Functional connectivity changes in neurodegenerative biomarker-positive athletes with repeated concussions.
Atrophy
Biomarkers
Concussion
Functional connectivity
Neurodegeneration
Journal
Journal of neurology
ISSN: 1432-1459
Titre abrégé: J Neurol
Pays: Germany
ID NLM: 0423161
Informations de publication
Date de publication:
08 Apr 2024
08 Apr 2024
Historique:
received:
05
12
2023
accepted:
19
03
2024
revised:
27
02
2024
medline:
9
4
2024
pubmed:
9
4
2024
entrez:
8
4
2024
Statut:
aheadofprint
Résumé
Multimodal biomarkers may identify former contact sports athletes with repeated concussions and at risk for dementia. Our study aims to investigate whether biomarker evidence of neurodegeneration in former professional athletes with repetitive concussions (ExPro) is associated with worse cognition and mood/behavior, brain atrophy, and altered functional connectivity. Forty-one contact sports athletes with repeated concussions were divided into neurodegenerative biomarker-positive (n = 16) and biomarker-negative (n = 25) groups based on positivity of serum neurofilament light-chain. Six healthy controls (negative for biomarkers) with no history of concussions were also analyzed. We calculated cognitive and mood/behavior composite scores from neuropsychological assessments. Gray matter volume maps and functional connectivity of the default mode, salience, and frontoparietal networks were compared between groups using ANCOVAs, controlling for age, and total intracranial volume. The association between the connectivity networks and sports characteristics was analyzed by multiple regression analysis in all ExPro. Participants presented normal-range mean performance in executive function, memory, and mood/behavior tests. The ExPro groups did not differ in professional years played, age at first participation in contact sports, and number of concussions. There were no differences in gray matter volume between groups. The neurodegenerative biomarker-positive group had lower connectivity in the default mode network (DMN) compared to the healthy controls and the neurodegenerative biomarker-negative group. DMN disconnection was associated with increased number of concussions in all ExPro. Biomarkers of neurodegeneration may be useful to detect athletes that are still cognitively normal, but with functional connectivity alterations after concussions and at risk of dementia.
Identifiants
pubmed: 38589629
doi: 10.1007/s00415-024-12340-1
pii: 10.1007/s00415-024-12340-1
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Alzheimer's Association
ID : ZEN-21-848495
Pays : United States
Informations de copyright
© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.
Références
Abbas K, Shenk TE, Poole VN, Breedlove EL, Leverenz LJ, Nauman EA, Talavage TM, Robinson ME (2015) Alteration of default mode network in high school football athletes due to repetitive subconcussive mild traumatic brain injury: a resting-state functional magnetic resonance imaging study. Brain Connect 5:91–101
pubmed: 25242171
doi: 10.1089/brain.2014.0279
Amir J, Nair JKR, Del Carpio-O’Donovan R, Ptito A, Chen JK, Chankowsky J, Tinawi S, Lunkova E, Saluja RS (2021) Atypical resting state functional connectivity in mild traumatic brain injury. Brain Behav 11:e2261
pubmed: 34152089
pmcid: 8413771
doi: 10.1002/brb3.2261
Ashburner J, Friston KJ (2000) Voxel-based morphometry–the methods. Neuroimage 11:805–821
pubmed: 10860804
doi: 10.1006/nimg.2000.0582
Balthazar ML, de Campos BM, Franco AR, Damasceno BP, Cendes F (2014) Whole cortical and default mode network mean functional connectivity as potential biomarkers for mild Alzheimer’s disease. Psychiatry Res 221:37–42
pubmed: 24268581
doi: 10.1016/j.pscychresns.2013.10.010
Barrio JR, Small GW, Wong KP, Huang SC, Liu J, Merrill DA, Giza CC, Fitzsimmons RP, Omalu B, Bailes J, Kepe V (2015) In vivo characterization of chronic traumatic encephalopathy using [F-18]FDDNP PET brain imaging. Proc Natl Acad Sci USA 112:E2039-2047
pubmed: 25848027
pmcid: 4413350
doi: 10.1073/pnas.1409952112
Bigler ED (2018) Structural neuroimaging in sport-related concussion. Int J Psychophysiol 132:105–123
pubmed: 28916167
doi: 10.1016/j.ijpsycho.2017.09.006
Blennow K (2004) Cerebrospinal fluid protein biomarkers for Alzheimer’s disease. NeuroRx: J Am Soc Exp Neurother 1:213–225
doi: 10.1602/neurorx.1.2.213
Buckner RL, Snyder AZ, Shannon BJ, LaRossa G, Sachs R, Fotenos AF, Sheline YI, Klunk WE, Mathis CA, Morris JC, Mintun MA (2005) Molecular, structural, and functional characterization of Alzheimer’s disease: evidence for a relationship between default activity, amyloid, and memory. J Neurosci 25:7709–7717
pubmed: 16120771
pmcid: 6725245
doi: 10.1523/JNEUROSCI.2177-05.2005
Churchill NW, Hutchison MG, Graham SJ, Schweizer TA (2021) Concussion risk and resilience: relationships with pre-injury salience network connectivity. J Neurotrauma 38:3097–3106
pubmed: 34314246
doi: 10.1089/neu.2021.0123
Churchill NW, Hutchison MG, Graham SJ, Schweizer TA (2018) Connectomic markers of symptom severity in sport-related concussion: whole-brain analysis of resting-state fMRI. NeuroImage Clin 18:518–526
pubmed: 29560308
pmcid: 5857899
doi: 10.1016/j.nicl.2018.02.011
Coppens S, Lehmann S, Hopley C, Hirtz C (2023) Neurofilament-light, a promising biomarker: analytical, metrological and clinical challenges. Int J Mol Sci 24(14):11624
pubmed: 37511382
pmcid: 10380627
doi: 10.3390/ijms241411624
Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, Roses AD, Haines JL, Pericak-Vance MA (1993) Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science 261:921–923
pubmed: 8346443
doi: 10.1126/science.8346443
DiFabio MS, Smith DR, Breedlove KM, Pohlig RT, Buckley TA, Johnson CL (2023) Altered brain functional connectivity in the frontoparietal network following an ice hockey season. Eur J Sport Sci 23:684–692
pubmed: 35466861
doi: 10.1080/17461391.2022.2069512
Dillen KNH, Jacobs HIL, Kukolja J, Richter N, von Reutern B, Onur OA, Langen KJ, Fink GR (2017) Functional disintegration of the default mode network in prodromal Alzheimer’s disease. J Alzheimer’s Dis: JAD 59:169–187
pubmed: 28598839
doi: 10.3233/JAD-161120
Dosenbach NU, Nardos B, Cohen AL, Fair DA, Power JD, Church JA, Nelson SM, Wig GS, Vogel AC, Lessov-Schlaggar CN, Barnes KA, Dubis JW, Feczko E, Coalson RS, Pruett JR Jr, Barch DM, Petersen SE, Schlaggar BL (2010) Prediction of individual brain maturity using fMRI. Science 329:1358–1361
pubmed: 20829489
pmcid: 3135376
doi: 10.1126/science.1194144
Gaetani L, Blennow K, Calabresi P, Filippo MD, Parnetti L, Zetterberg H (2019) Neurofilament light chain as a biomarker in neurological disorders. J Neurol 90:870–881
Gallo V, Motley K, Kemp SPT, Mian S, Patel T, James L, Pearce N, McElvenny D (2020) Concussion and long-term cognitive impairment among professional or elite sport-persons: a systematic review. J Neurol Neurosurg Psychiatry 91:455–468
pubmed: 32107272
doi: 10.1136/jnnp-2019-321170
Giannini LAA, Seelaar H, van der Ende EL, Poos JM, Jiskoot LC, Dopper EGP, Pijnenburg YAL, Willemse EAJ, Vermunt L, Teunissen CE, van Swieten JC, Meeter LH (2023) Clinical value of longitudinal serum neurofilament light chain in prodromal genetic frontotemporal dementia. Neurology 101:e1069–e1082
pubmed: 37491327
pmcid: 10491440
doi: 10.1212/WNL.0000000000207581
Gili T, Cercignani M, Serra L, Perri R, Giove F, Maraviglia B, Caltagirone C, Bozzali M (2011) Regional brain atrophy and functional disconnection across Alzheimer’s disease evolution. J Neurol Neurosurg Psychiatry 82:58–66
pubmed: 20639384
doi: 10.1136/jnnp.2009.199935
Goswami R, Dufort P, Tartaglia MC, Green RE, Crawley A, Tator CH, Wennberg R, Mikulis DJ, Keightley M, Davis KD (2016) Frontotemporal correlates of impulsivity and machine learning in retired professional athletes with a history of multiple concussions. Brain Struct Funct 221:1911–1925
pubmed: 25721800
doi: 10.1007/s00429-015-1012-0
Green RE, Melo B, Christensen B, Ngo LA, Monette G, Bradbury C (2008) Measuring premorbid IQ in traumatic brain injury: an examination of the validity of the Wechsler test of adult reading (WTAR). J Clin Exp Neuropsychol 30:163–172
pubmed: 18213530
doi: 10.1080/13803390701300524
Greicius MD, Srivastava G, Reiss AL, Menon V (2004) Default-mode network activity distinguishes Alzheimer’s disease from healthy aging: evidence from functional MRI. Proc Natl Acad Sci USA 101:4637–4642
pubmed: 15070770
pmcid: 384799
doi: 10.1073/pnas.0308627101
Gronwall DM (1977) Paced auditory serial-addition task: a measure of recovery from concussion. Percept Mot Skills 44:367–373
pubmed: 866038
doi: 10.2466/pms.1977.44.2.367
Hampshire A, MacDonald A, Owen AM (2013) Hypoconnectivity and hyperfrontality in retired American football players. Sci Rep 3:2972
pubmed: 24135857
pmcid: 6505675
doi: 10.1038/srep02972
Han K, Chapman SB, Krawczyk DC (2016) Disrupted intrinsic connectivity among default, dorsal attention, and frontoparietal control networks in individuals with chronic traumatic brain injury. J Int Neuropsychol Soc: JINS 22:263–279
pubmed: 26888622
doi: 10.1017/S1355617715001393
Hansson O (2021) Biomarkers for neurodegenerative diseases. Nat Med 27:954–963
pubmed: 34083813
doi: 10.1038/s41591-021-01382-x
Hazrati LN, Tartaglia MC, Diamandis P, Davis KD, Green RE, Wennberg R, Wong JC, Ezerins L, Tator CH (2013) Absence of chronic traumatic encephalopathy in retired football players with multiple concussions and neurological symptomatology. Front Hum Neurosci 7:222
pubmed: 23745112
pmcid: 3662898
doi: 10.3389/fnhum.2013.00222
Hulstaert F, Blennow K, Ivanoiu A, Schoonderwaldt HC, Riemenschneider M, De Deyn PP, Bancher C, Cras P, Wiltfang J, Mehta PD, Iqbal K, Pottel H, Vanmechelen E, Vanderstichele H (1999) Improved discrimination of AD patients using beta-amyloid(1–42) and tau levels in CSF. Neurology 52:1555–1562
pubmed: 10331678
doi: 10.1212/WNL.52.8.1555
Jack CR Jr, Knopman DS, Jagust WJ, Petersen RC, Weiner MW, Aisen PS, Shaw LM, Vemuri P, Wiste HJ, Weigand SD, Lesnick TG, Pankratz VS, Donohue MC, Trojanowski JQ (2013) Tracking pathophysiological processes in Alzheimer’s disease: an updated hypothetical model of dynamic biomarkers. Lancet Neurol 12:207–216
pubmed: 23332364
pmcid: 3622225
doi: 10.1016/S1474-4422(12)70291-0
Jo S, Kim S-O, Park KW, Lee SH, Hwang YS, Chung SJ (2021) The role of APOE in cognitive trajectories and motor decline in Parkinson’s disease. Sci Rep 11:7819
pubmed: 33837234
pmcid: 8035327
doi: 10.1038/s41598-021-86483-w
Johnson B, Neuberger T, Gay M, Hallett M, Slobounov S (2014) Effects of subconcussive head trauma on the default mode network of the brain. J Neurotrauma 31:1907–1913
pubmed: 25010992
pmcid: 4238241
doi: 10.1089/neu.2014.3415
Karikari TK, Benedet AL, Ashton NJ, Lantero Rodriguez J, Snellman A, Suarez-Calvet M, Saha-Chaudhuri P, Lussier F, Kvartsberg H, Rial AM, Pascoal TA, Andreasson U, Scholl M, Weiner MW, Rosa-Neto P, Trojanowski JQ, Shaw LM, Blennow K, Zetterberg H, Alzheimer’s Disease Neuroimaging I (2021) Diagnostic performance and prediction of clinical progression of plasma phospho-tau181 in the Alzheimer’s disease neuroimaging initiative. Mol Psychiatry 26:429–442
pubmed: 33106600
doi: 10.1038/s41380-020-00923-z
Karikari TK, Pascoal TA, Ashton NJ, Janelidze S, Benedet AL, Rodriguez JL, Chamoun M, Savard M, Kang MS, Therriault J, Scholl M, Massarweh G, Soucy JP, Hoglund K, Brinkmalm G, Mattsson N, Palmqvist S, Gauthier S, Stomrud E, Zetterberg H, Hansson O, Rosa-Neto P, Blennow K (2020) Blood phosphorylated tau 181 as a biomarker for Alzheimer’s disease: a diagnostic performance and prediction modelling study using data from four prospective cohorts. Lancet Neurol 19:422–433
pubmed: 32333900
doi: 10.1016/S1474-4422(20)30071-5
Khalil M, Teunissen CE, Otto M, Piehl F, Sormani MP, Gattringer T, Barro C, Kappos L, Comabella M, Fazekas F, Petzold A, Blennow K, Zetterberg H, Kuhle J (2018) Neurofilaments as biomarkers in neurological disorders. Nat Rev Neurol 14:577–589
pubmed: 30171200
doi: 10.1038/s41582-018-0058-z
Koriath C, Lashley T, Taylor W, Druyeh R, Dimitriadis A, Denning N, Williams J, Warren JD, Fox NC, Schott JM, Rowe JB, Collinge J, Rohrer JD, Mead S (2019) ApoE4 lowers age at onset in patients with frontotemporal dementia and tauopathy independent of amyloid-β copathology. Alzheimers Dement (Amst) 11:277–280
pubmed: 30949567
doi: 10.1016/j.dadm.2019.01.010
Lantero Rodriguez J, Karikari TK, Suarez-Calvet M, Troakes C, King A, Emersic A, Aarsland D, Hye A, Zetterberg H, Blennow K, Ashton NJ (2020) Plasma p-tau181 accurately predicts Alzheimer’s disease pathology at least 8 years prior to post-mortem and improves the clinical characterisation of cognitive decline. Acta Neuropathol 140:267–278
pubmed: 32720099
pmcid: 7423866
doi: 10.1007/s00401-020-02195-x
Lewczuk P, Ermann N, Andreasson U, Schultheis C, Podhorna J, Spitzer P, Maler JM, Kornhuber J, Blennow K, Zetterberg H (2018) Plasma neurofilament light as a potential biomarker of neurodegeneration in Alzheimer’s disease. Alzheimer’s Res Ther 10:71
doi: 10.1186/s13195-018-0404-9
Lezak MD, Howieson DB, Loring DW, Fischer JS (2004) Neuropsychological assessment. Oxford University Press, USA
Livingston G, Huntley J, Sommerlad A, Ames D, Ballard C, Banerjee S, Brayne C, Burns A, Cohen-Mansfield J, Cooper C, Costafreda SG, Dias A, Fox N, Gitlin LN, Howard R, Kales HC, Kivimaki M, Larson EB, Ogunniyi A, Orgeta V, Ritchie K, Rockwood K, Sampson EL, Samus Q, Schneider LS, Selbaek G, Teri L, Mukadam N (2020) Dementia prevention, intervention, and care: 2020 report of the Lancet commission. Lancet 396:413–446
pubmed: 32738937
pmcid: 7392084
doi: 10.1016/S0140-6736(20)30367-6
Maddalena A, Papassotiropoulos A, Muller-Tillmanns B, Jung HH, Hegi T, Nitsch RM, Hock C (2003) Biochemical diagnosis of Alzheimer disease by measuring the cerebrospinal fluid ratio of phosphorylated tau protein to beta-amyloid peptide42. Arch Neurol 60:1202–1206
pubmed: 12975284
doi: 10.1001/archneur.60.9.1202
Manley G, Gardner AJ, Schneider KJ, Guskiewicz KM, Bailes J, Cantu RC, Castellani RJ, Turner M, Jordan BD, Randolph C, Dvorak J, Hayden KA, Tator CH, McCrory P, Iverson GL (2017) A systematic review of potential long-term effects of sport-related concussion. Br J Sports Med 51:969–977
pubmed: 28455362
doi: 10.1136/bjsports-2017-097791
Marklund N, Vedung F, Lubberink M, Tegner Y, Johansson J, Blennow K, Zetterberg H, Fahlstrom M, Haller S, Stenson S, Larsson EM, Wall A, Antoni G (2021) Tau aggregation and increased neuroinflammation in athletes after sports-related concussions and in traumatic brain injury patients: a PET/MR study. NeuroImage Clinical 30:102665
pubmed: 33894460
pmcid: 8091173
doi: 10.1016/j.nicl.2021.102665
Mattsson N, Andreasson U, Zetterberg H, Blennow K, Alzheimer’s Disease Neuroimaging I (2017) Association of plasma neurofilament light with neurodegeneration in patients with Alzheimer disease. JAMA Neurol 74:557–566
pubmed: 28346578
pmcid: 5822204
doi: 10.1001/jamaneurol.2016.6117
Mayer AR, Mannell MV, Ling J, Gasparovic C, Yeo RA (2011) Functional connectivity in mild traumatic brain injury. Hum Brain Mapp 32:1825–1835
pubmed: 21259381
pmcid: 3204375
doi: 10.1002/hbm.21151
McCrory P, Meeuwisse W, Dvorak J, Aubry M, Bailes J, Broglio S, Cantu RC, Cassidy D, Echemendia RJ, Castellani RJ, Davis GA, Ellenbogen R, Emery C, Engebretsen L, Feddermann-Demont N, Giza CC, Guskiewicz KM, Herring S, Iverson GL, Johnston KM, Kissick J, Kutcher J, Leddy JJ, Maddocks D, Makdissi M, Manley GT, McCrea M, Meehan WP, Nagahiro S, Patricios J, Putukian M, Schneider KJ, Sills A, Tator CH, Turner M, Vos PE (2017) Consensus statement on concussion in sport-the 5(th) international conference on concussion in sport held in Berlin, October 2016. Br J Sports Med 51:838–847
pubmed: 28446457
McKee AC, Cantu RC, Nowinski CJ, Hedley-Whyte ET, Gavett BE, Budson AE, Santini VE, Lee HS, Kubilus CA, Stern RA (2009) Chronic traumatic encephalopathy in athletes: progressive tauopathy after repetitive head injury. J Neuropathol Exp Neurol 68:709–735
pubmed: 19535999
doi: 10.1097/NEN.0b013e3181a9d503
McKee AC, Mez J, Abdolmohammadi B, Butler M, Huber BR, Uretsky M, Babcock K, Cherry JD, Alvarez VE, Martin B, Tripodis Y, Palmisano JN, Cormier KA, Kubilus CA, Nicks R, Kirsch D, Mahar I, McHale L, Nowinski C, Cantu RC, Stern RA, Daneshvar D, Goldstein LE, Katz DI, Kowall NW, Dwyer B, Stein TD, Alosco ML (2023) Neuropathologic and clinical findings in young contact sport athletes exposed to repetitive head impacts. JAMA Neurol 80:1037–1050
pubmed: 37639244
pmcid: 10463175
doi: 10.1001/jamaneurol.2023.2907
Mez J, Daneshvar DH, Kiernan PT, Abdolmohammadi B, Alvarez VE, Huber BR, Alosco ML, Solomon TM, Nowinski CJ, McHale L, Cormier KA, Kubilus CA, Martin BM, Murphy L, Baugh CM, Montenigro PH, Chaisson CE, Tripodis Y, Kowall NW, Weuve J, McClean MD, Cantu RC, Goldstein LE, Katz DI, Stern RA, Stein TD, McKee AC (2017) Clinicopathological evaluation of chronic traumatic encephalopathy in players of American football. JAMA 318:360–370
pubmed: 28742910
pmcid: 5807097
doi: 10.1001/jama.2017.8334
Mielke MM, Hagen CE, Xu J, Chai X, Vemuri P, Lowe VJ, Airey DC, Knopman DS, Roberts RO, Machulda MM, Jack CR Jr, Petersen RC, Dage JL (2018) Plasma phospho-tau181 increases with Alzheimer’s disease clinical severity and is associated with tau- and amyloid-positron emission tomography. Alzheimer’s Dement 14:989–997
doi: 10.1016/j.jalz.2018.02.013
Mielke MM, Syrjanen JA, Blennow K, Zetterberg H, Skoog I, Vemuri P, Machulda MM, Graff-Radford J, Knopman DS, Jack CR Jr, Petersen RC, Kern S (2019) Comparison of variables associated with cerebrospinal fluid neurofilament, total-tau, and neurogranin. Alzheimer’s Dement 15:1437–1447
doi: 10.1016/j.jalz.2019.07.009
Misquitta K, Dadar M, Tarazi A, Hussain MW, Alatwi MK, Ebraheem A, Multani N, Khodadadi M, Goswami R, Wennberg R, Tator C, Green R, Colella B, Davis KD, Mikulis D, Grinberg M, Sato C, Rogaeva E, Louis Collins D, Tartaglia MC (2018) The relationship between brain atrophy and cognitive-behavioural symptoms in retired Canadian football players with multiple concussions. NeuroImage Clin 19:551–558
pubmed: 29984163
pmcid: 6029563
doi: 10.1016/j.nicl.2018.05.014
Morey LC, Lowmaster SE (2010) Personality assessment inventory. The Corsini encyclopedia of psychology. Wiley, pp 1–4
Moscoso A, Grothe MJ, Ashton NJ, Karikari TK, Rodriguez JL, Snellman A, Suarez-Calvet M, Zetterberg H, Blennow K, Scholl M, Alzheimer’s Disease Neuroimaging I (2021) Time course of phosphorylated-tau181 in blood across the Alzheimer’s disease spectrum. Brain J Neurol 144:325–339
doi: 10.1093/brain/awaa399
Neselius S, Brisby H, Theodorsson A, Blennow K, Zetterberg H, Marcusson J (2012) CSF-biomarkers in Olympic boxing: diagnosis and effects of repetitive head trauma. PLoS ONE 7:e33606
pubmed: 22496755
pmcid: 3319096
doi: 10.1371/journal.pone.0033606
Newsome MR, Li X, Lin X, Wilde EA, Ott S, Biekman B, Hunter JV, Dash PK, Taylor BA, Levin HS (2016) Functional connectivity is altered in concussed adolescent athletes despite medical clearance to return to play: a preliminary report. Front Neurol 7:116
pubmed: 27504104
pmcid: 4958621
doi: 10.3389/fneur.2016.00116
Ossenkoppele R, Cohn-Sheehy BI, La Joie R, Vogel JW, Moller C, Lehmann M, van Berckel BN, Seeley WW, Pijnenburg YA, Gorno-Tempini ML, Kramer JH, Barkhof F, Rosen HJ, van der Flier WM, Jagust WJ, Miller BL, Scheltens P, Rabinovici GD (2015) Atrophy patterns in early clinical stages across distinct phenotypes of Alzheimer’s disease. Hum Brain Mapp 36:4421–4437
pubmed: 26260856
pmcid: 4692964
doi: 10.1002/hbm.22927
Ossenkoppele R, Iaccarino L, Schonhaut DR, Brown JA, La Joie R, O’Neil JP, Janabi M, Baker SL, Kramer JH, Gorno-Tempini ML, Miller BL, Rosen HJ, Seeley WW, Jagust WJ, Rabinovici GD (2019) Tau covariance patterns in Alzheimer’s disease patients match intrinsic connectivity networks in the healthy brain. NeuroImage Clin 23:101848
pubmed: 31077982
pmcid: 6510968
doi: 10.1016/j.nicl.2019.101848
Rivara FP, Tennyson R, Mills B, Browd SR, Emery CA, Gioia G, Giza CC, Herring S, Janz KF, LaBella C, Valovich McLeod T, Meehan W, Patricios J, Four Corners Youth C (2020) Consensus statement on sports-related concussions in youth sports using a modified Delphi approach. JAMA Pediatr 174:79–85
pubmed: 31710349
doi: 10.1001/jamapediatrics.2019.4006
Rohrer JD, Woollacott IO, Dick KM, Brotherhood E, Gordon E, Fellows A, Toombs J, Druyeh R, Cardoso MJ, Ourselin S, Nicholas JM, Norgren N, Mead S, Andreasson U, Blennow K, Schott JM, Fox NC, Warren JD, Zetterberg H (2016) Serum neurofilament light chain protein is a measure of disease intensity in frontotemporal dementia. Neurology 87:1329–1336
pubmed: 27581216
pmcid: 5047041
doi: 10.1212/WNL.0000000000003154
Saltiel N, Tripodis Y, Menzin T, Olaniyan A, Baucom Z, Yhang E, Palmisano JN, Martin B, Uretsky M, Nair E, Abdolmohammadi B, Shah A, Nicks R, Nowinski C, Cantu RC, Daneshvar DH, Dwyer B, Katz DI, Stern RA, Alvarez VE, Huber B, Boyle PA, Schneider JA, Mez J, McKee AC, Alosco ML, Stein TD (2023) Relative contributions of mixed pathologies to cognitive and functional symptoms in brain donors exposed to repetitive head impacts. Ann Neurol 95(2):314–324
pubmed: 37921042
doi: 10.1002/ana.26823
Sandmo SB, Filipcik P, Cente M, Hanes J, Andersen TE, Straume-Naesheim TM, Bahr R (2020) Neurofilament light and tau in serum after head-impact exposure in soccer. Brain Inj 34:602–609
pubmed: 32096660
doi: 10.1080/02699052.2020.1725129
Saunders AM, Strittmatter WJ, Schmechel D, George-Hyslop PH, Pericak-Vance MA, Joo SH, Rosi BL, Gusella JF, Crapper-MacLachlan DR, Alberts MJ et al (1993) Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer’s disease. Neurology 43:1467–1472
pubmed: 8350998
doi: 10.1212/WNL.43.8.1467
Seeley WW, Crawford RK, Zhou J, Miller BL, Greicius MD (2009) Neurodegenerative diseases target large-scale human brain networks. Neuron 62:42–52
pubmed: 19376066
pmcid: 2691647
doi: 10.1016/j.neuron.2009.03.024
Shahim P, Politis A, van der Merwe A, Moore B, Chou YY, Pham DL, Butman JA, Diaz-Arrastia R, Gill JM, Brody DL, Zetterberg H, Blennow K, Chan L (2020) Neurofilament light as a biomarker in traumatic brain injury. Neurology 95:e610–e622
pubmed: 32641538
pmcid: 7455357
doi: 10.1212/WNL.0000000000009983
Shahim P, Tegner Y, Marklund N, Blennow K, Zetterberg H (2018) Neurofilament light and tau as blood biomarkers for sports-related concussion. Neurology 90:e1780–e1788
pubmed: 29653990
pmcid: 5957307
doi: 10.1212/WNL.0000000000005518
Shahim P, Zetterberg H, Tegner Y, Blennow K (2017) Serum neurofilament light as a biomarker for mild traumatic brain injury in contact sports. Neurology 88:1788–1794
pubmed: 28404801
pmcid: 5419986
doi: 10.1212/WNL.0000000000003912
Sharp DJ, Beckmann CF, Greenwood R, Kinnunen KM, Bonnelle V, De Boissezon X, Powell JH, Counsell SJ, Patel MC, Leech R (2011) Default mode network functional and structural connectivity after traumatic brain injury. Brain J Neurol 134:2233–2247
doi: 10.1093/brain/awr175
Sharp DJ, Scott G, Leech R (2014) Network dysfunction after traumatic brain injury. Nat Rev Neurol 10:156–166
pubmed: 24514870
doi: 10.1038/nrneurol.2014.15
Sihag S, Naze S, Taghdiri F, Gumus M, Tator C, Green R, Colella B, Blennow K, Zetterberg H, Dominguez LG, Wennberg R, Mikulis DJ, Tartaglia MC, Kozloski JR (2022) Functional brain activity constrained by structural connectivity reveals cohort-specific features for serum neurofilament light chain. Commun Med 2:8
pubmed: 35603281
pmcid: 9053240
doi: 10.1038/s43856-021-00065-5
Strain JF, Womack KB, Didehbani N, Spence JS, Conover H, Hart J Jr, Kraut MA, Cullum CM (2015) Imaging correlates of memory and concussion history in retired national football league athletes. JAMA Neurol 72:773–780
pubmed: 25985094
pmcid: 6761828
doi: 10.1001/jamaneurol.2015.0206
Sugarman MA, McKee AC, Stein TD, Tripodis Y, Besser LM, Martin B, Palmisano JN, Steinberg EG, O’Connor MK, Au R, McClean M, Killiany R, Mez J, Weiner MW, Kowall NW, Stern RA, Alosco ML (2019) Failure to detect an association between self-reported traumatic brain injury and Alzheimer’s disease neuropathology and dementia. Alzheimer’s Dement 15:686–698
doi: 10.1016/j.jalz.2018.12.015
Taghdiri FKM, Sadia N, Mushtaque A, Scott OFT, Hirsch-Reinhagen V, Tator C, Wennberg R, Kovacs GG, Tartaglia MC (2024) Unusual combinations of neurodegenerative pathologies with chronic traumatic encephalopathy (CTE) complicates clinical prediction of CTE. Eur J Neurol 25:e16259
doi: 10.1111/ene.16259
Taghdiri F, Multani N, Ozzoude M, Tarazi A, Khodadadi M, Wennberg R, Mikulis D, Green R, Colella B, Davis KD, Blennow K, Zetterberg H, Tator C, Tartaglia MC (2020) Neurofilament-light in former athletes: a potential biomarker of neurodegeneration and progression. Eur J Neurol 27:1170–1177
pubmed: 32281206
doi: 10.1111/ene.14251
Tripodis Y, Alosco ML, Zirogiannis N, Gavett BE, Chaisson C, Martin B, McClean MD, Mez J, Kowall N, Stern RA (2017) The effect of traumatic brain injury history with loss of consciousness on rate of cognitive decline among older adults with normal cognition and Alzheimer’s disease dementia. J Alzheimer’s Dis: JAD 59:251–263
pubmed: 28655133
doi: 10.3233/JAD-160585
van Amerongen S, Kamps S, Kaijser KKM, Pijnenburg YAL, Scheltens P, Teunissen CE, Barkhof F, Ossenkoppele R, Rozemuller AJM, Stern RA, Hoozemans JJM, Vijverberg EGB (2023) Severe CTE and TDP-43 pathology in a former professional soccer player with dementia: a clinicopathological case report and review of the literature. Acta Neuropathol Commun 11:77
pubmed: 37161501
pmcid: 10169296
doi: 10.1186/s40478-023-01572-3
van der Ende EL, Meeter LH, Poos JM, Panman JL, Jiskoot LC, Dopper EGP, Papma JM, de Jong FJ, Verberk IMW, Teunissen C, Rizopoulos D, Heller C, Convery RS, Moore KM, Bocchetta M, Neason M, Cash DM, Borroni B, Galimberti D, Sanchez-Valle R, Laforce R, Moreno F, Synofzik M, Graff C, Masellis M, Carmela Tartaglia M, Rowe JB, Vandenberghe R, Finger E, Tagliavini F, de Mendonça A, Santana I, Butler C, Ducharme S, Gerhard A, Danek A, Levin J, Otto M, Frisoni GB, Cappa S, Pijnenburg YAL, Rohrer JD, van Swieten JC, Rossor MN, Warren JD, Fox NC, Woollacott IOC, Shafei R, Greaves C, Guerreiro R, Bras J, Thomas DL, Nicholas J, Mead S, van Minkelen R, Barandiaran M, Indakoetxea B, Gabilondo A, Tainta M, de Arriba M, Gorostidi A, Zulaica M, Villanua J, Diaz Z, Borrego-Ecija S, Olives J, Lladó A, Balasa M, Antonell A, Bargallo N, Premi E, Cosseddu M, Gazzina S, Padovani A, Gasparotti R, Archetti S, Black S, Mitchell S, Rogaeva E, Freedman M, Keren R, Tang-Wai D, Öijerstedt L, Andersson C, Jelic V, Thonberg H, Arighi A, Fenoglio C, Scarpini E, Fumagalli G, Cope T, Timberlake C, Rittman T, Shoesmith C, Bartha R, Rademakers R, Wilke C, Karnath H-O, Bender B, Bruffaerts R, Vandamme P, Vandenbulcke M, Ferreira CB, Miltenberger G, Maruta C, Verdelho A, Afonso S, Taipa R, Caroppo P, Di Fede G, Giaccone G, Prioni S, Redaelli V, Rossi G, Tiraboschi P, Duro D, Rosario Almeida M, Castelo-Branco M, João Leitão M, Tabuas-Pereira M, Santiago B, Gauthier S, Schonecker S, Semler E, Anderl-Straub S, Benussi L, Binetti G, Ghidoni R, Pievani M, Lombardi G, Nacmias B, Ferrari C, Bessi V (2019) Serum neurofilament light chain in genetic frontotemporal dementia: a longitudinal, multicentre cohort study. Lancet Neurol 18:1103–1111
pubmed: 31701893
doi: 10.1016/S1474-4422(19)30354-0
Vasilevskaya A, Martinez-Valbuena I, Anastassiadis C, Taghdiri F, Khodadadi M, Tarazi A, Green R, Colella B, Wennberg R, Mikulis D, Davis KD, Kovacs GG, Tator C, Tartaglia MC (2023) Misfolded alpha-synuclein in cerebrospinal fluid of contact sport athletes. Mov Disord: Off J Mov Disord Soc 38(11):2125–2131
doi: 10.1002/mds.29621
Vasilevskaya A, Taghdiri F, Burke C, Tarazi A, Naeimi SA, Khodadadi M, Goswami R, Sato C, Grinberg M, Moreno D, Wennberg R, Mikulis D, Green R, Colella B, Davis KD, Rusjan P, Houle S, Tator C, Rogaeva E, Tartaglia MC (2020) Interaction of APOE4 alleles and PET tau imaging in former contact sport athletes. NeuroImage Clin 26:102212
pubmed: 32097865
pmcid: 7037542
doi: 10.1016/j.nicl.2020.102212
Vasilevskaya A, Taghdiri F, Multani N, Ozzoude M, Tarazi A, Khodadadi M, Wennberg R, Rusjan P, Houle S, Green R, Colella B, Blennow K, Zetterberg H, Karikari T, Mikulis D, Hazrati LN, Kovacs GG, Davis KD, Tator C, Tartaglia MC (2022) Investigating the use of plasma pTau181 in retired contact sports athletes. J Neurol 269:5582–5595
pubmed: 35751688
doi: 10.1007/s00415-022-11223-7
Vermunt L, Otte M, Verberk IMW, Killestein J, Lemstra AW, van der Flier WM, Pijnenburg YAL, Vijverberg EGB, Bouwman FH, Gravesteijn G, van de Berg WDJ, Scheltens P, van Harten AC, Willemse EAJ, Teunissen CE (2022) Age- and disease-specific reference values for neurofilament light presented in an online interactive support interface. Ann Clin Transl Neurol 9:1832–1837
pubmed: 36196979
pmcid: 9639622
doi: 10.1002/acn3.51676
Whitfield-Gabrieli S, Nieto-Castanon A (2012) Conn: a functional connectivity toolbox for correlated and anticorrelated brain networks. Brain Connect 2:125–141
pubmed: 22642651
doi: 10.1089/brain.2012.0073
Wilson A, Stevens WD, Sergio L, Wojtowicz M (2022) Altered brain functional connectivity in female athletes over the course of a season of collision or contact sports. Neurotrauma reports 3:377–387
pubmed: 36204391
pmcid: 9531888
doi: 10.1089/neur.2022.0010
Yeo BT, Krienen FM, Sepulcre J, Sabuncu MR, Lashkari D, Hollinshead M, Roffman JL, Smoller JW, Zollei L, Polimeni JR, Fischl B, Liu H, Buckner RL (2011) The organization of the human cerebral cortex estimated by intrinsic functional connectivity. J Neurophysiol 106:1125–1165
pubmed: 21653723
doi: 10.1152/jn.00338.2011
Zetterberg H, Smith DH, Blennow K (2013) Biomarkers of mild traumatic brain injury in cerebrospinal fluid and blood. Nat Rev Neurol 9:201–210
pubmed: 23399646
pmcid: 4513656
doi: 10.1038/nrneurol.2013.9
Zhu DC, Covassin T, Nogle S, Doyle S, Russell D, Pearson RL, Monroe J, Liszewski CM, DeMarco JK, Kaufman DI (2015) A potential biomarker in sports-related concussion: brain functional connectivity alteration of the default-mode network measured with longitudinal resting-state fMRI over thirty days. J Neurotrauma 32:327–341
pubmed: 25116397
doi: 10.1089/neu.2014.3413