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The Rivermead Post-Concussion Symptoms Questionnaire (RPQ) assesses post-concussion symptoms (PCS) after traumatic brain injury (TBI). The current study examines the applicability of self-report and proxy versions of the German RPQ in adolescents (13–17 years) after TBI. We investigated reliability and validity on the total and scale score level. Construct validity was investigated by correlations with the Post-Concussion Symptoms Inventory (PCSI-SR13), Generalized Anxiety Disorder Scale 7 (GAD-7), and Patient Health Questionnaire 9 (PHQ-9) and by hypothesis testing regarding individuals’ characteristics. Intraclass correlation coefficients (ICC) assessed adolescent–proxy agreement. In total, 148 adolescents after TBI and 147 proxies completed the RPQ. Cronbach’s α (0.81–0.91) and McDonald’s ω (0.84–0.95) indicated good internal consistency. The three-factor structure outperformed the unidimensional model. The RPQ was strongly correlated with the PCSI-SR13 (self-report: r = 0.80; proxy: r = 0.75) and moderately–strongly with GAD-7 and PHQ-9 (self-report: r = 0.36, r = 0.35; proxy: r = 0.53, r = 0.62). Adolescent–proxy agreement was fair (ICC [2,1] = 0.44, CI95% [0.41, 0.47]). Overall, both self-report and proxy assessment forms of the German RPQ are suitable for application in adolescents after TBI. As proxy ratings tend to underestimate PCS, self-reports are preferable for evaluations. Only if a patient is unable to answer, a proxy should be used as a surrogate.

Purpose Flourine-18-flortaucipir tau positron emission tomography (PET) was developed for the detection for Alzheimer’s disease. Human imaging studies have begun to investigate its use in chronic traumatic encephalopathy (CTE). Flortaucipir-PET to autopsy correlation studies in CTE are needed for diagnostic validation. We examined the association between end-of-life flortaucipir PET and postmortem neuropathological measurements of CTE-related tau in six former American football players. Methods Three former National Football League players and three former college football players who were part of the DIAGNOSE CTE Research Project died and agreed to have their brains donated. The six players had flortaucipir (tau) and florbetapir (amyloid) PET prior to death. All brains from the deceased participants were neuropathologically evaluated for the presence of CTE. On average, the participants were 59.0 (SD = 9.32) years of age at time of PET. PET scans were acquired 20.33 (SD = 13.08) months before their death. Using Spearman correlation analyses, we compared flortaucipir standard uptake value ratios (SUVRs) to digital slide-based AT8 phosphorylated tau (p-tau) density in a priori selected composite cortical, composite limbic, and thalamic regions-of-interest (ROIs). Results Four brain donors had autopsy-confirmed CTE, all with high stage disease (n = 3 stage III, n = 1 stage IV). Three of these four met criteria for the clinical syndrome of CTE, known as traumatic encephalopathy syndrome (TES). Two did not have CTE at autopsy and one of these met criteria for TES. Concomitant pathology was only present in one of the non-CTE cases (Lewy body) and one of the CTE cases (motor neuron disease). There was a strong association between flortaucipir SUVRs and p-tau density in the composite cortical (ρ = 0.71) and limbic (ρ = 0.77) ROIs. Although there was a strong association in the thalamic ROI (ρ = 0.83), this is a region with known off-target binding. SUVRs were modest and CTE and non-CTE cases had overlapping SUVRs and discordant p-tau density for some regions. Conclusions Flortaucipir-PET could be useful for detecting high stage CTE neuropathology, but specificity to CTE p-tau is uncertain. Off-target flortaucipir binding in the hippocampus and thalamus complicates interpretation of these associations. In vivo biomarkers that can detect the specific p-tau of CTE across the disease continuum are needed.

Background Exposure to repetitive head impacts (RHI) is associated with an increased risk of later‐life neurobehavioral dysregulation and neurodegenerative disease. The underlying pathomechanisms are largely unknown. Purpose To investigate whether RHI exposure is associated with later‐life corpus callosum (CC) microstructure and whether CC microstructure is associated with plasma total tau and neuropsychological/neuropsychiatric functioning. Study Type Retrospective cohort study. Population Seventy‐five former professional American football players (age 55.2 ± 8.0 years) with cognitive, behavioral, and mood symptoms. Field Strength/Sequence Diffusion‐weighted echo‐planar MRI at 3 T. Assessment Subjects underwent diffusion MRI, venous puncture, neuropsychological testing, and completed self‐report measures of neurobehavioral dysregulation. RHI exposure was assessed using the Cumulative Head Impact Index (CHII). Diffusion MRI measures of CC microstructure (i.e., free‐water corrected fractional anisotropy (FA), trace, radial diffusivity (RD), and axial diffusivity (AD)) were extracted from seven segments of the CC (CC1‐7), using a tractography clustering algorithm. Neuropsychological tests were selected: Trail Making Test Part A (TMT‐A) and Part B (TMT‐B), Controlled Oral Word Association Test (COWAT), Stroop Interference Test, and the Behavioral Regulation Index (BRI) from the Behavior Rating Inventory of Executive Function, Adult version (BRIEF‐A). Statistical Tests Diffusion MRI metrics were tested for associations with RHI exposure, plasma total tau, neuropsychological performance, and neurobehavioral dysregulation using generalized linear models for repeated measures. Results RHI exposure was associated with increased AD of CC1 (correlation coefficient (r) = 0.32, P < 0.05) and with increased plasma total tau (r = 0.34, P < 0.05). AD of the anterior CC1 was associated with increased plasma total tau (CC1: r = 0.30, P < 0.05; CC2: r = 0.29, P < 0.05). Higher trace, AD, and RD of CC1 were associated with better performance (P < 0.05) in TMT‐A (trace, r = 0.33; AD, r = 0.31; and RD, r = 0.28) and TMT‐B (trace, r = 0.31; RD, r = 0.34). Higher FA and AD of CC2 were associated with better performance (P < 0.05) in TMT‐A (FA, r = 0.36; AD, r = 0.28), TMT‐B (FA, r = 0.36; AD, r = 0.27), COWAT (FA, r = 0.36; AD, r = 0.32), and BRI (AD, r = 0.29). Data Conclusion These results suggest an association among RHI exposure, CC microstructure, plasma total tau, and clinical functioning in former professional American football players. Level of Evidence: 3 Technical Efficacy Stage: 1