Mini Elizabeth Jacob, MD, PhD, Assistant Professor, Biggs Institute UT Health San Antonio, Glenn Biggs Institute for Alzheimer’s and Degenerative Diseases talks about a study that involves patients walking across a mat that monitors and tracks a persons gait, and how this could create a link to better understanding and treating Alzheimer’s disease.
So you guys actually have a mat that you’re testing gait. Very basic explanation of how that works.
Dr. Jacob: The gait mat; it looks like a mat but it has got sensors underneath. Those are pressure sensors and it captures your gait as you walk over it. It is connected to a computer, which has software that will capture all the different variables of your gait. For example the speed at which you are walking, the number of steps that you take per minute, your step width, your step length. Those are some of the variables that you capture.
So those variables, let’s take those down to one at a time.
Dr. Jacob: One of the most important characteristics that we know changes with the early Alzheimer’s is the speed at which you walk. So with age, speed decreases. But there could be acceleration in that decline which could happen almost a decade before actual diagnosis of cognitive impairment, and that could indicate the risk for dementia, so that is one. There are other changes as well, not just gait speed. And we’re still doing research to identify what are the different variables and how they might change in very early preclinical Alzheimer’s.
Describe that for me. Would it be a distance between steps? Would it be feet turned outward or inward?
Dr. Jacob: There are different changes. One of the changes that has been identified is the variability. Step to step variability in speed, step-to-step variability in other measures of gait. That is one other factor that has come out as being very important next to gait speed.
How is it different? What are you looking for in particular?
Dr. Jacob: It is a combination of things, a pattern. We cannot say OK this person’s gait speed is less so you are at a significant risk for dementia. It is there, but in our research in the gait study here, what we are trying to see is, is there a combination of variables? Is there a pattern? Is there a signature that would indicate that this person is at a greater risk for dementia? And that would be numerous variables put together. And we’re still working on that.
Give me that signature that – you know this person was on the mat, the algorithm goes to town, and it says OK this is it. They’re a decade away. What does that look like?
Dr. Jacob: Again one of the most important things is a slow gait speed. We’re still working on identifying the signature and different studies have shown different things. And we don’t have a complete gait signature yet. So that is what we are attempting to do.
In addition to the speed though what might be other indicators? I know you’re not finished with the study but I need some particulars on what you’re at least seeking in this study.
Dr. Jacob: Yes. What we hope to do is we have 50 participants on whom we are doing this gait mat testing. We also do cognition testing. We have multiple cognitive assessments, which examine memory, attention, and language. And so we have a complete profile of the cognitive state of individual. Then we have the gait characteristics. What we hope to do is to put these together and see how it correlates with each other; we hope to come up with the gait signature of cognitive impairment.
So isolating the other cognitive impairments from the mat – and the computer algorithm, what is it seeking in addition to gait speed? What’s it actually looking for?
Dr. Jacob: So there are almost 50 variables that are measured by the gait mat and the computer software. And like I mentioned, some of the variables include gait speed, the cadence which is the number of steps you take per minute, the step width, the step length and the variability in these measures. And we don’t have the same speed for each step. We don’t have the same step width for each step. So it might change and the gait variability increases with age. And so we measure that as well.
Is it something where the length of the steps in between steps is at a variable length? Or is it a particular light, OK, if they’re six inches or more.
Dr. Jacob: Your step length and step width are different. It depends on your height and the speed at which you’re walking, so per se you cannot look at one of the variables and say this is abnormal. What you want to do is put multiple things together. And we combine data from multiple people. So we have a population study and that says, this is the average gait speed, this is the average step width. And obviously we may adjust for the height of the people in the study and that tells you… and we associate that with the cognitive state or the risk for dementia. Then we say on an average in this population this step length or this step width or gait speed seems to demonstrate an association with an increased risk for dementia.
That’s exactly what I’m getting at. So your baseline is that average and I know it’s going to vary with height weight age and all of that, but you do have a baseline that you’re measuring against. So just go into a little bit of detail about that.
Dr. Jacob: An average speed of one meter per second is pretty average gait speed measurement. When it gets to less than .8 meter per second that is associated with an increased risk for falls. And if it’s going below .6 meters per second that gait speed among older adults is associated with a very high risk of poor health outcomes including falls, disability, hospitalization and risk for dementia.
I’m going to take a little sightseeing trip right now because you mentioned something interesting. Older people walk more slowly. Some older people a lot more slowly because they’re afraid they’re going to fall. And yet you’re saying sometimes if you slow down you’re at greater risk for falling?
Dr. Jacob: Yes that is a dilemma right there. Slow gait speed is associated with an increased risk for falls and the fear of falling is another factor that makes you walk slower. And we have evidence that both that are associated with an increased risk for falls, yes. So it is fine sometimes if you have a high risk of falling, walking slow is better.
Walking slower is better?
Dr. Jacob: Yes.
See, I misunderstood you. I thought you said if you slow down your gait you’re at greater risk of falling, no? You purposely slow it down because you’re afraid of falling.
Dr. Jacob: No, not purposely slowing down. If you are a slow walker then you have a high risk for falls, but if you are slowing your walk to protect yourself from falls, then that is good because there is also some evidence that in a person who is at risk for falls, fast walking might not be a good thing. We still do not have cutoffs saying this is how you walk. You know how it’s a vicious cycle. You’re slow, you tend to fall; and then you get slower because you fear falling, yes.
So there are a lot of other things. As people age they get vertigo. They get dizzier. Their balance goes off. How does all of that intertwine with this?
Dr. Jacob: Those are also very important factors that contribute to falls and disabilities. What happens is with aging our vestibular system, the system in your ear, which kind of sends messages to your brain about the position of your head and your spatial location; that is affected. We are measuring that in one of our studies, the vestibular function. It helps with your balance, and that is very important for your mobility. When that is affected, you can have falls and disability.
So in other words, if you’re older and you have vertigo or you get dizzy or whatever, you guys account for that in a computer algorithm. That’s all factored in, right?
Dr. Jacob: Not in the gait mat. We will have to get that history from the participant and account for that, yes.
So for somebody like Bruce who has a hurt ankle or hurt knee, does that impact how the gait mat reads the individual?
Dr. Jacob: Yes. Obviously there will be a difference in the way he walks on the gait mat, so we will have to account for that. We do take a really good history of any kind of injury, any falls, any difficulty in walking before we actually have the person walk on the gait mat.
And this gait mat is picking up very subtle changes so it’s not like you look at somebody walk and say, oh, I can tell – before they get on the mat.
Dr. Jacob: Yes there would be some participants in whom the change is rather obvious. But what we hope is to also additionally capture the more subtle changes in the gait as well.
And when you talk about the obvious changes that you see in the walk, what would some of those be?
Dr. Jacob: It could be a stiff gait. It could be sometimes the slowness is rather obvious. Sometimes the stance is really wide. They have a wide-stance step. Those are some of the things that are rather obvious.
And the wide stance, they’re doing that I’m guessing for imbalance, correct?
Dr. Jacob: Absolutely.
So if you have say a person with dyspraxia that comes in, does it account for that kind of thing too?
Dr. Jacob: Yes. There would be changes in the gait. That would be – I didn’t quite get the question.
Dyspraxia where you have no spatial reference, you know what I mean? I’ve seen a doctor give a test where you stand like this, jump around in a complete circle and if you can’t land it, they know you’re dyspraxic. How might that factor in?
Dr. Jacob: We have to account for whatever gait changes that they have given the clinical situation that they are in. But in this particular study we are not including people with neurological disorders obviously because their gait is affected by the condition they are having. We are specifically choosing people who do not have neurological conditions that are affecting their gait. So we are getting people whose changes are more subtle.
And what are you hoping at the end of this study of 50 patients to accomplish?
Dr. Jacob: We would have comprehensive cognitive measures in 50 people and comprehensive gait assessment. And what we hope to do is put those two together and identify the pattern in the gait, which is indicative of a certain kind of cognitive impairment. Essentially looking for what is the signature in the gait, which identifies cognitive impairment in these people.
And cognitive impairment is a pretty – cutting a pretty wide swath.
Dr. Jacob: Yes.
So specifically as Alzheimer’s or any form of dementia?
Dr. Jacob: No. Our participants do not have any form of dementia at all. But we know that with aging there is a certain amount of cognitive impairment and then there is pathology. So there could be vascular dementia pathology related to Alzheimer’s and we know that some of the changes are preclinical. Like even if you check our brains, sometimes we can see Alzheimer’s pathology. You might have amyloid and tau; which are the proteins that are deposited in Alzheimer’s disease that might be present in our brains too. And these can cause changes in gait but we may not develop Alzheimer’s in our lifetime. Some people who have the pathology may develop Alzheimer’s in their lifetime. But this we know from our research in the Framingham Heart Study. We know that even this preclinical deposition of amyloid and tau in the brain can affect on gait.
And so this is a predictive tool?
Dr. Jacob: Yes. We hope that it can be developed as a predictive tool so we can identify who’s at risk. Also we hope to identify the pathway, how is gait related to changes in the brain. And hopefully we’ll also come up with some preventive interventions that can reduce falls that can reduce disability that can reduce the risk for dementia.
I think that person sitting in their easy chair watching this, A is going to think about how they walk and become very conscious of it after seeing the story, and then B sort of wonder why walking would play into it? And by that I mean we do a lot of stories on cross-pollination. You’ve got a bad gut; you’ve got a bad brain. Is that one of those kind of things that you’re predicting?
Dr. Jacob: Well the thing is at this stage in Alzheimer’s disease, nothing is very clear. What we are trying to understand is by examining gait, will we be able to capture very, very early at risk and do something about it? Just because you’re walking slow or in a certain way doesn’t mean that you will get Alzheimer’s or any other kind of dementia. What we are trying to do is, if we can identify a pattern in the walking using the gait mat that identifies a higher risk for dementia, maybe it will help us understand the disease better – how it progresses and also consider preventive interventions? So here’s a group of people who are at higher risk. What can we do to give them an intervention that will help reduce the risk.
And one of the 50 patients we’re going to go interview, specifically why was he recruited into the study?
Dr. Jacob: He was recruited because he qualified. He was eligible because he had subjective complaints of memory loss although he was not diagnosed with dementia. And he also has some difficulty in mobility. Those are the eligibility criteria for our study, you should either have some complaints of memory loss without being diagnosed with dementia or you should have mobility difficulty. What we intended to do is to capture this population who is just at that border line who has some memory loss, maybe very, very early and then some mobility difficulty so that we can put that together and correlate the mobility issues with the cognitive change.
All right. Two final questions. What’s the length of the entire study and then how soon before people might see this in their doctor’s office? And as part two of that is going back to the beginning, how did the gait mat get invented and how’d you come to be testing it?
Dr. Jacob: The current gait study that we have at the Biggs Institute is a cross-sectional study, what we call a one-time study. As of now we have these 50 people; we test them once. We look at their cognition and gait. In the future we hope to follow them up for some time to see how their cognition changes, but as of now this is just a one-time study. But we hope to be recruiting for another study called the MarkVCID Study which is a multi-site study. And the Biggs Institute is one of the sites for the MarkVCID Study. The aim is to validate markers of vascular disease in the brain that contributes to dementia. And so we are one site and as part of the study the Biggs Institute is also measuring gait and trying to identify if that could potentially be a biomarker, an early indicator, of Alzheimer’s disease.
And the beginning of the mat I want to say it had to do with sports. Is that right or am I off the mark there?
Dr. Jacob: Sports?
Yeah. Something to do with the testing of sports. Who invented it?
Dr. Jacob: I don’t have the answer to that. But who invented it? There are a lot of companies who are developing and improving the mat at this point. And it’s just so many groups, yes. The programs are being updated as we talk and they are able to capture more and more. Regarding sports, yes they did start using it for athletes to identify what are the best variables and especially to treat injury among athletes, they did start using it. But we have mostly been using it for understanding gait in older adults – the gait changes.
When you recruited, what ages were you looking for?
Dr. Jacob: We are recruiting people who are 65 and older. That excludes the early onset dementia. There are two kinds of Alzheimer’s disease. There’s early onset, which is a strong genetic background. And then there is the late onset Alzheimer’s that happens to older people. And we are focusing on the late onset Alzheimer’s dementia, which is more common.
END OF INTERVIEW
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