The Parkinson’s Paradox

New studies show that it’s more than a movement disorder.

Illustrated by Jon KrauseThis much we know: Parkinson’s disease is a neurodegenerative movement disorder caused by the loss of the chemical messenger dopamine, which disrupts the brain’s organizing center and its ability to coordinate and control body movements. The link between dopamine-producing nerve cells and the area of the brain affecting motor skills makes the more common symptoms—tremors, slowed movement, balance problems, rigidity—relatively easy to identify. Less cut-and-dry are the changes in mood, sleep and thinking that have only recently been studied, suggesting new PD risk factors.

In its early stages, dopamine loss leaves more subtle clues. A person may be introverted or reserved. They might be perceived as ambitious and industrious, or serious, plodding and single-minded. A study published in May 2009 issue of the medical journal Brain suggests that even PD patients with little or no physical impairment can lack the mental capacity to process rewarding aspects of life.

Dopamine has already been linked to energy levels and risk-taking. PD patients gradually lose a significant amount of dopamine-producing cells, and experts have surmised that cautious, reserved behavior could be the result. It also makes sense that many PD sufferers show signs of depression—including lack of energy and motivation—long before they experience loss of motor control.

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Before my father died last year of complications from Parkinson’s, he’d become more reserved and depressed, attributing the latter to “getting old.” He was a physician—one of two occupations linked to PD. But he was also a coffee drinker and a smoker, which are said to decrease your chances of developing the disease.

Still, researchers point out that there’s probably no “neuroprotective” benefit to tobacco smoke, nicotine or caffeine. “If you consider that person with PD is somewhat reserved and risk-adverse, it makes sense that you’re not going to see them with habits—drinking and smoking—generally associated with risk-takers,” says Daniel Kremens, a neurologist at Thomas Jefferson University Hospital who specializes in movement disorders.

At Jefferson, researchers are working to explain Parkinson’s-related damage to dopamine-producing cells. They’re also focusing on new risk factors. “There really are two hot areas of research right now,” Kremens says. “One has to do with the notion that we can no longer consider PD as strictly a motor-movement disorder. We also know now that there are non-motor symptoms like constipation and loss of a sense of smell that show up long before the tremors or rigidity.”

In a long-term research project known as the “Honolulu Heart Study,” depression and daytime sleepiness were recently linked to an increased risk of developing PD. These and other symptoms may have been identified as early as 1817 by James Parkinson, the British physician who gave his name to the disease.

Despite the high-profile struggles of actor Michael J. Fox, who was diagnosed with Parkinson’s disease at age 30, PD is one of the few disorders linked to getting older. In fact, the interplay between the disease process and normal aging has only complicated matters. The older you get, the more likely you are to develop PD. But if you define “old” as over 65, keep in mind that the mean age of Parkinson’s onset is 55.

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Continued on page 2 with a list of Signs and Symptoms …

The real paradox of PD is that, while it’s a fairly straightforward ailment with one cause—dopamine loss—it remains one of the few progressive diseases that have neither a cure nor definitive blood or laboratory tests to determine its presence. And there are no disease-modifying drugs—those that could arrest, delay or counteract further progression.

Still, patients generally do well for a number of years after PD’s onset. One reason: Since the 1950s, neurologists have focused their efforts on treating symptoms with dopamine agonists. Among the most common is Levodopa (L-Dopa), which targets only a few symptoms. Early in his illness, my father refused to take L-Dopa, claiming that the side effects—everything from nausea, hair loss, disorientation and confusion to anxiety, hallucinations and narcolepsy—were far worse than having to cope with his lack of balance and occasional difficulty walking on his own.

Kremens cites a broad range of recent developments in Parkinson’s research, including those involving genetics. Scientists no little about the inherited aspects of the disease, but they have honed in on mutations in the LRRK2 “susceptibility gene.” Google co-founder Sergey Brin discovered he had the LRRK2 mutation and has since established a website ( that offers DNA testing at reduced rates.

Kremens doesn’t necessarily endorse the site, but he appreciates the public discourse it’s inspired. “The ultimate goal would be to develop a system of diagnosing PD’s onset before serious motor symptoms appear,” he says.

It’s just such a possibility that motivates Dr. Matthew Stern at the Penn Neurological Institute in Philadelphia. He helped coin the term “Parkinson’s Associated Risk Syndrome” or PARS. Over the past two years, some 7,000 tests have been administered to relatives of PD patients as part of a clinical trial that could lead to a universal screening process.

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“Hopefully, we can initiate therapies that will delay or even prevent the onset of the disease,” says Stern.

For information about taking part in the PARS clinical trial, call (800) 789-7366. To learn more about Parkinson’s disease, visit

Subtle Symptoms of Parkinson’s Disease

Parkinson’s disease has long been associated with tremors, slowed movements, balance problems and stiffness. But researchers at the University of Pennsylvania have identified three other symptoms that may change the definition of PD.

1. Sleep disturbances. Especially the kind of tossing and turning that indicates an active “dream” state or REM sleep behavior disorder (RBD).
2. Loss of sense of smell.
3. Gastrointestinal problems.
Especially constipation.

Six Early Signs of Parkinson’s Disease

1. Depression or apathy. PD sufferers may seem more depressed than usual or may have trouble making decisions.
2. Increased anxiety or panic attacks. Dopamine loss often makes anxiety worse.
3. Slowness in thinking or acting. A person with PD often can only focus on one goal or concept at a time.
4. Struggles with “executive” mental functions. Many PD sufferers are easily distracted or impulsive. They may need special help in situations where they’re forced to prioritize, problem solve or multitask.
5. Language issues. Just as dopamine levels affect the thinking process, they may be linked to how the brain retrieves information. This may translate into difficulty finding the right word—either misnaming a common object or being unable to recall the name in the first place.
6. Problems with visual-spatial perception. People with Parkinson’s often have difficulty navigating around furniture, recognizing common landmarks or determining distances, leading to falls or accidents while driving.

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