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Someone tells you their memory is slipping. What you say next can decide whether treatment is still an option for them. Emer MacSweeney is a neuroradiologist and the cofounder and CEO of Re:Cognition Health. This episode is based on her article “Early Alzheimer’s diagnosis now decides who gets treated,” published on KevinMD. She explains why two licensed treatments work only inside a narrow early window, and why a year spent waiting for an appointment can put a patient past it. You will hear how the three biomarker tests compare, including the blood test that is now widely available, and why she says not to order one unless the patient has symptoms. She also names the early signs she takes seriously: short-term memory trouble, losing words, getting lost in familiar places. If you have ever told someone their memory is just getting older, this conversation explains what that reassurance can cost.
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Transcript
Kevin Pho: Hi, and welcome to the show. Subscribe at KevinMD.com/podcast. Today we welcome Emer MacSweeney. She’s a neuroradiologist and cofounder of Re:Cognition Health. Today’s KevinMD article is “Early Alzheimer’s diagnosis now decides who gets treated.” Emer, welcome to the show.
Emer MacSweeney: Thank you.
Kevin Pho: All right, let’s start by briefly sharing your story and then talking about why you decided to write this article on KevinMD.
Emer MacSweeney: Thanks so much for inviting me to the show. The reason that I wrote this article is that this is something so important to millions of people today. For really the first time in history, we now have the possibility of doing two things. One is to diagnose Alzheimer’s disease very early, when symptoms are just emerging. The second is to provide treatment: Two treatments have come on the market which, when given really early, can slow down progression of this disease and therefore change its outcome.
But the key to this is that you can only accurately diagnose this disease very early if you use the right biomarkers. You can’t diagnose it just by asking somebody questions and talking to them. You need to detect that they do have a problem with short-term memory or other aspects of the cognitive domain, but in order to make an accurate diagnosis, you need a special biomarker test. If that test is positive, then we can give people treatment to slow down further progression of the disease.
I wrote the article because this is something that we obviously know about, but it’s incredibly important to get it out to the public. Bill Ritter was, I think, very brave, because a lot of people obviously worry about this diagnosis. He published everywhere about his experience. He’s a well-known, longtime anchor on New York TV. What he stood up and said is, “I realized I needed to get a diagnosis really early. I had a biomarker test, and now I can access treatments to slow down progression of my disease.”
This is the critical message to get out to people, because treating Alzheimer’s disease today is exactly the same as treating cancer. Alzheimer’s disease is not cancer, but treating Alzheimer’s disease is the same as treating cancer insofar as you have to treat it really early, and the earlier you treat it, the better the results. Not only that, but there’s actually a very small window when the new treatments that have come on the market are helpful, suitable, and actually licensed. Once the disease has progressed beyond a certain point, these treatments are no longer effective.
So it’s like treating cancer. If you have a diagnosis of cancer, you need to get treatment as soon as possible, because if you leave it, the treatments that work when the cancer is early and mild will not work once the cancer has metastasized. That is the reason for urgency in the diagnosis and the treatment. So today, you’re not just getting a diagnosis because you want to know what’s going to happen to you in the future with a relentlessly progressive disease. The reason you want a diagnosis is so you can access treatments really early.
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Kevin Pho: For those who may not be familiar with the current state of biomarkers as it relates to the diagnosis of Alzheimer’s disease, give us the current context in the United States. How available are they? How effective are they in terms of screening? Just give us a basic primer on the current state of biomarkers.
Emer MacSweeney: Sure. Essentially, there are three main biomarkers. These are tests that indicate whether or not you have the disease pathology in your brain. The hallmark of Alzheimer’s disease is abnormally elevated toxic amyloid protein in the brain. We can detect that today by doing a test called a PET amyloid scan, which has incredibly high sensitivity and specificity and is the gold standard. If that is positive and you have some cognitive symptoms, you have a diagnosis of Alzheimer’s disease, hopefully very early Alzheimer’s disease.
You can also detect the presence of abnormally elevated amyloid and tau protein in the brain by doing a lumbar puncture, or spinal tap, and measuring the spinal fluid. In the spinal fluid, you can see whether or not the results reflect high amyloid protein in the brain.
The third test, and this is the most important one and is becoming increasingly available to people, is just a blood test. Obviously, for any disease that is incredibly common, you need a cheap, ubiquitous test. The blood tests are much easier to access, and they’re much less expensive than lumbar punctures, or spinal taps, and PET scans. With the blood test, you can measure something in the blood called p-tau217, and if your p-tau217 is high, that indicates that you have high amyloid protein in the brain.
The good thing about doing a test like this, as long as you have cognitive symptoms, is that it’s as important to know if the result is abnormal and high as it is to know if it’s low and normal. If it’s low and normal, something else is causing your mild cognitive symptoms. If it’s high, then it’s almost definitely due to Alzheimer’s disease, and you need to get access to these treatments, which are approved by Medicare.
The really important thing then is not to find yourself on a waiting list to see somebody for treatment. The problem with being on a waiting list is, again, that this is like cancer. The whole time you’re sitting on the waiting list, your disease is progressing in your brain, and you don’t have time to wait. You need to get access to a center that’s providing treatment as quickly as possible.
In fact, we now know, because people are analyzing this type of data, what happens when you have mild cognitive symptoms, which is what we call mild cognitive impairment, and lots of doctors use this terminology. If you have mild cognitive impairment and you are on a waiting list for more than 12 months, 25 percent of those people will not be eligible for treatment, because their disease will have advanced too far by the time they get to the front of the waiting list. If your cognitive impairment is slightly more advanced, it’s what we call mild AD dementia. It’s still mild, but it’s called mild AD dementia. Fifty percent of those people waiting on a waiting list for 12 months will not be eligible for treatment by the time they get to the front of the list.
So again, you wouldn’t sit on a waiting list for 12 months, or for any time, if you knew you had a diagnosis of cancer and you wanted treatment. We have to think about this disease now not as some weird thing that we get when we get older and just need to live with. No, this is the same as any other condition. It’s a neuroinflammation that results in elevated amyloid protein, which then in time triggers another protein called tau. That tau protein spreads through the brain, destroying brain cells, and our brain cells, unlike other cells in the body, cannot regenerate. When you lose brain cells, they’re gone forever.
That’s why it’s a race against time. You’ve got to get in and get your amyloid protein out, and when you do that, it drives down the way the tau spreads through the brain, killing more brain cells.
Kevin Pho: Specific to this biomarker that looks for p-tau217, I believe it was FDA-approved, correct, back in 2025. How accurate is the biomarker test when compared to the gold standard, which I believe is the PET scan?
Emer MacSweeney: The PET scan is as close as you can get. Nothing in medicine is 100 percent, but it’s about 99 percent sensitive and specific. The spinal tap, the CSF or spinal fluid analysis, and the p-tau217 blood test are pretty much equivalent, so the answer is very, very sensitive.
The way the p-tau217 result comes back is, in most instances, on a scale of 0 to 100. If you’re 0 to 40, you’re negative, just negative, and you can be happy you’re negative. You’ve got to find another reason for your cognitive symptoms. If you’re 40 to 60, that result is indeterminate, which is different from intermediate. It’s indeterminate, and that means the people in that 40 to 60 range need to go and get a PET scan, because it could be high, or it might not be. If it’s above 60, and the higher above 60 it is, that’s positive.
Now, in the U.S. today, you still ultimately need a PET scan in order to tick the box to have the licensed treatment. In many countries, for example in the U.K., we can actually treat on a higher p-tau217. But right at this moment, you’ll need a PET scan or CSF in the U.S. Still, if you have the p-tau217 blood test, that’s a quick indicator. But any of these tests are accurate.
Kevin Pho: And again, from my understanding, this is not a general screen. You have to have some clinical suspicion of cognitive decline in order to obtain the biomarker. Is that correct?
Emer MacSweeney: In theory, and in practice, yes. That is correct insofar as the two medications, one called Kisunla, or donanemab, and one called Leqembi, or lecanemab, are only licensed for people who have cognitive symptoms along with the abnormally elevated biomarker. Therefore, I think as a general rule, don’t do a test unless you know what you’re going to do with the answer. Today there’s no point in doing the test if you don’t have symptoms, because there’s not going to be a treatment available.
The next thing is that Alzheimer’s disease is quite an interesting disease. In a way, it’s honestly the same as high cholesterol or high blood sugar, diabetes, or anything else, insofar as this amyloid protein actually rises in the brain over about twenty years before you get the first symptom. So what’s coming next will be the scenario where the medications have been proven to be effective as a preventive medication. In that context, people who have a high amyloid protein, ideally if they wish to do so, will decrease that amyloid protein, removing it with Kisunla or Leqembi to prevent them from developing symptoms.
The logic for that is that what correlates most closely with the symptoms is actually not so much the amyloid protein. It’s this other protein called tau. The amyloid protein rises, and when it reaches a certain level, it triggers another neuroinflammatory process called microgliosis. That microgliosis causes the intracellular tau protein to start behaving abnormally. Once it behaves abnormally and gets nucleated, it can no longer stabilize the brain cells, which is its normal function. In its abnormal form, it not only replicates and bursts the brain cell, which leaves you with this thing called a tau tangle, but it jumps from one brain cell to the next, and it kills brain cells as it jumps through them.
Now, if you think about it, if you had 100 brain cells affected at a particular time, then at time X, you might have 400 brain cells affected. But if you have 100 million brain cells affected, then in the same time X, you’re going to have 400 million brain cells affected with abnormal tau. This is why with this disease, symptoms start very, very mild, but then the rate of progression of the symptoms increases with time. The reason for that is that the tau protein is spreading exponentially through the brain and killing brain cells at an exponential rate.
So this is why you have to get the treatment while the main problem is just amyloid, before the tau protein has taken off. It’s almost like treating before it’s metastasized, if you like. If you get the amyloid protein out, it drives down the microgliosis, which drives down the propagation of tau, which slows down the progression of disease.
Kevin Pho: So I’m a primary care physician. What would be some common scenarios with patients in front of me in the exam room where I need to think about ordering this biomarker test?
Emer MacSweeney: Obviously, as you know, the biggest risk factor for this disease is age. As we all get older, we’re all at higher risk of getting this disease. Now, look at anyone who is concerned about certain facets of their cognition. The most important ones, and the earliest ones, are short-term memory loss, sort of inexplicable levels of anxiety, and what I’d call visuospatial problems: They’re getting a bit lost in a familiar environment, or they can’t see things right in front of them. Or they’ve got problems with using more generic words instead of specific words, and they can’t think of exactly the right word they want to use. They’re finding that they’ve got more difficulty manipulating numbers, or more difficulty sequencing events or making decisions, anything that’s affecting what you’d call your intellectual function.
People are actually exquisitely sensitive to noticing that there’s something wrong with their brain. After a period of time, they lose insight and become less aware of it, but to begin with, they really are aware. I would take anyone who says that to you very seriously, particularly if they’ve been pretty fit and healthy all along, because there are two really dangerous myths.
One is that it’s normal to start losing our memory as we get older. That just isn’t true. There are plenty of people in their nineties who’ve got perfectly good memories. So number one, that isn’t true. It’s really similar to how people, before we really understood cataracts, I don’t know, three hundred years ago, would have thought that as they get older, their eyesight just gets a bit dim and isn’t so good. No, they’ve just got cataracts. It’s not normal to have cataracts, but it is incredibly common. It’s not normal to have arthritis, but it’s very common. This is the same. It’s not normal to start having difficulties with your thinking ability as you get older. It’s just incredibly common, because Alzheimer’s disease is incredibly common.
So for anyone where either you think, “You know what, there’s something wrong there,” or their partner, their adult son or daughter, or a really good friend says, “Look, I know there’s something wrong. They’re just forgetting stuff,” take it seriously. Do a simple p-tau217 test, or run something like a cognitive assessment. If you think this isn’t right for this person, don’t ignore it, because the time when you ignore it is the very time when they’re going to benefit most from treatment.
The other problem is that most people have already had to pluck up lots of courage to come and tell you, “You know what, I think there’s something wrong with my thinking ability,” because everyone’s frightened of Alzheimer’s disease. They’ve plucked up so much courage to come and tell you, and then you go, “Oh, no, I think it’s fine.” They go away thinking, “Oh my goodness, thank goodness for that,” and they don’t come back to you for another year and a half. Then their friend says, “I know there’s something wrong,” and they say, “No, I went to see my doctor. My doctor said it’s fine.”
So the most dangerous thing is a doctor inappropriately telling the patient, “Ah, no, don’t worry about that. That’s fine. You’re just getting a bit older,” because you have falsely reassured that patient. Now, it may well be that they have just got a bit of anxiety, or, I don’t know, they’ve been taking too much alcohol, or whatever it happens to be. There’s just something else going on. But it’s much better to exclude the most common cause, and the cause you can treat, first. Don’t make a diagnosis of “Ah, it’s just normal, and they’re just making it up,” except by exclusion, only having checked that it’s not something else more serious. They’re not going to thank you when they come back in a year’s time and say, “Hang on a minute, there were treatments on the market, and there was a test on the market this time last year, or eighteen months ago, when I came to tell you I knew there was something wrong, and you just went, ‘Nah, don’t worry.'” I would not risk doing that in today’s medical environment.
Kevin Pho: We’re talking to Emer MacSweeney. She’s a neuroradiologist and cofounder of Re:Cognition Health. Today’s KevinMD article is “Early Alzheimer’s diagnosis now decides who gets treated.” Emer, we’re going to end with some of the take-home messages that you want to leave with the KevinMD audience.
Emer MacSweeney: The biggest take-home message: Problems with your short-term memory and your brain function as you get older are not normal. Get it tested. Do a biomarker test, and if that biomarker for Alzheimer’s disease is abnormal, get access to treatment as soon as you possibly can.
Kevin Pho: Emer, thank you so much for sharing your perspective and insight. Thanks again for coming on the show.
Emer MacSweeney: Thank you.
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