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Parkinson's, the disease Muhammad Ali lived with for decades, explained

Muhammad Ali speaks during a Michael J. Fox Foundation 2010 Parkinson's benefit.
Photo by Stephen Lovekin/MJF/WireImage

Boxing legend and humanitarian Muhammad Ali died on Friday at the age of 74.

Though the cause of death was respiratory complications, Ali had battled Parkinson's since 1984, when, three years after his retirement, he was diagnosed with the disease and became one of the world's most famous people to battle it.

Parkinson's is a chronic, progressive disorder of the nervous system, and it's typically discovered with the onset of symptoms that include hand tremors and body stiffness.

When Ali was diagnosed, the disease was very poorly understood. Back then, researchers didn't know that genes play a role, especially in people who start to experience symptoms before the age of 50 — like Ali, who was 42.

Today, scientists believe Parkinson's is caused by some mixture of genetic predisposition and triggers from the environment. But it remains a largely mysterious and vexing condition affecting an estimated 7 to 10 million people worldwide.

Ali's star power helped draw a lot of attention to Parkinson's. He lent his name to a Parkinson's center at Barrow Neurological Institute in Phoenix, Arizona, and appeared in TV spots to raise awareness about the disease (sometimes along with fellow patient Michael J. Fox). There are more research initiatives today to try to demystify the disease than ever before.

But while Ali's chosen occupation drew a lot of attention to a possible link with head injuries, even better understood is that the disease can be brought on after exposure to pesticides. Smoking, on the other hand, seems to protect people from Parkinson's. Here are five facts to know about the disease.

1) Living in rural areas and doing farm work are clearly associated with Parkinson's

Researchers have isolated several genetic mutations linked to Parkinson's, and testing is available for some of them. But interpretation of the tests is tricky because not everyone who carries the genetic mutations will develop Parkinson's.

Meanwhile, a less appreciated but even more certain risk factor is exposure to pesticides.

"It's been recognized for 50 years that rates of Parkinson's disease are higher in rural populations and in farmers," Samuel Goldman, a Parkinson's researcher at the University of California San Francisco, said. Researchers think pesticides are the key cause here, and even consider farming an occupational risk.

The best-understood offenders are the pesticides rotenone and paraquat (which are now highly restricted and used only in very specific situations). There may be other chemicals linked to Parkinson's, but human and animal studies have only so far shown a clear link between exposure to rotenone and paraquat and increased risk of the disease.

Why these pesticides are associated with Parkinson's is less clear. One hypothesis is that they seem to attack the brain cells that make dopamine, and it's the degeneration of those cells that causes the disease.

2) The link between head injuries and Parkinson's is less well-understood

The link between Parkinson's and head injury is a little less clear, as the evidence has been somewhat contradictory, said Joseph Quinn, director of the Parkinson’s Center at Oregon Health and Science University. This may be, in part, because the question is really tricky to study.

The disease typically appears late in life, decades after any head injuries, so cause and effect are difficult to tease out. Not to mention that many people have difficulty recalling old head injuries. There's also no diagnostic tool available for Parkinson's, which introduces more potential for misdiagnosis (more on that later).

Still, Quinn thinks the balance of evidence favors an association here too.

The reason head injuries may play a role is that they damage the blood-brain barrier, which keeps toxins out of the brain. "When you get a head injury, the blood-brain barrier becomes leaky — and more nasty stuff from the environment or within your body is able to leak into the brain," Goldman said.

3) The disease is very rare among people under 40, and men are at a much greater risk

Two of the main risk factors for the disease are advanced age and being a man.

It's very rare for someone under 40 to be diagnosed, and the incidence rapidly increases over the age of 60. According to the National Parkinson Foundation, the average age of diagnosis is around 62.

The disease also seems to be much more common among men than women, though the reason is still unclear.

4) There's no diagnostic tool or cure for Parkinson's

Parkinson's is brought on by the degeneration and death of the neurons in the part of the brain that produces dopamine. The main symptoms of the disease are tremor, bradykinesia (or slowness of movement), and rigidity. Onset of Parkinson's is always asymmetric in the body, so one side is affected first.

Goldman said clinicians have no diagnostic test to rely on, so they typically look for that asymmetry and then administer a dopamine therapy to see if some of the symptoms dissipate. If a patient responds to dopamine treatment, that means she more likely than not has Parkinson's.

There's also no cure for Parkinson's, nor is there a standard treatment. Doctors usually prescribe medicines (most commonly dopamine therapies) and lifestyle modifications (rest and exercise) or surgery (deep-brain stimulation). But these therapies simply control symptoms and can't slow down disease progression or cure the disease.

5) Cigarette smoking seems to be protective

This is definitely not a reason to take up cigarette smoking, but one incredibly consistent finding in the literature is that smokers seem to have much lower rates of the disease.

"There's probably 100 papers about this," Goldman said, but researchers still don't quite understand why. One hypothesis is that nicotine may protect the nervous system from the disorder.

Another, said Quinn, "is that people who are prone to Parkinson's … might just be less prone to smoke cigarettes as part of their genetic makeup."

Watch: Ali's biggest fights were outside the ring