Cholinergic Autonomic Dysfunction in Veterans With Gulf War Illness

JAMA neurology 02/2013; 70(2):191-200. DOI: 10.1001/jamaneurol.2013.596
Source: PubMed


BACKGROUND The authors of prior small studies raised the hypothesis that symptoms in veterans of the 1991 Gulf War, such as chronic diarrhea, dizziness, fatigue, and sexual dysfunction, are due to cholinergic autonomic dysfunction. OBJECTIVE To perform a confirmatory test of this prestated hypothesis in a larger, representative sample of Gulf War veterans. DESIGN Nested case-control study. SETTING Clinical and Translational Research Center, University of Texas Southwestern Medical Center, Dallas. PARTICIPANTS Representative samples of Gulf War veterans meeting a validated case definition of Gulf War illness with 3 variants (called syndromes 1-3) and a control group, all selected randomly from the US Military Health Survey. MAIN OUTCOME MEASURES Validated domain scales from the Autonomic Symptom Profile questionnaire, the Composite Autonomic Severity Score, and high-frequency heart rate variability from a 24-hour electrocardiogram. RESULTS The Autonomic Symptom Profile scales were significantly elevated in all 3 syndrome groups (P < .001), primarily due to elevation of the orthostatic intolerance, secretomotor, upper gastrointestinal dysmotility, sleep dysfunction, urinary, and autonomic diarrhea symptom domains. The Composite Autonomic Severity Score was also higher in the 3 syndrome groups (P = .045), especially in syndrome 2, primarily due to a significant reduction in sudomotor function as measured by the Quantitative Sudomotor Axon Reflex Test, most significantly in the foot; the score was intermediate in the ankle and upper leg and was nonsignificant in the arm, indicating a peripheral nerve length-related deficit. The normal increase in high-frequency heart rate variability at night was absent or blunted in all 3 syndrome groups (P < .001). CONCLUSION Autonomic symptoms are associated with objective, predominantly cholinergic autonomic deficits in the population of Gulf War veterans.

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    • "Circardian rhythms are another characteristic of sleep that may be associated with cognitive impairment. Disruptions in circadian rhythms may be common during military service [130], and there is some evidence to suggest circadian variation in heart rate variability as it relates to autonomic dysfunction in Gulf War Illness [131] [132], but little is known about circadian disturbances in sleep among veterans. In older adults, altered circadian rhythms, including decreased amplitude and robustness as well as shifted time of peak activity, have also been associated with higher risk of developing dementia [133]. "
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    ABSTRACT: Lifestyle and health-related factors are critical components of the risk for cognitive aging among veterans. Because dementia has a prolonged prodromal phase, understanding effects across the life course could help focus the timing and duration of prevention targets. This perspective may be especially relevant for veterans and health behaviors. Military service may promote development and maintenance of healthy lifestyle behaviors, but the period directly after active duty has ended could be an important transition stage and opportunity to address some important risk factors. Targeting multiple pathways in one intervention may maximize efficiency and benefits for veterans. A recent review of modifiable risk factors for Alzheimer's disease estimated that a 25% reduction of a combination of seven modifiable risk factors including diabetes, hypertension, obesity, depression, physical inactivity, smoking, and education/cognitive inactivity could prevent up to 3 million cases worldwide and 492,000 cases in the United States. Lifestyle interventions to address cardiovascular health in veterans may serve as useful models with both physical and cognitive activity components, dietary intervention, and vascular risk factor management. Although the evidence is accumulating for lifestyle and health-related risk factors as well as military risk factors, more studies are needed to characterize these factors in veterans and to examine the potential interactions between them.
    Full-text · Article · Jun 2014 · Alzheimer's and Dementia
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    • "Long-lasting neurologic consequences of these toxic fumes might explain, at least in part, the constellation of symptoms that is observed in Gulf War syndrome. A recent representative study of affected Persian Gulf War veterans provided strong evidence that dysregulation of the autonomic nervous system is linked to the observed symptoms of Gulf War syndrome including SD (Haley et al., 2013). SD is also strongly influenced by psychosocial determinants. "
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    ABSTRACT: Objectives: The aim of the study was to assess the prevalence of sexual dysfunction (SD) in war veterans injured due to chemical warfare exposure during deployment. Methods: Eighty-five chemically injured veterans (CIVs) and 100 non-CIVs were enrolled. Participants were interviewed using a predesigned questionnaire, developed according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision description of spectrum of SD. Results: The prevalence of SD in CIVs was 65.9% as opposed to 33.0% in non-CIVs (p =.0001). CIVs had higher prevalence rates in all domains examined (p <.05). The most commonly affected domain in both groups was erectile dysfunction (51.6% in CIVs and 15.0% in non-CIVs). Two thirds of CIVs had been diagnosed with at least one type of SD. Conclusions: The involvement of multiple areas of sexual functioning in CIVs suggests that a combination of physical and psychological factors may contribute to SD. Further efforts are needed to determine the precise etiological factors.
    Preview · Article · Apr 2014 · International Journal of Sexual Health

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