Dan Keller 0:02 Dan, 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.
When people think of Parkinson's disease, they often envision an elderly person with slowness of movement, short shuffling steps, or tremor, but the disease can and does occur earlier in life, and this is called Young Onset Parkinson's Disease, or YOPD for short. About 4% of cases in the US are of the young onset PD variety. Younger people will experience Parkinson's symptoms differently due to their unique life circumstances. In this first of two episodes on young onset Parkinson's disease, Dr. Bart Post of Radboud University in the Netherlands explains how young onset Parkinson's disease differs from later onset disease in terms of genetics, progression, treatment, and medication side effects. I first asked him about when the disease is considered young onset PD.
Dr. Bart Post 1:46 There's a lot of discussion about it at the moment in literature. They say it's under the age of 40 or 50 years old at the onset of the disease, and there is this separation between juvenile Parkinson's—that's an age at onset below 21—and then between 21 and 40, or 21 and 50, we call it young onset Parkinson's disease. So there's not a real hard cutoff age in literature. In the Netherlands, we say it's 50, but it's arbitrary to choose that age.
Dan Keller 2:25 What does the literature say about a genetic component for young onset Parkinson's disease versus later onset? And how would that impact going backwards family history and going forwards having a family?
Dr. Bart Post 2:40 I think genetics are especially in the young onset population interesting. I think the younger the onset, the higher the chances that it's genetic, especially in the juvenile Parkinson's. You see a lot of genetic causes, but I think we leave that out of our discussion now. So we are talking about the patients from 20 years, 30 years, and in the 40s, and what we see in more literature at the moment, that around 15 to 20% of this population—and again, when you're in your 20s, the chances are higher, but around 15 to 20%—have a genetic mutation. A lot of the mutations are GBA mutations, so there are risk mutations, and LRRK2 mutations, and then a lot of parkin mutations, so it's quite a group that have this genetic component.
The next step is when you look at your family to come, look at your children, then it's quite difficult. We do a lot of genetic counseling for our young onset patients, but genetic counseling is not easy, because for example, when you have the GBA mutation, then there's a 50% risk that you give it to your children, but if one of your children has it, there's only a 30% chance that they will develop Parkinson's disease during life. So, it's quite complicated. These genetics, we put in a lot of time to explain to patients before taking the test.
Dan Keller 4:17 So it sounds like it's a dominant gene, but with imperfect penetrance.
Dr. Bart Post 4:23 Yes, yeah, it's a risk gene. It's the same in LRRK2 mutations, it's around 40 to 50% chance of getting the disease. So, yeah, for the dominant genes it is. For these two dominant genes—and there are these like alpha-synuclein mutations, or the VPS35 that's rarer, and they have a higher penetrance. And then we have the recessive, the parkin, the PINK1, and DJ-1, but especially PINK1 and DJ-1 are rare. Parkin mutations are more frequent, and what you have, like a gene from your father and from your mother, that's not good, then you get the disease. If you're sick with, like, for instance, a parkin mutation, then you only give one gene that's not good to your children, so your children won't be sick. They're only a carrier. Especially dominant genes are difficult.
Dan Keller 5:20 When someone does develop young onset Parkinson's disease, how does it manifest? Is it different from what you would see at a later onset?
Dr. Bart Post 5:30 We looked at it, and there are several other studies in Europe and in the US, and what we see is that young onset, especially, they have much more dystonia at the onset. A lot of patients have dystonia, for instance, in the foot, and you see around between 10 and 20% of patients have early dystonia, and some of them, they have dystonia before they get their bradykinesia and rigidity. What's really typical, what we see in this patient group is exercise-induced dystonia of the foot, for instance, during exercise. So, when they do running, and after five or 10 ks of running, they get this inversion of the foot, and that can be the first sign of a young onset Parkinson's disease. You don't see that that often in later onset disease.
The other thing, we see less tremor in young onset PD, so tremor is more prevalent in the older age group. And after diagnosis you see a lot of delay in the diagnosis, more than in later onset, and we think it's because of the features it presents with. For instance, the exercise-induced dystonia, they are not recognized, and the second is that, oh, you don't expect it in a patient of 32 or 34, and in 65 it's a normal age to get PD, then you're triggered to think about it. Those are the biggest differences between presentation or diagnosing young onset PD, when compared to late onset PD.
Dan Keller 7:11 Are there implications for daily clinical practice? Do they respond differently to drugs, or are there other differences you have to take into consideration in the office?
Dr. Bart Post 7:22 Yes. After diagnosing young onset Parkinson's disease, then that comes to discussion about treatment. Well, as we all know, we have levodopa and dopamine agonists are the mainstay of therapy for Parkinson's disease, and what we know is that levodopa-induced dyskinesias are more prevalent in young onset patients. Under 40, after five years of disease duration and treatment with levodopa, almost all of the patients have levodopa-induced dyskinesia, as opposed to an older age at onset, for example, above 70 years, we know that after five years, only around 30% have this dyskinesia. You see a lot more levodopa-induced dyskinesia, and that's why there's a lot of discussion—as there still is in the world—discussion about should we start with levodopa in young onset, or do we prefer a dopamine agonist? And at the moment in the Netherlands, but I also know that, for instance, we all start with levodopa, and then under a low dose and slowly titrating, and then we combine it after a few years with a dopamine agonist. I think that's a main point in treating young onset PD in the beginning.
Dan Keller 8:48 What do you see in terms of progression, speed of progression, or when it may begin?
Dr. Bart Post 8:55 When I talk to young onset people—and I do it every day—I call it the paradox of getting young onset Parkinson's disease. When you get it at a young age, your progression rate is slower than when you get it at an older age. For instance, when you get it at age 35, you have a considerable chance that you will live with the disease for 20 to 30 years. When you get it at an age of 60 or 65, these chances are much lower. I think it's around 15 years normal progression till you really get problems like dementia, falling, and eventually you die of a complication. So, getting it at a young age means that the progression rate is slower, but you have to live with the disease for a longer time and be impaired a longer time. That's what we know from literature.
Dan Keller 9:47 How do younger onset people respond to exercise? Is it as recommended for them as for later onset?
Dr. Bart Post 9:57 Yeah, we recommend it to all the patients. And we did a study in the Netherlands, a trial for exercise, and we compared it to stretching. As far as I know, we didn't see any differences between younger and older age people in this cohort. So for me it's the same when I counsel patients; we say exercise is important for all. That's not a difference between late onset and young onset.
Dan Keller 10:26 Very good, I appreciate it. Next time we'll pick up on talking about some of the emotional issues and some of the counseling issues. So, thanks for being with us today. Thank you.
The Parkinson's Foundation website has many useful articles and other resources relevant to young onset PD. An excellent starting point is an article called Young Onset Parkinson's, and you can go directly to it on our website at parkinson.org/yopd. If you search the website on YOPD, you can find an article called Navigating the Challenges of Young Onset Parkinson's. Among other things, it emphasizes the importance of expert team-based healthcare to bring in the right practitioners to help slow progression and decrease symptoms. This is important for all people with PD, but especially for individuals with young onset Parkinson's disease.
Younger brains have greater neuroplasticity, meaning the ability to grow and change in response to therapy. Since people with YOPD have many years of life ahead of them, starting early with optimal care may result in benefits all along the way. In addition, the article links to information about dyskinesias and dystonia from common PD medications. Also included is a link to an article called 10 Helpful Young Onset Parkinson's Resources, which discusses or leads to further targeted information. Finally, for even more resources, take a look in our library at parkinson.org/library. There's a drop-down topic menu at the bottom of which is YOPD.
As always, our helpline information specialists are available to answer questions in English or Spanish about today's topic or anything else having to do with Parkinson's. News and updates about future events and resources are available by joining our email list at the bottom of our website's homepage. 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. Till next time, 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. Thank you.
