Repetitive Head Impacts and Perivascular Space Volume in Former American Football Players
Authors: Jung Leonard B. , Wiegand Tim L. T. , Tuz-Zahra Fatima , Tripodis Yorghos , Iliff Jeffrey J. , Piantino Juan , Arciniega Hector , Kim Cara L. , Pankatz Lara , Bouix Sylvain , Lin Alexander P. , Alosco Michael L. , Daneshvar Daniel H. , Mez Jesse , Sepehrband Farshid , Rathi Yogesh , Pasternak Ofer , Coleman Michael J. , Adler Charles H. , Bernick Charles , Balcer Laura , Cummings Jeffrey L. , Reiman Eric M. , Stern Robert A. , Shenton Martha E. , Koerte Inga K. ,   DIAGNOSE CTE Research Project, Su Yi , Chen Kewei , Protas Hillary , Boker Conni , Au Rhoda , Cantu Robert C. , Farrer Lindsay , Helm Robert , Kowall Neil , Mercier Gustavo , Otis James , Weller Jason , Simkin Irene , Andino Alondra , Conneely Shannon , Diamond Courtney , Fagle Tessa , Haller Olivia , Hung Tennyson , Gullotti Nicole , Mariani Megan , Mayville Brian , McLaughlin Kathleen , Nanna Mary , Platt Taylor , Pulukuri Sury , Rica Fiona , Sestak Madison , McClean Michael , Annis Douglas , Chaisson Christine , Dixon Dianne B. , Finney Carolyn , Gallagher Kerrin , Hartlage Kaitlin , Lu Jun , Martin Brett , Ojo Emmanuel , Palmisano Joseph N. , Pine Brittany , Ramachandran Janani , Fitzsimmons Jennifer , Bonke Elena M. , Breedlove Katherine , Coello Eduardo , Liao Hujiun , Rizzoni Elizabeth , Schultz Vivian , Silva Annelise , Vessey Brynn , Banks Sarah , Miller Jason , Ritter Aaron , Sabbagh marwan , de la Cruz Raelynn , Durant Jan , Golceker Moragn , Harmon Nicolette , Kaylegian Kaeson , Long Rachelle , Nance Christin , Sandoval Priscilla , Turner Robert W. , Marek Kenneth L. , Serrano Andrew , Dodick David W. , Geda Yonas , Wethe Jennifer V. , Falk Bryce , Duffy Amy , Howard Marci , Montague Michelle , Osgood Thomas , Babcock Debra , Barr William , Goldberg Judith , Wisniewski Thomas , Kirov Ivian , Lui Yvonne , Marmar Charles , Hasanaj Lisene , Serrano Liliana , Al-Kharafi Alhassan , George Allan , Martin Sammie , Riley Edward , Runge William , Peskind Elaine R. , Colasurdo Elizabeth , Marcus Daniel S. , Gurney Jenny , Johnson Keith A. , Greenwald Richard 
Published: August 2024

Importance

Exposure 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.

Objective

To investigate whether perivascular space (PVS) volume is associated with lifetime exposure to RHI in individuals at risk for RHI-associated neurodegeneration.

Design, Setting, and Participants

This 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.

Exposure

Prior 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 Measures

Individual 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.

Results

Analyses 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 Relevance

These findings suggest that impaired perivascular brain clearance, as indicated by larger PVS volume, may contribute to the association observed between RHI exposure and neurodegeneration.