Dr Rania Habib (Host): Dementia is a general term for memory loss. The CDC estimates that over 5 million adults over the age of 65 years old are living with dementia and this number is expected to nearly triple by 2060. What is dementia? Does it have different forms? And what is Alzheimer's disease?

This is Expert Insights with the Carle Foundation Hospital. I'm your host, Dr. Rania Habib. Joining me today is Dr. Daniel Llano, a board-certified neurologist and Professor at Carlee Illinois College of Medicine. He is here to discuss the details about dementia, Alzheimer's disease, treatment options, and emerging therapies. Welcome to the podcast, Dr. Llano.

Dr Daniel Llano: Well, thanks very much for having me.

Host: We are so honored to have you with us today to give us more insight into this very important and timely topic.

Dr Daniel Llano: Great. Thanks.

Host: Let's begin with just a really simple question. What is dementia?

Dr Daniel Llano: Sure. Well, dementia is really an umbrella term. It refers to any condition that affects our thinking to the point that we're unable to do our day-to-day activities. So, there are many different kinds of dementia. Alzheimer's disease is the most common kind of dementia. But other things can cause dementia, trauma to the brain, stroke, hydrocephalus, various other degenerative diseases. So, the term dementia just refers to any disease that affects our thinking to the point that we can no longer manage our day-to-day affairs on our own.

Host: What are some of the signs and symptoms of dementia?

Dr Daniel Llano: Well, that does depend on the particular kind of dementia. Typically, if it's something like Alzheimer's disease, which accounts for about two-thirds of all dementia, the earliest signs and symptoms are usually a memory issue where people don't remember conversations that they've had. They may not remember a shared experience. A very common thing that people will report, and it's often the loved one that's reporting this, is that, "Yeah, we went out to see a movie and my loved one couldn't remember any of the details of the movie that we just saw one or two days ago," or they might report that their loved one is repeating themselves. They might ask the same question multiple times in a short interval, because they're just not remembering what the answer was. And so, those are the earliest signs that people will report. And I should also mention it's often not the patient themselves that notice these issues, it's almost always their loved one, spouse, adult child, et cetera.

Host: Now, I know you mentioned that there's multiple different forms and causes for dementia and we'll get into that. But is dementia considered to be a part of normal aging?

Dr Daniel Llano: By definition, no. Dementia refers to cognitive loss, which is beyond what would be expected for normal aging. Now, it is true, as we age, there are certain cognitive functions that we don't do as well as we did when we were younger. So, for example, something like multitasking, being able to do multiple cognitive tasks at once, or keeping track of a list of objects while performing another task. That tends to decline as we age. And there is some memory loss that comes as a normal consequence of aging, but that's pretty mild.

And so, one of the challenges that we often face in the clinic is when someone's presented to us with concerns about memory, is trying to separate, well, is this just normal memory loss for aging, or is this something more worrisome that requires more of an evaluation? And there's formal ways of being able to distinguish between normal aging-associated cognitive impairment, which again is usually pretty mild, and something that's more concerning and requires additional testing.

Host: What are some of the most common risk factors for developing dementia?

Dr Daniel Llano: So, aging is the most common risk factor. That's the common denominator with most forms of dementia, certainly with Alzheimer's disease and then with other types of dementia that are a little bit less common, things like frontotemporal dementia or dementia with Lewy bodies. But beyond aging, we know that there are other risk factors as well. So, things that impact our general health, which are often reflected in our brain's health will be risk factors for dementia, so for example, chronic uncontrolled high blood pressure or other cardiovascular risk factors. We don't exactly know what's happening in the brain in those cases to predispose to dementia. But certainly, what we often see in the brain when we do advanced imaging are microscopic areas that are not getting quite enough blood.

So, untreated cardiovascular risk factors are something that really need to be addressed in midlife, so that later on, 20 years later, that individual is less likely to develop a dementia. And then, there are other risk factors that are little bit more mysterious. So for example, hearing loss is a risk factor for Alzheimer's disease. We don't really understand that relationship. Smoking is a risk factor for the development of dementia, which is likely related to its cardiovascular effects. So, there are quite a few things that we have some control over that can limit our risk for dementia. Aging, obviously, we have no control over that, but these other cardiovascular risk factors, we can control with lifestyle and with visits to our primary care doctors, and paying attention to the advice that they're giving us.

Host: You've given us a lot of information of just overall what is dementia. We know aging is a huge risk factor for it, and we're all going to age at some point. So for our audience, could you please describe the different forms of dementia, Dr. Llano?

Dr Daniel Llano: So, as I mentioned, the most common form of dementia is Alzheimer's disease. And Alzheimer's disease is typically defined as an illness where there is progressive loss of memory, what we call episodic memory, but what most individuals refer to as short-term memory. And the reason that we lose short-term memory is because there's a particular part of the brain, it's called the hippocampus, that loses its function and then ultimately degenerates in Alzheimer's disease. And that's often what we look for when we do scans on people with Alzheimer's disease, MRI scans. We're looking at this brain region to see if there's been some degeneration there. What we also know happens in Alzheimer's is that there's deposition of proteins that shouldn't be there. Something called amyloid, another protein called tau. They both deposit in the Alzheimer's brain, and that's an accumulation that occurs over time. And this disease slowly does progress over time.

There are other forms of dementia though as well as I mentioned. So, frontotemporal dementia is one that we see in sometimes younger patients, meaning in their 50s. And in this case, it's not typically a memory problem, it's more of a behavioral problem. Someone's personality might change. They might make some large, extravagant purchases that are really out of character for them, or they might say something that's a little bit inappropriate or off color, which again very out of character for them. And this could be very difficult to distinguish from non-neurological conditions. Somebody might be worried that their loved one is developing a psychological disorder. And in fact, many patients with frontal temporal dementia are often brought first to a psychologist or psychiatrist. And then, eventually, we find that it's the frontal lobes that have been affected by dementia. And it's our frontal lobes that are very important for regulating our behavior.

Another form of dementia, which we're seeing quite a bit of is something called dementia with Lewy bodies. Dementia with Lewy bodies is in the family of diseases where Parkinson's disease is found. And these are individuals who, in addition to memory loss, will often develop some walking difficulties and some tremor and balance problems, almost as if they're developing a Parkinson's-related disorder. They may even develop some hallucinations, often visual hallucinations. And this is treated quite a bit differently than we treat Alzheimer's disease, for example. And so, that's something that's important to be recognized.

And then, probably the fourth one that I'll mention, which is fairly common, is what's called vascular cognitive impairment, what we used to call vascular dementia, where people can have strokes. Sometimes strokes they never knew that they had, but strokes that we can often see on advanced imaging. And it's those strokes, small strokes often, that accumulate over time that will cause people to have cognitive problems. Sometimes it's memory problems, sometimes it's language, sometimes it's visual spatial dysfunction. But these are important to identify because sometimes we'll identify somebody who's had these small strokes and we uncover a risk factor for stroke that hadn't been treated before, for example, atrial fibrillation or another heart-related problem. So, vascular cognitive impairment is an important type of problem to identify.

Host: Now, you've given us a lot of the different forms of dementia. Dr. Llano, how are these different forms of dementia currently diagnosed?

Dr Daniel Llano: I'm a neurologist, so patients will be referred to me often with a general complaint of memory or cognitive loss. The thing that I want to do when I meet a patient and their family is to get a thorough history. Often the history will guide us to tell us what the kind of dementia is, meaning is it a memory predominant problem, is it a behavior predominant problem, and so on. But then, typically, once we've met with the patient and their family, done a history and a full examination, we'll often get some additional testing.

One really important test is something called neuropsychological testing. That's a formal way of assessing someone's cognitive functioning. And to go back to the point that was made earlier about normal aging versus worse than normal aging with cognition, formal testing is really the way to do that, where you would meet with a psychologist. Typically, it takes about three or four hours, so it's a long test. But you'd meet with that psychologist and they would test the individual's memory, they would test their attention functioning, their visual spatial functioning, multiple different domains and will give us a report back about here's where the patient is doing well, here's where the patient is struggling. And it's that pattern of peaks and valleys that will often be very instrumental to both give us a diagnosis and then also give us a good baseline to compare over time.

The second kind of test that we will normally get for our patients is some kind of brain image, almost always an MRI of the brain, because we'd like to know have there been strokes, have there been other things going on in the brain that haven't been diagnosed like something called hydrocephalus, people often call water on the brain, or sometimes even brain tumors, can be seen with this kind of imaging that could be accounting for the memory loss. And then, sometimes some laboratory tests. We typically want to make sure that the thyroid function has been monitored because if that's abnormal, that can cause memory loss. We'll check vitamin levels like vitamin B12 to make sure that that isn't low because that can also cause memory loss. And that would be what I would call a pretty standard, evaluation.

Once in a while, we do all this testing and it's still not clear. And in those cases, we might have a patient do what I would consider to be more advanced testing. Something called a PET scan, which is a brain scan that tells us more about brain function rather than structure, is something that we may want to get, or sometimes even what's called a lumbar puncture or spinal tap can be very informative because that will give us a sample of the same fluid that bathes the brain, that same fluid collects in the lower back, and we can take a sample of it and often that could be really instrumental in making a diagnosis.

Host: Well, thank you for that very thorough description of how you diagnose these patients. I'd like to switch gears just a little bit and focus on Alzheimer's disease. You did mention that it is the most common form of dementia. Could you please describe the current and emerging therapies for Alzheimer's disease, Dr. Llano?

Dr Daniel Llano: Sure, absolutely. This is a very exciting time right now, because there's new therapies that have emerged just in the past couple of years. So, for the past 20 years, we have had essentially two drugs or two types of drugs available for patients with Alzheimer's disease. One of them is called donepezil, and it has some what I'll call cousin drugs, very similar mechanistic drugs. And the second drug is something called memantine. You may recognize the brand names Aricept and Namenda for these two drugs. These are drugs that have modest benefits for symptoms, but don't change the underlying physiology of the brain or pathophysiology of the brain. And so, they don't change outcomes. They aren't considered to be disease-modifying, but they're generally safe and they can be helpful for symptoms, as I've mentioned. So, we've been prescribing them for 20 years, and they've been pretty heavily used by the Alzheimer's community.

In the past couple of years, there have been drugs that have been approved by the FDA that work in a very different way. These are drugs that remove amyloid from the brain. So, I mentioned earlier, amyloid is a protein that accumulates in the Alzheimer's brain. We don't exactly understand what amyloid is doing, but it's certainly there when there's pathology. And for decades, scientists have been trying to develop ways to remove amyloid from the brain, and we are finally at a point that we can remove amyloid from the brain successfully. And the way that we do that is with an antibody. It's kind of like a vaccination. It's an antibody that gets into the brain and it removes the amyloid. It does that actually very effectively. And that approach has been approved by the FDA, both this past year in 2023 and prior to that with a previous version of a related drug.

And the jury, I would say, is still out in terms of what the long-term impact is going to be of drugs of this type. But it certainly is a very exciting time. These drugs are now becoming rapidly available, but they do require quite a bit of monitoring. There are some potential side effects, some of which are serious, from these medications. They require infusions to be given frequently for the one that was just approved this past year, lecanemab, or Leqembi, which is the brand name that requires infusions every two weeks. There are many MRI scans that have to be done to monitor for some of the potential side effects of this particular drug. And the drug is really intended for people in the earliest stages of the illness. So, there's still some limitations, and a lot yet to be learned, but an exciting time and there are many new drugs that are coming down the pike behind the ones that were just approved. So, I think we'll see many new things happening over the next couple of years.

Host: That is fantastic. And now, these amyloid antibody drugs. Are they considered to be disease-modifying drugs?

Dr Daniel Llano: Well, I would say we don't yet know. They clearly modify the brain because they remove amyloid. What we don't yet know is how that's going to affect the course of the illness. And so, in fact, what the FDA has required appropriately, is that when patients are given these drugs that the patients be enrolled into a registry so that we can follow their progress over time. And it's going to take, I think, a fair amount of time to really understand the impact of these drugs. The disease is a slow-moving disease. So, to be able to really know if you've impacted the long haul of a disease course, it's going to take many more than just one or two years, probably about five years, to be able to really know the long-term impact of these drugs and if they're really disease-modifying.

Host: Dr. Llano, you mentioned in the beginning that Alzheimer's or dementia is often picked up by the family members. If a family member suspects that a loved one has dementia or Alzheimer's disease or one of the forms of the dementia that you already mentioned, what should they do?

Dr Daniel Llano: I definitely think they should be evaluated, bring it to the primary care doctor. Often they'll make a referral to see a dementia specialist, because sometimes the cause of the memory loss is something that's easily remedied. So for example, if somebody has a thyroid abnormality, a B12 deficiency, or sometimes we uncover that somebody has had strokes that they didn't realize they were having., and that might uncover a risk factor for stroke that needs to be treated. And it's also important, even if it is something like Alzheimer's disease, to have us take a look so we can be sure that they're getting the appropriate therapies. And then, sometimes, We need to make sure that the individual is capable of doing all the things that they're taking on, including driving and handling the finances, et cetera.

And then, in the end, one of the most important things that a family member can encourage their loved one to do if they have a memory problem, really irrespective of the cause, is to take good care of themselves in terms of their cardiovascular health. So, that means exercise on a regular basis. There's lots of good data supporting exercise as a way to protect the brain. And often, we rely pretty heavily on family members to encourage our patients to exercise because that's a tough thing to do. And so, families often are the ones that are really helping us when it comes to trying to prevent the things that we know could lead to dementia.

Host: Thank you for really bringing up the fact that the family has to play a big role in helping care for these patients. And, you know, I didn't realize that something as simple as exercise can really help prevent those signs of dementia or progression of the disease. Now, as we wrap up, what is your final take home message for our audience, Dr. Llano? You provided us with such a wonderful deep dive into dementia and Alzheimer's and all the different forms, but what is your final take home message?

Dr Daniel Llano: Well, as I said, there's lots of things that we can do to prevent dementia. Most of those have to do with taking good care of our bodies, handling all of the cardiovascular risk factors that tend to come along with age. That is diabetes, high blood pressure, high cholesterol. We know that if all of those are managed well, that can help prevent dementia later in life. Smoking is another one that we know we can control that could lead to dementia in later life and then, as I just mentioned, physical exercise. So, keeping your body healthy through these approaches are definitely the thing that we have under our own control to help prevent dementia later in life.

Host: Well, thank you so much for providing us such a deep delve into this very important topic.

Dr Daniel Llano: Well, thank you very much. It's been my pleasure.

Host: Once again, that was Dr. Daniel Llano, a board-certified neurologist with the Carle Urbana South Clinic. For more information and to get connected with one of our providers, please visit carle.org. For a listing of Carle providers and to view Carle-sponsored educational activities, head on over to our website at carleconnect.com. I'm your host, Dr. Rania Habib, wishing you well. That wraps up this episode of Expert Insights with the Carle Foundation Hospital.