Another large study has confirmed that people with Parkinson’s disease are significantly more likely to report a history of pesticide exposure than are people who do not have the disease. Reported March 28 in the online journal BioMed Central Neurology, the study also suggested that adult exposures to pesticides are more important than childhood exposures and that rarer familial cases of Parkinson’s are less likely to be related to pesticide exposure.

From 2000 to 2006, geneticists and epidemiologists at Duke University, led by William Scott, studied 319 people with Parkinson’s as well as 296 of their family members. Study participants provided blood samples for DNA analyses and medical and family histories. Each was interviewed by telephone concerning his or her history of exposure to pesticides and other suspected environmental risk factors.

People in the study who had a confirmed diagnosis of Parkinson’s were about 60 percent more likely than their unaffected relatives to report having been exposed to pesticides through direct application, typically on farms or at home, prior to their first symptoms. The association between reported pesticide exposure and disease held up for both men and women, but was considerably stronger for the highest exposure-frequency category and for typical, sporadic Parkinson’s cases with no apparent genetic link.

“[I]ndividuals with Parkinson’s disease and no family history were over three times as likely to report being exposed at the highest cumulative exposure level as their unaffected relatives,” reported Scott and his colleagues.

By contrast, the study’s statistical analyses did not find significant associations between Parkinson’s and reported histories of well-water drinking or farm living.

Gary Miller of Emory University, whose lab studies environmental factors in neurodegenerative diseases, finds it noteworthy that “a different type of study—this family-based study—continued to show this connection between pesticides and Parkinson’s.”

The family-study design also meant that patients and unaffected family members were more likely to have had the same childhood environment, differing only in their adult environments, which “does tend to suggest that we might need to look [more] at people’s activities as adults,” says Scott, who has since moved his lab to the University of Miami.

Questions of unintentional bias

Studies based on retrospective analysis and the personal recall of subjects can never be conclusive. Scott and his colleagues used standard techniques to minimize the influence of variables that might have biased the results. But the subjects with sporadic, unexplained Parkinson’s might well have been more likely than their unaffected relatives to remember exposure to pesticides, which have long been suspected as a contributor to the disease.

“It’s something we have to be concerned about in any study that starts with people that already have Parkinson’s and then asks them about things in their past,” Scott says. “People with Parkinson’s are searching for a reason, and so they’ve thought about these things a lot more.”

Scott suggests that the design of the family study might have reduced this “recall bias” effect. Also, his group’s results agree with those of forward-looking studies, which have more or less eliminated the recall-bias risk by determining pesticide exposure at the outset, before Parkinson’s is diagnosed. In 2006, for example, Harvard researchers led by Alberto Ascherio analyzed lifestyle questionnaires filled out by more than 143,000 people at the start of a long-term health study, and found that those with self-reported pesticide exposure were about 70 percent more likely to be diagnosed with Parkinson’s later during the nine-year study period.

In 2007 a group led by National Institutes of Health epidemiologist Freya Kamel published preliminary results from a very large, ongoing health study of agricultural workers, and despite the fact that fewer than 100 subjects had been diagnosed with Parkinson’s since the start of the study, Kamel and her colleagues found a significant link to pesticides: Those who had used them frequently turned out to be roughly twice as likely to receive a Parkinson’s diagnosis during the period studied.

Pesticides are just part of the picture

Scott says his study “is part of a larger effort to look comprehensively at both genes and environment, to understand how they work together to cause Parkinson’s. And one of the things that we’re interested in doing next is to examine pesticide exposure in the context of particular genetic susceptibilities, to see if some people carry a gene which is more sensitive to the effects of pesticides.”

Scott and Miller agree that the research now needs to start moving away from “pesticides” as a broad category and to focus instead on specific compounds. “Pesticides are a huge group of chemicals, most of which probably have no association with Parkinson’s,” says Scott, whose study did seem to narrow the list of suspects to organochlorines (Chlordane, DDT) and organophosphorus compounds (Malathion).

Miller points out, however, that it is inherently difficult to get subjects to recall accurately their past exposures to specific compounds and that more objective studies of pesticide use patterns and Parkinson’s disease are needed. “People remember using paraquat because it has a catchy name, but they might not remember using 2,4-D,” he says.

Given their greater ability to accumulate in the brain and cause damage, organochlorines seem more plausible as suspects than organophosphates, Miller says. “The association with organophosphate use in that study might have shown up only because people who used organophosphates were more likely [also] to have used organochlorines,” he says.

But whatever pesticides turn out to be the culprits, they might only be promoting or accelerating a disease process rooted more deeply and subtly in genes and the aging process, Miller says. “We’ve had Parkinson’s disease long before all these different pesticides were introduced, and if these compounds were overt causes of the disease, everyone that worked with them would get Parkinson’s. But we know that not everyone does.”