What are the Different Types of Dementia? A Primer for those of us who aren’t Healthcare Clinicians

Matt Davis: 

AD, ADRD, AD/ADRD, AD/D. These are just a few of the abbreviations used by researchers when they write about the population of individuals with dementia. AD refers to Alzheimer's disease. ADRD can refer to different things, but typically it refers to Alzheimer's disease and related dementias. I'm always impressed by the creativity of folks who continue to expand on a seemingly endless list of dementia abbreviationsTaking a step back, though, from the nuts and bolts of a research article and how we go about describing a study population, I started wondering, though, about the various types of individuals with different underlying causes. What clinicians refer to as etiologies, who make up this all too easy to aggregate dementia population. Or should I say AD/ADRD population?

Donovan and I are both researchers, so we're well aware of the decision making process in regards to identifying a particular study group. We think carefully about this in our own work. Sometimes, although I hate to admit it, sample size plays a part with how I group people up. But ideally, the decisions we make are based on who we want to generalize our findings to. In this regard, from a population health and perhaps policy perspective, it can make sense to combine Alzheimer's disease with other types of dementia, but other times it might not. It depends on your objective and the perspective of your research.

First, not to get too personal, but Donovan, what's your preferred dementia abbreviation?

Donovan Maust:

If it's somebody I've been seeing in clinic, it's just dementia, or specifically the type of dementia that they have. In a grant, usually I'll go with ADRD. Or a lot of times, I'll use PLWD, which is person or persons living with dementia. So it depends a little bit on the context.

Matt Davis:

That's one I don't see as often, but I like it. Am I alone in being a little bit distracted by some of the lengths of the abbreviations that people use when they go about describing the dementia population? I think it's because when I read the article, I'm stating the abbreviation in my mind. So that when you set things like AD/ADRD, it can get a little bit annoying.

Donovan Maust:

I work in the VA and we're surrounded by abbreviations and acronyms. And then also honestly, clinically, so many clinical notes. Just there's tons of shorthand and abbreviations. So I think my threshold for abbreviations is maybe higher than yours is, Matt.

Matt Davis:

I suppose I should be grateful, though, that people haven't started using some catchy acronym for dementia. And perhaps I am exaggerating a little bit about the amount of dementia abbreviations. It just seems like every paper I read, I have to get reoriented to the abbreviation those authors happen to be using.

So I've been looking forward to this episode for my own education. I recall that we were at a meeting where we were discussing different topics for this podcast. And Edward Norton, who leads the pilot research program for the Center to Accelerate Population Research in Alzheimer's, suggested we do an episode to just discuss the various types of dementia. Which brings up an important point. A lot of people doing research on dementia don't have a clinical background. So we thought this was a great idea, especially before we get too in depth with some of our topics. So in this episode, we'll talk with a leading clinical expert to get a better handle on the different types of dementia. I'm Matt Davis.

Donovan Maust:

And I'm Donovan Maust.

Matt Davis:

You're listening to Minding Memory, a podcast devoted to exploring research on Alzheimer's disease and other related dementias.

Today we're joined by Dr. Henry Paulson. Dr. Paulson is a Lucile Groff Professor of Neurology at the University of Michigan and Director of the Michigan Alzheimer's Disease Center. His research focuses on the causes and treatment of age related neurodegenerative diseases. Nationally, Dr. Paulson has taught popular courses on dementia. He regularly serves on scientific advisory boards of national organizations and is the past chair of the Board of Scientific Counselors at the National Institute for Neurological Disorders and Stroke at the NIH. He's here to help us disentangle the various types of dementia. No pun intended. The hope here is to give us researchers that study dementia a better understanding of the most common types and the underlying causes. Hank, thanks so much for joining us today.

Henry Paulson: 

It's good to be with you.

Matt Davis:

I must say, it always feels like a bit of an extreme transition after I share the credentials of our incredible guests and then shift to a first name basis. But we're casual in this podcast.

My partner and I are in our 40s. We were joking the other day about how we've already lost a little bit of cognitive clock speed. When we compare ourselves to back when we were in our 20s, we're a little more likely to forget things occasionally and mix up words. So let's start with something really basic. From a clinical perspective, what exactly is dementia and how is it any different from just normal cognitive aging?

Henry Paulson:

 Dementia is the term we use, it's a clinical term, when someone has impairments in cognitive domains. Might be memory, language, behavior, decision making, in which those impairments are severe enough that they actually lead to functional impairment for that person. Inability to do certain things that they normally would have been able to do. That is, for us, that barrier that leads to what we call dementia. It's a very gray, murky barrier, and it's not easy for us to always to make the decision whether someone has mild cognitive impairment, but not dementia versus actual dementia.

Donovan Maust:

Hank, when you talk about functional change, can you give us an example of the types of things that folks come in talking about or their family member talks about?

Henry Paulson: 

Yeah. It ranges so much, Donovan, from patient to patient. But someone who used to be able to do the bills, could actually organize the writing of the bills, make sure it's done in a timely manner, can no longer do that or can't do the calculations in the balancing of the bank book. That'd be one numbers based type of functional impairment. It might be someone who has a job, but can no longer do some of the tasks that seem to be part of that job that had been fairly straightforward for them no longer possible to be done.

Matt Davis:

So it sounds like dementia is best thought of as a collection of symptoms that have a variety of underlying causes. Before we get into the underlying causes, just briefly, what are the most common types of dementia and how do you go about distinguishing them?

Henry Paulson: 

The most common dementia is Alzheimer's disease, and everyone's heard of that. There are other types of dementia that are slightly less common, including vascular dementia, where there are changes in the vasculature of the brain that can cause cognitive impairment; frontotemporal dementia, Lewy body dementia or dementia with Lewy bodies. Those would be the big categories of dementia that we speak of when we talk about age related dementia.

Matt Davis:

Is that in rank order of how common they are, more or less?

Henry Paulson: 

Alzheimer's, I would say, far outweighs the other ones in frequency. If you had a big pie chart that showed the frequency of these diseases, the big pie slice by far, more than half the pie, would be Alzheimer's. And then the other parts of the pie that are roughly the same would be vascular and dementia with Lewy bodies, and then probably frontotemporal dementia a little bit further behind. Of course, there's a lot of overlap. And so when we talk about the slices of the pie, they are not clean slices, they are runny and lots of overlaps. It's almost as common to find someone who has some of the pathology of Alzheimer's and vascular as to have someone who just has pure Alzheimer's. But if we wanted to categorize them as the most common dementias that occur as a function of age, they're number one, Alzheimer's; probably number two, vascular; right behind it number three, dementia with Lewy bodies; and then number four, frontotemporal dementia.

Matt Davis:

So now that we've talked about some of the most common types of dementia, let's talk a little bit more about some of the causes or pathologies that underlie them. So from my understanding, Alzheimer's disease, when people talk about Alzheimer's disease, people talk a lot about plaques and tangles. Sometimes I hear similar things come up around other types of dementia, like frontotemporal dementia. Could you give us a brief overview of some of the pathology behind the most common types of dementia?

Henry Paulson: 

The description of a dementia, whether it's Alzheimer's or dementia with Lewy bodies or frontotemporal dementia, does ultimately depend on what the pathology is underlying it. In Alzheimer's, it is required, in order to make a definitive diagnosis at autopsy, that there are both plaques and tangles. Those are the two types of abnormal protein accumulations that occur in Alzheimer's disease. You have to have both of those pathologically to have Alzheimer's by definition. Now we can actually visualize the plaques and the tangles using imaging techniques in people who are alive. So we can definitively establish that someone has an Alzheimer's pathology as the basis of their dementia.

For dementia with Lewy bodies, the name tells you that Lewy bodies are the pathology that exist in dementia with Lewy bodies. Lewy bodies are small accumulations of a protein, the same type of protein that accumulates in Parkinson's disease. So dementia with Lewy bodies and Parkinson's disease are on a spectrum of disorders in which there's an abnormal accumulation of that protein called synuclein.

And for frontotemporal dementia, there are many different flavors of what we call FTD, frontotemporal dementia or FTD. The most common flavor is this accumulation of a protein called TDP-43. But there are other people with FTD who have accumulation of the tau protein, the very same protein that accumulates in Alzheimer's. But in that case with FTD, because it's simply tau that accumulates but no plaques, it's not Alzheimer's, it's a different thing. It's FTD.

Finally, vascular dementia doesn't have an accumulation of proteins in this way. Vascular dementia is a dementia that occurs because of subtle usually, or sometimes major changes, to the vasculature of the brain that leads to damages to the white matter tracts in the brain or leads to small strokes in the brain, or in some cases, multiple big strokes in the brain. So that's a very different type of pathology.

Matt Davis:

I was curious, because of someone that I knew in my childhood [00:10:30] who took a really bad fall off a ladder and badly hurt her head, and shortly thereafter, ended up going on and having some cognitive issues that led to dementia. I know it's really hard to connect the dots sometimes. Is there any evidence around trauma being a potential etiology or a bad head injury with dementia that you're aware of?

Henry Paulson: 

Yeah. I think it's important to say dementia, as opposed to Alzheimer's. Some people say is trauma from a childhood a later predictor of Alzheimer's? And that's not the case. But it's definitely the case that traumatic injury to the brain or repetitive concussive injuries to the brain, smaller level trauma as we know about it, what people call sometimes pro-football dementia. That these kinds of trauma to the brain can set one up for developing later life dementia. We don't think that it's simply the trauma. It's probably other factors that go into determining whether someone develops a later life dementia that has trauma as a basis for it, including genetic factors, including perhaps other environmental or medical factors. But yes, I think that trauma can be.

Now, I had several concussions in sports as a kid. I don't think that my risk of developing dementia is any greater from those concussions. They were small concussions. I was knocked out. I was back on my feet within minutes. I didn't miss school. I didn't have any long term sequelae of those concussions. And I don't think those concussions would be sufficient to increase my risk of developing dementia. But if someone has repetitive concussive injuries in contact sports or someone has a major traumatic injury to the brain, yeah, I think those are definite risks for dementia later on.

Matt Davis: 

Now, this probably is a bit of a departure from some of these different categories, different types of dementia, with established causes and biological phenomenon, those types of things. But what about something like severe alcoholism that can lead to cognitive impairments later? Is that considered a type of dementia or is that just a risk factor that could increase the likelihood of other types of dementia?

Henry Paulson: 

It's a really good question. When we see someone in the clinic who has cognitive impairment and we're trying to figure out what's going on, there's a broad range of potential diagnoses that we're thinking about. Some of them are these age related degenerative brain processes, such as Alzheimer's, FTD, and dementia with Lewy bodies. But there are other things that can lead to cognitive impairment, including chronic alcohol use, very poor sleep, obstructive sleep apnea. Multiple risk factors for vascular disease that can cause changes to the brain. Depression itself can be a cause of cognitive impairment. So we think about these things. We look for these things in the clinic, and we treat those things because these are often reversible, very treatable causes of cognitive impairment. That's different from a progressive degenerative process that causes dementia.

You brought up alcohol. And the thing about alcohol is that chronic alcohol use, particularly if you're not eating well, if you're having a poor diet, can lead to damage to the brain. And so it itself can chronically over time cause a dementia.

Matt Davis:

So I'm thinking about trying to unpack some of the different types. And I'm thinking about how, along the line of risk factors and those types of things, typically in this field, there's an assumption that you're talking about older adults. So when we think about something like Alzheimer's, like you said, it's the most common type and established type, obviously it's highly correlated with age. Advanced age is one of the strongest risk factors of something like dementia. Now, as we go across the other types, I'm curious which types are correlated also with advanced age. And are there any specific that perhaps actually affect younger individuals?

Henry Paulson: 

The four big dementias that we've talked about, Alzheimer's, FTD, dementia with Lewy bodies, and vascular dementia, are all age related. That is, they increase in likelihood as we get older. Among those four, FTD is more likely to occur at a younger old age. In the 50s, for example. Whereas Alzheimer's is more likely to occur in an older age, such as 65 to 70 to 80.

But even a disease like Alzheimer's, which we typically think of as occurring after age 65, that's when the symptoms really begin, can occur at a much younger age because a small fraction of Alzheimer's has a very strong genetic cause to it. That's called familial Alzheimer's disease and it's early onset Alzheimer's. Individuals with these disease causing Alzheimer's genes inherit it in their family, and they either get it or they don't, as they inherit it from a parent. They might develop dementia in their 30s or 40s. In fact, most commonly in the 40s, people with familial Alzheimer's disease will develop dementia. But that's a very, very small percentage of all Alzheimer's. Maybe at most, 1.5% to 2%. The bulk of Alzheimer's is late onset Alzheimer's disease. It has a genetic element to it, but it doesn't have a strong genetic element in the way that early onset familial AD does.

So those are the four big ones, and they're definitely age related. There also some rare causes of dementia that are genetic. A good example would be Huntington's disease. Huntington's disease is a genetic form of dementia that typically starts in the 30s and 40s, and it's still age dependent. Most people don't get Huntington's disease in their teens, but they do get a dementia in their midlife as opposed to late life. There are other even rarer causes of dementia that we look for on occasion.

Matt Davis: 

The vascular type sticks in my mind a little bit as being... It feels different to me, but it probably is due to stroke and those types of things, which is also correlated with advanced age.

Henry Paulson: 

Yeah. So yes, vascular changes in the brain tend to occur as a function of age. I think the bulk of vascular cognitive impairment that we see is occurring in the setting of other things as well. So this is one of the things that most people are not aware of in dementia. When you look at the brain of someone who's died from dementia, it's usually not the case that it's pure Alzheimer's or pure Lewy body dementia. It's usually the case that more than one thing is going on. The most common thing is a bit of vascular changes and a bit of Alzheimer's or a bit of vascular changes and a bit of Lewy body pathology. In some cases, there are four different proteins that are accumulated in the brain. So we now recognize that although we aspire to have a very neat and tidy evaluation of dementia for research and precision diagnosis, the reality is very often, it's a complicated and multifactorial and mixed pathology.

Donovan Maust:

I was wondering if we could just take a step back from the pathology a minute. Hank, you described the big four, the four most common types. I was wondering if you could just maybe give the listeners just a snapshot of what the phenotype. Are there particular clinical characteristics that help folks get an idea for what these patients can look like?

Henry Paulson: 

One of the first things we do in the clinic when we evaluate someone who has cognitive concerns is what precisely are those concerns? Is it language? Is it memory? Is it behavior? Is a decision making? Those kinds of domains of cognitive function really allow us to get a sense of what the potential type of dementia is.

So for example, if someone comes into the clinic and they have profound memory issues that have progressed over four or five years, maybe subtle language issues, maybe subtle problems in decision making or planning, but mostly it's memory and the neurologic examination is entirely normal. Most often, that's going to end up being an Alzheimer's type pathology.

If someone comes in and they have some problems with attention and maybe has some memory and some visual spatial difficulties, they're getting lost, they can't navigate as well as they used to. And let's say they have a little bit of stiffness and slowness and some Parkinsonism on the examination. And let's say they actually are having visual hallucinations. We know clinically, that's not likely to be Alzheimer's. It's much more likely to be dementia with Lewy body disease. I think of dementia with Lewy body disease, and this is probably a gross simplification, is that dementia with Lewy body disease it's like a mixture of Alzheimer's and Parkinson's disease together. People with Lewy body disease may have some memory issues, but it's not so profound in the way it is with Alzheimer's. It's usually mixed with problems with confusion, difficulties with way finding, with visual spatial navigation skills, and often with fluctuations and sleep behavior issues and visual hallucinations. So that is a clinical set of hallmarks that will allow us to say, this looks like it might be Lewy body as opposed to Alzheimer's.

And then for frontotemporal dementia, frontotemporal dementia, in a way, is very complicated because there are different flavors of FTD. Some people with frontotemporal dementia have profound behavioral changes. The person is simply not what they were like five years ago, behaviorally. An upstanding, morally upright, solid citizen suddenly is acting in really bizarre ways. Inappropriate, disinhibited. That would be behavioral FTD, and that would be something we would think about first. Some people with FTD just have profound language issues. It's not memory so much as it is language. They can't get their words out or they have trouble saying the right words. They say words that don't make sense.

So there are different clinical components that allow us to say I think this might be Alzheimer's. This might be dementia with Lewy body, this might be frontotemporal dementia.
Of course, the vascular dementia is something that we think about more when there are lots of vascular risk factors, and when imaging actually shows us that there's evidence of mini strokes or major strokes that are contributing there. And as you know, the neuropsychological problems that occur in someone who has vascular cognitive impairment are slightly different. They're not so focused on memory. They're more broadly distributed effecting cognitive domains.

So we definitely spend a lot of time trying to get the history from the patient and their family. We definitely spend a lot of time looking at neuropsychological performances, with neuropsychological testing. And then imaging becomes a very important factor that helps us say, we think this might be one of these dementias.

I'm going to stop really quickly and say none of those types of clinical trends or imaging are very precise. We don't have definitive biomarkers from those alone. But I think we're moving very quickly in the field toward definitive biomarkers in the blood or in imaging that can help us say yes, this is definitely Alzheimer's, or yes, this is definitely dementia with Lewy body. And that will be helpful when we think about giving therapies to people.

Donovan Maust:

Great. Thank you.

Henry Paulson: 

I do, I agree that, Donovan, we went way too much in the pathology, not enough into what it's like to have cognitive impairment. I will say that the most common question that I get in the clinic is... I get the statement, "Well, I'm so glad to hear that I have dementia and I don't have Alzheimer's." Because there's still a lot of confusion in the public about what's the distinction between Alzheimer's and dementia? And what I say all the time is that dementia is an umbrella term. It's a broader term under which Alzheimer's sits. Under that umbrella are the other dementias as well. So when we think about dementia, it's a broader term. And then we get more specific in trying to say, is it Alzheimer's? Is it dementia with Lewy bodies? Is it FTD?

Why does that matter? I think it matters because patients want to know. It tells us something about what the future holds for them. It gives them the right kind of support groups to go and talk to. Someone who has dementia with Lewy body disease and their families are dealing with a different set of problems than someone who has the early signs of Alzheimer's disease. And in addition, it helps us really guide what the appropriate therapies are for that person with that dementia. And maybe even most important, trying to avoid certain medications that could be a problem for specific dementias.

Donovan Maust:

I was mainly feeling good and reassured, because I was just doing a lot of head nodding that I would have given similar answers to my esteemed neurologist colleagues. So that was good and reassuring.

I do think your point about the mental distinction people make between dementia and Alzheimer's disease continues to be interesting to me. And even in, say, discussions at home with family members about some of the research or the their work that I do, clearly that they think about or talk about dementia in a different way than Alzheimer's disease and what that's about and where that comes from. It always, frankly, is a little bit of a surprise to me.

And then the final thing I'd just maybe add is in your comments about the behavioral variant of frontotemporal dementia. An example for folks of what this can look like is there's actually several years ago a case report in the American Journal of Psychiatry of somebody in their mid to late 50s who presented to multiple clinics and was given a diagnosis of late onset bipolar disorder because their behavior became disinhibited. [00:24:30] They were staying up and spending a lot of money, and just a complete departure from baseline. Even got put on lithium. Wasn't helpful. And finally got referred to a clinic where they made the diagnosis that this was, in fact, frontotemporal dementia. So it really can be a place where the memory, so people think of dementia as a memory impairment, but their memory wasn't really impaired. It was the behavior that really profoundly changed.

Henry Paulson: 

It's interesting. I think many people who are in the communication space on dementia didn't like to use the word dementia, so they say memory loss. And the reality is dementia sometimes involves memory loss and sometimes it doesn't. I think that I've tried to resist the term memory loss as a euphemism for dementia or for Alzheimer's because it's not fair to all those people who are experiencing cognitive issues that are not related to memory.

Frankly, when I see someone in the clinic who has a form of Alzheimer's that is slowly progressive that's a memory predominant, where they have completely normal neurologic function otherwise and still have social graces, and they're able to laugh in the clinic and make a joke and dance down the hallway. I think to myself, yes, I wish this person didn't have Alzheimer's. But there are so many skills and talents that this person still has. They're still the same person, and they'll for many years be able to continue to be that person despite these changes. I think in comparison to some of the other conditions I see that are rarer, that are much more devastating in a way because there's profound neurologic impairment. People are falling down or they have tremendous great difficulty in interacting with people socially.

And so I never say to a patient that you have a good type of dementia. But I do try to emphasize to patients, "The dementia that you have has allowed you to have preserved so many skills. I want you to tap into those. I don't want this disease own you. I want you to own this disease. You still have a lot you can do and go with it." I think it's important really to try to emphasize that positive component. I think in my clinic, sometimes residents who work with me are surprised how much laughter and warmth we have in the clinic. Because I really spent a lot of time on saying, "What can we do positively to move forward here?" As opposed to looking at this as a death sentence. But rather, saying, "We know what this is. Let's now manage what it is. Let's have expectations and let's move forward." And that's helpful to patients. Very helpful.

Donovan Maust:

I think that's a great note to wrap up on.

Matt Davis:

I learned a lot. I want to thank our guest, Dr. Paulson, for spending a little time with us. And thanks to all of you who listened in.
If you enjoyed our discussion today, please consider subscribing to our podcast. Other episodes can be found on Apple Podcasts, Spotify and SoundCloud, as well as directly from us at capra.med.umich.edu, where a full transcript of this episode is also available. On our website, you'll also find links to our seminar series and the data products we've created for dementia research.

Music and engineering for this podcast was provided by Dan Langa. More information available at www.danlanga.com. Minding Memory is part of the Michigan Medicine Podcast Network. Find more shows at uofmhealth.org/podcast. Support for this podcast comes from the National Institute on Aging at the National Institutes of Health, as well as the Institute for Healthcare Policy and Innovation at the university of Michigan.

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