Dispersion-based cognitive intra-individual variability in former American football players: Association with traumatic encephalopathy syndrome, repetitive head impacts, and biomarkers

Authors

• Caroline Altaras, Department of Neurology, Boston University Alzheimer's Disease Research Center, Boston University CTE Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
• Monica T. Ly, Department of Neurology, Boston University Alzheimer's Disease Research Center, Boston University CTE Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
• Olivia Schultz, Department of Neurology, Boston University Alzheimer's Disease Research Center, Boston University CTE Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
• William B. Barr, Department of Neurology, NYU Grossman School of Medicine, New York, NY, USA.
• Sarah J. Banks, Department of Psychiatry, University of California San Diego Health, La Jolla, CA, USA.
• Jennifer V. Wethe, Department of Psychiatry and Psychology, Mayo Clinic School of Medicine, Mayo Clinic Arizona, Scottsdale, AZ, USA.
• Yorghos Tripodis, Department of Neurology, Boston University Alzheimer's Disease Research Center, Boston University CTE Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
• Charles H. Adler, Department of Neurology, Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale, AZ, USA.
• Laura J. Balcer, Departments of Neurology, Population Health and Ophthalmology, NYU Grossman School of Medicine, New York, NY, USA.
• Charles Bernick, Department of Neurology, Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale, AZ, USA.
• Henrik Zetterberg, Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK.
• Kaj Blennow, Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
• Nicholas Ashton, Banner Alzheimer's Institute, Phoenix, AZ, USA.
• Elaine Peskind, Department of Psychiatry and Behavioral Sciences, University of Washington Medicine, Seattle, WA, USA.
• Robert C. Cantu, Department of Neurology, Boston University Alzheimer's Disease Research Center, Boston University CTE Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
• Michael J. Coleman, Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Boston, MA, USA.
• Alexander P. Lin, Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Boston, MA, USA.
• Inga K. Koerte, Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Boston, MA, USA.
• Sylvain Bouix, Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Boston, MA, USA.
• Daniel Daneshvar, Department of Physical Medicine & Rehabilitation, Massachusetts General Hospital, Spaulding Rehabilitation Hospital, Harvard Medical School, Charlestown, MA, USA.
• David W. Dodick, Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, USA.
• Yonas E. Geda, Department of Neurology, the Franke Barrow Global Neuroscience Education Center, Neurological Institute, Barrow Phoenix, AZ, USA.
• Douglas L. Katz, Department of Neurology, Boston University Alzheimer's Disease Research Center, Boston University CTE Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
• Jason L. Weller, Department of Neurology, Boston University Alzheimer's Disease Research Center, Boston University CTE Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
• Jesse Mez, Department of Neurology, Boston University Alzheimer's Disease Research Center, Boston University CTE Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
• Joseph N. Palmisano, Biostatistics and Epidemiology Data Analytics Center (BEDAC), Boston University School of Public Health, Boston, MA, USA.
• Brett Martin, Biostatistics and Epidemiology Data Analytics Center (BEDAC), Boston University School of Public Health, Boston, MA, USA.
• Jeffrey L. Cummings, Department of Brain Health, School of Integrated Health Sciences, Chambers-Grundy Center for Transformative Neuroscience, University of Nevada Las Vegas, Las Vegas, NV, USA.
• Eric M. Reiman, Banner Alzheimer's Institute, Phoenix, AZ, USA.
• Martha E. Shenton, Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Boston, MA, USA.
• Robert A. Stern, Department of Neurology, Boston University Alzheimer's Disease Research Center, Boston University CTE Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.

Document Type

Article

Abstract

Exposure to repetitive head impacts (RHI), such as those experienced in American football, is linked to cognitive dysfunction later in life. Traumatic encephalopathy syndrome (TES) is a proposed clinical syndrome thought to be linked to neuropath-ology of chronic traumatic encephalopathy (CTE), a condition associated with RHI from football. Cognitive intra-individual variability (d-CIIV) measures test-score dispersion, indicating cognitive dysfunction. This study examined d-CIIV in former football players and its associations with TES diagnosis, RHI exposure, and DTI and CSF biomarkers. Data included 237 males (45-74 years) from DIAGNOSE CTE Research Project, including former professional and college football players (COL) (n = 173) and asymptomatic men without RHI or TBI (n = 55). Participants completed neuropsychological tests. TES diagnosis was based on 2021 NINDS TES criteria. Years of football play and a cumulative head impact index (CHII) measured RHI exposure. Lumipulse technology was used for CSF assays. DTI fractional anisotropy assessed white matter integrity. Coefficient of variation (CoV) measured d-CIIV. ANCOVA compared d-CIIV among groups (football versus control; TES-status). Pearson correlations and linear regressions tested associations between d-CIIV, RHI exposure, and CSF and DTI biomarkers. Former professional players had higher d-CIIV than controls (F(7, 194) = 2.87, p = .007). d-CIIV was associated with TES diagnosis (F(8, 146) = 9.063, p < .001), with highest d-CIIV in TES Possible/Probable-CTE. Higher d-CIIV correlated with higher CHII scores (r = 0.19), reduced CSF Aβ (β = -0.302), increased p-tau (β= 0.374), and reduced DTI FA (β = -0.202). d-CIIV is linked to RHI exposure and TES diagnosis in former football players, with associated changes in CSF biomarkers and white matter integrity.

Medical Subject Headings

Humans; Male; Football (injuries); Middle Aged; Biomarkers (cerebrospinal fluid); Neuropsychological Tests; Aged; Chronic Traumatic Encephalopathy (cerebrospinal fluid, diagnostic imaging); Diffusion Tensor Imaging; tau Proteins (cerebrospinal fluid); Cognitive Dysfunction (etiology, cerebrospinal fluid); White Matter (diagnostic imaging); Athletes

Publication Date

11-1-2025

Publication Title

The Clinical neuropsychologist

E-ISSN

1744-4144

Volume

39

Issue

8

First Page

2295

Last Page

2326

PubMed ID

39865747

Digital Object Identifier (DOI)

10.1080/13854046.2025.2453103

Recommended Citation

Altaras, Caroline; Ly, Monica T.; Schultz, Olivia; Barr, William B.; Banks, Sarah J.; Wethe, Jennifer V.; Tripodis, Yorghos; Adler, Charles H.; Balcer, Laura J.; Bernick, Charles; Zetterberg, Henrik; Blennow, Kaj; Ashton, Nicholas; Peskind, Elaine; Cantu, Robert C.; Coleman, Michael J.; Lin, Alexander P.; Koerte, Inga K.; Bouix, Sylvain; Daneshvar, Daniel; Dodick, David W.; Geda, Yonas E.; Katz, Douglas L.; Weller, Jason L.; Mez, Jesse; Palmisano, Joseph N.; Martin, Brett; Cummings, Jeffrey L.; Reiman, Eric M.; Shenton, Martha E.; and Stern, Robert A., "Dispersion-based cognitive intra-individual variability in former American football players: Association with traumatic encephalopathy syndrome, repetitive head impacts, and biomarkers" (2025). Neurology. 2019.
https://scholar.barrowneuro.org/neurology/2019