Alzheimer’s Disease and Insecticide Exposure: Background and Epidemiologic Studies

Alzheimer’s disease (AD) is a neurodegenerative disease marked by progressive impairment in cognition and memory. It is the most common form of dementia in older people, with a prevalence of about 5% over the age of 65 years. AD is more common in women than in men. A variety of risk factors have been studied, but only age, family history, head trauma, fewer years of formal education, and presence of the apolipoprotein 4 allele show consistent results (CSHA, 1994; Hendrie, 1998). Nonsteroidal anti-inflammatory drugs and estrogen have been reported to be protective in a few studies (Paganini-Hill and Henderson, 1994; Wolfson et al., 2002). There is no evidence of a geographic gradient in incidence or prevalence. Because of the cognitive deficit in those suffering from AD, epidemiologic studies require the use of proxy respondents to obtain information on past exposure and lifestyle factors (Weiss et al., 1996).

In reviewing the evidence of insecticide exposure as a risk factor for AD, it is worth noting that one particular OP insecticide, metrifonate, has been investigated in the clinical setting as a potential treatment for AD. Because its mechanism of action involves the depletion of acetylcholine (Ormrod and Spencer, 2000), metrifonate was proposed to raise acetylcholine through its action as an irreversible acetylcholinesterase inhibitor with relatively low potency (Spencer et al., 2000). Metrifonate (under the insecticide name trichlorfon) had been tested in clinical trials, but the manufacturer withdrew its application to the Food and Drug Administration in 2000, when the trials uncovered a small number of cases of respiratory paralysis. Metrifonate has been used outside the United States since the 1960s by the World Health Organization to treat schistosomiasis.

The committee identified two studies that focused specifically on the relationship between insecticides and AD. Several other epidemiologic studies examined the relationship between the disease and pesticides but not insecticides (CSHA, 1994; French et al., 1985). Two other studies used occupational classes (such as farming) as proxies for exposure and so were too general for the committee’s consideration (Amaducci et al., 1986; Schulte et al., 1996).

Gauthier and colleagues (2001) studied environmental risk factors in a randomly selected group of 1924 older residents of Quebec, Canada. Of this group, 68 cases were compared with nondemented controls through structured questionnaires of subjects and proxy respondents. The investigators also used residential histories and agriculture census histories for herbicide and insecticide spraying (1970–1991). The study found no association between past insecticide (or herbicide) exposure and AD.

Gun and colleagues (1997) examined past occupational risk factors in 170 patients with AD and 170 medical-practice-based controls (matched for age and sex). Occupational exposures included “organophosphates” and “hydrocarbon solvents.” Occupational histories were gathered from informants (proxies) for both patients and controls, and exposure was assessed by a panel of occupational hygienists (blinded to case or control status). The study found no association between OP insecticides and AD.

Summary and Conclusion

The two case-control studies reviewed found no associations between insecticides and Alzheimer’s disease (Gauthier et al., 2001; Gun et al., 1997). Other studies did not



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