3

Exploring the Evidence on Health Outcomes of Youth Exposure to Repetitive Head Impacts

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¹ This list is the rapporteurs’ summary of points made by the individual speakers identified, and the statements have not been endorsed or verified by the National Academies of Sciences, Engineering, and Medicine. They are not intended to reflect a consensus among workshop participants.

The second aim of the workshop was to examine what is known, and not known, about health outcomes associated with youth exposure to repetitive head impacts (RHI), including both short- and long-term effects and the factors that may influence them. Presentations and discussions over three sessions explored evidence on acute neurological and clinical changes following RHI; pathological and epidemiological findings on potential long-term outcomes; and the role of biological, behavioral, and social modifiers in shaping risk across the life course. Speakers emphasized the complexity of linking early exposures to later health trajectories, the lack of consistent short-term clinical findings, and the need for longitudinal, population-based studies to clarify cumulative risks.

ASSESSING SHORT-TERM OUTCOMES OF RHI EXPOSURE IN YOUTH

Jeffrey Bazarian, professor of emergency medicine and neurology at the University of Rochester, introduced and moderated a session on short-term outcomes following exposure to RHI in youth. These outcomes were defined as those occurring from the immediate aftermath through several months postexposure. While concerns about long-term effects such as chronic traumatic encephalopathy (CTE) have driven interest in RHI, Bazarian emphasized the importance of understanding short-term biological and clinical changes to clarify whether such exposures may lead to later impairment. “Is there anything we see clinically or on a cellular or organ level that tells us that an athlete’s brain health is in jeopardy?” he asked. Because causal links are difficult to draw across decades, he suggested that detecting early effects could illuminate pathways to long-term outcomes and create opportunities

for timely intervention. The session explored current evidence on how RHI may affect brain structure, function, and behavior in the short term, and highlighted emerging insights—as well as uncertainties—about the clinical relevance of these early changes.

Short-Term Neurological Responses to RHI in Youth

Kei Kawata, associate professor at the Indiana University Blooming-ton School of Public Health, opened his remarks by noting that although awareness around RHI has grown over the past 15 years, more questions remain than answers regarding the diagnostic and prognostic implications of RHI exposure. His presentation focused on four areas: the biomechanics of head injury, potential effects of RHI in adolescent football players, factors that can modulate RHI effects, and contextual factors such as cannabis use or attention deficit hyperactivity disorder (ADHD) that may modulate the effects of RHI.

Kawata began by examining the biomechanics of concussion, drawing on early research—including National Football League (NFL) concussion video reconstructions using dummy models—that identified an average concussive threshold around 98 g of linear acceleration (Pellman et al., 2003). Similar thresholds were reported in clinical studies across amateur football and soccer, reinforcing the idea of a 100 g benchmark, Kawata noted. However, more recent large-scale data challenge this notion. A study involving over 1,000 high school and college football players found that diagnosed concussions occurred at impact forces ranging from as low as 29 g to over 200 g (Beckwith et al., 2013). This variability, Kawata emphasized, reveals that a single threshold may not be predictive of injury risk. Instead, responses to impact are shaped by within-person and between-person heterogeneity. These findings have shifted research priorities away from identifying a single threshold toward understanding the cumulative and individualized effects of repeated subconcussive impacts (i.e., nonconcussive head impacts that are below the clinical threshold for concussion).

Near Point of Convergence Testing

Kawata highlighted near point of convergence (NPC) testing as an example of a simple, and accessible measure to assess subtle changes following RHI exposure (Bellini et al., 2024; Kawata et al., 2016a,b; Nowak et al., 2020, 2023; Stephen et al., 2022; Zonner et al., 2019a; Zuidema et al., 2023). NPC assessments evaluate oculomotor function by determining how closely the eyes can focus before diplopia (double vision) occurs. In a longitudinal study of high school football players, players with higher head impact exposure—measured via instrumented mouthguards—showed

significantly greater NPC distance over the course of the season compared to lower-impact peers. These impairments did not resolve after 2 weeks of rest during the off-season (Zuidema et al., 2022; Kawata et al., 2016a). Unexpectedly, daily tracking during summer camp revealed that three players showed elevated NPC measurements the morning before sustaining a concussion during full-contact practice, suggesting that convergence changes may signal accumulating neurological stress, Kawata said. While labor intensive to collect for each player over multiple time points during a season, Kawata suggested that NPC could serve as a noninvasive clinical marker of early oculomotor disruption from repetitive head impacts—even prior to a diagnosed concussion.²

Brain Structure and Function Outcomes

Kawata discussed an ongoing longitudinal study conducted by his laboratory and highlighted longitudinal neuroimaging findings comparing high school football players and non-contact athletes over a single season. While noncontact athletes showed the expected pattern of cortical thinning—a hallmark of adolescence neurodevelopment—football players did not (Zuidema et al., 2024). These results support previous findings that football athletes show a decreased rate of age-related cortical thinning compared to noncontact athletes (Mills et al., 2020). Kawata speculated that RHI may disrupt normal neurodevelopment, potentially through mechanisms like neuroinflammation. These data come from an ongoing 4-year study aimed at understanding how cumulative exposure to subconcussive impacts affects adolescent brain structure over time.

Biomarkers and Brain Strain

Kawata also discussed changes in brain-injury biomarkers following RHI exposure. In a study of adolescent football players, blood biomarker levels for GFAP, a marker of astrocyte activation, increased over the course of the season. UCH-L, a marker of neuronal injury, also rose and was significantly associated with both head impact kinematics and estimated brain strain. Similar biomarker elevations were observed across all playing positions (Zuidema et al., 2023). Kawata also described findings related to S100B, a protein released by astrocytes in response to injury. While low

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² Workshop speakers discussed measures to detect brain or symptom changes after head impacts while noting that the utility of many measures for understanding effects of repeated, nonconcussive impacts remain open questions. For example, some studies have found within-athlete test–retest variability on oculomotor screening (Broglio, 2018a; Ferris, 2022), highlighting the need for ongoing research to refine measurement and interpretation in the context of RHI.

levels may be trophic, excessive release can be harmful, Kawata explained. In a study of high school football players, head impact kinematics predicted changes in S100B levels, after controlling for physical exertion using excess postexercise oxygen consumption (Zonner et al., 2019b), recapitulating findings from prior work (Marchi et al., 2013).

Soccer Heading Model–––Understanding How Different Factors Affect RHI Exposure Outcomes

Kawata discussed how his laboratory reduces confounding factors present in field studies by employing a controlled soccer heading model to examine how repeated mild exposures—10 or 20 head impacts—affect neurophysiological outcomes. This model induces changes in oculomotor function and elevates blood biomarkers (e.g., neurofilament light chain) 24 hours postexposure, indicating that it effectively mirrors RHI exposure observed in athletic settings (Hwang et al., 2017; Nowak et al., 2020; Wirsching et al., 2019), Kawata said. Crucially, this model also enables researchers to test whether individual or contextual factors, such as hypoxia, sleep deprivation, fasting, cannabis use, and ADHD, modulate responses to RHI. Kawata presented recent findings focused on two such factors: cannabis use and ADHD.

Responses to RHI Exposure for Chronic Cannabis Users

Research is beginning to examine the potential influence of cannabis use on outcomes following RHI exposure, particularly in light of evolving policies—such as the NFL and the National Collegiate Athletic Association (NCAA) no longer testing for cannabis. One study using a soccer heading model exposed athletes to 20 controlled headers and measured outcomes before and after the exposure. The findings suggest that chronic cannabis use may be associated with enhanced oculomotor functional resilience and a dampened neuroinflammatory response following RHI (Kalbfell et al., 2023), raising new questions about the potential neuroprotective effects of cannabinoids in contact sports, Kawata said.

Responses to RHI Exposure for Youth with ADHD

Kawata shared recent evidence that suggests that athletes with ADHD may be more likely to choose team contact sports (OSU, 2017). ADHD is also tied to increased concussion risks for kids (Liou et al., 2018), and concussions may also have greater psychological effects in athletes with ADHD (Moore, 2018). Kawata’s group was curious whether mild hits affect youth with ADHD differently than their peers. Athletes with ADHD

who experienced 10 headers showed declines in recovery of verbal and visual memory not observed in non-ADHD athletes (Nowak et al., 2022).

Future Directions

Kawata concluded that short-term neurophysiological outcomes from exposure to RHI in youth have been observed across biomarkers, brain structure, and oculomotor function. These responses may be influenced by variables such as ADHD, sleep, and cannabis use. Further research is needed to determine the mechanisms and duration required for these effects to become persistent or irreversible. Kawata highlighted an ongoing clinical trial testing omega-3 fatty acids as a potential countermeasure for subconcussive head impacts (Beauregard et al., 2025).³

Short-Term Clinical Outcomes After Repetitive Head Impacts in Youth

Sean Rose, a pediatric neurologist at Nationwide Children’s Hospital, reviewed the current body of evidence on short-term clinical outcomes following RHI in youth. He outlined the range of clinical measures that have been studied in this context, including self- or parent-reported symptoms; self- or parent-reported behavioral and social function (e.g., mood, quality of life, social adjustment); cognitive or neuropsychological testing; balance testing (e.g., the Balance Error Scoring System); visual tracking and scanning (e.g., King-Devick test); and quantitative pupillometry, which uses light response testing to assess autonomic and neurological function. These tools have been used across a variety of research designs to examine whether RHI exposure results in observable changes in child and adolescent health outcomes.

Acute Effects of RHI Exposure

Both controlled and observational studies have assessed the acute effects of RHI in youth immediately following exposure. In one example, adolescent soccer players wore mouth guard sensors and completed 10 intentional headers in a single session. Players completed balance, symptom, and visual assessments immediately before and within 24 hours after the exposure. No changes were observed across any of the measured outcomes (Huber et al., 2023). Similarly, a study of high school football players using helmet impact sensors found changes in pupillary reactivity both directly after high-magnitude impacts, as well as pre- and postseason. However,

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³ See https://clinicaltrials.gov/study/NCT06736925 (accessed August 8, 2025).

these physiological changes were not accompanied by changes in symptom reporting, cognitive screens, or balance testing (Joseph et al., 2019).

One-Season Studies on Clinical Outcomes

Rose then reviewed findings from observational studies examining outcomes across one season of youth contact sport participation. Across more than 10 studies—including soccer and football players ranging in age from 8 to 18 years—results were mixed (see Table 3-1). Most studies found no correlations between the number or magnitude of head impacts and changes in cognitive, behavioral, or balance measures from preseason to postseason. Some studies did report small effects in subgroups, including one in which players with over 50 impacts per week showed worse cognitive processing in postseason testing compared to preseason testing (Nauman et al., 2015).

Assessing Cumulative Effects

Longitudinal studies tracking participants over multiple seasons of play to assess the cumulative effects of RHI on health outcomes in youth are limited, Rose said. However, findings from a longitudinal study following youth football players across up to four consecutive seasons may provide insight into cumulative effects over time. Players, ages 9 to 12 at enrollment, completed repeated assessments across more than 15 outcome measures. No associations were found between higher cumulative impacts and worse outcome measures; instead, performance differences were more strongly linked to ADHD, anxiety, and depression (Rose et al., 2019b, 2021).

Evidence Gaps

Rose concluded by emphasizing the lack of consistent acute changes in clinical outcomes after exposure to RHI in childhood. However, he noted substantial gaps in the evidence base, including a lack of data on girls and younger children, limited longitudinal studies to understand the effects of multiseason exposure, and minimal research on youth with ADHD and other mood or behavioral disorders—groups that may be both more likely to participate in contact sports and more vulnerable to adverse outcomes. Addressing these gaps will be essential to a deeper understanding of potential short-term risks associated with RHI in youth.

TABLE 3-1 Select One-Season Studies of Youth Repetitive Head Impact Exposure and Outcomes

NOTE: * indicates a subset of participants.

SOURCE: Presented by Sean Rose, April 15, 2025.

Discussion

Bazarian moderated a wide-ranging exchange that explored key tensions and open questions on the short-term effects of RHI. Panelists Kawata and Rose were joined by several planning committee members in addressing the limitations of current clinical measures, the potential disconnection between biological signals and functional outcomes, and the need for new paradigms in RHI research.

Measurement Validity Across Injury Types

Michael Alosco opened the discussion by asking Rose whether domains and measures—largely derived from concussion research—are suitable for assessing the clinical sequelae of RHI, which often involve impacts that do not rise to the level of diagnosable injury. Rose acknowledged the challenge, noting that the use of concussion-derived tools reflects a practical starting point but may miss subtler or distinct outcomes associated with lower-magnitude impacts. He expressed openness to novel measurement strategies, especially those sensitive to cognitive or neurologic changes outside the typical postconcussion framework.

Balancing Biological and Clinical Signals

Yeates highlighted a central tension in the field: while biologically based markers (e.g., blood-based proteins or imaging changes) may show consistent changes post-RHI, their clinical relevance remains unclear in the absence of measurable symptoms or functional deficits. Rose described this disconnection as “the elephant in the room,” and emphasized the need to better understand whether, and if so how, biomarker changes translate into meaningful health outcomes. He suggested that one important step may be to explore novel outcome measures that extend beyond traditional concussion tools. Compensatory mechanisms may also mask measurable clinical outcomes, Kawata added.

Interpretation of Transient Changes

Building on this point, Arbogast asked whether transient biomarker or functional changes—those that resolve within hours or days—should be cause for concern. Kawata noted that while some changes resolve quickly, it remains unknown whether repeated exposures over short intervals might have cumulative effects. Rose agreed, adding that it is unclear whether such exposures are more like temporary soreness or represent injuries with longer-term consequences that current tools may not detect.

Biomarkers in RHI Research

An audience participant asked about the usefulness of biomarkers for RHI. Rose discussed several biomarkers, including proteins and microRNAs in the blood or saliva, that are being used to assess the diagnosis and recovery of concussions. If reliable associations are confirmed between biomarkers and diagnosing concussions, these markers could be “tailored and refined”

to explore whether subconcussive exposures elicit similar, if subtler, biological changes, he suggested.

Possibility of Adaptive Responses

Drawing from ischemia literature showing that mild, repetitive exposures can promote adaptability and resilience, Christopher Giza asked whether some acute biomarker changes observed after RHI might reflect a brain defense mechanism rather than injury alone. Rose responded that if RHI promoted adaptability, studies would be expected to show measurable improvements in performance over time in athletes with higher exposure, which current evidence does not demonstrate. Kawata agreed that adaptive responses to RHI would be valuable to investigate. Individual differences in adaptation or vulnerability may exist, he noted, referencing preliminary data suggesting habituation to RHI in some athletes. However, he emphasized the challenge of distinguishing potential brain adaptation from accumulating harm and underscored the need for strategies to disentangle these effects.

Potential Connections Between Acute RHI Exposure and Long-Term Neurodegeneration

An audience member asked if there are connections between acute effects from experiencing RHI and the development of CTE pathology. Kawata argued that the biological signals observed acutely—including astrocyte activation and changes in cortical morphology—mirror pathologies seen in CTE, such as glial inflammation and tau aggregation. He suggested that cumulative acute responses, if unchecked, could plausibly set the stage for long-term neurodegeneration.

ASSESSING LONG-TERM OUTCOMES OF RHI EXPOSURE IN YOUTH

RHI in Youth and Long-Term Neuropathological Outcomes

Jesse Mez, a behavioral neurologist specializing in neurodegenerative disease, presented research on youth RHI and long-term neuropathological outcomes, with a focus on CTE.

CTE and the Exposome

Mez opened by highlighting the importance of examining the exposome—cumulative exposures across the life course—to better understand neurodegenerative disease risk. “There’s a question about whether trauma that

happens many years before the neurodegenerative process could play a role,” he said. Testing this hypothesis, he noted, requires large sample sizes or large effect sizes, given the long latency between youth exposure and later-life outcomes: “Those are the studies we really need.”

CTE is one such disease of interest. It is a progressive neurodegenerative condition pathologically defined by deposits of hyperphosphorylated tau (p-tau) at the depths of cortical sulci around blood vessels (McKee et al., 2016). CTE progresses through four stages of increasing severity and is associated with gross brain changes including cortical atrophy, ventricular enlargement, and hippocampal shrinkage. CTE is not only a pathological change, Mez said, but one associated with significant clinical outcomes. In a study of 364 brain donors with autopsy-confirmed CTE, p-tau pathology explained up to 49 percent of the variance in cognitive and functional impairments, including deficits in memory, attention, executive function, and daily living skills (Alosco et al., 2024).

Relationship Between RHI and CTE

Despite the challenge of studying long-term outcomes of RHI, Mez noted that a relationship between CTE and RHI has been found across several studies.

A 2015 study of a neurodegenerative disorders brain bank provides evidence for a relationship between RHI and CTE. Among 66 male contact sport athletes, 21 were found to have CTE pathology, while none of the 132 matched noncontact male athletes, women, or individuals with a single TBI showed evidence of the disease (Bieniek et al., 2015). Mez also presented findings from the Boston University UNITE Brain Bank, which includes over 1,500 brain donors with a history of trauma exposure—predominantly former male American football players, as well as individuals from the military and other high-exposure groups (Mez et al., 2015). Analyses reveal an increase in both CTE prevalence and severity with higher levels of play. Among the sample of brain donors whose highest level of play was before high school or high school, about 40 percent showed evidence of CTE (7 of 17). The proportion rose to about 70 percent among former college players, more than half of whom had severe pathology, and to nearly 90 percent among former professional athletes, with over 75 percent at the most advanced stages (Daneshvar et al., 2023). Mez cautioned, however, that these findings are likely not representative of the broader athlete population. Brain donations often occur when families are concerned about symptoms, which means donors are more likely to be symptomatic and thus more likely to have CTE. “We’re not proposing these figures reflect prevalence,” he said, “but they stand in stark contrast to findings from community-based brain banks.” In those banks, CTE remains rare, with

reported rates ranging from 0 percent to 3.2 percent (Adams et al., 2018; Agrawal et al., 2024; Forrest et al., 2019; McCann et al., 2022; Postupna et al., 2021).

Based on the observations for level of play, Mez hypothesized that there would be a dose–response relationship between years of football play (a proxy for RHI exposure) and prevalence of CTE pathology. He discussed a study of a convenience sample of 266 deceased American football players in which 223 of 266 participants (84 percent) met neuropathological diagnostic criteria for CTE. Analyses demonstrated that the odds of CTE increased by 30 percent for each additional year played. For each 2.6 additional years played, the odds of developing CTE doubled. In simulation analyses to account for brain bank selection bias, the estimated magnitude of the relationship between years of football played and CTE status remained consistent. Referencing these data, Mez suggested that this dose–response relationship may generalize to the larger football playing population, even if the brain bank prevalence does not (Mez et al., 2020).

To better estimate exposure across an athlete’s playing career and improve prediction of disease risk, risk models have begun incorporating biomechanical data. Mez described a systematic review of 34 helmet sensor studies showing that duration-of-play models that include cumulative linear and rotational acceleration better predicts CTE pathology than duration of play alone (Daneshvar et al., 2023). These findings suggest that integrating biomechanical exposure improves risk estimation.

Similar dose–response patterns have been reported in other contact sports. A study of 77 hockey players found that CTE pathology increased with years of play, with only 2 of 21 youth/high school players showing evidence of the disease (Abdolmohammadi et al., 2024). In both football and hockey, risk was approximately 10 times lower among those who played fewer than 4.5 and 7.5 years, respectively, Mez said.

CTE also frequently co-occurs with other neurodegenerative pathologies, Mez noted, including amyloid beta, alpha-synuclein, TDP-43, and white matter changes. However, unlike these conditions—which often appear in the absence of trauma—CTE is rarely seen without a history of RHI.

Key Lessons

In closing, Mez urged a shift away from arbitrary age exposure cutoffs and toward a cumulative exposure model. The risk of CTE increases with each additional year of play, he said, regardless of when that exposure occurs. More large-scale research, particularly involving youth and high school athletes, is needed to clarify these relationships and inform risk mitigation strategies.

Concussion, RHI Exposure, and Long-Range Outcomes

Michael McCrea, a professor of neurosurgery and codirector of brain injury research at the Medical College of Wisconsin, provided an overview of the current clinical research on long-term outcomes related to youth exposure to RHI. He noted that while public attention to sport-related concussion spans several decades, research on RHI exposure is only about 10–15 years old, and no prospective longitudinal studies yet exist that could definitively link youth sports exposure to outcomes later in life. In their absence, the field relies on cross-sectional and retrospective studies, which present mixed findings.

Age of First Exposure (AFE) and Long-Term Outcomes

Reviewing studies on age of first exposure (AFE) to contact sports, McCrea noted that early research suggested that starting American football before age 12 might carry increased risk for later-life neuropsychiatric symptoms (Stamm et al., 2015). However, subsequent work has not supported this conclusion (Alosco et al., 2017). He highlighted a study of roughly 200 middle-aged men, which found that although those who began playing before age 12 reported a slightly higher number of lifetime concussions, there were no differences in physical, cognitive, or mental health outcomes compared with those who started later (Iverson et al., 2021a). A narrative review of 21 studies by the same group similarly concluded that across high school, collegiate, and community samples, earlier AFE was not consistently linked to adverse cognitive or mental health outcomes (Iverson et al., 2021b).

While findings among former NFL players have been more mixed, McCrea argued that the literature overall does not justify policy changes using age 12 as a “magic number.” Instead, he emphasized that questions of when to allow participation remain valid for families and pediatricians, particularly amid pressures to begin organized sports at younger ages. He added that placing very young children, such as 4-year-olds, into full-contact football raises developmental concerns, and emphasized that more exposure is not necessarily better for either athlete development or long-term brain health. McCrea pointed to current national efforts to design developmentally appropriate models of youth football as a more promising approach than reliance on an arbitrary age cutoff.

Cognitive Impairment and Mental Health Outcomes

Turning to broader health outcomes, McCrea reviewed two large studies of former high school athletes, both of which relied on participants’

self-reported histories. One study of more than 1,700 men in their 30s and 40s examined whether playing football in adolescence was associated with later depression or suicidality. The analysis found no increased risk among those who had played high school football. Instead, self-reported adolescent depression or suicidality was associated with an increased likelihood of lifetime depression and suicidal ideation (Iverson and Terry, 2022). McCrea noted that these results suggest that early mental health—not sport participation—was the key driver of risk. Another study compared men who had played high school football with those who did not participate in the sport. Again, there were no group differences in reported outcomes for long-term cognitive or mental health. However, football players were more likely to report persistent sleep problems and prior prescriptions for pain or headache medication (Iverson et al., 2022). He emphasized that these differences should be interpreted with caution but warrant further attention.

Additional evidence comes from the Wisconsin Longitudinal Study, which followed nearly 4,000 men who graduated high school in 1957 and were evaluated at age 65. After matching football players with controls on demographic, educational, and social variables, investigators found no harmful association between playing high school football and later-life cognitive impairment, depression, or other mental health outcomes (Deshpande et al., 2017). Similarly, a Mayo Clinic study comparing men who played high school football in the 1940s and 1950s to classmates who participated in noncontact activities such as band or choir found no increased risk of dementia, Parkinson’s disease, or amyotrophic lateral sclerosis (ALS) among the football players (Savica et al., 2012). More recent work from the same group reinforced these findings, reporting no elevation in late-life neurodegenerative disease among men who had played high school football (Janssen et al., 2017).

Longitudinal, Large Cohort Studies with Former Athletes

McCrea referenced a review he coauthored surveying the literature on repetitive concussion and RHI exposure, which found the evidence base sparse, with no prospective longitudinal studies demonstrating that youth or high school contact sport participation predicted long-term cognitive decline, psychiatric disorders, or neurodegenerative disease. That review, he emphasized, underscored the pressing need for large-scale, prospective studies to establish true population-level risks (McAllister and McCrea, 2017).

Turning to efforts that begin to fill this gap, McCrea highlighted findings from two major efforts: the NFL-LONG study and the NCAA–Department of Defense (now Department of War) Concussion Assessment, Research,

and Education (CARE) Consortium.^4,5 The NFL-LONG study, which has tracked more than 2,000 former players, including a core cohort followed for over 20 years, has provided the largest dataset to date on the long-term health of professional football athletes. Analyses from this cohort show that players with a very high concussion burden (e.g., 10 or more concussions, a scenario McCrea noted is far less common today) demonstrate elevated risks for cognitive and mental health concerns (Brett et al., 2022c). However, across the broader sample, outcomes in domains such as memory, executive function, mood, and overall quality of life are largely consistent with those of the general male U.S. population, and age of first exposure and years of participation appear to have minimal, if any, effect on long-range outcomes (Walton et al., 2022).

The CARE Consortium, which has enrolled more than 50,000 NCAA athletes and military service academy cadets across 25 sports, was designed from the outset as a prospective longitudinal study. Early phases focused on acute and intermediate recovery after injury, and the cohort is now in a 10-year follow-up stage capturing long-term trajectories. McCrea emphasized that this effort is uniquely positioned to provide population-based estimates of long-range outcomes, including how cumulative exposure relates to later-life health. McCrea shared preliminary results currently in peer review, which suggest that comorbid and modifiable health factors—such as preexisting or adolescent mental health conditions, sleep quality, chronic pain, and educational attainment achieved after sport participation—are often stronger predictors of long-term outcomes than RHI exposure alone. These findings, he argued, reinforce the importance of addressing known, preventable risk factors across the lifespan while continuing to monitor head impact exposure.

Final Remarks

In closing, McCrea emphasized that while concerns about concussion and RHI remain important, the overall weight of evidence suggests that sport participation—including contact and collision sports—confers benefits that generally outweigh long-term risks. He noted that concussion and RHI exposure appear to account for minimal, if any, variance in long-range health outcomes, while underscoring that “more is not better” in terms of exposure. Instead, he observed that long-range outcomes in athletes are likely shaped primarily by the same modifiable factors that influence brain and body health in the general population, such as mental health, education, and cardiovascular risk (Senff et al., 2025). Framing concussion

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⁴ See https://www.childrenshospital.org/nfl-long-study (accessed September 9, 2025).

⁵ See https://careconsortium.net/ (accessed September 9, 2025).

and RHI within this broader context, he argued, supports a balanced and evidence-based approach to policy and practice: continuing to implement measures that minimize head impacts while also preserving the many physical, social, and cognitive benefits of sport across the lifespan.

Discussion

Alosco moderated a discussion about potential long-term outcomes following RHI exposure in youth. Panelists highlighted the complexity of connecting pathological findings to health outcomes and underscored the need for longitudinal, prospective studies to better define risk.

Discrepancies Between Pathology and Population-Based Outcomes

Alosco opened the discussion by asking how to reconcile pathological findings—high percentages of CTE found in brain bank samples of contact sport athletes (McKee et al., 2023; Mez et al., 2017)—with McCrea’s presentation of population-level data showing little evidence of elevated clinical risk of contact sport participation in youth. McCrea pointed to the critical distinction between the presence of pathology and its functional significance, especially at the population level. He underscored the need for longitudinal, prospective studies to quantify the magnitude of risk and identify why only a subset of exposed individuals go on to develop adverse outcomes.

Mez responded that the discrepancy likely reflects the complexity of epidemiology and the slowly progressive nature of neurodegenerative disease. Drawing a parallel to Alzheimer’s disease, he noted that pathology may be present decades before symptoms manifest, with dementia often not emerging until the 70s or 80s. For youth and high school athletes, he suggested, RHI may play only a small role—comparable in scale to vascular risk factors such as hypertension or diabetes—but larger contributions are likely among those who go on to elite play. He argued that bridging perspectives from the neurodegeneration and TBI fields will be essential, as each brings unique tools and insights.

McCrea added that if Mez is correct that youth and high school exposure contributes only modestly to long-range health outcomes, then the field deserves credit for safety gains over the past 30 years. He highlighted evidence that most concussions and head impact exposures in football occurred in August practices and have since been substantially reduced through rule changes and limits on contact, measures that he said will improve athlete health moving forward.

Relevance of Historical Cohorts to Today’s Players

Mannix, speaking as a pediatric emergency medicine physician, raised a practical challenge: how should clinicians interpret older studies—such as a 2020 paper showing a median of 90 self-reported concussions in individuals with mild CTE (Mez et al., 2020)—given that such concussion burdens are less common in athletes today? McCrea acknowledged this as a challenge, noting that it is difficult to “counsel a high school football player based on data in former NFL players.” Mez emphasized that risk likely increases with cumulative exposure, and that while the contribution of youth-level play may be small, it becomes more significant for those who continue onto college and elite levels. He encouraged clinicians to help their patients understand this dose–response relationship, along with the benefits of contact sports, to empower families to make informed decisions. McCrea further advised that disqualification decisions should never be made during the acute recovery phase and should instead follow a full return to baseline functioning.

DISCUSSING FACTORS THAT MAY INFLUENCE OUTCOMES AFTER RHI

Christopher Giza, professor of pediatric neurology and neurosurgery at UCLA and director of the UCLA Steve Tisch BrainSPORT program, introduced and moderated a session on biological and social factors that may modify outcomes after RHI exposure in youth. Building on earlier discussions of how RHI are defined, measured, and distinguished from concussion, Giza emphasized that not all individuals with similar exposure histories will experience the same outcomes. Variability, he noted, can stem from both biological characteristics—such as sex, age, genetic background, and physiological response—and from sociodemographic conditions, including access to medical care, educational opportunities, and exposure to chronic or toxic stress. These factors may amplify or mitigate the effects of RHI across the life course, shaping both immediate responses and long-term health trajectories, Giza said. The session examined emerging evidence on these potential modifiers and considered implications for research and intervention strategies aimed at protecting youth brain health.

Potential Biological Effect Modifiers of RHI in Youth

Benjamin Brett, associate professor in the Departments of Neurosurgery and Neurology at the Medical College of Wisconsin, examined potential biological effect modifiers of youth exposure to RHI. He emphasized that while most individuals who play contact sports do not go on to develop

adverse long-term outcomes—and some evidence even suggests equal or better functioning in certain health domains—there may be a subset of athletes who are particularly vulnerable. RHI alone do not show a clear dose–response relationship with later problems. Instead, Brett proposed a framework that considers RHI in combination with other modifying factors for better understanding the causes of later-life conditions.

Individual-Specific Factors and History

Brett highlighted medical and developmental histories that may heighten cerebral vulnerability. Conditions such as ADHD and other neurodevelopmental disorders, mood and psychiatric conditions, prior concussions, and histories of headache or migraine have all been linked in the concussion literature to greater risk for prolonged symptoms. Neuroimaging studies show that these conditions are often associated with alterations in white matter microstructure and atypical functional connectivity, suggesting that some individuals may carry a biological substrate of vulnerability before ever sustaining RHI (see, for example, Brett et al., 2022a; Koshiyama et al., 2020; Michelini et al., 2019; Rahimi et al., 2022). Brett’s work with high school and collegiate athletes has demonstrated that years of contact sport exposure are associated with white matter changes, even among those without a recent concussion, underscoring the potential interaction between prior vulnerabilities and exposure (Brett et al., 2021).

Functional connectivity studies add another dimension: Pre- to postseason imaging has consistently shown alterations in default mode network connectivity (Monroe et al., 2020; Wilson et al., 2022), which Brett noted is one of the most replicated patterns observed in youth athletes. While such alterations do not inevitably lead to clinical symptoms, they have been linked to a neuropsychiatric conditions (Doucet et al., 2020; Wise et al., 2017). When combined with RHI, Brett suggested default mode network connectivity changes may represent an additional layer of vulnerability.

Health and Lifestyle Factors During Sport

Factors present during sports participation may influence how RHI affect the brain. Brett highlighted systemic inflammation as one such pathway. Data from cohorts of high school and collegiate athletes suggest that higher levels of inflammatory markers, such as interleukin-6 or C-reactive protein, interact with concussion history and years of participation to predict smaller hippocampal volumes and subtle decrements in cognitive performance (Brett et al., 2020). Brett suggested these findings may point to inflammation as a biological amplifier of repetitive neurotrauma. Sleep is another important factor. Because sleep facilitates clearance of metabolic

waste and beta-amyloid (Hauglund et al., 2025; Shokri-Kojori et al., 2018; Xie et al., 2013), inadequate or disrupted sleep during periods of RHI exposure could impair repair processes and exacerbate injury effects. Brett situated these findings within the broader dementia prevention literature, noting that many modifiable health behaviors—ranging from cardiovascular fitness to diet—may shape long-term vulnerability in athletes just as in the general population.

Postsport Discontinuation and Beyond the Lifespan

Brett emphasized the long interval between youth RHI exposure and potential late-life outcomes, noting that biological and lifestyle factors operating during this time may shape whether adverse effects emerge. Longitudinal imaging studies show that hippocampal volume decreases over 4 years of collegiate football (Parivash et al., 2019), and his team has reported that such changes can persist into midlife, with advanced head impact metrics correlating with hippocampal volume in athletes 15 years removed from the sport (Brett et al., 2022b). Yet, studies of older former athletes, such as those in the Diagnose CTE Research Project, have found no significant associations between RHI proxies (e.g., level of play, years of participation) and hippocampal or cortical measures (Arciniega et al., 2024). Brett suggested that intervening biological and lifestyle modifiers across adulthood may help explain these discrepancies, potentially attenuating or intensifying the trajectory of earlier exposure.

He pointed to educational attainment achieved after sport participation as a particularly striking example: In former football players, those who went on to complete higher levels of education showed no association between RHI exposure and hippocampal volume, a finding not accounted for by premorbid IQ or resilience factors (Brett et al., 2022b). Brett noted that this pattern mirrors animal research on environmental enrichment, in which cognitive stimulation promotes neurogenesis and plasticity even after injury, highlighting the importance of lifespan modifiers in shaping outcomes.

In conclusion, Brett emphasized that RHI in youth cannot be viewed in isolation. Identifying which modifiers contribute most to long-term risk—and when interventions will have the greatest effect—will require prospective longitudinal studies with sufficient statistical power. He emphasized that this research agenda is essential to clarify the biological underpinnings of vulnerability, inform targeted interventions, and ultimately reduce the long-term risks associated with RHI.

Effect of Sociodemographic Factors on RHI in Youth

Tamerah Hunt, professor and certified athletic trainer at Georgia Southern University, centered her presentation on how social determinants of health (SDoH) may influence exposure to and outcomes from RHI in youth. While RHI-specific research on SDoH is essentially nonexistent, Hunt drew on concussion research to illustrate why these factors may be relevant and warrant targeted study.

According to the World Health Organization, SDoH are the conditions in which people are born, grow, live, work and age. These circumstances are shaped by the distribution of money, power, and resources at global, national, and local levels.⁶ Healthy People 2030 categorizes SDoH into five domains: education access and quality, neighborhood and built environment, health care access and quality, social and community context, and economic stability.⁷ Hunt noted that the most frequently studied domain in youth sports is socioeconomic status, while “race and ethnicity” is often treated as a stand-alone variable. She emphasized that race and ethnicity, along with other domains, are best understood in relation to one another, and that privilege—not only disparity—can influence both risk and recovery, as seen in examples such as access to advanced protective equipment or immediate evaluation by a sports medicine specialist. Hunt concluded by underscoring the importance of recognizing the intersectionality of these determinants, which often overlap and interact to shape an individual’s experiences and outcomes in complex ways.

Because of the absence of direct data on RHI, Hunt turned to concussion studies to demonstrate how SDoH might affect injury and recovery. Hunt shared preliminary data from a study of 596 high school athletes: The incidence of concussion was similar for athletes with high or low socioeconomic status (SES), but recovery trajectories differed. High-SES athletes took longer to self-report being symptom free, to return to learning, and to return to play, despite all being served by the same medical staff. Hunt suggested that factors such as parental caution, childcare needs, or food security concerns might influence decisions to return to school and play.

Hunt noted geographic and demographic disparities in access to concussion care. Rural settings tend to be more conservative in their treatment approach, have less access to advanced diagnostic tools like magnetic resonance imaging (MRI), and have reduced availability of athletic trainers (Yue et al., 2020). Further, Hispanic youth athletes are less likely to have access to athletic trainers, and they are more likely to seek care in an emergency

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⁶ See https://www.who.int/health-topics/social-determinants-of-health (accessed September 5, 2025).

⁷ See https://odphp.health.gov/healthypeople/priority-areas/social-determinants-health (accessed September 5, 2025).

department compared to their white peers (Copley et al., 2020). Education-related variables such as health literacy, language barriers, knowledge about symptoms, and school resource availability may further shape both prevention and recovery efforts, Hunt noted.

Next, Hunt turned to the domain of social and community context, which she described as perhaps the most significant factor for youth. Young athletes, she explained, spend much of their time embedded in social environments that shape how they participate in and experience sport. Parents and stakeholders, she suggested, must pay attention not only to the individual athlete but also to the community structures around them—county recreation departments that decide what sports are offered, religious or civic organizations that provide activities and support, and government entities that influence rules and policies related to youth sport participation and safety. Schools also play a central role, she added, both through the opportunities they provide and through their policies around health and reintegration.

Hunt shared an early qualitative study that examined the psychological impacts of sports-related concussion but offers a useful point of comparison for considering RHI. Focus groups with athletes of both high and low socioeconomic status revealed that young people value sports as a form of social connection. They looked to coaches, peers, and mentors for support and described the difficulty of losing those connections when sidelined by injury. One participant explained, “Boredom went to loneliness, and being lonely was bad,” capturing the importance of sport as a space for social engagement. Hunt noted that when athletes are told they cannot participate—particularly in communities with limited alternatives—they also lose opportunities for socialization and positive developmental experiences. Coping strategies varied, but in some cases withdrawal and isolation led to negative outcomes. Peer-mentoring programs piloted as part of the study helped to address this by reestablishing a sense of connection and support (Hunt and Harris, 2017).

Hunt closed by underscoring the significant gaps in research on RHI in youth. She noted that isolating exposures is difficult without intentional study designs and is especially challenging in low-resource communities where specialized equipment such as instrumented helmets is unavailable. Much of the existing evidence comes from contact or collegiate sports, leaving younger athletes and females underrepresented. She highlighted the lack of knowledge regarding whether repetitive impacts may have neutral or even positive effects, observing that research often assumes harm without sufficient evidence in youth populations. Barriers to care and uneven data collection further complicate understanding of vulnerability and potential protective factors, particularly in diverse populations.

Hunt also pointed to the influence of sport culture, with some athletes reluctant to disclose head impacts. She concluded by emphasizing that while concussion research demonstrates the role of social determinants of health in shaping outcomes in domains such as economic stability, education, and social context, no studies have examined these factors in relation to RHI without symptoms. Intentional research, she argued, is needed “to make sure that we are ensuring adequate intervention, support systems, and education for our entire community.”

Discussion

Giza moderated a discussion on how outcomes after RHI exposure in youth may be shaped not only by the exposures themselves but also by a wide constellation of biological, social, and environmental factors. Panelists considered whether it is possible to distinguish determinants of brain health from modifiers that are specific to RHI, and how such distinctions might shape future research and guidance. The discussion also touched on the feasibility of personalized risk estimates, the importance of community trust in research, and RHI exposures beyond organized sports.

Distinguishing Modifiers of Brain Health from Modifiers of RHI Outcomes

Giza opened by asking whether long-term predictors of brain health can be meaningfully separated from factors that specifically modulate the response to RHI, and whether the distinction matters. Brett replied that many health and lifestyle factors are broadly applicable to both athletes and the general population, making it difficult to parse. He argued that progress will likely come from combining mechanistic research on the biological consequences of RHI with the identification of modifiable factors that directly interact with those processes.

RHI Beyond Sports: Violence and Adverse Childhood Experiences

An audience member raised the issue of RHI exposure related to interpersonal violence, including intimate partner violence and child abuse, and asked how biological and sociodemographic moderators apply in these contexts. Hunt emphasized that adverse childhood experiences are closely tied to economic stability, food security, language environment, and access to social support. She emphasized the role of community support as a protective factor but also noted the psychological scars and triggers that can complicate recovery. She added that for some youth, sports may serve as a positive outlet for aggression, while for others, high-impact play may

be retraumatizing. Brett observed that exposures from intimate partner violence or child abuse may represent overlapping but distinct biological insults—such as repetitive injuries clustered in time or brain damage from strangulation—underscoring the heterogeneity of nonsport RHI.

Toward Personalized Risk Estimates

Yeates asked how far the field is from being able to provide families with quantitative risk estimates based on individualized neurobiological and psychosocial factors. Brett responded that the scale of evidence needed is substantial, with population-level studies involving thousands of participants. In the meantime, he suggested that even partial models explaining most of the variance through a few key factors could guide personalized approaches. Hunt described ongoing work to develop a practical screening tool for athletic trainers and clinicians, and emphasized that no single factor operates in isolation.

Using Existing Large-Scale Studies

Rivara noted that existing large-scale longitudinal studies, such as the Adolescent Brain Cognitive Development (ABCD) cohort and the All of Us research program, provide opportunities to collect information about RHI exposure. Incorporating head impact exposure into such studies could supply the population-level data needed to answer many of the questions raised during the session.

Building Trust in Community-Based Research

Giza turned to Hunt with a question about community-based research in regions where sports participation is highly valued, asking how to address concerns that studies might be perceived as threatening opportunities for participation. Hunt described her community-engaged approach, noting that “people don’t care how much you know until they know how much you care,” particularly for populations that may have cultural mistrust of health care or research. She highlighted the importance of trusted community champions who can advocate for research goals, ensuring that community members see how studies will benefit them. She also noted the importance of codeveloping interventions with communities, tailoring goals and outcomes to local priorities, and even using gestures, like providing food, to help build trust and encourage participation.

Pathological Findings in Young Adults

An audience member asked whether pathological cases of early-stage CTE observed in adults younger than 30 years of age who were youth athletes with RHI exposure reflect susceptibility factors beyond sports exposure (McKee et al., 2023). Brett cautioned against overinterpreting as these findings come from individuals who may have confounding factors related to early death. He noted that there is no consensus on whether low-stage CTE is symptomatically meaningful or inherently progressive, and that more evidence is needed before drawing conclusions about susceptibility.

Sociodemographic Approaches to Reducing Risk

Giza asked Hunt whether interventions should focus on expanding access to “safer” sports or on mitigating risks within high-exposure sports. Hunt responded that strategies must be context specific, and the answer may not be an “either/or.” In communities where football is deeply embedded, efforts to reduce head impacts within the sport and bolster coaching education and equipment standards may be the most pragmatic path. In other settings, expanding access to alternative activities may yield greater returns.

Interactions with Neurodevelopmental Conditions

Rivara closed the session by asking how conditions such as ADHD might interact with RHI to affect outcomes. Brett suggested that atypical white matter microstructure or divergent functional connectivity associated with ADHD may lower the threshold for adverse effects, echoing broader concepts of risk and resilience seen in neurodegenerative disease.

REFERENCES