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Chronic traumatic encephalopathy is a common co-morbidity, but less frequent primary dementia in former soccer and rugby players

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Lee, Edward B., Kinch, Kevin, Johnson, Victoria E., Trojanowski, John Q., Smith, Douglas H., Stewart, William·2019·Acta Neuropathologica
DOI 10.1007/s00401-019-02030-yPMC PMC6689293
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Abstract

Chronic traumatic encephalopathy (CTE) is reported at high prevalence in selected autopsy case series of former contact sports athletes. Nevertheless, the contribution of CTE pathology to clinical presentation and its interaction with co-morbid neurodegenerative pathologies remain unclear. To address these issues, we performed comprehensive neuropathology assessments on the brains of former athletes with dementia and considered these findings together with detailed clinical histories to derive an integrated clinicopathological diagnosis for each case. Consecutive, autopsy-acquired brains from former soccer and rugby players with dementia were assessed for neurodegenerative pathologies using established and preliminary consensus protocols. Thereafter, next of kin interviews were conducted to obtain detailed accounts of the patient's clinical presentation and course of disease to inform a final, integrated clinicopathological diagnosis. Neuropathologic change consistent with CTE (CTE-NC) was confirmed in five of seven former soccer and three of four former rugby players' brains, invariably in combination with mixed, often multiple neurodegenerative pathologies. However, in just three cases was the integrated dementia diagnosis consistent with CTE, the remainder having alternate diagnoses, with the most frequent integrated diagnosis Alzheimer's disease (AD) (four cases; one as mixed AD and vascular dementia). This consecutive autopsy series identifies neuropathologic change consistent with preliminary diagnostic criteria for CTE (CTE-NC) in a high proportion of former soccer and rugby players dying with dementia. However, in the majority, CTE-NC appears as a co-morbidity rather than the primary, dementia causing pathology. As such, we suggest that while CTE-NC might be common in former athletes with dementia, in many cases its clinical significance remains uncertain.

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Fig. 1 Representative macroscopic and histologic images from Case 8, a former rugby union player who first presented in his 50 s with a change in behavior marked by increasing levels of frustration and agitation associated with aggressive outbursts. In the following years, these behavioral and personality symptoms progressed, with cognitive disturbance evolving late in the course of disease. The patient died in his 70 s, 18 years after first presentation. On examination of the whole brain, there is gyral atrophy with associated sulcal thinning, most evident in frontal lobes (a). Sectioning the brain in the coronal plain through the mammillary bodies reveals ventriculomegally, consistent with the atrophy noted externally, in addition to fenestration of the septum pellucidum (b; white arrow). Staining sections for hyperphosphorylated tau (p-tau; PHF1) reveal widespread cortical immunoreactivity, within which are multiple patches of increased staining density towards the depths of cortical sulci (c), which on higher power are seen to coincide with neuronal and astroglial immunoreactive profiles clustered around small blood vessels (d; black arrows). In addition to widespread p-tau pathology, numerous Aβ plaques are present (e; 6f3d). The final integrated dementia diagnosis was CTE-D
Fig. 1 Representative macroscopic and histologic images from Case 8, a former rugby union player who first presented in his 50 s with a change in behavior marked by increasing levels of frustration and agitation associated with aggressive outbursts. In the following years, these behavioral and personality symptoms progressed, with cognitive disturbance evolving late in the course of disease. The patient died in his 70 s, 18 years after first presentation. On examination of the whole brain, there is gyral atrophy with associated sulcal thinning, most evident in frontal lobes (a). Sectioning the brain in the coronal plain through the mammillary bodies reveals ventriculomegally, consistent with the atrophy noted externally, in addition to fenestration of the septum pellucidum (b; white arrow). Staining sections for hyperphosphorylated tau (p-tau; PHF1) reveal widespread cortical immunoreactivity, within which are multiple patches of increased staining density towards the depths of cortical sulci (c), which on higher power are seen to coincide with neuronal and astroglial immunoreactive profiles clustered around small blood vessels (d; black arrows). In addition to widespread p-tau pathology, numerous Aβ plaques are present (e; 6f3d). The final integrated dementia diagnosis was CTE-DCC BY · PubMed Central
Fig. 2 Representative images from Case 3, a former soccer player who first came to attention in his 60 s with mild cognitive impairment. There followed a steady progression in these symptoms, with exacerbations in the post-operative period, and with the development of visual hallucinations and motor signs leading to a clinical suspicion of Parkinson’s disease, or related disorder. After an 8-year course, the patient died in his 70 s. Staining for p-tau reveals patches of neuronal and astroglial immunoreactivity at the depths of cortical sulci (a), which on higher power are clustered around small cortical vessels (b; PHF1). Frequent Aβ plaques are also present (c; 6f3d). In addition, staining for alpha-synuclein reveals extensive cortical staining (d), with numerous cortical Lewy bodies present (e; black arrows). Sections of the midbrain also reveal scattered classical Lewy bodies (f; white arrow) within remaining pigmented neurons of the substantia nigra. Given the stereotypical clinical presentation and associated neuropathological features, an integrated diagnosis of dementia with Lewy bodies was made, with co-morbid CTE-NC noted
Fig. 2 Representative images from Case 3, a former soccer player who first came to attention in his 60 s with mild cognitive impairment. There followed a steady progression in these symptoms, with exacerbations in the post-operative period, and with the development of visual hallucinations and motor signs leading to a clinical suspicion of Parkinson’s disease, or related disorder. After an 8-year course, the patient died in his 70 s. Staining for p-tau reveals patches of neuronal and astroglial immunoreactivity at the depths of cortical sulci (a), which on higher power are clustered around small cortical vessels (b; PHF1). Frequent Aβ plaques are also present (c; 6f3d). In addition, staining for alpha-synuclein reveals extensive cortical staining (d), with numerous cortical Lewy bodies present (e; black arrows). Sections of the midbrain also reveal scattered classical Lewy bodies (f; white arrow) within remaining pigmented neurons of the substantia nigra. Given the stereotypical clinical presentation and associated neuropathological features, an integrated diagnosis of dementia with Lewy bodies was made, with co-morbid CTE-NC notedCC BY · PubMed Central

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Research works printed but not linked: 1

  1. McKee AC, Stein TD, Nowinski CJ, Stern RA, Deneshvar DH, Alvarez VE et al (2012) The spectrum of disease in chronic traumatic encephalopathy. Brain 136:43–64 · DOI · Paper page

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Metadata

Authors
Lee, E. B., Kinch, K., Johnson, V. E., Trojanowski, J. Q., Smith, D. H., & Stewart, W.
Affiliations
  • University of Pennsylvania (US)
  • Queen Elizabeth University Hospital (GB)
ORCID
Venue
Acta Neuropathologica
Publisher
Springer Science and Business Media LLC
Published
2019-06-01
Volume
138
Issue
3
Pages
389-399
ISSN
  • 0001-6322 (ISSN-L)
  • 1432-0533
DOI
10.1007/s00401-019-02030-y
PMC
PMC6689293
OpenAlex
W2947253577
Cited by
157
References
51
Citations by year
2026: 7 · 2025: 23 · 2024: 12 · 2023: 29 · 2022: 19 · 2021: 26 · 2020: 34 · 2019: 4
FWCI
15.80
Type
journal article
Language
en
Open access
Licence
Locations
  • Acta Neuropathologica (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion, cc-by-sa)
Funders
  • National Institute of Neurological Disorders and Stroke (R01NS092398, R01NS094003, R01NS038104)
  • The Football Association
Topics
  • Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury Research
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Keywords
chronic traumatic encephalopathy, dementia, comorbidities, Alzheimer's disease, clinicopathological diagnosis, contact sports, neuropathology
MeSH terms
Chronic Traumatic Encephalopathy, Aged, Athletic Injuries, Dementia, Football, Humans, Male, Middle Aged, Soccer, Comorbidity

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