Episode 65: Recognizing Non-motor Symptoms in PD

Dan Keller 0:08

Welcome to this episode of Substantial Matters: Life and Science of Parkinson's. I'm your host, Dan Keller. At the Parkinson's Foundation, we want all people with Parkinson's and their families to get the care and support they need. Better care starts with better research and leads to better lives. In this podcast series, we highlight the fruits of that research—the treatments and techniques that can help you live a better life now, as well as research that can bring a better tomorrow.

Parkinson's disease is much more than just a movement disorder. While the motor symptoms of slowness of movement, stiffness, and tremor can be troublesome or even disabling, non-motor symptoms can be just as concerning. These symptoms, including constipation, urinary and sexual problems, sweating, fatigue, sleep disturbances, anxiety, and diminished cognition, can affect basic daily activities and quality of life. While L-dopa and dopaminergic drugs can alleviate motor symptoms, they usually do not control non-motor symptoms, but there is help in other drugs, types of therapy, and activities to address the discomfort of these symptoms. In this episode, I speak with Dr. Daniel van Wamelen, a neurologist and senior clinical research fellow at King's College in London. He describes the more prominent non-motor symptoms and how they affect patients differently.

Dr. Daniel van Wamelen 1:45

Of course, every patient is individual, so everyone has their own symptoms and their own problems. They occur throughout the course of Parkinson's disease. I think some of the more common problems are things like constipation, having difficulties with bowel movements. Sleep problems are very common in Parkinson's disease, and also one of the probably most prevalent non-motor symptoms is hyposmia, which is a decreased sense of smell, and is actually one of the prodromal features of Parkinson's—so something that occurs before you develop any other symptoms, such as the motor symptoms that we still need to make a formal diagnosis of Parkinson's. And also the sleep disorders are some of the symptoms that occur prior to the onset of motor symptoms. Actually, the first one I mentioned, the constipation as well, is one of those features that occur very early on in the disease and probably are among the first signs to occur, and it makes them very prevalent in Parkinson's.

Dan Keller 2:33

Are these necessarily a sign of Parkinson's, or is it sort of the constellation of these non-motor symptoms that make you more suspicious?

Dr. Daniel van Wamelen 2:41

Well, it's probably the latter, I would say. Obviously, if you just look at the individual symptoms, obviously they're very common in a general population as well—things like constipation or sleeping problems. But if you look at the sort of combination and the sequence in which they occur prior to the development of other symptoms, they're quite specific to Parkinson's. And especially one of the most prominent features, or one of the things that always points us towards the direction of Parkinson's, is something that's called REM sleep behavior disorder, which is a very specific sleep disorder where people sort of act out their dreams while they're sleeping. So usually we're quite quiet when we sleep. We don't move a lot, but these people literally act out their dreams. So they're very vivid dreams; they move a lot in bed; they might even hurt themselves. If you have that, there's a very high chance of developing Parkinson's later down the line. Usually after five or 10 years, you'll see most of these people—around 80%—will turn out to have Parkinson's disease.

Dan Keller 3:32

How effective are levodopa and dopaminergic drugs in alleviating any of the non-motor symptoms?

Dr. Daniel van Wamelen 3:39

Well, surprisingly, they are actually quite effective. So levodopa—depends, obviously, on the dose, and there are no formal trials as such assessing the effect of levodopa on non-motor symptoms. But what we know, for example, from other drugs like rotigotine, which is one of the dopamine agonists as a long-acting drug—works for about 24 hours—is quite effective in addressing things like pain or even sleeping problems because it also works during the night. And we know from the advanced therapies—so therapies you would introduce later on in the course of Parkinson's disease, things like apomorphine or duodopa (I think it's called Duopa in the States)—address quite a number of these non-motor symptoms, such as sleep, mood, cognitive problems, memory issues, but also, interestingly, of gastrointestinal problems and urinary problems as well. So some of these drugs are actually quite useful in addressing non-motor symptoms.

Dan Keller 4:30

Are there other drugs adjunctive that would be more specific to the non-motor symptoms?

Dr. Daniel van Wamelen 4:36

Yes, there are. So again, obviously it depends on which one of the non-motor symptoms you look at. So for example, for memory problems, you could introduce a medication which is called rivastigmine, which comes in a patch as well, works for 24 hours a day, and that's actually quite effective in addressing memory issues, but also things like hallucinations and psychosis in Parkinson's. And if you were to think more about, let's say, depressive symptoms—depression—we could go for the usual medication we would also give to patients who don't have Parkinson's, but just depression. So things like, we call them SSRIs, drugs like citalopram, and there are more examples, and those are usually relatively effective as well in treating depression in Parkinson's.

Dan Keller 5:15

So it sounds like Parkinson's is not only a dopamine deficiency disease; there's probably some other things going on.

Dr. Daniel van Wamelen 5:22

Exactly. In fact, most of these non-motor symptoms are probably not related to dopamine. So we always tend to think of dopamine being the main culprit in Parkinson's, in that if you have too little dopamine, you'll develop the disease, which is true for most of the motor symptoms. But we know for many of the non-motor symptoms—for example, the memory issues I've already mentioned—they are probably linked to a neurotransmitter which is called acetylcholine, which works in a very similar way as dopamine but works in different systems in the brain. And if you have too little of it, it probably causes memory issues, dementia. Rivastigmine is a medication that actually works on that. To give you one example, another neurotransmitter which is involved in Parkinson's is called noradrenaline—again, a very important neurotransmitter, mainly for what we call autonomic problems, things like low blood pressure on standing, having difficulties voiding, constipation. It's also among those non-motor symptoms that are probably not dopaminergic, but it's an overlap. So it's a disease where all these neurotransmitters, all these systems, are affected, and it's difficult to single one out and say "this symptom is due to this neurotransmitter" and another symptom to another neurotransmitter. You probably have to look at it as a whole holistic approach with both the motor and the non-motor symptoms.

Dan Keller 6:31

How troubling are the non-motor symptoms, and do people generally recognize them as part of Parkinson's, or do they just pass them off as "everybody gets something"?

Dr. Daniel van Wamelen 6:39

Well, I think you have two approaches, and I think you mentioned them both. So for some people, they will find it difficult to recognize that these non-motor symptoms are actually part of the disease. But we know, if you look carefully, probably most of these issues people experience are part of their disease, are part of the Parkinson's, and they're very troubling. Actually, there are quite a number of studies now showing that if you look at what affects quality of life in people who have Parkinson's, you see that mostly—for most people—the non-motor symptoms are actually more of an issue, have a higher burden than motor symptoms. For example, one of the studies that was done a few years ago at King's, they asked people with Parkinson's, "Can you rate your 10 most bothersome symptoms?" and actually seven of them were non-motor symptoms. So clearly, these symptoms are very important and impact on quality of life quite a lot in Parkinson's.

Dan Keller 7:27

Are there non-drug techniques or things people can do that would help?

Dr. Daniel van Wamelen 7:32

Yes, there are several, actually. So we tend to do most of the things in Parkinson's with drugs. But if you think about non-drug approaches, for example, we know if you're able to move more or be sort of more active throughout the day, that helps, for example, with constipation. So one of the things you could do is try to engage a physiotherapist to make people a little bit more active, which will take care of some of their constipation. And there are also several studies into alternative medicine. Probably the best evidence we have is for acupuncture, and if you look at the effects acupuncture has on some of these non-motor symptoms, there's some indication that it might improve sleep, pain—although, unfortunately, only a few trials have been conducted, so the evidence is very limited, especially for acupuncture. It appears to be some effect on specific non-motor symptoms, but most of what we do will involve drugs.

Dan Keller 8:18

What other health professionals can be helpful in that regard?

Dr. Daniel van Wamelen 8:22

Actually, most of the people we work with normally as part of our multidisciplinary team are very useful. So to give you a few examples of that, clearly speech and language therapy has a big role in things like dysphagia—so difficulty swallowing. Again, I already briefly mentioned the physiotherapist as being able to make people more active, address their motor symptoms, and hopefully along with that the constipation will improve as well. If people, for example, have neuropsychiatric issues such as hallucinations or maybe some of them might be psychotic, sometimes you need to help a psychiatrist or a psychologist, but there's actually lots of people you can involve depending, obviously, on what kind of symptoms the patient has at any given time during the disease.

Dan Keller 9:00

Are sometimes non-motor symptoms related to medication that they're already on?

Dr. Daniel van Wamelen 9:05

Yeah. So sometimes we see that some of these symptoms are indeed related to medication. I think the best evidence in terms of what we see in terms of research, but also what we see in clinic, comes from the neuropsychiatric problems—so things like obsessive-compulsive behavior, having the urge to buy lots of things or to do any kind of activity excessively, is often related to medication and most often related to dopamine agonists, not so much to levodopa, although some people have it on levodopa as well, but it's mainly to dopamine agonists. And also things like hallucinations, psychosis can be related to medication, although we tend to see most of these problems occurring later on in the disease—so part of it might be due to the disease progression as well. We usually tend to see, if you make a few adjustments to the medication, that some of these symptoms might actually improve.

Dan Keller 9:52

Do you see anything new coming along in terms of alleviating non-motor symptoms, and what might those approaches be?

Dr. Daniel van Wamelen 10:00

Well, as far as I know, there are not many trials, unfortunately, ongoing in terms of how to improve non-motor symptoms. Some examples of what we see happening is people are trying to address things like pain. So there have been a few trials ongoing with one of the medication I already mentioned, the rotigotine patch, which appears to have quite a good effect on pain. But I think what we should be aiming for as well is that non-motor symptoms are maybe not as well known as motor symptoms, so people tend to forget a little bit about them. So it's good to see in new trials in any kind of drug that gets tested to have an eye for these non-motor symptoms as well—to not only have a motor outcome, but also a non-motor outcome. And we see slowly more and more trials being published and more and more trials being undertaken to address this issue, to see what the effect of any given medication on the non-motor symptoms is. For example, we also see that with trials into things like apomorphine, duodopa, or Duopa in the States, where they look at the effect on the non-motor symptoms. So that looks quite promising. As far as I know, there are not any specific drugs being developed at the moment to specifically address these non-motor issues.

Dan Keller 11:02

Is pain something in itself? Or can it be related to stiffness and posture and things like that? Or is there sort of a neuropathic pain that comes along with Parkinson's disease?

Dr. Daniel van Wamelen 11:13

Actually, we know in Parkinson's disease there's several kinds of pain. So obviously, when people are in their "off" state, when they're very stiff, very slow, we know that there's a high prevalence of people reporting pain, so that's one that's clearly related to the motor state. We also know there are pains which are more neuropathic, so usually in the legs or might be in the arms, radicular pain—so sort of a sciatica radiating down one leg or one arm. And these are not necessarily related to the motor state the patient is in. And we also know there's a kind of pain which is associated when people have dyskinesia—so when they have too much movement as a complication of the dopaminergic treatment. And obviously all of these has their own approach in how you would address them and how you would improve the pain they have. So it's a very heterogeneous group when it comes to pain in Parkinson's disease, and probably most of it is related to the disease itself, although people can also have other conditions and other problems which cause them to have pain and they also have Parkinson's disease, so sometimes it's difficult to distinguish the two, but most of the pain is probably related to the disease itself.

Dan Keller 12:16

Is there anything important we've missed, or to add?

Dr. Daniel van Wamelen 12:20

What I might add, sort of thinking about your question now, is I briefly mentioned sort of non-motor symptoms are not always recognized by people, and I think it's very important that healthcare professionals are aware of the fact that Parkinson's disease is not only motor symptoms. It's not only tremor, it's not only slowness of movement, it's not only rigidity, but also all of these other issues that come along with the disease and that have a very clear impact on quality of life. And if we at least recognize them, then we can at least acknowledge that it's an important issue, and hopefully, with certain therapeutic strategies, we might even be able to improve it. So I think what I would say is, let's not forget non-motor symptoms, although luckily we see, especially over the last couple of years, that things are improving. People tend to pick up more of these symptoms, are more aware of them, and obviously more and more studies get published on this topic. So I think we're heading the right way. But I think the only thing I would say is: let's not forget about the non-motor symptoms.

Dan Keller 13:13

Thank you. More information and resources about non-motor symptoms are available on our website at parkinson.org. Simply select "non-motor symptoms" within the "Understanding Parkinson's" tab, and you'll find a list of descriptions and tips to alleviate the symptoms. You can also view our expert briefing by Dr. Ronald Pfeiffer addressing the topic on parkinson.org/eb. Several of the past podcasts in this series may also be helpful, such as episodes 3 and 19 on exercise, episode 23 on hallucinations, episode 27 on cognitive and behavioral challenges, and numbers 36, 37, and 38 on mental health. Other episodes, such as 40 and 41, address helpful therapeutic options such as music and dance therapy.

As always, our PD Information Specialists can answer questions and provide information in English or Spanish about this topic or anything else having to do with Parkinson's. You can reach them at 1-800-4PD-INFO. For questions about the topics discussed today, or if you want to leave feedback on this podcast or any other subject, you can do it at parkinson.org/feedback. If you enjoyed this podcast, be sure to subscribe and rate and review the series on Apple Podcasts or wherever you get your podcasts. At the Parkinson's Foundation, our mission is to help every person diagnosed with Parkinson's live the best possible life. Today, to that end, we'll be bringing you a new episode in this podcast series every other week. Until then, for more information and resources, visit parkinson.org or call our toll-free helpline at 1-800-4PD-INFO. That's 1-800-473-4636. Thank you for listening.

Daniel van Wamelen received his medical degree from Leiden University, the Netherlands, in 2008. Following this, he obtained his PhD entitled ‘Hypothalamic pathology in Huntington’s Disease’ at the same university with a large part of the work carried out at the Netherlands Institute for Neuroscience in Amsterdam. He trained as a neurologist at the Leiden University Medical Centre where he obtained his degree in 2016. He became interested in movement disorders during this time and later undertook a clinical fellowship with Professor Bas Bloem in Nijmegen, the Netherlands. He currently works with Professor Ray Chaudhuri as a postdoctoral clinical research fellow at King’s College London and the Parkinson’s Foundation Centre of Excellence, King’s College Hospital, London.

His research interests are the non-motor aspects of movement disorders, in particular Parkinson’s and Huntington’s disease. In his research, the focus has been on understanding the functional anatomy of non-motor symptoms, such as sleep and autonomic dysfunction, in movement disorders using neuropathological methods and clinical (translational) research. The current focus of his research activities is on repurposing existing medication for Parkinson’s disease, such as the potential effect of Apomorphine on cerebral amyloid deposition, and wearable sensors for non-motor symptoms in Parkinson’s disease.