Despite uncertainty in the Department of Defense (DOD) ''plume''model assumptions of sarin (GB;o-isopropyl methylphosphonoflouridate) and cyclosarin (GF;cyclohexyl methylphosphonoflouridate) exposure following the destruction of an Iraqi munitions storage complex at Khamisiyah, Iraq during the first Gulf War (GW), we and others have found evidence of brain atrophy in three separate cohorts of GW veterans with suspected exposure at 8-19 years after the incident.[1-3] We believe this makes it the most replicated biological finding in GW veterans to date and worthy of additional research. However, the combined total number of GW veterans with suspected exposure in the past studies (N=130) represents only a tiny fraction of the more than 100,000 GW veterans with suspected GB/GF exposure. Therefore, it is important to confirm and extend the findings of structural and functional brain changes in a larger, non-overlapping sample of GB/GF exposed GW veterans. The goal of this study is to replicate and extend our previous findings of brain atrophy and cognitive impairment in a new sample of 150 GB/GF exposed relative to a new sample of 150 matched non-GB/GF exposed GW veterans.
The first aim i s to replicate our previous findings of reduced brain volume in GB/GF exposed veterans.
Aim 2 will expand our previous finding of hippocampal atrophy in GB/GF exposed veterans by examining the effect of GB/GF exposure on hippocampal subfields.
Aim 3 will expand our previous finding of reduced total brain white matter volume in GB/GF-exposed veterans by using diffusion tensor imaging (DTI) to examine the effects of GB/GF exposure on white matter microstructure integrity.
Aim 4 will replicate and extend our previous finding of impaired cognitive function (i.e., attention and memory) in GB/GF exposed GW veterans. Exploratory analyses will: 1) examine the relationship between estimated cumulative GB/GF exposure levels, based on the DOD reanalysis of the 2000 plume models using improved meteorological modeling and more accurate estimates of the total number of GB/GF-containing rockets destroyed with measures of brain and hippocampal subfield volumes, DTI indices, and cognitive performance;2) assess potential differences in wartime experiences between exposed and non-exposed groups using Dr. Lea Steele's Kansas Gulf War Military and Health Questionnaire [4,5] and the relationship between these wartime experiences with measures of brain and hippocampal subfield volumes, DTI values, and cognitive performance. The exposed and unexposed GW veterans will be a priori matched for age, sex, and Gulf War Illness status. We will account for other potentially confounding variables such as years of education, posttraumatic stress disorder and depression symptom severity, smoking, alcohol and non-alcohol substance use, apolipoprotein ? 4 genotype, and for analyses of brain volume, intracranial volume as covariates in the statistical analyses. Evidence suggests that reduced brain volume and impaired cognitive function may increase vulnerability to the pathological effects of neurodegenerative disease, such as Alzheimer's disease. Therefore, if we find confirmatory evidence of neurodegeneration and cognitive impairment in yet another cohort of GB/GF exposed GW veterans, this could have implications for the VA to employ non-pharmacological, and pharmacological, when they become available, dementia preventive measures in the treatment of GW veterans with suspected GB/GF exposure as these veterans approach old age.

Public Health Relevance

We and others have found evidence of brain atrophy and cognitive impairment in three separate cohorts of Gulf War (GW) veterans with suspected low-level exposure to sarin (GB) and cyclosarin (GF). Thus, there is strong justification for continued study of the consequences of such exposure. However, the combined total number of GB/GF exposed veterans in these past studies (N=130) represents a tiny fraction of the more than 100,000 GW veterans with suspected exposure. Therefore, the goal of this study is to replicate and extend our previous findings in a new, non-overlapping sample of 150 GW veterans from the exposure zone and 150 unexposed matched veterans with cognitive tests, structural, and diffusion tensor imaging. Because reduced brain volume and cognitive impairment may increase one's vulnerability to dementia, if we find evidence of neurodegeneration in yet another cohort of GB/GF-exposed GW veterans, this could have implications for the VA to employ dementia preventive measures in the treatment of these veterans as they approach old age.

Agency
National Institute of Health (NIH)
Institute
Veterans Affairs (VA)
Type
Non-HHS Research Projects (I01)
Project #
1I01CX000798-01A2
Application #
8581089
Study Section
Special Emphasis - Research on Gulf War Veterans' Illnesses (SPLD)
Project Start
2013-10-01
Project End
2017-09-30
Budget Start
2013-10-01
Budget End
2014-09-30
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Veterans Affairs Medical Center San Francisco
Department
Type
DUNS #
078763885
City
San Francisco
State
CA
Country
United States
Zip Code
94121