Repetitive Head Impacts and Perivascular Space Volume in Former American Football Players

Author:

Jung Leonard B.12,Wiegand Tim L. T.12,Tuz-Zahra Fatima3,Tripodis Yorghos34,Iliff Jeffrey J.567,Piantino Juan8,Arciniega Hector19,Kim Cara L.12,Pankatz Lara12,Bouix Sylvain110,Lin Alexander P.111,Alosco Michael L.12,Daneshvar Daniel H.13,Mez Jesse12,Sepehrband Farshid14,Rathi Yogesh115,Pasternak Ofer11516,Coleman Michael J.1,Adler Charles H.17,Bernick Charles18,Balcer Laura192021,Cummings Jeffrey L.22,Reiman Eric M.23,Stern Robert A.122425,Shenton Martha E.11516,Koerte Inga K.121526, ,Su Yi27,Chen Kewei27,Protas Hillary27,Boker Conni27,Au Rhoda27,Cantu Robert C.27,Farrer Lindsay27,Helm Robert27,Kowall Neil27,Mercier Gustavo27,Otis James27,Weller Jason27,Simkin Irene27,Andino Alondra27,Conneely Shannon27,Diamond Courtney27,Fagle Tessa27,Haller Olivia27,Hung Tennyson27,Gullotti Nicole27,Mariani Megan27,Mayville Brian27,McLaughlin Kathleen27,Nanna Mary27,Platt Taylor27,Pulukuri Sury27,Rica Fiona27,Sestak Madison27,McClean Michael27,Annis Douglas27,Chaisson Christine27,Dixon Dianne B.27,Finney Carolyn27,Gallagher Kerrin27,Hartlage Kaitlin27,Lu Jun27,Martin Brett27,Ojo Emmanuel27,Palmisano Joseph N.27,Pine Brittany27,Ramachandran Janani27,Fitzsimmons Jennifer27,Bonke Elena M.27,Breedlove Katherine27,Coello Eduardo27,Liao Hujiun27,Rizzoni Elizabeth27,Schultz Vivian27,Silva Annelise27,Vessey Brynn27,Banks Sarah27,Miller Jason27,Ritter Aaron27,Sabbagh marwan27,de la Cruz Raelynn27,Durant Jan27,Golceker Moragn27,Harmon Nicolette27,Kaylegian Kaeson27,Long Rachelle27,Nance Christin27,Sandoval Priscilla27,Turner Robert W.27,Marek Kenneth L.27,Serrano Andrew27,Dodick David W.27,Geda Yonas27,Wethe Jennifer V.27,Falk Bryce27,Duffy Amy27,Howard Marci27,Montague Michelle27,Osgood Thomas27,Babcock Debra27,Barr William27,Goldberg Judith27,Wisniewski Thomas27,Kirov Ivian27,Lui Yvonne27,Marmar Charles27,Hasanaj Lisene27,Serrano Liliana27,Al-Kharafi Alhassan27,George Allan27,Martin Sammie27,Riley Edward27,Runge William27,Peskind Elaine R.27,Colasurdo Elizabeth27,Marcus Daniel S.27,Gurney Jenny27,Johnson Keith A.27,Greenwald Richard27

Affiliation:

1. Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts

2. cBRAIN, Department of Child and Adolescent Psychiatry, Psychosomatics, and Psychotherapy, Ludwig-Maximilians-Universität, Munich, Germany.

3. Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts

4. Boston University Alzheimer’s Disease Research Center, Boston University CTE Center, Boston University School of Medicine, Boston, Massachusetts

5. Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle

6. Department of Neurology, University of Washington School of Medicine, Seattle

7. VISN 20 Northwest Network Mental Illness Research, Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington

8. Department of Pediatrics, Division of Child Neurology, Doernbecher Children’s Hospital, Oregon Health and Science University, Portland

9. Department of Rehabilitation Medicine, NYU Grossman School of Medicine, New York, New York

10. Département de génie logiciel et TI, École de technologie supérieure, Université du Québec, Montreal, Canada

11. Center for Clinical Spectroscopy, Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts

12. Boston University Alzheimer’s Disease Research Center, Boston University CTE Center, Department of Neurology, Boston University School of Medicine, Boston, Massachusetts

13. Department of Physical Medicine and Rehabilitation, Massachusetts General Hospital, Harvard Medical School, Boston

14. Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of USC, University of Southern California, Los Angeles

15. Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston

16. Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts

17. Department of Neurology, Mayo Clinic College of Medicine, Mayo Clinic Arizona Scottsdale, Arizona

18. Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, Nevada

19. Department of Neurology, NYU Grossman School of Medicine, New York, New York

20. Department of Population Health, NYU Grossman School of Medicine, New York, New York

21. Department of Ophthalmology, NYU Grossman School of Medicine, New York, New York

22. Chambers-Grundy Center for Transformative Neuroscience, Pam Quirk Brain Health and Biomarker Laboratory, Department of Brain Health, School of Integrated Health Sciences, University of Nevada, Las Vegas

23. Banner Alzheimer’s Institute, University of Arizona, Arizona State University, Translational Genomics Research Institute, and Arizona Alzheimer’s Consortium, Phoenix

24. Department of Anatomy & Neurobiology, Boston University School of Medicine, Boston, Massachusetts

25. Department of Neurosurgery, Boston University School of Medicine, Boston, Massachusetts

26. Graduate School of Systemic Neurosciences, Ludwig-Maximilians-Universität, Munich, Germany

27. for the DIAGNOSE CTE Research Project

Abstract

ImportanceExposure to repetitive head impacts (RHI) is associated with increased risk for neurodegeneration. Accumulation of toxic proteins due to impaired brain clearance is suspected to play a role.ObjectiveTo investigate whether perivascular space (PVS) volume is associated with lifetime exposure to RHI in individuals at risk for RHI-associated neurodegeneration.Design, Setting, and ParticipantsThis cross-sectional study was part of the Diagnostics, Imaging, and Genetics Network for the Objective Study and Evaluation of Chronic Traumatic Encephalopathy (DIAGNOSE CTE) Research Project, a 7-year multicenter study consisting of 4 US study sites. Data were collected from September 2016 to February 2020 and analyses were performed between May 2021 and October 2023. After controlling for magnetic resonance image (MRI) and processing quality, former American football players and unexposed asymptomatic control participants were included in analyses.ExposurePrior exposure to RHI while participating in American football was estimated using the 3 cumulative head impact indices (CHII-G, linear acceleration; CHII-R, rotational acceleration; and CHII, number of head impacts).Main Outcomes and MeasuresIndividual PVS volume was calculated in the white matter of structural MRI. Cognitive impairment was based on neuropsychological assessment. Linear regression models were used to assess associations of PVS volume with neuropsychological assessments in former American football players. All analyses were adjusted for confounders associated with PVS volume.ResultsAnalyses included 224 participants (median [IQR] age, 57 [51-65] years), with 170 male former football players (114 former professional athletes, 56 former collegiate athletes) and 54 male unexposed control participants. Former football players had larger PVS volume compared with the unexposed group (mean difference, 0.28 [95% CI, 0.00-0.56]; P = .05). Within the football group, PVS volume was associated with higher CHII-R (β = 2.71 × 10−8 [95% CI, 0.50 × 10−8 to 4.93 × 10−8]; P = .03) and CHII-G (β = 2.24 × 10−6 [95% CI, 0.35 × 10−6 to 4.13 × 10−6]; P = .03). Larger PVS volume was also associated with worse performance on cognitive functioning in former American football players (β = −0.74 [95% CI, −1.35 to −0.13]; P = .04).Conclusions and RelevanceThese findings suggest that impaired perivascular brain clearance, as indicated by larger PVS volume, may contribute to the association observed between RHI exposure and neurodegeneration.

Publisher

American Medical Association (AMA)

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