Insights Into Prodromal Parkinson's and REM Sleep Behavior Disorder

Indu Subramanian speaks with REM sleep behavior disorder expert Ron Postuma about when RSD is prodromal Parkinsons's disease and new strategies to classify PD.
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-- TRANSCRIPT --
Indu Subramanian, MD: Hi, and welcome to Medscape. We're so excited today to be talking to Professor Ronald Postuma. He's a professor of neurology at McGill University. I am Dr Indu Subramanian. I am a professor of neurology at UCLA, and I run the Center of Excellence at the West Los Angeles VA for Parkinson's Disease.
Welcome, Ron. We're very excited to cover some areas, especially around prodromal Parkinson's disease; touching on REM sleep behavior disorder, which has really been something that you've been a world leader in; and finally touching on some very new classification systems and some of the new ways that we're thinking about a biological definition of Parkinson's disease. Thanks for agreeing to talk to me today.
Perhaps you could just define a little bit about prodromal Parkinson's disease.
Prodromal Parkinson's
Ronald B. Postuma, MD: When we think of Parkinson's disease, we classically think of tremor. In fact, tremor is probably the least important symptom. It's mostly slowness, stiffness, and difficulty walking - that's Parkinson's disease. By the time you show up in a doctor's office with Parkinson's, on average, you've had the disease in your brain for somewhere between 10 and 20 years, or even more than that.
There's a whole period where the Parkinson's pathology is progressing and you have no symptoms or signs. After that, you start to develop some early symptoms and signs. For a period, probably on average, 10-15 years, you have subtle symptoms and signs of Parkinson's disease, but you're still not ready to be diagnosed with Parkinson's disease by a doctor. That's what prodromal Parkinson's is.
Subramanian: What kind of signs and symptoms are we talking about?
Postuma: They follow an order. Probably the most reliable early thing that you can get is loss of the sense of smell. Maybe 20-25 years before, there's often very gradual loss of sense of smell and people are completely unaware of it, at least half the time. Family members will sometimes know it, but people will say, "Oh, I never smelled well."
Another one that happens, but is very nonspecific because many people have this, is constipation. If you look at people who are constipated in their 30s, they have an increased risk of developing Parkinson's. Is it a prodromal factor? Is it a risk factor? Who knows? There are a few other things, like people who have depression or anxiety have an increased risk for Parkinson's disease.
The one that I mostly work on is called REM sleep behavior disorder. That's really unique because it's so powerful. Normally, when you or I dream, we're supposed to be paralyzed and we're not able to move when we dream. If you dream you're running and the legs don't work, or you're dreaming that you're trying to yell and your voice isn't coming out, that's your body going, you're trying to run and something's wrong. Your legs aren't working. That's the normal thing.
People with this condition lose the ability to be paralyzed, and so whatever they dream, they do. If I'm dreaming about speaking in a lecture like this, my wife will hear it. If I'm running in in my dream, I'll be making running movements in bed. That's REM sleep behavior disorder.
It turns out that probably on the order of 80% of people who get this condition in their 40s, 50s, and 60s in fact have Parkinson's at an early stage. They'll either get Parkinson's proper, as we classically define it, or they'll get dementia with Lewy bodies, which, of course, overlaps with Parkinson's almost completely in many cases, or sometimes multiple system atrophy.
Everything else is rare, at 1% or 2%. Really, most people with this disorder get Parkinson's. That's what we've been studying for a long time.
Subramanian: You said 80% go on to develop Parkinson's. What do the other 20% with REM behavior disorder end up getting?
Postuma: Of course, that's 80%, assuming you survive long enough. When we follow over, say, 15 years, you can see a curve that just keeps going down. It never actually levels off. At 20 years or 25 years, is it at 100%? Some people think so. I don't think there's such a thing as 100% in life, but it's a large majority.
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