Comprehensive Biomarker Panel for Trauma-Related Dementia: Mechanistic Links Among Axonal Injury, Neuroinflammation, and Neurodegeneration
Abstract
NEED – For tens of thousands of traumatic brain injury (TBI) war-wounded survivors, the future is clouded by uncertainty regarding risk for later dementia such as Alzheimer s disease (AD). At present, trauma-related dementia can only be confirmed on autopsy examination of the brain, as there is currently no validated method to diagnose the condition during the life of the patient. For the wounded warrior, the lack of definitive medical tests for predicting TBI subjects at-risk for developing dementia later in life can lead to missing out on treatment interventions designed to limit the risk of long-term brain injury consequences. Without a way to detect neurodegeneration following TBI in the living brain, wounded warriors also potentially face a lifetime of suspicions of malingering and the emotional strains that accompany an uncertain prognosis. PROJECT GOAL – This project will establish a comprehensive panel of tests for trauma-related dementia so that the underlying mechanisms that cause late trauma-induced cognitive impairments may be understood and targeted for therapy. The ultimate goal is to provide a quantitative, early, non-invasive assessment of AD pathology in TBI survivors to identify individuals likely to benefit from therapies under development for treating traumatic encephalopathy as well as the common sporadic form of AD. We plan to provide key insights into the relationship between white matter axonal injury and downstream neurodegenerative pathology. We also intend to deliver tools that can inform the clinical team and the patient of the potential chronic ramifications of TBI with innovative neuroimaging modalities. The panel of tests to be developed, magnetic resonance imaging (MRI) and positron emission tomography (PET) imaging of multiple markers of neurodegeneration combined with spinal fluid and blood biomarkers, will improve both our understanding of the disorder and the diagnostic accuracy of trauma-related dementia. ENCOURAGING CLINICAL RESULTS – The core technology in this proposal has been used extensively to visualize deposits in the brain that are characteristic of AD and, more recently, acute TBI. The imaging and biomarker modalities employed are the most promising tools available today to bridge the gap between TBI and classical AD research to the field of trauma-related dementia. HELPING WAR-WOUNDED AND CIVILIAN TBI – TBI-wounded warriors and their families potentially face decades of anguish, doubt, and poor treatment outcomes. It is imperative to develop tools to identify those TBI survivors who may be at increased risk for cognitive impairment/neurodegeneration. The neuroimaging, spinal fluid, and blood biomarker panel in this study will allow the mechanisms underlying persistent cognitive impairments and neurodegeneration after traumatic brain injury to be teased apart and better understood. Wounded warriors who are at elevated risk can be identified for potential therapeutic intervention and the response to therapy monitored. CLINICAL RESEARCH ADVANCEMENT – To improve evidence-based diagnosis of trauma-related AD neurodegeneration, this project will test and deploy a comprehensive panel consisting of advanced MRI and PET scans and blood tests that will be applied to this condition for the first time in this fashion. The project will further establish whether spinal fluid or blood can be used to identify patients at risk for or suffering from trauma-related neurodegeneration. It will examine patients with documented cognitive consequences and relate those consequences to specific changes in brain metabolism and/or neuroanatomy. It will provide actionable clinical information for clinicians to communicate to TBI survivors the exact nature of their injury. This may help evaluate alternative rehabilitation methods to heal or compensate for damage and lower risk for late consequences of TBI such as cognitive or emotional disturbances.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810739
Entities
People
- David O. Okonkwo
Organizations
- United States Army
- University of Pittsburgh