Dose-dependent white matter changes associated with repetitive head impacts in former American football players
Year: 2026
Type: article
Study design: Observational Study
Abstract: Repetitive head impacts sustained during American football have been associated with neuropathological changes such as white matter shear injuries. However, the impact of specific factors, such as age of first exposure and cumulative head impact burden, on white matter integrity remains unclear. This study investigated in vivo white matter microstructural changes using diffusion tensor imaging and tract-based spatial statistics in 165 male former American football players (mean age 57.3 years, range 45–74) and 52 unexposed asymptomatic male controls (mean age 59.4 years, range 45–74) in the DIAGNOSE CTE Research Project. Compared to controls, former football players exhibited significantly higher fractional anisotropy (FA) in 1.97% of the white matter skeleton (1552 voxels; Cohen’s d = 0.587) and higher tissue-corrected FA (FAt) in 1.48% of the white matter skeleton (1004 voxels; Cohen’s d = 0.616). No significant differences were observed for mean diffusivity, axial diffusivity, radial diffusivity, or free water between football players and controls. Among football players, there were no significant differences in the white matter microstructure between players diagnosed with traumatic encephalopathy syndrome and those without the diagnosis. Lower FA was significantly associated with older age (P < 0.00001) and an earlier age of first exposure to tackle football (P < 0.01), while lower FAt was associated with greater cumulative head impact burden, specifically higher linear acceleration (P < 0.04) and rotational force (P < 0.02). This study highlights the influential role of exposure factors on white matter microstructure in former American football players, as well as the utility of diffusion tensor imaging to aid in characterizing the long-term effects of repetitive head impacts in contact sport athletes.
Source: Brain Communications
Authors: Hector Arciniega, Alana Wickham, Brian Szekely, Nicholas Kim, Kang I Cho, Holly Carrington, Evdokiya E Knyazhanskaya, Omar John, Leonard B Jung, Katherine Breedlove, Anya S Mirmajlesi, Jared Stearns, Richard Jarrett Rushmore, Daniel H Daneshvar, Tim L T Wiegand, Tashrif Billah, Ofer Pasternak, Suheyla Cetin-Karayumak, Yogesh Rathi, Michael J Coleman, Charles H Adler, Charles Bernick, Laura J Balcer, Brian S Im, Shae Datta, Michael L Alosco, Inga K Koerte, Alexander P Lin, Jeffrey L Cummings, Eric M Reiman, Robert A Stern, Martha E Shenton, Sylvain Bouix, Eric Reiman, Yi Su, Kewei Chen, Hillary Protas, Connie Boker, Michael L Alosco, Rhoda Au, Robert C Cantu, Lindsay Farrer, Robert Helm, Douglas I Katz, Neil Kowall, Jesse Mez, Gustavo Mercier, James Otis, Robert A Stern, Jason Weller, Irene Simkin, Alondra Andino, Shannon Conneely, Courtney Diamond, Tessa Fagle, Olivia Haller, Tennyson Hunt, Nicole Gullotti, Megan Mariani, Brian Mayville, Kathleen McLaughlin, Mary Nanna, Taylor Platt, Surya Pulukuri, Fiona Rice, Madison Sestak, Michael McClean, Yorghos Tripodis, Douglas Annis, Christine Chaisson, Diane B Dixon, Carolyn Finney, Kerrin Gallagher, Kaitlin Hartlage, Jun Lu, Brett Martin, Emmanuel Ojo, Joseph N Palmisano, Brittany Pine, Janani Ramachandran, Sylvain Bouix, Jennifer Fitzsimmons, Alexander P Lin, Inga K Koerte, Ofer Pasternak, Martha E Shenton, Hector Arcinieago, Tashrif Billah, Elena Bonke, Katherine Breedlove, Eduardo Coello, Michael J Coleman, Leonhard Jung, Huijun Liao, Maria Loy, Elizabeth Rizzoni, Vivian Schultz, Annelise Silva, Brynn Vessey, Tim L T Wiegand, Sarah Banks, Charles Bernick, Jason Miller, Aaron Ritter, Marwan Sabbagh, Raelynn de la Cruz, Jan Durant, Morgan Golceker, Nicolette Harmon, Kaeson Kaylegian, Rachelle Long, Christin Nance, Priscilla Sandoval, Robert W Turner, Kenneth L Marek, Andrew Serrano, Charles H Adler, David W Dodick, Yonas Geda, Jennifer V Wethe, Bryce Falk, Amy Duffy, Marci Howard, Michelle Montague, Thomas Osgood, Debra Babcock, Patrick Bellgowan, Laura Balcer, William Barr, Judith Goldberg, Thomas Wisniewski, Ivan Kirov, Yvonne Lui, Charles Marmar, Lisena Hasanaj, Liliana Serrano, Alhassan Al-Kharafi, Allan George, Sammie Martin, Edward Riley, William Runge, Jeffrey L Cummings, Elaine R Peskind, Elizabeth Colasurdo, Daniel S Marcus, Jenny Gurney, Richard Greenwald, Keith A Johnson
Institutions: NYU Langone Health, New York University, Brigham and Women's Hospital, Harvard University, LMU Klinikum, Ludwig-Maximilians-Universität München, Boston University, Massachusetts General Hospital, Spaulding Rehabilitation Hospital, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Charité – Universitätsmedizin Berlin, Mayo Clinic in Arizona, Cleveland Clinic, University of Washington, Lou Ruvo Brain Institute, University of Nevada, Las Vegas, Translational Genomics Research Institute, University of Arizona, Banner Alzheimer’s Institute, Arizona Alzheimer’s Consortium, Arizona State University, École de Technologie Supérieure
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,024
Awards: Alzheimer's Disease Research Center, Chronic Traumatic Encephalopathy: Detection, Diagnosis, Course, and Risk Factors, G6349021916, Sex Differences in Brain Structure and Function After Sports-Related Concussion, Head Impacts & Neurodegeneration, Understanding the Cognitive and Neural Consequences of Repetitive Head Impacts, Understanding the Neuroanatomical Abnormalities of Repetitive Head Impacts
OpenAlex ID: W7162937851