Parkinson's: The Pesticide Link

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Parkinson's is the second most common neurodegenerative disease (after Alzheimer's) in the United States, affecting between 1 million and 1.5 million Americans. The majority of cases occur in people over 65, about 60 percent of them male. It leads to uncontrollable tremors, muscle rigidity, and the inability to direct your arms or legs to move when you want them to. People with Parkinson's often have a masklike, impassive expression. They may have difficulty speaking clearly and develop a characteristic shuffling gait. Cognitive skills usually are not affected, though some functions like memory and decision-making can be impaired, and, in the face of the gradual and inevitable encroachment of physical limitations, people with Parkinson's often become depressed.

In part because it can take many forms, Parkinson's disease is difficult to diagnose. Several movement disorders have been classified in the general category known as Parkinson's-like syndrome, or parkinsonism. Scientists are divided about whether Parkinson's disease and parkinsonism are even related in any meaningful way, beyond sharing some symptoms. The two conditions may not even involve the same brain defects. The strict definition of Parkinson's disease is a loss of cells in the substantia nigra, a small structure in the basal ganglia region of the midbrain (though other brain structures are now thought to be involved as well). The substantia nigra ordinarily secretes the neurotransmitter dopamine, which is involved in many of the brain's functions, including the control of motor activity.

Often a diagnosis of Parkinson's disease is made the way it was made for Christensen: by a trial run of L-dopa, which boosts dopamine in the brain. If it works, the problem must be Parkinson's. It's a circular kind of logic, but it's all that most doctors have. There still are no definitive blood tests or brain scans to make the diagnosis.

In trying to establish risk factors for Parkinson's, one of the first decisions investigators must make is which cases to include in their epidemiological studies. Some studies include all patients, those with parkinsonian syndrome as well as those with definitively diagnosed Parkinson's. Some researchers limit their study subjects to people with Parkinson's disease and a demonstrated reduction of dopamine.

One of the more restrictive studies is a small subset of the massive Agricultural Health Study (AHS), which began in 1993 and involves nearly 90,000 individuals licensed to apply pesticides to crops, as well as their families. The AHS, conducted by the National Cancer Institute and the National Institute for Environmental Health Sciences with funding from the Environmental Protection Agency and the National Institute of Occupational Safety and Health, has tracked these workers to determine their risk of developing cancer and other serious diseases.

In 2002, scientists decided to look at a segment of this large database to assess the environmental risks for Parkinson's. This study-within-a-study, with the catchy acronym FAME (Farming and Movement Evaluation), compared the pesticide exposure of 114 AHS participants who have Parkinson's disease, as diagnosed by two specialists from the team, with exposure among 384 control cases matched for age, sex, and state of residence (either Iowa or North Carolina, where all the subjects are from). A group of scientists led by Caroline Tanner of the Parkinson's Institute of Sunnyvale, California, and Freya Kamel of the National Institute of Environmental Health Sciences looked at five possible risk factors in these 498 individuals: pesticide exposure; exposure to other neurotoxins; lifestyle factors such as diet, smoking, and caffeine use; the amount of melanin, or pigment, in the skin; and specific genetic variations, particularly those in genes involved in the production of dopamine or the metabolism of xenobiotics -- non-natural chemicals such as drugs and toxins that are transported and detoxified through pathways that scientists already understand.

The FAME study, the results of which are being prepared for publication next year, found that pesticide exposure was a significant risk factor for Parkinson's disease. The parent AHS study found that people who had been exposed to pesticides sporadically over a lifetime were 1.2 times more likely to develop Parkinson's than those who had not been. And when the exposure was heavy -- the kind of lifetime exposure seen in career pesticide applicators, or a single massive exposure as the result of a spill -- that increased risk jumped to 2.3 times. The riskiest pesticides were found to be some of those most commonly used in American agriculture, among them Paraquat and Trifluralin, both herbicides used to kill broadleaf weeds in food crops. (Paraquat is now restricted to commercially licensed users in the United States because of its toxicity, but it remains the second most widely used herbicide in the world, applied to more than 50 crops in 120 countries.)

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