Browsing by Author "Pasquina, Paul F."
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Item Age of First Concussion and Cognitive, Psychological, and Physical Outcomes in NCAA Collegiate Student Athletes(Springer, 2022-11) Moody, Jena N.; Hayes, Jasmeet P.; Buckley, Thomas A.; Schmidt, Julianne D.; Broglio, Steven P.; McAllister, Thomas W.; McCrea, Michael; Pasquina, Paul F.; Caccese, Jaclyn B.; CARE Consortium Investigators; Psychiatry, School of MedicineObjective: Concussions are common among youth athletes and could disrupt critical neurodevelopment. This study examined the association between age of first concussion (AFC) and neurocognitive performance, psychological distress, postural stability, and symptoms commonly associated with concussion in healthy collegiate men and women student athletes. Methods: Participants included 4267 collegiate athletes from various contact, limited-contact, and non-contact sports (1818 women and 2449 men) who completed baseline assessments as part of the Concussion Assessment, Research and Education (CARE) Consortium. Psychological distress was assessed with the Brief Symptom Inventory 18; neurocognitive performance was assessed with the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT); symptoms commonly associated with concussion were assessed with the ImPACT Post-Concussion Symptom Scale; postural stability was assessed with the Balance Error Scoring System. Generalized linear models were used to examine the effects of AFC on clinical outcomes separately in men and women. Results: Later AFC was associated with lower global (Exp(B) = 0.96, P = 0.001) and somatic (Exp(B) = 0.96, P = 0.002) psychological distress on the Brief Symptom Inventory 18 and faster ImPACT reaction time (B = - 0.003, P = 0.001) in women. AFC was not associated with any clinical outcomes in men. Conclusion: Younger AFC was associated with some differences in psychological distress and reaction time among women but not men; however, these results are likely not clinically meaningful. Sociodemographic disparities, pre-existing conditions, and sport type may impact clinical and cognitive outcomes in collegiate athletes more than concussion history. Future work should examine the relationship between AFC and lifespan-related outcomes.Item Age of First Concussion and Cognitive, Psychological, and Physical Outcomes in NCAA Collegiate Student Athletes(Springer, 2022) Moody, Jena N.; Hayes, Jasmeet P.; Buckley, Thomas A.; Schmidt, Julianne D.; Broglio, Steven P.; McAllister, Thomas W.; McCrea, Michael; Pasquina, Paul F.; Caccese, Jaclyn B.; Psychiatry, School of MedicineObjective: Concussions are common among youth athletes and could disrupt critical neurodevelopment. This study examined the association between age of first concussion (AFC) and neurocognitive performance, psychological distress, postural stability, and symptoms commonly associated with concussion in healthy collegiate men and women student athletes. Methods: Participants included 4267 collegiate athletes from various contact, limited-contact, and non-contact sports (1818 women and 2449 men) who completed baseline assessments as part of the Concussion Assessment, Research and Education (CARE) Consortium. Psychological distress was assessed with the Brief Symptom Inventory 18; neurocognitive performance was assessed with the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT); symptoms commonly associated with concussion were assessed with the ImPACT Post-Concussion Symptom Scale; postural stability was assessed with the Balance Error Scoring System. Generalized linear models were used to examine the effects of AFC on clinical outcomes separately in men and women. Results: Later AFC was associated with lower global (Exp(B) = 0.96, P = 0.001) and somatic (Exp(B) = 0.96, P = 0.002) psychological distress on the Brief Symptom Inventory 18 and faster ImPACT reaction time (B = - 0.003, P = 0.001) in women. AFC was not associated with any clinical outcomes in men. Conclusion: Younger AFC was associated with some differences in psychological distress and reaction time among women but not men; however, these results are likely not clinically meaningful. Sociodemographic disparities, pre-existing conditions, and sport type may impact clinical and cognitive outcomes in collegiate athletes more than concussion history. Future work should examine the relationship between AFC and lifespan-related outcomes.Item Association of Alzheimer’s disease polygenic risk score with concussion severity and recovery metrics(Wiley, 2025-01-09) Dybing, Kaitlyn M.; McAllister, Thomas W.; Wu, Yu-Chien; McDonald, Brenna C.; McCrea, Michael A.; Broglio, Steven P.; Pasquina, Paul F.; Brooks, M. Alison; Mihalik, Jason P.; Guskiewicz, Kevin M.; Giza, Christopher C.; Goldman, Joshua; Duma, Stefan; Rowson, Steve; Svoboda, Steven; Cameron, Kenneth L.; Houston, Megan N.; Campbell, Darren E.; McGinty, Gerald; Jackson, Jonathan; Risacher, Shannon L.; Saykin, Andrew J.; Nudelman, Kelly N.; Radiology and Imaging Sciences, School of MedicineBackground: Shared genetic risk between Alzheimer’s disease (AD) and concussion may help explain the association between concussion and elevated risk for dementia. However, there has been little investigation into whether AD risk genes also associate with concussion severity/recovery, and the limited findings are mixed. We used AD polygenic risk scores (PRS) and APOE genotypes to investigate associations between AD genetic risk and concussion severity/recovery in the NCAA‐DoD Grand Alliance CARE Consortium (CARE) dataset. Method: There were 1,917 injuries in the dataset upon project initiation. After removing repeated injuries, related participants, and those without genetic/outcome data, we had 931 participants. Outcomes were number of days to return to play (RTP) as a recovery measure, and four severity measures (scores on SAC and BESS, SCAT symptom severity and total number of symptoms). We calculated PRS using a published score (de Rojas et al., 2021) and performed a linear regression (MLR) of RTP by PRS in normal (<24 days) and long (>24 days) RTP subgroups. We then compared severity measures by PRS using MLR. Next, we used t‐tests to examine outcomes by APOE genotype in military and civilian subgroups. We also performed chi‐squared tests of RTP category (normal vs. long) by APOE genotype. Finally, we analyzed outcomes by PRS in European or African genetic ancestry subgroups using MLR. Result: Higher PRS was associated with longer injury to RTP interval in the normal RTP (<24 days) subgroup (estimate = 0.0412, SE = 0.182, p = 0.0237). 1 SD increase in PRS resulted in a 0.412 day (9.89 hours) increase to the interval. This may be clinically meaningful in the collegiate athlete environment. We did not identify any other significant differences. Conclusion: Our preliminary results provide limited evidence for an impact of AD PRS on concussion recovery, though the pattern was inconsistent and its clinical significance is uncertain. Future studies should attempt to replicate these findings in larger samples with longer follow‐up using PRS calculated from multiple/diverse populations, which will be especially relevant for diverse datasets like CARE.Item Bifactor Model of the Sport Concussion Assessment Tool Symptom Checklist: Replication and Invariance Across Time in the CARE Consortium Sample(Sage, 2020-09) Brett, Benjamin L.; Kramer, Mark D.; McCrea, Michael A.; Broglio, Steven P.; McAllister, Thomas; Nelson, Lindsay D.; Hazzard, Joseph B., Jr.; Kelly, Louise A.; Ortega, Justus; Port, Nicholas; Pasquina, Paul F.; Jackson, Jonathan; Cameron, Kenneth L.; Houston, Megan N.; Goldman, Joshua T.; Giza, Christopher; Buckley, Thomas; Clugston, James R.; Schmidt, Julianne D.; Feigenbaum, Luis A.; Eckner, James T.; Master, Christina L.; Collins, Michael W.; Kontos, Anthony P.; Chrisman, Sara P.D.; Duma, Stefan M.; Miles, Christopher M.; Susmarski, Adam; Psychiatry, School of MedicineBackground: Identifying separate dimensions of concussion symptoms may inform a precision medicine approach to treatment. It was previously reported that a bifactor model identified distinct acute postconcussion symptom dimensions. Purpose: To replicate previous findings of a bifactor structure of concussion symptoms in the Concussion Assessment Research and Education (CARE) Consortium sample, examine measurement invariance from pre- to postinjury, and evaluate whether factors are associated with other clinical and biomarker measures. Study design: Cohort study (Diagnosis); Level of evidence, 2. Methods: Collegiate athletes were prospectively evaluated using the Sport Concussion Assessment Tool-3 (SCAT-3) during preseason (N = 31,557); 2789 were followed at <6 hours and 24 to 48 hours after concussion. Item-level SCAT-3 ratings were analyzed using exploratory and confirmatory factor analyses. Bifactor and higher-order models were compared for their fit and interpretability. Measurement invariance tested the stability of the identified factor structure across time. The association between factors and criterion measures (clinical and blood-based markers of concussion severity, symptom duration) was evaluated. Results: The optimal structure for each time point was a 7-factor bifactor model: a General factor, on which all items loaded, and 6 specific factors-Vestibulo-ocular, Headache, Sensory, Fatigue, Cognitive, and Emotional. The model manifested strict invariance across the 2 postinjury time points but only configural invariance from baseline to postinjury. From <6 to 24-48 hours, some dimensions increased in severity (Sensory, Fatigue, Emotional), while others decreased (General, Headache, Vestibulo-ocular). The factors correlated with differing clinical and biomarker criterion measures and showed differing patterns of association with symptom duration at different time points. Conclusion: Bifactor modeling supported the predominant unidimensionality of concussion symptoms while revealing multidimensional properties, including a large dominant General factor and 6 independent factors: Headache, Vestibulo-ocular, Sensory, Cognitive, Fatigue, and Emotional. Unlike the widely used SCAT-3 symptom severity score, which declines gradually after injury, the bifactor model revealed separable symptom dimensions that have distinct trajectories in the acute postinjury period and different patterns of association with other markers of injury severity and outcome. Clinical relevance: The SCAT-3 total score remains a valuable, robust index of overall concussion symptom severity, and the specific factors identified may inform management strategies. Because some symptom dimensions continue to worsen in the first 24 to 48 hours after injury (ie, Sensory, Fatigue, Emotional), routine follow-up in this time frame may be valuable to ensure that symptoms are managed effectively.Item Current State, Needs, and Opportunities for Wearable Robots in Military Medical Rehabilitation and Force Protection(MDPI, 2024) Cooper, Rory A.; Smolinski, George; Candiotti, Jorge L.; Satpute, Shantanu; Grindle, Garrett G.; Sparling, Tawnee L.; Nordstrom, Michelle J.; Yuan, Xiaoning; Symsack, Allison; Lee, Chang Dae; Vitiello, Nicola; Knezevic, Steven; Sugar, Thomas G.; Schneider, Urs; Kopp, Verena; Holl, Mirjam; Gaunaurd, Ignacio; Gailey, Robert; Bonato, Paolo; Poropatich, Ron; Adet, David J.; Clemente, Francesco; Abbas, James; Pasquina, Paul F.; Occupational Therapy, School of Health and Human SciencesDespite advances in wearable robots across various fields, there is no consensus definition or design framework for the application of this technology in rehabilitation or musculoskeletal (MSK) injury prevention. This paper aims to define wearable robots and explore their applications and challenges for military rehabilitation and force protection for MSK injury prevention. We conducted a modified Delphi method, including a steering group and 14 panelists with 10+ years of expertise in wearable robots. Panelists presented current wearable robots currently in use or in development for rehabilitation or assistance use in the military workforce and healthcare. The steering group and panelists met to obtain a consensus on the wearable robot definition applicable for rehabilitation or primary injury prevention. Panelists unanimously agreed that wearable robots can be grouped into three main applications, as follows: (1) primary and secondary MSK injury prevention, (2) enhancement of military activities and tasks, and (3) rehabilitation and reintegration. Each application was presented within the context of its target population and state-of-the-art technology currently in use or under development. Capturing expert opinions, this study defines wearable robots for military rehabilitation and MSK injury prevention, identifies health outcomes and assessment tools, and outlines design requirements for future advancements.Item Diffusion tensor analysis of white matter tracts is prognostic of persisting post-concussion symptoms in collegiate athletes(Elsevier, 2024) Bertò, Giulia; Rooks, Lauren T.; Broglio, Steven P.; McAllister, Thomas A.; McCrea, Michael A.; Pasquina, Paul F.; Giza, Christopher; Brooks, Alison; Mihalik, Jason; Guskiewicz, Kevin; Goldman, Josh; Duma, Stefan; Rowson, Steven; Port, Nicholas L.; Pestilli, Franco; Psychiatry, School of MedicineBackground and objectives: After a concussion diagnosis, the most important issue for patients and loved ones is how long it will take them to recover. The main objective of this study is to develop a prognostic model of concussion recovery. This model would benefit many patients worldwide, allowing for early treatment intervention. Methods: The Concussion Assessment, Research and Education (CARE) consortium study enrolled collegiate athletes from 30 sites (NCAA athletic departments and US Department of Defense service academies), 4 of which participated in the Advanced Research Core, which included diffusion-weighted MRI (dMRI) data collection. We analyzed the dMRI data of 51 injuries of concussed athletes scanned within 48 h of injury. All athletes were cleared to return-to-play by the local medical staff following a standardized, graduated protocol. The primary outcome measure is days to clearance of unrestricted return-to-play. Injuries were divided into early (return-to-play < 28 days) and late (return-to-play >= 28 days) recovery based on the return-to-play clinical records. The late recovery group meets the standard definition of Persisting Post-Concussion Symptoms (PPCS). Data were processed using automated, state-of-the-art, rigorous methods for reproducible data processing using brainlife.io. All processed data derivatives are made available at https://brainlife.io/project/63b2ecb0daffe2c2407ee3c5/dataset. The microstructural properties of 47 major white matter tracts, 5 callosal, 15 subcortical, and 148 cortical structures were mapped. Fractional Anisotropy (FA) and Mean Diffusivity (MD) were estimated for each tract and structure. Correlation analysis and Receiver Operator Characteristic (ROC) analysis were then performed to assess the association between the microstructural properties and return-to-play. Finally, a Logistic Regression binary classifier (LR-BC) was used to classify the injuries between the two recovery groups. Results: The mean FA across all white matter volume was negatively correlated with return-to-play (r = -0.38, p = 0.00001). No significant association between mean MD and return-to-play was found, neither for FA nor MD for any other structure. The mean FA of 47 white matter tracts was negatively correlated with return-to-play (rμ = -0.27; rσ = 0.08; rmin = -0.1; rmax = -0.43). Across all tracts, a large mean ROC Area Under the Curve (AUCFA) of 0.71 ± 0.09 SD was found. The top classification performance of the LR-BC was AUC = 0.90 obtained using the 16 statistically significant white matter tracts. Discussion: Utilizing a free, open-source, and automated cloud-based neuroimaging pipeline and app (https://brainlife.io/docs/tutorial/using-clairvoy/), a prognostic model has been developed, which predicts athletes at risk for slow recovery (PPCS) with an AUC=0.90, balanced accuracy = 0.89, sensitivity = 1.0, and specificity = 0.79. The small number of participants in this study (51 injuries) is a significant limitation and supports the need for future large concussion dMRI studies and focused on recovery.Item Effects of Pre-Collegiate Sport Specialization on Cognitive, Postural, and Psychological Functions: Findings from the NCAA-DoD CARE Consortium(MDPI, 2022-02) Chou, Tsung-Yeh; Caccese, Jaclyn B.; Huang, Yu-Lun; Glutting, Joseph J.; Buckley, Thomas A.; Broglio, Steven P.; McAllister, Thomas W.; McCrea, Michael A.; Pasquina, Paul F.; Kaminski, Thomas W.; Psychiatry, School of MedicineBackground: Early sport specialization has been associated with an increased risk of musculoskeletal injuries and unfavorable psychological outcomes; however, it is unknown whether sport specialization is associated with worse cognitive, postural, and psychological functions in first-year collegiate student-athletes. Methods: First-year collegiate multisport (MA) and single-sport (SA) student-athletes were identified using a pre-collegiate sport experience questionnaire. The cognitive, postural, and psychological functions were assessed by the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT), Standardized Assessment of Concussion (SAC), Balance Error Scoring System (BESS), and Brief Symptom Inventory 18 (BSI-18). Results: MA student-athletes performed higher in cognitive outcomes (e.g., higher ImPACT visual memory composite scores [ß = 0.056, p < 0.001]), but had higher psychological distress (e.g., higher BSI-18 global severity index [ß = 0.057, p < 0.001]) and no difference in postural stability (p > 0.05) than SA student-athletes. Conclusions: This study indicated first-year collegiate athletes with a history of sport specialization demonstrate lower cognitive performance but decreased psychological distress and no differences in static postural stability as compared to their MA counterparts. Future studies should consider involving different health measures to better understand the influence of sport specialization on overall physical and mental health.Item Estimated age of first exposure to American football and outcome from concussion(Wolters Kluwer, 2020-11-24) Caccese, Jaclyn B.; Houck, Zac; Kaminski, Thomas W.; Clugston, James R.; Iverson, Grant L.; Bryk, Kelsey N.; Oldham, Jessie R.; Pasquina, Paul F.; Broglio, Steven P.; McAllister, Thomas W.; McCrea, Michael; Reed Hoy, April Marie; Hazzard, Joseph B., Jr.; Kelly, Louise A.; Ortega, Justus D.; Port, Nicholas; Putukian, Margot; Langford, T. Dianne; Giza, Christopher C.; Goldman, Joshua T.; Benjamin, Holly J.; Schmidt, Julianne D.; Feigenbaum, Luis A.; Eckner, James T.; Mihalik, Jason P.; Dysart Miles, Jessica; Anderson, Scott; Master, Christina L.; Collins, Micky W.; Kontos, Anthony P.; Chrisman, Sara P.D.; Brooks, Alison; Jackson, Jonathan C.; McGinty, Gerald; Cameron, Kenneth L.; Susmarski, Adam; O'Donnell, Patrick G.; Duma, Stefan; Rowson, Steve; Miles, Christopher M.; Bullers, Christopher T.; Dykhuizen, Brian H.; Lintner, Laura; Buckley, Thomas A.; Psychiatry, School of MedicineObjective: To examine the association between estimated age at first exposure (eAFE) to American football and clinical measures throughout recovery following concussion. Methods: Participants were recruited across 30 colleges and universities as part of the National Collegiate Athletic Association (NCAA)-Department of Defense Concussion Assessment, Research and Education Consortium. There were 294 NCAA American football players (age 19 ± 1 years) evaluated 24-48 hours following concussion with valid baseline data and 327 (age 19 ± 1 years) evaluated at the time they were asymptomatic with valid baseline data. Participants sustained a medically diagnosed concussion between baseline testing and postconcussion assessments. Outcome measures included the number of days until asymptomatic, Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) composite scores, Balance Error Scoring System (BESS) total score, and Brief Symptom Inventory 18 (BSI-18) subscores. The eAFE was defined as participant's age at the time of assessment minus self-reported number of years playing football. Results: In unadjusted regression models, younger eAFE was associated with lower (worse) ImPACT Visual Motor Speed (R 2 = 0.031, p = 0.012) at 24-48 hours following injury and lower (better) BSI-18 Somatization subscores (R 2 = 0.014, p = 0.038) when the athletes were asymptomatic. The effect sizes were very small. The eAFE was not associated with the number of days until asymptomatic, other ImPACT composite scores, BESS total score, or other BSI-18 subscores. Conclusion: Earlier eAFE to American football was not associated with longer symptom recovery, worse balance, worse cognitive performance, or greater psychological distress following concussion. In these NCAA football players, longer duration of exposure to football during childhood and adolescence appears to be unrelated to clinical recovery following concussion.Item Gene Expression Alterations in Peripheral Blood Following Sport-Related Concussion in a Prospective Cohort of Collegiate Athletes: A Concussion Assessment, Research and Education (CARE) Consortium Study(Springer Nature, 2024-04) Simpson, Edward; Reiter, Jill L.; Ren, Jie; Zhang, Zhiqi; Nudelman, Kelly N.; Riggen, Larry D., Jr.; Menser, Michael D.; Harezlak, Jaroslaw; Foroud, Tatiana M.; Saykin, Andrew J.; Brooks, Alison; Cameron, Kenneth L.; Duma, Stefan M.; McGinty, Gerald; Rowson, Steven; Svoboda, Steven J.; Broglio, Steven P.; McCrea, Michael A.; Pasquina, Paul F.; McAllister, Thomas W.; Liu, Yunlong; CARE Consortium Investigators; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public HealthBackground Molecular-based approaches to understanding concussion pathophysiology provide complex biological information that can advance concussion research and identify potential diagnostic and/or prognostic biomarkers of injury. Objective The aim of this study was to identify gene expression changes in peripheral blood that are initiated following concussion and are relevant to concussion response and recovery. Methods We analyzed whole blood transcriptomes in a large cohort of concussed and control collegiate athletes who were participating in the multicenter prospective cohort Concussion Assessment, Research, and Education (CARE) Consortium study. Blood samples were collected from collegiate athletes at preseason (baseline), within 6 h of concussion injury, and at four additional prescribed time points spanning 24 h to 6 months post-injury. RNA sequencing was performed on samples from 230 concussed, 130 contact control, and 102 non-contact control athletes. Differential gene expression and deconvolution analysis were performed at each time point relative to baseline. Results Cytokine and immune response signaling pathways were activated immediately after concussion, but at later time points these pathways appeared to be suppressed relative to the contact control group. We also found that the proportion of neutrophils increased and natural killer cells decreased in the blood following concussion. Conclusions Transcriptome signatures in the blood reflect the known pathophysiology of concussion and may be useful for defining the immediate biological response and the time course for recovery. In addition, the identified immune response pathways and changes in immune cell type proportions following a concussion may inform future treatment strategies.Item Interpreting Clinical Reaction Time Change and Recovery After Concussion: A Baseline Versus Norm-Based Cutoff Score Comparison(National Athletic Trainers' Associaton, 2021) Caccese, Jaclyn B.; Eckner, James T.; Franco-MacKendrick, Lea; Hazzard, Joseph B.; Ni, Meng; Broglio, Steven P.; McAllister, Thomas W.; McCrea, Michael A.; Pasquina, Paul F.; Buckley, Thomas A.; Psychiatry, School of MedicineContext: Preseason testing can be time intensive and cost prohibitive. Therefore, using normative data for postconcussion interpretation in lieu of preseason testing is desirable. Objective: To establish the recovery trajectory for clinical reaction time (RTclin) and assess the usefulness of changes from baseline (comparison of postconcussion scores with individual baseline scores) and norm-based cutoff scores (comparison of postconcussion scores with a normative mean) for identifying impairments postconcussion. Design: Case-control study. Setting: Multisite clinical setting. Patients or other participants: An overlapping sample of 99 participants (age = 19.0 ± 1.1 years) evaluated within 6 hours postconcussion, 176 participants (age = 18.9 ± 1.1 years) evaluated at 24 to 48 hours postconcussion, and 214 participants (age = 18.9 ± 1.1 years) evaluated once they were cleared to begin a return-to-play progression were included. Participants with concussion were compared with 942 control participants (age = 19.0 ± 1.0 years) who did not sustain a concussion during the study period but completed preseason baseline testing at 2 points separated by 1 year (years 1 and 2). Main outcome measure(s): At each time point, follow-up RTclin (ie, postconcussion or year 2) was compared with the individual year 1 preseason baseline RTclin and normative baseline data (ie, sex and sport specific). Receiver operating characteristic curves were calculated to compare the sensitivity and specificity of RTclin change from baseline and norm-based cutoff scores. Results: Clinical reaction time performance declined within 6 hours (18 milliseconds, 9.2% slower than baseline). The decline persisted at 24 to 48 hours (15 milliseconds, 7.6% slower than baseline), but performance recovered by the time of return-to-play initiation. Within 6 hours, a change from baseline of 16 milliseconds maximized combined sensitivity (52%) and specificity (79%, area under the curve [AUC] = 0.702), whereas a norm-based cutoff score of 19 milliseconds maximized combined sensitivity (46%) and specificity (86%, AUC = 0.700). At 24 to 48 hours, a change from baseline of 2 milliseconds maximized combined sensitivity (64%) and specificity (61%, AUC = 0.666), whereas a norm-based cutoff score of 0 milliseconds maximized combined sensitivity (63%) and specificity (62%, AUC = 0.647). Conclusions: Norm-based cutoff scores can be used for interpreting RTclin scores postconcussion in collegiate athletes when individual baseline data are not available, although low sensitivity and specificity limit the use of RTclin as a stand-alone test.