IMAGING [18F]AV1451 AND [18F] AV-45 IN SERVICE MEMBERS WITH BLAST RELATED MILD TRAUMATIC BRAIN INJURY

Traumatic brain injury (TBI) is recognized as one of the key injuries sustained by military personnel in the recent conflicts in Iraq and Afghanistan. It is estimated that between 2000 and 2010 over 200,000 veterans have been diagnosed with mild TBI (mTBI) due to single or multiple exposures to improvised explosive devices (IEDs). As such, active duty service members and veterans will be facing significant health issues related to mTBI and dementia, which will become increasingly costly for both military service members and for federal programs that provide medical treatment. TBI has an acute impact on neurologic function; however, the potential long-term effects of TBI are poorly understood. Severe single TBI has been associated with an elevated incidence of Alzheimer’s disease (AD) along with a reduced age of onset for AD. mTBI, which generally results from multiple mild head injuries such as concussions and blast exposure from IEDs, has been shown to be associated with a tauopathy referred to as chronic traumatic encephalopathy (CTE). CTE shares some of the pathological hallmarks and cognitive deficits observed in AD such as the aggregation of a protein called tau, which is important for maintaining cellular structure, and the aggregation of a protein called amyloid beta, which is thought to be a causative factor in the development of AD. Also, CTE, like AD, can only be diagnosed postmortem. There are growing concerns about the potential long-term neurologic consequences of blast exposure. It is known that retired boxers and National Football League players develop CTE at a higher rate and a younger age compared with the general population. However, the relationship between mTBI, blast exposures, and the subsequent development of chronic neurodegenerative disease has not been established in military populations. Further, as the definitive diagnosis CTE is presently made at autopsy, clinical tools, and biomarkers for detecting and diagnosing this condition in life remain to be defined. Therefore, there is a critical need for clinical tools and biomarkers for detecting mTBI in early stages and setting a baseline measurement of brain abnormalities in order to allow for proper treatment and to monitor treatment efficacy. With the advent of FDA-approved brain imaging biomarkers, it has become easier to make more accurate diagnoses of brain disorders. On such imaging modality is positron emission tomography (PET). PET is a functional imaging technique that can be used to produce a three-dimensional image of the brain. It relies on the system detecting a positron-emitting radionuclide (tracer), which is injected into the body. PET imaging for amyloid is commonly used by clinicians to estimate the density of amyloid deposits in the brains of living patients thought to have AD. Recently, a radioactive tracer has been created for that detects the presence of tau deposits in the brain if living individuals. This tracer is being tested for its efficacy in detecting tau in various brain disorders in both animal models of disease and in humans.The goal of this interdisciplinary proposal is to determine the relationship between mTBI and chronic neurodegeneration in blast-exposed active duty military service members and examine their risk for developing neurodegenerative disorders such as CTE. We plan to use neuropsychological testing in conjunction with existing, emerging, and experimental imaging technologies to identify the most promising methods for detecting changes in brain structure and/or function that are attributable to mTBI. Specifically, we will perform two different PET scans, one that identifies tau deposits, and one that identifies amyloid beta deposits. We will also utilize structural and functional magnetic resonance imaging (MRI) and we will administer a battery of neuropsychological tests that assess various behavioral and memory functions. All of these measures together will be used to assess the brain pathology associated with blast exposure. This study will be one of the first to use PET imaging to investigate tau and amyloid in active duty military service members with a history of blast exposure and mTBI, to determine whether these individuals are at risk fro developing CTE. The results from this proposal will aid in the delineation of the cognitive and neurobiological profile of blast-related mTBI in the military population and will provide currently unavailable and crucial information with regard to the risk for developing CTE-like dementia and aid in the development of adequate intervention, new treatments, and improved long-term care planning. Furthermore, the findings from this study may advance scientific knowledge with regard to the neurobiological underpinnings of the complex interaction of mTBI and concomitant cognitive and functional deficits that can develop with age.