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The Parkinson’s Mystery

JOHANNESBURG – Parkinson’s disease is a degenerative neurological disorder that affects around seven million people globally, and one million in the United States alone, usually afflicting people older than 50. The disease strikes 2% of those over age 65, and 5-10% of cases occur in people under 50. The cause remains unknown, preventing us from arresting the disease’s development – though environmental and occupational factors loom large in recent research.

Chinese and Indian texts from 1000 BC appear to describe a similar affliction. But James Parkinson was the first to describe the disease in detail, in 1817. Those developing Parkinson’s suffer slow movement, tremors, stiffness, difficulty walking, and gait instability. As the disease progresses, it may affect thinking and can also cause behavioral and psychological problems, including dementia, sleep disturbances, and depression, as well as low blood pressure. Though many of these symptoms can be ameliorated, therapeutic efficacy often wanes over time.

The symptoms result from the loss of brain cells generating the neurotransmitter dopamine. Many studies demonstrate that these cells’ degeneration is preceded by cell loss in other brain regions, and even nerve cells in the gastrointestinal system. This occurs decades before symptoms of motor impairment develop.

Ultimately, people with Parkinson’s develop progressive disability and die prematurely. There is no treatment to slow the inevitable progression of the disease, and we do not know why the dopamine-generating brain cells begin to die off.

It is likely that Parkinson’s develops as a result of multiple risk factors. Demographic traits are one major influence, with the highest rates found in older white men; those with African or Asian ancestry face a much lower risk. Several gene mutations account for 5-10% of cases. Certain diseases or symptoms – including constipation, loss of smell, malignant melanoma, and impaired rapid eye movement (REM) sleep – also appear to be associated with a higher risk of developing the disease. However, most Parkinson’s cases arise without a known cause.

Interestingly, the variable most strongly associated with Parkinson’s is smoking, which actually reduces the risk, even after accounting for early death from smoking-related diseases. Caffeine also appears to be associated with a modest reduction in Parkinson’s risk.

Despite our frustrating lack of knowledge about the causes of Parkinson’s, there are many promising areas of research. Exposure to environmental and occupational factors – including pesticides, heavy metals, and solvents – probably play an important causal role, either independently or in tandem with a genetic predisposition to the disease.

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In the 1980s, six drug addicts developed acute Parkinson-like symptoms after accidentally injecting drugs contaminated with MPTP, which is structurally similar to the pesticide paraquat. Numerous studies then investigated the link between Parkinson’s risk and exposure to pesticides and herbicides; several, though not all, studies demonstrated an increased risk. The most consistently implicated pesticides are paraquat, a broad-spectrum herbicide, and maneb, a fungicide that contains manganese.

The association between occupational exposure to manganese and Parkinson’s-like symptoms was first described in the early 1800s in four manganese-ore crushers. Exposure to manganese can occur through dust, fumes, and air pollution. It is used extensively in the steel and welding industries, where there is a high risk of overexposure to fumes. Workers in ferromanganese smelters and nearby communities are at particular risk of developing Parkinson’s-like symptoms. Lead, copper, and mercury have also been implicated as risk factors, though more research is needed to confirm these findings.

Overexposure to certain solvents may also increase the risk of Parkinson’s. Occupational exposure to hydrocarbon-containing solvents, such as n-hexane, has been associated with earlier-age onset of Parkinson’s. There is some evidence of increased risk associated with exposure to trichloroethylene, commonly used in the textile industry and in the manufacture of pesticides and other chemicals. Up to one-third of America’s water supplies contain trichloroethylene, the most common organic contaminant of groundwater.

It is only by identifying the various causes of Parkinson’s that we will be able to develop preventive strategies. For example, as studies begin to show consistent associations between the disease and environmental toxins, researchers will design long-term studies to demonstrate the benefit of reducing exposure to these agents, especially in high-risk communities.

Much work remains to be done. But the benefits of solving the two-century-old mystery of Parkinson’s causes are potentially enormous.

Gill Nelson is a professor and Head of the Occupational Health Cluster at the School of Public Health, University of the Witwatersrand in Johannesburg, South Africa. Brad A. Racette is Professor and Vice Chairman of Neurology at Washington University School of Medicine, St. Louis.

Copyright: Project Syndicate, 2015.

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