Current Health Status of Gulf War Deployed and Gulf War Era Veterans Who Use Veterans Affairs Health Care.

Background: Although some recent studies have examined the health of female Gulf War (GW) deployed and non-deployed GW era veterans, these all relied on self-report, which can be inaccurate and subject to recall bias. This study investigated the current health of GW deployed and non-deployed GW era female and male veterans using Veterans Health Administration (VHA) electronic health records (EHR). Methods: We performed a cohort study of deployed GW and non-deployed GW era veterans, identified from a list from the Defense Manpower Data Center (DMDC). We used the VA-Frailty Index (VA-FI), calculated with VHA administrative claims and EHR, as a proxy measure of current health. Results: We identified 402,869 veterans (351,496 GW deployed; 51,3373 non-deployed GW era; 38,555 female) in VHA databases. Deployed female veterans had the highest VA-FI (i.e., were frailest) despite being younger than deployed and non-deployed male veterans and non-deployed female veterans. Compared with deployed male veterans, deployed females were more likely to be pre-frail, mildly, and moderately frail. Health differences between deployed and non-deployed female veterans were more prominent among older (60+ years) than younger (<60 years) veterans. Conclusions: Mirroring reports from recent, smaller survey studies of users and non-users of VA health care, findings from this cohort study indicate that deployed female GW veterans who use VA health care are frailer and have more health deficits than non-deployed female GW era and deployed male GW veterans. Because deployed female GW veterans appear to have additional health care needs, this may warrant increased outreach from women's clinics at VA hospitals.

Livestream, group movement program for people living with cognitive impairment and care partners: A randomized clinical trial.

INTRODUCTION: There are few widely-available, evidence-based options to support quality of life (QOL) for people living with Alzheimer's disease and related dementias. METHODS: We performed a randomized, controlled trial with a Waitlist control group to determine whether an online, livestream, mind-body, group movement program (Moving Together, 1 hour, 2 days/week, 12 weeks) improves QOL in people with cognitive impairment (PWCI) or care partners (CPs) and explore mechanisms of action. The primary outcome for both participants was self-reported QOL. Secondary outcomes and potential mediators included mobility, isolation, well-being, cognitive function, and sleep in PWCI and burden, positive emotions, caregiver self-efficacy, stress management, and sleep in CPs. Blinded assessors collected outcome data at baseline, 12, and 24 weeks. We assessed adverse events including falls through monthly check-in surveys and collected qualitative data through evaluation surveys. Intention-to-treat analyses used linear mixed models to compare mean change over time between groups and calculated standardized effect sizes (ESs). RESULTS: Ninety-seven dyads enrolled (PWCI: age 76 ± 11 years, 43% female, 80% non-Hispanic White; CPs: age 66 ± 12 years, 78% female, 71% non-Hispanic White); 15% withdrew before 12 weeks and 22% before 24 weeks. PWCI self-reported significantly better QOL from baseline to 12 weeks in the Moving Together group compared to the Waitlist group (ES = 0.474, p = 0.048) and CPs self-reported improved ability to manage stress (ES = 0.484, p = 0.021). Improvements in participant self-reported QOL were mediated by improvements in their self-reported well-being and CP-reported ability to manage stress. Results were similar when the Waitlist group participated in the program (QOL ES = 0.663, p = 0.006; stress management ES = 0.742, p = 0.002) and were supported by qualitative data. Exploratory analyses suggested possible fall reduction in PWCI. There were no study-related serious adverse events. DISCUSSION: Online programs such as Moving Together offer a scalable strategy for supporting high QOL for PWCI and helping CPs manage stress. TRIAL REGISTRATION: ClinicalTrials.gov NCT04621448. Highlights: The approval of new medications that slow cognitive decline in people living with Alzheimer's disease and related disorders (ADRD) has raised hope and excitement. However, these medications do not appear to impact quality of life, which is often considered by patients and care partners to be the most important outcome.In this randomized clinical trial, we found that an evidence-based, online, livestream, mind-body, group movement program significantly and meaningfully improves self-rated quality of life in people with ADRD and helps care partners manage stress. Mediation analyses revealed that the key drivers of improvements in participants' quality of life were improvements in their feelings of well-being and care partners' ability to manage stress. Exploratory analyses also suggested a 30% reduction in falls.These results are important because they suggest that an online program, which is available now and can be performed by people from the comfort of home or other location of choice, could be recommended as a complement or alternative to new therapies to help maximize quality of life for people living with ADRD and their care partners.

Olfactory and cognitive decrements in 1991 Gulf War veterans with gulf war illness/chronic multisymptom illness.

BACKGROUND: Gulf War illness (GWI)/Chronic Multisymptom Illness (CMI) is a disorder related to military service in the 1991 Gulf War (GW). Prominent symptoms of GWI/CMI include fatigue, pain, and cognitive dysfunction. Although anosmia is not a typical GWI/CMI symptom, anecdotally some GW veterans have reported losing their sense smell shortly after the war. Because olfactory deficit is a prodromal symptom of neurodegenerative diseases like Parkinson's and Alzheimer's disease, and because we previously reported suggestive evidence that deployed GW veterans may be at increased risk for Mild Cognitive Impairment (MCI) and dementia, the current study examined the relationship between olfactory and cognitive function in deployed GW veterans. METHODS: Eighty deployed GW veterans (mean age: 59.9 ±7.0; 4 female) were tested remotely with the University of Pennsylvania Smell Identification Test (UPSIT) and the Montreal Cognitive Assessment (MoCA). Veterans also completed self-report questionnaires about their health and deployment-related exposures and experiences. UPSIT and MoCA data from healthy control (HC) participants from the Parkinson's Progression Markers Initiative (PPMI) study were downloaded for comparison. RESULTS: GW veterans had a mean UPSIT score of 27.8 ± 6.3 (range 9-37) and a mean MoCA score of 25.3 ± 2.8 (range 19-30). According to age- and sex-specific normative data, 31% of GW veterans (vs. 8% PPMI HCs) had UPSIT scores below the 10th percentile. Nearly half (45%) of GW veterans (vs. 8% PPMI HCs) had MoCA scores below the cut-off for identifying MCI. Among GW veterans, but not PPMI HCs, there was a positive correlation between UPSIT and MoCA scores (Spearman's ρ = 0.39, p < 0.001). There were no significant differences in UPSIT or MoCA scores between GW veterans with and without history of COVID or between those with and without Kansas GWI exclusionary conditions. CONCLUSIONS: We found evidence of olfactory and cognitive deficits and a significant correlation between UPSIT and MoCA scores in a cohort of 80 deployed GW veterans, 99% of whom had CMI. Because impaired olfactory function has been associated with increased risk for MCI and dementia, it may be prudent to screen aging, deployed GW veterans with smell identification tests so that hypo- and anosmic veterans can be followed longitudinally and offered targeted neuroprotective therapies as they become available.

Examining the current health of Gulf War veterans with the veterans affairs frailty index.

Introduction: Gulf War Illness (GWI) is a chronic, multisymptom (e.g., fatigue, muscle/joint pain, memory and concentration difficulties) condition estimated to affect 25-32% of Gulf War (GW) veterans. Longitudinal studies suggest that few veterans with GWI have recovered over time and that deployed GW veterans may be at increased risks for age-related conditions. Methods: We performed a retrospective cohort study to examine the current health status of 703 GW veterans who participated in research studies at the San Francisco VA Health Care System (SFVAHCS) between 2002 and 2018. We used the Veterans Affairs Frailty Index (VA-FI) as a proxy measure of current health and compared the VA-FIs of GW veterans to a group of randomly selected age- and sex-matched, non-GW veterans. We also examined GW veterans' VA-FIs as a function of different GWI case definitions and in relationship to deployment-related experiences and exposures. Results: Compared to matched, non-GW veterans, GW veterans had lower VA-FIs (0.10 ± 0.10 vs. 0.12 ± 0.11, p < 0.01). However, the subset of GW veterans who met criteria for severe Chronic Multisymptom Illness (CMI) at the time of the SFVAHCS studies had the highest VA-FI (0.13 ± 0.10, p < 0.001). GW veterans who had Kansas GWI exclusionary conditions had higher VA-FI (0.12 ± 0.12, p < 0.05) than veterans who were Kansas GWI cases (0.08 ± 0.08) and controls (i.e., veterans with little or no symptoms, 0.04 ± 0.06) at the time of the SFVAHCS research studies. The VA-FI was positively correlated with several GW deployment-related exposures, including the frequency of wearing flea collars. Discussion: Although GW veterans, as a group, were less frail than non-GW veterans, the subset of GW veterans who met criteria for severe CDC CMI and/or who had Kansas GWI exclusionary conditions at the time of the SFVAHCS research studies were frailest at index date. This suggests that many ongoing studies of GWI that use the Kansas GWI criteria may not be capturing the group of GW veterans who are most at risk for adverse chronic health outcomes.

The prevalence of mild cognitive impairment in Gulf War veterans: a follow-up study.

Introduction: Gulf War Illness (GWI), also called Chronic Multisymptom Illness (CMI), is a multi-faceted condition that plagues an estimated 250,000 Gulf War (GW) veterans. Symptoms of GWI/CMI include fatigue, pain, and cognitive dysfunction. We previously reported that 12% of a convenience sample of middle aged (median age 52 years) GW veterans met criteria for mild cognitive impairment (MCI), a clinical syndrome most prevalent in older adults (e.g., ≥70 years). The current study sought to replicate and extend this finding. Methods: We used the actuarial neuropsychological criteria and the Montreal Cognitive Assessment (MoCA) to assess the cognitive status of 952 GW veterans. We also examined regional brain volumes in a subset of GW veterans (n = 368) who had three Tesla magnetic resonance images (MRIs). Results: We replicated our previous finding of a greater than 10% rate of MCI in four additional cohorts of GW veterans. In the combined sample of 952 GW veterans (median age 51 years at time of cognitive testing), 17% met criteria for MCI. Veterans classified as MCI were more likely to have CMI, history of depression, and prolonged (≥31 days) deployment-related exposures to smoke from oil well fires and chemical nerve agents compared to veterans with unimpaired and intermediate cognitive status. We also replicated our previous finding of hippocampal atrophy in veterans with MCI, and found significant group differences in lateral ventricle volumes. Discussion: Because MCI increases the risk for late-life dementia and impacts quality of life, it may be prudent to counsel GW veterans with cognitive dysfunction, CMI, history of depression, and high levels of exposures to deployment-related toxicants to adopt lifestyle habits that have been associated with lowering dementia risk. With the Food and Drug Administration's recent approval of and the VA's decision to cover the cost for anti-amyloid ß (Aß) therapies, a logical next step for this research is to determine if GW veterans with MCI have elevated Aß in their brains.

Regional gray matter oligodendrocyte- and myelin-related measures are associated with differential susceptibility to stress-induced behavior in rats and humans.

Individual reactions to traumatic stress vary dramatically, yet the biological basis of this variation remains poorly understood. Recent studies demonstrate the surprising plasticity of oligodendrocytes and myelin with stress and experience, providing a potential mechanism by which trauma induces aberrant structural and functional changes in the adult brain. In this study, we utilized a translational approach to test the hypothesis that gray matter oligodendrocytes contribute to traumatic-stress-induced behavioral variation in both rats and humans. We exposed adult, male rats to a single, severe stressor and used a multimodal approach to characterize avoidance, startle, and fear-learning behavior, as well as oligodendrocyte and myelin basic protein (MBP) content in multiple brain areas. We found that oligodendrocyte cell density and MBP were correlated with behavioral outcomes in a region-specific manner. Specifically, stress-induced avoidance positively correlated with hippocampal dentate gyrus oligodendrocytes and MBP. Viral overexpression of the oligodendrogenic factor Olig1 in the dentate gyrus was sufficient to induce an anxiety-like behavioral phenotype. In contrast, contextual fear learning positively correlated with MBP in the amygdala and spatial-processing regions of the hippocampus. In a group of trauma-exposed US veterans, T1-/T2-weighted magnetic resonance imaging estimates of hippocampal and amygdala myelin associated with symptom profiles in a region-specific manner that mirrored the findings in rats. These results demonstrate a species-independent relationship between region-specific, gray matter oligodendrocytes and differential behavioral phenotypes following traumatic stress exposure. This study suggests a novel mechanism for brain plasticity that underlies individual variance in sensitivity to traumatic stress.

Ventromedial and insular cortical volume moderates the relationship between BDNF Val66Met and threat sensitivity.

While the BDNF Val66Met polymorphism has been linked to various trauma and anxiety - related psychiatric disorders, limited focus has been on the neural structures that might modulate its relationship with objective measures of threat sensitivity. Therefore, we assessed whether there was an interaction of Val66Met polymorphism with brain area volumes previously associated with anxiety and PTSD, such as the ventromedial prefrontal cortex (vmPFC), insular cortex (IC), and dorsal and ventral anterior cingulate cortices (dACC and vACC), in predicting fear-potentiated psychophysiological response in a clinical sample of Veterans. 110 participants engaged in a fear-potentiated acoustic startle paradigm and provided genetic and imaging data. Fear conditions included no, ambiguous, and high threat conditions (shock). Psychophysiological response measures included electromyogram (EMG), skin conductance response (SCR), and heart rate (HR). PTSD status, trauma history, and demographics were also assessed. There was an interaction of Met allele carrier status with vmPFC, IC, dACC, and vACC volumes for predicting SCR (p < 0.001 for all regions). However, only vmPFC and IC significantly moderated the relationship between Val66Met and psychophysiological response (SCR). The Val66met polymorphism may increase susceptibility to PTSD and anxiety disorders via an interaction with reduced vmPFC and IC volume. Future research should examine whether these relationships might be associated with a differential course of illness longitudinally or response to treatments.

Preventing Loss of Independence through Exercise (PLIÉ): A Pilot Trial in Older Adults with Subjective Memory Decline and Mild Cognitive Impairment.

BACKGROUND: Preventing Loss of Independence through Exercise (PLIÉ) is a group movement program initially developed for people with mild-to-moderate dementia that integrates principles from several well-established traditions to specifically address the needs of people with cognitive impairment. OBJECTIVE: To investigate whether PLIÉ would benefit cognitive and behavioral outcomes and functional brain connectivity in older adults with milder forms of cognitive impairment. METHODS: Participants (≥55 y) with subjective memory decline (SMD) or mild cognitive impairment (MCI) were assessed with tests of cognitive and physical function, self-report questionnaires, and resting state functional magnetic resonance imaging (rs-fMRI) on a 3 Tesla scanner before and after participating in twice weekly PLIÉ classes for 12 weeks at the San Francisco Veterans Affairs Medical Center. RESULTS: Eighteen participants completed the pre-post intervention pilot trial. We observed significant improvements on the Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog; effect size 0.34, p = 0.002) and enhanced functional connections between the medial prefrontal cortex (mPFC) and other nodes of the default mode network (DMN) after PLIÉ. Improvements (i.e., lower scores) on ADAS-cog were significantly correlated with enhanced functional connectivity between the mPFC and left lateral parietal cortex (Spearman's ρ= -0.74, p = 0.001) and between the mPFC and right hippocampus (Spearman's ρ= -0.83, p = 0.001). After completing PLIÉ, participants reported significant reductions in feelings of social isolation and improvements in well-being and interoceptive self-regulation. CONCLUSION: These preliminary findings of post-PLIÉ improvements in DMN functional connectivity, cognition, interoceptive self-regulation, well-being and reduced feelings of social isolation warrant larger randomized, controlled trials of PLIÉ in older adults with SMD and MCI.

Cognitive behavioral therapy for insomnia in veterans with gulf war illness: Results from a randomized controlled trial.

AIMS: To examine whether cognitive behavioral therapy for insomnia (CBT-I), delivered by telephone, improves sleep and non-sleep symptoms of Gulf War Illness (GWI). MAIN METHODS: Eighty-five Gulf War veterans (21 women, mean age: 54 years, range 46-72 years) who met the Kansas GWI case definition, the Centers for Disease Control and Prevention (CDC) case definition for Chronic Multisymptom Illness (CMI), and research diagnostic criteria for insomnia disorder were randomly assigned to CBT-I or monitor-only wait list control. Eight weekly sessions of individual CBT-I were administered via telephone by Ph.D. level psychologists to study participants. Outcome measures included pre-, mid-, and post-treatment assessments of GWI and insomnia symptoms, subjective sleep quality, and continuous sleep monitoring with diary. Outcomes were re-assessed 6-months post-treatment in participants randomized to CBT-I. KEY FINDINGS: Compared to wait list, CBT-I produced significant improvements in overall GWI symptom severity, individual measures of fatigue, cognitive dysfunction, depression and anxiety, insomnia severity, subjective sleep quality, and sleep diary outcome measures. The beneficial effects of CBT-I on overall GWI symptom severity and most individual GWI symptom measures were maintained 6-months after treatment. SIGNIFICANCE: GWI symptoms have historically been difficult to treat. Because CBT-I, which is associated with low stigma and is increasingly readily available to veterans, improved both sleep and non-sleep symptoms of GWI, these results suggest that a comprehensive approach to the treatment of GWI should include behavioral sleep interventions.

The Prevalence of Mild Cognitive Impairment in a Convenience Sample of 202 Gulf War Veterans.

Gulf War Illness (GWI) is a chronic, multisymptom disorder estimated to affect approximately 25-32% of Gulf War veterans (GWVs). Cognitive dysfunction is a common symptom of GWI. On the continuum of cognitive decline, mild cognitive impairment (MCI) is conceptualized as a transitional phase between normal aging and dementia. Individuals with MCI exhibit cognitive decline but have relatively spared activities of daily function and do not meet criteria for dementia. The current study sought to investigate the prevalence of MCI in a convenience sample of 202 GWVs (median age: 52 years; 18% female). Twelve percent of the sample (median age: 48 years) had MCI according to an actuarial neuropsychological criterion, a rate materially higher than expected for this age group. GWVs with MCI also had a smaller hippocampal volume and a thinner parietal cortex, higher rates of current posttraumatic stress disorder and major depressive disorder compared to GWVs without MCI. Because people with MCI are more likely to progress to dementia compared to those with normal cognition, these results may portend future higher rates of dementia among deployed GWVs.

Changes in Brain Function and Structure After Self-Administered Home Photobiomodulation Treatment in a Concussion Case.

Traumatic brain injury (TBI) is a common neurological disorder among athletes. Although there are no widely accepted treatments for TBI, new investigational approaches, such as photobiomodulation (PBM), are being tested. PBM is a light therapy that uses red to near-infrared (NIR) light to stimulate, heal, and protect tissue that has been injured or is at risk of dying. Benefits following transcranial PBM treatments in animal models of acute TBI and a small number of chronic TBI patients have been reported. However, the human PBM TBI studies published to date have been based on behavioral assessments. This report describes changes in behavioral and neuroimaging measures after 8 weeks of PBM treatments. The subject was a 23-year professional hockey player with a history of concussions, presumed to have caused his symptoms of headaches, mild anxiety, and difficulty concentrating. He treated himself at home with commercially available, low-risk PBM devices that used light-emitting diodes (LEDs) to emit 810-nm light pulsing at 10 or 40 Hz delivered by an intranasal and four transcranial modules that targeted nodes of the default mode network (DMN) with a maximum power density of 100 mW/cm2. After 8 weeks of PBM treatments, increased brain volumes, improved functional connectivity, and increased cerebral perfusion and improvements on neuropsychological test scores were observed. Although this is a single, sport-related case with a history of concussions, these positive findings encourage replication studies that could provide further validation for this non-invasive, non-pharmacological modality as a viable treatment option for TBI.

Effects of Home Photobiomodulation Treatments on Cognitive and Behavioral Function, Cerebral Perfusion, and Resting-State Functional Connectivity in Patients with Dementia: A Pilot Trial.

Objective: To examine the effects of transcranial and intranasal photobiomodulation (PBM) therapy, administered at home, in patients with dementia. Background: This study sought to replicate and build upon a previously published case series report describing improved cognitive function in five patients with mild-to-moderate dementia after 12 weeks of transcranial and intranasal near-infrared (NIR) PBM therapy. Materials and methods: Eight participants (mean age: 79.8 ± 5.8 years old) diagnosed with dementia by their physicians were randomized to 12 weeks of usual care (UC, n = 4) or home PBM treatments (n = 4). The NIR PBM treatments were administered by a study partner at home three times per week with the Vielight Neuro Gamma device. The participants were assessed with the Alzheimer's Disease Assessment Scale-cognitive (ADAS-cog) subscale and the Neuropsychiatric Inventory (NPI) at baseline and 6 and 12 weeks, and with arterial spin-labeled perfusion magnetic resonance imaging (MRI) and resting-state functional MRI at baseline and 12 weeks. Results: At baseline, the UC and PBM groups did not differ demographically or clinically. However, after 12 weeks, there were improvements in ADAS-cog (group × time interaction: F1,6 = 16.35, p = 0.007) and NPI (group × time interaction: F1,6 = 7.52, p = 0.03), increased cerebral perfusion (group × time interaction: F1,6 = 8.46, p < 0.03), and increased connectivity between the posterior cingulate cortex and lateral parietal nodes within the default-mode network in the PBM group. Conclusions: Because PBM was well tolerated and associated with no adverse side effects, these results support the potential of PBM therapy as a viable home treatment for individuals with dementia.

Improvements in Gulf War Illness Symptoms After Near-Infrared Transcranial and Intranasal Photobiomodulation: Two Case Reports.

At least one-fourth of US veterans who served in the 1990-1991 Gulf War (GW) are affected by the chronic symptomatic illness known as Gulf War illness (GWI). This condition typically includes some combination of fatigue, headaches, cognitive dysfunction, musculoskeletal pain, and respiratory, gastrointestinal and dermatologic complaints. To date, effective treatments for GWI have been elusive. Photobiomodulation (PBM) describes the non-pharmacological, non-thermal use of light to stimulate, heal, and protect tissue that has either been injured, is degenerating, or else is at risk of dying. Significant benefits have been reported following application of transcranial PBM to humans with acute stoke, traumatic brain injury (TBI), and dementia. This report describes the first documentation of improved GWI symptoms in two GW veterans following 12 weeks of PBM treatments.

Child abuse interacts with hippocampal and corpus callosum volume on psychophysiological response to startling auditory stimuli in a sample of veterans.

Child abuse (CA), which is linked to posttraumatic stress disorder (PTSD), has been associated with a reduction in both hippocampal and corpus callosum (CC) volume. However, few studies have explored these relationships on psychophysiological variables related to trauma exposure. Therefore, we assessed whether the interaction between CA and hippocampal and CC volume were associated with enhanced fear potentiated psychophysiological response patterns in a sample of Veterans. 147 Veteran participants who were part of a larger study of Gulf War Illness were exposed to startling sounds in no, ambiguous, and high threat conditions and also provided MRI data. The Clinician Administered PTSD Scale and Trauma History Questionnaire were used to measure PTSD and CA respectively. Psychophysiological response was measured by EMG, SCR, and heart rate. Repeated-measures mixed linear models were used to assess the significance of CA by neural structure interactions. CA interacted with both hippocampal and CC volume on psychophysiological response magnitudes, where participants with CA and smaller hippocampal volume had greater EMG (p < 0.01) and SCR (p < 0.05) magnitudes across trials and over threat conditions. Participants with CA and smaller CC volume had greater SCR magnitudes across trials and over threat conditions (p < 0.01). Hippocampal and genu volume mediated CA and psychophysiological response magnitude. CA may impact psychophysiological response via a reduction in hippocampal and CC volume. Volumetric reduction in these structures may indicate a neurofunctional, CA-related increase in threat sensitivity, which could portend increased PTSD susceptibility and adverse interpersonal and social consequences across the lifespan.

Effects of low-level sarin and cyclosarin exposure on hippocampal microstructure in Gulf War Veterans.

In early March 1991, shortly after the end of the Gulf War (GW), a munitions dump was destroyed at Khamisiyah, Iraq. Later, in 1996, the dump was found to have contained the organophosphorus (OP) nerve agents sarin and cyclosarin. We previously reported evidence of smaller hippocampal volumes in GW veterans with predicted exposure to the Khamisiyah plume compared to unexposed GW veterans. To investigate whether these macroscopic hippocampal volume changes are accompanied by microstructural alterations in the hippocampus, the current study acquired diffusion-tensor imaging (DTI), T1-, and T2-weighted images from 170 GW veterans (mean age: 53 ±â€¯7 years), 81 of whom had predicted exposure to the Khamisiyah plume according to Department of Defense (DOD) plume modeling. We examined fractional anisotropy (FA), mean diffusivity (MD), and grey matter (GM) density from a hippocampal region of interest (ROI). Results indicate that, even after accounting for total hippocampal GM density (or hippocampal volume), age, sex, apolipoprotein ε4 genotype, and potential confounding OP pesticide exposures, hippocampal MD significantly predicted Khamisiyah exposure status (model p = 0.005, R2 = 0.215, standardized coefficient ß = 0.26, t = 2.85). Hippocampal MD was also inversely correlated with verbal memory learning performance in the entire study sample (p = 0.001). There were no differences in hippocampal FA or GM density; however, veterans with predicted Khamisiyah exposure had smaller hippocampal volumes compared to unexposed veterans. Because MD is sensitive to general microstructural disruptions that lead to increased extracellular spaces due to neuronal death, inflammation and gliosis, and/or to axonal loss or demyelination, these findings suggest that low-level exposure to the Khamisiyah plume has a detrimental, lasting effects on both macro- and micro-structure of the hippocampus.

The Relationship Between Traumatic Brain Injury and Rates of Chronic Symptomatic Illness in 202 Gulf War Veterans.

Introduction: Although not a "signature injury" of Operation Desert Shield/Desert Storm (i.e., Gulf War, GW), some GW veterans have a history traumatic brain injury (TBI). For example, a previous study found that 12.2% of the GW veterans from the Fort Devens Cohort Study had self-reported TBIs. The present study sought to build upon this finding by examining the relationship between TBI and chronic symptomatic illness in a different sample of GW veterans. Materials and Methods: Participants were 202 GW veterans recruited from 2014 to 2018 at the San Francisco Veterans Affairs Medical Center as part of a VA-funded study on the effects of predicted exposure to low levels of sarin and cyclosarin on brain structure and function. The Ohio State University TBI identification method was used to determine lifetime history of TBI. The Kansas Gulf War Military History and Health Questionnaire was used to assess symptoms and to determine cases of Kansas Gulf War Illness (GWI) and Centers for Disease Control and Prevention (CDC) Chronic Multisymptom Illness (CMI). Results: Nearly half (47%) the sample had a history of TBI, but only 7% of the TBIs were sustained in injuries that occurred during the GW. Most of the TBIs were sustained in injuries that occurred prior to (73%) or after (34%) the GW. History of TBI was not associated with higher rates of symptomatic illness when it was narrowly defined (i.e., Kansas GWI cases or cases of severe CMI). History of TBI was only associated with higher rates of symptomatic illness when it is broadly defined (i.e., CDC CMI or mild-moderate CMI). There was suggestive evidence that veterans who sustained TBIs during the GW (only seven in the present sample) have poorer functional outcomes compared with GW veterans with non-GW related TBIs. Conclusions: While TBIs were uncommon during the GW, many GW veterans sustained TBIs prior or after the GW. Because TBI and GWI/CMI share some overlapping symptoms, history of TBI may appear to be associated with increased rates of chronic symptomatic illness in GW veterans if chronic symptomatic illness is defined broadly (i.e., CDC CMI or mild-moderate CMI). History of pre-GW TBI did not affect the veterans' response to exposures/experiences from the GW; however, there was suggestive evidence that veterans who sustained TBIs during the GW may have poorer functional outcomes that GW veterans without TBI or even GW veterans with non-GW-related TBIs. Future, better powered studies with randomly and systematically select participants from the larger population of GW veterans will need to confirm this finding.

Evidence of Objective Memory Impairments in Deployed Gulf War Veterans With Subjective Memory Complaints.

INTRODUCTION: Despite the fact that many veterans returned from the 1991 Gulf War (GW) with complaints of memory difficulties, most neuropsychological studies to date have found little evidence of a correspondence between subjective and objective measures of cognitive function in GW veterans. However, if GW veterans complain about memory problems, it is likely that they experience memory problems in their daily lives. In this respect, it is notable that the past studies that have investigated the relationship between subjective and objective measures of cognitive function in GW veterans used composite measures to quantify subjective complaints and batteries of neuropsychological tests that assessed multiple domains to objectively measure cognitive function. The study's focus on memory was motivated by the suggestive evidence that subjective memory complaint may be a harbinger of further cognitive decline and increased risk for dementia. MATERIALS AND METHODS: This study examined the association between subjective memory complaint (probed with single question: "Do you have difficulty remembering things?") and performance on a single objective test of verbal learning and memory (i.e., California Verbal Learning Test, CVLT-II) in a sample of 428 deployed GW veterans. RESULTS: GW veterans who endorsed memory difficulties performed more poorly on CVLT-II measures of total learning, retention, and delayed recall than GW veterans without subjective memory complaints (p < 0.001), even after accounting for demographic (e.g., age, sex, education) and clinical variables (e.g., diagnoses of current post-traumatic stress disorder [PTSD], depressive disorder, and/or anxiety disorder) that could potentially contribute to memory deficits. Among GW veterans who met the Centers for Disease Control and Prevention criteria for chronic multisymptom illness (N = 272), subjective memory complaint significantly predicted CVLT-II retention scores (ß = -0.12, p = 0.04) and marginally predicted CVLT-II delayed recall scores (ß = -0.11, p = 0.05) over and above potentially confounding demographic and clinical variables. CONCLUSION: This study suggests that deployed GW veterans with subjective memory complaints have objective memory impairments. In light of the evidence linking subjective memory complaint to increased risk for dementia in the elderly, these findings suggest that aging GW veterans with subjective memory complaints should be closely monitored for further cognitive decline.

Evidence of Hippocampal Structural Alterations in Gulf War Veterans With Predicted Exposure to the Khamisiyah Plume.

OBJECTIVES: To replicate and expand our previous findings of smaller hippocampal volumes in Gulf War (GW) veterans with predicted exposure to the Khamisiyah plume. METHODS: Total hippocampal and hippocampal subfield volumes were quantified from 3 Tesla magnetic resonance images in 113 GW veterans, 62 of whom had predicted exposure as per the Department of Defense exposure models. RESULTS: Veterans with predicted exposure had smaller total hippocampal and CA3/dentate gyrus volumes compared with unexposed veterans, even after accounting for potentially confounding genetic and clinical variables. Among veterans with predicted exposure, memory performance was positively correlated with hippocampal volume and negatively correlated with estimated exposure levels and self-reported memory difficulties. CONCLUSIONS: These results replicate and extend our previous finding that low-level exposure to chemical nerve agents from the Khamisiyah pit demolition has detrimental, lasting effects on brain structure and function.

Insomnia Severity, Subjective Sleep Quality, and Risk for Obstructive Sleep Apnea in Veterans With Gulf War Illness.

Despite the fact that sleep disturbances are common in veterans with Gulf War Illness (GWI), there has been a paucity of published sleep studies in this veteran population to date. Therefore, the present study examined subjective sleep quality (assessed with the Pittsburgh Sleep Quality Index), insomnia severity (assessed with the Insomnia Severity Index), and risk for obstructive sleep apnea (assessed with the STOP questionnaire) in 98 Gulf War veterans. Veterans with GWI, defined either by the Kansas or Centers for Disease Control and Prevention criteria, had greater risk for obstructive sleep apnea (i.e., higher STOP scores) than veterans without GWI. This difference persisted even after accounting for potentially confounding demographic (e.g., age, gender) and clinical variables. Veterans with GWI, defined by either the Kansas or Centers for Disease Control and Prevention criteria, also had significantly greater insomnia severity and poorer sleep quality than veterans without GWI (p < 0.05), even after accounting for potentially confounding variables. Furthermore, there were significant, positive correlations between insomnia severity, subjective sleep quality, and GWI symptom severity (p ≤ 0.01). In stepwise linear regression models, insomnia severity significantly predicted GWI status over and above demographic and clinical variables. Together these findings provide good rationale for treating sleep disturbances in the management of GWI.

Associations Between the Self-Reported Frequency of Hearing Chemical Alarms in Theater and Visuospatial Function in Gulf War Veterans.

OBJECTIVE: The aim of this study was to examine the relationship between the self-reported frequencies of hearing chemical alarms during deployment and visuospatial function in Gulf War (GW) veterans. METHODS: The relationship between the self-reported frequency of hearing chemical alarms, neurobehavioral, and volumetric brain imaging data was examined with correlational, regression, and mediation analyses. RESULTS: The self-reported frequency of hearing chemical alarms was inversely associated with and significantly predicted performance on a visuospatial task (ie, Block Design) over and above potentially confounding variables, including concurrent, correlated GW-related exposures. This effect was partially mediated by the relationship between hearing chemical alarms and lateral occipital cortex volume. CONCLUSIONS: Exposure to substances that triggered chemical alarms during GW deployment likely had adverse effects on veterans' brain structure and function, warranting further investigation of whether these GW veterans are at an increased risk for dementia.