war zone between 1910 and 1982 (Weisskopf et al., 2005). On the basis of this study a previous IOM committee (2006) termed the evidence for ALS and military deployment as limited and suggestive. Horner et al. (2008), however, also emphasized that their follow-up period was still too short to draw any conclusions about ALS in nondeployed military personnel when compared to a general population. However, due to small numbers of cases overall, it remains unclear whether the observed pattern represents random fluctuations in ALS rates among the deployed or an episodic post war increase as suggested by the authors.

Summary and Conclusions

One primary study with extended follow-up and one secondary study found that deployed veterans appear to be at increased risk for ALS. The primary study by Horner et al. (2003, 2008) possibly underascertained cases in the nondeployed population. However, they investigated ascertainment bias analytically and concluded that it was unlikely to explain their results (in Coffman et al., 2005); they also extended follow-up through 2001 and described a short-term increase in ALS risk in the deployed during the decade after the war. These analyses together support an estimate of a nearly doubling in risk among deployed veterans compared with nondeployed veterans. A secondary study by Haley (2003), using general population rates for comparison purposes, found a similar increase in relative risk. Other US and UK mortality studies and a hospitalization study have not found excess risk of ALS.

Therefore, the committee concludes that there is limited but suggestive evidence of an association between deployment to the Gulf War and ALS; however, further follow-up is warranted.

Other Neurodegenerative Diseases

Alzheimer dementia is the most common neurodegenerative disorder in the elderly population and Parkinson’s disease—primarily considered a movement disorder—is the second most common. Both have progressive courses and no known cure. The dopaminergic neurodegeneration in Parkinson’s disease is thought to be caused by a combination of repeated, prolonged, or chronic exposures to toxicants, genetic factors, gene–toxicants interactions, and aging-related effects. Over the last decade and a half, evidence has accumulated that exposure to certain pesticides can produce the anatomical, neurochemical, behavioral, or neuropathological features of Parkinson’s disease in animal models (Sherer et al., 2001), and recently some high-quality studies have confirmed the pesticide hypothesis for Parkinson’s disease in humans (Elbaz et al., 2009; Kamel et al., 2007; Ritz et al., 2009).

Environmental factors are also suspected to contribute to Alzheimer disease to a lesser degree. High-quality human studies are not available except for lead exposures (Shih et al., 2007), for which data from both animal experiments and human epidemiologic studies suggest an influence of lead exposure on Alzheimer-like cognitive impairment. Of special importance for Gulf War veterans is that brain injuries are an established risk factor for Alzheimer dementia, especially among susceptible individuals (for example, carriers of the APOE 4 allele). Brain injury has been shown to result in widespread hippocampal damage in mice and may lead to Alzheimer disease in humans (reviewed in Van Den Heuvel et al., 2007).

The committee was unable to identify any studies of dementia or Alzheimer’s disease in Gulf War veterans and only one study on Parkinson’s disease. Barth et al. (2009) compared mortality from neurological disease in 621,902 deployed and 746,248 nondeployed veterans



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