In this bonus episode, we continue our conversation with Dr. Howie Rosen on Frontotemporal Dementia (FTD). On last week’s episode, Dr. Rosen spoke on the genetic risk factors, trajectories and family caregiving experiences of FTD. Now, our conversation turns to the research looking into how the disease affects self-awareness, biomarkers and early detection, as well as ways people can volunteer for a research study. Guest: Howard “Howie” Rosen, MD, behavioral neurologist at the University of California San Francisco Memory and Aging Center
- FTD and self-awareness: 1:10
- Research into biomarkers for Frontotemporal Dementia: 4:42
- How can people help the research: 11:40
Make sure to listen to our full-length interview with Dr. Howie Rosen, "Understanding and Managing Frontotemporal Dementia." That episode covers symptoms, risk factors, diagnosis, and what families and caregivers can do after diagnosis.
Dr. Rosen mentioned a few resources where people could find information about volunteering for a FTD study. They are the FTD Disorders Registry and Genetic Frontotemporal dementia Initiative (GENFI).
Learn more about Frontotemporal Disorders at the National Institute on Aging website.
NATHANIEL CHIN: I'm Dr. Nathaniel Chin and you're listening to Dementia Matters, a podcast about Alzheimer's disease. Dementia Matters is a production of the Wisconsin Alzheimer's Disease Research Center. Our goal is to educate listeners on the latest news on Alzheimer's disease research and caregiver strategies. Thanks for joining us.
NATHANIEL CHIN: Welcome to this bonus episode of Dementia Matters where we continue our conversation with Dr. Howie Rosen on frontotemporal dementia. On last week's episode, Dr. Rosen and I talked about the genetic risk factors, trajectories and familiar caregiving experiences of frontotemporal dementia, also referred to as FTD. If you didn't hear that episode, I encourage you to go back and listen. In this bonus episode, our conversation about FTD turns to research. We discuss research into how the disease affects self-awareness, biomarkers and early detection and how people can volunteer for a research study. Now here's the episode.
NATHANIEL CHIN: I'd like to move into the research realm of frontotemporal dementia. You're looking at how this disease affects self-awareness as well as how imaging and other biomarkers can be used to track the disease in the brain over time. Can you explain to us how and why frontotemporal dementia affects a person's self-awareness and what you've found in your research?
HOWIE ROSEN: It's a great question. The ultimate answer is we don't know. It's a particularly relevant question to FTD because one of the things we know about all degenerative diseases is they usually get to a point if they affect the mind that the person with the disease may not understand they have a problem. If they do, they don't understand the degree to which it's affecting them at some point. A person even with moderate Alzheimer's might acknowledge they have memory problems but not realize that it's gotten to the point where they can't do their own taxes, or that they don't understand why they're not doing their own taxes. They might acknowledge their son’s doing it. But they might say ‘It's cause I asked them to’, which really wasn't the case. That’s true in everything, but in frontotemporal dementia, this lack of self-awareness comes quite early and it's much more common than in Alzheimer's or any other degenerative disease. There's something we believe about the regions of the brain and which regions are affected that is the cause of this loss of self-awareness. What it teaches us is that there are regions of the brain that do this and that their job is monitoring and helping us to understand when we've made a mistake or when we've done something that that needs correction and those regions must get hit more in frontotemporal dementia.
My research is actually connected to the emotional problem. I always like to give the analogy, if you grew up in the United States and you're my age in my fifties; if you played soccer very well, it wasn't a particularly important thing. If you weren't a great soccer player, nobody really cared. But if he couldn't hit a baseball, that was a big deal. So what we know is if you're on the soccer field and maybe you didn't play so well, a lot of us would just let that slide. But if you struck out on the baseball diamond, you would really get angry at yourself and that might motivate you to work harder and to go to the batting cage or whatever. The point is that emotions actually play a lot of role in our self-monitoring and they help us to decide whether we need to change or not change. The inference might be that when our emotions aren't there, we may notice that we make a mistake but not care. Essentially, a lot of the way we might decide we're not the same person we were is if we've seen certain of our actions happen and they didn't come out the way they're supposed to. When we say, ‘I guess I'm not good at memory anymore or language anymore’, because that part of the brain that's supposed to care about those things doesn't work, it might ignore those things. I know they happen, but I don't care. Therefore why would I come to the conclusion that something's wrong with me even if I made a few extra mistakes. It's really something maybe unique about emotions and their role in our self-monitoring that I think FTD might be teaching us. That was some of the work I was doing there.
NATHANIEL CHIN: Some of the other work that you're currently doing is looking at biomarkers and tracking disease. I speak to a lot of researchers about biomarkers of Alzheimer's disease. We talk about this amyloid protein, the tau protein in the shrinkage of the brain center, the hippocampus. What biomarkers do you have in frontotemporal dementia?
HOWIE ROSEN: I think you were going to get to ask me about any biomarkers for the protein specifically. So the two proteins, tau and TDP 43; we unfortunately don't have any specific biomarkers for those proteins yet. In fact there are some PET scans and other blood tests that are being developed to detect the tau in Alzheimer's disease that look very promising. But unfortunately, we now know that they probably don't label the kind of tau in FTD very well. We really have to go back to the drawing board, which we are doing to try to develop those biomarkers. There are some promising hints and developments, but we're not there yet.
I consider cognitive and neuropsychological testing somewhat of a biomarker. And as I said, that has its value. Brain imaging which images the structure of the brain- atrophy and basically how much brain there is - you can measure that and quantify it, and that is a valuable biomarker. The more atrophy you have, we know the more symptoms you have in any disease. Therefore, the less atrophy you have or the more atrophy you prevent in a study might indicate that you're going to prevent cognitive decline or social and emotional decline. There are other related things, other kinds of more sophisticated imaging techniques. I don't know if you've ever talked about imaging of the white matter that we do called fusion imaging, and there's this thing called functional MRI where you actually look at activity of the nerve cells indirectly. Those things are also relevant in frontotemporal degeneration. We’re doing our best to creatively use those in the most useful way possible. That's what we have right now.
Oh, there's another one called neurofilament light chain. Have you ever talked about that one? Neurofilament light chain I think is going to be an extremely valuable marker in all neurodegenerative disease. What's good is that it's not limited to Alzheimer's disease, but it's true in frontotemporal degeneration too. It seems to be a marker that indicates somehow, and we don't really understand all the details, that nerve cells are being injured. We could detect it in the spinal fluid, so you'd do a spinal tap to find that. But what's really, really good about neurofilament light changes, it can also be detected in the blood and it has the same value detecting it in the blood as it does in the spinal fluid. It’s really going to be a valuable, but obviously because it goes up in frontotemporal degeneration and in Alzheimer's, you can't use it to decide which of those diseases that you have. But if you're worried that somebody's getting one and you want to see if that's really true or not, a low level of neurofilament might suggest that these symptoms that you're hearing are not related to a neurodegenerative disease. We have some work to do to figure out how true that might be or not, but that would be a good use of them. There is a study that's been published which compared people with frontotemporal degeneration to other people who had psychiatric illness with some overlapping symptoms and showed that the neurofilament level was much higher in the frontotemporal generation group. To conclude, that's always going to be the case that it’s tricky, but it's promising.
NATHANIEL CHIN: In Alzheimer's disease and according to how we view it, amyloid protein develops that leads to problems in the brain and then tau develops. There’s that sequence. Do you see TDP-43, that abnormal protein first leading to changes that cause this different version of tau?
HOWIE ROSEN: The problem is, I can't answer that because we can't measure the TDP 43 protein in life. In fact, we have a big problem with frontotemporal degeneration because certain kinds of presentations, certain kinds of symptoms are very closely associated with one of the proteins. If you have that weird kind of language problem where you don't recognize words and can't think of words that I mentioned, almost always at autopsy that turns out to have the TDP 43 protein. In life, if that's the symptom you have, I know what is causing the problem. In the kind of FTLD where you have the social and emotional problems, it turns out that about half the cases have tau and half the cases have TDP 43 and we have no real way to predict which one it is right now. It's just another example of how important that kind of biomarker is. I think the first place that's going to teach us more about that is genetics. There’s a large project in Europe called GENFI, the Genetic Frontotemporal Dementia Initiative. We have a similar project in the U.S. called ALLFTD, which I won't even tell you what the acronym’s for. ALLFTD and GENFI are both enrolling lots of people. We're enrolling people who are in these families, including people who have the mutation and are not affected, they seem to be fine, as well as people who have the mutation and already are affected. We're enrolling family members who are in the family but don't have the mutation. Through enrolling all of those people, it's going to help teach us about what the earliest manifestations of these diseases are. That is a group where we're working very hard to make sure if there's any useful biomarker, we're testing in these groups because if you have a certain mutation, we know what protein you're going to develop even before you get it, in theory. I think we are going to learn something about the evolution of these diseases and as the biomarker develops, which biomarker- which protein happens when and how that relates to symptoms.
NATHANIEL CHIN: One of my ending questions for you is what can people do if they're worried or they want to contribute to research? It seems like that website in the United States is one of the places to go.
HOWIE ROSEN: The Association for Frontotemporal Degeneration or A-F-T-D. Also, there's a frontotemporal dementia disorders registry, which has its own website, but it's related to that too. I think if you look up A-F-T-D and dementia, you'll probably land on this. It might not be in the first 10 of the Google's search. I hope it is. Keep an eye out for this. AFTD or the Association for Frontotemporal Degeneration.
NATHANIEL CHIN: Are there other ongoing clinical studies that people can register for or enroll?
HOWIE ROSEN: Yes. ALLFTD, for instance, is a multisite study that involves 19 sites around the U.S. ALLFTD also has a website, allftd.org. It may be that there are lots of centers like this one, that might have a related study, but they're not part of ALLFTD. That's why I think looking at the ALLFTD website would be great. But I also think you have to be familiar with AFTD because they would have even a broader knowledge of kind of the resources in the US, Canada and Mexico, etc. that might be relevant.
NATHANIEL CHIN: Well, Dr. Rosen, thank you for spending time with us and shedding light on this very important disease that we don't often talk about. It needs to be discussed and so with that I'd like to have you come on again in the future but thank you for being here today.
HOWIE ROSEN: Thanks very much and I was happy to do it and I hope it was useful and it was fun.
NATHANIEL CHIN: Dementia Matters is brought to you by the Wisconsin Alzheimer's Disease Research Center. The Wisconsin Alzheimer's Disease Research Center combines academic, clinical, and research expertise from the University of Wisconsin School of Medicine and Public Health, and the Geriatric Research Education and Clinical Center of the William S. Middleton Memorial Veterans Hospital in Madison, Wisconsin. It receives funding from private, university, state, and national sources, including a grant from the National Institutes of Health for Alzheimer's disease centers. This episode was produced by Rebecca Wasieleski and edited by Bashir Aden. Our musical jingle is Cases to Rest by Blue Dot Sessions. Check out our website at adrc.wisc.edu. You can also follow us on Twitter and Facebook. If you have any questions or comments email us at firstname.lastname@example.org. Thanks for listening.