Sports-Related Concussion in Collegiate Athletes: The Potential Benefits of Using Graded Neuropsychological Tests With High Ceilings.

OBJECTIVE: Sports-related concussion management in collegiate athletes has been focused on return-to-play. However, resuming schoolwork without a gradual stepwise reintroduction contributes to symptom exacerbation, delayed recovery, and adverse academic performance. Return-to-learn guidelines are limited by a lack of sensitivity in methods monitoring cognitive function. This study evaluated 2 neuropsychological tests, the Sternberg test and the Paced Auditory Serial Addition Test (PASAT), with high ceilings for sensitivity to deficits in speed of information processing, cognitive efficiency, and complex attention. SETTING: Academic center research laboratory. PARTICIPANTS: We recruited 56 male and female collegiate contact and noncontact sports athletes. They were categorized into as follows: (1) nonconcussed (n = 23; 7F, 16M); (2) chronic (n = 21; 4F, 17M), at least 1 year from their last concussion; and (3) acute (n = 12; 1F, 11M), within 2 weeks from concussion. DESIGN: Observational cohort study. MAIN MEASURES: The PASAT assesses complex attention. The Sternberg test examines processing speed and cognitive efficiency. Cognitive difficulty increases with progression through the tasks for both the PASAT and the Sternberg test. The mean outcome differences of the 3 groups (nonconcussed, acute, and chronic) across the 3 or 4 conditions (difficulty level) were measured with repeated-measures analysis of variance and subsequent pairwise comparison. RESULTS: For processing speed (Sternberg reaction time), the acute group responded slower than the chronic group on the medium (P = .021, Bonferroni corrected) and hard difficulty tasks (P = .030, Bonferroni corrected). For cognitive efficiency (Sternberg reaction time variability), the acute group had increased reaction time variability compared with the chronic group on the medium difficulty task (P = .04, Bonferroni corrected). For complex attention (PASAT omissions), there was a difference between the acute and nonconcussed groups on the moderate-hard difficulty trial (P = .023, least significant difference [LSD] corrected) and between the acute and chronic groups for hard difficulty trial (P = .020, LSD corrected). The acute group performed worse, with progressively shorter interstimulus intervals. CONCLUSION: Neuropsychological testing without ceiling effects can capture higher-level cognitive dysfunction and use of such tests can contribute to the understanding of how collegiate athletes are affected by SRC. Future studies can investigate optimal testing batteries that include neuropsychological testing with high ceilings and whether the pattern of performance has implications for the return-to-learn process after SRC in the college setting.

Accuracy of Video-Based Gait Analysis Using Pose Estimation During Treadmill Walking Versus Overground Walking in Persons After Stroke.

OBJECTIVE: Video-based pose estimation is an emerging technology that shows significant promise for improving clinical gait analysis by enabling quantitative movement analysis with little costs of money, time, or effort. The objective of this study is to determine the accuracy of pose estimation-based gait analysis when video recordings are constrained to 3 common clinical or in-home settings (ie, frontal and sagittal views of overground walking and sagittal views of treadmill walking). METHODS: Simultaneous video and motion capture recordings were collected from 30 persons after stroke during overground and treadmill walking. Spatiotemporal and kinematic gait parameters were calculated from videos using an open-source human pose estimation algorithm and from motion capture data using traditional gait analysis. Repeated-measures analyses of variance were then used to assess the accuracy of the pose estimation-based gait analysis across the different settings, and the authors examined Pearson and intraclass correlations with ground-truth motion capture data. RESULTS: Sagittal videos of overground and treadmill walking led to more accurate measurements of spatiotemporal gait parameters versus frontal videos of overground walking. Sagittal videos of overground walking resulted in the strongest correlations between video-based and motion capture measurements of lower extremity joint kinematics. Video-based measurements of hip and knee kinematics showed stronger correlations with motion capture versus ankle kinematics for both overground and treadmill walking. CONCLUSION: Video-based gait analysis using pose estimation provides accurate measurements of step length, step time, and hip and knee kinematics during overground and treadmill walking in persons after stroke. Generally, sagittal videos of overground gait provide the most accurate results. IMPACT: Many clinicians lack access to expensive gait analysis tools that can help identify patient-specific gait deviations and guide therapy decisions. These findings show that video-based methods that require only common household devices provide accurate measurements of a variety of gait parameters in persons after stroke and could make quantitative gait analysis significantly more accessible.

Sitagliptin elevates plasma and CSF incretin levels following oral administration to nonhuman primates: relevance for neurodegenerative disorders.

The endogenous incretins glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) possess neurotrophic, neuroprotective, and anti-neuroinflammatory actions. The dipeptidyl peptidase 4 (DPP-4) inhibitor sitagliptin reduces degradation of endogenous GLP-1 and GIP, and, thereby, extends the circulation of these protective peptides. The current nonhuman primate (NHP) study evaluates whether human translational sitagliptin doses can elevate systemic and central nervous system (CNS) levels of GLP-1/GIP in naive, non-lesioned NHPs, in line with our prior rodent studies that demonstrated sitagliptin efficacy in preclinical models of Parkinson's disease (PD). PD is an age-associated neurodegenerative disorder whose current treatment is inadequate. Repositioning of the well-tolerated and efficacious diabetes drug sitagliptin provides a rapid approach to add to the therapeutic armamentarium for PD. The pharmacokinetics and pharmacodynamics of 3 oral sitagliptin doses (5, 20, and 100 mg/kg), equivalent to the routine clinical dose, a tolerated higher clinical dose and a maximal dose in monkey, were evaluated. Peak plasma sitagliptin levels were aligned both with prior reports in humans administered equivalent doses and with those in rodents demonstrating reduction of PD associated neurodegeneration. Although CNS uptake of sitagliptin was low (cerebrospinal fluid (CSF)/plasma ratio 0.01), both plasma and CSF concentrations of GLP-1/GIP were elevated in line with efficacy in prior rodent PD studies. Additional cellular studies evaluating human SH-SY5Y and primary rat ventral mesencephalic cultures challenged with 6-hydroxydopamine, established cellular models of PD, demonstrated that joint treatment with GLP-1 + GIP mitigated cell death, particularly when combined with DPP-4 inhibition to maintain incretin levels. In conclusion, this study provides a supportive translational step towards the clinical evaluation of sitagliptin in PD and other neurodegenerative disorders for which aging, similarly, is the greatest risk factor.