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The objective of this study was to examine associations of lifetime concussion history (CHx) and an advanced metric of lifetime repetitive head impact exposure with resting-state functional connectivity (rsFC) across the whole-brain and among large-scale functional networks (Default Mode; Dorsal Attention; and Frontoparietal Control) in former collegiate football players. Individuals who completed at least one year of varsity collegiate football were eligible to participate in this observational cohort study ( n = 48; aged 36–41 years; 79.2% white/Caucasian; 12.5±4.4 years of football played; all men). Individuals were excluded if they reported history/suspicion of psychotic disorder with active symptoms, contraindications to participation in study procedures (e.g., MRI safety concern), or inability to travel. Each participant provided concussion and football playing histories. Self-reported concussion history was analyzed in two different ways based on prior research: dichotomous “High” (≥3 concussions; n = 28) versus “Low” (<3 concussions; n = 20); and four ordinal categories (0–1 concussion [ n = 19]; 2–4 concussions [ n = 8]; 5–7 concussions [ n = 9]; and ≥8 concussions [ n = 12]). The Head Impact Exposure Estimate (HIEE) was calculated from football playing history captured via structured interview. Resting-state fMRI and T1-weighted MRI were acquired and preprocessed using established pipelines. Next, rsFC was calculated using the Seitzman et al., (2020) 300-ROI functional atlas. Whole-brain, within-network, and between-network rsFC were calculated using all ROIs and network-specific ROIs, respectively. Effects of CHx and HIEE on rsFC values were examined using separate multivariable linear regression models, with a-priori α set to 0.05. We observed no statistically significant associations between rsFC outcomes and either CHx or HIEE ( p s ≥ .12). Neither CHx nor HIEE were associated with neural signatures that have been observed in studies of typical and pathological aging. While CHx and repetitive head impacts have been associated with changes in brain health in older former athletes, our preliminary results suggest that associations with rsFC may not be present in early midlife former football players.

Purpose of ReviewSport-related concussion (SRC) and mild traumatic brain injury (mTBI) have been thrust into the national spotlight, with youth athletes bearing the burden of this public health problem. The current review aims to provide a practical summary of pediatric SRC, including key terminology, return to play/school, and risk factors for post-concussion syndrome (PCS).Recent FindingsWhile the majority of youth athletes recover within 2 to 4 weeks, approximately 10% of athletes experience a protracted recovery with symptoms lasting months, impacting social, scholastic, and sporting activities.SummaryIn the pediatric population, the strongest predictors of PCS are initial symptom burden and prior concussion, with mixed results behind the factors of gender, headaches, and learning disability. The role of psychiatric, family history, sports, and socioeconomic factors remain in their infancy.

This study examined the relationship between patient performance on multiple memory measures and regional brain volumes using an FDA-cleared quantitative volumetric analysis program - Neuroreader™. Ninety-two patients diagnosed with mild cognitive impairment (MCI) by a clinical neuropsychologist completed cognitive evaluations and underwent MR Neuroreader™ within 1 year of testing. Select brain regions were correlated with three widely used memory tests. Regression analyses were conducted to determine if using more than one memory measures would better predict hippocampal z-scores and to explore the added value of recognition memory to prediction models. Memory performances were most strongly correlated with hippocampal volumes than other brain regions. After controlling for encoding/Immediate Recall standard scores, statistically significant correlations emerged between Delayed Recall and hippocampal volumes (rs ranging from .348 to .490). Regression analysis revealed that evaluating memory performance across multiple memory measures is a better predictor of hippocampal volume than individual memory performances. Recognition memory did not add further predictive utility to regression analyses. This study provides support for use of MR Neuroreader™ hippocampal volumes as a clinically informative biomarker associated with memory performance, which is a critical diagnostic feature of MCI phenotype.

ObjectiveDetermine the role of fluid-based biomarkers, advanced neuroimaging, genetic testing and emerging technologies in defining and assessing neurobiological recovery after sport-related concussion (SRC).DesignSystematic review.Data sourcesSearches of seven databases from 1 January 2001 through 24 March 2022 using keywords and index terms relevant to concussion, sports and neurobiological recovery. Separate reviews were conducted for studies involving neuroimaging, fluid biomarkers, genetic testing and emerging technologies. A standardised method and data extraction tool was used to document the study design, population, methodology and results. Reviewers also rated the risk of bias and quality of each study.Eligibility criteria for selecting studiesStudies were included if they: (1) were published in English; (2) represented original research; (3) involved human research; (4) pertained only to SRC; (5) included data involving neuroimaging (including electrophysiological testing), fluid biomarkers or genetic testing or other advanced technologies used to assess neurobiological recovery after SRC; (6) had a minimum of one data collection point within 6 months post-SRC; and (7) contained a minimum sample size of 10 participants.ResultsA total of 205 studies met inclusion criteria, including 81 neuroimaging, 50 fluid biomarkers, 5 genetic testing, 73 advanced technologies studies (4 studies overlapped two separate domains). Numerous studies have demonstrated the ability of neuroimaging and fluid-based biomarkers to detect the acute effects of concussion and to track neurobiological recovery after injury. Recent studies have also reported on the diagnostic and prognostic performance of emerging technologies in the assessment of SRC. In sum, the available evidence reinforces the theory that physiological recovery may persist beyond clinical recovery after SRC. The potential role of genetic testing remains unclear based on limited research.ConclusionsAdvanced neuroimaging, fluid-based biomarkers, genetic testing and emerging technologies are valuable research tools for the study of SRC, but there is not sufficient evidence to recommend their use in clinical practice.PROSPERO registration numberCRD42020164558.

ObjectivesTo systematically review the scientific literature regarding the acute assessment of sport-related concussion (SRC) and provide recommendations for improving the Sport Concussion Assessment Tool (SCAT6).Data sourcesSystematic searches of seven databases from 2001 to 2022 using key words and controlled vocabulary relevant to concussion, sports, SCAT, and acute evaluation.Eligibility criteria(1) Original research articles, cohort studies, case–control studies, and case series with a sample of >10; (2) ≥80% SRC; and (3) studies using a screening tool/technology to assess SRC acutely (<7 days), and/or studies containing psychometric/normative data for common tools used to assess SRC.Data extractionSeparate reviews were conducted involving six subdomains: Cognition, Balance/Postural Stability, Oculomotor/Cervical/Vestibular, Emerging Technologies, and Neurological Examination/Autonomic Dysfunction. Paediatric/Child studies were included in each subdomain. Risk of Bias and study quality were rated by coauthors using a modified SIGN (Scottish Intercollegiate Guidelines Network) tool.ResultsOut of 12 192 articles screened, 612 were included (189 normative data and 423 SRC assessment studies). Of these, 183 focused on cognition, 126 balance/postural stability, 76 oculomotor/cervical/vestibular, 142 emerging technologies, 13 neurological examination/autonomic dysfunction, and 23 paediatric/child SCAT. The SCAT discriminates between concussed and non-concussed athletes within 72 hours of injury with diminishing utility up to 7 days post injury. Ceiling effects were apparent on the 5-word list learning and concentration subtests. More challenging tests, including the 10-word list, were recommended. Test–retest data revealed limitations in temporal stability. Studies primarily originated in North America with scant data on children.ConclusionSupport exists for using the SCAT within the acute phase of injury. Maximal utility occurs within the first 72 hours and then diminishes up to 7 days after injury. The SCAT has limited utility as a return to play tool beyond 7 days. Empirical data are limited in pre-adolescents, women, sport type, geographical and culturally diverse populations and para athletes.PROSPERO registration numberCRD42020154787.

[...]some have maintained that we must not only consider those cases that are considered ‘false positives’ (i.e., those who believe they have CTE, but in reality do not), but also the possible ‘false negatives’ (i.e., those who do not believe they have CTE, but may in fact do) (14). [...]efforts have been made to pass legislation that bans youth tackle football (16). Based on this notion, our commentary aims to: 1)summarize the concerns related to reduced team sport participation and declining physical activity in our youth; 2)describe the benefits of team sports; and 3)offer recommendations regarding team sport participation that address both concerns over long-term adverse neurologic outcomes and our collective role to ensure safe sport settings. Given that children’s confidence and self-esteem have been associated with their decision to participate in physical activity/sport (49), limiting sport options may result in decreased participation (34). [...]it is important that as we argue for the benefits of team sport participation, we acknowledge the potential limitations in its availability and advocate for the equitable creation of a variety of team sport opportunities for boys and girls.

The susceptibility of athletes to long‐term adverse outcomes following recurrent concussion remains controversial. Acute concussion precipitates a transient reduction in cerebral blood flow (CBF) that typically returns to pre‐injury levels. Recent work suggests that long‐term CBF alterations may be sex‐specific. We assessed whether concussion history was associated with chronic CBF alterations and whether sex moderated this relationship in otherwise healthy, active collegiate‐aged athletes. Collegiate‐aged athletes from the community (N = 204, 37.8% female, Mage = 21.0 ± 1.7) underwent magnetic resonance imaging with pseudo‐continuous arterial spin labeling to quantify global and regional CBF and spatial coefficient of variation. Participants also completed measures of depression, anxiety, and cognition. Multiple linear regressions incorporating prior concussion‐by‐sex interaction terms adjusted for relevant covariates were fit to estimate the extent to which sex moderated the concussion history—CBF relationship. Exploratory analyses further assessed whether oral contraceptive use or pill formulation moderated this association in females. The number of prior concussions was negatively associated with global and regional gray‐matter CBF in female but not male athletes, with the strongest associations localizing to frontotemporal regions. CBF metrics were not related to cognitive performance or affective symptom burden. Contraceptive use did not appear to substantially moderate the concussion history—CBF association in female athletes. Female‐specific associations between concussion history and cerebral hypoperfusion in early adulthood suggest potential sex differences in pathways and trajectories of adverse long‐term outcomes. Early chronic CBF alterations may represent one vulnerability to future risk in a sex‐specific manner. Summary Among collegiate‐aged female athletes, the cumulative number of concussions was associated with global and frontotemporal hypoperfusion beyond the acute phase of injury. These associations were independent of key demographic and clinical covariates and were not associated with differences in cognitive performance, current affective symptom burden, nor oral contraceptive use. Future work is warranted to elucidate whether sustained perturbations in cerebral blood flow interact with other comorbidities to shape long‐term trajectories of clinical outcomes. In a sample of healthy collegiate‐aged athletes, we observed that greater lifetime concussion history was associated with global and frontotemporal hypoperfusion, an effect seen exclusively in female athletes. These findings suggest a potentially modifiable, sex‐specific marker that could support earlier detection and intervention in concussion‐related disease processes later in life.

ObjectiveThis study investigated the longitudinal course of depressive symptom severity over 19 years in former American football players and the influence of concussion history, contact sport participation and physical function on observed trajectories.MethodsFormer American football players completed a general health questionnaire involving demographic information, medical/psychiatric history, concussion/football history and validated measures of depression and physical function at three time points (2001, 2010 and 2019). Parallel process latent growth curve modelling tested associations between concussion history, years of football participation, and overall and change in physical function on the overall level and trajectory of depressive symptoms.ResultsAmong the 333 participants (mean(SD) age, 48.95 (9.37) at enrolment), there was a statistically significant, but small increase in depressive symptom severity from 2001 (48.34 (7.75)) to 2019 (49.77 (9.52)), slope=0.079 (SE=0.11), p=0.007. Those with greater concussion history endorsed greater overall depressive symptom severity, B=1.38 (SE=0.33), p<0.001. Concussion history, B<0.001 (SE=0.02), p=0.997 and years of participation, B<0.001 (SE=0.01), p=0.980, were not associated with rate of change (slope factor) over 19 years. Greater decline in physical function, B=−0.71 (SE=0.16), p<0.001, was predictive of a faster growth rate (ie, steeper increase) of depression symptom endorsement over time.ConclusionsConcussion history, not years of participation, was associated with greater depressive symptom severity. Neither factor was predictive of changes over a 19-year period. Decline in physical function was a significant predictor of a steeper trajectory of increased depressive symptoms, independent of concussion effects. This represents one viable target for preventative intervention to mitigate long-term neuropsychiatric difficulties associated with concussion across subsequent decades of life.

Background Potential links between a history of sport-related concussions and later-life neurobiological and psychological brain health have been studied in former collision-sport athletes. However, empirical studies of how former athletes perceive the future of their brain health as a result of these injuries are missing. Objectives We aimed to (1) identify the extent to which former National Football League players currently have concerns about their long-term psychological and cognitive functioning as a result of concussions sustained while playing football; (2) examine whether current concerns are different than concerns they had while playing football; (3) examine the relationship between current brain health concerns and self-reported concussion history (SR-CHx); and (4) explore other important factors associated with these concerns. Methods In this cross-sectional study, former National Football League players with a SR-CHx of one or more concussions ( n  = 1514; aged mean [standard deviation] = 52.3 [15.7] years) completed a general health questionnaire. Participants reported their lifetime concussion history, as well as both their current concerns and concerns while playing football (i.e., retrospective concerns) regarding the long-term effects of concussions on their memory, thinking skills, and risk of developing chronic traumatic encephalopathy. Current and retrospective concerns were self-reported on a five-point Likert scale. Four concussion history categories were created based on SR-CHx: 1–2 ( n  = 309); 3–5 ( n  = 413); 6–9 ( n  = 356); and 10 + ( n  = 436) lifetime concussions. Proportions of participants reporting each level of current and retrospective concerns were examined to identify whether concerns presently exist in these former players, and whether their current concerns are different than retrospective concerns. Next, we explored associations between current concerns and SR-CHx. Results More than one-third of participants reported being currently “extremely concerned” about memory problems (36.9%), thinking skills (37.8%), and developing chronic traumatic encephalopathy (39.5%). In contrast, when asked about concerns while playing, most reported being “not at all concerned” regarding memory = 61.2%, thinking skills = 56.1%, and developing chronic traumatic encephalopathy = 71.2%. Of those who retrospectively endorsed being “not at all” or “slightly” concerned regarding memory ( n  = 1159/1514), thinking skills ( n  = 1080/1514), and developing chronic traumatic encephalopathy ( n  = 1219/1514), approximately half reported being currently “moderately” or “extremely” concerned about those same issues ( n  = 586/1159; n  = 534/1080; n  = 619/1219, respectively). Current concerns regarding memory ( χ 2 16  = 316.61; p  < 0.001; V  = 0.264), thinking skills ( χ 2 16  = 333.17; p  < 0.001; V  = 0.271), and developing chronic traumatic encephalopathy ( χ 2 16  = 280.85; p  < 0.001; V  = 0.249) were significantly related to SR-CHx, with more concussions being associated with greater current concerns. Conclusions Former National Football League players reported significant concerns regarding the potential effects of their prior concussions on long-term brain health, and these concerns are more prevalent now than when they were playing football. Cognitive and mental health concerns are readily identifiable targets for clinical intervention. Clinicians working with former players may wish to explore the extent to which individual players experience these concerns, the nature and depth of these concerns, and the impact of these concerns on the player’s functioning and well-being.