[Rhonda]: So, can you talk a little bit about what Parkinson's disease is maybe just from a like basic standpoint?

[Giselle]: 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 and/or stiffness. So it has a kind of, as I said, kind of a motor movement, big strong moving component. And then, of course, there is tremor. I think one thing though, that people, in general, don't realize is tremor isn't necessary. So tremor definitely brings people in to see a neurologist, and certainly, it can be Parkinson's disease, but tremor can have other causes besides Parkinson's.

So generally speaking, it's really more, I would say about the slowness and the stiffness, and it can affect any part of the body, meaning it can affect the legs and therefore cause slow walking, as an example, but it can also affect the hands and arms where people can actually feel that they can't use the arm as well, they feel that things are taking longer to do. And sometimes that might even be associated with some pain, an element of pain. So as I mentioned, Parkinson's is sort of recognized as a motor problem. What we're realizing and recognizing more over time is that there's what we call a non-motor issue, many non-motor related phenomenon that occur. And some of these non-motor phenomena can occur even before the motor and people don't connect it necessarily with Parkinson's. Examples of that may be loss of smell.

Now, again, some of these other features are not specific, so none of these are specific. We're kind of evaluating everything together, but the non-motor features, as I said, could be the smell, changes in smell. Other non-motor, so that means things that aren't affecting mobility could be mood, for example, so anxiety and depression. In fact, we're now realizing or recognizing...there are a number of papers that have come out now years ago, that anxiety and depression may even predate motor symptoms by two years. And that anxiety and depression may manifest in functional things like not being able to drive in a car on the highway, feeling really anxious about that. And even family members may comment that the person just seems a little bit more depressed. So those things are now really well appreciated and recognized.

Other things that are non-motor that again may precede the motor features are even what we call the autonomic nervous system. So the autonomic nervous system is part of the nervous system that involves or innervates smooth muscle. So this is things like your gut, your heart, your sweat glands, and those smooth muscles are a part of your, as I said, your gut and your blood vessels, when they're not acting normally or behaving normally, it can cause disruption in your gut like constipation. So constipation, again, in retrospect, we find people may have problems with constipation even before they describe and note problems with movement. Blood pressure, changes in blood pressure may be dropping in blood pressure or heart rate abnormalities because of changes in the innervation to the heart. These are all kinds of examples of non-motor that aren't necessarily specific to Parkinson's disease, but kind of come together...once we see the motor features, we can say, "Oh, yeah, before that there were these other sorts of non-motor features that were really predating it." So the point is, is that Parkinson's is certainly more than that. And we're appreciating that more.

And then finally, I would say now, really coming out in the forefront again, even more, is the cognitive issue of Parkinson's. And I think what we're recognizing is, again, cognitive issues are pretty predominant in Parkinson's. The literature's sort of all over the place, but essentially, they are reporting about 40 percent even upon diagnosis may already have some cognitive issues. Now, that's not the same thing as dementia. So this is called mild cognitive impairment, and mild cognitive impairment is defined by the idea that a person may be noticing some memory-related issues or their family members are noting that, but they're not functionally impaired, meaning they could do all their ADLs but they themselves are noting this. And we can actually pick that up on some diagnostic testing as well.

So these things, again, happen quite early. There's some understanding of why this may be happening but they're certainly part of Parkinson's disease. And also the idea that they are very much interrelated. So motor and cognition probably have some relationship too in terms of the idea that cognitive issues can sometimes contribute to more motor problems or cognitive issues can contribute to more mood-related issues. So they're not really separated. They're very much interrelated and we're beginning to understand how and why that may be happening either from a neurochemical point of view or from a circuit point of view.