The first signs of Parkinson's disease are so subtle that they are all but invisible. By the time the telltale tremors appear - perhaps the shaking of a fork or the unintentional rustling of a newspaper - the neurological disease has already done more than half its damage.
Now scientists in New Haven say they have found a way to strip the cloak of invisibility from the debilitating disease that afflicts about 1 million Americans.
Using brain imaging technology, the scientists can take a snapshot of Parkinson's, or, more accurately, levels of dopamine, a key brain chemical that governs motor control and other functions. In theory, these images can help doctors diagnose and treat the disease before the first symptoms appear and more than half of the dopamine activity in the brain already has been lost.
The imaging test "demystifies the disease for people," says Dr. Kenneth Marek, a neurologist at the Institute for Neurodegenerative Disorders, a New Haven nonprofit research group that has developed a new radioactive marker used in imaging technology. "If there is one key message, it is that people need to deal with Parkinson's earlier rather than later."
Researchers from the institute who used the imaging technology recently reported that the drug pramipexole seems to be better than another widely used Parkinson drug, levodopa, at slowing the loss of dopamine-producing neurons in patients.
"This is at least one method of evaluating" the efficacy of new Parkinson's drugs, says Marek, who is also a principal in a for-profit biotechnology company in New Haven, Molecular Neuroimaging LLC.
The imaging technique, developed by Marek while he was an associate professor of neurology at Yale University School of Medicine, uses radioactive tags that bind to a dopamine transporter protein on the surface of brain cells. An imaging system called Single Photon Emission Computerized Tomography, or SPECT, detects the tag attached to the dopamine transporter. The pictures give a close approximation of dopamine activity in the brain, Marek says.
The imaging test can discriminate between patients who have Parkinson's and those who don't with 98 percent accuracy, the researchers claim.
Parkinson's disease can kill up to 80 percent of dopamine-producing cells before it is detected, usually by a specialist trained to observe physical symptoms.
Once the disease becomes established, the symptoms become all too easy to spot. Parkinson's patients initially have weakness and tremors on one side of the body, but both sides soon become affected. Patients lose their sense of smell, and tasks like handwriting and dressing can become difficult or impossible. The face of a Parkinson's patient can become wooden, lacking much expression.
Current drugs help at first, but they gradually become less effective and have side effects.
However, dozens of new drugs that have shown promise in fighting Parkinson's are under development, says Jeanne Rosner, director of educational programs at the Parkinson's Disease Foundation, a nonprofit educational and research group.
Along with better drugs, SPECT technology is the second major innovation that may help change the way Parkinson's is treated, she says.
"If we can catch it at an early stage, and with new medication that can slow or stop progression of the disease, it is possible that we can stop Parkinson's from physically appearing at all," she says.
However, major obstacles must be overcome before SPECT scans are used widely as a diagnostic tool, Rosner and Marek acknowledge.
Medical scientists have yet to clearly define risk factors for Parkinson's. In most cases, the disease does not appear to be inherited. Exposure to heavy metals seems to be one environmental cause, but the major risk factor seems to be old age.
Without such risk factors, there is no way of knowing who needs testing. Using SPECT technology on the general population would not be economically practical, Marek concedes.
"It's not something insurance companies are going to be willing to pay for unless we can find a way to define the population that might benefit," Rosner says.
Eventually, a blood test might be developed or a genetic or other physical abnormality identified that might indicate the possibility of Parkinson's. Then imaging tests could confirm the diagnosis, Marek says.
Scientists also might be able to use SPECT scans to identify those abnormalities, says Dr. Mohamed Hassan, a neurologist at the University of Connecticut Health Center who, like Marek, is enrolling patients for an international clinical trial of Parkinson's drugs.
"We're only at Chapter 1 with SPECT scans, and I think there will be thousands of chapters," Hassan says. "I think it is a breakthrough."
For now, SPECT will remain a valuable way to confirm an often tricky diagnosis, Marek says.
The days are numbered when patients and their doctors view Parkinson's as an invisible and irresistible disease, Marek predicts.
"We have to change the mind-set," Marek says. "People need to start thinking that maybe we can treat and even slow down this illness."
A version of this story first ran on April 9.