Joe Verghese, MBBS, MS, Professor of Neurology and of Medicine at Albert Einstein College of Medicine and Chief of Geriatrics at Montefiore Medical Center talks about the C-REM study and which older adults are at risk for cognitive impairment.
Interview conducted by Ivanhoe Broadcast News in April 2018.
I want to ask you about the C-REM study, can you tell me what that stands for?
Dr. Verghese: Sure. C-REM stands for cognitive remediation to improve mobility. And it’s based on the idea that to walk in the real world you need to engage your brain and specific cognitive processes in the brain that are important for walking. And the idea behind the C-REM study is that if you could enhance these processes, maybe, we could improve people’s walking.
So it enhances brain function and you see the impact on mobility?
Dr. Verghese: Exactly. In these kinds of studies people use the term “Near Transfer,” which is if you train the brain on a specific cognitive process you might see improvements in that cognitive process. So that’s not too surprising. What’s been a challenge is to show that training then can lead to increase in abilities that are distal to that cognitive process. For instance if you improve a cognitive process like the speed of processing, could it also improve the speed at which you walk? That’s a “Far Transfer” of skills that we’re trying to show in this particular study.
Tell me how the study is set up, what are you doing?
Dr. Verghese: We’re doing a randomized clinical trial and the goal is to enroll 420 older adults who are sedentary and who walk a little slowly because these are the people at the highest risk for their gait failing or developing disability. And we are randomizing them into two groups, so one group which is our intervention group gets to play computer brain games for three days a week for about 45 minutes each. And these games are selected so that they target those cognitive processes that we think are important in improving mobility. And the control group also comes in and people in the group are exposed to the computer. But what they do is they play low intensity computer games or they get health education through computer programs. This helps control for the amount of time they spend in front of the computer because if you take an older person who has not had exposure to computer technology just learning how to use computers might improve some of the brain processes. This is to control for that difference between the two groups.
What kind of computer brain games are they playing, is it Luminosity or what?
Dr. Verghese: It’s a commercially available program called MindFit. It comes with some different games that target different cognitive processes. And with this particular program, we’re able to pick those games that target the processes that we think are the most important.
And which are those?
Dr. Verghese: Things like paying attention, thinking at a faster rate, improving your judgment, improving overall what we call executive function—that’s the ability to think, plan and maneuver in the real world.
So after weeks of playing the brain games what is your measuring in the results of some gait tasks?
Dr. Verghese: Our primary measure is walking but we measure walking under two conditions. One is just plain walking where people just walk at their normal speed. And then we have a condition that we call walking while talking. In this condition, we have people walking and reciting alternate letters of the alphabet. So it’s a challenging condition. It’s been called a divided attention condition because you have to divide your attention between reciting alternate letters of the alphabet and walking. And older people and especially people who have slight cognitive impairment find this very challenging. It’s normal to slow down while you’re doing this. We’ve shown that people who have difficulty either doing this task or who slow down significantly during this task are at high risk of multiple outcomes. They’re more likely to fall, they’re more likely to become disabled. And recently we had a paper where we showed that people who slowed down quite a bit on this task were at increased risk of a type of dementia we call vascular dementia. So it’s an easy clinical tool that challenges the brain. But it is also in many ways reflective of what we do while walking in the real world. Because walking in the real world often is not walking quietly as you would in a laboratory. You have to pay attention to your environment, the pavement might have cracks on it or the ground might be uneven. Often you’re talking to somebody so the walking while talking test is a better reflection of what happens in the real world.
There was also a maze task, what is that designed to measure?
Dr. Verghese: The maze task is not one of the primary outcomes for this study but we are going to study how they do on the maze test. And the maze task is a navigation task. What we do is we have a maze that we’ve laid out on the floor– it’s a floor maze task. We time participants as they go from the start of the maze to the end of the maze. And we found the people that take longer to do that even if they were cognitively normal are the ones at higher risk of developing cognitive impairment in the future. This is one of the secondary measures that we are looking at in the study. But the primary measure is: does it improve walking? We do have some other secondary measures—like we expect some of the brain processes to improve as well. We are measuring executive function, attention, and processing speed as well to see if that Near Transfer is taking place.
Down the road what is the potential impact with this information? Could there be earlier interventions?
Dr. Verghese: I think there are a lot of practical implications if we show our study works, which we hope it does. Even though walking is the best way of improving walking. If somebody came to me as a clinician and asked me, what’s the best way of improving walking I would say go on an exercise program, walk regularly. But it’s obviously not practical either because of the weather or access to the facilities. A lot of older people can’t go and do these kinds of exercises. A lot of times people are frail so it’s difficult to start an exercise program. In other conditions people start an exercise program but they seem to hit a plateau where they’re not improving their walking any further. And in all these conditions, if we pair walking with the brain games then you’re trying to improve walking not just by improving what’s happening in your legs and in your body but also trying to improve your brain power. So together we hope this would be the new model for exercise in older people, where you’re exercising your brain as well as your body.
What is the time frame for this study?
Dr. Verghese: The study is to be done over five years. We’ve finished two years and we’re about halfway through the trial in recruiting the number of participants that we need.
From earlier studies what findings do you have?
Dr. Verghese: We did an interesting pilot study a few years ago. What we did is we recruited 24 frail sedentary older people. And half of them went through the same brain game program that I described where they came in and had brain game activities for three times a week for about 45 minutes. And the other group is what we call usual care so they did not receive any intervention—they just went back home. We kept in touch with them periodically. And the intervention was over in an eight-week period. In this pilot study what we showed is that after the eight weeks both the groups improved their walking a little bit. That’s because if you give a participant the same task twice there’s a bit of learning that takes place. So the control group also showed a slight improvement in their walking. But the group that got the brain games showed a dramatic improvement in the walking speed even though during that period they did not exercise. They didn’t participate in any exercise program. Nor did they walk more during that period. The pilot study seemed to suggest that just training the brain improved walking.
Is there anything I didn’t ask you that you want to make sure that people know about this line of research?
Dr. Verghese: What we have hopes of doing in this study is we’re quite interested in finding what’s happening in the brain while this is taking place. We have access to some of the technology in our laboratory, which is not available in a lot of settings. For example, we have a technology called functional near infrared spectroscopy. It’s a sensor based technology that we place on people’s foreheads and it enables us to peek into the brain while people are walking. So as part of this clinical trial, we’re also measuring their brain activity. And the idea is that the less you need to use your brain, the more efficient your brain. And we hope to see at the end of the trial that we would have reduced the amount of effort the brain has to do while walking, in other words making the brain more efficient.
I think that’s it unless there’s anything else.
Dr. Verghese: No I think we listed the main points. Do you want to talk about how old the participants are? You want to talk about how old the participants are in all of those?
You said forty five hundred?
Dr. Verghese: They are about 70 and they have to walk slowly and they have to be sedentary. Exercise less than three times a week.
And the average age is seventy, do you have a cut off?
Dr. Verghese: No, the age of entry is 70-plus so the average age would be around 78 to 79. It’s an older sample we’re looking at.
Is this the only center, is this the only site for that study or do you have colleagues elsewhere?
Dr. Verghese: No, for this particular study we’re recruiting and conducting the study over here at the Montefiore Einstein Center for the Aging Brain. Also because this is the first proof of concept clinical trial we want to make sure that we have control over all the parameters so we do it as rigorously as possible. If this works we could consider future trials where we combine this brain game approach with walking exercises, we do it at home so people don’t have to come in to a center to do it. I think this will be the first of many studies that we would hopefully conduct to try and get this kind of approach out to the real world.
When you’re doing it at home is there a higher participation rate or do you have fall off where the participants fall off when they’re not monitored?
Dr. Verghese: Yes, I think so. A lot of it depends on motivation. So I think convincing the participants that this is something important that they benefit from it would be it. Since most of our patients are frail and sedentary, I think they would prefer that they stay at home and do this. From a practicality point of view I think it would be better if we do it at home. But from a scientific research perspective we are observing them over here so we have more control over all the parameters. It’s a tradeoff between feasibility and having a rigorous scientific design.
END OF INTERVIEW
This information is intended for additional research purposes only. It is not to be used as a prescription or advice from Ivanhoe Broadcast News, Inc. or any medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the depth or accuracy of physician statements. Procedures or medicines apply to different people and medical factors; always consult your physician on medical matters.
If you would like more information, please contact:
Elaine Iandoli, Science Media Relations Manager
718-430-4137
Elaine.iandoli@einstein.yu.edu
Sign up for a free weekly e-mail on Medical Breakthroughs called
First to Know by clicking here.
