Brain glucose metabolism and gray matter volume in retired professional soccer players: a cross-sectional [¹⁸F]FDG-PET/MRI study

Abstract

Background Professional soccer athletes are exposed to repetitive head impacts and are at risk of developing chronic traumatic encephalopathy.

Objective To evaluate regional brain glucose metabolism (rBGM) and gray matter (GM) volume in retired soccer players (RSPs).

Methods Male RSPs and age and sex-matched controls prospectively enrolled between 2017 and 2019 underwent neurological and neuropsychological evaluations, brain MRI and [18F]FDG-PET in a 3.0-Tesla PET/MRI scanner. Visual analysis was performed by a blinded neuroradiologist and a blinded nuclear physician. Regional brain glucose metabolism and GM volume were assessed using SPM8 software. Groups were compared using appropriate statistical tests available at SPM8 and R.

Results Nineteen RSPs (median [IQR]: 62 [50–64.5] years old) and 20 controls (60 [48–73] years old) were included. Retired soccer players performed worse on mini-mental state examination, digit span, clock drawing, phonemic and semantic verbal fluency tests, and had reduced rBGM in the left temporal pole (pFDR = 0.008) and the anterior left middle temporal gyrus (pFDR = 0.043). Semantic verbal fluency correlated with rBGM in the right hippocampus, left temporal pole, and posterior left middle temporal gyrus (p ≤ 0.042). Gray matter volume reduction was observed in similar anatomic regions but was less extensive and did not survive correction for multiple comparisons (pFDR ≥ 0.085). Individual [18F]FDG-PET visual analysis revealed seven RSPs with overt hypometabolism in the medial and lateral temporal lobes, frontal lobes, and temporoparietal regions. Retired soccer players had a higher prevalence of septum pellucidum abnormalities on MRI.

Conclusion Retired soccer players had reduced rBGM and GM volume in the temporal lobes and septum pellucidum abnormalities, findings possibly related to repetitive head impacts.

Resumo

Antecedentes Jogadores profissionais de futebol estão expostos a impactos cranianos repetitivos e ao risco de desenvolver encefalopatia traumática crônica.

Objetivo Avaliar o metabolismo glicolítico cerebral regional (MGCr) e o volume de substância cinzenta (vSC) em jogadores de futebol aposentados (JFAs).

Métodos Jogadores de futebol aposentados masculinos e controles pareados por idade e sexo foram incluídos prospectivamente entre 2017 e 2019. Foram realizadas avaliações neurológica e neuropsicológica, ressonância magnética (RM) e [18F]FDG-PET cerebrais (3.0-Tesla PET/RM). As imagens foram analisadas visualmente por um neurorradiologista e um médico nuclear cegos ao grupo de cada participante. O metabolismo glicolítico cerebral regional e o vSC foram avaliados através do programa SPM8. Os grupos foram comparados através de testes estatísticos apropriados disponíveis em SPM8 e R, de acordo com a distribuição e o tipo dos dados.

Resultados Dezenove JFAs (mediana [IIQ]: 62 [50–64.5] anos) e 20 controles (60 [48–73] anos) foram incluídos. Os JFAs tiveram pior desempenho no mini-exame do estado mental e nos testes de dígitos, desenho do relógio, fluência verbal e fluência semântica e apresentaram MGCr significativamente reduzido no polo temporal e no giro temporal médio anterior esquerdos. Fluência semântica (animais) apresentou correlação positiva com MGCr no hipocampo direito, no polo temporal esquerdo e no aspecto posterior do giro temporal médio esquerdo. Menor vSC foi observado nas mesmas regiões, porém este achado não sobreviveu à correção para comparações múltiplas. Análise individual do [18F]FDG-PET cerebral revelou sete JFAs com claro hipometabolismo nas faces medial e lateral dos lobos temporais, nos lobos frontais e nas regiões temporoparietais. Os JFAs apresentaram ainda maior prevalência de anormalidades do septo pelúcido.

Conclusão Os JFAs apresentam MGCr e vSC reduzidos nos lobos temporais, além de anormalidades do septo pelúcido, achados possivelmente relacionados a impactos cranianos repetitivos.

Keywords

Soccer - Brain Injuries, Traumatic - Chronic Traumatic Encephalopathy - Positron-Emission Tomography - Magnetic Resonance Imaging

Palavras-chave

Futebol - Lesões Encefálicas Traumáticas - Encefalopatia Traumática Crônica - Tomografia Por Emissão De Pósitrons - Imageamento Por Ressonância Magnética

Authors' Contributions

MRA, AMC: conceptualization, data curation, formal analysis, investigation, project administration, resources, software, visualization, writing – original draft, writing – review & editing, contributed equally to this work and shared first co-authorship; CGC: data curation, formal analysis, resources, software; BFP: data curation, investigation, project administration, resources, software; ASN, JNI: data curation, investigation, resources; CCG: investigation; MHT: formal analysis; ELSM: data curation, formal analysis; RA, RN: conceptualization, funding acquisition, methodology, resources, writing – review & editing; GGC: funding acquisition, methodology, resources, writing – review & editing; JF: writing – review & editing; CAB: conceptualization, funding acquisition, methodology, supervision, writing – review & editing; CCL: Conceptualization, funding acquisition, methodology, project administration, resources, supervision, writing – review & editing. All authors read and approved the manuscript, and all data were generated in-house and no paper mill was used.

Support

The present study was supported by funding from General Electric (GE Healthcare). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit for publication.

Publikationsverlauf

Eingereicht: 16. September 2022

Angenommen: 15. Januar 2023

Artikel online veröffentlicht:
31. Mai 2023

• References

• 1 Baugh CM, Stamm JM, Riley DO. et al. Chronic traumatic encephalopathy: neurodegeneration following repetitive concussive and subconcussive brain trauma. Brain Imaging Behav 2012; 6 (02) 244-254
• 2 Martland HS. Punch Drunk. J Am Med Assoc 1928; 91 (15) 1103-1107
• 3 Robinson ME, McKee AC, Salat DH. et al. Positron emission tomography of tau in Iraq and Afghanistan Veterans with blast neurotrauma. Neuroimage Clin 2019; 21: 101651
• 4 Peskind ER, Petrie EC, Cross DJ. et al. Cerebrocerebellar hypometabolism associated with repetitive blast exposure mild traumatic brain injury in 12 Iraq war Veterans with persistent post-concussive symptoms. Neuroimage 2011; 54 (Suppl 1, Suppl 1) S76-S82
• 5 Barrio JR, Small GW, Wong KP. et al. In vivo characterization of chronic traumatic encephalopathy using [F-18]FDDNP PET brain imaging. Proc Natl Acad Sci U S A 2015; 112 (16) E2039-E2047
• 6 Mantyh WG, Spina S, Lee A. et al. Tau Positron Emission Tomographic Findings in a Former US Football Player With Pathologically Confirmed Chronic Traumatic Encephalopathy. JAMA Neurol 2020; 77 (04) 517-521
• 7 Stern RA, Adler CH, Chen K. et al. Tau Positron-Emission Tomography in Former National Football League Players. N Engl J Med 2019; 380 (18) 1716-1725
• 8 Provenzano FA, Jordan B, Tikofsky RS, Saxena C, Van Heertum RL, Ichise M. F-18 FDG PET imaging of chronic traumatic brain injury in boxers: a statistical parametric analysis. Nucl Med Commun 2010; 31 (11) 952-957
• 9 McKee AC, Cairns NJ, Dickson DW. et al; TBI/CTE group. The first NINDS/NIBIB consensus meeting to define neuropathological criteria for the diagnosis of chronic traumatic encephalopathy. Acta Neuropathol 2016; 131 (01) 75-86
• 10 Lesman-Segev OH, La Joie R, Stephens ML. et al. Tau PET and multimodal brain imaging in patients at risk for chronic traumatic encephalopathy. Neuroimage Clin 2019; 24: 102025
• 11 Salat DH, Robinson ME, Miller DR, Clark DC, McGlinchey RE. Neuroimaging of deployment-associated traumatic brain injury (TBI) with a focus on mild TBI (mTBI) since 2009. Brain Inj 2017; 31 (09) 1204-1219
• 12 Matser JT, Kessels AG, Jordan BD, Lezak MD, Troost J. Chronic traumatic brain injury in professional soccer players. Neurology 1998; 51 (03) 791-796
• 13 Mackay DF, Russell ER, Stewart K, MacLean JA, Pell JP, Stewart W. Neurodegenerative Disease Mortality among Former Professional Soccer Players. N Engl J Med 2019; 381 (19) 1801-1808
• 14 Grinberg LT, Anghinah R, Nascimento CF. et al. Chronic Traumatic Encephalopathy Presenting as Alzheimer's Disease in a Retired Soccer Player. J Alzheimers Dis 2016; 54 (01) 169-174
• 15 Ling H, Morris HR, Neal JW. et al. Mixed pathologies including chronic traumatic encephalopathy account for dementia in retired association football (soccer) players. Acta Neuropathol 2017; 133 (03) 337-352
• 16 Lee EB, Kinch K, Johnson VE, Trojanowski JQ, Smith DH, Stewart W. Chronic traumatic encephalopathy is a common co-morbidity, but less frequent primary dementia in former soccer and rugby players. Acta Neuropathol 2019; 138 (03) 389-399
• 17 Shellock FG, Crues JV. MR procedures: biologic effects, safety, and patient care. Radiology 2004; 232 (03) 635-652
• 18 Brucki SMD, Nitrini R, Caramelli P, Bertolucci PHF, Okamoto IH. [Suggestions for utilization of the mini-mental state examination in Brazil]. Arq Neuropsiquiatr 2003; 61 (3B): 777-781
• 19 Ryan JJ, Lopez SJ. Wechsler Adult Intelligence Scale-III. In: Dorfman WI, Hersen M. eds. Understanding Psychological Assessment. Springer US; 2001: 19-42
• 20 Nitrini R, Bucki SMD, Yassuda MS, Fichman HC, Caramelli P. The Figure Memory Test: diagnosis of memory impairment in populations with heterogeneous educational background. Dement Neuropsychol 2021; 15 (02) 173-185
• 21 Crossley M, D'Arcy C, Rawson NS. Letter and category fluency in community-dwelling Canadian seniors: a comparison of normal participants to those with dementia of the Alzheimer or vascular type. J Clin Exp Neuropsychol 1997; 19 (01) 52-62
• 22 Caramelli P, Nitrini R, Carthery-Goulart MT, Porto CS, Fichmann HC, Bahia VS. Teste de fluência verbal no diagnóstico da doença de Alzheimer leve: notas de corte em função da escolaridade. Arq Neuropsiquiatr 2003; 61: 32
• 23 Sunderland T, Hill JL, Mellow AM. et al. Clock drawing in Alzheimer's disease. A novel measure of dementia severity. J Am Geriatr Soc 1989; 37 (08) 725-729
• 24 Vitiello APP, Ciríaco JGM, Takahashi DY, Nitrini R, Caramelli P. [Brief cognitive evaluation of patients attended in a general neurological outpatient clinic]. Arq Neuropsiquiatr 2007; 65 (2A): 299-303
• 25 Montenigro PH, Baugh CM, Daneshvar DH. et al. Clinical subtypes of chronic traumatic encephalopathy: literature review and proposed research diagnostic criteria for traumatic encephalopathy syndrome. Alzheimers Res Ther 2014; 6 (05) 68
• 26 Meltzer CC, Cantwell MN, Greer PJ. et al. Does cerebral blood flow decline in healthy aging? A PET study with partial-volume correction. J Nucl Med 2000; 41 (11) 1842-1848
• 27 Schmidt P, Gaser C, Arsic M. et al. An automated tool for detection of FLAIR-hyperintense white-matter lesions in Multiple Sclerosis. Neuroimage 2012; 59 (04) 3774-3783
• 28 Mosconi L, Tsui WH, Herholz K. et al. Multicenter standardized 18F-FDG PET diagnosis of mild cognitive impairment, Alzheimer's disease, and other dementias. J Nucl Med 2008; 49 (03) 390-398
• 29 Teune LK, Bartels AL, de Jong BM. et al. Typical cerebral metabolic patterns in neurodegenerative brain diseases. Mov Disord 2010; 25 (14) 2395-2404
• 30 Harper L, Barkhof F, Fox NC, Schott JM. Using visual rating to diagnose dementia: a critical evaluation of MRI atrophy scales. J Neurol Neurosurg Psychiatry 2015; 86 (11) 1225-1233
• 31 Harper L, Fumagalli GG, Barkhof F. et al. MRI visual rating scales in the diagnosis of dementia: evaluation in 184 post-mortem confirmed cases. Brain 2016; 139 (Pt 4): 1211-1225
• 32 Fazekas F, Chawluk JB, Alavi A, Hurtig HI, Zimmerman RA. MR signal abnormalities at 1.5 T in Alzheimer's dementia and normal aging. AJR Am J Roentgenol 1987; 149 (02) 351-356
• 33 Nichols K. CHAPTER 20 - False Discovery Rate procedures. In: Friston K, Ashburner J, Kiebel S, Nichols T, Penny W. eds. Statistical Parametric Mapping. Academic Press; 2007: 246-252
• 34 Lancaster JL, Woldorff MG, Parsons LM. et al. Automated Talairach atlas labels for functional brain mapping. Hum Brain Mapp 2000; 10 (03) 120-131
• 35 Brett M, Anton JL, Valabregue R, Poline JB. Region of interest analysis using an SPM toolbox [abstract]. In: Vol Aailable on CD-ROM in NeuroImage, Vol 16, No 2, abstract 497.
• 36 Mendez MF, Owens EM, Reza Berenji G, Peppers DC, Liang LJ, Licht EA. Mild traumatic brain injury from primary blast vs. blunt forces: post-concussion consequences and functional neuroimaging. NeuroRehabilitation 2013; 32 (02) 397-407
• 37 Raji CA, Merrill DA, Barrio JR, Omalu B, Small GW. Progressive Focal Gray Matter Volume Loss in a Former High School Football Player: A Possible Magnetic Resonance Imaging Volumetric Signature for Chronic Traumatic Encephalopathy. Am J Geriatr Psychiatry 2016; 24 (10) 784-790
• 38 Patel JB, Wilson SH, Oakes TR, Santhanam P, Weaver LK. Structural and Volumetric Brain MRI Findings in Mild Traumatic Brain Injury. AJNR Am J Neuroradiol 2020; 41 (01) 92-99
• 39 Meabon JS, Huber BR, Cross DJ. et al. Repetitive blast exposure in mice and combat veterans causes persistent cerebellar dysfunction. Sci Transl Med 2016; 8 (321): 321ra6
• 40 Koerte IK, Hufschmidt J, Muehlmann M. et al. Cavum Septi Pellucidi in Symptomatic Former Professional Football Players. J Neurotrauma 2016; 33 (04) 346-353
• 41 Blennow K, Brody DL, Kochanek PM. et al. Traumatic brain injuries. Nat Rev Dis Primers 2016; 2: 16084
• 42 Berginström N, Nordström P, Nyberg L, Nordström A. White matter hyperintensities increases with traumatic brain injury severity: associations to neuropsychological performance and fatigue. Brain Inj 2020; 34 (03) 415-420
• 43 Dubois B, Albert ML. Amnestic MCI or prodromal Alzheimer's disease?. Lancet Neurol 2004; 3 (04) 246-248
• 44 Dubois B, Villain N, Frisoni GB. et al. Clinical diagnosis of Alzheimer's disease: recommendations of the International Working Group. Lancet Neurol 2021; 20 (06) 484-496