Even as a large European study reinforces links between Parkinson's disease and genetics, head injury, pesticide exposure and other potential causes, the disease's specific origins remain a mystery.
Researchers at Aberdeen University in Scotland worked with those in Italy, Sweden, Romania and Malta to look at the life histories of 959 patients suffering from Parkinson's and 1,989 patients who were not to try and tease out the possible causes for the disease.
They found that having close family members with Parkinson's increased an individual's risk for the disease by five times, being knocked unconscious more than once increased the risk two and a half times and having high pesticide exposure in work or hobbies made someone 33 percent more likely to contract Parkinson's.
The study was published this week in the Journal of Occupational and Environmental Medicine.
"It's a solid study, [but] it has the limitations of many studies of this type," said Harvey Checkoway, an epidemiologist at the University of Washington who was not involved with the research.
Parkinson's is the second most common degenerative brain disease, following Alzheimer's, afflicting around 1 million Americans, including 1 percent of all Americans above the age of 60.
The World's Most Famous Parkinson's Patient
Parkinson's supposed link to head injury is most commonly associated with three-time heavyweight boxing champion Muhammad Ali, who was diagnosed in 1983, nearly two years after his retirement from the sport.
But many experts dispute the connection.
"I'm a little lost to understand why they believe that is related to his head injuries," said Thomas Hammeke, co-chief of the neuropsychology division at the Medical College of Wisconsin.
He said that the rate of Parkinson's disease for boxers has not been shown to be any higher than for other professions. He added that football players, despite often suffering multiple concussions, have not been shown to suffer widely from the disease.
Hammeke also points out that Ali, who won 56 of his 61 professional bouts, would be less likely than most boxers to suffer from his fighting days.
"Muhammad Ali probably had less in the way of head injury than many or most," he said. "It's not clear to me how the link was made in his case."
Hammeke said the strong association in this study could just as easily be explained by Parkinson's patients' balance problems leading to head injuries -- an assessment Checkoway and Dr. Finlay Dick, the study's lead author, agreed with.
"We can't conclude that it's causal," said Dick. "However, we have shown that the more you're knocked out, the greater your risk."
The Pesticide Link
One limitation of the study, Dick said, is that despite the associations between pesticides and Parkinson's they were unable to figure out which specific pesticides may have been responsible.
At the same time, the study took a step further from previous ones by looking at potential pesticide exposure through both work and hobbies, said the authors.
While the lifetime exposures were only projected based on those activities, Checkoway said that method may have aided the study by avoiding recall bias.
Parkinson's patients, he said, tend to have a strong knowledge of the medical literature on the illness, and may have given different answers to questions if they related obviously and directly to pesticides.
Checkoway added that conclusions based on recalls of head injuries can suffer from a similar problem, as Parkinson's patients would be more likely to remember things, like head injuries, that they feel could have caused their illness.
Another finding of the study, reinforcing previous research, was that tobacco use appeared to have a protective effect for Parkinson's. Study participants who had used tobacco at some point were only half as likely to have contracted Parkinson's.
While researchers looked at a number of other potential causes for Parkinson's, such as exposure to certain metals and solvents and alcohol consumption, they found little association between them.
Dick is hesitant to make sweeping generalizations based on his study. While he said people should try and avoid head injury from contact sports like boxing and workers should follow manufacturer's instructions on pesticides, he referred to that as "generally good advice."
Checkoway remains skeptical of tying anything to Parkinson's, saying there is nothing on the level of the connection between cigarettes and asbestos with lung cancer.
"The contribution of environmental factors [to Parkinson's] does not appear to be very large," he said.