INS NYC 2024 Program

Poster	Poster Session 03 Program Schedule 02/15/2024 09:30 am - 10:40 am Room: Shubert Complex (Posters 1-60) Poster Session 03: Neurotrauma \| Neurovascular Final Abstract #55 Inflammatory, neurodegenerative, and axonal blood and brain marker associations to memory performance in chronic to remote mild TBI. Samantha Penhale, University of Florida, Gainesville, United States Abigail Waters, University of Florida, Gainesville, United States Damon Lamb, University of Florida, Gainesville, United States Claudia Robertson, Baylor College of Medicine, Houston, United States Richard Rubenstein, SUNY Downstate Health Sciences University, Brooklyn, United States Amy Wagner, University of Pittsburgh, Pittsburgh, United States Firas Kobeissy, Morehouse School of Medicine, Atlanta, United States Kevin Wang, Morehouse School of Medicine, Atlanta, United States John Williamson, University of Florida, Gainesville, United States Category: Concussion/Mild TBI (Adult) Keyword 1: learning Keyword 2: concussion/ mild traumatic brain injury Objective: The mechanistic relationship of chronic to remote traumatic brain injury (TBI) to cognitive outcomes is unclear, but there is elevated risk in some patients for neurodegenerative disease and accelerated aging-related brain changes. The objective of the present study was to determine the associations between learning and brain and systemic indicators of brain health including blood biomarkers of white matter injury and neurodegeneration (serum neurofilament light [NFL], phosphorylated neurofilament heavy [pNFH], and phosphorylated tau [pTau]) and neuroimaging indicators of neuronal integrity and inflammation (total N-acetylaspartate [tNAA], myo-inositol [mI], total choline-containing compounds [tCho], glutamate and glutamine [Glx], and their ratios to total creatine and phosphocreatine [tCr]) in a sample of Veterans and non-Veterans with and without a history of chronic, remote TBI (i.e., >6 months). Participants and Methods: Participants with mild to moderate TBI and age-matched controls who completed neuropsychological testing, blood assays (pTau n = 105, NFL n = 92, pNFH n = 63), and MRI (TBI only n = 54) were sampled from a larger multisite study of chronic mild-severe TBI. Participants ranged in age from 18 to 58 years old (mean age = 36, SD = 9.92). T1-weighted MPRAGE and magnetic resonance spectroscopy (MRS) data were collected on a 3T Siemens Prisma scanner and used to determine brain structure and metabolite concentration in a large frontal lobe voxel. We performed a series of linear regressions on the relationships of NFL, pNFH, pTau, and metabolites of interest to learning as assessed by the CVLT-II, including age as a covariate of no interest. Further, we evaluated an indicator of TBI severity (AOC versus LOC) and the volume of a key brain structure in memory encoding, the hippocampus. Results: CVLT-II total learning score on trials 1 through 5 was negatively associated with NFL (r = -0.300), pTau (r = -0.246), and Glx/tCr (r = -0.457), and positively associated with tCho/tCr (r = 0.314) above and beyond the effect of age. Serum NFL was negatively associated with tCho/tCr (r = -0.361), but had no association with Glx/tCr (r = 0.029). No relationship to hippocampal volume was observed. tCho/tCr was found to be significantly lower in those who experienced LOC compared to those with AOC. CVLT-II learning had no relationships with pNFH or the remaining cerebral metabolites of interest. Conclusions: Results suggest that, in a sample of individuals with chronic, remote mild-moderate TBI, blood and MRS markers of brain health and possible white matter injury are associated with a critical cognitive process, learning. Higher pTau, associated with poorer learning in this sample, may reflect pathological changes in neurophysiology. Elevations of cholinergic-containing compounds are often associated with inflammation; thus, it is not clear why we see degraded performance associated with higher Cho/tCr. It is also counterintuitive that NFL is negatively associated with Cho/tCR. We previously demonstrated NFL associations to cognitive outcomes in the acute to <6-month time frame. Though causality is unclear, NFL association with a key cognitive process in this sample of chronic to remote TBI is notable.

Poster

02/15/2024
09:30 am - 10:40 am
Room: Shubert Complex (Posters 1-60)

Poster Session 03: Neurotrauma | Neurovascular

Final Abstract #55

Inflammatory, neurodegenerative, and axonal blood and brain marker associations to memory performance in chronic to remote mild TBI.

Samantha Penhale, University of Florida, Gainesville, United States
Abigail Waters, University of Florida, Gainesville, United States
Damon Lamb, University of Florida, Gainesville, United States
Claudia Robertson, Baylor College of Medicine, Houston, United States
Richard Rubenstein, SUNY Downstate Health Sciences University, Brooklyn, United States
Amy Wagner, University of Pittsburgh, Pittsburgh, United States
Firas Kobeissy, Morehouse School of Medicine, Atlanta, United States
Kevin Wang, Morehouse School of Medicine, Atlanta, United States
John Williamson, University of Florida, Gainesville, United States

Category: Concussion/Mild TBI (Adult)

Keyword 1: learning
Keyword 2: concussion/ mild traumatic brain injury

Objective:

The mechanistic relationship of chronic to remote traumatic brain injury (TBI) to cognitive outcomes is unclear, but there is elevated risk in some patients for neurodegenerative disease and accelerated aging-related brain changes. The objective of the present study was to determine the associations between learning and brain and systemic indicators of brain health including blood biomarkers of white matter injury and neurodegeneration (serum neurofilament light [NFL], phosphorylated neurofilament heavy [pNFH], and phosphorylated tau [pTau]) and neuroimaging indicators of neuronal integrity and inflammation (total N-acetylaspartate [tNAA], myo-inositol [mI], total choline-containing compounds [tCho], glutamate and glutamine [Glx], and their ratios to total creatine and phosphocreatine [tCr]) in a sample of Veterans and non-Veterans with and without a history of chronic, remote TBI (i.e., >6 months).

Participants and Methods:

Participants with mild to moderate TBI and age-matched controls who completed neuropsychological testing, blood assays (pTau n = 105, NFL n = 92, pNFH n = 63), and MRI (TBI only n = 54) were sampled from a larger multisite study of chronic mild-severe TBI. Participants ranged in age from 18 to 58 years old (mean age = 36, SD = 9.92). T1-weighted MPRAGE and magnetic resonance spectroscopy (MRS) data were collected on a 3T Siemens Prisma scanner and used to determine brain structure and metabolite concentration in a large frontal lobe voxel. We performed a series of linear regressions on the relationships of NFL, pNFH, pTau, and metabolites of interest to learning as assessed by the CVLT-II, including age as a covariate of no interest. Further, we evaluated an indicator of TBI severity (AOC versus LOC) and the volume of a key brain structure in memory encoding, the hippocampus.

Results:

CVLT-II total learning score on trials 1 through 5 was negatively associated with NFL (r = -0.300), pTau (r = -0.246), and Glx/tCr (r = -0.457), and positively associated with tCho/tCr (r = 0.314) above and beyond the effect of age. Serum NFL was negatively associated with tCho/tCr (r = -0.361), but had no association with Glx/tCr (r = 0.029). No relationship to hippocampal volume was observed. tCho/tCr was found to be significantly lower in those who experienced LOC compared to those with AOC. CVLT-II learning had no relationships with pNFH or the remaining cerebral metabolites of interest.

Conclusions:

Results suggest that, in a sample of individuals with chronic, remote mild-moderate TBI, blood and MRS markers of brain health and possible white matter injury are associated with a critical cognitive process, learning. Higher pTau, associated with poorer learning in this sample, may reflect pathological changes in neurophysiology. Elevations of cholinergic-containing compounds are often associated with inflammation; thus, it is not clear why we see degraded performance associated with higher Cho/tCr. It is also counterintuitive that NFL is negatively associated with Cho/tCR. We previously demonstrated NFL associations to cognitive outcomes in the acute to <6-month time frame. Though causality is unclear, NFL association with a key cognitive process in this sample of chronic to remote TBI is notable.