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9 Serum Neurofilament is Associated with Diffusion Kurtosis Imaging in Chronic Mild-Moderate Traumatic Brain Injury
- Erin R Trifilio, Robert D Claar, Aditi Venkatesh, Sarah Bottari, David Barton, Claudia S Robertson, Richard Rubenstein, Amy K Wagner, Kevin K W Wang, Damon G Lamb, John B Williamson
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, p. 121
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Objective:
To determine the association between blood markers of white matter injury (e.g., serum neurofilament light and phosphorylated neurofilament heavy) and a novel neuroimaging technique measuring microstructural white matter changes (e.g., diffusion kurtosis imaging) in regions (e.g., anterior thalamic radiation and uncinate fasciculus) known to be impacted in traumatic brain injury (TBI) and associated with symptoms common in those with chronic TBI (e.g., sleep disruption, cognitive and emotional disinhibition) in a heterogeneous sample of Veterans and non-Veterans with a history of remote TBI (i.e., >6 months).
Participants and Methods:Participants with complete imaging and blood data (N=24) were sampled from a larger multisite study of chronic mild-moderate TBI. Participants ranged in age from young to middle-aged (mean age = 34.17, SD age = 10.96, range = 19-58) and primarily male (66.7%). The number of distinct TBIs ranged from 1-5 and the time since most recent TBI ranged from 0-30 years. Scores on a cognitive screener (MoCA) ranged from 22-30 (mean = 26.75). We performed bivariate correlations with mean kurtosis (MK) in the anterior thalamic radiation (ATR; left, right) uncinate fasciculus (UF; left, right), and serum neurofilament light (NFL), and phosphorylated neurofilament heavy (pNFH). Both were log transformed for non-normality. Significance threshold was set at p<0.05.
Results:pNFH was significantly and negatively correlated to MK in the right (r=-0.446) and left (r=-0.599) UF and right (r=-0.531) and left (r=-0.469) ATR. NFL showed moderate associations with MK in the right (r=-0.345) and left (r=-0.361) UF and little to small association in the right (r=-0.063) and left (r=-0.215) ATR. In post-hoc analyses, MK in both the left (r=0.434) and right (r=0.514) UF was positively associated with performance on a frontally-mediated list-learning task (California Verbal Learning Test, 2nd Edition; Trials 1-5 total).
Conclusions:Results suggest that serum pNFH may be a more sensitive blood marker of microstructural complexity in white matter regions frequently impacted by TBI in a chronic mild-moderate TBI sample. Further, it suggests that even years after a mild-moderate TBI, levels of pNFH may be informative regarding white matter integrity in regions related to executive functioning and emotional disinhibition, both of which are common presenting problems when these patients are seen in a clinical setting.
25 Associations between Diffusion Kurtosis Imaging, Tau, and Cognitive Outcomes in TBI
- Robert D Claar, Aditi Venkatesh, Richard Rubenstein, Kevin Wang, Amy Wagner, Claudia Robertson, Erin Trifilio, John Williamson, Damon Lamb
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 134-135
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- Article
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Objective:
Determine associations between cognitive outcomes in remote TBI (i.e., at least 6 months post injury), a blood marker of neural degeneration (i.e., Tau), and diffusion kurtosis imaging (DKI) measures (e.g., mean or radial kurtosis). Because DKI imaging is sensitive to the environmental complexity of the imaged area, we sought to investigate regions known to be associated with the cognitive and emotional sequalae of TBI, such as the anterior thalamic radiations, uncinate fasciculus, and the corpus callosum.
Participants and Methods:41 individuals with mild-to-moderate TBI and a mean age(SD) of 36.1(10.4) years underwent DKI, a blood draw, and neuropsychological assessments. 23 healthy controls (HC) with a mean age(SD) of 35.2(15.2) years underwent the blood draw and assessments, but no imaging. Higher diffusion kurtosis indicates more restricted diffusion, possibly due to greater complexity within the imaged region. Thus, in the context of TBI, DKI can be used as a proxy measurement for biological processes that alter the complexity of imaged environments, such as reactive gliosis. Some people show cognitive deficits long after TBI and this could be associated with increased inflammation and membrane protein aggregates in damaged brain regions. We used bivariate correlations and general linear models to investigate the association of mean kurtosis (MK) in long white matter tracts and Tau (total or phosphorylated) to color-word Stroop scores; a measure of fronto-subcortical function.
Results:In patients with TBI, MK was significantly associated with serum total Tau (TTau) in the right (r=-0.396) and left (r=-0.555) uncinate fasciculus (UF), right (r=-0.402) and left (r=-0.504) anterior thalamic radiations (ATR), and the genu (r=-0.526) and body (r=-0.404) of the corpus callosum (CC). TTau had a significant association with word Stroop scores, F(1,63)=-2.546, p=0.013. However, there was no significant effect of group (i.e., TBI or HC), F(2,63)=-0.426, p=0.672, on cognitive performance. When models were implemented that included both TTau and MK in either the UF or ATR as explanatory variables to predict word Stroop scores, TTau levels and MK in the right UF explained a significant amount of the variance in Stroop performance, F(1,29)=2.215, p=0.025. Further, there was also a significant association between radial kurtosis in the right UF and Stroop word scores (r= 0.366).
Conclusions:Our results show that an indicator of biological complexity (DKI) in cognitively important brain regions is associated with cognitive performance and Tau in patients with remote mild-to-moderate TBI. The UF is a critical fronto-temporal/subcortical pathway that has previously been implicated in the manifestation of executive dysfunction and mood dysregulation in TBI. Tau is an important marker of neurodegeneration implicated in Alzheimer’s disease, Parkinson’s disease, and chronic traumatic encephalopathy (CTE), and DKI is potentially sensitive to markers of neurodegeneration. The association of Tau and DKI measures is novel and shows concordance between blood and brain imaging markers and cognitive performance in patients with mild to moderate TBI.