Traumatic brain injury (TBI) is associated with an accelerated course of dementia, although biological relationships are incompletely understood.
The study examined 1124 participants, including 343 ...with Alzheimer disease (AD), 127 with AD with TBI, 266 cognitively normal adults with TBI, and 388 cognitively normal adults without TBI. Cortical thickness was quantified from T1-weighted magnetic resonance imaging data. Multiple linear regression was used to determine the interaction between AD and TBI on cortical thickness.
Among those with AD, TBI was associated with an earlier age of AD onset but, counterintuitively, less cortical thinning in frontotemporal regions relative to non-AD controls.
AD with TBI represents a distinct group from AD, likely with distinct pathologic contributions beyond gray matter loss. This finding has important implications for the diagnosis and treatment of AD in the presence of TBI and indicates that models of AD, aging, and neural loss should account for TBI history.
Inflammation appears to be an important component of concussion pathophysiology. However, its relationship to symptom burden is unclear. Therefore, the purpose of this study was to evaluate the ...relationship between symptoms and inflammatory biomarkers measured in the blood of male and female athletes following a sport-related concussion (SRC).
Forty athletes (n = 20 male, n = 20 female) from nine interuniversity sport teams at a single institution provided blood samples within one week of an SRC. Twenty inflammatory biomarkers were quantitated by immunoassay. The Sport Concussion Assessment Tool version 5 (SCAT-5) was used to evaluate symptoms. Partial least squares (PLS) analyses were used to evaluate the relationship(s) between biomarkers and symptoms. In males, a positive correlation between interferon (IFN)-γ and symptom severity was observed following SRC. The relationship between IFN-γ and symptoms was significant among all symptom clusters, with cognitive symptoms displaying the largest effect. In females, a significant negative relationship was observed between symptom severity and cytokines IFN-γ, tumor necrosis factor (TNF)-α, and myeloperoxidase (MPO); a positive relationship was observed between symptom severity and MCP-4. Inflammatory mediators were significantly associated with all symptom clusters in females; the somatic symptom cluster displayed the largest effect.
These results provide supportive evidence of a divergent relationship between inflammation and symptom burden in male and female athletes following SRC. Future investigations should be cognizant of the potentially sex-specific pathophysiology underlying symptom presentation.
The Letter Cancellation Task (LCT) is a widely used pen-and-paper probe of attention in clinical and research settings. Despite its popularity, the neural correlates of the task are not well ...understood. The present study uses functional magnetic resonance imaging (fMRI) and specialized tablet technology to identify the neural correlates of the LCT in 32 healthy older adults between 50-85 years of age, and further investigates the effect of healthy aging on performance. Subjects performed the LCT in its standard pen-and-paper administration and with the tablet during fMRI. Performance on the tablet was significantly slower than on pen-and-paper, with both response modes showing slower performance as a function of age. Across all ages, bilateral brain activation was observed in the cerebellum, superior temporal lobe, precentral gyrus, frontal gyrus, and occipital and parietal areas. Increasing age correlated with reduced brain activity in the supplementary motor area, middle occipital gyrus, medial and inferior frontal gyrus, cerebellum and putamen. Better LCT performance was correlated with increased activity in the middle frontal gyrus, and reduced activity in the cerebellum. The brain regions activated are associated with visuospatial attention and motor control, and are consistent with the neural correlates of LCT performance previously identified in lesion studies.
The long-term health effects of concussion and sub-concussive impacts in sport are unknown. Growing evidence suggests both inflammation and neurodegeneration are pivotal to secondary injury processes ...and the etiology of neurodegenerative diseases. In the present study we characterized circulating brain injury and inflammatory mediators in healthy male and female athletes according to concussion history and collision sport participation. Eighty-seven university level athletes (male, n = 60; female, n = 27) were recruited before the start of the competitive season. Athletes were healthy at the time of the study (no medications, illness, concussion or musculoskeletal injuries). Dependent variables included 29 inflammatory and 10 neurological injury analytes assessed in the peripheral blood by immunoassay. Biomarkers were statistically evaluated using partial least squares multivariate analysis to identify possible relationships to self-reported previous concussion history, number of previous concussions and collision sport participation in male and female athletes. Multiple concussions were associated with increases in peripheral MCP-1 in females, and MCP-4 in males. Collision sport participation was associated with increases in tau levels in males. These results are consistent with previous experimental and clinical findings that suggest ongoing inflammatory and cerebral injury processes after repetitive mild head trauma. However, further validation is needed to correlate systemic biomarkers to repetitive brain impacts, as opposed to the extracranial effects common to an athletic population such as exercise and muscle damage.
•Analyzed neurometabolite changes associated with sport-related concussion.•Followed concussed athletes from acute injury to one year after return to play (RTP).•Myo-inositol was elevated at RTP but ...had resolved at one year post-RTP.•Neurometabolite response was greater in athletes without history of concussion.•Myo-inositol levels were significantly correlated with DTI and fMRI parameters.
Sport-related concussion is associated with acute disturbances in neurometabolic function, with effects that may last weeks to months after injury. However, is presently unknown whether these disturbances resolve at medical clearance to return to play (RTP) or continue to evolve over longer time intervals. Moreover, little is known about how these neurometabolic changes correlate with other measures of brain physiology. In this study, these gaps were addressed by evaluating ninety-nine (99) university-level athletes, including 33 with sport-related concussion and 66 without recent injury, using multi-parameter magnetic resonance imaging (MRI), which included single-voxel spectroscopy (SVS), diffusion tensor imaging (DTI) and resting-state functional MRI (fMRI). The concussed athletes were scanned at the acute phase of injury (27/33 imaged), medical clearance to RTP (25/33 imaged), one month post-RTP (25/33 imaged) and one year post-RTP (13/33 imaged). We measured longitudinal changes in N-acetyl aspartate (NAA) and myo-inositol (Ins), over the course of concussion recovery. Concussed athletes showed no significant abnormalities or longitudinal change in NAA values, whereas Ins was significantly elevated at RTP and one month later. Interestingly, Ins response was attenuated by a prior history of concussion. Subsequent analyses identified significant associations between Ins values, DTI measures of white matter microstructure and fMRI measures of functional connectivity. These associations varied over the course of concussion recovery, suggesting that elevated Ins values at RTP and beyond reflect distinct changes in brain physiology, compared to acute injury. These findings provide novel information about neurometabolic recovery after a sport-related concussion, with evidence of disturbances that persist beyond medical clearance to RTP.
Concussion is associated with acute cognitive impairments, with declines in processing speed and reaction time being common. In the clinical setting, these issues are identified
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symptom ...assessments and neurocognitive test (NCT) batteries. Practice guidelines recommend integrating both symptoms and NCTs into clinical decision-making, but correlations between these measures are often poor. This suggests that many patients experience difficulties in the self-appraisal of cognitive issues. It is presently unclear what neural mechanisms give rise to appraisal mismatch after a concussion. One promising target is the insula, which regulates aspects of cognition, particularly interoception and self-monitoring. The present study tested the hypothesis that appraisal mismatch is due to altered functional connectivity of the insula to frontal and midline structures, with hypo-connectivity leading to under-reporting of cognitive issues and hyper-connectivity leading to over-reporting. Data were collected from 59 acutely concussed individuals and 136 normative controls, including symptom assessments, NCTs and magnetic resonance imaging (MRI) data. Analysis of resting-state functional MRI supported the hypothesis, identifying insular networks that were associated with appraisal mismatch in concussed athletes that included frontal, sensorimotor, and cingulate connections. Subsequent analysis of diffusion tensor imaging also determined that symptom over-reporting was associated with reduced fractional anisotropy and increased mean diffusivity of posterior white matter. These findings provide new insights into the mechanisms of cognitive appraisal mismatch after a concussion. They are of particular interest given the central role of symptom assessments in the diagnosis and clinical management of concussion.
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