Washington University School of Medicine neurologist, Dr. Suzanne Schindler talks about a new way to test for Alzheimer’s before symptoms start.
Interview conducted by Ivanhoe Broadcast News in 2023.
Until now, how did doctors diagnose Alzheimer’s?
Schindler: So in the past, what doctors have done is to do really a clinical assessment where they talked to people who know the patient well to try to determine whether the patient has had a decline in their memory and thinking as compared to the past. We do cognitive testing. So there’s a variety of different tests that we routinely perform. We do blood work to check for conditions like problems with the thyroid or vitamin B12 that can in some cases be associated with memory and thinking problems. And then we do brain imaging where we primarily look for evidence of strokes, but also any other issues that might show up on these images. And we take all of that information together along with talking to the patient and doing a neurological examination and try to understand. First of all, does the patient really have a significant decline in their memory and thinking? If so, how severe is it? And then the next question is, well, what’s causing it? And oftentimes it’s not just one thing, it can be multiple different things. And then we try to figure out how to help them. How do we address all of those things that are causing their memory and thinking problems? In the case of Alzheimer disease, what we typically see is that patients have had a slowly progressive decline in their memory and thinking for at least six months, sometimes a number of years. It typically starts with short-term memory difficulties and then progresses to cause increasing concerns with their activities of daily life. So things like balancing checkbooks, being able to keep track of appointments, being able to drive. And when we see a consistent pattern, especially when it’s consistent with other evidence we’ve gotten from for example brain imaging, then we feel relatively confident that the patient has dementia due to Alzheimer’s disease.
Seems very time-consuming and costly.
Schindler: It is. So when I see a patient in my clinic, it typically takes me about an hour and a half to do a thorough evaluation. And that’s not including the time that I take to read and review all of the documentation and brain imaging, blood tests. So it is very time-consuming.
And the cost? I can’t imagine PET scans are cheap.
Schindler: So, we very rarely do PET scans in clinical practice. So amyloid PET scans in particular are relatively widely used by research studies. But in clinical care, they are very rarely reimbursed. So they cost about $6,000 out-of-pocket typically. And nearly all of our patients cannot afford $6,000 for an amyloid PET scan. So what we do when we want to perform specialized testing for Alzheimer’s disease is typically a spinal tap or a lumbar puncture is another term for it. So we have the patient come in, we prepare their back, we gave them a little bit of numbing medicine and then we take a small amount of fluid and send it off for analysis. And it turns out that there’s a very specific change in the proteins that we can detect in the spinal fluid that is associated with having the amyloid plaques and tau tangles in the brain that are characteristic of Alzheimer’s disease. So we actually do biomarker testing, probably in 5-10% of our patients and a specialty clinic setting. Very few patients generally get this testing. So if you don’t come see a dementia specialist, it’s almost certainly you are not going to get this testing. But even when you come see us, we don’t use it in most cases. And part of that is that it’s time-consuming and expensive. And patients generally don’t like to get a spinal tap.
Sounds horrible.
Schindler: Yes.
But now there could be a very simple solution to all of this, right?
Schindler: Yes.
Is it as simple as in the process?
Schindler: Logistically, yes.
Not developing it, right?
Schindler: Yes. So over the last about five years, a number of groups have developed blood tests for Alzheimer disease. And these tests have been getting better and better. Currently, there are more than 10 different types of tests. Only three of those are currently available in the clinic. But these tests tell us relatively accurately whether someone is likely to have the amyloid plaques and tau tangles of Alzheimer disease in their brain. Something that’s exciting though is that these tests are getting much better very quickly. And so I expect that within a year or two we will probably have blood tests available in the clinic that are about as accurate as spinal fluid tests are in terms of telling people whether you have plaques and tangles in your brain.
Now, you have a blood test that is 93% accurate. That’s pretty accurate, right?
Schindler: It is. We think that these, and of course, there’s lots of different ways to look at accuracy. It turns out the accuracy also depends on the patient population that you’re looking at.
What do you mean?
Schindler: I thought I’d show you a bunch of slides. So basically, if you start with a patient population where very few people have Alzheimer disease, the blood tests are extremely good at ruling out saying no, this person doesn’t have it. So we call it a negative predictive value. So extremely high, probably 96-97% of the time. If the blood test is negative, the person does not have Alzheimer’s disease. The situation is, it can be different if you’re looking at a population where a lot of people do have brain amyloid. And so it’s a little bit more complicated how you use this in clinical care depending on the rates of amyloid in the population. But yes, the blood tests are really getting very good in terms of telling us whether people have this pathology in their brain.
But it could and it can tell you if you have the pathology without the symptoms, right?
Schindler: That’s correct. And that’s actually in some ways a good thing and in some ways not. So certainly when patients come in with symptoms and want to know what is the cause of my symptoms, am I having these memory problems because I’m depressed, because of the medications I’m taking or is it because I have Alzheimer disease? So in cases like that, these tests can be very helpful in telling us what’s going on and whether the real underlying problem is Alzheimer’s disease or it’s something else that we need to be looking for dealing with. So it’s very helpful in that scenario. And this scenario where someone doesn’t have symptoms, it’s a lot harder to know what do you do with the result. So if if you’re 65 and you have a family history of Alzheimer disease and you want to know, am I going to get it or not? These tests can tell you whether you have these brain changes, but actually what they can’t do right now is tell you with certainty whether you will get them or when you will get them. They’ll tell you that you’re at risk, but they won’t tell you for sure when you’re going to get them.
And you can have amyloid plaques and never show the signs of Alzheimer’s.
Schindler: That’s exactly right. So we know that there are a large number of older individuals that have these plaques and their brains. We have learned that these plaques actually accumulate in the brain for about 10-20 years. So by the time people have symptoms, they’ve had these in their brain for a long time and these individuals would have tested positive. But of course, if they pass away at 75 and they weren’t going to develop symptoms. So they were 85, then they’ve spent 10 years worrying about something that maybe it never was going to happen.
But this could be a real pivotal point for medicine if and when a drug is developed that stops Alzheimer’s in its tracks, correct?
Schindler: Absolutely, there are what we call prevention trials going on right now where we have identified individuals with these Alzheimer disease brain changes who are cognitively normal. And we enroll these participants in a study where we give them medications that are aimed to slow or prevent the onset of symptoms and those studies are ongoing. We will have to see whether they actually work. But if they do that means that maybe we should screen cognitively normal older individuals with these tests and try to treat them before they develop symptoms.
Could you give just another tests when you go and get your physical every year?
Schindler: So I think that we’re still a ways off from that. But certainly that’s, you could imagine that happening. When we think about this a model is, what we call lipid testing or HDL, LDL testing that you have sometimes done by your primary care doc, where on a semi regular basis you get tested and if you have high cholesterol, you start on a cholesterol lowering agent. And at that point, you don’t necessarily have any heart problems or strokes, but starting on that medication lowers your risk of developing all of those complications. So I think that we’re still a ways off from that. But it’s certainly possible that at some point in the future, when the tests are better, we have good drugs, that that’s what we’re aiming for, that you’ll get these tests and then get treated before you ever get symptoms.
Would you say the blood test is the next big thing coming around the corner for Alzheimer’s?
Schindler: I think it is the big thing right now. Actually, there’s an incredible amount of interests in blood tests generally. And as I mentioned, there’s more than 10 of them that are being studied right now. There’s a number of different types of tests and they’re measured in different ways and different tests have different levels of performance. But yes, blood tests for Alzheimer’s disease is really a major area of interest and development generally in the field. Especially now that we expect the drugs that may hopefully reduce the decline from Alzheimer disease appear to be entering clinical practice in the not too distant future.
What do the blood tests pick up in the amyloid plaques?
Schindler: So there’s a variety of different blood tests. The one that is offered by C2N diagnostics. That it actually incorporates a couple of different factors, but the most important is something called the plasma, A Beta 42:40 ratio. So we all make amyloid. This is just normal. And as we get older, well, there’s two common forms of amyloid, so one is amyloid Beta peptide 42 amino acids, and one is 40 amino acids. So there’s a longer form and a shorter form. As we get older, that longer form clumps together into these structures called plaques. And we think that these plaques are what set off this whole cascade of events that leads to Alzheimer’s. So they aren’t the direct cause of the dementia, but what starts it? So what we’re measuring is we’ve looked at the levels of A Beta 42, amyloid Beta 40 to the long form in the short form. And it turns out that this ratio is very good at telling us whether people have these plaques in their brain. The reason for that is this long form keeps getting stuck in the plaques versus a shorter form doesn’t get stuck as much. And so when you look at the ratio, the ratio is lower in people that have the plaques because more of the longer form is getting stuck, essentially, we call it being sequestered. So basically the A beta 42 is getting stuck in the plaque, so it’s not ending up in the spinal fluid or in the blood, but the 40 is not getting stuck as much so we can normalize for how much people we would expect they would have.
We can see this actually happening a lot of times. You talked about medical advances and it’ll be 10 years, 15 years. We’re talking two or three.
Schindler: Yes. I think these tests are being developed very rapidly. There are already two tests, three tests that are available in the clinic. And we expect that more will be available in the next year or two.
Do you use that regularly now?
Schindler: So I use it in select patients right now. So I’m primarily using the blood test in patients where I for whatever reason, can’t do a spinal tap. So some of the reasons for that include someone is taking a blood thinner. So if someone is taking a blood thinner, you can’t do a lumbar puncture safely without stopping the blood thinner for several days and then that could put them at risk for blood clots. Another scenario is some people really, really don’t want to get a spinal tap.
Why not do the spinal tap anymore if this is just as accurate?
Schindler: Well, I think that it’s not that the tests that are currently available in the clinic are not quite as good as CSF. But I think they will be very close soon. So I’m hopeful that in the next couple of years we’ll be to the point where they are as accurate as CSF. When the blood tests are as accurate as CSF, it’s going to be hard to get people to do a spinal tap. One issue is that we’ve gotten used to doing spinal taps. And a lot of clinicians are not used to using these blood tests. So there may be a period of time where people are getting used to these. I would expect that some people will do a blood test and then do a spinal fluid test just to make sure. So it’ll take some time before people I think, really feel comfortable using these but I think the data looks good and I think it’s going to happen.
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:
Judy Martin Finch Diane Duke Williams
martinju@wustl.edu williamsdia@wustl.edu
Sign up for a free weekly e-mail on Medical Breakthroughs called First to Know by clicking here
