Exercise is considered to be an important therapy for individuals with Parkinson's disease. Research shows that exercise, particularly intense and skillful exercise, can have several benefits for individuals with Parkinson's disease.
Exercise can improve motor function, gait, and balance in individuals with Parkinson's disease .
Intense exercise has been shown to slow the progression of Parkinson's disease. In one study, individuals who engaged in high-intensity exercise experienced no disease progression over six months .
Exercise increases the expression of dopamine receptors, which is clinically meaningful and correlates with improved postural control .
Different types of exercise can be beneficial, including activities like Tai Chi, yoga, surfing, and non-contact boxing .
Skillful, challenging exercise that engages the brain and requires problem-solving can have additional benefits .
It is recommended to engage in exercise at least three times a week, with each session lasting around 30 minutes. Making the exercise as intense as possible is also important .
Having a personal trainer or working with a physical therapist can be beneficial to receive feedback and guidance for challenging oneself during exercise .
While exercise is beneficial for individuals with Parkinson's, it is important to note that exercise is not a replacement for medication such as L-DOPA. Medication and exercise can work together to improve symptoms and quality of life .
It is recommended that individuals with Parkinson's disease consult with their healthcare provider for personalized recommendations and guidance regarding exercise and treatment options .
(someone): You know, you get the speed up, you have to make it more accurate, all those sorts of things is going to make it harder for you. So the idea would be getting out of your comfort zone, problem-solving, how to get more accurate, how to get that speed up, how to become more dynamic on that task. And as I said, that can be done even with a physical therapist working on gain and balance, right? That itself is going to be more skillful over time.
Rhonda Patrick: So the skillful exercise that you're describing seems really independent of... talking about something else, which would be the intensity of your exercise, the vigorousness, like that's another aspect. What you're talking about specifically has to do...I mean, you're obviously getting some physical activity, but it's a very specific type of activity where you're focusing on something, you're getting that feedback of learning, and you're basically engaging your brain a lot more than just like... Right.
(someone): And I think fundamentally, you're sort of getting at the two kind of... two kinds of discussions that are going on with exercise. Actually, there's other discussions with muscle resistance and those sorts of things. But I think, fundamentally, some of the questions that are coming up are intensity in the context of learning. So one is learning, more about motor learning, right, which definitely requires lots of practice and challenge to get good, right? Like tennis, as an example, right? And the other type of intensity was the heart rate, getting your heart rate up, feeling your heart pounding in your chest and sweating. That's also intense. So they can both be very intense, but for different reasons, right?
(someone): It's play. which is all those things, really.
Rhonda Patrick: Definitely increases compliance that you'll keep doing it if it's something you enjoy doing and like doing. It's play, right? But to a certain extent, you also want to make sure it's not...I mean, it's play, but you're also, like, pushing yourself, right? You're not... You know, I... Hard play, okay. There was that study, I think it was JAMA Medicine, the one that was published in December 2017, where they did the dose response and intensity of exercise that took Parkinson's patients and had a group of them, you know, basically not do any exercise. Another group did moderate intense, so they were doing about 60% to 65% maximum heart rate. And the other one was high intense, where they're about 80% to 85%. Again, people that aren't measuring their heart rate, you know, when you're sweating and you're flush, I mean, that's kind of a good indicator. When you feel uncomfortable because you're pushing it, you know. Right. Exactly. That's a good example. This was a six-month trial, and the people that did not exercise according to the various...the tests that they measure for disease progression, and we talked a little bit about this, and maybe, you know, there's some caveats there, but according to that, you know, test they do, The people that did not exercise progressed 15% worse over the six-month trial. The ones that did moderate intensity progressed 7.5%, so about half of what the ones that didn't exercise.
Rhonda Patrick: The people that did not exercise progressed 15% worse over the six-month trial. The ones that did moderate intensity progressed 7.5%, so about half of what the ones that didn't exercise. And the people that did high intensity had zero progression over six months, which to me is huge. When I think about Parkinson's disease and a friend of mine, a really close friend of mine who happens to be a neurologist as well, she specializes in motor dysfunction as well. Her mother has Parkinson's disease and I've watched her progress over the last And I've seen it progress from tremor, a little bit of the gait problems, to now she can't walk, she can't dress herself. I mean, you know, it's progressed now to full-blown dementia. So there's definitely a progression there. And I'm wondering, it's like, if you could take someone and have them...sorry, in the study, it was three times a week and it was about 30 minutes of the intense exercise with a little bit of a warm-up and cool-down. And if you could take someone and have them do an intense workout like that three times a week... And slow the progression where you're talking, you know, just having a little bit of a tremor and maybe some of the slowness, you know, maybe just a little bit of that initial stage, but like having their quality of life where they can still dress themselves and put their makeup on and, you know, like they still have their mind. That's a huge difference in quality of life.
Rhonda Patrick: How people with Parkinson's disease have higher circulating levels of pro-inflammatory cytokines. which might contribute to the disease, and we discussed how diet may play a role. Dr. Petzinger's bottom line on frequency, dosing, and type of exercise that is therapeutically beneficial in Parkinson's disease, and so much more. But before we jump in, I want to mention a couple of things. If you've been enjoying our podcast, I encourage you to subscribe to our newsletter and get the most up-to-date information on our new podcast episodes and ongoing in-depth analysis on crucial health-related topics. Subscribing to our newsletter is the easiest way to make sure that you don't miss when we post one of our fully referenced topics pages or when we have a really exciting podcast coming up. To sign up, just head over to foundmyfitness.com. There, you can also check out the benefits of our premium membership. If you appreciate the work we are doing at Found My Fitness, our premium membership is a great way to give back and enjoy some added benefits as well. For example, once a month you can join a live Q&A with me and listen to my answers to questions submitted by you and other supporters. Plus, a lot of other great benefits including the Aliquot, our new members-only podcast that curates and remixes the best of FoundMyFitness. Head over to foundmyfitness.com to learn more. One final note before we jump into the interview. If you or a loved one has Parkinson's disease, this episode is not intended as medical advice, and it is not a substitute for professional medical treatment or care. If you need medical advice, seek it out.
Rhonda Patrick: The functional symptoms of Parkinson's don't manifest until about half of the dopamine-producing neurons are lost. Using imaging studies, scientists can detect changes in dopamine receptor density in the brains of living patients, allowing them to assess the effects of exercise-based interventions. For example, one study showed that eight weeks of intensive treadmill training increased dopamine receptor expression by 80% to 90%. These changes in dopamine receptor expression are clinically meaningful and correlate with improved postural control. The take-home from these imaging studies is that the right intervention can be profoundly helpful in Parkinson's disease. Other clinical trials show that moderate to high-intensity exercise increases neurotrophic factors, such as brain-derived neurotrophic factor, improves gait and balance, and may even slow the disease progression. In one trial, high intensity exercisers experienced no disease progression over six months, while non-exercisers got 15% worse. This is remarkable because no drug or treatment has been shown to slow the progression of Parkinson's disease. Delaying this neurodegenerative disease progression can profoundly improve a person's quality of life. What I hope that most of you will take home from this conversation today is that even devastating diagnoses like Parkinson's disease have the potential for very different trajectories, at least partly affected by the lifestyle choices we make each day. In today's episode, Dr. Petzinger and I discuss what Parkinson's disease is, what causes it, and how common it is in the population. How a tragic event in the 1980s involving IV drug users propelled the field forward and illustrated to scientists that environmental factors such as pesticides could cause Parkinson's disease. How genetic mutations and pesticides can disrupt mitochondrial complex one, leading to the death of dopamine producing neurons in the brain.
(someone): Absolutely. And I think...so there's the issue of the different types of exercise and also kind of getting into that discussion. Sort of underlying that is obviously the mechanism question, right? So are they doing something differential, right? And I think the reason we care about things like that is because I think one of the general early concepts of exercise in general has been really more about body's effect on the brain, you know, as though the brain is a passive recipient of all these sorts of benefits somehow, right? I think when we're teasing apart these different types of exercise, I think one of the questions that come up is, we care about these different types of exercise because we do believe that there are certain circumstances where the brain may play a more active role, meaning it's driving some circuit-specific effect. And what I mean by that is this whole idea, for example, if I'm more engaged in what I'm doing, if I'm more top-down, cognitively involved in my process of movement through space and learning something, then I may be activating certain circuits, right? And that activation of circuitry, by virtue of using it harder, may itself drive some of these benefits, right?
Rhonda Patrick: Can you give an example of that type of physical activity?
(someone): Right. So, for example, let's say something that would be more skillful, right? So, where I'm actually having to get better at it, it's actually quite challenging. For example, I...we're in Southern California, so surfing as an example. where I'm not only considering obviously how I'm bouncing on the board, but I'm watching the weights. I'm thinking about my speed getting up on the board, my weight distribution.
(someone): And what's interesting about that field, though, is even in the context of environmental enrichment, many times it's also what else is in there, like the wheel or...I mean, there's always a physical component that they find is also important. So I think it kind of just, as I said, kind of goes back to the idea that movement through space is a big deal for our brain. It itself is a cognitive load. we can definitely ramp that up in a lot of different ways. Certainly, from a skill point of view, we can. From an environmental enrichment, making it a novel environment for us, moving effectively through space is also, in a new space, in a novel environment, is also pretty big. I know there's a lot of interest now looking at natural spaces and what that does for cognition as well, and there's some really interesting things coming out of that. Again, kind of tying it back into movement, though, is really where it gets really interesting, yeah.
Rhonda Patrick: Right. I mean, certainly, so in addition to, you know, all the benefits that exercise...I mean, there's been studies showing that, you know, in Parkinson's disease patients, Parkinson's disease patients that do, you know, a certain amount of, you know, 30 minutes of exercise, you know, moderate to high intense, intensity increased BDNF in their plasma, and BDNF crosses the blood-brain barrier. It's a growth factor. It's important for maintaining synaptic connections, it's important for growing new neurons, and it's certainly important for repair of damaged brains. So there's definitely lots of factors that probably, as you were mentioning, there's
(someone): But yeah, the idea that there is, you know, TNF-alpha, IL-6, so the idea that there may be higher pro-inflammatories cytokines, and that's something that we're going to try to explore in some of the work that we're doing right now. So, you know, people do believe that, you know, Again, it may not be the cause of Parkinson's, but it may be something that's adding to the progression, which is things like inflammation, what role diet and the microbiome, I mean, they all start tidying together there. That may play as a mechanism that's going to be important and something that definitely needs to be investigated further. So, again, another place where we may be able to modulate the disorder.
Rhonda Patrick: But right now, it seems as though the thing that's pretty repeatable is the exercise. Do you tell them three times a week?
(someone): Yeah. I mean, basically, most of the studies are about three times a week. So I would say about three times a week, minimally, 30 minutes, three times a week, and trying to make it as intense as possible. Intense as possible. Yeah. And then we add that as part of that, that should also have some skill. component, particularly involving gait and balance-related tasks. And there's a lot of things that do that. So I don't pick out any one in particular. Whether that's Tai Chi, yoga, surfing, whatever they like to do, I think that's important as well.
(someone): That's correct. But the idea there is once L-DOPA makes it into the brain, it gets converted in the brain in those remaining cells to dopamine. And that is now targeting those circuits that I mentioned, the automatic circuits, right? And that's what allowing it to work more efficiently. And then the idea is with adding exercise, it may also drive repair.
Rhonda Patrick: So you're saying that exercise is not a replacement for the L-DOPA, the carbidopa, but it's in combination, you know, because you obviously still need the dopamine and I think that the L-DOPA and the carbidopa itself doesn't actually slow disease progression, but it does help treat symptoms. But after a certain time, doesn't some of those become refractory?
(someone): Well, I would say there are several points. One is that because those cells are not storing it as well, you're having to dose more frequently, so that's a cell dysfunction problem. And then secondarily, there are other circuits, cognitive circuits, as an example, that are getting affected, and we know cognition plays a big role. in my ability to move safely through space, and so that's going to be a big contributor. And L-DOPA does not do as much. It's not as effective for cognitive function. It has a role there, but it's one of many different chemicals, acetylcholine being another one, serotonin or epinephrine being other ones.
Rhonda Patrick: These things are also modulated by exercise.
(someone): It has a role there, but it's one of many different chemicals, acetylcholine being another one, serotonin or epinephrine being other ones.
Rhonda Patrick: These things are also modulated by exercise. And there have been meta-analyses that have been done looking at various types of exercise and their effect on cognitive function, executive function, global cognitive function, memory. And those things can be improved by intense.
(someone): Right. And aging field, I'd say, is a little further ahead of us in terms of their data. Probably the strongest data is in the aging field right now.
Rhonda Patrick: Absolutely. It is. But there are some with Parkinson's patients that they have looked at. It certainly is affecting cognition as well at the exercise. So again, it's just like doing that, I just feel like it's like driving at home. We hear about exercise and how important it is like every day in the press. I mean, everyone's heard it. The question is like, how do you get your patients? that have Parkinson's that may be sedentary. There's quite a few people that are sedentary in their late 60s. And how do you convey the importance How critically important it is to do exercise along with their treatment? Yeah.
(someone): I think one of the first things I would say is education. I mean, I think, you know, having the data, you know, that's huge. So, you know, it's one thing to say, okay, exercise is important.
(someone): I mean, we can make it, you know, have you be more accurate with it, make you go through an obstacle course. So we can make it harder yet to get you even better for balance, as an example.
Rhonda Patrick: No, what I was saying is when someone's diagnosed, like, does their balance, like, for example, if they were just diagnosed, you know, are they going to be having problems with their balance or is that as the disease progresses or is it very... No, it is as the disease progresses in general, but gait is very common.
(someone): I mean, not normal gait, so they'll have slowness in the gait, for example. And by gait, you mean like how they're walking.
Rhonda Patrick: Exactly.
(someone): Yeah. So, I mean, we tend to target...and that's why you see many of the exercise programs really target gait and balance because many times...I mean, so people definitely can have slowness in their hand and stiffness in their trunk. But targeting gain and balance is huge because that's really ultimately probably where the biggest deficits are. And many times in targeting gain and balance, you're really engaging different parts of the body as well, arm swing, posture, and these sorts of things. So it's a good place to start, if you will. Now, obviously, you can add more with things in your arms, boxing is an example, that way you can add more and make it more complicated tasks.
Rhonda Patrick: And if people that are doing this rock steady boxing, as it's called, the non-contact, are they just like doing like a bag or is it like...
Rhonda Patrick: It sounds like having a personal trainer may be a good idea because you're getting all of these things that you're mentioning. You're getting that feedback. You're getting someone to help challenge you more. It's that challenge. You don't want to just be in your comfort zone like you would if you were walking your dog. You want to push yourself more. And so, it helps to have someone... It does. ...for a group class, you know, with the feedback and, you know, I mean, it's just... Yeah.
(someone): And I think it's great. You've touched on a number of different things. I think, first of all, number one, I think, in general, we like having patients with Parkinson's have exposure to physical therapy one-on-one periodically. And I think the idea there is what you've said. for a couple reasons. Obviously, one, you want to make sure you're challenging yourself. You want to make sure you're not hurting yourself. But also, you really are gaining kind of a tool set and feedback on what you need to be working on. And it is, as I said, you know, getting the feedback to be accurate and problem solved to do it again better, right? And so, you know, you definitely want to progress and get better, number one. And two, you can kind of use those tool sets to apply now to a class. So you're doing your class, but you kind of know what you need to be working on. So I kind of like that combination.
Rhonda Patrick: That's correct. Exactly. And, I mean, exercise is pretty much...it's like a panacea. I mean, you're talking about decreasing the risk of Alzheimer's disease. In fact, it's been shown to help, you know, with recovering from traumatic brain injury. In a way, Parkinson's disease is kind of like a... traumatic brain injury, you know, like just extend it out, right?
(someone): Not something that just... Yeah. And I think that's also why...so, yeah. So exercise, obviously, there's a lot of... Interesting data, compelling data, certainly from an epidemiologic point of view that it may lower risk for Parkinson's disease. I like to kind of think about exercise and lifestyle in general. Obviously, we're going to talk a little bit more specifically about exercise. It's sort of the counterweight to everything we talked about before. So, the idea that, you know, multiple things, genetic risk factors, environmental risk factors, and disuse, if you will, of lifestyle factors, kind of contribute to brain injury, brain changes over time, so sort of an insult, if you will, to the brain that bring out diseases. Parkinson's is an example of that. And it sort of plays out fundamentally at a circuit level, meaning behavior is what is underlying circuitry. So if we see behavioral issues, then whatever that damage is occurring is happening because of synaptic connection losses, either physical loss or functional loss of connections, right?
(someone): That's also intense. So they can both be very intense, but for different reasons, right? So more from the aspect of learning and practice and problem-solving to get better at something from a physical point of view. So things can be very physically challenging to learn, you know, like skateboarding or tai chi or yoga. And Parkinson's disease, the bottom line is their gait isn't normal. The balance is not normal. We're starting all over again. So this is not normal walking. And this is not normal dynamic balance. They have impairments in that. So we can start at that level. We're concentrating on getting their balance better, the walking stride better, the posture better. All those things are what we call more normal automatic gait. That's practice to them to get it good and to make it harder.
Rhonda Patrick: And now, is that as the disease progresses, those things are dysfunctional? Or you're saying like... Even from the beginning, right.
(someone): We're already working on it and making it harder. We can make it harder yet. I mean, we can make it, you know, have you be more accurate with it, make you go through an obstacle course. So we can make it harder yet to get you even better for balance, as an example.
(someone): And it's like, yeah, no. No, no, no, no. People are afraid of falling. They're afraid... No, I think it's this idea that somehow you can't gain something from or you just can't do it. I'm not sure. But yeah, so forget that. Yeah, no.
Rhonda Patrick: Everyone is... Do you see improvements like with your people that have more severe... Everybody gets better.
(someone): I mean, we see improvement in everybody. I think that's the thing. And even small gains are good gains. I mean, so yeah, and I like them to mix it up. I tell them to play instruments even to get more hand skill going. I mean, yeah, I mean, I think that's the thing. In a way, we're too easy on each other. And as people get older, it's like, yeah, get out there and learn something. Go out there and learn a new skill.
Rhonda Patrick: Take up racquetball. I mean... Are there...like, is this a common...for clinicians in the Parkinson's field, are they commonly emphasizing exercise? Do you know...is this, like, something that's been more embraced or do we have to push it more?
(someone): In general, it's been more embraced, but I have to say, in general, I mean, I'm very
Rhonda Patrick: Well, you do research on it. I'm harsh. Yeah, I'm harsh. You've got the data.
(someone): where I'm not only considering obviously how I'm bouncing on the board, but I'm watching the weights. I'm thinking about my speed getting up on the board, my weight distribution. So there's a lot of different things I'm thinking about as I'm trying to get better on that. I fall off and I do it again and getting through a lot of different practices. So it's a lot of practice, repetition, learning, feedback. where I'm really thinking hard about what I'm doing. So that as a skill versus, for example, a stationary bike, right, where I'm just moving my legs, trying to get up to a certain speed, but maybe not having to think about balance as much, these sorts of things.
Rhonda Patrick: What would be an example for someone, for example, that has Parkinson's disease? They probably aren't going to be out surfing.
(someone): So, Tai Chi or yoga as an example, right? And boxing as an example.
Rhonda Patrick: So, non-contact boxing.
(someone): Right. But also, many of the physical therapists, what they'll do as an example is just even gait and balance practice, make it harder. Anytime you're making something harder, more challenging, whether it's through balance, whether it's through weight change, through dynamic balance, working harder with dynamic balance, speed. You know, you get the speed up, you have to make it more accurate, all those sorts of things is going to make it harder for you. So the idea would be getting out of your comfort zone, problem-solving, how to get more accurate, how to get that speed up, how to become more dynamic on that task.
Rhonda Patrick: If you or a loved one has Parkinson's disease, this episode is not intended as medical advice, and it is not a substitute for professional medical treatment or care. If you need medical advice, seek it out. Please enjoy this great conversation with the brilliant Dr. Giselle Petzinger, and watch out for more interview episodes like this one coming soon. And now onto the podcast. Hello, everyone. I'm sitting here with Dr. Giselle Petzinger, who is a clinical neurologist who specializes in Parkinson's disease. She is at the University of Southern California, where she splits her time between clinical care and research. One of the reasons I reached out to Giselle is because I'm particularly interested in some of her research on the role of exercise in Parkinson's disease. Excellent. So can you talk a little bit about... what Parkinson's disease is, maybe just from a, like, basic standpoint.
(someone): Absolutely. So Parkinson's disease is a progressive neurodegenerative disorder. It's a disorder that affects individuals that are over the age of 50, generally speaking. So we consider it a disorder of aging. And, generally speaking, we think of Parkinson's disease as a problem with mobility. In fact, clinically, that's how we tend to recognize it. And most people, when they're trying to or feeling that something's changed, it's often because of mobility problems. And what I mean by that is slowness. People will describe feeling slow or dragging a leg.
(someone): So I don't pick out any one in particular. Whether that's Tai Chi, yoga, surfing, whatever they like to do, I think that's important as well. And I think, as you pointed out before, having someone to give you the feedback so that you're accurate and challenging yourself is actually quite important. So I think having that one-on-one, particularly in Parkinson's, is a smart thing. And we do try to get people into some one-on-one therapy. I usually do at least two times a year. And actually, I start right away. And there isn't anybody that I don't send because we can always make it challenging for you.
Rhonda Patrick: I think, absolutely, that's really key. I think that having someone there that's going to really help push you past your comfort zone, give you that feedback. It's really important for people, particularly people that are less prone to push themselves. I'm one of those people that I'm pushing myself. I want to be the hardest working girl in my spin class. But I'm also...I don't have these neurological problems and apathy and all this other stuff that comes along with Parkinson's disease. I've been younger and this is sort of my personality. And getting someone to do that, push themselves, it's so key. Oftentimes, you know, I might say to someone, you know, exercise is really important. They're like, well, I walk my dog. And it's like... Yes, I hear that a lot around here.
(someone): Now, obviously, you can add more with things in your arms, boxing is an example, that way you can add more and make it more complicated tasks.
Rhonda Patrick: And if people that are doing this rock steady boxing, as it's called, the non-contact, are they just like doing like a bag or is it like...
(someone): Yeah, so I have to tell you, I've never gone to a Rocksteady boxing class, but the idea would be that, yeah, they're learning different types of patterns of movements, for example. So it may not just be pure moving of the arm, but it may be a pattern that they have to replicate, for example. So that would make it more skillful.
Rhonda Patrick: So like palm to the skill that you were talking about.
(someone): Exactly, right. And I don't think anybody thinks that one type of exercise necessarily negates the other. No one thinks that one is necessarily better. They're just different. You know what I'm saying? And I think, fundamentally, the reason we care is we think that the mechanisms which underlie them may be different. And that's why I think, in terms of some of the work that we're doing, we're very interested in that idea. And some of the work that a colleague, Dr. Holschneider at USC has shown, is certainly in the animal models that we've been doing, looking or trying to separate out or tease apart these different mechanisms, where one group of rodents with Parkinson's have gone through a type of exercise practice, more skillful, meaning they're on a motorized wheel with spokes removed.
(someone): And when you train gated balance, it's going to incorporate many other different things, making it intense, partly aerobic, partly from practice. Those are all important. One of the things I have to say, though, that I always try to make clear to people is, one, there's no data that it stops disease. So that's the one thing. It's never shown that it cures Parkinson's. And two, I also want to make sure that we inform patients that it's not a replacement for dopamine. And the reason that's important is because we also had some experience with individuals who were frightened of dopamine, and I know there's a lot of literature out there that can be very frightening for people, but the idea that they weren't taking dopamine at all, all they wanted to do was exercise. And what we noticed is that those people really struggled. I mean, they really were not able to get the most out of practice. They got a lot of fatigability when they tried to exercise. And so, the point was they didn't really get the benefits of exercise because they couldn't do it, right? And so, the other part of the equation is there's a reason for dopamine, right? And so, dopamine has a role for synaptic plasticity. Obviously, practice is important, but dopamine enables.
Rhonda Patrick: Can you talk a little bit about...so the standard of care treatment right now is levodopa, carbidopa, right?
(someone): Right, that is huge. That is huge. And I think, and again, I mean, we still have a lot of room to go. I mean, understanding how this affects Parkinson's disease, we've got some really great promising data. I think there's still gaps, particularly, I would say, still in the cognitive realm. We've got a lot to do there in terms of understanding what that cognitive impact really is. And again, we talked about the idea that cognition impairment is common in Parkinson's disease, probably is finally the biggest disability over time. So, obviously, work to do there, but certainly we're heading in the right direction in terms of, one, trying to understand through many different types of studies, both clinical and in animal models, to try to understand how well they can impact these different circuits, particularly cognitive circuitry, as an example. And then also, I think the cool thing is, you're right, we actually have some data, without a doubt, that we can use now, right? And so the idea of definitely making sure that our patients are well-informed in terms of the idea that it's important, right? So they need to be using, you know, we always say 50% of treatment should absolutely be lifestyle and particularly exercise and all the things we just talked about in making it intense, having a physical therapist that can help you really challenge yourself. We talked about gated balance because that tends to be the bigger issue. And when you train gated balance, it's going to incorporate many other different things, making it intense, partly aerobic, partly from practice. Those are all important.