et al. The delayed neuropathological consequences of traumatic brain injury in a community-based sample. Front Neurol. 2021;12: 624696.CrossRefPubMedPubMedCentral
32.
go back to reference Forrest SL, Kril JJ, Wagner S, Hönigschnabl S, Reiner A, Fischer P, et al. Chronic traumatic encephalopathy (CTE) is absent from a European community-based aging cohort while cortical aging-related tau astrogliopathy (ARTAG) is highly prevalent. J Neuropathol Exp Neurol. 2019;78(5):398–405.CrossRefPubMed Forrest SL, Kril JJ, Wagner S, Hönigschnabl S, Reiner A, Fischer P, et al. Chronic traumatic encephalopathy (CTE) is absent from a European community-based aging cohort while cortical aging-related tau astrogliopathy (ARTAG) is highly prevalent. J Neuropathol Exp Neurol. 2019;78(5):398–405.CrossRefPubMed
33.
go back to reference Ling H, Holton JL, Shaw K, Davey K, Lashley T, Revesz T. Histological evidence of chronic traumatic encephalopathy in a large series of neurodegenerative diseases. Acta Neuropathol. 2015;130(6):891–3.CrossRefPubMed Ling H, Holton JL, Shaw K, Davey K, Lashley T, Revesz T. Histological evidence of chronic traumatic encephalopathy in a large series of neurodegenerative diseases. Acta Neuropathol. 2015;130(6):891–3.CrossRefPubMed
34.
go back to reference Eagle SR, Okonkwo DO. Telling the whole story: bibliometric network analysis to evaluate impact of media attention on chronic traumatic encephalopathy research. J Neurotrauma. 2023;40(1–2):148–54.CrossRefPubMed Eagle SR, Okonkwo DO. Telling the whole story: bibliometric network analysis to evaluate impact of media attention on chronic traumatic encephalopathy research. J Neurotrauma. 2023;40(1–2):148–54.CrossRefPubMed
35.
go back to reference Wolfson DI, Kuhn AW, Kerr ZY, Brett BL, Yengo-Kahn AM, Solomon GS, et al. Chronic traumatic encephalopathy research viewed in the public domain: what makes headlines? Brain Inj. 2020;34(4):528–34.CrossRefPubMed Wolfson DI, Kuhn AW, Kerr ZY, Brett BL, Yengo-Kahn AM, Solomon GS, et al. Chronic traumatic encephalopathy research viewed in the public domain: what makes headlines? Brain Inj. 2020;34(4):528–34.CrossRefPubMed
36.
go back to reference Iverson GL, Gardner AJ, Shultz SR, Solomon GS, McCrory P, Zafonte R, et al. Chronic traumatic encephalopathy neuropathology might not be inexorably progressive or unique to repetitive neurotrauma. Brain. 2019;142(12):3672–93.CrossRefPubMedPubMedCentral Iverson GL, Gardner AJ, Shultz SR, Solomon GS, McCrory P, Zafonte R, et al. Chronic traumatic encephalopathy neuropathology might not be inexorably progressive or unique to repetitive neurotrauma. Brain. 2019;142(12):3672–93.CrossRefPubMedPubMedCentral
37.
go back to reference Schwab N, Wennberg R, Grenier K, Tartaglia C, Tator C, Hazrati LN. Association of position played and career duration and chronic traumatic encephalopathy at autopsy in elite football and hockey players. Neurology. 2021;96(14):e1835–43.CrossRefPubMedPubMedCentral Schwab N, Wennberg R, Grenier K, Tartaglia C, Tator C, Hazrati LN. Association of position played and career duration and chronic traumatic encephalopathy at autopsy in elite football and hockey players. Neurology. 2021;96(14):e1835–43.CrossRefPubMedPubMedCentral
38.
go back to reference Kuhn AW, Yengo-Kahn AM, Kerr ZY, Zuckerman SL. Sports concussion research, chronic traumatic encephalopathy and the media: repairing the disconnect. Br J Sports Med. 2017;51(24):1732–3.CrossRefPubMed Kuhn AW, Yengo-Kahn AM, Kerr ZY, Zuckerman SL. Sports concussion research, chronic traumatic encephalopathy and the media: repairing the disconnect. Br J Sports Med. 2017;51(24):1732–3.CrossRefPubMed
Metadata
Title
Interaction of Medical Conditions and Football Exposures Associated with Premortem Chronic Traumatic Encephalopathy Diagnosis in Former Professional American Football Players
Authors
Shawn R. Eagle
Rachel Grashow
Heather DiGregorio
Douglas P. Terry
Aaron Baggish
Marc G. Weisskopf
David O. Okonkwo
Ross Zafonte
Publication date
06-10-2023
Publisher
Springer International Publishing
Published in
Sports Medicine / Issue 3/2024
Print ISSN: 0112-1642
Electronic ISSN: 1179-2035
DOI
https://doi.org/10.1007/s40279-023-01942-w

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