Special Episode: Robert Kolker & The Vanishing Family

Thank you for watching.

Hi, I'm Erin Welsh, and this is This Podcast Will Kill You. You're listening to the newest episode in our TPWKY Book Club series, where I bring on authors of popular science and medicine books to discuss their latest work. We've been making these episodes for a few years now, which means that we've gotten to feature some excellent books that delve into all sorts of diverse subjects, like the science behind plant derived poisons, the substantial obstacles faced by whistleblowers of unethical medical experiments, the history of the pelvic exam, and so much more. This also means that we've got a very robust list of science books to add to.

Your to read list.

Or to help you find the perfect birthday present for your bookworm friend. To check out the full list of books we've featured on this series so far, as well as get a peek at the ones coming up in future months, head over to our website, thispodcastwillkillyou.com. Under the extras tab, there's a link to our bookshop.org affiliate page, which will take you to a site with a bunch of podcast-related book lists, including one for this book club and one for the TPWKY Kids Book Club hosted by Erin Updike on our socials. We'd love your help in adding to these lists, so if you've got any book suggestions or topic suggestions, a firsthand account you'd like to share, or any other thoughts you have, the best way to

get in touch is through the Contact Us form or the firsthand account form on our website. A couple of things before getting to the book of the week, and that is to please rate, review, and subscribe. We would love to make this podcast forever, and this really helps us out. And second, you can now find full video versions of most of our newest episodes on YouTube. Make sure you're subscribed to the Exactly Right Media YouTube channel so you never miss a new episode drop. Dementia, in all its forms, is a disease of erasure. It blurs the edges of identity and erodes the history and memory that is foundational to relationships. This loss of self and our limited understanding of why it happens or what we

can do about it is what makes dementia such a profoundly devastating and feared disease. For many of us, our destiny with dementia is unknowable. But for others, such as those who carry the allele for frontotemporal dementia, a genetic test can reveal the future. Frontotemporal dementia, or FTD, is a particularly cruel form of dementia. Symptoms appear in middle age and are more often associated with behavioral and personality changes than with memory loss.

And it's hereditary.

Those who have a parent with FTD often have a 50% chance of inheriting the condition. But even if someone tests negative for the condition, they may have to watch as their loved ones slowly slip away. In The Vanishing Family, Love, Fate, and the Quest to End Dementia, Robert Kolker paints an intimate and heart-wrenching portrait of a family stalked by frontotemporal dementia and the complex choices and challenges the nine siblings face over decades. Kolker, an award-winning journalist whose previous book Hidden Valley Road won critical acclaim for its exploration of schizophrenia, writes with such compassion that as he tells the story of how this family came to learn of their destiny with dementia. As sibling after sibling begins to show signs

of FTD, those yet unaffected must make painful decisions over whether they want to learn their own fate, a fate which also holds profound implications for their children. After years of struggling to find answers, the siblings join forces with the dementia research community. in the hopes that their family's tragedy will help shed light on the mechanism of FTD and possibly lead to a cure. Kolker's storytelling is both enthralling and empathetic, and since reading it, The Vanishing Family has never fully left my thoughts. I am very excited to share this conversation with you all, so let's just take a quick break and begin.

Bob, thank you so much for joining me today.

Oh, I'm really glad to be talking to you, Erin. Thank you.

In The Vanishing Family, you present readers with a deeply moving, very intimate portrait of a family haunted by frontotemporal dementia and how this disease, it changes relationships, it changes identity in nuanced and sometimes unexpected ways. And to start us off, could you share how you became connected with this family and give me a broad overview of their journey?

I first got in touch with this family about four years ago. They had read my previous book, Hidden Valley Road, which is about a family with schizophrenia. one of the members of the family called me and said, we're a family, we have nine siblings, and we all have inherited a 50-50 chance of developing early onset dementia. They said it wasn't Alzheimer's, it was frontotemporal dementia, which was a very rare form. And in their case, it's early onset and it's incurable. At first, I wasn't sure what I could have to offer having already written about a family with an illness, but then the woman I was speaking with said something amazing to me.

She said, we know exactly what this mutation is.

I just spent three or four years writing a book about schizophrenia where they still haven't found a smoking gun gene for schizophrenia. They found maybe more than 100 genetic mutations that have some impact, but it's all tiny impacts.

So they're still searching.

And I said, do you mean to tell me that someone could look at a slide or something and say, yep, there it is, the mutation?

And she said, yes.

And I said, aren't we living in the age of CRISPR and gene editing? And why can't someone map this gene and cure you guys by lunchtime tomorrow?

And she said, we would like to know the same thing.

And so I proposed it as a magazine story about a family on the front lines of the genetic editing revolution. But then along the way, I learned about FTD. And it's astonishing. It is very different from Alzheimer's in the beginning. Instead of losing cognition, or losing memory, you lose your personality.

You become compulsive or apathetic. Some people stop caring about the people around them, including their children, or just sit around watching TV. Other people start to drink or have affairs or break the law. And so it's very hard to diagnose because these behaviors aren't necessarily They don't necessarily scan in our society as dementia. So people believe that FTD is underdiagnosed in our society. They think they've counted 60,000 people, but it could easily be double that. Because it's incurable, a lot of doctors don't go looking for it because why give bad news anyway? There's just all kinds of issues with it. Recently, you guys talked about ALS.

This is a close cousin of ALS. ALS has its own horrifying incurable symptoms, but there is a variety of FTD that.

Overlaps genetically with ALS.

And so you see it's in the company of these rare diseases that are desperately searching for cures. What astonished me about FTD is that when it happens in an inherited way with families, you have people who are watching the people they love most in their life change completely. Their personality is changing completely. They're still driving a car.

They still might even be working, but they aren't the same person they were before.

And they're constantly wondering.

Where the FTD begins and the personality ends. The other big thing, and this is the biggest thing, is that they can all test for it. You could be in this family and be 20 years old and decide to take a genetic test and know whether sometime in your 40s or hopefully your 50s, you will develop this early onset form of dementia. And everybody has a different response to that question, the crystal ball question.

As you mentioned, it is this really remarkable and terrifying and cruel way of eroding this line between self and disease and, you know, raising all of these questions of where does the person end and the disease begin? And this also is heartbreaking because it emerges so much earlier than many other forms of dementia, making it easy to ascribe symptoms to something else. And this was the case for Jean, the matriarch of the family in your book.

Can you take me through some of the earliest signs in Jean's case that something wasn't quite right, that she wasn't herself and how her disease then progressed?

The matriarch of this family is a woman named Jean, and she died in her 50s in 1990.

In 1990.

And in the 10 or 15 years before she died, she went through some pretty significant changes, but those changes could always be blamed on something else. FTD wasn't even a diagnosis back in the 80s and 90s when she was changing. She went from being an outgoing, very well put together, very responsible woman who was a mother of nine and keeping it all together to to someone who would spend every day hanging out waiting for the liquor store to open and who stopped cooking for the family and just sort of hung around the house and who lost, she was already a very tiny person, but she lost so much weight that she was well under 100 pounds.

A lot of her children had already left the house by the time the worst of it happened. And so they were either trying to move on with their lives or they just weren't They were willfully looking away.

They also blamed it on depression. They blamed it on alcoholism.

And mostly they blamed it on the changes that their father was going through, which is that he was having an affair and leaving the marriage. And so there were a lot of things going on in that house. And so the chances that somebody would have stood up and said, no, no, no, this is a neurodegenerative illness, were zero. And by the time she died, it was a breast cancer and too late to even consider it as an issue. So these nine children of Jean go on to become adults. Many of them go on to marry and have children, all not knowing that there is something potentially inside them.

And that That is such an important aspect of FTD as well, is its heritability pattern. Can you take me through a little bit of the genetics of FTD and what makes it different than some of the other diseases that are genetic in nature or heritable in nature?

It's a very rare illness, but it's so brutal in the way that it can be inherited. And not all FTD is inherited. Some of it are sporadic cases. And so when you hear about a celebrity out there who says they have FTD, it's not necessarily true that their kids might inherit it. It might be important for people to know that. But when it is inherited, it's assumed to be the very basic autosomal dominant 50-50 chance, a coin flip.

Either you have it or you don't. But if you do have it, your.

Kids have that same 50-50 coin toss to make about whether or not they're going to have it. When there's no cure, sometimes you would think there's no upside in wanting to know your future. Maybe you think it'll spoil you or ruin your life or drain you of all ambition. Or maybe you're holding out hope for a cure sometime in the next. you know, 10 to 15 years. There are all sorts of reasons not to know. What gets me about this question of would you want to know is that it's a question all of us are going to be facing in one way or another. We do a lot of crystal ball work these days in medicine, a lot of blood tests to see if potentially the child that's in utero might actually get a particular disease

one day. Of course, the dream in treating dementia is that they'll treat it one day like heart disease, that you'll have something in a blood test when you're 30 that shows that your numbers are climbing and you'll start to take a medicine to bring your numbers down on whatever that thing is that might contribute to dementia. I think the other thing about dementia that really struck me and really surprised me is that if you or I or anyone are lucky enough to live into our 90s, you might have two or three of them. that not every dementia is Alzheimer's, that Alzheimer's actually might only be 60% of the dementias out there. And that by the time you're in your 90s and if they happen to check out your brain after you die, they might detect some

Parkinson's in there, they might detect Alzheimer's, they might detect Lewy body's dementia, front to temple dementia, even ALS. There'd be all kinds of different neurodegenerative conditions that just sort of happen the longer your brain is on the planet and alive.

And dementia has long been a part of human life, of getting older. And today, it holds a place among some of the most feared diseases that humans can get. You know, this slow slipping away of self, the loss of control. I mean, anyone who has witnessed this happen to a loved one knows how deeply devastating it can be.

Has dementia always been perceived in this way? Or historically, how did people think about or experience feel about dementia?

I think hundreds of years ago, before science got involved in the brain, well, lifespans weren't as long, so there was a little bit less of it. But if you were lucky enough to live longer and you had developed dementia, that might even be seen as your soul leaving your body, as proof that there is a dualism between the mind and the body. But then Once people start studying neuroscience and getting to show that there are actually things inside your brain that have something to do with your reflexes or your ability to develop language or even your personality, then the game changes and people wonder, wait a minute, this thing that happens to people when they get older, is this a feature or is it a bug?

Like, is this something maybe we can cure?

And then the game is on and it takes decades and decades for people for scientists to try and find ways to treat it. And in a way, we're sort of still at the start of that of that project.

Let's take a quick break. And when we get back, there's still so much to discuss. Welcome back, everyone. I've been chatting with Robert Kolker about his book, The Vanishing Family, Love, Fate, and the Quest to End Dementia.

Let's get back into things. In your book, you.

Talk about the history of neuropsychology, which you can't do without, of course, talking about Phineas Gage, which is the classic story we love to learn about.

It is fascinating.

I was hoping you could give me just a quick recap of what happened to Gage and how his experience truly altered the way that we think about the division between the brain and the self and how it makes up who we are.

If you've taken a psychology class, you've heard of this guy. The thing about him is when it happened. It happened at a moment before scientists or people really accepted necessarily that the brain controlled personality. So this is a man who was working with a lot of other people to build a railroad in New England. And he shows up for work today and there's an accident and an iron pole goes straight through his head. and he flies 25 feet, and everybody thinks he's dead, but he's not.

He's alive. He's alive, and he's talking.

He's alive, and he's talking, and he actually makes his way onto a horse and cart that takes him to go see a doctor. He gets to the doctor, and he actually talks to the doctor. It's a miracle, and nobody can understand why it happened. And then the meaning of that miracle starts to change. A couple of things happen. First, within a year or two, it's clear that his personality has changed. He's demonstrating a lot of the same behavior that I was telling you about with FTD. He's become kind of a different personality. He's rude. He's impulsive. He's hard to work with. He never really works on the railroad again. He has to find jobs there. He's working alone, like taking care of horses and So he makes a living,

but he is not the same guy. But something else happens too, which is that just within a few years of his death, The Origin of Species is published. And all of science is suddenly interested in finding ways in which the human body might have evolved in complexity.

And that includes people who are thinking about the brain.

And everybody suddenly wants to know, wait a minute, What really happened to Phineas Gage in there, you know, where he could still talk, but his personality changed?

Where exactly did it hit him in the brain? But it's too late. His brain's gone. It's been destroyed in an autopsy.

And all people can do is exhume his body and look at his skull and try and infer exactly where the iron pole went through and which parts of the brain it might have hit. And I kid you not, like there have been at least four different studies using different various forms of technology that have evolved over the years to try to guess at exactly where that.

Iron pole went.

And the skull is still on display at Harvard Medical School in their museum, along with the iron rod, actually, you know, right next to it. There'll never be a real answer because we will not have seen his brain. But the question becomes one that changes over time the more we understand what the brain does.

We understand that.

The frontal lobe, which is The general area where Phineas Gage got hit involves executive function.

And when diseases attack.

The frontal lobes or the temporal lobes, executive function can fly out the window as well. That's why it's in this book, because it's a good way in to talk about what happens to people like the family I'm writing about.

Getting back to this family, that is the focus of your book. In 1990, as you mentioned, Jean, the matriarch, dies from metastatic breast cancer. And this is before she receives any answer as to why she had drastically altered from her younger self. And just a few years later, two of her daughters, Christy and then Mary, also began to show these small changes in personality and behavior, things that in retrospect were the earliest signs of frontotemporal dementia.

Can you take me through how they eventually got the diagnosis of frontotemporal dementia that finally answered so many questions that they had had over the years?

Christy's life starts to fall apart in the mid-90s. And FTD as a diagnosis doesn't really become a real thing until maybe 98 or 99. And she doesn't develop an alcohol problem, but she certainly does do a lot of the things that her mother did.

Her marriage falls apart.

She sits around and doesn't Her personality seems to change. People start to wonder, is this a family trait? When things go bad in our lives, do we just fall to pieces? What's really happening here? They take her to a neurologist and she's diagnosed with Pick's disease, which is sort of an early name for what became one of the FTD varieties out there. They think that she has a short life expectancy, but she blows all expectations away.

And while her personality continues to change, she's as healthy as a horse and keeps on living. And of course, there are some people in the family saying, what's happening genetically in our family? And there are other people in the family saying, I don't want to hear about this. And then years go on and another child, another sibling, Mary, starts to develop some of the same behavior. And that's when at least a few people in the family stand up and say, you've got to be kidding me. Something is happening. It could get us all. What is going on?

And they push hard for a diagnosis. And even then, it takes until 2008 for their diagnosis to be confirmed. They find the genetic mutation in 2008, but science knew about that genetic mutation as far back as 1998. I bring this up because between 1998 and 2008, a lot of people in this family had children. perhaps they wouldn't have if they had known they might inherit a neurodegenerative illness.

And so the disease potentially continues down through not just one but two generations at this point.

When they learned that this was caused by a genetic mutation and they learned about, in their case, that there was a 50-50 chance of each of them developing it, as well as their kids, if they had carried the particular allele, How did they react? I'm sure there was a range of emotions. You mentioned denial. Did some want to get tested? Can you take me through some of these reactions?

There's a woman, Barb, who is sort of one of the main characters of the book. She's the youngest of the nine siblings, and she's the one who's quite often pushing the hardest for a diagnosis. And as soon as there's a diagnosis, you would think she would be first in line to get tested. But the opposite happens. She suddenly shuts down and says, I don't want to know.

And she spends 10 years not knowing. But it's this not knowing that is such torture. I mean, it's like saying, don't think of elephants. Like all day long, you're thinking of elephants. You know, she's monitoring her own behavior. She's monitoring the changes her siblings are going through. She's wondering whether or not to tell the kids. She's trying very hard not to talk about it with her husband because she doesn't want it to dominate their marriage, she is basically terrified and white knuckling it for the next 10 years until she's finally tested. On the other hand, there are other members of the family who decide never to be tested and to remove themselves from the conversation entirely saying, well,

Nothing I can do about it. I'm going to keep living my life. And then there's the complete other side of that. There's at least a couple of people who learned as soon as they had the opportunity. And one of them turns out to be positive. So he spent his entire 20s knowing that he had this mutation. And it changes everything about his life. He no longer wanted to become a college professor because why work for eight or nine years to get a Ph.D.? if that means you're just going to have a career for 10 or so years, you know, it kind of reframes everything about your life. The biggest thing emotionally that hits me about this family, and they're just an amazing family, is that a lot of them say, hypothetically, if I test positive,

I want to, I don't want to live anymore, you know, help me find a way to end my life. And The other siblings say, oh, yeah, I get it.

Sure. No problem.

And then one by one, the people who get diagnosed with the mutation, the last thing they want to do is end their life. And in fact, as the symptoms come, they're even less inclined to end their life because they're quite often quite joyful, friendly people or they're obstinate and oppositional people.

And so you what we think might happen is. isn't always what happens.

And that to me is the window into human nature that the vanishing family offers to all of us who want to get tested for heart disease or want to get tested for these new tests that might test the propensity for Alzheimer's.

You don't know how you're going to act when you know these things.

And one day we'll all know these things at age 10, you'll do a little genetic workup saying what's going to happen to you. And what does that say about how we're going to live our lives after that?

So with this family, they had a test.

They had this ability to see, did they inherit this allele or did they not? But in other cases, like in sporadic cases, it might not be as crystal ball where you can see into the future, will I develop FTD? Can you take me through some of the ways in which FTD is diagnosed? You know, tests like the my girl test and the up test, you know, what do these various different tests measure or capture?

It might start with MRIs to see if there's atrophy in the regions of the brain that are appropriate for FTD in the front or the temporal lobes. And then from there, it might be time for genetic tests. And genetic testing used to be ridiculously onerous. But now, these days, they know that there are at least three major groups out there of genes that are affected, that within those groups, there are lots of different mutations.

But it's less of a needle in a haystack.

So doing a test for those three groupings, you might get a hit and then you go drill down from there and find out exactly what the mutation is.

By groupings, I mean the gene that mutates.

In this family's case, it's the MAPT gene or it creates the tau protein, which you hear about a lot with Alzheimer's disease as well. With the type of FTD that overlaps with ALS, it's a gene called C9 ORF72. And because it's connected to ALS, there's actually perhaps a little more momentum on the research front for the folks with FTD with the C9 mutations.

And then there is a protein called progranulin.

That's another very common among this group, common change in FTD. And that's an interesting one because... that's a protein that reduces. It doesn't overproduce.

It goes away.

And so intuitively, you could think, well, we could cure that one just by giving people more progranulin, inject it into their brain or inject it into their spinal fluid or do something to do it. And so in theory, at least, there's a lot more momentum for the progranulin people too. So it's interesting to see that FTD is really more of an umbrella term than anything else. And then there are other sporadic cases that even if it's a MAPT mutation, it's not something that they necessarily inherited.

And so if you developed FTD, you'd be fortunate to find that your mutation is a common one.

Otherwise, it might be very hard to find.

In which case, is it just clinical diagnosis at that point?

Yeah. And that's the issue with all these dementias, including Alzheimer's.

They talk now about how there are improvements with testing for Alzheimer's, but really they're testing for the presence of a protein that points to Alzheimer's. It's not a There is no Alzheimer's gremlin inside your brain that waves at the scientist from the microscope. It's an inference. The best way to know if you have these diseases is to look at your brain after you're gone. And that's always been the case. And that's one of the things that makes this so tricky for everyone. The other thing I feel the need to say at this point is that we really are at the start of everything, including Alzheimer's.

There are a lot of headlines now about Alzheimer's drugs and how there are people taking them. And that's great that they're taking them and perhaps they're getting some.

Impact from that.

But the fact is that the drugs they've been working on that people are taking now, they've been working on for decades, and they expected them to work way, way better than they have. And it's caused a lot of researchers to scratch their heads and wondering what else they've been ignoring about Alzheimer's.

The people... who teach.

Classes in neuroscience and talk about Alzheimer's will tell you about plaques and tangles. And the plaques are the amyloid beta amyloid protein and the tangles are the tau protein. And I only mentioned plaques and tangles because it took me a lot of time to finally realize that after all these years, scientists really aren't sure still exactly what these plaques and tangles do. They know there's too many of them, but they don't know why. They don't know what they're for. They don't know how to get rid of them exactly. They don't know whether getting rid of them is even a good idea. Don't you need at least a few? They don't know what might happen if you get rid of them, what kind of collateral damage

it might cause to the brain. Fiddling around with the brain is a tricky thing. Sometimes the treatments come in from a left field, like things for other diseases. So we're really at the starting line. And for years, scientists in Alzheimer's have been going after the plaques. They've been going after the beta amyloid protein. And it's only doing a little bit. So now it might be time to check out tau. After, what, 40 years of ignoring it, it's time to pay attention to tau. And then they might have to pay attention to a third thing or a fourth thing. There might have to be precision medicine for people. So we're still at the starting line in a lot of ways with dementia.

Let's take a quick break here. We'll be back before you know it. Welcome back, everyone. I'm here chatting with Robert Kolker about his book, The Vanishing Family. Let's get into some more questions. I want to go back to what we kind of touched on earlier, which was, you know, as you're getting to know this family, as you are learning about their experiences with the diagnosis, with the learning of the results, with the not knowing results, all of these different swirling decisions, did you find your perspective shift at all when it comes to your views on dementia, your relationship with dementia, or whether or not you would choose to get tested for something like this?

Certainly.

Dementia really, as you said earlier, it really hits us close to the bone. When we think about the life we want to be leading when we're older, we think about things like, oh, I want to be at an old folks home with good food, or, oh, I never want to leave my house, or I want to be at the beach. What you don't think about is, will I still be me? Will I still know myself? Will I still know the people I love? Will they look at me and see someone who's gone or will I still be there? That's where you, the place you don't want to go. It's what frightens us the most. And here's a family that will know this sooner rather than later.

They all can take a test to know it. And so it hangs over them. It really weighs on them. But through them, I think readers can process what it means to have this news, what it is to know for sure that this.

Might happen to you.

The loss of oneself isn't just something that's limited to the vanishing family.

It's for all of us. We're all a moving target.

We're different at 80 than we are when we were 20, with or without illness. And so we all are wondering how long we'll be ourselves. This family's just living an exaggerated version of it. So let's take Barb, for example. She's, as a girl, she was a teenager when her mother was falling apart. And nobody knew why. So she kind of had to raise herself. But this is a traumatic period in her life, at least two or three years where the older siblings are all out of the house.

And she's alone with a mother who is really not capable of taking care of her. And so she's raising herself from, say, middle school onward. And There's termites in the house. Sometimes she eats a raw potato for dinner. Like it's grim. It's something she never forgets. So then years go by and some of her older sisters start to get symptoms like her mother and she becomes sure that this is happening to them too. And she has two little children. First of all, she looks at herself and says, I might become like my mother one day.

Then she looks at her children and she says, my children may become like me one day. My children may have to live through something like the most traumatic period of my life, watching their mother fall apart and not be able to do anything about it. And then she looks at her children a second time and says, and they might have it too.

They might end up just like my mother. So it's a triple.

Hit and hard to function after and hard to deal with that.

And then in Barb's case.

She doesn't even see a therapist because she's convinced, at least in her mind, that the therapist would have nothing to say to her. They're not going to change the situation, that it's so uncommon and so unusual that nobody's ever heard about it before. So she really does white knuckle it in those years. And so the book provides a window into her thinking almost year to year as she goes through the question of whether or not to be tested and how to convince the rest of the family that this is genetic, how to get it diagnosed, and then what to do about the question of her children and the question of her marriage, for that matter. At one point, she turns to her husband and says, maybe it'd be better if I just went away. And that

would save everybody a lot of trouble. And they have long conversations about it. It's stunning what they go through, and yet... also in a way kind of relatable because, you know, we all are going to be facing uncertain and unthinkable things that are going to change our lives. Not just dementia, but sometimes it's depression, sometimes it's cancer, autoimmune diseases, things that make us not the people we want to be.

And so I think through this family, there's.

A lot of emotional work that you can get accomplished reading about them.

It is so moving. And And it provides such insight into how different people react to things. And for example, you know, Barb's siblings. Some of them are in denial about this running in the family, even though they are initially contacted by a kind of an extended member of the family saying, hey, this is something else that's happened, which is how they eventually learned. Can you give me a little bit of a window into that first contact through?

I think it was learning about their grandfather who had maybe developed similar signs to FTD.

They had a grandfather who they never knew because he died when the oldest kids in the family were just little kids. Their grandmother remarried, and so they really knew the other grandfather. They didn't know that this genetic grandfather had a sister or they might have heard about it but not been in touch with her. They didn't know that that sister had kids and that one of those kids had a kid. And so they had a second cousin named George who they never met and never heard of.

George was in Los Angeles and his marriage falls apart and he becomes homeless.

I think it's important to pause.

Here and to say there are a lot of researchers out there who believe that a lot of people who are unhoused and who are disturbed may not have just necessarily have drug addiction problems or mental illness problems. They might actually have neurodegenerative diseases like FTD. But anyway, back to George. He gets discovered by his ex-wife who takes him in and starts to take care of him and actually takes care.

Of his mother too.

They are diagnosed eventually with what is most likely frontotemporal dementia, although they don't have a genetic mutation yet. So it's time to try and find other relatives who might be able to help them test. This is long before the era of genetic genealogy. This is like 2005, 2006. So she becomes a detective and she writes a letter to 120 people around the country who have the same last name as George saying, are you related to... this man, and she includes a photograph. And the photograph is of the grandfather, the grandfather who the kids never knew. And one of the siblings gets it and sends it over to Barb. He sits on it for a month or two before sending it to Barb, but he sends it to Barb. This is how complicated and how emotionally thorny

the whole situation is. Barb looks at it and says, you know, holy crap. And they're off to the races. Suddenly there's a whole other wing of the family that can be tested for this. And nobody needs convincing anymore. And off to the Mayo Clinic they go, you know, 14 of them maybe to get tested. And suddenly it becomes easier to potentially find a genetic culprit here. But this is after an enormous coincidence that may never have happened.

And who knows how many other families are out in the cold in this way.

One thing I really appreciated about your book was how you drew attention to the immense challenges faced by caregivers of people who have frontotemporal dementia, which often ends up being family members, as it was in this family. What impact does this disease have on the individuals who are caretakers of those with FTD?

In the book, I focus on a sister in the family named Sue, who ends up becoming a full-time caretaker for Christy, who has FTD.

And she doesn't start out thinking that.

It's going to be the rest of her adult life taking care of her sister, but it sort of creeps up on her. So you see the frame of mind she's in in the beginning when it's time to, you know, someone needs to come in and look after Christy and nobody knows what she has. And then you see her frame of mind as she's finally diagnosed and it's time to look after her for maybe a short amount of time.

And then you see her a few years after that when it's really diagnosed and it becomes clear that she could lead a normal lifespan. And so that means decades more with Christy.

And you see just how enmeshed the two have become.

Caregivers are amazing people, but they aren't necessarily learning what you might expect from the movies. Just an emotionally fraught person who is crying and on their knees and pushing hard. Or instead, A lot of caregivers who are in it for the long haul have very good control over their emotions. They're able to mourn the person that they are losing in kind of a compartmentalized way. And then they can lead their lives minute to minute or challenge to challenge or day to day. What do we have to do today?

What has to get done today? And they can sort of keep those emotions in a box. And in this case, Sue really fits that profile. There's good research at Berkeley actually done on caregivers and their psychology. And the more successful ones all seem to share this ability to change channels in a way. When you need to, you change to that channel where you're crying and you're really sad.

But otherwise, you're able to really get things done.

You said that this family reached out to you four years ago and you began getting to know them, getting to know their story and tracing developments as they happened. Can you give me an update on how the family is doing today?

I'm pleased to tell you that just this morning, I was texting with some members of the family who are at the biggest Alzheimer's and dementia conference of the year.

You know, we're taping this in July right now.

So, This morning, there was a big talk from Biogen, which has a drug that they hope reduces the tau protein in people with Alzheimer's. This is a drug that the family that I wrote about and lots of other MAPT gene FTD families have been dying to get their hands on ever since they first heard about it for maybe a few years now. And the news from phase two of this drug is extremely positive. It actually is reducing tau in people with Alzheimer's disease. And so this family wants in. now, if not sooner. They're wondering what took so long. The theory here is that if the MAP-TFTD people produce too much of this protein, and if this drug can actually reduce the amount of protein, maybe it can slow the progress of the illness.

Maybe this is the first of several drugs.

And for Alzheimer's, it's a huge game changer because, as I said before, everybody's been putting their eggs in the other basket. And they've been working on the beta amyloid protein. So the tau people now are sitting there saying, at last, our time has come. There's probably going to be a pharmaceutical feeding frenzy, other people trying to do other tau drugs.

So it's an optimistic day for this family. Two of the three family members I talked to who are there, they are positive for this mutation.

So it's personally good news for them.

And it is encouraging.

I mean, as you mentioned, awareness of FTD is still quite low. And we really only knew about this disease within the last few decades. Can you take me a little bit through how we came to learn about FTD and how awareness is still an issue today?

Yeah, it's a story really about scientific groupthink and about institutional momentum.

And it takes place over decades.

Without getting too historical on you, Alzheimer's first becomes a named condition in 1910 or so. And for the next 50 years, nobody really does anything about it because there isn't much to be done about it. And it's thought of as sort of a rare dementia and it's sort of put in a box and thought to be different from senility, different from.

Old people, you know, losing their faculties.

It's thought to be like a very peculiar thing But then some technology happens. The 60s turn into the 70s. Everyone has electron microscopes. They're starting to develop technologies that later become like MRI technology.

You can actually look at brains.

And by 1976, somebody publishes an essay in a publication that says, you know, if all of the people out there who we say are senile actually had Alzheimer's, then it would be the third or fourth generation biggest killer behind cancer and heart disease and auto accidents. And very, very quickly, this semantic change happens. And so by 1980, Alzheimer's disease becomes almost interchangeable with senility. I think all of us have this experience. You say, you know, somebody has Alzheimer's and you go, oh, that's too bad. But the fact is they may not really know if that person has Alzheimer's until that person dies. So it's good news in a way because it means hundreds of millions of dollars in research money because now the whole medical

establishment and research establishment has a goal. They have a thing that they want to attack, like cancer. But in a way, it's bad news, too, because if everything's Alzheimer's, these rarer dementias like Lewy body's dementia, FTD, they all get sort of lumped in together with Alzheimer's and it pollutes the test pools.

It pollutes all of the scientific studies.

And there's this bad situation from the 80s up until the late 90s where FTD gets sort of overlooked. Only in the late 90s when there was better and better genetic technology available that did a minority of researchers come forward and say, hey, you've been looking at the plaques, but the tangles are up to something. We keep finding more and more dementia disorders where there are no plaques, but the tangles are causing the trouble. Don't you think maybe you should be looking at the tangles in Alzheimer's too?

And the Alzheimer's field pushes back. They push back for years thinking, no, no, no, it's all amyloid all the time.

20 years goes by.

Until finally, a few years ago, they finally have success with their amyloid drugs, but it's a drop in the bucket. It's just slowing down the progress of the disease.

A small amount.

So now, finally, it's time to look at tau, which is, again, it's a player in a lot of FTD, and it's a player in a lot of other rare dementias as well.

In the process of writing this book, in researching the long history of dementias, the more recent history of frontotemporal dementia, in getting to know this family, becoming friends on a text basis with them, just taking a step back and seeing the scope of frontotemporal dementia, where are you hopeful about?

I think we are inching closer.

I think that So far, the meds that have come forward that help with the symptoms are being given to people who are basically already symptomatic. But I think we're just a few years away from some people wanting to take these drugs when they're 30 because their mother and their grandfather both had Alzheimer's. And then, you know, perhaps it actually really helps. Like there might actually be a preventative aspect to some of these medications. So we're, I think 20 years from now, the world may like be very different with dementia. I also think that people understand there's a diversity of dementia now, that it's a lot of different conditions.

Certainly, Parkinson's has.

As big a profile now as Alzheimer's, and there are people like Bruce Willis who... raising awareness about FTD. And so that's important too. And also I think the knowledge that everyone gets something is interesting too. I should mention, I'm in my 50s and the other day I forgot Ryan Reynolds's name, right? Like I was looking at a picture and I was like, I know that guy, I know who it is, but I can't think of the name.

There is a certain very common form of cognitive decline that happens that has nothing to do with Alzheimer's, has nothing to do with the severe dementias, and isn't progressive and doesn't get worse.

And primary age-related.

Typopathy is one of them, but there are a couple of others as well. And so all of this focus on cognition and cognitive decline, sometimes it's the bad thing, but sometimes it's the normal thing. And so I think that's important for listeners to keep in mind as well.

Bob, I mean, this has been such a wonderful conversation. Your book was truly impactful. It has stayed with me and will stay with me for such a long time. And I want to thank you so much for taking the time to chat today.

Oh, please. Thank you, Erin.

I'm just glad to talk about this amazing family, and I'm sure that people will get something out of learning about them.

A big thank you again to Robert Kolker for taking the time to chat with me. If you enjoyed today's episode and would like to learn more, check out our website, thispodcastwillkillyou.com, where I'll post a link to where you can find The Vanishing Family, Love, Fate, and the Quest to End Dementia, as well as a link to Bob's website where you can find his other work. And don't forget, you can check out our website for all sorts of other cool things.

including but not limited to transcripts, quarantini recipes, show notes and references for all of our episodes, links to merch, our bookshop.org affiliate page, our Goodreads list, a firsthand account form, and music by Bloodmobile. Speaking of which, thank you to Bloodmobile for providing the music for this episode and all of our episodes. Thank you to Liana Squilacci and Tom Breyfogle for our audio mixing, and thanks to you listeners for listening. I hope you liked this episode and are loving being part of the TPWKY Book Club. A special thank you, as always, to our fantastic patrons. We appreciate your support so very much. Well, until next time, keep washing those hands.

Special Episode: Robert Kolker & The Vanishing Family

Kapitelklicken springt direkt hin

Shownotes

Transkriptvom Podcast bereitgestellt · Zeitmarken springen hin