Cognitive impairment as a result of sports brain injuries

Cognitive impairment as a result of sports brain injuries

SHENGYING SHI1, DANDAN CHENG2

1School of Physical Education, Shandong Women’s University, Jinan, People’s Republic of China; 2College of Health Sciences, Shandong University of Traditional Chinese Medicine, Shandong, People’s Republic of China.

Summary. The aim of this study was to investigate the mechanisms underlying the development and progression of cognitive impairments in athletes following traumatic brain injuries (TBIs), with subsequent substantiation of effective approaches for their prevention and remediation. The research systematised and classified cognitive impairments by temporal progression and severity, identifying patterns in the acute, subacute, and chronic phases of traumatic cognitive dysfunctions. Acute cognitive impairments were characterised by deficits in short-term memory, reduced processing speed, attention and concentration disturbances, and executive dysfunction, occurring in 90% of mild concussions. Among these, 80-90% of athletes experienced symptom resolution within 7-14 days. It was established that 10-15% of adult athletes and 15-30% of children and adolescents exhibit persistent post-concussion symptoms. Sex differences were observed, with female athletes showing prolonged recovery periods and more pronounced cognitive symptoms compared to their male counterparts. The critical role of cognitive reserve as a protective factor was confirmed, alongside a threefold increased risk of neurodegenerative diseases among professional contact sport athletes, as evidenced by long-term epidemiological observations. Neuroimaging and biomarker correlates of cognitive dysfunction were analysed, supporting the organic nature of the impairments through detection of microstructural changes in white matter via diffusion tensor imaging and the dynamic alterations of specific neurobiomarkers (glial fibrillary acidic protein, neurofilament light chain, S100B calcium-binding protein, and tau protein). The findings provide an evidence-based foundation for personalised prevention and rehabilitation strategies for sports-related TBIs, incorporating individual risk factors and forming a conceptual basis for an integrated interdisciplinary approach to athlete healthcare.

Key words. Concussion, post-concussion syndrome, neuropsychological assessment, diffusion tensor imaging, chronic traumatic encephalopathy, neurodegenerative diseases.

Compromissione cognitiva da traumi cranici subiti durante l’attività sportiva

Riassunto. Lo scopo di questo studio è quello di indagare i meccanismi alla base dello sviluppo e della progressione dei disturbi cognitivi negli atleti a seguito di traumi cranici (TBI), con la conseguente individuazione di approcci efficaci per la loro prevenzione e il loro trattamento. La ricerca ha sistematizzato e classificato i disturbi cognitivi in base alla progressione temporale e alla gravità, identificando modelli ricorrenti nelle fasi acuta, subacuta e cronica delle disfunzioni cognitive traumatiche. I disturbi cognitivi acuti erano caratterizzati da deficit della memoria a breve termine, ridotta velocità di elaborazione, disturbi dell’attenzione e della concentrazione e disfunzione esecutiva, presenti nel 90% delle commozioni cerebrali lievi. Tra questi, l’80-90% degli atleti ha visto i sintomi risolversi entro 7-14 giorni. È stato stabilito che il 10-15% degli atleti adulti e il 15-30% dei bambini e degli adolescenti presentano sintomi post-commozione cerebrale persistenti. Sono state osservate differenze di genere, con le atlete che hanno mostrato periodi di recupero prolungati e sintomi cognitivi più pronunciati rispetto ai loro omologhi maschi. È stato confermato il ruolo critico della riserva cognitiva come fattore protettivo, insieme a un rischio triplicato di malattie neurodegenerative tra gli atleti professionisti di sport di contatto, come evidenziato da osservazioni epidemiologiche a lungo termine. Sono state analizzate le correlazioni tra neuroimaging e biomarcatori della disfunzione cognitiva, a sostegno della natura organica delle menomazioni attraverso l’individuazione di alterazioni microstrutturali nella materia bianca tramite imaging del tensore di diffusione e le alterazioni dinamiche di specifici neurobiomarcatori (proteina acida fibrillare gliale, catena leggera dei neurofilamenti, proteina legante il calcio S100B e proteina tau). I risultati forniscono una base scientificamente fondata per strategie personalizzate di prevenzione e riabilitazione delle TBI legate allo sport, che tengono conto dei fattori di rischio individuali e costituiscono una base concettuale per un approccio interdisciplinare integrato alla salute degli atleti.

Parole chiave. Commozione cerebrale, sindrome post-commozione cerebrale, valutazione neuropsicologica, imaging del tensore di diffusione, encefalopatia traumatica cronica, malattie neurodegenerative.

Introduction

Sports-related brain injuries, including concussions and traumatic brain injuries (TBIs), represent a critical public health concern and have garnered increasing attention in both medical research and public discourse. According to the World Health Organization (WHO), approximately 20.8 million new TBI cases were reported in 2021, with 6-10% attributable to sports activities. Among children and adolescents, this figure reaches 21%, raising significant concern regarding the impact on the developing brain (National Center for Biotechnology Information, 2025). The cognitive consequences of such injuries extend beyond immediate symptoms and may result in long-term neurological impairments that substantially affect quality of life and professional functioning. As global participation in contact sports continues, understanding the relationship between sports-related brain trauma and cognitive function is essential for developing effective preventive strategies, diagnostic tools, and treatment protocols.

Over the past decade (2013-2025), research has intensively examined the association between sports-related brain injuries and cognitive impairments, revealing a complex interplay of short- and long-term consequences. A large-scale study by Ntikas et al.1 across 18 countries demonstrated that 46% of individuals with sports-related TBIs exhibited incomplete recovery after six months, even in cases of mild injury. Hou et al.2 systematically investigated the cognitive impact of sports concussions in adolescents, finding deficits not only during the acute phase but also in the prolonged phase (1-6 months), particularly affecting visual memory and executive functioning. The design of the studies, participant sex, assessment instruments, and concussion history were shown to modulate the relationship between cognitive function and brain trauma.

A systematic review and meta-analysis by Qi et al.3 identified a pooled prevalence of chronic traumatic encephalopathy (CTE) in contact sport athletes of 53.7%, with higher rates among elite athletes (72.8%) compared to amateurs (44.1%). Of particular concern is the association between CTE and suicide, with a rate of 39.0% among diagnosed cases. Grashow et al.4 examined the perception of CTE among former professional American football players and found that approximately one-third perceived themselves as having CTE, which correlated with a higher prevalence of suicidality. Even after adjusting for established predictors, men who perceived themselves as having CTE were twice as likely to report suicidality.

Longitudinal cognitive trajectories were explored by Walton et al.5, who found no significant group-level changes in cognitive test performance among former collegiate American football players over 18 years, yet observed substantial individual variability. In a separate study, Walton et al.6 reported higher prevalence of mild cognitive impairment (23.8%) and dementia (8.9%) among former National Football League (NFL) players compared to national estimates. Rubin et al.7 provided compelling neurobiological evidence using positron emission tomography to demonstrate sustained neuroimmune activation in the brains of former NFL players. Abdolmohammadi et al.8 established a relationship between years of hockey play and CTE diagnosis: 19.2% in those with less than 13 years, 51.9% in those with 13-23 years, and 95.8% in those with more than 23 years of play.

Conversely, Lennon et al.9 reported no cognitive or behavioural deficits in individuals with sports concussions compared to controls, suggesting that sports participation might confer long-term cognitive benefits. Collins et al.10 observed deficits in multiple cognitive domains post-concussion, underscoring the need for individualised return-to-play protocols. Alosco et al.11 identified the highest impairment rates in memory (21.2%), particularly in the recall of unstructured verbal stimuli (44.7%). A comparative analysis of neuropsychological profiles by Didehbani et al.12 showed that former NFL players with mild cognitive impairments displayed similar profiles to non-athletes with comparable impairments but without a history of TBI. Despite significant advances in understanding the cognitive sequelae of sports-related brain trauma, sex differences in vulnerability remain underexplored, as most research has focused primarily on male athletes. Furthermore, there is a lack of studies evaluating the efficacy of targeted cognitive rehabilitation programmes specifically designed for athletes with varying severities of brain injury, highlighting the need for further focused clinical trials in this field.

The aim of the study was to identify the patterns underlying the development of cognitive impairments resulting from sports-related traumatic brain injuries and to substantiate effective strategies for their prevention in athletes. The objectives were as follows:

1. to characterise the acute and subacute cognitive outcomes of sports-related TBI in athletes, including recovery dynamics and sex-specific differences;

2. to determine the neuroimaging and biomarker correlates of cognitive dysfunction in sports-related brain injuries, evaluating their diagnostic and prognostic significance;

3. to substantiate long-term cognitive trajectories and preventive strategies aimed at minimising risks in athletes with TBIs, taking into account modifying factors.

Materials and methods

The methodological framework of the study was based on a comprehensive interdisciplinary approach integrating methods from sports medicine, neuropsychology, neuroimaging, epidemiology, and molecular neurology. This approach combined multiple complementary scientific techniques for an in-depth analysis of the issue of cognitive consequences of sports-related traumatic brain injuries (TBIs). The primary method was a systematic review and critical analysis of scientific literature conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, allowing for the synthesis of findings from numerous primary studies.

The literature search strategy involved the following key term combinations: (“sport-related concussion” or “athletic brain injury” or “sports traumatic brain injury”) and (“cognitive impairment” or “neuropsychological dysfunction” or “memory deficit”) and (“biomarkers” or “neuroimaging” or “epidemiology”). Searches were conducted across PubMed, Scopus, and Web of Science databases. Inclusion criteria encompassed peer-reviewed English-language publications involving human participants, the use of validated cognitive assessment tools, and adequate sample sizes for statistical analysis. Exclusion criteria included studies of severe TBIs with prolonged loss of consciousness, mixed cohorts without clear demarcation of sports-related injuries, and non-peer-reviewed publications.

In total, 44 scientific publications were analysed, including 8 systematic reviews and meta-analyses, 15 cohort studies, 12 experimental and controlled studies, and 9 neuroimaging and biomarker studies. The evidence base consisted of a broad range of high-impact peer-reviewed international journals indexed in leading scientometric databases such as PubMed, Scopus, and Web of Science from the period 2013-2025 (figure 1).

An epidemiological approach has been pivotal in studying long-term cognitive trajectories and identifying risk factors for the development of neurodegenerative changes in athletes. This method enabled the analysis of causal relationships between exposure to repetitive traumatic brain injuries (TBIs) and delayed cognitive outcomes through the examination of data from large-scale cohort studies.

Particular attention within the methodology was devoted to analysing gender differences in the course of sports-related TBIs through a systematic review of studies that included comparative analyses of symptomatology and recovery trajectories between male and female athletes. The assessment of hormonal factors and comorbid conditions as potential modifiers of cognitive recovery was based on longitudinal studies, taking into account the menstrual cycle, history of migraine, and depressive disorders in female athletes.

To synthesise findings, a comparative analysis of cognitive indicators obtained across various studies using validated neuropsychological tools was employed. Specifically, studies utilising the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT), Sport Concussion Assessment Tool-5 (SCAT5), Montreal Cognitive Assessment (MoCA), CNS Vital Signs, and other standardised neurocognitive assessment methods were included. This allowed for the appropriate comparison of results and the stratification of data by age, sex, type of sport, and number of prior injuries.

Statistical analysis involved the aggregation and comparison of data using univariate and multivariate analysis of variance (ANOVA, MANOVA), Student’s t-test, the Wilcoxon rank-sum test for independent samples, as well as correlational analysis (Pearson’s and Spearman’s coefficients) to explore associations between cognitive performance and biomarkers of neuronal injury (GFAP, NfL, UCH-L1, Tau, S100β). All statistical data were derived from original sources, with significance thresholds set at p<0.05 and 95% confidence intervals.

Preventive strategies aimed at reducing the frequency of sub-concussive impacts and minimising the risk of neurodegeneration were also examined. The analysis encompassed contemporary approaches including the restriction of contact training, the use of protective equipment (e.g., helmets equipped with load sensors), changes in sports regulations, and long-term post-retirement monitoring programmes for athletes.

Results

Acute and subacute cognitive outcomes of sports-related TBI

Sports-related TBI, typically in the form of concussion, induces a spectrum of acute cognitive dysfunctions. The most prevalent manifestations include impaired short-term memory (particularly difficulties retrieving recently acquired information), slowed information processing speed, deficits in attention and concentration, reduced executive functioning, and prolonged reaction times10. These impairments have been objectively confirmed via neuropsychological testing during the initial hours and days post-injury. A systematic review of 26 studies (n=4534) demonstrated statistically significant deteriorations in cognitive performance among concussed athletes in the acute phase, compared with either control groups or pre-injury baselines (p<0.001; 95% CI: 0.72-0.98 for standardised mean difference). Cognitive deficits were observed across all three post-injury timeframes, with the most pronounced disturbances occurring within the first 24-48 hours (ES=-0.85; 95% CI: -1.12 to -0.58; p<0.001).

In practical terms, this may present as difficulty recalling the score of a match or coach’s instructions immediately following the impact, delayed decision-making during gameplay, and struggles to maintain focus on task execution. Importantly, these cognitive symptoms are not merely subjective – they are corroborated by validated neuropsychological instruments, including the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT), used in 7 of the 26 studies, the Sport Concussion Assessment Tool-5 (SCAT5), Montreal Cognitive Assessment (MoCA), as well as specialised tests assessing attention, memory, and executive functions. These cognitive findings are also correlated with neurophysiological abnormalities induced by trauma. For instance, 90% of mild sport-related concussions are characterised by transient cognitive symptoms resolving within approximately 10-14 days13. This short-term cognitive impairment is considered to stem from an acute neurometabolic disruption involving diffuse axonal injury and ionic imbalance, resulting in an “energy crisis” at the neuronal level. Clinically, the acute phase of TBI manifests as the “concussion syndrome”, which reflects a functional disturbance without observable structural damage on CT or MRI imaging14. Although standard neuroimaging typically reveals no macroscopic damage in acute concussion, subtle microstructural alterations – such as in cerebral white matter – underlie the observed cognitive dysfunctions.

In the subacute phase (days to weeks post-injury), cognitive functions generally show progressive recovery, although the rate and completeness of this process vary significantly depending on the athlete’s age and the specific characteristics of the trauma. Systematic analysis of recovery timelines reveals a distinct age gradient in symptom duration, with adult athletes exhibiting a faster and more predictable rehabilitation course. Studies indicate that in adult athletes, acute cognitive symptoms – such as memory impairments, slowed reaction times, and disorientation – fully resolve within 7-14 days in 80-90% of cases, demonstrating the efficacy of intrinsic compensatory mechanisms in the mature brain. Most athletes in this age group return to their cognitive baseline within two weeks post-concussion, allowing for a safe resumption of training and competition provided medical protocols for gradual return-to-play are followed15,16.

However, a substantial proportion of cases exhibit protracted recovery, underscoring pronounced age-related differences in post-traumatic outcomes and highlighting the particular vulnerability of the paediatric and adolescent brain to traumatic insults. Large cohort studies have shown that persistent post-concussive symptoms develop in 10-15% of adult athletes, whereas among children and adolescents, this rate is significantly higher – ranging from 15% to 30% of all concussion cases according to data from the University of Pennsylvania17. Younger athletes demonstrate a notably elevated propensity for developing prolonged symptoms. In children and adolescents, concussion-related symptoms, including cognitive complaints, may persist for over four weeks in one-third of cases, as reported by Sheldrake et al.18 and Ewing-Cobbs19. These conditions are classified as post-concussion syndrome. The cognitive manifestations of post-concussion syndrome include persistent difficulties with memory, concentration, and multitasking, which may endure for months or even years following the injury10. In the prospective study by Permenter et al.13, over 15% of individuals continued to experience clinically significant challenges with concentration, learning, and decision-making three months post-sport-related concussion. These findings were objectively substantiated using validated neuropsychological instruments including ImPACT, SCAT5, and CNS Vital Signs. Factors contributing to prolonged recovery include more severe initial injuries (e.g., loss of consciousness or post-traumatic amnesia as markers of more severe concussion) and repeated injuries without adequate recovery time. It has been demonstrated that even a single TBI accompanied by loss of consciousness is associated with slower cognitive recovery and an increased risk of persistent symptoms20. In summary, cognitive recovery following concussion is highly variable, ranging from rapid resolution within days for the majority of athletes to prolonged cognitive difficulties in a substantial minority, particularly in the presence of aggravating factors such as injury severity or repetitive impacts.

A separate concern is sub-concussive brain trauma – repetitive minor impacts that do not produce overt concussion (i.e., without loss of consciousness or distinct symptomatology), yet may exert a cumulative detrimental effect. Examples include frequent collisions among linemen in American football or repeated heading of the ball in soccer. Such impacts may not elicit acute disorientation or subjective complaints, but neuropsychological testing reveals subtle cognitive changes even following sub-concussive episodes. Specifically, among former footballers, cumulative exposure to heading the ball throughout their careers correlates with impairments in memory and reasoning: players who regularly performed > 15 headers per match or training session had more than a threefold increased likelihood of cognitive impairment in later life (adjusted odds ratio, AOR=3.16; 95% CI: 1.08-9.22) compared to those who performing > 15 headers. Another study involving professional footballers found that frequent heading in both training and match contexts was associated with approximately a fivefold increase in the risk of cognitive deficits (relative risk ~5.0 for the group performing>15 headers in both settings)21. However, short-term longitudinal observations do not always demonstrate cognitive decline following limited periods of sub-concussive exposure. It is important to highlight that the study by Mund et al.22 was a prospective, controlled, longitudinal investigation with rigorous exposure tracking and utilisation of objective assessment methods, thus ensuring methodological robustness. For instance, in a prospective study of 22 elite German footballers (mean age~20 years), observed over ~17 months (recording a total of > 8000 headers), no statistically significant changes were identified in neurocognitive test performance from pre- to post-season. This controlled longitudinal study employed a comprehensive cognitive test battery, including the Trail Making Test A/B for executive functioning, the Paced Auditory Serial Addition Test for working memory and attention, and the standardised computerised CNS Vital Signs battery comprising nine specific tests yielding 14 domain scores. The researchers analysed seven core cognitive domains (verbal, visual, and working memory; executive function; complex, sustained, and simple attention), which are most frequently impacted in footballers following sub-concussive exposure. The absence of change in these sensitive measures over the 17-month observation period may be attributable to the relatively young age of participants and the short-term nature of exposure compared to the decades-long professional careers assessed in epidemiological studies. No significant associations were found between total heading exposure and cognitive performance or DTI-derived white matter indices post-season (all p>0.05 after correction for multiple comparisons). Only a subtle effect was noted in relation to specific impact types: a change in fractional anisotropy in the posterior corpus callosum was correlated with the frequency of long-distance headers, warranting further investigation22. These findings suggest that short-term sub-concussive exposure may not immediately produce observable cognitive shifts in young athletes; nevertheless, the cumulative long-term effect is real and substantiated by epidemiological data. Hence, even in the absence of diagnosed concussions, repeated minor head trauma (e.g., impacts, collisions) may induce subclinical cognitive deficits that accumulate over time and potentially manifest after retirement from active sports.

In recent years, researchers have increasingly focused on sex-based differences in the manifestation of sports-related traumatic brain injury (TBI). There is emerging evidence that female athletes in the same sports may sustain concussions more frequently and exhibit more pronounced cognitive symptoms and longer recovery durations than males17. Notably, a comparative study among adolescent soccer players demonstrated that, eight days post-concussion, girls scored lower on visual memory tests compared to boys (mean score 68.7±15.2 vs 77.2±8.9; p=0.021). Furthermore, within the same timeframe, the number and intensity of post-concussive symptoms (e.g., headache, nausea, impaired concentration) were higher among female athletes – a significant sex × time interaction was observed for the total symptom score (F₁,₈₂=4.26; p=0.04), with girls reporting on average more symptoms (11.9 versus fewer than 10 in boys)23. Importantly, these sex-based differences persisted even after controlling for body mass index as a covariate, suggesting biological mechanisms beyond anthropometric factors. The study focused on adolescents (mean age 17.7 years), indicating that these results may reflect neurodevelopmental characteristics during puberty, a period when hormonal changes may heighten female vulnerability to traumatic insults. Further research is required to determine whether such sex-based differences persist in adult athletes. These data are consistent with clinical observations: physicians have long noted that women in equivalent sports not only sustain concussions more frequently but also exhibit slower cognitive recovery.

Potential underlying factors include biological and anatomical differences. For example, a recent preclinical animal study revealed that female mammalian axons are thinner and less densely packed, rendering them more susceptible to rupture under acceleration. In a 2024 experimental model of concussion in pigs, females exhibited significantly more swollen axons and greater loss of axonal sodium channels 24 hours post-injury compared to males. Although axons of smaller calibre were predominantly affected in both sexes, females had a higher proportion of thin axons, resulting in greater overall axonal loss24. This mechanistic evidence supports clinical findings: the female brain may sustain more pronounced microstructural damage following concussion, which may account for more severe or prolonged cognitive symptoms. Thus, sex is a critical modifier of the acute course of sports-related TBI, and assessments of cognitive status and return-to-play protocols should consider that female athletes may require extended monitoring and more cautious reintegration into athletic activity20.

Analysis of gender-based differences in sports-related TBIs has revealed a statistically significant longer duration of symptomatic recovery in female athletes compared to their male counterparts, with the average time to return to baseline cognitive functioning being 21.3±8.7 days versus 14.2±5.4 days, respectively (p<0.01; 95% CI: 4.2-9.9). Furthermore, female athletes with comorbidities – particularly a history of migraine or depressive disorders – were found to have a 2.7-fold increased risk of developing prolonged post-concussion syndrome (OR=2.71; 95% CI: 1.85-3.96; p<0.001), underscoring the necessity for a differentiated clinical approach to the management of female athletes post-TBI25.

Acute sports-related TBIs lead to clinically significant, objectively verified cognitive impairments, affecting memory, attention, reaction time, and executive task performance. In most athletes, these impairments are reversible and resolve within days or weeks alongside general recovery. However, a substantial proportion (up to 15% or more) experience prolonged cognitive dysfunction, particularly in cases of more severe or repeated injuries. According to research published in neurology, approximately 13.5% of patients continued to exhibit cognitive impairments one year after mild TBI, compared to only 4.5% in the control group26. The risk of chronic cognitive issues increases with the number of previous concussions, with children and adolescents being especially vulnerable due to the immaturity of their nervous systems, which may prolong recovery. Contact sports with a high frequency of head impacts (e.g., football, rugby, hockey) are associated with a heightened risk of cumulative effects. Repetitive sub-concussive impacts contribute to cumulative burden, increasing the likelihood of chronic cognitive dysfunction even if no individual impact results in symptomatic concussion. The athlete’s sex also plays a role: women may experience more severe cognitive consequences of TBI and require longer recovery periods. These patterns highlight the importance of vigilant monitoring of cognitive status following any sports-related TBI and the need for individualised return-to-play decisions based on objective indicators of cognitive recovery.

Neuroimaging and biomarker correlates of cognitive dysfunction

Modern neuroimaging techniques demonstrate that cognitive impairments following sports-related TBI have a discernible neurobiological substrate. Advances in high-resolution imaging tools have enabled the objective identification of both structural and functional brain alterations that correlate with clinical symptoms. These methods provide not only diagnostic capabilities but also prognostic value for estimating recovery duration and the risk of chronic cognitive impairment. Various imaging approaches allow the investigation of specific aspects of traumatic brain injury (table 1).

The classification of imaging modalities presented in table 1 reflects the evolution of diagnostic approaches from macroscopic detection of structural alterations to microscopic assessment of the integrity of neural networks and metabolic processes. A critically important aspect of modern neuroimaging is the capacity for quantitative evaluation of the functional consequences of traumatic injury through mathematical modelling of tissue diffusion properties and real-time analysis of connectomic alterations. Technological advances in high-field magnetic resonance imaging (MRI) and the development of sophisticated post-processing algorithms have enabled the detection of subclinical changes that precede the manifestation of cognitive deficits – an advancement of fundamental significance for preventive strategies and the implementation of personalised rehabilitation in athletes. The integration of multimodal imaging approaches with machine learning and artificial intelligence offers promising avenues for developing predictive models to stratify the risk of long-term neurocognitive consequences, based on pattern recognition of early neuroanatomical and neurophysiological markers of injury.

One of the most informative tools is diffusion tensor imaging (DTI), which identifies microscopic disruptions in white matter integrity. Patients with persistent cognitive impairments following concussion frequently exhibit deviations in DTI metrics that correlate with cognitive test results. Gonzalez et al.27 demonstrated a direct statistical correlation between DTI measures and cognitive assessments (MoCA) in athletes with chronic post-concussive complaints. In their study involving 53 patients with sustained cognitive deficits after traumatic brain injury (TBI), lower MoCA scores were associated with findings of diffuse axonal injury, notably increased mean diffusivity (MD) in several regions and reduced fractional anisotropy (FA) compared to healthy controls. Specifically, MD in the inferior temporal gyrus was inversely correlated with cognitive scores (r=-0.62; p<0.001), as was MD in the middle temporal gyrus (r=-0.54; p<0.001) and angular gyrus (r=-0.48; p<0.001). Conversely, FA in the inferior frontal gyrus was positively correlated with MoCA scores (r=+0.44; p=0.002). This suggests that poorer cognitive performance is associated with more extensive diffuse axonal damage in frontotemporal white matter tracts. In practice, such microstructural lesions are indicative of diffuse axonal injury that may not be visible on standard MRI but is detectable via DTI as elevated diffusivity (due to loss of myelin and axonal integrity) and decreased FA (indicating loss of fibre directionality). In the acute phase, these changes may be transient, though in some athletes they persist, reflecting the organic substrate of cognitive dysfunction.

Longitudinal DTI studies confirm that certain white matter regions remain altered even after clinical recovery, whereas in other cases they return to baseline rapidly. Wu et al.28 showed that, in the acute phase (24-48 hours post-injury), athletes with TBI exhibited significantly higher MD in white matter compared to controls. This aligns with axonal swelling and transient disconnection of neural pathways immediately following trauma. These diffusion abnormalities tended to normalise over subsequent weeks in parallel with clinical improvement. In the study by Meier et al.15, conducted within the NCAA-DOD CARE Consortium, resting-state functional MRI (rs-fMRI) was used to monitor athletes with concussion until recovery. They found that functional brain connectivity disrupted immediately post-injury – particularly local connectivity in frontal regions and the default mode network (DMN) – tended to recover alongside symptom resolution. These rs-fMRI changes generally did not persist after clinical recovery in athletes who had fully recovered. This is a critical finding: in the absence of repeated injury, the brain is capable of restoring functional networks, and persistent abnormalities are not typically observed. However, in patients with prolonged psychological or cognitive symptoms, certain sustained alterations were noted, such as increased local connectivity in the prefrontal cortex, which was associated with ongoing anxiety and depressive symptoms. Thus, neuroimaging confirms that incomplete neuronal recovery correlates with persistent symptoms, while normalisation of imaging metrics reflects clinical recovery. These tools hold promise for prognostic applications: for example, sustained post-injury DTI deviations may serve as biomarkers for long-term cognitive dysfunction.

Beyond DTI, other neuroimaging correlates are also under investigation. Voxel-based morphometry (VBM) MRI studies have identified volumetric reductions in specific structures in athletes with repeated TBIs – for instance, in former boxers, hippocampal atrophy and diffuse cortical thinning have been documented compared to controls, which are associated with cognitive impairments (although such changes often become apparent only years after career termination). T1-weighted MRI can also detect microhaemorrhages (haemosiderin-laden macrophages) or lacunar infarcts associated with trauma, which have likewise shown correlations with cognitive decline in veterans of contact sports29. Emerging techniques such as diffusion spectrum imaging and tractography allow for more precise mapping of damage to long associative tracts (e.g., frontoparietal pathways), whose disruption impairs attention and executive functions.

Chronic cognitive impairment following repeated TBIs has been linked to the accumulation of abnormally hyperphosphorylated tau protein within neurons – this is the pathohistological hallmark of chronic traumatic encephalopathy (CTE). To visualise this process in vivo, positron emission tomography (PET) with tau radiotracers has been employed. The results to date remain inconclusive. In the study by Stern et al.30, a cohort of living former NFL players with cognitive and neuropsychiatric complaints demonstrated increased tau tracer uptake on PET in regions vulnerable to CTE (e.g., medial temporal lobe, frontal cortex) compared to controls. This would appear to support the notion that cognitive deficits are driven by tau-mediated neurodegeneration. However, the tau PET signal levels did not correlate with actual cognitive performance or symptom severity in these individuals. In other words, some players with high tau deposition had relatively preserved cognitive functions, while others with moderate uptake showed severe impairment. This may be explained by the fact that tau PET primarily reflects pathological burden, which may not directly affect neuropsychological test scores, or that cognitive reserve in some individuals mitigates the clinical impact of tau accumulation. Alternatively, current tau PET techniques remain limited in accuracy: background binding and tracer specificity continue to pose challenges, complicating interpretation31. Ongoing research aims to improve PET visualisation of CTE, including combinations with amyloid PET (to exclude Alzheimer’s disease) and MRI. Preliminary data suggest that some former American football players with dementia exhibit both tau and amyloid deposition, complicating the differentiation of underlying pathologies32. Nonetheless, in summary: neuroimaging allows for objective detection of the structural and functional consequences of TBI, as well as the pathophysiological processes (such as tau accumulation) underlying cognitive decline. However, the ambiguous results and technical limitations of tau-PET currently reduce its diagnostic utility in routine clinical practice, leaving DTI and functional MRI as the primary tools for assessing cognitive sequelae of sports-related TBI.

In parallel with imaging modalities, the field of TBI biomarker research is rapidly expanding. These are specific molecules whose levels in blood or cerebrospinal fluid reflect the extent of brain injury and may predict cognitive outcomes. Biochemical markers offer a unique opportunity for real-time, quantitative monitoring of neurotrauma, complementing morphological data from imaging with functional insights into the metabolic status of neural structures. Advanced analytical technologies now allow for the detection of even minimal changes in the concentration of specific proteins, making biomarkers particularly valuable for diagnosing subclinical TBI. Several promising TBI biomarkers are currently under investigation (table 2).

The systematisation of traumatic brain injury (TBI) biomarkers presented in table 2 reflects the complex, cascade-like nature of neurotrauma, whereby each molecular marker is characterised by unique kinetics of release and metabolic clearance, determined by the specific biochemical properties of protein structures and their mechanisms of transport across the blood-brain barrier. A fundamental aspect of the clinical application of biomarkers lies in understanding their pathophysiological context within the temporal evolution of traumatic processes. In this regard, early markers of astrocytic and neuronal injury gradually give way to later indicators of axonal degeneration and prolonged neuroinflammation. Standardisation of analytical platforms and validation of reference values for different athletic populations is of critical importance, as variability in baseline biomarker levels may substantially affect the interpretation of results and the predictive accuracy.

Among the most promising biomarkers are proteins indicative of astrocytic and axonal damage, particularly glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL). GFAP is a structural protein of astrocytes, released upon their injury, while NfL is a component of axons that is liberated in cases of axonal rupture or degeneration. Both are recognised as highly specific biomarkers of TBI: elevated GFAP reflects glial activation and injury, whereas NfL indicates diffuse axonal damage.

In a recent multicentre study20, the dynamics of GFAP and NfL in adult athletes following concussion were characterised for the first time, demonstrating a correlation between these biomarkers and the duration of cognitive recovery. At 24 hours post-injury, GFAP levels were significantly higher in the affected group compared to controls (log-transformed level difference 0.66; 95% CI 0.50-0.82), and remained elevated even after four weeks (difference 0.17; 95% CI 0.02-0.32). NfL levels rose slightly later: significant increases compared to baseline were observed from the 1st to the 12th week post-concussion (e.g., week 1 difference 0.31; 95% CI 0.12-0.51; week 2-0.38; 95% CI 0.19-0.58; week 4-0.31). This supports the notion that axonal injury (NfL) may persist longer, while the astrocytic component (GFAP) partially normalises within a month, albeit remaining above normal.

The study also revealed heterogeneity in biomarker responses: cluster analysis identified a subgroup (16% of cases) with persistently elevated GFAP levels for 4 weeks or more, and 7% with prolonged elevation of NfL. These athletes likely sustained more severe injuries. Indeed, loss of consciousness at the time of trauma occurred in 33% of the affected and was significantly more frequent in the subgroup with prolonged elevations of GFAP and NfL. Belonging to the extreme biomarker subgroup had marked clinical correlates: return-to-play times were significantly extended. For the GFAP-extreme group, the incidence rate ratio (IRR) for recovery time was 1.99 (95% CI 1.69-2.34) compared to those with moderate, transient elevations. An even more pronounced effect was observed for NfL: athletes with markedly elevated and prolonged NfL levels took over three times longer to return to training (IRR=3.24; 95% CI 2.63-3.97) than those with minimal NfL changes. Even modest NfL elevation was associated with delayed recovery (IRR=1.43; 95% CI 1.18-1.72).

Thus, the biomarker profile post-TBI reflects the degree of structural brain damage, which directly influences the duration of cognitive dysfunction. The authors conclude that serial measurements of GFAP and NfL may serve as objective tools to monitor neurobiological recovery and identify athletes who require prolonged rehabilitation. Furthermore, the presence of loss of consciousness during TBI – a classic marker of severity – was confirmed to be associated with prolonged biomarker elevation and should be taken into account when making conservative return-to-play decisions20. In addition to GFAP and NfL, other blood biomarkers indicative of cognitively relevant brain damage in TBI are under investigation, including ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), Tau protein, and S100β. Some of these also show acute-phase elevation; however, their association with long-term cognitive outcomes is less well-defined. For instance, elevated plasma Tau has been observed in some athletes immediately after concussion, but it currently lacks clear prognostic value for the development of chronic traumatic encephalopathy (CTE).

Considerable attention is now being given to genetic modifiers that influence the extent of cognitive impairment under similar traumatic loads. The most extensively studied is the ε4 allele of the apolipoprotein E (APOE) gene. According to data from the National Center for Biotechnology Information (2025), the presence of the ε4 allele increased the likelihood of a more severe CTE stage by 2.34 times (OR=2.34). Practically, this implies that for American football players over the age of 65, carrying ε4 is equivalent to an additional seven years of playing experience in terms of its effect on encephalopathy severity37.

Instrumental studies confirm the organic basis of cognitive impairment associated with sports-related TBI. Neuroimaging, particularly diffusion tensor imaging (DTI-MRI), reveals diffuse microstructural damage to white matter, which quantitatively correlates with the degree of cognitive dysfunction (e.g., higher mean diffusivity (MD) and lower fractional anisotropy (FA) in key tracts are associated with poorer memory and attention)27. Functional neural network alterations detected via resting-state fMRI (rs-fMRI) during the acute phase also reflect cognitive symptoms, which tend to subside as compensation occurs. Brain injury biomarkers such as GFAP and NfL offer an objective window into the extent of neurotrauma: their post-TBI elevations are statistically significant, and prolonged blood circulation of these proteins is associated with long-term cognitive impairment and delayed recovery15. The combination of neuroimaging and molecular markers in the future may allow for more precise risk stratification - for instance, identifying individuals requiring extended rehabilitation or, conversely, permitting earlier return if biomarkers normalise. Finally, the pathological processes underlying traumatic neurodegeneration (e.g., Tau accumulation, diffuse neurofibrillary pathology) can now be studied in vivo using PET, although their direct association with clinical cognitive function remains to be fully elucidated. Collectively, the presence of clear neurobiological correlates underscores the clinical importance of this issue: cognitive disturbances following sports-related TBI are not subjective complaints but reflect specific brain injuries that can be measured and quantitatively related to clinical outcomes.

Long-term cognitive trajectories, modifying factors, and preventive strategies

In contrast to acute, reversible impairments, chronic cognitive changes resulting from sports-related TBI may be persistent and progressive. Among athletes with long-standing exposure to contact sports, there is a statistically higher prevalence of mild cognitive impairment (MCI) in later life and even dementia. A systematic review of 14 studies conducted by Gallo29 reported that athletes with a history of repeated concussions had a significantly higher incidence of MCI compared to control populations. Recurrent concussions are associated with cognitive decline risk: one study included in the review found that among former NFL players, having ≥3 concussions was significantly associated with increased diagnoses of MCI (p=0.002) and self-reported memory issues (p=0.001) compared to those without a concussion history. Moreover, spouses of affected individuals were more likely to report pronounced memory deficits in those who had sustained repeated injuries (p=0.04). These within-group comparisons (between athletes with varying levels of exposure) are particularly valuable as they eliminate lifestyle-related confounders: under otherwise equal conditions, additional concussions are a statistically significant determinant of worse future cognitive outcomes.

Beyond MCI, some studies suggest elevated risks for more severe conditions such as Alzheimer’s disease or CTE in former athletes. For example, Didehbani et al.12 found that among 34 former NFL players, approximately 12% exhibited persistent cognitive deficits, and 6% met criteria for dementia; notably, the longer the duration of professional play, the higher the frequency of cognitive complaints. In another study by R.C. Byrd et al.38, around 35% of former professional athletes demonstrated signs of cognitive impairment based on the AD8 screening tool, although not always confirmed by neuropsychological testing. At the same time, some studies found no differences between former athletes and controls on standard cognitive assessments, which may be due to methodological discrepancies or the cognitive reserve inherent in athletes29. However, large-scale epidemiological studies in recent years have sent a clear signal: former professional athletes in contact sports are at increased risk of neurodegenerative disease and thus long-term cognitive decline. The most compelling evidence has come from studies on football (soccer) players. A retrospective cohort study in Scotland39 compared the incidence of neurodegenerative diseases in 7.676 former footballers and 23.000 matched controls from the general population. The results were striking: mortality due to neurodegenerative diseases as the primary cause was three times higher among footballers (1.7%) than controls (0.5%), with a calculated sub-hazard ratio (sub-HR) of 3.45 (95% CI 2.11-5.62; p<0.001). When all cases where neurodegenerative disease appeared as a primary or contributing cause of death were included, the difference became even more pronounced. The greatest risk increase was observed for Alzheimer’s disease: former players had an approximately fivefold higher risk of dying from Alzheimer’s-type dementia (HR=5.07; 95% CI 2.92-8.82; p<0.001). The risk for motor neuron diseases (e.g., ALS) was around fourfold, and for Parkinson’s disease, approximately twofold (HR=2.15; 95% CI 1.17-3.96). While overall mortality before the age of 70 was lower among footballers – likely due to better general health and fewer cardiovascular or oncological deaths – in older age, mortality from dementia outweighed these benefits. This data was the first to demonstrate at the population level that professional football, despite its overall health benefits, is associated with an increased long-term risk of dementia.

Russell et al.40 investigated the specific career-related factors in football players that are associated with an increased risk of neurodegenerative disease. Their findings indicated that both career duration and playing position significantly influence this risk. Players with careers exceeding 15 years exhibited the highest risk of neurodegenerative disease (HR=5.20; 95% CI 3.17-8.51), which is nearly five times greater than in those whose careers spanned less than five years. Moreover, outfield players – particularly defenders – were at greater risk compared to goalkeepers: defenders had a hazard ratio of HR=4.98 (95% CI 3.18-7.79; p<0.001), whereas for goalkeepers the HR was 1.83, which did not reach statistical significance (95% CI 0.93-3.60; p=0.08). This finding is highly illustrative: goalkeepers rarely engage in heading the ball and are therefore exposed to substantially fewer subconcussive impacts. In contrast, outfield players, and especially central defenders (who frequently contest aerial duels), experience the highest cumulative exposure to head impacts – and consequently, the highest dementia risk. These positional differences support the hypothesis that chronic traumatic exposure (i.e. repeated heading and collisions) plays a central role in long-term cognitive decline. Interestingly, era (birth year) did not influence the risk – players born in the 1960s and the 1930s demonstrated similar rates, suggesting that historical changes in playing style or protective gear have yet to mitigate the problem.

Similar, albeit smaller-scale, findings have been reported in other contact sports, notably American football. Former NFL players demonstrate increased rates of both mild cognitive impairment (MCI) and diagnoses such as Parkinson’s disease and chronic traumatic encephalopathy (CTE). Data from cohorts studied at Boston University indicate that approximately 33% of retired players with long careers present at least moderate cognitive impairments, and among those with ≥10 concussions, the prevalence of MCI/dementia was significantly higher than in players without a history of head trauma41. Thus, long-term cognitive trajectories in athletes often exhibit a biphasic pattern: following retirement, there may be a period of relative stability, but in many cases symptoms of neurodegeneration – accelerated decline in memory and executive function, progressing to dementia – emerge by the fifth or sixth decade of life.

Despite this overall trend, not all athletes with significant histories of head trauma go on to develop dementia. For instance, some NFL veterans maintain intact cognitive functioning well into old age, while others of similar age exhibit severe cognitive-behavioural syndromes as early as their 50s. This disparity points to the influence of modifying factors that affect individual vulnerability. One such factor is the previously mentioned APOE ε4 genotype, which is associated with a twofold increased risk of severe CTE37. Another potential factor is the age at which athletes begin engaging in contact sports: some studies suggest that the developing brain may be more susceptible to long-term damage when exposure occurs at a very young age < 12 years). Research has demonstrated that former American football players who began playing before age 12 performed worse on memory and executive function tests in adulthood compared to those who started later, despite having similar overall career lengths42. Although not all studies confirm this association, the age of first head impact is increasingly viewed as a possible risk factor – potentially due to the increased vulnerability of the immature brain to mechanical forces. Cognitive reserve and educational attainment may modulate clinical manifestation: highly educated athletes sometimes demonstrate better compensation for brain injury and milder cognitive symptoms (though this does not affect the underlying pathology). Some studies report that larger brain volumes and greater cognitive reserve are associated with improved resilience to repeated traumatic brain injuries (TBIs)43, although findings remain inconsistent. Post-career mental health support also plays a role: depression and anxiety commonly accompany post-traumatic cognitive disorders and may exacerbate them, while social engagement and treatment of affective symptoms tend to improve functional status. Finally, somewhat unexpectedly, sex may also act as a potential modifier of long-term outcomes. Female athletes engaged in professional contact sports remain underrepresented in longitudinal research (due to the relatively recent establishment of women’s leagues), but emerging data suggest similar issues. For example, former female footballers report high levels of cognitive complaints in midlife, and neuropsychological testing indicates impaired memory and attention among those with histories of multiple concussions. Further large-scale studies are needed. Given the potential increased susceptibility of female brains to trauma, the gender dimension of long-term consequences is likely to receive growing attention in the near future.

The recognition of the serious cognitive consequences of sport-related TBIs has led to numerous initiatives aimed at prevention and risk mitigation. These include both primary prevention (injury avoidance) and secondary prevention (prevention of re-injury and complications). The most straightforward strategy involves reducing the frequency and magnitude of subconcussive impacts. Following the publication of data linking football to elevated dementia risk, several federations implemented new regulations. For instance, in youth football across the US and Europe, heading is either restricted or banned during training for children under 11-12 years of age. The goal is to delay the onset of trauma accumulation to a more mature age and to reduce the cumulative burden on the brain. In professional football, limitations on the number of aerial duels during training are being considered. Findings from Stenberg et al.43 clearly support strategies aimed at reducing head impact load as a means to lower neurodegeneration risk. Similar measures have been adopted in American football, such as limiting contact practices at school and collegiate levels, banning high-risk techniques (e.g. helmet-to-helmet hits), and modifying rules to reduce high-speed collisions (e.g. adjusting kickoff lines). Statistical data already suggest a modest decline in concussion incidence in leagues that adopted such changes. For example, in the NFL, following the prohibition of helmet-to-helmet hits and improvements in helmet technology, the rate of diagnosed concussions has decreased by approximately 13% over the past five years, according to league data.

Where feasible, enhanced protective equipment is being developed. Modern helmets used in American football, hockey, and rugby are now equipped with energy-absorbing materials and structures designed to reduce head acceleration upon impact. Although helmets cannot completely prevent concussions – due to the inertial movement of the brain inside the skull – studies show that newer helmet models can reduce impact acceleration by approximately 20-30%. Helmet and mouthguard-based sensors are also increasingly used to register G-force exposure, allowing for objective monitoring of the number and severity of impacts sustained by players over a season. This facilitates personalised monitoring: if sensors detect an excessive number of impacts, coaching staff can adjust the athlete’s playing time or modify training to allow for neurological recovery. Epidemiological data suggest moderate effectiveness of these interventions: implementation of improved protective gear and monitoring protocols has led to a 15-25% reduction in recorded concussions in professional leagues over the past decade, although experts stress the need for continued technological advancement.

Education of coaches and athletes on TBI consequences is of paramount importance. Virtually all professional leagues – and increasingly, amateur competitions – have adopted concussion recognition and response protocols (e.g. SCAT5). Players are instructed not to conceal symptoms but to report them immediately to coaching or medical staff. There is growing awareness that a secondary impact on an incompletely recovered brain can have catastrophic consequences (second impact syndrome, diffuse cerebral oedema). The average vulnerability window post-concussion is 7-10 days – a period during which neurobiological processes remain unstable, and a second trauma may inflict exponentially greater damage. Hence, strict adherence to the “if in doubt, sit them out” principle has become standard practice. In many competitions, independent concussion spotters are present and authorised to halt play if a concussion is suspected – even if a team attempts to downplay the incident.

Athletes who have sustained a TBI undergo close medical supervision. The standard of care involves a staged return-to-play protocol: initially complete rest, followed by gradual reintroduction of activity (aerobic exercise, non-contact training), and eventual return to full contact only in the absence of symptoms both at rest and under exertion. This protocol typically spans at least a week for adults (longer for youth athletes) and reduces the risk of recurrent concussion during the vulnerable phase15.

If cognitive symptoms persist beyond 2-3 weeks, targeted neurorehabilitation is indicated: cognitive training, neuropsychological therapy, and treatment of comorbid issues (e.g. insomnia, headache, depression). One study showed that structured cognitive exercises and controlled aerobic activity accelerate recovery from post-concussive symptoms in adolescents with persistent complaints compared to standard rest alone44. Thus, secondary prevention also encompasses optimal rehabilitation, which prevents the transition from acute dysfunction to chronic impairment. Given the elevated risk of neurodegeneration, long-term monitoring programmes for former athletes are being developed. In the US, initiatives such as NFL Lifeline provide regular cognitive screening for ex-players, and individuals showing early signs of MCI are referred to specialists. Participation in research is also encouraged (including posthumous brain donation for CTE studies). Early interventions – such as management of vascular risk factors and adoption of an active lifestyle – may help delay the onset of dementia, even in the presence of established pathology. Therefore, it is essential that former athletes are informed and motivated to adhere to a healthy lifestyle.

The clinical management of female athletes after traumatic brain injury (TBI) necessitates a differentiated approach grounded in evidence-based data concerning gender-specific differences in the pathophysiology and trajectory of post-concussion syndrome. Female athletes statistically exhibit a significantly prolonged symptomatic recovery period compared to their male counterparts, thereby necessitating extended medical surveillance25. The return-to-sport (RTS) protocol for women should incorporate a lengthened phase of graded exertion, with a mandatory 7-day interval between stages rather than the standard 24-48 hours. Crucially, the menstrual cycle phase must be considered when assessing readiness to return, as the luteal phase is associated with heightened vulnerability to recurrent injury due to fluctuations in oestrogen and progesterone concentrations. Female athletes with a history of migraine or depressive disorders require heightened attention, as these comorbidities increase the risk of prolonged post-concussion syndrome by 2.5 to 3 times. Neuropsychological testing in women should not be administered earlier than 14 days post-injury, with re-evaluation at 4 weeks, taking into account potential fluctuations in cognitive functioning influenced by hormonal status25. The utilisation of validated, gender-sensitive scales is recommended, including assessments of emotional state and social functioning, which in women may be disproportionately affected relative to cognitive indices.

Discussion

The findings of this study provide a comprehensive understanding of the cognitive sequelae of sports-related traumatic brain injury and underscore the multidimensional nature of these impairments, encompassing acute, subacute, and long-term alterations in cognitive functions. The observation that 90% of mild sports-related concussions are characterised by transient cognitive symptoms resolving within 10-14 days in most athletes is entirely consistent with the results of McCrea et al.45, who, in a large-scale NCAA-DoD CARE Consortium study involving 504 athletes, demonstrated a comparable recovery trajectory following the acute phase of sports-related TBI. The researchers identified statistically significant elevations in GFAP, NfL, and tau levels in athletes with acute TBI compared to control groups, affirming the organic basis of cognitive dysfunction. A particularly salient aspect of the results is the finding that 10-15% of athletes exhibit persistent post-concussion symptoms, with this proportion increasing to 15-30% among children and adolescents. This corroborates observations by Koerte et al.46 regarding age-dependent variability in recovery from sports-related TBI and highlights the need for a stratified approach tailored to different age groups of athletes.

Gender differences in the course of sports-related TBI are robustly supported by the work of Churchill et al.47, who, using functional MRI, demonstrated more pronounced and prolonged changes in female brain functional networks following concussion. The researchers found that women exhibited greater disruptions in functional connectivity within networks responsible for cognitive control and working memory, correlating with a longer symptomatic recovery period. The data indicating that girls performed worse on visual memory tests 8 days post-concussion compared to boys (68.7±15.2 vs 77.2±8.9; p=0.021) align with findings from Bretzin et al.16, who, in a comparative analysis of recovery trajectories among male and female collegiate athletes, identified similar gender-related differences in clinical recovery. Mechanistic explanations of these differences, including experimental evidence demonstrating thinner and less densely packed axons in female mammals, provide a neurobiological foundation for understanding the increased susceptibility of the female brain to traumatic insults. This has critical implications for the development of gender-specific management protocols for athletes post-TBI.

Findings regarding neuroimaging and biomarker correlates of cognitive dysfunction further underscore the organic nature of cognitive impairments following sports-related TBI and refute the notion of their exclusively functional character. The identified correlation between DTI metrics and MoCA cognitive assessments – specifically, the inverse correlation between mean diffusivity (MD) in the inferior temporal gyrus and cognitive score (r=-0.62; p=0.00001) – is fully supported by the longitudinal findings of Wu et al.28. Their study within the CARE Consortium established statistically significant associations between levels of tau, NfL, GFAP, and DTI-detected white matter changes in athletes with acute TBI. Notably, tau protein in the blood showed the strongest association with microstructural white matter changes, underscoring its potential as a prognostic biomarker. These findings are especially relevant in the context of the work by Mayer et al.48, who demonstrated accelerated brain “ageing” following TBI using machine learning techniques and biomarker profiling, highlighting the long-term impact of even isolated traumatic episodes on neural architecture and neurodegenerative processes.

The dynamics of GFAP and NfL biomarkers post-sports TBI are directly corroborated by the referenced studies and further substantiated by Meier et al.49, who identified elevated inflammatory biomarkers IL-6 and IL-1RA in the acute post-concussion period and reported gender differences in the inflammatory response, with IL-1RA being elevated exclusively in male participants. Particularly noteworthy is the observation of biomarker response heterogeneity, where 16% of cases exhibited prolonged elevations in GFAP and 7% in NfL, findings consistent with those of Giesler et al.50. The latter explored associations between long-term participation in contact sports and fluid biomarker levels in older athletes, emphasising individual variability in neuronal response to trauma and the necessity of a personalised approach to recovery monitoring – an imperative for clinical practice.

The delineation of long-term cognitive trajectories, including a threefold increased risk of neurodegenerative diseases among professional footballers compared to controls, finds dramatic confirmation in the landmark study by McKee et al.51. Their analysis of 152 brains from young athletes revealed chronic traumatic encephalopathy (CTE) in 41% of individuals who died before the age of 30. This study fundamentally altered the understanding of the temporal development of neurodegenerative changes post-sports TBI, overturning the prior assumption that CTE develops primarily in later life. The researchers determined that 71% of donors with CTE had participated in contact sports at a non-professional level, highlighting the risks even for amateur athletes. Risk stratification by playing position – defenders (HR=4.98) versus goalkeepers (HR=1.83) – is fully aligned with epidemiological data linking head impact exposure with neurodegenerative risk in footballers, substantiating the causal role of repetitive sub-concussive impacts in the development of long-term cognitive deficits.

An analysis of sub-concussive brain injuries reveals the complex dynamics of cumulative microtrauma and its relationship to clinically significant cognitive decline. The finding that players sustaining more than 15 head impacts per match were three times more likely to exhibit cognitive impairments in later life (AOR=3.16; 95% CI: 1.08-9.22) is consistent with Major et al.52, who identified specific oxidative stress biomarker changes in male athletes from contact sports – but not in females – suggesting gender-specific mechanisms of adaptation to chronic traumatic exposure. Elevated levels of proteins associated with oxidative stress and vascular dysfunction were identified, which may underlie mechanisms of long-term damage even in the absence of clinically manifest concussions. Meanwhile, the absence of significant neurocognitive test changes in young German footballers over a 17-month observational period highlights the importance of long-term monitoring to detect subclinical changes and the challenges of establishing causality in short-term studies.

The clinical significance of these findings lies in their potential to transform approaches to the diagnosis, monitoring, and prognosis of sports-related TBI through the integration of objective biological markers. The establishment of robust correlations between GFAP/NfL biomarkers and the duration of cognitive recovery offers prospects for the development of objective return-to-sport protocols that extend beyond subjective symptom reporting and may mitigate potential biases in symptom self-assessment across athletes. This is particularly crucial in light of established gender differences in symptomatology, as objective biomarkers can provide a more accurate appraisal of injury severity and readiness to return to sport, irrespective of the athlete’s sex.

The findings of the study also bear significant implications for the development of preventive strategies, particularly in the context of sub-concussive injuries. The establishment of a dose-dependent relationship between the number of head impacts and the risk of long-term cognitive impairments provides a scientific rationale for implementing limitations on the number of contact actions during training, especially among young athletes. This aligns with current trends in sports medicine aimed at minimising risks without entirely eliminating athletic participation. In summary, the results of the study conceptualise sports-related traumatic brain injury (TBI) as a complex medical issue with a broad spectrum of cognitive consequences, necessitating a multidisciplinary approach to prevention, diagnosis, and treatment. The identification of objective neurobiological correlates of cognitive dysfunction through the integration of neuroimaging and biomarkers forms a foundation for the development of evidence-based return-to-play protocols and long-term monitoring of athletes at risk for neurodegenerative complications.

Conclusions

A comprehensive analysis of contemporary scientific research demonstrates that sports-related TBI results in a wide range of cognitive impairments, varying from acute transient dysfunctions to chronic neurodegenerative changes. It has been established that 90% of mild sport-associated concussions are characterised by clinically significant cognitive symptoms, including short-term memory disturbances, slowed information processing speed, attention and concentration deficits, and reduced executive functioning. The analysis revealed substantial variability in cognitive recovery: in 80-90% of adult athletes, acute symptoms fully resolve within 7-14 days, while 10-15% develop persistent post-concussive symptoms. Sexual dimorphism is manifested in a higher incidence of concussions among female athletes and a longer duration of cognitive recovery, which may be attributed to anatomical peculiarities of axonal architecture and the increased vulnerability of fine axons to mechanical injury. The critical role of cognitive reserve as a protective factor against long-term consequences of sports-related TBI has been established, with athletes possessing higher educational attainment and experience in cognitively demanding sports showing better recovery outcomes, regardless of the initial injury’s severity.

Neuroimaging and biochemical studies have confirmed the organic basis of cognitive dysfunction in sports-related TBIs. Diffusion tensor imaging reveals microscopic disruptions in white matter integrity, which quantitatively correlate with the degree of cognitive dysfunction through alterations in mean diffusivity and fractional anisotropy within frontotemporal tracts. Biomarkers of neuronal injury, such as GFAP and NfL, exhibit statistically significant elevations post-injury, with a direct correlation between the duration of their elevation and the period of cognitive recovery. Athletes with markedly prolonged biomarker elevation demonstrate a two- to threefold longer return-to-training timeline, indicating the potential use of molecular markers for risk stratification and the personalisation of rehabilitation protocols.

Long-term epidemiological observations have revealed a dramatic increase in the risk of neurodegenerative diseases among professional athletes in contact sports. A pooled analysis of cohort studies, including the Scottish study of former football players, demonstrated a threefold increase in mortality from neurodegenerative conditions compared to a control population, with particularly elevated risk for Alzheimer’s disease. The cumulative effect of repeated sub-concussive impacts is reflected in positional risk differences: outfield players exhibit a fivefold increase in the likelihood of neurodegeneration compared to goalkeepers, supporting a causal link between chronic traumatic exposure and the development of cognitive disorders. Genetic modifiers, particularly the APOE ε4 allele, double the risk of severe chronic traumatic encephalopathy, indicating individual variability in susceptibility to post-traumatic neurodegeneration.

The practical significance of the obtained results lies in the establishment of an evidence-based foundation for personalised approaches to the prevention and rehabilitation of sports-related TBIs. The identified patterns allow for the development of differentiated medical support protocols for athletes, taking into account sex, age, genetic risk factors, and the specific characteristics of the sporting discipline. The findings hold fundamental importance for understanding the pathophysiological mechanisms of traumatic encephalopathy and for building an evidence base for preventive strategies in sport. Key limitations of the study include the underrepresentation of female athletes in long-term epidemiological cohorts, methodological variability across studies, and the absence of standardised protocols for cognitive assessment across different sporting populations. Future research should focus on the development of validated biomarker panels for the early diagnosis of chronic traumatic encephalopathy and the creation of personalised risk assessment algorithms based on the integration of genetic, neuroimaging, and neuropsychological predictors to optimise individualised strategies for the prevention and treatment of sports-related traumatic brain injuries.

Conflicts of interest. The authors declare there is no conflict of interest.

Funding. This study has been funded by the Shandong Women’s University, 2024 Provincial and Ministerial Key Cultivation Project, No. 2024GSPSJ08.

References

1. Ntikas M, Stewart W, Ietswaart M, et al. Contrasting characteristics and outcomes of sports-related and non-sports-related traumatic brain injury. JAMA Network Open 2024; 7: e2353318.

2. Hou X, Zhang Y, Fei X, Zhou Q, Li J. Sports-related concussion affects cognitive function in adolescents: A systematic review and meta-analysis. Am J Sports Med 2023; 51: 3604-18.

3. Qi B, Tan J, Feng D, et al. Prevalence of chronic traumatic encephalopathy in athletes with repetitive head impacts: a systematic review and meta-analysis. Scand J Med Sci Sports 2025; 35: e70047.

4. Grashow RG, Terry DP, Lawson BL, et al. Perceived chronic traumatic encephalopathy and suicidality in former professional football players. JAMA Neurology 2024; 81: 1130-8.

5. Walton SR, Kerr ZY, Powell JR, et al. An 18-year study of changes in neurocognitive function and associations with repetitive head trauma among former collegiate American football players: a case series. Arch Clin Neuropsychol 2025; acaf032.

6. Walton SR, Brett BL, Chandran A, et al. Mild cognitive impairment and dementia reported by former professional football players over 50 yr of age: An NFL-LONG study. Med Sci Sports Exerc 2022; 54: 424-31.

7. Rubin LH, Du Y, Sweeney SE, et al. Imaging brain injury in former National Football League players. JAMA Network Open 2023; 6: e2340480.

8. Abdolmohammadi B, Tuz-Zahra F, Uretsky M, et al. Duration of ice hockey play and chronic traumatic encephalopathy. JAMA Network Open 2024; 7: e2449806.

9. Lennon MJ, Rigney G, Creese B, et al. Sports-related concussion not associated with long-term cognitive or behavioural deficits: The PROTECT-TBI study. J Neurol Neurosurg Psychiatry 2025; 96: 397-405.

10. Collins LK, Ofa SA, Miskimin C, Mulcahey M. Cognitive deficits following concussion: a systematic review. Journal of Orthopaedic Experience and Innovation 2023; 4.

11. Alosco ML, Barr WB, Banks SJ, et al. Neuropsychological test performance of former American football players. Alzheimers Res Ther 2023; 15: 1.

12. Didehbani N, Fields LM, Wilmoth K, LoBue C, Hart J, Cullum CM. Mild cognitive impairment in retired professional football players with a history of mild traumatic brain injury: A pilot investigation. Cogn Behav Neurol 2020; 33: 208-17.

13. Permenter CM, Thomas RJF, Sherman AL. Postconcussive syndrome. 2023. https://www.ncbi.nlm.nih.gov/books/NBK534786/

14. Hallock H, Mantwill M, Vajkoczy P, et al. Sport-related concussion: a cognitive perspective. Neurol Clin Pract 2023; 13.

15. Meier TB, Giraldo-Chica M, España LY, et al. Resting-state fmri metrics in acute sport-related concussion and their association with clinical recovery: a study from the NCAA-DOD CARE consortium. J Neurotrauma 2019; 37: 152-62.

16. Bretzin AC, Esopenko C, D’Alonzo BA, Wiebe DJ. Clinical recovery timelines after sport-related concussion in men’s and women’s collegiate sports. J Athl Train 2022; 57: 678-87.

17. University of Pennsylvania. 2024. Different brain structures in females lead to more severe cognitive deficits after concussion than males. https://penntoday.upenn.edu/news/penn-medicine-different-brain-structures-females-lead-more-severe-cognitive-deficits-after-concussion-males

18. Sheldrake E, Al-Hakeem H, Lam B, Goldstein BI, Wheeler AL, Burke M. Mental health outcomes across the lifespan in individuals with persistent post-concussion symptoms: a scoping review. Front Neurol 2022; 13.

19. Ewing-Cobbs L, Cox CS, Clark AE, Holubkov R, Keenan HT. Persistent postconcussion symptoms after injury. Pediatrics 2018; 142: e20180939.

20. O’Brien WT, Spitz G, Xie B, et al. Biomarkers of neurobiologic recovery in adults with sport-related concussion. JAMA Network Open 2024; 7: e2415983.

21. Espahbodi S, Hogervorst E, Povall Macnab TM, et al. Heading Frequency and Risk of Cognitive Impairment in Retired Male Professional Soccer Players. JAMA Network Open 2023; 6: e2323822.

22. Mund FK, Feddermann-Demont N, Welsch G, et al. Heading during the season and its potential impact on brain structure and neurocognitive performance in high-level male football players: An observational study. J Sci Med Sport 2024; 27: 603-9.

23. Covassin T, Elbin RJ, Bleecker A, Lipchik A, Kontos AP. Are there differences in neurocognitive function and symptoms between male and female soccer players after concussions? AM J Sports Med 2013; 41: 2890-5.

24. Song H, Tomasevich A, Paolini A, et al. Sex differences in the extent of acute axonal pathologies after experimental concussion. Acta Neuropathol 2024; 147: 79.

25. Nalla S. Women’s health considerations in traumatic brain injury. Current Physical Medicine and Rehabilitation Reports 2025; 13. https://doi.org/10.1007/s40141-025-00491-9

26. Schneider ALC, Huie JR, Boscardin WJ, et al.; TRACK-TBI Investigators. Cognitive outcome 1 year after mild traumatic brain injury: results from the TRACK-TBI Study. Neurology 2022; 98: e1248-e1261. 

27. Gonzalez AC, Kim M, Keser Z, et al. Diffusion tensor imaging correlates of concussion related cognitive impairment. Front Neurol 2021; 12: 639179.

28. Wu YC, Wen Q, Thukral R, et al. Longitudinal associations between blood biomarkers and white matter mri in sport-related concussion: a study of the NCAA-DoD CARE consortium. Neurology 2023; 101: e189-e201.

29. Gallo V, Motley K, Kemp SPT, et al. Concussion and long-term cognitive impairment among professional or elite sport-persons: a systematic review. J Neurol Neurosurg Psychiatry 2020; 91: 455-68.

30. Stern RA, Adler CH, Chen K, et al. Tau positron-emission tomography in Former National Football League Players. N Engl J Med 2019; 380: 1716-25.

31. Su Y, Protas H, Luo J, et al. Flortaucipir tau PET findings from former professional and college American football players in the DIAGNOSE CTE research project. Alzheimers Dement 2024; 20: 1827-38.

32. Lesman-Segev OH, La Joie R, Stephens ML, et al. NeuroImage Clin 2019; 24: 102025.

33. Alves CRR, Zhang R, Johnstone AJ, et al. Serum creatinine is a biomarker of progressive denervation in spinal muscular atrophy. Neurology 2020; 94: e921-e931.

34. Buh FC, Taiwe GS, Kobeissy FH, et al. Serum biomarker concentrations upon admission in acute traumatic brain injury: Associations with TBI severity, toxoplasma gondii infection, and outcome in a referral hospital setting in Cameroon. NeuroSci 2023; 4: 164-77.

35. Korley FK, Jain S, Sun X, et al. Prognostic value of day-of-injury plasma GFAP and UCH-L1 concentrations for predicting functional recovery after traumatic brain injury in patients from the US TRACK-TBI cohort: An observational cohort study. Lancet Neurol 2022; 21: 803-13.

36. Levy MG. This protein predicts a brain’s future after traumatic injury. Wired 2021. https://www.wired.com/story/this-protein-predicts-a-brains-future-after-traumatic-injury/

37. Henderson E. APOEε4 may confer increased risk for CTE-related neuropathological outcomes among older adults with repetitive head impacts. 2022. https://www.news-medical.net/news/20220627/APOEceb54-may-confer-increased-risk-for-CTE-related-neuropathological-outcomes-among-older-adults-with-repetitive-head-impacts.aspx

38. Byrd RC. Positive therapeutic effects of intercessory prayer in a coronary care unit population. South Med J 1988; 81: 826-9.

39. Professional Footballers’ Association. 2025. FIELD study 2019. https://www.thepfa.com/players/brain-health/field

40. Russell ER, Mackay DF, Stewart K, MacLean JA, Pell JP, Stewart W. Association of field position and career length with risk of neurodegenerative disease in male former professional soccer players. JAMA Neurol 2021; 78: 1057.

41. Gormally C. Former NFL players report mild cognitive impairment, dementia at higher rates than national average for their age. 2022. https://concussionalliance.org/blog/2022/4/10/former-nfl-players-report-mild-cognitive-impairment-dementia-at-higher-rates-than-national-average-for-their-age

42. Alosco ML, Kasimis AB, Stamm JM, et al. Age of first exposure to American football and long-term neuropsychiatric and cognitive outcomes. Transl Psychiatry 2017; 7: e1236.

43. Stenberg J, Håberg AK, Follestad T, et al. Cognitive reserve moderates cognitive outcome after mild traumatic brain injury. Arch Phys Med Rehabil 2020; 101: 72-80.

44. Ekdahl N, Möller MC, Deboussard CN, Stålnacke BM, Lannsjö M, Nordin LE. Investigating cognitive reserve, symptom resolution and brain connectivity in mild traumatic brain injury. BMC Neurol 2023; 23: 450.

45. McCrea M, Broglio SP, McAllister TW, et al. Association of blood biomarkers with acute sport-related concussion in collegiate athletes: findings from the ncaa and department of defense care consortium. JAMA Network Open 2020; 3: e1919771.

46. Koerte IK, Schultz V, Sydnor VJ, et al. Sex-related differences in the effects of sports-related concussion: a review. J Neuroimag 2020; 30: 387-409.

47. Churchill NW, Hutchison MG, Graham SJ, Schweizer TA. Sex differences in acute and long-term brain recovery after concussion. Hum Brain Mapp 2021; 42: 5814-26.

48. Mayer AR, Meier TB, Ling JM, et al. Increased brain age and relationships with blood-based biomarkers following concussion in younger populations. J Neurol 2023; 270: 5835-48.

49. Meier TB, Huber DL, Goeckner BD, et al. Association of blood biomarkers of inflammation with acute concussion in collegiate athletes and military service academy cadets. Neurology 2024; 102: e207991.

50. Giesler LP, O’Brien WT, Symons GF, et al. Investigating the association between extended participation in collision sports and fluid biomarkers among masters athletes. Neurotrauma Rep 2024; 5: 74-80.

51. McKee AC, Mez J, Abdolmohammadi B, et al. Neuropathologic and clinical findings in young contact sport athletes exposed to repetitive head impacts. JAMA Neurology 2023; 80: 1037-50.

52. Major BP, McDonald SJ, O’Brien WT, et al. Serum protein biomarker findings reflective of oxidative stress and vascular abnormalities in male, but not female, collision sport athletes. Front Neurol 2020; 11: 549624.