HAI Book 2025 - Flipbook - Page 721
Groh, Jenna
Association of a unique pattern of white matter T2 FLAIR hyperintensities
with plasma and tau PET biomarkers in former American football players
Jenna R. Groh1, Chad Farris1, Adam M. Brickman2, Mohamad J. Alshikho2, Annalise E. Miner1,
Yorghos Tripodis3, Anna Cui1, Charles H. Adler4, Laura J. Balcer5, Charles Bernick6, Robert C.
Cantu1, Michael J Coleman8, David Dodick4, Nicholas Ashton9, Henrik Zetterberg9, Kaj
Blennow9, Elaine R. Peskind10, Ann C. McKee1, Jesse Mez1, Sylvain Bouix11, Jeffrey L.
Cummings12, Eric M. Reiman13, Robert A. Stern1, Martha Shenton8,14, Michael L. Alosco1
1
Boston University Chobanian & Avedisian School of Medicine, Boston, MA, US
Columbia University, Department of Neurology, New York, NY, US
3
Boston University School of Public Health, Boston, MA, US
4
Mayo Clinic College of Medicine, Department of Neurology, Scottsdale, AR, US
5
NYU Grossman School of Medicine, Departments of Neurology, Population Health and Ophthalmology, New York, NY,
US
6
Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, US
7
University of Washington, Department of Neurology, Seattle, WA, US
8
Brigham and Women’s Hospital, Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Boston, MA, US
9
The Sahlgrenska Academy at the University of Gothenburg, Institute of Neuroscience and Physiology, Department of
Psychiatry and Neurochemistry, Mölndal, SE
10
University of Washington School of Medicine, Department of Psychiatry and Behavioral Sciences, Seattle, WA, US
11
École de technologie supérieure, Department of Software Engineering and Information Technology, Montreal, QC,
CA
12
University of Nevada Las Vegas, Chambers-Grundy Center for Transformative Neuroscience, Department of Brain
Health, School of Integrated Health Sciences, Las Vegas, NV, US
13
Banner Alzheimer’s Institute, University of Arizona, Arizona State University, Translational Genomics Research
Institute, and Arizona Alzheimer’s Consortium, Phoenix, AR, US
14
Brigham and Women’s Hospital, Harvard Medical School, Department of Radiology, Boston, MA, US
2
Background: Repetitive head impacts (RHI) can lead to long-term white matter injury visualized on FLAIR scans as
white matter hyperintensities (WMH). Anecdotally, we observed a distinct pattern of WMH in individuals with RHI
exposure: small, punctate, discrete lesions near the cortex at the depths of the sulci (Figure 1a). The goal of this
study was to empirically characterize this pattern in former elite American football players.
Methods: The sample included 164 male football players (n=111 professional and n=53 college players) and n=55
asymptomatic males without RHI from the DIAGNOSE Project with available MRI, 18F-flortaucipir (FTP), and
florbetapir PET data. (Table 1). Visual ratings blind to information about the participant9s exposure status and
clinical status were conducted to count WMH that were a.) within 1.0cm of the gray/white matter boundary, b.) as
bright as the cortex, c.) spherical and d.) less than 1.0cm in size. ANCOVA compared groups on total number of
WMH adjusted for age and vascular risk factors. Among football players, multivariable linear regression models
assessed relationships between WMH and plasma biomarkers including p-tau181, p-tau231, A´42/40 ratio,
neurofilament light (NfL), glial fibrillary acidic protein (GFAP) and FTP composite SUVRs.
Results: Number of WMH was greater in football players compared to controls (p=0.007) (Figure 1b). Among
former players, elevated p-tau231 (padj=0.041) and NfL (padj=0.034) were associated with greater WMH but p-tau181
(padj=0.295), GFAP (padj=0.784), and the ratio A´42/40 (padj=0.697) were not (Figure 2). Number of WMH was
associated with tau PET composite regions frontal SUVR (padj=0.046) and left-parietal SUVR (padj=0.046) but not
mesial-temporal SUVR (padj=0.285) (Figure 2).
HAI2025 - 721
