Pauline Anderson
From Medscape Medical News
July 23, 2009 — Two new studies have added to the growing body of evidence pointing to a link between pesticide exposure and the risk for neurological disorders.
One study linked high levels of an organochlorine pesticide called beta-hexachlorocyclohexane (beta-HCH) to an increased risk for Parkinson's disease (PD), while another showed an association between agricultural pesticide exposure and dementia, including Alzheimer's disease (AD).
The first study, published in the July issue of Archives of Neurology, included 50 patients with PD treated at the Clinical Center for Movement Disorders at the University of Texas (UT) Southwestern Medical Center at Dallas and 20 patients with AD and 43 controls from the Alzheimer's Disease Center at the UT Southwestern Medical Center.
Using blood samples, researchers tested for 16 organochlorine pesticides, including beta-HCH. The specific pesticides included in the study were chosen on the basis of how often they show up in environmental samples.
Banned During the 1970s
Used extensively across the United States beginning in the 1950s, organochlorine pesticides were banned during the 1970s because of concerns about their bioaccumulation and toxic effects. Animal studies show that these pesticides are neurotoxic, cause oxidative stress, and damage the brain's dopaminergic system.
The study, 1 of the largest of its kind to date and perhaps the first to link a particular pesticide with PD, found that 9 of the 16 pesticides tested were present in study subjects. The pesticide found most often was p.pDDE. It was detected in 100% of the AD patients, 72% of the PD patients, and 86% of the controls.
Beta-HCH was also present in elevated levels in some patients. It was detected most often in the serum of patients with PD: 38 of 50 (76%) compared with 17 of 43 (40%) in controls and 6 of 20 (30%) in patients with AD.
Compared with controls, the odds ratio for PD risk associated with beta-HCH levels was 4.39. The median level of beta-HCH was significantly higher in patients with PD (median, 0.36 ng/mL) compared with controls and patients with AD (median, 0 ng/mL for both).
This pesticide was widely used during the 1960s and 1970s, particularly on cotton plants, said Dr. Richardson. Although banned as a pesticide more than 30 years ago, traces of beta-HCH can still be found in water and soil.
Factors That Alter Risk
Researchers found beta-HCH in samples of some controls, although generally at lower levels than in patients with PD. This, said Dr. Richardson, suggests that other factors may interact with beta-HCH exposure to alter the risk for PD. While caffeine consumption and cigarette smoking have been associated with a decreased risk for PD, Dr. Richardson said it is most likely genetic factors that determine risk.
Blood samples from 18 of the PD patients taken 5 years apart showed that mean levels of beta-HCH did not change significantly over time. "This suggested that there may be some people who, because of their genetics, may not get rid of this pesticide as well as others, and these people may be the ones who are at risk for Parkinson's," said Dr. Richardson. "That's something we're very interested in trying to determine."
The authors noted that since 12 PD patients did not have detectable levels of beta-HCH, exposure to this pesticide may contribute to PD in only a subset of patients.
Exposure Through Food
Dr. Richardson speculated that most of the pesticide exposure is through food consumption. He noted that other studies have found a high rate of PD among populations that consume large quantities of fish and whale meat.
The second study, presented earlier this month at the Alzheimer's Association 2009 International Conference on Alzheimer's Disease (ICAD 2009), in Vienna, Austria, was part of a longitudinal cohort study of memory in aging among residents of Cache County, Utah, aged 65 years and older. These residents were asked detailed questions about their pesticide exposure.
Of 4012 study participants who had no dementia at baseline in 1995, 743 reported some exposure to pesticides, said Kathleen M. Hayden, PhD, assistant professor of psychiatry and behavioral sciences at Duke University, in Durham, North Carolina, who presented the findings.
Pesticides Only 1 Piece of Dementia Puzzle
Unlike patients in the first study, most of the exposure to pesticides in this analysis was likely through farming. Cache County is 1 of the primary agricultural regions in Utah, leading the state in barley production, said Dr. Hayden. Pesticide exposure of some study participants extended to 12 or more years.
Over 7 years of follow-up, 412 patients were identified with incident dementia, most with AD. Of these, 85 had reported exposure to pesticides.
After adjusting for age, sex, education, and APOE genotype, researchers determined that residents exposed to pesticides had an increased risk for dementia (OR, 1.56; 95% CI, 1.16 – 2.09). The OR for AD was 1.53 (95% CI, 1.02 – 2.26).
Although the study was not ideal (exposure classifications were less than perfect, for example), its strengths were that it had a relatively large sample size, the residents were followed for several years, and they underwent regular diagnostic assessments, said Dr. Hayden.
"It's definitely not a definitive study, but it does add to a growing body of literature linking pesticides to dementia," she said.
Pesticide exposure is likely only 1 piece of the AD puzzle. "Pesticides represent only 1 environmental factor; there are many environmental factors that may increase risk, and some that decrease risk," said Dr. Hayden. "These probably combine with genetic risk factors that we know about and others we have yet to discover."
Arch Neurol. 2009;66:870-875. Abstract
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