Dr. Adam Woods, an associate professor at the University of Florida and an associate director of the Center for Cognitive Aging and Memory at the University of Florida’s McKnight Brain Institute, talks about AI’s potential to help combat Alzheimer’s disease.
With Alzheimer’s, it feels like, if you live long enough, you might be getting Alzheimer’s or dementia.
WOODS: Right. I mean, we’re expecting, in our population, the representation of older adults will double by the year 2050. So those that are 65 and over will have double the representation. In addition to that, in Alzheimer’s disease alone, not even other forms of dementia, we’re expecting those numbers in terms of the representation to triple by 2050, double by 2030, which is not far off. So, you’re right, we have to do more than we’re already doing to find ways to stave off or prevent the onset of Alzheimer’s disease. Whether that is six months, one year, five years or to end of life, all of those are in the win category and something we have to work steadily on right now.
And I think whenever you can come up with something that’s not medication and not intrusive is a win for everybody.
WOODS: Yeah, it’s something we’re very excited about working in this space of non-pharmacological interventions. Pharmaceuticals are great and they have great purpose, but with that also comes a wide array of side effects, right? And sometimes we come into contact with technologies that allow us to do some of these similar things in targeted ways without the side effect profile. So, a safe, non-invasive technology has great potential for rapid deployment across the community.
And that’s TDCS?
WOODS: Right, transcranial direct current stimulation. It’s a weak form of electrical stimulation applied to the scalp. You typically feel a tingling or prickling sensation on the scalp that usually subsides after about 60 seconds or so. And this weak electric current actually has the ability to alter how the neurons behave. We can actually shape how they perform or how they change in terms of their firing to improve their firing rate or decrease their firing rate. And all of that is to say, really, what we’re trying to do is interface with learning at the neural level… so this concept of neuroplasticity.
Do you use this before symptoms show up? Do you use it once you see plaques and tau show up? When would this come into play?
WOODS: Right. So the work that we’re doing is we’re trying to take a preventative medicine approach, if you will, to where we’re trying to work in people who are currently healthy, and they may have higher risk of Alzheimer’s disease or other dementias, but interface or intervene at the point when you’re still healthy with the idea that, as we get older. One of the things that happens as we get older is we have certain declines in certain thinking and memory skills. It happens to all of us. In fact, it starts in our late 20s and slowly declines. But then it’s a much sharper decline in our seventh, eighth and ninth decade of life. What we’re trying to do is intervene at that point when it starts to sharply decline to bring those skills back up, to improve those skills which, in effect, can help us in a number of ways. One of the most important is that rate of decline is heavily associated with the development of Alzheimer’s disease. If we can change that rate, we have the potential to push this off further down the road in the future, potentially past the end of life.
And electrical stimulation does that?
WOODS: So, what we’re finding with electrical stimulation is that, by itself, it can do some very interesting things. It’s shown some efficacy for treatment of depression, some efficacy for treatment of chronic pain. But what we’re doing is trying to interface in terms of cognition to improve cognitive or thinking and memory skills that are significantly impacted once you develop Alzheimer’s disease. And we’re pairing that with something called cognitive training, which is a behavioral intervention that involves computerized games that stress certain domains of cognition that we decline in to try to improve them. That in and of itself can improve these skills, but when you add the stimulation to it, the goal there is to actually further enhance that increase that neural communication through stimulation while you’re doing this intervention training to improve cognition from kind of two avenues.
How often do you have to do this? Is it something that you have to continue forever and ever?
WOODS: Right. So, an important point to make is this is not yet an FDA-approved treatment for any clinical indication. This is still very much a research tool where we’re running clinical trials, including phase three definitive trials, to try to demonstrate that it has clinically meaningful impact on these specific domains or these specific disorders. And we’re still determining these dosing characteristics. Some of the dosing characteristics can be how often you do this. And one of our large phase three trials, people come in for the first two weeks and do this five days a week. Then, after that, they do that once a week for the next three months. But there’s still that remaining question, do we need to do boosters every year? Every two years? And we don’t know the answer to that yet. But there’s also other features. How much current do you apply? Where do you place electrodes on the head to optimize how you’re stimulating the brain to get better outcomes? And these are open questions in the field at present we’re trying to answer.
And everybody’s different, right?
WOODS: Everyone is different. It’s like a fingerprint, our brains, right? You look at it and no two are different. We can put side by side our fingerprints and our brain side by side and they would both have very clear differences. Yes, they’re both brains, but the folds… the peaks and valleys, if you will, the gyri and sulci, which are those nice little folds in the brain we see in all the pretty pictures, those are all subtly different. The thickness of certain tissue, the amount of different tissue, they’re all different. And those differences have an impact. And it’s not just brain differences, there can be different amounts of fatty tissue on the scalp, you can have differences in skull thickness. And for each individual person, that will impact how much of that current actually gets into the brain, and we think that amount really matters when it comes to the outcomes that we see.
And that’s where AI plays a role?
WOODS: Yes. One of the fascinating things about the work that we’re doing is that we’ve had access to this information to predict where and how much current is going different places in the brain, and that’s great because we can kind of see where current’s going individually in each person. But that produces millions upon millions of data points. Using classic analytic approaches, we can ask really crude questions. Using artificial intelligence, our questions can get closer and closer to the reality of the complexity. And in this case, we’re using artificial intelligence to dive into this really robust individual data and really understand, what are the patterns of current and where in the brain are most associated with positive clinical outcomes? Which can then be taken full circle to customize that dosing to each individual person so that perhaps I need two milliamps to get optimal clinical results but perhaps the person next to me needs 2.5 or 1.8. But in the field at present, a very crude, fixed dosing approach is used. So, in my trials at present that are funded by the National Institute on Aging, we’re using the standard technologies, which is everyone gets exactly the same dose at exactly same locations. And that’s been the state of the field the world over. But imagine if we treated pharmaceuticals that way. If we took any specific drug and said, everyone takes exactly this amount, well, we’d be shocked if we got any efficacy from those drugs. Well, here’s the thing, we’re getting some efficacy from electrical brain stimulation using fixed dosing but imagine what we could do if we can identify the individual variance that impacts that and then use that to our advantage to create a precision dose to enhance clinical outcomes, and that’s what we’re trying to do.
And electrical stimulation is being used for a lot of things.
WOODS: Yes.
Parkinson’s, depression… I mean, a lot of different things. So, would this have a wide range of uses?
WOODS: Yes, that’s a wonderful question, and that’s exactly the hope. And you’re right, there are different technologies like deep brain stimulation, where you have an implanted electrode for treatment of Parkinson’s. You also have transcranial magnetic stimulation, which uses an electromagnetic pulse to induce electrical currents in the brain, and it’s an FDA-approved treatment for depression. You’ve actually had the application of electric current to the head happening since the 1800s when electric eels were placed on the head for various reasons. Turns out, our technology’s a little more advanced than that now and our applications are far more advanced. But in the context of what we’re developing, if you’re using electricity to interface with the brain to impact clinical outcomes, the technology we’re working on in developing, leveraging, AI and computational neuroscience in clinical trial approaches can be applied across any of these types of electrical therapeutic approaches.
I mean, you don’t have results yet, right?
WOODS: Right, right, right.
But have you seen a difference in people? Can you tell a difference?
WOODS: So, we have run a number of smaller pilot trials. We’re finishing up our large phase three trial at present for cognition in older adults that actually will be unblinded in April of 2022, so very soon, and we’ll see what our results are there. And our earlier small pilot trials that had a lower dose where people only underwent two weeks of intervention versus three months of intervention, we’ve seen positive effects on working memory and other thinking and memory skills from before to after intervention. We’ve also seen change in brain-based markers that correspond with that – the functional communication of different tissue, the amount of glutamate that is associated – or increases over time. That’s our excitatory neurotransmitters. So, in our early pilot trials, we’ve seen promising effects. And others in the field have shown early promising effects in depression, pain and a variety of other domains. Where the field’s at now is really the need for these large phase three trials to demonstrate definitively that, for these clinical indications, we can have a significant impact. And so should we demonstrate that, it opens up all kinds of new avenues for clinical applications. But we think, no matter those initial results with a fixed dose, we can enhance those effects because, if you personalize it to the individual, those outcomes will improve.
Do you see this moving past just the preventative part? Because I think I was watching “60 Minutes” the other night about Alzheimer’s and dementia and that you can train your neurons or whatever to talk differently, just like a stroke victim reroutes – they can get it to reroute and prevent – stop, maybe, Alzheimer’s in its track.
WOODS: So that’s the concept of neuroplasticity, the idea that you can plastically change how your neurons communicate. And this technology is based exactly in this principle. Through the application of electric current, we’re able to get these neurons to talk a little bit more or a little bit less. And in certain contexts, you want them talking more, you want them talking less. It depends on the clinical application. You know, in the work that we’re doing here, by and large, we’re working in the preventative medicine space. However, we’re also running trials in collaboration to treat chronic pain and other domains. And others in the field are interfacing at the level of people already diagnosed with Alzheimer’s disease. At that phase, when someone already has Alzheimer’s disease, you’re in the symptom treatment phase – I want to reduce the symptoms you presently have. And there’s no element of this where I expect electrical stimulation to cure Alzheimer’s disease, but a version of cure is prevention. And so, for us, at least in the space of Alzheimer’s, we feel like we can have the greatest impact by moving that time point where mild cognitive impairment or dementia develop. And when you talk to patients, which we have, and you say, OK, how long? How long for you would be meaningful? And you talk to family members, how long would be meaningful? And you might be expecting a year, five years, ten years. And the answer comes back – days. We think we can do better than days. We think we can do better than weeks. But this technology is our best push right now to try to move this needle further and further back. Right now, it’s a technology under development. Our hope is, as soon as we have a form of this technology that’s finalized, to put that in pilot trials to literally demonstrate whether or not we can drive this further back than the standard old, fixed dosing approach.
Is there any risk to this?
WOODS: So, no, it’s actually very safe. We did a review in 2016 of over 30,000 stimulation sessions and there were zero significant or serious adverse events associated. The things that are associated are a slight reddening of the skin underneath from the electrical current stimulating, a slight warming of the skin, tingling, itching, a slight burning sensation that’s very mild from the current passing through that typically subsides within about 60 seconds. You can get transient nausea, which is very rare, right? You can get transient dizziness, which is very rare. These things stop when you stop stimulation. And that’s roughly the side effect profile you’re talking about. You can look at any over-the-counter medication in your medicine cabinet and compare those side effect profiles, and I’ll take the one associated with TDCS. So, it’s very safe, which is why the technology, to me, has a lot of excitement behind it.
Interview conducted by Ivanhoe Broadcast News.
END OF INTERVIEW
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