Testing for smelling ability could provide early signs

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Joe and Jim Herzberg resemble each other, but the big difference between them is in the nose.

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Joe Herzberg (left) and his brother, Jim Herzberg, talk in the Outpatient Neurology Clinic at the Medical College of Georgia in Augusta. Joe's sense of smell is keen, but Jim, who has Parkinson's disease, can't smell very well.  Rainier Ehrhardt/Staff
Rainier Ehrhardt/Staff
Joe Herzberg (left) and his brother, Jim Herzberg, talk in the Outpatient Neurology Clinic at the Medical College of Georgia in Augusta. Joe's sense of smell is keen, but Jim, who has Parkinson's disease, can't smell very well.

"I can smell strong stuff. But if you tell me to smell a rose, I can't smell it," said Jim Herzberg, 52, who was diagnosed with Parkinson's disease five years ago.

"You can't smell a rose? See, I can smell a rose," said Joe Herzberg, 56.

The brothers are taking part in a clinical trial at the Medical College of Georgia that hopes to take advantage of an odd early sign of Parkinson's: a diminished sense of smell. The Parkinson Associated Risk Study, which is being conducted at 17 centers in the United States including MCG, will study close relatives of Parkinson's patients who might be at slightly higher risk. By using a simple smell test, researchers hope to pick up on those in the early stages of the disease.

"We believe the loss of smell is one of the earliest symptoms of Parkinson's disease, even before you develop the motor symptoms," such as trembling and stiffness, said Nicolaas Bohnen, an associate professor of neurology and radiology at the University of Michigan.

In a study published this year, Dr. Bohnen showed that not only do Parkinson's patients lose their sense of smell but they also have a hard time detecting certain odors, such as banana and licorice.

Why this happens is unknown.

"It's a mystery, actually," said Kapil Sethi, the director of the MCG Movement Disorders Program, who is overseeing an arm of the ongoing clinical trial.

There are some dopamine-producing neurons in the olfactory area of the brain, Dr. Sethi said, and it is the loss of those neurons in another area of the brain that causes the trembling and stiffness that comes with the disease. Dopamine is a neurotransmitter, and Dr. Bohnen said he has some preliminary data that show it could be involved in odor memory, which might explain why specific smells are lost. Dr. Sethi believes the overall loss of smell is a more important indicator. On the 40-item test his study uses, Parkinson's patients typically score below 20, "which is really significantly impaired," he said.

Other diseases, such as Alzheimer's, and even just getting older can cause a loss of smell, Dr. Bohnen said.

"If somebody fails the smell test, that doesn't mean that he or she is developing Alzheimer's or Parkinson's disease," he said.

But for those with a first-degree relative who has Parkinson's, it could be a chance to intervene early, Dr. Sethi said.

"Because in Parkinson's, the motor symptoms are just the tip of the iceberg," he said. "All of these other things can give us a window. Just imagine delaying the onset of Parkinson's by three years vs. giving a patient three years to live at the tail end. It's much better upfront."

There are no good agents approved by the Food and Drug Administration to control the damage, though there are many in clinical trials, Dr. Bohnen said.

"I think it is going to be a cocktail of drugs," Dr. Sethi said. "The ideal cocktail is unknown. I think it is all in the future, but we have to keep working from many different directions."

The chance to identify patients early, and potentially help them early, is what the studies are hoping to define, he said.

"Because if you have something that slows down Parkinson's, and at the same time you've developed standard risk profiles and you know who is going to get it, then we should be ready to apply those agents to this population," he said.

The chance to help find those early markers is what is motivating the Herzbergs. Jim Herzberg lost much of his sense of smell more than 15 years ago, but it wasn't until 2002 that he started to notice stiffness in his left arm.

"I thought I was just stressing out," said Mr. Herzberg, who was working as a district manager for Kroger grocery stores. When he had trouble controlling his left hand, a doctor diagnosed it as Parkinson's and referred him to Dr. Sethi.

Joe Herzberg recently went through a bout of prostate cancer and had genetic testing done so his family would know their risks. The MCG study is just another part of that, he said.

"It's for my kids and for his kids, too," he said. "We just want to make sure they're equipped as best they can be to avoid problems, whether that be genetic or environmental."

"Well, you'd like to know, too," Jim Herzberg said.

Reach Tom Corwin at (706) 823-3213 or tom.corwin@augustachronicle.com.

STUDY BASICS

SUBJECTS: The Parkinson Associated Risk Study wants to follow 15,000 close relatives of Parkinson's patients for three to five years in hopes of finding early markers for the disease.

SCREENING: One of the initial screenings is a smell test because Parkinson's patients often first develop a diminished sense of smell.

TO PARTICIPATE: The study is open to those 50 or older who do not have Parkinson's but have a close relative (mother, father, child or sibling) who has been diagnosed with Parkinson's. For more information, call (706) 721-2798 or (877) 401-4300.


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