HJAR Sep/Oct 2023

CTE 26 SEP / OCT 2023 I  HEALTHCARE JOURNAL OF ARKANSAS INTRODUCTION Chronic traumatic encephalopathy (CTE) is a neurogenerative disease identified in individuals with exposure to repetitive head impacts (RHI), including military veterans, victims of physical violence, and contact and collision sports (CCS) athletes, includ- ing American football players 1,2 . CTE is dis- tinguished from other neuropathologies by the pathognomonic lesion of perivascular accumulation of hyperphosphorylated tau in neurofibrillary tangles (NFTs), typically at the sulcal depths of the cerebral cortex, as well as diffuse NFTs in medial temporal lobe, diencephalon, basal ganglia, and brain stem 3 . Effectively quantifying the RHI expo- sure needed to develop CTE has been lim- ited and challenging. Importantly, self or informant reported symptomatic concus- sion has not been associated with the pres- ence or severity of CTE pathology 1,4,5 . How- ever, total years of football played, thought to serve as a proxy for RHI, demonstrated a significant dose-response relationship with both CTE presence and CTE severity 5 . The finding that years of play is positively asso- ciated with CTE pathology, whereas symp- tomatic concussion is not, suggests that other regularly occurring exposures, such as RHI, may have an instrumental role in influencing CTE development. However, the assessment of concussion is problematic, as concussion definitions and diagnoses have changed over time, and many athletes report vastly different numbers of concus- sions based on definitions applied 6 . This dif- ficulty accurately quantifying concussions experienced is further compounded in stud- ies that attempt to estimate concussion bur- den based on informant report. American football provides a unique model to better understand the relationship between RHI and CTE. Athletes begin play- ing football at different ages and for differ- ent career durations. The average frequency of impacts that an athlete experiences over a given season, and the average intensity of those impacts, varies based on position and level played 7 . We hypothesized that these differences could be leveraged to investi- gate the relationships between RHI-related factors and CTE pathology, potentially with implications relevant for football players, as well as other contact sport athletes. To estimate an athlete’s RHI exposure based on football position, duration, and level of play, data can be obtained from hel- met accelerometers. Helmet accelerometers measure the head impact count and acceler- ation across different levels and positions of football play 8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28, 29,30,31,32,33,34,35,36,37,38,39,40,41 . Building on the use of exposure matrices to quantify risks associ- ated with exposures in other domains, data from helmet sensors have been previously utilized to approximate the potential num- ber of head impacts that a football player may have received 42,43,44,45 . This cumulative head impact index (CHII), which incorpo- rates an individual’s career length, positions, and levels of play, represents an athlete’s estimated lifetime number of football- related hits to the head 42,43,44,45 . CHII has been linked to former athletes’ mood and cog- nitive symptoms, cerebrospinal fluid total tau levels, and all-cause mortality, but the relationship to CHII and underlying pathol- ogy has not been previously studied 42,43,44,45 . Further, since the CHII was developed, more recent helmet sensor data from youth, high school, and collegiate football players have been published. These additional data (as well as older data) include estimates of aver- age linear and rotational acceleration, mea- sures of acceleration that were not included in the original CHII. Incorporation of these additional data may improve estimation of an athletes’ exposure to RHI and, by exten- sion, improve estimation of the effect of RHI on CTE risk. In this study, we sought to update the pre- viously published CHII with updated data. ABSTRACT Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy associated with repetitive head impacts (RHI), but the components of RHI exposure underlying this relationship are unclear.We create a position exposure matrix (PEM), composed of American football helmet sensor data, summarized from literature review by player position and level of play. Using this PEM, we estimate measures of lifetime RHI exposure for a separate cohort of 631 football playing brain donors. Separate models examine the relationship between CTE pathology and players’ concussion count, athletic positions, years of football, and PEM-derived measures, including estimated cumulative head impacts, linear accelerations, and rotational accelerations. Only duration of play and PEM-derived measures are significantly associated with CTE pathology. Models incorporating cumulative linear or rotational acceleration have better model fit and are better predictors of CTE pathology than duration of play or cumulative head impacts alone. These findings implicate cumulative head impact intensity in CTE pathogenesis. Leveraging football accelerometer data to quantify associations between repetitive head impacts and chronic traumatic encephalopathy in males © 2023 LLS. Printed with permission. https://creativecommons.org/licenses/by/4.0/ Daneshvar, D.H., Nair, E.S., Baucom, Z.H. et al. Leveraging football accelerometer data to quantify associations between repetitive head impacts and chronic traumatic encephalopathy in males. Nature Communications 14, 3470 (2023). https://doi.org/10.1038/s41467-023-39183-0