Pesticide Exposure and Head Blows Increase Parkinson's Risk

ABERDEEN, Scotland, May 30 -- People with a family history of Parkinson's disease may be more susceptible to it after pesticide exposure or repeated blows to the head, European investigators reported.

In a case-control study of nearly 1,000 patients with Parksinon's disease or parkinsonism and almost 2,000 controls, high exposure to pesticides increased the risk of the disease by 41%, according to Finlay Dick, M.D., of the University of Aberdeen here, and colleagues.

A history of traumatic head blows causing a loss of consciousness, an occupational hazard of boxing and other sports, was associated with a 2.5-fold greater risk, the authors reported in Occupational and Environmental Medicine, a BMJ specialty journal, in an early online release.

"It seems likely that Parkinson's disease is not a single disease but a number of phenotypically similar illnesses," the investigators wrote. "A variable range of genetic and environmental interactions may produce these conditions and it may be that any individual risk factor will only affect susceptible subjects."

Occupational and environmental risk factors implicated in Parkinson's and other movement disorders include exposure to pesticides, solvents, and metals, the authors noted, but just which toxins are at fault, and what level of exposure is required, is unclear.

"The current evidence for occupational risk factors for Parkinson's disease has several weaknesses," they wrote. "Many studies of occupational exposures have had small sample sizes. There have been few studies of occupational exposures to solvents or metals. The exposure estimates employed in some studies have been relatively crude, sometimes as simple as ever/never exposed or job title classifications. It is known that such exposure surrogates may lead to misclassification of exposure."

The authors' case-control study was conducted with patients in Scotland, Sweden, Italy, Romania, and Malta.

They enrolled 959 patients with prevalent parkinsonism, 767 of whom had a diagnosis of Parkinson's according to the United Kingdom Parkinson's Disease Society Brain Bank clinical diagnostic criteria. Patients with drug-induced parkinsonism, vascular parkinsoism, or dementia were excluded.

The patients were matched by age and gender with 1,989 controls from a variety of clinical and community settings.

Trained interviewers administered to participants a questionnaire about lifetime occupational and hobby exposure to solvents, pesticides, iron, copper, and manganese. Investigators blinded to disease status estimated lifetime and average annual exposures using a job-exposure matrix modified by subjective exposure modeling. The subjective exposure modeling takes into consideration factors such as ventilation, methods of chemical application, and whether the worker used protective measures.

The investigators created multiple logistic regression models to analyze results, controlling for age, gender, country, tobacco use, ever knocked unconscious, and family history of Parkinson's disease.

They found that compared with patients with no exposure, the odds ratio for low pesticide exposure and Parkinson'-parkinsonism was not significant, at 1.13 (95% confidence interval 0.82 to 1.57) but high pesticide exposure was significantly associated with risk (odds ratio 1.41, 95% CI, 1.06 to 1.88).

In addition, they found that being knocked unconscious even once carried a significant risk for Parkinson's compared with never being knocked unconscious (odds ratio 1.35, 95% CI 1.09 to 1.68). Patients who had been knocked out more than once vs. never had an odds ratio for Parkinson's or parkinsonism of 2.53, (95% CI 1.78 to 3.59).

Hypnotic, anxiolytic or antidepressant drug use for more than one year were associated with odds ratios ranging from 1.33 to 1.92 for Parkinson's, and a family history of the disease in a first-degree relative was associated with a nearly five-fold risk (odds ratio 4.85, 95% CI, 3.43 to 6.86).

As other studies have suggested, tobacco use was protective (odds ratio 0.48, 95% CI, .40 to 0.58), but alcohol was not (odds ratio 0.92, 95% CI, 0.74 to 1.15).

When the authors restricted their analyses to the 767 patients with a diagnosis of Parkinson's disease, the results were similar, they noted.

"This study has provided important evidence of the increased risk of Parkinson's disease in relation to exposure to pesticides. The exposure-response relationship suggests that pesticide exposure may be a causative and potentially modifiable risk factor," the investigators wrote.

They noted that their results may be limited by recall bias and by an underestimation of pesticide exposure because of the seasonal nature of pesticides use.

They also pointed out that "no information as to the timing of head injury, or use of medication was sought and accordingly we cannot state that these exposures predate symptom onset. Thus, the observed association with head injury may be due to recall bias or to an increased risk of falls in Parkinson's disease. Equally, the use of psychotropic medication may simply reflect the well recognized psychiatric effects of Parkinson's disease."