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.
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.
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.
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.
To examine the effects of transcranial and intranasal photobiomodulation (PBM) therapy, administered at home, in patients with dementia.
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.
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,
= 4) or home PBM treatments (
= 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.
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:
= 16.35,
= 0.007) and NPI (group × time interaction:
= 7.52,
= 0.03), increased cerebral perfusion (group × time interaction:
= 8.46,
< 0.03), and increased connectivity between the posterior cingulate cortex and lateral parietal nodes within the default-mode network in the PBM group.
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.
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.
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.
We used fMRI to examine the neural response in frontal and parietal cortices associated with viewing and naming pictures of different categories of objects. Because tools are commonly associated with ...specific hand movements, we predicted that pictures of tools, but not other categories of objects, would elicit activity in regions of the brain that store information about motor-based properties. We found that viewing and naming pictures of tools selectively activated the left ventral premotor cortex (BA 6). Single-unit recording studies in monkeys have shown that neurons in the rostral part of the ventral premotor cortex (canonical F5 neurons) respond to the visual presentation of graspable objects, even in the absence of any subsequent motor activity. Thus, the left ventral premotor region that responded selectively to tools in the current study may be the human homolog of the monkey canonical F5 area. Viewing and naming tools also selectively activated the left posterior parietal cortex (BA 40). This response is similar to the firing of monkey anterior intraparietal neurons to the visual presentation of graspable objects. In humans and monkeys, there appears to be a close link between manipulable objects and information about the actions associated with their use. The selective activation of the left posterior parietal and left ventral premotor cortices by pictures of tools suggests that the ability to recognize and identify at least one category of objects (tools) may depend on activity in specific sites of the ventral and dorsal visual processing streams.
The aim of the study was to evaluate the value of assessing white matter integrity using diffusion tensor imaging (DTI) for classification of mild cognitive impairment (MCI) and prediction of ...cognitive impairments in comparison to brain atrophy measurements using structural MRI. Fifty-one patients with MCI and 66 cognitive normal controls (CN) underwent DTI and T1-weighted structural MRI. DTI measures included fractional anisotropy (FA) and radial diffusivity (DR) from 20 predetermined regions-of-interest (ROIs) in the commissural, limbic and association tracts, which are thought to be involved in Alzheimer's disease; measures of regional gray matter (GM) volume included 21 ROIs in medial temporal lobe, parietal cortex, and subcortical regions. Significant group differences between MCI and CN were detected by each MRI modality: In particular, reduced FA was found in splenium, left isthmus cingulum and fornix; increased DR was found in splenium, left isthmus cingulum and bilateral uncinate fasciculi; reduced GM volume was found in bilateral hippocampi, left entorhinal cortex, right amygdala and bilateral thalamus; and thinner cortex was found in the left entorhinal cortex. Group classifications based on FA or DR was significant and better than classifications based on GM volume. Using either DR or FA together with GM volume improved classification accuracy. Furthermore, all three measures, FA, DR and GM volume were similarly accurate in predicting cognitive performance in MCI patients. Taken together, the results imply that DTI measures are as accurate as measures of GM volume in detecting brain alterations that are associated with cognitive impairment. Furthermore, a combination of DTI and structural MRI measurements improves classification accuracy.
Veterans of the 1991 Gulf War (GW) were exposed to a myriad of potentially hazardous chemicals during deployment. Epidemiological data suggest a possible link between chemical exposures and ...Parkinson’s disease (PD); however, there have been no reliable data on the incidence or prevalence of PD among GW veterans to date. This study included the following 2 questions: 1. Do deployed GW veterans display PD-like symptoms? and 2. Is there a relationship between the occurrence and quantity of PD-like symptoms, and the levels of deployment-related exposures in GW veterans?
Self-reports of symptoms and exposures to deployment-related chemicals were filled out by 293 GW veterans, 202 of whom had undergone 3 Tesla volumetric measurements of basal ganglia volumes. Correlation analyses were used to examine the relationship between the frequency of the veterans’ self-reported exposures to deployment-related chemicals, motor and non-motor symptoms of PD, and the total basal ganglia volumes.
Healthy deployed GW veterans self-reported few PD-like non-motor symptoms and no motor symptoms. In contrast, GW veterans with Gulf War illness (GWI) self-reported more PD-like motor and non-motor symptoms, and more GW-related exposures. Compared to healthy deployed veterans, those with GWI also had lower total basal ganglia volumes.
Although little is known about the long-term consequences of GWI, findings from this study suggest that veterans with GWI show more symptoms as those seen in PD/prodromal PD, compared to healthy deployed GW veterans. Int J Occup Med Environ Health. 2019;32(4):503–26
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 ± 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 β = 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.
•Gulf War Veterans with predicted sarin exposure have greater hippocampal mean diffusivity (MD) than unexposed veterans.•Higher hippocampal MD was also associated with poorer with verbal memory learning.•Low-level sarin exposure may have resulted in microstructural disruption in the hippocampus.
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.
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).
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.
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.
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.
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.
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 (β = -0.12, p = 0.04) and marginally predicted CVLT-II delayed recall scores (β = -0.11, p = 0.05) over and above potentially confounding demographic and clinical variables.
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.
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