Michael Harrington, M.D., Director of Neurosciences Huntington Medical Research Institutes in Los Angeles, California, talks about a test that can possibly predict Alzheimer’s 20 years early.
Interview conducted by Ivanhoe Broadcast News in November 2016.
Tell me about the brain’s stress test. It’s really interesting that you could diagnose Alzheimer’s so early. How does it work?
Dr. Harrington: Well we’re very interested to pick up pre-clinical, pre-symptomatic changes that are occurring for maybe twenty years before any clinical onset of Alzheimer’s. We’re doing a lot of tests, spinal fluid, molecular markers, urine tests and the brain challenge test. All of our current work is very early so I want to stress that. It’s not established by any means. The idea was to have a brain challenge test similar to the cardiac treadmill test that people understand. You can pick up early heart disease by running on a treadmill we’d like to do the same for the brain except you don’t run the brain on the treadmill but you ask it a few questions and that’s how this developed. With EEG, scalp electrodes, dry electrodes the individuals answer simple questions while the EEG is running. What we found is a difference between people who are cognitively indistinguishable but who have early chemistry of Alzheimer’s disease. They have to use their brains more; they work harder in their brains. We can see that in changes in the brain wave patterns.
You can’t tell just by watching them but it’s something inside that you can see with the brain recorder.
Dr. Harrington: Exactly. When they’re looking at the challenge on the computer, they perform as well as the people with normal chemistry but you can see the change on the brain waves.
Can you elaborate a little, you’re asking them the same questions that you wouldn’t be able just from talking to them that something was different but the brain is working harder.
Dr. Harrington: That’s correct.
What kind of questions do you ask them?
Dr. Harrington: Well they have to read letters on that computer screen and they have to press a keyboard when they see a particular letter popping up. It sends a simple reaction but they have to use their memory to perform that test. They don’t have any difference in their memory and ask me again.
Okay letters, colors?
Dr. Harrington: We showed them blocks that have different colors, red, green, blue and they’re words spelling out those color names and they repeat them back. Then we give them the blocks where the colors don’t match the words and that’s quite a challenging test.
Or can be.
Dr. Harrington: Yes.
What was it that made you think that this would work?
Dr. Harrington: Well we had some prior knowledge that the brain is affected for over twenty years before any symptoms. It’s particularly in the frontal lobes which is the frontal cortex, the front half of the cerebral cortex. Where a lot of our decision making, working memory are performed. I wanted to use tests that challenge that part of the brain and so we selected those tests.
If it’s going to be ten or twenty years before Alzheimer’s shows up, it’s going to be a little while before you get results to find out if this is going to work or not, am I right?
Dr. Harrington: Absolutely, it will take quite a few years to really test this with more people, with different people just to establish how useful it is. I think it has the promise to be very useful as a screen because it’s very simple to do. It’s a brain challenge but it’s a lot simpler really than walking on a treadmill.
We’re running into the same issue with genetic testing, it’s like what do you do with the information should somebody turn up positive.
Dr. Harrington: Right and I think that a variety of tests that we’re trying to build in this pre-symptomatic stage are screens that should be simple whether it’s urine testing or this brain challenge test so that people can have these on an annual basis. They’ll be much more powerful for each individual than they will be comparing one person with a different person. That over time when there’s a change occurring it will be really much clearer for that individual and the indication would be you need a serious workup something is happening. This is not necessarily indicating therapy but it could be very useful to trigger the start of a therapy or when a treatment is developed to follow it to monitor it.
Obviously people who are signing up to be in this trial want to know so obviously you’ll tell them if they turn up positive it looks like their brain is working harder.
Dr. Harrington: Absolutely, not at this stage because we’re still doing the research but once it gets established we know the parameters and the predictability and the sensitivity and the specificity, then we can give people very simple results just like they get for any of their normal tests in blood or scanning.
How many people are in the study right now?
Dr. Harrington: We’ve got a hundred and fifty people in the study we’ve only got six that we’ve followed with this initial cognitive challenge so we’ve got a lot of work to do still.
Six people have started it are you calling it a brain stress test?
Dr. Harrington: Yes. Well we call it a brain challenge test. Yeah, stress has so many implications.
Six people have gone through it so far?
Dr. Harrington: That’s correct.
Have you found anything that looks suspicious yet?
Dr. Harrington: Yeah, well we have three people that have good chemistry; three people have bad chemistry of the Alzheimer’s type from their spinal fluid and they have differences. The ones with the bad chemistry show that they have to work harder in their brain from the EEG even though their behavior is totally the same.
Does that mean that they’re definitely going to have Alzheimer’s down the road?
Dr. Harrington: No, we can’t say that at this stage but we’re following these people longitudinally over time we should find out.
Did you tell them, do they know?
Dr. Harrington: No, not at this stage. We’ve followed seventy people over four years so far. We know that the people with the bad chemistry deteriorate over thirty percent of them have developed mild cognitive impairment or Alzheimer’s disease in four years. The people with good chemistry none of them have developed any deterioration. We know the chemistry is pretty accurate.
So the people who have good chemistry— the people who have had bad chemistry are already showing some symptoms with cognitive?
Dr. Harrington: Yes, of the three people we examined with the challenge test with bad chemistry they were having to use their brain more as seen on the brain wave changes in this test compared to the three that had good chemistry. That was quite clear. It looks very attractive that this could become a useful test. We are going to look at it in a lot more people.
When you say bad chemistry what do you mean?
Dr. Harrington: Sure they have abnormal proteins that are characteristic of Alzheimer’s in their spinal fluid and that’s decreased beta amyloid and increased tau protein. The amyloid and tau are two known established markers of the Alzheimer’s pathology. We can pick changes of that up in the spinal fluid up to twenty years before any symptoms start. That’s what we measure. We’ve also looked in the urine at some brain derived lipids that are changing there and Dr. Fontain in our group has found changes with early pre-symptomatic Alzheimer’s people and they match the spinal fluid Alzheimer’s marker so that looks promising as a urine predictive test.
If this brain challenge tests turns out to be as accurate as the chemistry test it’s a way to find out as an early indicator of Alzheimer’s much less invasively. Right it’s just simply putting the cap on and asking some questions rather than going in and having to take spinal fluid.
Dr. Harrington: That’s right. Our goal is to have a simple test that could be used anywhere in the world economically, quickly, noninvasively and one could imagine that a small electrode set up and there are lots of commercial systems already. Once we know what we’re looking for it could be used in a matter of a few minutes because this test does not take long.
If this is accurate it sounds pretty attractive to me.
Dr. Harrington: That’s right, that’s right. I think it’s very reasonable to expect that we could have our test simplified much more than it is just now. Even now it takes ten minutes.
What is your thought on time frame, size of study, anything like that?
Dr. Harrington: Well we’ve just started this work.
Like how recently?
Dr. Harrington: Less than a year and so it’s based on some work we were doing with concussion studies we decided to apply the same study to this Alzheimer’s population. And for the future within—within a couple of years we should have many more people tested, evaluated, followed longitudinally. We expect to publish on this fairly soon in the preliminary stage within a matter of months.
Do you have a number, a target number of study participants that you want or that you need?
Dr. Harrington: Yes. We have seventy cognitively healthy people just now half of whom have good chemistry half of whom have bad chemistry. We want to work through the majority of those. If we get a chance to look at fifty of these I think this will give us very good information. Then we would follow them for four years. We’ll need to follow them for another few years to see how they progress. That would be important.
Is this something then that will eventually go through the FDA and will be made available to hospitals and institutions?
Dr. Harrington: That would be our intension for sure.
But it’s way too early to tell? Especially if the FDA is involved.
Dr. Harrington: That’s right, that’s right. I think it’s going to take some years before this becomes widely accepted and used.
It’s pretty neat.
Dr. Harrington: I think it’s simple enough, it’s got the potential to be a very valuable early screen.
Sometimes people don’t want to know, I suppose you wouldn’t run into that with somebody who is in your study?
Dr. Harrington: That’s right. The people who don’t want to know don’t come to our study. But we talk about this with many of them. Should we know, when will we know, when will we be told. I think the majority of people are becoming much more interested in finding out. As we get older, we forget things and we ask ourselves, we’re all terrified of getting dementia. We all know people who are older who lose their memories and we forget our keys the names of our friends. That’s maybe not for young people but we all as we get older worry about that. I think we also want to find out measures of this because it’s so vague and subjective and it fluctuates from day to day week to week. If we have something that’s objective that can measure our brain decline which will happen normally, but if it declines more severely then obviously there is a process going on. I believe the research is developing new treatments that may help stop this decline or delay it. I think people will want to do this by the time it gets developed much more than now.
We’re talking about people that not everybody wants to know but in your study they probably do, your comments on that.
Dr. Harrington: That’s right, so those people in our study often discuss this or ask this question as we all do because we’re terrified about dementia as we get older. We forget, we forget names of people we’ve met, people we never used to forget. I think we fluctuates there’s days when our memories are much better than others. It’s really hard to know is this decline just something of normal aging or is there a disease process. There’s really no objective way of measuring that very easily just now. I think this test will provide a really objective measure. Is the brain being used more actively in a disease form or in a healthy aging form.
What haven’t I asked you about this study that you want to get across?
Dr. Harrington: The research in to early onset Alzheimer’s is picking up a lot now. Most of the techniques that are very promising including imaging with a magnetic resonance which is very exciting and incredibly valuable. MEG and EEG, which we’re describing here, are different because they show acute changes in brain activity. If you’re emotionally upset you can pick this up with these fast measures and I think they’re very complimentary to molecular studies, genetic studies, imaging studies of magnetic resonance. The way we and others detect pre-symptomatic Alzheimer’s disease just now is either with very expensive imaging studies, PET studies or what we do are spinal fluid measures of the same molecule that changes a brain derived amyloid. But the spinal fluid which we do very routinely and it’s very safe but it is somewhat invasive. A lot of people just are not comfortable having that test. The distinction is that if ours becomes established, if we can show that its got the rigor to do an equivalent detection you wouldn’t need to have a spinal tap. You wouldn’t need the expensive PET imaging.
You could get it as early as you currently can with the spinal, the same kind of twenty year early?
Dr. Harrington: We took a bunch of just normal people and tested mid-morning, midafternoon, independent blood sugar and your cognitive, your reaction time is ten percent worse in the middle of the afternoon than the morning.
I believe that.
Dr. Harrington: Isn’t that, because I’m wasted in the afternoon in comparison. It’s 330 milliseconds down to 300 milliseconds it’s real interesting. PET imaging and spinal fluid amyloid testing are very similar. There’s some possibility the spinal fluid amyloid change can be twenty, twenty five years before clinical onset. The earliest spinal fluid and PET imaging shows changes of amyloid is about twenty, twenty five years they’re similar, spinal fluid might occur a little earlier. We have every reason to suspect this brain challenge test will be equally fast at picking up these changes. Maybe a little faster because it shows brain synaptic function changes. We know those are the earliest that have been recorded every in Alzheimer’s disease pathology.
What have you done with Anne?
Dr. Harrington: Anne Snyder joined our study five years ago and there’s several things that are very valuable. She joined because her husband died of Alzheimer’s disease and she was very keen to participate because of that reason. She’s been wonderful. She’s come several times for our studies. We do spinal fluid, she’s very compliant and helpful with this. Her goal is just as our total goal to find what the pathology of Alzheimer’s is. This is something I did want to tell you. We don’t know the fundamental cause of Alzheimer’s disease how do we treat something if we don’t know what’s going on. That’s the primary goal of all of our studies. Is to learn why it’s happening in the first place. Anne has bought in to that she does all of our studies. She also happens to be when we started an ultra-generian tennis player in South Pasadena and within a short period of time we had a lot of her female ultra-generian tennis players in our study. She’s been a great at recruiting people.
How is she looking in the study?
Dr. Harrington: She’s super normal.
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:
James Chisum
562-493-6023
Sign up for a free weekly e-mail on Medical Breakthroughs called
First to Know by clicking here.
