Promoting Growth in Behavioral Neurology: A Path Forward.

Behavioral neurology & neuropsychiatry (BNNP) is a field that seeks to understand brain-behavior relationships, including fundamental brain organization principles and the many ways that brain structures and connectivity can be disrupted, leading to abnormalities of behavior, cognition, emotion, perception, and social cognition. In North America, BNNP has existed as an integrated subspecialty through the United Council for Neurologic Subspecialties since 2006. Nonetheless, the number of behavioral neurologists across academic medical centers and community settings is not keeping pace with increasing clinical and research demand. In this commentary, we provide a brief history of BNNP followed by an outline of the current challenges and opportunities for BNNP from the behavioral neurologist's perspective across clinical, research, and educational spheres. We provide a practical guide for promoting BNNP and addressing the shortage of behavioral neurologists to facilitate the continued growth and development of the subspecialty. We also urge a greater commitment to recruit trainees from diverse backgrounds so as to dismantle persistent obstacles that hinder inclusivity in BNNP-efforts that will further enhance the growth and impact of the subspecialty. With rapidly expanding diagnostic and therapeutic approaches across a range of conditions at the intersection of neurology and psychiatry, BNNP is well positioned to attract new trainees and expand its reach across clinical, research, and educational activities.

Preliminary evidence of transcutaneous vagus nerve stimulation effects on sleep in veterans with post-traumatic stress disorder.

Sleep problems are common among veterans with post-traumatic stress disorder and closely associated with hyperarousal symptoms. Transcutaneous vagus nerve stimulation (tVNS) may have potential to improve sleep quality in veterans with PTSD through effects on brain systems relevant to hyperarousal and sleep-wake regulation. The current pilot study examines the effect of 1 h of tVNS administered at "lights out" on sleep architecture, microstructure, and autonomic activity. Thirteen veterans with PTSD completed two nights of laboratory-based polysomnography during which they received 1 h of either active tVNS (tragus) or sham stimulation (earlobe) at "lights out" with randomised order. Sleep staging and stability metrics were derived from polysomnography data. Autonomic activity during sleep was assessed using the Porges-Bohrer method for calculating respiratory sinus arrhythmia (RSAP-B ). Paired t-tests revealed a small decrease in the total sleep time (d = -0.31), increase in N3 sleep (d = 0.23), and a small-to-moderate decrease in REM sleep (d = -0.48) on nights of active tVNS relative to sham stimulation. tVNS was also associated with a moderate reduction in cyclic alternating pattern (CAP) rate (d = -0.65) and small-to-moderate increase in RSAP-B during NREM sleep. Greater NREM RSAP-B was associated with a reduced CAP rate and NREM alpha power. This pilot study provides preliminary evidence that tVNS may improve sleep depth and stability in veterans with PTSD, as well as increase parasympathetically mediated nocturnal autonomic activity. These results warrant continued investigation into tVNS as a potential tool for treating sleep disturbance in veterans with PTSD.

Effects of sleep disturbance on trauma-focused psychotherapy outcomes in posttraumatic stress disorder: A systematic review.

This study aimed to synthesize existing research on the effects of sleep disturbances on trauma-focused psychotherapy outcomes in adults with posttraumatic stress disorder (PTSD). A systematic review using PubMed, PsycINFO, Embase, Web of Science, and PTSDpubs was performed up to April 2021. Two independent reviewers screened articles for inclusion, performed data extraction, and assessed risk of bias and certainty of the evidence. Narrative synthesis was conducted based on the type of sleep disorder symptom assessed. Sixteen primary studies were included in this review, the majority of which had a high overall risk of bias. Results suggested that sleep disorder symptoms were associated with higher overall PTSD severity across treatment; however, they did not interfere with treatment effectiveness, with the exception of sleep-disordered breathing. Improvements in insomnia, sleep duration, and sleep quality during treatment were associated with greater treatment gains. Certainty of the evidence ranged from low to very low. These results suggest that it may not be necessary to address sleep disorder symptoms prior to initiating trauma-focused psychotherapy. Instead, concurrent treatment of sleep- and trauma-related symptoms may be most beneficial. Continued research is needed to clarify the mechanistic relationship between sleep and treatment outcomes and to guide clinical decision-making.

Distinct cortical and subcortical predictors of Purdue Pegboard decline in Parkinson's disease and atypical parkinsonism.

Objective measures of disease progression are critically needed in research on Parkinson's disease (PD) and atypical Parkinsonism but may be hindered by both practicality and cost. The Purdue Pegboard Test (PPT) is objective, has high test-retest reliability, and has a low cost. The goals of this study were to determine: (1) longitudinal changes in PPT in a multisite cohort of patients with PD, atypical Parkinsonism, and healthy controls; (2) whether PPT performance reflects brain pathology revealed by neuroimaging; (3) quantify kinematic deficits shown by PD patients during PPT. Parkinsonian patients showed a decline in PPT performance that correlated with motor symptom progression, which was not seen in controls. Neuroimaging measures from basal ganglia were significant predictors of PPT performance in PD, whereas cortical, basal ganglia, and cerebellar regions were predictors for atypical Parkinsonism. Accelerometry in a subset of PD patients showed a diminished range of acceleration and irregular patterns of acceleration, which correlated with PPT scores.

A Computable Phenotype for the Identification of Sexual and Gender Minorities in Electronic Health Records.

Sexual gender minorities, including lesbian, gay, and bisexual (LGB) individuals face unique challenges due to discrimination, stigma, and marginalization, which negatively impact their well-being. Electronic health record (EHR) systems present an opportunity for LGB research, but accurately identifying LGB individuals in EHRs is challenging. Our study developed and validated a rule-based computable phenotype (CP) to identify LGB individuals and their subgroups using both structured data and unstructured clinical narratives from a large integrated health system. Validating against a sample of 537 chart-reviewed patients, our three best performing CP algorithms balancing different performance metrics, each achieved sensitivity of 1.000, PPV of 0.982, and F1-score of 0.875 in identifying LGB individuals, respectively. Applying the three best-performing CPs, our study also found that the LGB population is younger and experiences a disproportionate burden of adverse health outcomes, particularly mental health distress.

A consensus on optimization of care in patients with growth hormone deficiency and mild traumatic brain injury.

OBJECTIVE/DESIGN: Approximately 2.9 million children and adults in the US experience traumatic brain injuries (TBIs) annually, most of which are considered mild. TBI can induce varying consequences on pituitary function, with growth hormone deficiency (GHD) among the more commonly reported conditions. Panels of pediatric and adult endocrinologists, neurologists, physical medicine and rehabilitation specialists, and neuropsychologists convened in February and October 2020 to discuss ongoing challenges and provide strategies for detection and optimal management of patients with mild TBI and GHD. RESULTS: Difficulties include a low rate of seeking medical attention in the population, suboptimal screening tools, cost and complexity of GHD testing, and a lack of consensus regarding when to test or retest for GHD. Additionally, referrals to endocrinologists from other specialists are uncommon. Recommendations from the panels for managing such patients included multidisciplinary guidelines on the diagnosis and management of post-TBI GHD and additional education on long-term metabolic and probable cognitive benefits of GH replacement therapy. CONCLUSION: As patients of all ages with mild TBI may develop GHD and/or other pituitary deficiencies, a multidisciplinary approach to provide education to endocrinologists, neurologists, neurosurgeons, traumatologists, and other providers and guidelines for the early identification and management of persistent mild TBI-related GHD are urgently needed.

Neurology Access Clinic: A Model to Improve Access to Neurologic Care in an Academic Medical Center.

Background and Objectives: Delays in access to neurologic care are a major problem. In this pilot program, we aimed to evaluate the effectiveness of a novel staffing model for neurology outpatient clinic within an academic neurology center to increase access to neurologic care, while incorporating such a model into a growing academic neurology department. Methods: We created a new model for provision of access to neurologic care that could be introduced in an academic neurologic department, the access clinic. One attending was assigned to staff the access clinic for 1 week at a time. This was introduced as rotation equal to conventional on-service inpatient rotations. Descriptive analyses were performed to characterize the access clinic's performance characteristics. Comparisons were made to the previously established traditional faculty clinic model. Results: A total of 5,917 access clinic visits were compared with 6,000 traditional clinic visits. Lead time dropped from 142 to 18 days for new patients and from 64 to 0 days for return visits. Although total readmission rates were similar during both clinic periods, readmission through the emergency department was less for access clinic patients. The access clinic resulted in significant improvement in patient satisfaction ratings. The access clinic model was financially profitable. Discussion: Our findings suggest that introducing an access clinic as service rotation for neurology faculty is both effective in offering enhanced access for patients to neurologic care and for patient satisfaction. Future studies may test this model in other centers and should address the effect on provider satisfaction.

Prevalence of Alzheimer's and Related Dementia Diseases and Risk Factors Among Transgender Adults, Florida, 2012‒2020.

Objectives. To estimate the prevalence rates of Alzheimer's disease and related dementias (ADRD) and their risk factors in the transgender population and compare the rates to those in cisgender adults. Methods. We identified 1784 transgender adults in the linked electronic health records and claims data between 2012 and 2020 from the OneFlorida Clinical Research Consortium. We calculated the prevalence of ADRD and ADRD risk factors for the transgender and matched cisgender control adults. Results. The prevalence of ADRD was higher in the transgender adults compared with the cisgender control adults. Overall, the prevalence of ADRD risk factors was significantly higher in the transgender adults than the cisgender controls for 11 out of the 13 risk factors, with the only exceptions being traumatic brain injury and visual impairment. Conclusions. Transgender adults are at significantly higher risk for ADRD than cisgender adults. Our study highlights the urgent need for more research on the unique ADRD risks among the aging transgender and larger sexual- and gender-minority populations. (Am J Public Health. 2022;112(5):754-757. https://doi.org/10.2105/AJPH.2022.306720).

Impacts of Eligibility Criteria on Trial Participants' Age in Alzheimer's Disease Clinical Trials.

Overly restricted and poorly designed eligibility criteria reduce the generalizability of the results from clinical trials. We conducted a study to identify and quantify the impacts of study traits extracted from eligibility criteria on the age of study populations in Alzheimer's Disease (AD) clinical trials. Using machine learning methods and SHapley Additive exPlanation (SHAP) values, we identified 30 and 34 study traits that excluded older patients from AD trials in our 2 generated target populations respectively. We also found that study traits had different magnitudes of impacts on the age distributions of the generated study populations across racial-ethnic groups. To our best knowledge, this was the first study that quantified the impact of eligibility criteria on the age of AD trial participants. Our research is a first step in addressing the overly restrictive eligibility criteria in AD clinical trials.

Behavioral and Cognitive Aspects of Concussion.

PURPOSE OF REVIEW: This review provides the reader with an overview of concussion and mild traumatic brain injury (TBI). Key aspects of the pathophysiology, signs, and symptoms, treatment and rehabilitation, and recovery from concussion/mild TBI are reviewed with an emphasis on the variety of factors that may contribute to cognitive concerns following injury. RECENT FINDINGS: Concussion remains a clinical diagnosis based on symptoms that occur in the immediate aftermath of an applied force and in the hours, days, and weeks thereafter. Although advances have been made in advanced diagnostics, including neuroimaging and fluid biomarkers in hopes of developing objective indicators of injury, such markers currently lack sufficient specificity to be used in clinical diagnostics. The symptoms of concussion are heterogeneous and may be seen to form subtypes, each of which suggests a targeted rehabilitation by the interdisciplinary team. Although the majority of patients with concussion recover within the first 30 to 90 days after injury, some have persistent disabling symptoms. The concept of postconcussion syndrome, implying a chronic syndrome of injury-specific symptoms, is replaced by a broader concept of persistent symptoms after concussion. This concept emphasizes the fact that most persistent symptoms have their basis in complex somatic, cognitive, psychiatric, and psychosocial factors related to risk and resilience. This framework leads to the important conclusion that concussion is a treatable injury from which nearly all patients can be expected to recover. SUMMARY: Concussion/mild TBI is a significant public health problem in civilian, military, and organized athletic settings. Recent advances have led to a better understanding of underlying pathophysiology and symptom presentation and efficacious treatment and rehabilitation of the resulting symptoms. An interdisciplinary team is well-positioned to provide problem-oriented, integrated care to facilitate recovery and to advance the evidence base supporting effective practice in diagnosis, treatment, and prevention.

Posttraumatic Stress Disorder and Anxiety-Related Conditions.

PURPOSE OF REVIEW: This article provides a synopsis of current assessment and treatment considerations for posttraumatic stress disorder (PTSD) and related anxiety disorder characteristics. Epidemiologic and neurobiological data are reviewed as well as common associated symptoms, including sleep disruption, and treatment approaches to these conditions. RECENT FINDINGS: PTSD is no longer considered an anxiety-related disorder in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition classification and instead is associated with trauma/stressor-related disorders. PTSD symptoms are clustered into four domains including intrusive experiences, avoidance, mood, and arousal symptoms. Despite this reclassification, similarities exist in consideration of diagnosis, treatment, and comorbidities with anxiety disorders. PTSD and anxiety-related disorders are heterogeneous, which is reflected by the neural circuits involved in the genesis of symptoms that may vary across symptom domains. Treatment is likely to benefit from consideration of this heterogeneity.Research in animal models of fear and anxiety, as well as in humans, suggests that patients with PTSD and generalized anxiety disorder have difficulty accurately determining safety from danger and struggle to suppress fear in the presence of safety cues.Empirically supported psychotherapies commonly involved exposure (fear extinction learning) and are recommended for PTSD. Cognitive-behavioral therapy has been shown to be effective in other anxiety-related disorders. Selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) are commonly used in the treatment of PTSD and anxiety disorders in which pharmacologic intervention is supported. Treating sleep disruption including sleep apnea (continuous positive airway pressure [CPAP]), nightmares, and insomnia (preferably via psychotherapy) may improve symptoms of PTSD, as well as improve mood in anxiety disorders. SUMMARY: PTSD has a lifetime prevalence that is close to 10% and shares neurobiological features with anxiety disorders. Anxiety disorders are the most common class of mental conditions and are highly comorbid with other disorders; treatment considerations typically include cognitive-behavioral therapy and pharmacologic intervention. Developing technologies show some promise as treatment alternatives in the future.

Making a Difference: Affective Distress Explains Discrepancy Between Objective and Subjective Cognitive Functioning After Mild Traumatic Brain Injury.

OBJECTIVE: To assess the relationship between subjective cognitive symptoms and objective cognitive test scores in patients after concussion. We additionally examined factors associated with subjective and objective cognitive dysfunction, as well as their discrepancy. PARTICIPANTS: Eighty-six individuals (65.1% female; 74.4% adult) from an interdisciplinary concussion clinic. METHODS: Subjective and objective cognitive functioning was measured via the SCAT-Symptom Evaluation and the CNS Vital Signs Neurocognition Index (NCI), respectively. Cognitive discrepancy scores were derived by calculating standardized residuals (via linear regression) using subjective symptoms as the outcome and NCI score as the predictor. Hierarchical regression assessed predictors (age, education, time postinjury, attention-deficit/hyperactivity disorder, affective distress, and sleep disturbance) of cognitive discrepancy scores. Nonparametric analyses evaluated relationships between predictor variables, subjective symptoms, and NCI. RESULTS: More severe affective and sleep symptoms (large and medium effects), less time postinjury (small effect), and older age (small effect) were associated with higher subjective cognitive symptoms. Higher levels of affective distress and less time since injury were associated with higher cognitive discrepancy scores (ß = .723, P < .001; ß = -.204, P < .05, respectively). CONCLUSION: Clinical interpretation of subjective cognitive dysfunction should consider these additional variables. Evaluation of affective distress is warranted in the context of higher subjective cognitive complaints than objective test performance.

Impact of a Sleep Enhancement Protocol on Nighttime Room Entries in an Inpatient Rehabilitation Facility.

PURPOSE: This study examined whether a sleep enhancement protocol (SEP) could reduce nighttime room entries (NREs) for patients with orthopedic injury (OI) or acquired brain injury (ABI) in an inpatient rehabilitation facility. DESIGN: A two-wave prospective study assessing standard of care (SOC) versus SEP. METHODS: Sixty-five participants completed baseline and follow-up questionnaires and wore an actigraph for approximately 7 days. In the SEP, nighttime care was "bundled." FINDINGS: In SOC, NREs were associated with less efficient sleep and greater daytime fatigue. Nighttime room entries were approximately 50% lower in the SEP than SOC. Participants in the OI SOC had more room entries than any other group. There were no significant changes in room entries in the ABI SEP group. CONCLUSIONS: There was a relationship between NREs and sleep. The SEP was effective at reducing NREs for patients with OI, but not ABI. CLINICAL RELEVANCE: Sleep enhancement protocols in inpatient rehabilitation facilities may be effective at improving sleep. Future research may focus on developing individualized protocols to improve sleep across patients with a variety of presenting diagnoses.

Acute Effects of Sport-Related Concussion on Serum Glial Fibrillary Acidic Protein, Ubiquitin C-Terminal Hydrolase L1, Total Tau, and Neurofilament Light Measured by a Multiplex Assay.

We prospectively evaluated serum concentrations of glial fibrillary acidic protein (GFAP), ubiquitin c-terminal hydrolase L1 (UCH-L1), total tau (T-Tau), and neurofilament light (NF-L) from collegiate athletes at baseline and acutely after sport-related concussion (SRC) using the Quanterix Neurology 4Plex "B" (N4PB) multiplex assay. Uninjured controls were matched on age, sex, race, sport, and concussion history. Clinical outcomes included acute symptom severity, balance, rapid automated naming, computerized cognitive testing, and recovery duration. Baseline (n = 110; median [interquartile range] age = 19 [18-20] years, 54% male, 61% white/Caucasian) and post-SRC (n = 36; median [interquartile range] age = 19 [18-20] years, 50% male, 61% white/Caucasian) blood samples were analyzed. We observed post-SRC elevations from baseline for GFAP (p = 0.001, d = 1.7), T-Tau (p = 0.004, d = 1.3), and NF-L (p = 0.010, d = 1.1). GFAP (area under the curve [AUC] = 0.958, 95% confidence interval [CI] 0.927-0.989, p < 0.001) and NF-L (AUC = 0.904, 95% CI 0.851-0.957, p < 0.001) accurately discriminated SRC from control cases. There were no associations between biomarker concentrations and clinical measurements post-SRC or recovery duration. These findings suggest that, using the multiplex assay, GFAP, T-Tau, and NF-L elevate from baseline acutely after SRC, and both GFAP and NF-L excellently distinguished concussed from control cases. Serum biomarker changes do not necessarily correspond with clinical measurements or recovery duration.

King-Devick Test Time Varies by Testing Modality.

OBJECTIVE: To explore differences in baseline King-Devick Test (KD) completion time between 2 testing modalities: (1) spiral-bound paper cards (cards) and (2) iPad application (iPad). DESIGN: Cross-sectional cohort analysis. SETTING: National Collegiate Athlete Association (NCAA) institutions. PARTICIPANTS: Student athletes from 13 women's and 11 men's collegiate sports who completed KD baseline testing as part of their first year in the Concussion Assessment, Research and Education (CARE) Consortium from 2014 to 2016 (n = 2003, 52.2% male). INDEPENDENT VARIABLES: King-Devick Test modalities; cards or iPad. MAIN OUTCOME MEASURE: Baseline KD completion time (seconds). RESULTS: Mean baseline KD completion time of the iPad modality group [42.8 seconds, 95% confidence interval (CI), 42.1-43.3] was 2.8 seconds (95% CI, 2.1-3.4) greater than the cards group (40.0 seconds, 95% CI, 39.7-40.3) (t(1, 1010.7) = -8.0, P < 0.001, Cohen's d = 0.41). CONCLUSIONS: Baseline KD performance is slower when tested on an iPad than when tested on spiral-bound paper cards. The 2 KD modalities should not be used interchangeably in concussion assessments because differences in the modalities can lead to time differences similar in magnitude to those used to indicate concussion. From a research perspective, modality may influence interpretation and/or synthesis of findings across studies.

Predicting long-term cognitive and neuropathological consequences of moderate to severe traumatic brain injury: Review and theoretical framework.

Prognostic modeling in moderate to severe traumatic brain injury (TBI) has historically focused primarily on the projection of crude outcomes such as the risk of mortality and disability. Initial work in this area has perpetuated the notion that prognosis after moderate to severe TBI can be measured as a single, static, and dichotomous outcome. However, more recent conceptualizations describe moderate to severe TBI as the initiation of a chronic disease state with high levels of inter-individual variability in terms of symptom manifestation and disease progression. Unfortunately, existing prognostic models provide limited insight into the extent of chronic cognitive and neurodegenerative changes experienced by moderate to severe TBI survivors. Though prior research has identified a variety of acute factors that appear to influence post-injury cognitive and neuropathological outcomes, an empirically supported framework for prognostic modeling of these injury-distal outcomes does not exist. The current review considers the literature on an expanded array of empirically supported predictors (both premorbid and injury-related) in association with long-term sequelae of moderate to severe TBI. We also provide a theoretical framework and statistical approach for prognostic modeling in moderate to severe TBI in order to unify efforts across research groups and facilitate important progress in this research area.

Exploratory study of sport-related concussion effects on peripheral micro-RNA expression.

OBJECTIVE: Explore changes in micro-RNA (miRNA) expression in blood after sport-related concussion (SRC) in collegiate athletes. METHODS: Twenty-seven collegiate athletes (~41% male, ~75% white, age 18.8 ± 0.8 years) provided both baseline and post-SRC blood samples. Serum was analyzed for expression of miR-153-3p (n = 27), miR-223-3p (n = 23), miR-26a-5p (n = 26), miR-423-3p (n = 23), and miR-let-7a-5p (n = 23) at both time points via quantitative polymerase chain reaction (qPCR). Nonparametric analyses were used to compare miRNA expression changes between baseline and SRC and to evaluate associations with clinical outcomes (symptom severity, cognition, balance, and oculomotor function, and clinical recovery time). RESULTS: Participants manifested a significant increase in miRNA expression following SRC for miR153-3p (Z = -2.180, p = .029, 59% of the participants increased post-SRC), miR223-3p (Z = -1.998, p = .046, 70% increased), and miR-let-7a-5p (Z = -2.190, p = .029, 65% increased). There were no statistically significant associations between changes in miRNA expression and clinical test scores, acute symptom severity, or clinical recovery time. CONCLUSION: MiR-153-3p, miR-223-3p, and miR-let-7a-5p were significantly upregulated acutely following SRC in male and female collegiate athletes compared to baseline levels, though several athletes demonstrated no change or a decrease in expression. The biological mechanisms and functional implications of the increased expression of these circulating miRNA are unclear and require more research, as does their relevance to clinical outcomes.

Drill-Specific Head Impacts in Collegiate Football Practice: Implications for Reducing "Friendly Fire" Exposure.

This study investigated drill-specific head impact biomechanics in a Division 1 collegiate football team using the Head Impact Telemetry System (HITS). A total of 32,083 impacts were recorded across 2 years of practices. Precise tracking of instrumented athletes, head impacts, and drill participation allowed quantification of hits sustained per person per minute (H/P/M) for each specific drill. We found significant H/P/M variability between 14 drills and player position, ranging from 0.02 to 0.41 H/P/M for Linemen and 0.01 to 0.15 H/P/M for Non-Linemen. Impact magnitude data are also reported for practice term (Spring, Training Camp, In-Season) and dress-type (Helmets Only, Spyders, Shells, Full Pads). Recommendations for shortening high-risk drills, based on H/P/M drill impact frequencies, suggest possible "friendly fire" reductions of 1000 impacts for Linemen and 300 impacts for Non-Linemen over their collegiate career. Over 80% of potentially avoidable head impacts were attributable to just three drills-"Team Run," "Move the Field," and "Team." Recommending drill-specific modifications based on practical considerations (the drill's impact frequency, dress-types when performing the drill, and duration) could improve acceptance from coaches and efficiently reduce head impact exposure without drastically altering overall practice structure.

Concussion BASICS II: Baseline serum biomarkers, head impact exposure, and clinical measures.

OBJECTIVE: To examine the effect of concussion history and cumulative exposure to collision sports on baseline serum biomarker concentrations, as well as associations between biomarker concentrations and clinical assessments. METHODS: In this observational cohort study, ß-amyloid peptide 42 (Aß42), total tau, S100 calcium binding protein B (S100B), ubiquitin carboxy-terminal hydrolyzing enzyme L1 (UCH-L1), glial fibrillary acidic protein, microtubule associated protein 2, and 2',3'-cyclic-nucleotide 3'-phosphodiesterase serum concentrations were measured in 415 (61% male, 40% white, aged 19.0 ± 1.2 years) nonconcussed collegiate athletes without recent exposure to head impacts. Regression analyses were used to evaluate the relationship between self-reported history of concussion(s), cumulative years playing collision sports, clinical assessments, and baseline biomarker concentrations. Football-specific analyses were performed using a modified Cumulative Head Impact Index. Clinical assessments included symptom, cognitive, balance, and oculomotor tests. RESULTS: Athletes with a greater number of concussions had a higher baseline Aß42 concentration only (ρ = 0.140, p = 0.005, small effect size). No biomarker concentrations correlated with cumulative exposure to collision sports. Race status fully mediated the correlations of S100B, UCH-L1, and Aß42 with cognitive scores. Football exposure, specifically, was not associated with serum biomarker concentrations or clinical assessment scores based on the modified Cumulative Head Impact Index. CONCLUSION: Concussion-related serum biomarkers showed no consistent association with concussion history, cumulative exposure to collision sports, or clinical assessments in a sample of healthy collegiate athletes. Serum Aß42 concentrations could increase following multiple previous concussions. Considering race status is essential when investigating links between biomarkers and cognition. The biomarkers studied may not detect residual effects of concussion or repetitive head impact exposure in otherwise asymptomatic collegiate athletes without recent exposure to head impacts. Much more research is needed for identifying reliable and valid blood biomarkers of brain trauma history.