Introduction: Cognitive impairment after concussion has been widely reported, but there is no reliable imaging biomarker that predicts the severity of cognitive decline post-concussion. This study tests the hypothesis that patients with a history of concussion and persistent cognitive impairment have fractional anisotropy (FA) and mean diffusivity (MD) values from diffusion tensor imaging (DTI) that are specifically associated with poor performance on the Montreal Cognitive Assessment (MoCA).Methods: Fifty-three subjects (19 females) with concussions and persistent cognitive symptoms had MR imaging and the MoCA. Imaging was analyzed by atlas-based, whole-brain DTI segmentation and FLAIR lesion segmentation. Then, we conducted a random forest-based recursive feature elimination (RFE) with 10-fold cross-validation on the entire dataset, and with partial correlation adjustment for age and lesion load.Results: RFE showed that 11 DTI variables were found to be important predictors of MoCA scores. Partial correlation analyses, corrected for age and lesion load, showed significant correlations between MoCA scores and right fronto-temporal regions: inferior temporal gyrus MD (r = −0.62, p = 0.00001), middle temporal gyrus MD (r = −0.54, p = 0.0001), angular gyrus MD (r = −0.48, p = 0.0008), and inferior frontal gyrus FA (r = 0.44, p = 0.002).Discussion: This is the first study to demonstrate a correlation between MoCA scores and DTI variables in patients with a history of concussion and persistent cognitive impairment. This kind of research will significantly increase our understanding of why certain persons have persistent cognitive changes after concussion which, in turn, may allow us to predict persistent impairment after concussion and suggest new interventions.

Several common and debilitating neurodegenerative disorders are characterized by the intracellular accumulation of neurofibrillary tangles (NFTs), which are composed of hyperphosphorylated tau protein. In Alzheimer’s disease (AD), NFTs are accompanied by extracellular amyloid-beta (Aβ), but primary tauopathy disorders are marked by the accumulation of tau protein alone, including forms of frontotemporal dementia (FTD), corticobasal degeneration (CBD), and progressive supranuclear palsy (PSP), among others. ¹⁸F-THK5351 has been reported to bind pathological tau as well as associated reactive astrogliosis. The goal of this study was to validate the ability of the PET tracer ¹⁸F-THK5351 to detect early changes in tau-related pathology and its relation to other pathological hallmarks. We demonstrated elevated in vivo ¹⁸F-THK5351 PET signaling over time in transgenic P301S tau mice from 8 months that had a positive correlation with histological and biochemical tau changes, as well as motor, memory, and learning impairment. This study indicates that ¹⁸F-THK5351 may help fill a critical need to develop PET imaging tracers that detect aberrant tau aggregation and related neuropathology in order to diagnose the onset of tauopathies, gain insights into their underlying pathophysiologies, and to have a reliable biomarker to follow during treatment trials.