Applying the Bradford Hill Criteria for Causation to Repetitive Head Impacts and Chronic Traumatic Encephalopathy

Christopher J Nowinski¹, Samantha C Bureau¹, Michael E Buckland^{2

3}, Maurice A Curtis⁴, Daniel H Daneshvar^{5

6

7}, Richard L M Faull⁴, Lea T Grinberg^{8

9

10

11}, Elisa L Hill-Yardin^{12

13}, Helen C Murray⁴, Alan J Pearce¹⁴, Catherine M Suter^{2

3}, Adam J White^{15

16}, Adam M Finkel¹⁷, Robert C Cantu^{1

18

19}

Affiliations

¹ Concussion Legacy Foundation, Boston, MA, United States.
² Department of Neuropathology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
³ School of Medical Sciences, University of Sydney, Camperdown, NSW, Australia.
⁴ Department of Anatomy and Medical Imaging and Centre for Brain Research, Faculty of Medical and Health Science, University of Auckland, Auckland, New Zealand.
⁵ Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, MA, United States.
⁶ Department of Physical Medicine and Rehabilitation, Massachusetts General Hospital, Boston, MA, United States.
⁷ Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Boston, MA, United States.
⁸ Memory and Aging Center, Department of Neurology, University of California, San Francisco, San Francisco, CA, United States.
⁹ Global Brain Health Institute, University of California, San Francisco, San Francisco, CA, United States.
¹⁰ Department of Pathology, University of Sao Paulo Medical School, São Paulo, Brazil.
¹¹ Department of Pathology, University of California, San Francisco, San Francisco, CA, United States.
¹² School of Health and Biomedical Sciences, STEM College, RMIT University, Bundoora, VIC, Australia.
¹³ Department of Anatomy & Physiology, The University of Melbourne, Parkville, VIC, Australia.
¹⁴ College of Science, Health, and Engineering, La Trobe University, Melbourne, VIC, Australia.
¹⁵ Department of Sport, Health Science, and Social Work, Oxford Brookes University, Oxford, United Kingdom.
¹⁶ Concussion Legacy Foundation UK, Cheltenham, United Kingdom.
¹⁷ Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI, United States.
¹⁸ Department of Neurology, Boston University School of Medicine, Boston, MA, United States.
¹⁹ Department of Neurosurgery, Emerson Hospital, Concord, MA, United States.

PMID: 35937061
PMCID: PMC9355594
DOI: 10.3389/fneur.2022.938163

Review

Applying the Bradford Hill Criteria for Causation to Repetitive Head Impacts and Chronic Traumatic Encephalopathy

Christopher J Nowinski et al. Front Neurol. 2022.

. 2022 Jul 22:13:938163.

doi: 10.3389/fneur.2022.938163. eCollection 2022.

Authors

Affiliations

¹ Concussion Legacy Foundation, Boston, MA, United States.
² Department of Neuropathology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
³ School of Medical Sciences, University of Sydney, Camperdown, NSW, Australia.
⁴ Department of Anatomy and Medical Imaging and Centre for Brain Research, Faculty of Medical and Health Science, University of Auckland, Auckland, New Zealand.
⁵ Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, MA, United States.
⁶ Department of Physical Medicine and Rehabilitation, Massachusetts General Hospital, Boston, MA, United States.
⁷ Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Boston, MA, United States.
⁸ Memory and Aging Center, Department of Neurology, University of California, San Francisco, San Francisco, CA, United States.
⁹ Global Brain Health Institute, University of California, San Francisco, San Francisco, CA, United States.
¹⁰ Department of Pathology, University of Sao Paulo Medical School, São Paulo, Brazil.
¹¹ Department of Pathology, University of California, San Francisco, San Francisco, CA, United States.
¹² School of Health and Biomedical Sciences, STEM College, RMIT University, Bundoora, VIC, Australia.
¹³ Department of Anatomy & Physiology, The University of Melbourne, Parkville, VIC, Australia.
¹⁴ College of Science, Health, and Engineering, La Trobe University, Melbourne, VIC, Australia.
¹⁵ Department of Sport, Health Science, and Social Work, Oxford Brookes University, Oxford, United Kingdom.
¹⁶ Concussion Legacy Foundation UK, Cheltenham, United Kingdom.
¹⁷ Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI, United States.
¹⁸ Department of Neurology, Boston University School of Medicine, Boston, MA, United States.
¹⁹ Department of Neurosurgery, Emerson Hospital, Concord, MA, United States.

PMID: 35937061
PMCID: PMC9355594
DOI: 10.3389/fneur.2022.938163

Abstract

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with a history of repetitive head impacts (RHI). CTE was described in boxers as early as the 1920s and by the 1950s it was widely accepted that hits to the head caused some boxers to become "punch drunk." However, the recent discovery of CTE in American and Australian-rules football, soccer, rugby, ice hockey, and other sports has resulted in renewed debate on whether the relationship between RHI and CTE is causal. Identifying the strength of the evidential relationship between CTE and RHI has implications for public health and medico-legal issues. From a public health perspective, environmentally caused diseases can be mitigated or prevented. Medico-legally, millions of children are exposed to RHI through sports participation; this demographic is too young to legally consent to any potential long-term risks associated with this exposure. To better understand the strength of evidence underlying the possible causal relationship between RHI and CTE, we examined the medical literature through the Bradford Hill criteria for causation. The Bradford Hill criteria, first proposed in 1965 by Sir Austin Bradford Hill, provide a framework to determine if one can justifiably move from an observed association to a verdict of causation. The Bradford Hill criteria include nine viewpoints by which to evaluate human epidemiologic evidence to determine if causation can be deduced: strength, consistency, specificity, temporality, biological gradient, plausibility, coherence, experiment, and analogy. We explored the question of causation by evaluating studies on CTE as it relates to RHI exposure. Through this lens, we found convincing evidence of a causal relationship between RHI and CTE, as well as an absence of evidence-based alternative explanations. By organizing the CTE literature through this framework, we hope to advance the global conversation on CTE mitigation efforts.

Keywords: Bradford Hill; causation; chronic traumatic encephalopathy (CTE); epidemiology; public health; punch drunk; repetitive head impact.

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Conflict of interest statement

CN is a volunteer member of the Mackey-White Committee of the National Football League Players Association for which he receives travel support and an advisor to Oxeia Biopharmaceuticals, LLC, Aurora CTS, and PreCon Health. DD provides ad-hoc expert testimony in medico-legal matters pertaining to traumatic brain injury. EH-Y is a scientific advisor for Vernx Pty Ltd. No funding was received from Vernx. AP currently receives partial research salary funding from Erasmus+ strategic partnerships program (2019-1-IE01-KA202-051555) and previously received partial research funding from the Sports Health Check Charity (Australia), Australian Football League, Impact Technologies Inc., and Samsung Corporation, and is remunerated for expert advice to medico-legal practices. RC is a paid consultant to the National Football League Head, Neck and Spine Committee, a vice president and chair of the scientific advisory committee of the National Operating Committee on Standards for Athletic Equipment, and a consultant to the Concussion Legacy Foundation; he also receives royalties from Houghton Mifflin Harcourt and compensation for expert legacy opinion to the National Collegiate Athletic Association and National Hockey League and is a volunteer member of the National Football League Players Association for which he receives travel support. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor RA declared a shared affiliation with the author LG at the time of review.

References

1. Martland HS. Punch drunk. J Am Med Assoc. (1928) 91:1103–7. 10.1001/jama.1928.02700150029009 - DOI - PubMed
1. Montenigro PH, Corp DT, Stein TD, Cantu RC, Stern RA. Chronic traumatic encephalopathy: historical origins and current perspective. Annu Rev Clin Psychol. (2015) 11:309–30. 10.1146/annurev-clinpsy-032814-112814 - DOI - PubMed
1. Corsellis JAN, Bruton CJ, Freeman-Browne D. The aftermath of boxing. Psychol Med. (1973) 3:270–303. 10.1017/S0033291700049588 - DOI - PubMed
1. Roberts GW, Whitwell HL, Acland PR, Bruton CJ. Dementia in a punch-drunk wife. Lancet. (1990) 335:918–9. 10.1016/0140-6736(90)90520-F - DOI - PubMed
1. Hof PR, Bouras C, Buée L, Delacourte A, Perl DP, Morrison JH. Differential distribution of neurofibrillary tangles in the cerebral cortex of dementia pugilistica and Alzheimer's disease cases. Acta Neuropathol. (1992) 85:23–30. 10.1007/BF00304630 - DOI - PubMed

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Applying the Bradford Hill Criteria for Causation to Repetitive Head Impacts and Chronic Traumatic Encephalopathy

Affiliations

Applying the Bradford Hill Criteria for Causation to Repetitive Head Impacts and Chronic Traumatic Encephalopathy

Authors

Affiliations

Abstract

Conflict of interest statement

References

Publication types

Grants and funding

LinkOut - more resources

Full Text Sources

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