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Dr. Postuma has been studying sleep disorders in Parkinson's disease for several years. Professor Postuma, do you think there is still a room for idiopathic REM sleep behavior disorder?
[00:00:41] Dr. Ron Postuma: So I think by that question you're sort of meaning is anybody with REM sleep behavior sort of free of underlying neurodegenerative disease?
It's very clear that at least when you go into a sleep clinic, the large majority of people will develop a neurodegenerative disorder and it's almost always a synucleinopathy.
There are always a few patients that I see who I just go, [00:01:00] I really don't think you're like my other patients. They're often 50 years old, or 40 years old, and they've had it for 30 years. Ever since they remember they've been acting out their dreams.
And they often give me a family history of many people in their family doing this, and we look at their polysomnogram, it looks like REM sleep behavior disorder, but they look perfectly well. And then, so I think there might be a few who are free.
And then the other thing I think is important to say is that, Every time I would give a talk on RBD, in the old days, before I mentioned this every time, somebody would come down and they say, you know, three years ago I kicked out once during my sleep, or once every two years I scream in my sleep, or something like this.
I think there is a spectrum of normal. If your dream is bad enough, if you're stressed out enough, if your sleep is light, every once in a while you can move. So, true RBD, coming into a doctor's office, no probably 90 percent have synucleinopathy, but in the general population, I think there's a lot of people who don't actually.
[00:01:54] Sarah Camargos: Okay. Thank you very much for your explanation. Your lecture was [00:02:00] about the sleep parameters to predict motor and cognitive decline in Parkinson's disease. Could you tell our audience about your findings?
[00:02:10] Dr. Ron Postuma: Right, so this was an overall teaching of how sleep identifies prognosis in Parkinson's disease.
So we really ran through the sleep disorders sort of in ascending of order of importance. So, apnea doesn't tell you very much about prognosis. Insomnia also does not tell you very much about prognosis. Somnolence starts to tell you things. So, there are some people who are sleepy. related to maybe to high doses of dopamine or doping agonists, et cetera.
And I don't think that tells you much about prognosis, but clearly somnolence is incredibly associated with dementia. And so there must be something to it. And I think when the sleep cycle gets extremely dysregulated, very laden disease. I think that can be a sign that things are starting to go wrong generally in the brain.
And so there is some link with somnolence. I think the thing that's most interesting and most powerful and most replicated is this very strong connection between REM sleep behavior disorder [00:03:00] and outcome in Parkinson's disease. So this has been seen, and I think this has been over 50, maybe even as much as a hundred studies that have looked at Parkinson's patients with and without REM sleep behavior disorder and DLB patients with and without REM sleep behavior disorder. And they always find that those with REM sleep behavior disorder are worse. And typically it's not so much the motor system to some extent they might have a little less tremor, a little bit more achinetic rigid and more gait problems, but it's the rest of the non motor symptoms.
So there's a strong connection with autonomic dysfunction, particularly orthostatic hypotension and a very, very strong connection with dementia. And so, in fact, it is probably outside of measuring cognition itself, the strongest predictor of dementia in Parkinson's disease, with relative risks that are on the 5 to 10 to 20 range.
it's kind of almost unusual to get a patient who does not have REM sleep behavior disorder when they have dementia at the same time. And usually when they do, you can do a polysomnogram and you see it.
This, of course, leads the question, was RBD causing dementia? I don't think it's like that at all. I think what we've stumbled upon, just by [00:04:00] accident, is that REM sleep behavior sort of seems to mark a subtype of disease. It's really a marker that the disease is synuclein driven, first of all. And second of all, that the synuclein is no longer sitting nicely in the substantia nigra and not much else, okay?
It's starting to diffuse around the cortex. And so we've called it a diffuse malignant, a sub form of Parkinson's disease. It's also, as some people call it a body first or body predominant form of Parkinson's disease. And given the duration of disease, it's very, very clear that these people have just a more advanced generalized synucleinopathy.
And so of course they're going to get dementia. They're going to get all kinds of things first. Why that happens, it's unclear. I think you could make really interesting hypotheses about what maybe synuclein spreads differently or maybe some people with relatively pure motor and Parkinson's disease have just a very accelerated degenerative substantia nigra.
And just earlier in the stage of the disease, you can spin all kinds of hypotheses, but that's really the one thing. If you're talking to a patient, they have RBD, your heart sinks a little [00:05:00] bit because you know, there's trouble ahead.
[00:05:01] Sarah Camargos: Perfect. Very interesting. And another interesting thing is that Stephen Joza, your student was awardee.
Tell us about his study.
[00:05:13] Dr. Ron Postuma: This is shifting gears a little bit because now we're looking at the idiopathic RBD stage. So these are people who don't have Parkinson's yet or at least... don't have fully defined Parkinson's yet, don't have dementia yet. And so Steve has been working with large data sets from the International REM Sleep Behavior Disorder Study Group.
So this is a group of us clinicians who essentially are uniting our forces, sending data to each other, so that we can answer questions on a very large scale. And so he's already looked a little bit at the evolution of various symptoms of Parkinson's disease and the predictive value, for example, showing quite clearly that if you track patients forward in time you can track all the changes, motor changes fast, non motor changes fast, and sample size this out for neuroprotective trials and actually replicating a single center studies of results that [00:06:00] you can use clinically meaningful milestones of change in UPDRS and MoCA just motor and cognition.
And this is by far the most powerful primary outcome measure for trials. So that was the past and he showed that as part of the introduction. And then the second step was actually more of an academic question about how does cognition change when people are getting dementia with Lewy bodies?
So dementia with Lewy bodies and Parkinson's dementia, of course, which is highly similar, evolves differently than Alzheimer's disease. And so the question that he was asking is combining about 750 patients all together who've had cognitive testing, including neuropsychological testing. So all the sort of frontal domains, executive domains, and then following them over the years.
He took patients who had developed dementia. And then look backwards over time and see what's the first to go. What's the most sensitive to change? What do you see earliest? And it's actually a relatively clear message. So the number one test of, if you had to pick of any cognitive test is the trail making test, which is a pencil [00:07:00] paper test or an app test.
It's like 1a, 2b, takes a minute. And this is highly sensitive to change. So it's the first...
[00:07:08] Sarah Camargos: MoCA, right? It's the first question on the MoCA.
[00:07:10] Dr. Ron Postuma: It's on the MoCA, yeah exactly. It's the first question on the MoCA. This is the bigger one. Right? Because it goes all the way to 15 or something like this. But it's timed, then it takes a minute and this starts to look like it becomes abnormal 10 years before a person gets dementia.
A really long time before. This also, however, does identify Parkinson's patients as well, who are not yet demented. So these track early and they progress nicely over time. But they don't clearly distinguish those who are developing Parkinson's from those who are developing dementia with Lewy bodies.
Of course, these are not different patients, right? Everyone with Parkinson's gets DLB. Everyone with DLB gets Parkinson's. But one thing that you can tell, if you want to tell how a patient is going to do, is you could look at their verbal memory. And so, people destined to develop Parkinson's without dementia at the time don't seem to decline in their verbal memory, but the DLB patients do.
And this, I guess, isn't surprising because [00:08:00] verbal memory is the hallmark of Alzheimer's disease, which is the hallmark of amyloidopathy. DLB is Alzheimer's and Parkinson's at the same time, so you can tell these two things apart. So really, that's just the very brief summary, but there's a lot of data on just how each of these things evolve and how we might be able to use them in neuroprotective trials, for example, and to identify which patients are going to go where.
[00:08:18] Sarah Camargos: Wow, it's a lot of data.
[00:08:22] Dr. Ron Postuma: It is a lot. Yeah.
[00:08:23] Sarah Camargos: Yes, I can imagine. So thank you so much for your time. Enjoy the rest of the conference.
[00:08:29] Dr. Ron Postuma: Thank you very much.
[00:08:30] Sarah Camargos: Bye bye. [00:09:00]