# Mild TBI and Biomarkers of Neurodegeneration

> **NIH VA I01** · VA PUGET SOUND HEALTHCARE SYSTEM · 2024 · —

## Abstract

Mild traumatic brain injury (mTBI) caused by blast effects of explosive devices is the “signature injury”
of Servicemembers deployed to combat operations in Iraq and Afghanistan. Resultant persistent
postconcussive symptoms (PCS), such as impairment of memory and concentration, irritability, mood
instability, sleep disturbances, and migraine headaches frequently have disabling personal, professional and
domestic consequences. In addition to these immediate consequences, repetitive mTBI may initiate processes
leading to neurodegeneration and dementia.
 This competitive renewal application proposes to continue longitudinally a currently funded VA RR&D
Merit Review: B77421, "Mild TBI and Biomarkers of Neurodegeneration". In the current funding period, we
have made substantial progress in 1) identifying objective structural and functional neuroimaging biomarkers
that characterize the clinical phenotype of blast-induced mTBI, 2) identifying objective impairment and
longitudinal decline in cognitive function in mTBI Veterans using our refined neuropsychological assessment
battery, and 3) identifying in cerebrospinal fluid (CSF) and plasma a group mTBI-specific inter-related
neuroinflammatory chemoattractant, vascular disturbance, and neurodegeneration biomarkers. We have
integrated neuroimaging, cognitive, and biomarker findings into a consistent model of regional cerebellar-
thalamic-frontoparietal cortical and brainstem dysfunction in repetitive blast mTBI. Goals of this continuation
proposal are to determine whether cognitive performance is associated with neuroimaging and/or CSF and
plasma biomarkers of mTBI and/or genetic risk factors for neurodegenerative dementia, and to determine
whether neuroimaging and CSF and plasma biomarker abnormalities are transient, static, or progressive. We
also propose 1) a new plasma biomarker goal: central nervous system (CNS)-derived plasma exosomal cargo
proteins, 2) new clinical assessments of sleep: in-theater sleep history and sleep/activity monitoring via
Actigraphy, and 3) an additional advanced neuroimaging analyses: diffusion tensor imaging Automating-Fiber-
Tract Quantification.
Specific Aim 1: To continue characterizing longitudinally the clinical (neurocognitive, neurologic, behavioral)
and structural/functional neuroimaging characteristics of disrupted cerebellar-thalamic-frontoparietal cortical
and brainstem function in OIF/OEF/OND Veterans with repetitive blast trauma mTBI.
Specific Aim 2: To determine if OEF/OIF/OND Veterans with repetitive mTBI exhibit CSF and plasma
neurovascular, neuroinflammatory, and neurodegeneration biomarker changes associated with the onset and
progression of neurodegenerative dementing disorders.
Specific Aim 3: To determine the effects of genetic risk factors for neurodegeneration (apolipoprotein E
[APOE] polymorphisms and microtubule associated protein tau [MAPT] subhaplotypes) on clinical
characteristics and neuroimaging and biofluid biomarkers in OEF/OIF/OND Veterans w...

## Key facts

- **NIH application ID:** 10793480
- **Project number:** 5I01RX003087-05
- **Recipient organization:** VA PUGET SOUND HEALTHCARE SYSTEM
- **Principal Investigator:** ELAINE R. PESKIND
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2019-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10793480

## Citation

> US National Institutes of Health, RePORTER application 10793480, Mild TBI and Biomarkers of Neurodegeneration (5I01RX003087-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10793480. Licensed CC0.

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