between May 1991 and December 2004. The adjusted mortality rate ratio for Parkinson’s disease was 0.77 (95% CI 0.17-2.99); there were three cases among the deployed male veterans, eight cases among the nondeployed males, and no cases in either group of female veterans.

Summary and Conclusion

Parkinson’s and Alzheimer’s diseases generally present late in life (usually after age 60); thus, it is unlikely that Gulf War veterans would manifest symptoms or signs of these neurodegenerative disorders until they reach at least the sixth decade of life. The Update committee strongly believes that a very long latency period for these health outcomes is a possibility, and current studies have inadequate follow-up time to assess whether risk for these disorders is increased among Gulf War veterans.

Therefore, the committee concludes that there is inadequate/insufficient evidence of an association between deployment to the Gulf War and other neurodegenerative diseases. The committee recommends continued monitoring of Gulf War veterans (both deployed and nondeployed) for neurologic outcomes such as Parkinson’s disease, Alzheimer’s disease, and dementia.

Other Neurological Outcomes

Haley and colleagues performed detailed neurologic assessments in several case-control studies of the original cohort of Seabee reservists. The cases were veterans who had met criteria for factor-derived syndromes. Under the hypothesis that those veterans were ill from neurotoxic exposures, especially to organophosphates, the assessments covered broad neurologic function (Haley and Kurt, 1997), autonomic function (Haley et al., 2004), vestibular function (Roland et al., 2000), basal ganglia injury (Haley et al., 2000a,b), normalized regional cerebral blood flow (Haley et al., 2009); and paraoxonase (PON) genotype and serum concentrations (Haley et al., 1999). Separate groups of investigators also studied PON genotype or activity (Hotopf et al., 2003; Mackness et al., 1997). A case-control study of neuropsychologic functioning (Hom et al., 1997) is discussed elsewhere in this chapter.

The committee regarded those case-control studies as secondary studies primarily because of their lack of generalizability and strong potential for selection bias. Although their study design was characterized as nested case-control, the studies of Haley et al. were not true nested case-control studies. Cases were, appropriately, selected from the original cohort, but controls were not. Ten of the 20 controls were from 150 newly discovered members of the battalion who had not been deployed. Those 10 were not from the original cohort, and there is no indication that they were tested to determine whether they should be treated as cases. The selection of those controls raises the possibility of selection bias. With regard to the other concern, lack of generalizability, the authors selected as cases the most severely affected veterans—that is, those who scored highest on factor analysis-derived syndromes—rather than a random sample of those who met a particular case definition.

Summary and Conclusion

Haley and colleagues found evidence of basal ganglia injury and other abnormalities with detailed neurologic assessments in several case-control studies. The committee regarded the



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