Over the last 25 years, many Veterans who were deployed to the Gulf War (GW) have continued to report chronic health symptoms of unknown cause. Our research team first began following a cohort of Veterans who returned from deployment in 1991 through Ft. Devens, MA. This group was initially called the Ft. Devens Operation Desert Storm Reunion survey participants, and over time they have been known as the Ft. Devens Cohort (FDC). The participants first filled out questionnaires pertaining to their mood and reintegration status, but it became clear after speaking with many of these Veterans that not only were they ill, but they were reporting chronic or worsening health concerns and that more extensive health symptom and exposure surveys needed to be done. At that time (in the late 1990s), we began to see smaller groups of individuals to complete in-person evaluations, including environmental exposure questionnaires, memory and attention testing, and MRI (magnetic resonance imaging) brain scans (Time 3). Our goal was to more adequately document problems in memory/thinking abilities and to get a better idea about what individuals were exposed to in the Gulf region, including toxic chemicals such as chemical sprays, anti-nerve gas pills (PB), and sarin nerve gas. Our participants reported that joint pain, headaches, memory and attention difficulties, skin rash, gastrointestinal difficulties, and sleep problems were the most commonly reported chronic symptoms. It was also documented that toxicant exposures such as sarin gas was significantly correlated with slowed motor speed (reaction times) and visuospatial functioning on cognitive testing. At that same time period, our team conducted in-person cognitive, mood and exposure assessments on GW Veterans who were referred for neuropsychological clinics for cognitive concerns. This 200-member treatment-seeking GW Veteran cohort (known as the TSC) performed more poorly on measures of attention, visual memory, visuospatial functioning, and mood than non-deployed-era Veterans. In addition, MRI brain imaging findings on a subset of 54 of these individuals showed TSC participants reporting more chronic health symptoms had less total brain white matter. Follow-up studies of the FDC in the early 2000s found that individuals who encountered chemical odors during their GW deployment were 6 times more likely to meet criteria for severe chronic multi-symptom illness (CMI) of Fukuda et al., while those who consumed more than 20 anti-nerve gas (PB) pills during deployment were 2 to 4 times more likely to meet CMI criteria. Dr. Maxine Krengel currently leads the latest FDC resurvey effort where 600 participants are expected to participate and rates current of CMI and Kansas GWI criteria are being determined. In addition, 200 FDC participants are taking part in a study to assess genetic susceptibility to environmental exposures and one oxidative stress marker (PON1). We have also found that about two-thirds of GW Veteran respondents have a self-reported history of mild concussion or traumatic brain injury (mTBI). Results from this latest study show that toxic exposures and TBI significantly correlate with the criteria for CMI/GWI. Further, those who reported experiencing multiple TBIs reported significantly more health symptoms during the past month than those reporting a single TBI. We are now proposing a follow-up in-person study to reassess memory and attention and other cognitive functions in 150 FDC/TSC Veterans. In addition, we are proposing to use previously unavailable neuroimaging markers (MRS) of oxidative stress in the brain (GSH) that we will compare with blood markers. Oxidative stress has been found to occur after TBI and exposures to GW toxic chemicals. We aim to compare current cognitive functioning and MRI brain volumes to prior testing done with our FDC cohort and to determine current biological markers (MRI, MRS, blood) to aid in devising a diagnostic test for GWI. The overarching objective of this work is to improve our understanding of the pathology behind the chronic health symptoms GW Veterans have endured for 25 years and to identify targeted treatment strategies for these symptoms.

GWI can have a dramatic impact on the lives and well-being of GW Veterans who experience these chronic symptoms. The results of this study will help address a critical knowledge gap regarding the nature of continued cognitive symptoms and other chronic health effects of GWI by comparing data collected at Time 3 (1997) to current functioning (Time 6) in 150 sick and well GW Veterans. This project will distinguish itself by examining the nature and trajectory of symptoms by adding objective markers of cognitive decline, traditional structural MRI neuroimaging, and cutting-edge brain imaging techniques (MRS) in GW Veterans. This study provides an unprecedented opportunity to further characterize objective biomarkers of illness in GW Veterans and offers an opportunity to determine whether a given therapeutic strategy, such as antioxidants (co-enzyme Q-10, quercetin), may be chosen as treatment options by utilizing a personalized medicine approach to treatment based on the Veteran's chronic biomarkers. The hope is that results from this study can be quickly implemented into diagnostic tests and targeted treatments for GWI, which would improve the quality of life for thousands of ill GW Veterans.