[Rhonda]: 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...

[Giselle]: Yeah. Hard play.

[Rhonda]: 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. They took Parkinson's patients and had a group of them, you know, basically not do any exercise and other group did moderate intense. So they were doing about 60 percent to 65 percent maximum heart rate. And the other one was high intense where they were about 80 percent to 85 percent. Again, people that aren't measuring their heart rate, you know, when you're sweating and you're flushed, I mean, that's kind of a good indicator...when you feel uncomfortable because you're pushing it, you know?

[Giselle]: Right. Exactly. That's a good example.

[Rhonda]: This was a six-month trial and the people that did not exercise according to the tests that they measure for disease progression, and we talked a little bit about this. There, 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 percent worse over the six-month trial. The ones that did moderate-intensity progressed 7.5 percent, 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 15 years.

And I've seen it progress from tremor, 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 in this...sorry, in the study they did, it was 3 times a week, and it was about 30 minutes of the intense exercise. It was 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. I mean, that's a huge difference in quality of life.

[Giselle]: Right. That is huge. That is huge. 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 with 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 percent of treatment should absolutely be lifestyle and particularly exercise and all the things we just talked about and making it intense, having a physical therapist that can help you really challenge yourself. We talked about gait and balance because that tends to be the bigger issue. And when you try gait and balance, it's going to incorporate many other different things, making an 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 is no data that it stops disease. So that's the one thing. It's never shown 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, 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 have 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 as important, but dopamine enables plasticity.