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Objective: Concussion evaluations use a multidimensional assessment to evaluate unique patient function dimensions (e.g., subjective symptoms differ from balance assessments), but the overarching latent factor structure has not been empirically substantiated. Our objective was to determine the cumulative latent factor structure of pre-injury baseline and acute (<48-h) post-concussion assessment battery outcomes, and determine measurement equivalence among common factors in collegiate student-athletes. Methods: Collegiate student-athletes at baseline ( n  = 21,865) and post-concussion ( n  = 1,537) across 25-institutions completed standardized assessments. Individual items were used from the baseline and post-concussion assessments and consisted of: Sport Concussion Assessment Tool, Brief Symptom Inventory-18, Standardized Assessment of Concussion, Balance Error Scoring System, Immediate Post-Concussion Assessment and Cognitive Test, and vestibular-ocular motor screening. Exploratory factor analysis was used on half the baseline data, and confirmatory factor analysis on the remaining baseline data and post-concussion data separately. Measurement equivalence was assessed between sex, sport contact classification, concussion history, and time. Results: A 10-factor exploratory model was established and comprised of: depression, somatic, vestibulo-ocular, headache, postural stability, neurocognition, emotional, fatigue, cognitive, consciousness clouding. The 10-factor model was confirmed at baseline and post-concussion with strong measurement equivalence between timepoints. Strong to strict measurement equivalence was observed for sex, sport contact classification, and concussion history at both timepoints separately. Conclusion: Our findings established a robust 10-factor latent factor model equivalent across timepoints and common factors among healthy and concussed collegiate athletes. Clinicians can use these findings to target specific factors while reducing redundant elements to provide efficient, comprehensive post-concussion assessments.

Background: The Sport Concussion Assessment Tool (SCAT) could be improved by identifying critical subsets that maximize diagnostic accuracy and eliminate low information elements., Objective: To identify optimal SCAT subsets for acute concussion assessment., Methods: Using Concussion Assessment, Research, and Education (CARE) Consortium data, we compared student-athletes' and cadets' preinjury baselines (n = 2178) with postinjury assessments within 6 h (n = 1456) and 24 to 48 h (n = 2394) by considering demographics, symptoms, Standard Assessment of Concussion (SAC), and Balance Error Scoring System (BESS) scores. We divided data into training/testing (60%/40%) sets. Using training data, we integrated logistic regression with an engineering methodology-mixed integer programming-to optimize models with ≤4, 8, 12, and 16 variables (Opt-k). We also created models including only raw scores (Opt-RS-k) and symptom, SAC, and BESS composite scores (summary scores). We evaluated models using testing data., Results: At <6 h and 24 to 48 h, most Opt-k and Opt-RS-k models included the following symptoms: do not feel right, headache, dizziness, sensitivity to noise, and whether physical or mental activity worsens symptoms. Opt-k models included SAC concentration and delayed recall change scores. Opt-k models had lower Brier scores (BS) and greater area under the curve (AUC) (<6 h: BS = 0.072-0.089, AUC = 0.95-0.96; 24-48 h: BS = 0.085-0.093, AUC = 0.94-0.95) than Opt-RS-k (<6 h: BS = 0.082-0.087, AUC = 0.93-0.95; 24-48 h: BS = 0.095-0.099, AUC = 0.92-0.93) and summary score models (<6 h: BS = 0.14, AUC = 0.89; 24-48 h: BS = 0.15, AUC = 0.87)., Conclusion: We identified SCAT subsets that accurately assess acute concussion and improve administration time over the complete battery, highlighting the importance of eliminating "noisy" elements. These findings can direct clinicians to the SCAT components that are most sensitive to acute concussion., (Copyright © 2020 by the Congress of Neurological Surgeons.)

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.

Background: Sports medicine clinicians routinely use computerized neurocognitive testing in sport-related concussion management programs. Debates continue regarding the appropriateness of normative reference comparisons versus obtaining individual baseline assessments, particularly for populations with greater likelihood of having below- or above-average cognitive abilities. Improving normative reference methods could offer alternatives to perceived logistical and financial burdens imposed by universal baseline testing., Objectives: To develop and validate the Concussion Assessment, Research, and Education (CARE) Consortium Multiple Variable Prediction (MVP) norms for the Immediate Postconcussion Assessment and Cognitive Testing (ImPACT)., Methods: We developed the CARE-MVP norms for ImPACT composite scores using regression-based equations. Predictor variables included sex, race (white/Caucasian, black/African American, Asian, or Multiple Races), medical history [attention-deficit/hyperactivity disorder (ADHD), learning disorder (LD), prior concussion(s), prior psychiatric diagnosis], and an estimate of premorbid intellect (Wechsler Test of Adult Reading). CARE-MVP norms were first validated in an independent sample of healthy collegiate athletes by comparing predicted and actual baseline test scores using independent-samples t-tests and Cohen's d effect sizes. We then evaluated base rates of low scores in athletes self-reporting ADHD/LD (vs. non-ADHD/LD) and black/African American race (vs. white/Caucasian) across multiple normative reference methods (Chi square, Cramer's V effect size). Lastly, we validated the CARE-MVP norms in a concussed sample (dependent samples t test, Cohen's d effect size)., Results: A total of 5233 collegiate athletes (18.8 ± 1.2 years, 70.5% white/Caucasian, 39.1% female) contributed to the CARE-MVP norms (development N = 2616; internal validation N = 2617). Race and WTAR score were the strongest and most consistent ImPACT score predictors. There were negligible mean differences between observed and predicted (CARE-MVP) baseline scores (Cohen's d < 0.1) for all ImPACT composite scores except Reaction Time (predicted ~ 20 ms faster than observed, d = - 0.28). Low score base rates were similar for athletes across subpopulations when using CARE-MVP norms (ADHD/LD, V = 0.017-0.028; black/African American, V = 0.043-0.053); while, other normative reference methods resulted in disproportionately higher rates of low scores (ADHD/LD, V = 0.062-0.101; black/African American race, V = 0.163-0.221). Acute (24-48 h) postconcussion ImPACT scores were significantly worse than CARE-MVP norms but notably varied as a function of concussion symptom severity., Conclusions: Results support CARE-MVP norm use in populations typically underrepresented or not adjusted for in traditional normative reference samples, such as those self-reporting ADHD/LD or black/African American race. CARE-MVP norms improve upon prior normative methods and may offer a practical, simple alternative for collegiate institutions concerned about logistical and financial burden associated with baseline testing. An automated scoring program is provided.

Objective: Neuropsychological evaluations include hold tests like word-reading ability as estimates of premorbid intellect thought to be resilient to the effects of neurologic insult. We tested the alternative hypothesis that exposure to concussion or repetitive subclinical head impacts throughout early life may stunt acquisition of word-reading skills. Method: Data were obtained from student-athletes within the CARE Consortium that completed the Wechsler Test of Adult Reading (WTAR). Measures of head trauma burden included self-reported concussion history and cumulative years of exposure to collision sports. We evaluated the effects of head trauma, sociodemographic (race, SES), and academic (SAT/ACT scores, learning disorder) variables on WTAR standard score using linear regression. Analyses were repeated in a football-only subsample estimating age of first exposure to football as a predictor. Results: We analyzed data from 6,598 participants (72.2% white, 39.6% female, mean ± SD age = 18.8 ± 1.2 years). Head trauma variables collectively explained 0.1% of the variance in WTAR standard scores, with years of collision sport exposure weakly predicting lower WTAR standard scores ( β = .026-.035, very small effect). In contrast, sociodemographic and academic variables collectively explained 20.9-22.5% of WTAR standard score variance, with strongest effects noted for SAT/ACT scores (β = .313-.337, medium effect), LD diagnosis (β = -.115 to -.131, small effect), and SES ( β = .101-.108, small effect). Age of first exposure to football did not affect WTAR scores in a football-only sample. Conclusion: Wechsler Test of Adult Reading performance appears unrelated to history of self-reported concussion(s) and/or repetitive subclinical head trauma exposure in current collegiate athletes. Sociodemographic and academic variables should be incorporated in test score interpretations for diverse populations like athletes.

Objective: To evaluate the influences of sociodemographic factors, estimated head impact exposure, and academic aptitude on ImPACT scores in college athletes. Methods: Data were reported on 18,886 participants (58% male) from the NCAA/DoD CARE Consortium. Race, SES, concussion history, estimated repetitive head impact exposure (eRHIE), and academic aptitude (SAT or ACT score) were our predictors of interest. Cognition was measured using ImPACT composite scores. We evaluated the mediating effects of academic aptitude on sociodemographic predictors and eRHIE on ImPACT scores. We then evaluated a football-only subsample and added age of first exposure to football (AFE) to the model. Males, females, and football players were analyzed separately using structural equation modeling. Results: Academic aptitude was associated with Black/African American race, SES, and each of the ImPACT composite scores. There were significant indirect effects of Black/African American race and SES on all ImPACT composite scores. Academic aptitude fully mediated SES effects and either fully or partially mediated race effects. Contrary to expectation, greater concussion history and eRHIE predicted better ImPACT scores. Conclusions: Academic aptitude, a stable indicator of premorbid cognitive function, consistently and most strongly predicted baseline ImPACT scores in collegiate student-athletes. Concussion and eRHIE history demonstrated a small positive, but non-significant, relationship with cognitive scores at the time of college athletic participation. This study suggests that attempts to characterize cognitive ability across the lifespan must consider premorbid functioning and sociodemographic variables.

Context: Comprehensive assessments are recommended to evaluate sport-related concussion (SRC). The degree to which the King-Devick (KD) test adds novel information to an SRC evaluation is unknown., Objective: To describe relationships at baseline among the KD and other SRC assessments and explore whether the KD provides unique information to a multimodal baseline concussion assessment., Design: Cross-sectional study., Setting: Five National Collegiate Athletic Association institutions participating in the Concussion Assessment, Research and Education (CARE) Consortium., Patients or Other Participants: National Collegiate Athletic Association student-athletes (N = 2258, age = 20 ± 1.5 years, 53.0% male, 68.9% white) in 11 men's and 13 women's sports., Main Outcome Measure(s): Participants completed baseline assessments on the KD and (1) the Symptom Inventory of the Sport Concussion Assessment Tool-3rd edition, (2) the Brief Symptom Inventory-18, (3) the Balance Error Scoring System, (4) the Standardized Assessment of Concussion (SAC), (5) the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) test battery, and (6) the Vestibular/Ocular Motor Screening tool during their first year in CARE. Correlation coefficients between the KD and the 6 other concussion assessments in isolation were determined. Assessments with ρ magnitude >0.1 were included in a multivariate linear regression analysis to evaluate their relative association with the KD., Results: Scores for SAC concentration, ImPACT visual motor speed, and ImPACT reaction time were correlated with the KD (ρ = -0.216, -0.276, and 0.164, respectively) and were thus included in the regression model, which explained 16.8% of the variance in baseline KD time ( P < .001, Cohen f 2 = 0.20). Better SAC concentration score (β = -.174, P < .001), ImPACT visual motor speed (β = -.205, P < .001), and ImPACT reaction time (β = .056, P = .020) were associated with faster baseline KD performance, but the effect sizes were small., Conclusions: Better performance on cognitive measures involving concentration, visual motor speed, and reaction time was weakly associated with better baseline KD performance. Symptoms, psychological distress, balance, and vestibular-oculomotor provocation were unrelated to KD performance at baseline. The findings indicate limited overlap at baseline among the CARE SRC assessments and the KD.

Context: The King-Devick (KD) test has received considerable attention in the literature as an emerging concussion assessment. However, important test psychometric properties remain to be addressed in large-scale independent studies., Objective: To assess (1) test-retest reliability between trials, (2) test-retest reliability between years 1 and 2, and (3) reliability of the 2 administration modes., Design: Cross-sectional study., Setting: Collegiate athletic training facilities., Patients or Other Participants: A total of 3248 intercollegiate student-athletes participated in year 1 (male = 55.3%, age = 20.2 ± 2.3 years, height = 1.78 ± 0.11 m, weight = 80.7 ± 21.0 kg) and 833 participated in both years., Main Outcome Measure(s): Time, in seconds, to complete the KD error free. The KD test reliability was assessed between trials and between annual tests over 2 years and stratified by test modality (spiral-bound cards [n = 566] and tablet [n = 264])., Results: The KD test was reliable between trials (trial 1 = 43.2 ± 8.3 seconds, trial 2 = 40.8 ± 7.8 seconds; intraclass correlation coefficient [ICC] (2,1) = 0.888, P < .001), between years (year 1 = 40.8 ± 7.4 seconds, year 2 = 38.7 ± 7.7 seconds; ICC [2,1] = 0.827, P < .001), and for both spiral-bound cards (ICC [2,1] = 0.834, P < .001) and tablets (ICC [2,1] = 0.827, P < .001). The mean change between trials for a single test was -2.4 ± 3.8 seconds. Although most athletes improved from year 1 to year 2, 27.1% (226 of 883) of participants demonstrated worse (slower) KD times (3.2 ± 3.9 seconds) in year 2., Conclusions: The KD test was reliable between trials and years and when stratified by modality. A small improvement of 2 seconds was identified with annual retesting, likely due to a practice effect; however, 27% of athletes displayed slowed performance from year 1 to year 2. These results suggest that the KD assessment was a reliable test with modest learning effects over time and that the assessment modality did not adversely affect baseline reliability.

Objectives: To describe multivariate base rates (MBRs) of low scores and reliable change (decline) scores on Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) in college athletes at baseline, as well as to assess MBR differences among demographic and medical history subpopulations., Methods: Data were reported on 15,909 participants (46.5% female) from the NCAA/DoD CARE Consortium. MBRs of ImPACT composite scores were derived using published CARE normative data and reliability metrics. MBRs of sex-corrected low scores were reported at <25th percentile (Low Average), <10th percentile (Borderline), and ≤2nd percentile (Impaired). MBRs of reliable decline scores were reported at the 75%, 90%, 95%, and 99% confidence intervals. We analyzed subgroups by sex, race, attention-deficit/hyperactivity disorder and/or learning disability (ADHD/LD), anxiety/depression, and concussion history using chi-square analyses., Results: Base rates of low scores and reliable decline scores on individual composites approximated the normative distribution. Athletes obtained ≥1 low score with frequencies of 63.4% (Low Average), 32.0% (Borderline), and 9.1% (Impaired). Athletes obtained ≥1 reliable decline score with frequencies of 66.8%, 32.2%, 18%, and 3.8%, respectively. Comparatively few athletes had low scores or reliable decline on ≥2 composite scores. Black/African American athletes and athletes with ADHD/LD had higher rates of low scores, while greater concussion history was associated with lower MBRs (p < .01). MBRs of reliable decline were not associated with demographic or medical factors., Conclusions: Clinical interpretation of low scores and reliable decline on ImPACT depends on the strictness of the low score cutoff, the reliable change criterion, and the number of scores exceeding these cutoffs. Race and ADHD influence the frequency of low scores at all cutoffs cross-sectionally.

Computerized neuropsychological testing has become an important tool in the identification and management of sports-related concussions; however, the psychometric effect of repeat testing has not been studied extensively beyond test-retest statistics. The current study analyzed data from Division I collegiate athletes who completed Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) baseline assessments at four sequential time points that varied over the course of their athletic careers. Administrations were part of a larger National Institutes of Health (NIH) study. Growth curve modeling showed that the two memory composite scores increased significantly with successive administrations: Change in Verbal Memory was best represented with a quadratic model, while a linear model best fit Visual Memory. Visual Motor Speed and Reaction Time composites showed no significant linear or quadratic growth. The results demonstrate the effect of repeated test administrations for memory composite scores, while speed composites were not significantly impacted by repeat testing. Acceptable test-retest reliability was demonstrated for all four composites as well.

Hierarchical clustering is frequently used for grouping results in expression or haplotype analyses. These methods can elucidate patterns between measures that can then be applied to discerning their validity in discriminating between experimental conditions. Here a hierarchical clustering method is used to analyze the results of an imaging genetics study using multiple brain morphology and cognitive testing endpoints for older adults with amnestic mild cognitive impairment (MCI) or cognitive complaints (CC) compared to healthy controls (HC). The single nucleotide polymorphisms (SNPs) are a subset of those included on a larger array that are found in a reported Alzheimer's disease (AD) and neurodegeneration pathway. The results indicate that genetic models within the endpoints cluster together, while there are 4 distinct sets of SNPs that differentiate between the endpoints, with most significant results associated with morphology endpoints rather than cognitive testing of patients' reported symptoms. The genes found in at least one cluster are ABCB1, APBA1, BACE1, BACE2, BCL2, BCL2L1, CASP7, CHAT, CST3, DRD3, DRD5, IL6, LRP1, NAT1, and PSEN2. The greater associations with morphology endpoints suggests that changes in brain structure can be influenced by an individual's genetic background in the absence of dementia and in some cases (Cognitive Complaints group) even without those effects necessarily being detectable on commonly used clinical tests of cognition. The results are consistent with polygenic influences on early neurodegenerative changes and demonstrate the effectiveness of hierarchical clustering in identifying genetic associations among multiple related phenotypic endpoints., ((c) 2010 Wiley-Liss, Inc.)

Increased frequency of cavum septum pellucidum (CSP) has been inconsistently observed in schizophrenia, and little is known about its functional implications. We investigated whether patients with schizophrenia were more likely than healthy controls to have CSP, and among patients assessed the relationship between CSP, psychiatric symptoms, and selected neuropsychological functions. Seventy-seven patients with diagnoses of DSM-IV schizophrenia spectrum disorders and 55 healthy controls were studied and completed a 1.5 T MRI scan. Two raters, blind to group membership, determined the presence, length and grade of the CSP. A subset of participants also underwent neuropsychological testing. A CSP of at least 1 mm in length was present in 68.8% of patients and 76.4% of controls, and the groups did not differ significantly with respect to presence or absence, length, overall size, or percent with an abnormally large CSP (> or =6 mm). Patients with an abnormally large CSP demonstrated poorer performance on measures of verbal learning and memory than patients with smaller CSP. Among patients, CSP length was significantly correlated with negative symptoms, verbal learning, and sentence comprehension. Among patients with abnormally large CSP, CSP length was correlated with reaction time on two conditions of a Continuous Performance Test. CSP, while prevalent, was not more frequent in our sample of patients with schizophrenia, and had few associations with symptom severity or neuropsychological deficits.

Objective: The authors tested the hypothesis that the dopamine D2 receptor T allele (formerly described as the A1 allele) would be associated with poorer performance on memory and attention tasks following mild traumatic brain injury., Method: Thirty-nine patients with mild traumatic brain injury and 27 comparison subjects were genotyped. All subjects completed memory and attention tests, including the California Verbal Learning Test recognition task and the Continuous Performance Test., Results: In both groups the T allele was associated with poorer performance on the California Verbal Learning Test recognition task. There was also a significant diagnosis-by-allele interaction on measures of response latency (Continuous Performance Test): the subjects with mild traumatic brain injury and the T allele had the worst performance., Conclusions: Genetic polymorphisms modulating central dopaminergic tone can affect cognitive outcome following mild traumatic brain injury.

We have recently reported (Saykin et al., 1999b) selective activation of left medial temporal lobe structures during processing of novel compared to familiar words using functional magnetic resonance imaging (fMRI). The current study describes the relationship between a widely used clinical test of verbal learning, the California Verbal Learning Test (CVLT), and the previously reported fMRI activations. Thirteen right-handed healthy adult participants were studied with whole brain echo-planar fMRI while listening to novel and recently learned (familiar) words intermixed pseudorandomly in an event-related design. These participants were also tested with the CVLT. Scores for CVLT Trial 1 (immediate encoding of novel words) and recognition discriminability (recognition of familiar vs. novel words) were correlated with fMRI signal change during processing of novel versus familiar words using a covariance model implemented in SPM96. For the novel words analysis, voxels in the right anterior hippocampus correlated significantly with Trial 1 (r = .76 at the maxima). For the recognition analysis, a significant cluster of voxels was found in the right dorsolateral prefrontal cortex (r = .88 at the maxima). Our prior results of separable left medial temporal activation to novel and familiar words, together with results of the covariance analyses reported here, suggest that in addition to the left medial temporal lobe (MTL) regions that are engaged during novel and familiar word processing, the right hippocampus and right frontal lobe are also involved, particularly in those participants with better memory ability. This positive relationship between fMRI activation and CVLT performance suggests a role for these right hemisphere regions in successful memory processing of verbal material, perhaps reflecting more efficient encoding and retrieval strategies that facilitate memory.