Episode 52 | Dr. Lisa Genova, Ph.D. | What You Can Do To Prevent Alzheimer’s


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Kathy Smith:                   Lisa, welcome to the show and congratulations on the XPRIZE Award.

Lisa Genova:                   Thank you so much.

Kathy Smith:                   Let me ask you. It seems that there was so much press around it and about the win and the expectations of what’s to come. It seems like now is really a great time to start changing the world’s perception of this disease. Can you tell us a little bit more about what is the purpose and the focus of the prize?

Lisa Genova:                   The prize is–for people who aren’t familiar with the XPRIZE, the language can be a little confusing to those who are unfamiliar. The idea is to create a competition for anyone to get involved that can form teams to try and solve this problem that hasn’t been solved by the traditional established means. The folks who are typically working on Alzheimer’s tend to fall into two camps. They’re either academic professors, scientists who are associated with universities or people who are in biotech and pharmaceutical companies.

Those folks tend to be biologists, neuroscientists, people who have been trained very specific way to think about the problems of the brain, and they tend to work alone, and they tend to work on one project at a time. It’s very linear and so, it’s very slow. So, the idea behind this competition is that anyone who might want to think about this problem of how do we prevent or stop the progression or cure Alzheimer’s? Anyone who wants to jump in can. So, we might attract physicists or imaging specialists or data hackers or combinations of any of those folks who, then, can put together a proposal and work on a means of detecting the presence of Alzheimer’s pathology in its earliest stages, and such detection will, then, lead us to a way to prevent or stop the disease.

Kathy Smith:                   So, you don’t have to have an MD or a PhD or anything after your name. This could be somebody in the fitness world or nutrition world or somebody that has been, perhaps, even somebody in their immediate family that may have Alzheimer’s and they use some kind of techniques that they think might be effective in detecting or preventing?

Lisa Genova:                   Absolutely. Yeah, the idea is today that we’ve got the technology that exists now, the exponential technology, information being used and shared in ways that we just couldn’t imagine 10 to 20 years ago. So, this just brings more people to the table. This is a huge problem that is affecting humanity on a scale that we’ve not seen before. If we don’t do something about Alzheimer’s, there stands to be the economic, emotional sinkhole of the 21st century.

We have 50 million people worldwide who have this now. Baby boomers are getting older. Age is the number one risk factor for this disease. Right now, we have one in three people at the age of 85 will have Alzheimer’s. We’re going to have 150 million people worldwide who have this by 2050 if we don’t do something.

So, the idea is how do we invite the world’s best thinkers to solve this problem? I love thinking about–you talk about fitness a lot. You probably talk about heart health, so heart health is something we’ve gotten really good as a culture of thinking that we can do something about. We can prevent, we can go to the doctor, we can exercise, eat Mediterranean diet, on and on. This wasn’t the thinking 30, 50 years ago. Interestingly, one of the things that changed that field entirely is interventional cardiology, the way that minimally invasive cameras can go in and look at your blood vessels and see what’s going on and that helps inform what sorts of intervention might work to help prevent me from getting a heart attack and dying.

These imaging specialists aren’t cardiologists. They aren’t cardiothoracic surgeons. So, some of the solutions in heart health has come from people who never studied the heart is my point. So, we might find a solution to Alzheimer’s Disease from folks who aren’t neuroscientists and XPRIZE sort of leveled the playing field. Anyone who might be able to think about this is now invited to the table.

Kathy Smith:                   It gives more and more people the opportunity to give their input. Well, let’s talk about heart disease. We discovered that heart disease and the blood vessels and the plaque and the closing down of blood vessels and the hardening of blood vessels, but tell us about Alzheimer’s and the progression of Alzheimer’s and what exactly is happening in the brain and what are the first symptoms that people start noticing?

Lisa Genova:                   It’s interesting, because the biology of Alzheimer’s happens, we think, 10 to 20 years before we actually even notice any cognitive memory symptoms. The disease pathology, we think, begins as an increase in a protein called amyloid beta. It starts to accumulate in the synapses, which are the spaces between two neurons where they communicate.

At first, this accumulation – before it reaches what we refer to as a tipping point – you don’t notice it. The cells still communicate, the synaptic function isn’t compromised. The reasons why amyloid beta accumulate aren’t entirely understood, and there’s tons of research on this right now, with ideas having to do with Type 2 diabetes, a leaky blood/brain barrier, possibly having to do with a compromised immune system. There are lots of hypotheses floating around out there and lots of active research as to why amyloid starts to increase. But around the age of 40, we think it starts to increase and accumulate. But you don’t notice anything’s amiss yet.

Over time, as it reaches the tipping point, then you start to notice some memory glitches. So, instead of just, “Oh, where did I put my keys? Why did I come in this room? Oh, what’s her name.” Those are normal memory problems that don’t have to do with Alzheimer’s. In fact, as I said in the TED Talk, I always let people know who are panicked about those little senior moments and are like, I can’t remember the movie title or the actor’s name or this person’s name, you probably weren’t thoroughly paying attention to where you put your keys in the first place, so it’s not even a memory issue. We live in such a distracted world today. A lot of our “memory problems” have to do with probably with attention.

After the tipping point, the memory glitches are different. So, it’s like you’ll find your keys in the refrigerator or you find them and you’re not entirely sure–you can’t quite remember what they’re for. You forget someone’s name, but you can’t remember–and oftentimes when we have that tip of the tongue like “Oh, what’s her name,” you usually remember it begins with K or, oh, it has two syllables or I can picture her husband. You have some associations and some language clues that sort of are trying to help you get to that word. When you have Alzheimer’s, you don’t have any of those clues. The associations drop out.

There’s disorientation. There’s memory, language and cognition issues that start to happen that are different.

Kathy Smith:                   I know that you mentioned neurons and, then, you mentioned the synapses – the space between the neurons. Does amyloid beta cells–they start to accumulate and what’s interesting is with the information that I read in some of your interviews and such about how do we sweep away–how do we, on a regular basis, get rid of those amyloid beta cells. Also, how do we keep increasing the neurons so that we have more and more neurons to play upon, to call upon?

Lisa Genova:                   It has two distinctions. Amyloid beta is a protein. It’s not a cell. Your neurons are cells. In your brain, you have neurons and you have glial cells. So, how do we clear away–how do we prevent this accumulation from happening in just our day-to-day life? Is there anything we can do about this or are we all just destined to get Alzheimer’s as we get older?

It turns out, like heart health, we can have a big impact on our brain health. We can’t do anything about what you’ve inherited from Mom or Dad. Some of us have an increased risk of getting Alzheimer’s and some of us have less of a risk of getting the disease. Five percent of people who get Alzheimer’s have a hereditary form like Alice Howland in Still Alice where they’re going to get the disease no matter what happens. For 95% of us, we can actually have some impact on this. So, what can you do?

It turns out that heart healthy actually impacts brain health. So, we know that high blood pressure, obesity, diabetes and smoking increase your risk of Alzheimer’s significantly. We know that aerobic exercise clears away amyloid beta actually better than any pharmaceutical that we’ve seen so far. Lots of animal studies show that aerobic exercise clears away amyloid. So, we know that there’s a connection between heart health and Alzheimer’s.

There’s a couple of longitudinal studies out of Europe that came out this past year that showed that a Mediterranean diet decreases your risk of dementia by a third. So, while we don’t understand the mechanism yet, we know that heart health is going to improve your chances of not getting Alzheimer’s.

We also know that sleep has an impact on amyloid beta, which I found a little disturbing, because for many, many years between having three children and a career, I don’t often get enough sleep. But it turns out that in slow-wave deep sleep, our glial cells in our brains, these are sort of like the janitor cells that sweep away debris that’s accumulated in the synapses, in those spaces where cells communicate. They clear away metabolic debris that have built up there during the day. While we’re sleep, it’s a chance to clean up. So, normally in deep sleep, the glial cells do this.

But what happens if you don’t get enough sleep? If you deprive yourself of enough slow-wave deep sleep, the glial cells haven’t had enough chance to sweep away the debris. Well, one of the things in the debris is amyloid beta. So, if you don’t get enough sleep, you’re starting the next day with some extra amyloid accumulated.

Interestingly, studies have also shown that a lack of sleep actually leads to more amyloid being produced. So, it’s a positive feedback loop – that you don’t clear enough away and you make more if you’re not getting enough sleep.

Kathy Smith:                   So, sleep is a good thing, which I love to hear because I love to sleep. Let me ask you; can you clean away some of this metabolic debris through meditation? Would that take you down close to the slow-wave deep sleep? Is there any research on that?

Lisa Genova:                   That’s a great question. I don’t know if those studies have been done yet. I’m sure someone’s working on it. I do know that meditation is great for reducing stress levels. This isn’t just a feeling. The physiology of stress actually compromises our memory if we’re chronically stressed.

Normally, the stress cycle in our body is intended to be a response to an acute crisis. So, evolutionarily, if there’s a predator chasing us, it’s a quick fight or flight. In your brain, a neurotransmitter is released from the hypothalamus to the pituitary. The pituitary releases a hormone onto your adrenal glands, which sit on your kidneys, and those release adrenaline cortisol. So, it’s run, it’s heart-pumping, it’s big response to this thing that’s supposed to be quick. Interestingly, that adrenaline, then, goes back to the brain and shuts off the hypothalamus so that this whole thing is just an on and, then, a quick off.

With chronic stress, it turns out that the receptors in the brain start to either be down regulated or insensitive to the adrenaline, and the shut-off valve breaks essentially. So, we’re just constantly dumping adrenaline into our system.

In addition to that, we end up with a dampening of our ability to shuttle information from short-term memory into long-term memory, so we can have compromised memory with chronic stress. So, meditation, by reducing levels of stress by learning to be present and calm and non-reactive, we can get that balance back to that hypothalamic-pituitary-adrenal access.

Kathy Smith:                   Yeah, it sounds like that cortisol and that dumping of cortisol in our bloodstream is bad news for several reasons. It’s the domino effect.

Lisa Genova:                   Absolutely.

Kathy Smith:                   It creates everything from weight gain to anxiety, depression and, now, we’re hearing even–

Lisa Genova:                   Compromising the immune system. Yep. Memory problems. Yep.

Kathy Smith:                   Well, you mentioned exercise as being at the top of the list of what everybody–some aerobic exercise of what everybody should be doing to help stave off some of the symptoms and the disease itself. So, I wonder if there’s been much research done on exactly the type of exercise or if it matters, whether you go out for a walk or if it has to be intense exercise, like interval training or whether strength training falls in that category.

Of course, I always come up with yoga because that serves the purpose of not only giving the circulation through your body but also destressing you. Any thoughts on that or is there any exercise in particular that you’re seeing that gives the biggest bang for its buck?

Lisa Genova:                   Again, this is a great question, but these studies haven’t been done. The exercise studies have been done in mice in terms of actually measuring the amyloid beta that gets cleared away.

In terms of people, the studies that have been done have been putting them in a PET scan where they get injected with a radio-labeled amyloid and measuring for those levels. Yet, although the studies are interesting and people want to do them to show the direct connection between exercise and amyloid levels in the brain, the studies have been more correlational.

So, studying–again, these longitudinal studies where people in different groups are exercising or not exercising. There’s a study called the FINGER study that folks can look up to see what sorts of specific exercises they did. I can’t really remember the regimen, but some exercised and some didn’t, and some were on a Mediterranean diet and some weren’t. The folks who had the exercise and diet fared significantly better in terms of memory and cognition than those who were sedentary and didn’t eat the healthy food.

Kathy Smith:                   It’s such great news to think that that statistic that you said earlier – that only 5% of this whole disease is really genetically driven. Then, we have the other 95% that you can, with exercise and diet, you can create your own destiny in a sense.

So, let me ask you, because when it comes to exercise, we know there’s a couple of factors going on when it comes to the brain. One is this idea of creating new neurons and also this idea of neuroplasticity. We’ve all been told early – when we turn 40 to start doing your crossword puzzles, start doing your Sudoku or whatever it is that you do to stimulate the brain. Yet, there are so many studies that show that exercise is a key component in developing this plasticity. Am I accurate or not?

Lisa Genova:                   A little bit, yeah. There’s two things: one is can you stimulate the growth of new neurons and the other is can you make new neural connections. So, it turns out that yes, again, especially in animal models, we’ve seen that exercise can actually stimulate the growth of new neurons in certain parts of the brain. When I was being trained as a neuroscientist, we were actually taught that you could never make new neurons as adults. So, this is phenomenal news for lots of reasons and lots of areas of research where you might ideally want to grow new neurons in spinal cord injuries or ALS or Huntington’s or Parkinson’s and even Alzheimer’s. Without those advancements in medicine to grow new neurons and while exercise may have some effect on that or not, what we really know and what I really want to encourage your listeners is to learn new things, because every time we learn something new, we are creating and strengthening new neural connections, new synapses.

So, again, this is a disease of the synapse. Alzheimer’s begins in the synapse connection where neurons communicate information. It turns out that we make and lose those neural connections all the time. When you say neuroplasticity, that’s what we mean. The brain isn’t the same day to day. So, right now, I’m having a conversation with you and we’ve never talked before. So, I am listening to you and I’ve read your bio and gone to your podcast, and I’m developing new connections that will help me in the future if someone says, “Hey, have you ever listened to a Kathy Smith podcast,” I have lots of information now I can draw from that didn’t exist yesterday.

One of the things I tell folks is–so the idea exists with Alzheimer’s. So, say I have Alzheimer’s and say I only know one thing about you, Kathy. Say I know that you have a podcast and that’s the only thing I know. Say I have Alzheimer’s and that amyloid beta has reached the tipping point and it’s caused tangles in the neurons and information and cell death and that synapse is now dead and the neurons are gone. If someone asks me, “Hey do you know anything about Kathy Smith,” I can’t even remember who you are. That’s it. I’ve forgotten you forever. But what if I knew 10 things about you? What if I built nine additional neural connections, associations, things that can understand and know about you? Then, when someone says, “Hey do you know Kathy Smith,” I have nine other – think of them as roads – I have nine other roads to get around to detour that wreckage of that Alzheimer’s Disease.

So, I tell folks crossword puzzles aren’t really doing what we want because those tend to retrieve information that we already know. So, we’re traveling down roads that have already been paved and laid down and are there in our brains. We want to build more neural roads, more neural connections. So, this is really about reading a book, seeing a movie, making new friends, learning to play `piano, traveling to a new city, exploring new neighborhoods. Those actually build new connections in your brain.

Kathy Smith:                   Well, expanding upon that thought, then, I know for me–and I know that this is not scientific, but just from a personal point of view, I find that: one, if I go and do something like let’s say I read a book or I go see a movie. If I leave the movie and don’t discuss it, don’t think about, don’t talk about it, then I literally two weeks later might not remember the name, the people and I might even think, “What was that movie about?” But if I leave and, then, sit down and say, “What did you think about such and such,” or “What do you think they meant by that,” or “What did you think about that actor?” I, now, have imprinted that and it seems if I do it one more time in the next couple of days, I’m more likely to retain that information. So, that’s one little thing that I do.

Lisa Genova:                   You’re getting at something called rehearsal. So, think about anything that you do in life. If you do it once and never again, you’re probably going to have a hard time knowing how to do that. Likewise, remember something. If you think of something once and, then, you never think about it again, it’s hard to, then, remember anything about that. But if we rehearse that information, if we draw–so, if you see–this happens to everyone with books and movies. You go through it. Let’s say it’s a movie. It’s 90 minutes. If you never discuss it again, that information, went in your brain, you had the experience, but then, it might not get shuttled from short-term memory to long-term memory because it wasn’t rehearsed or reinforced in some way.

So, if you, then, go to dinner afterwards and you discuss it with friends and you talk about various details like, “Oh, that’s like when I was a kid, I remember this,” or you talk about the big emotions like, oh, when the husband died, there’s grief that you can recall from your own lives, and if you can draw rich associations especially if they’re emotionally based, you are going to help lock in that memory and it’ll be richly supported by sights, sounds, emotions, who you were with, where you were. It’s sort of like when we have for sort of I guess really upsetting, catastrophic, surprising events like when the Twin Towers were crashed into and came down or for older folks when JFK was shot. Big, upsetting, surprising information that big emotion helps most people remember where they were when those events happened or who they were with and what they were wearing that you normally wouldn’t remember what was going on, on that day. But that big emotion helps you rehearse it and experience it over and over.

Kathy Smith:                   So true. We all remember where we were those days that you mentioned.

So, Lisa, your brilliance to me – you can take all these scientific and complicated topics and explain them in such an easy-to-access way for most people to just understand. So, I think your storytelling is unbelievable, and I think that’s obviously why, as I mentioned earlier, you wrote the book Still Alice. Julianne Moore won best actress – the Oscar – in 2015.

One of the things that when I saw Still Alice that just stuck with me was the idea that–just to refresh our listeners’ memory if they’ve seen it or haven’t. If you haven’t seen it, go see Still Alice and read the book. She was a Harvard professor and she started to notice changes in her brain function, and all of a sudden, you see it, as we talked about today. It was impacting her daily routine and, then, her relationships with her husband and her children. One of the things that I find interesting when I hear you describe your books – and this book in particular – is that you call it a love story, and you call it this idea of how we love ourselves, how we view ourselves and, then, how we love the people around us. Can you expand on that a little bit?

Lisa Genova:                   Yeah, well, I think all of my books are really about empathy and love when you boil them all down. My background’s in neuroscience, but I write novels about people who are living with neurological diseases and disorders who tend to be ignored, feared and misunderstood. So, I think that narrative is a way for a way for us to walk in someone else’s shoes and to imagine what that experience is like. Because I think for a lot of us, if Alzheimer’s doesn’t affect your family directly, it’s easy not to think about it. Then, if it does affect your family directly, there might be some shame and stigma and alienation that goes along with that and you don’t tell people what’s going on and you feel you need to be quiet about it.

Unfortunately, a couple of things: if we’re not talking about these diseases, if people aren’t expressing a sense of urgency around Alzheimer’s, if they’re pretending it doesn’t exist for various reasons – whether it’s fear or shame or stigma – it’s awfully hard to cure something that seemingly doesn’t exist. Like, we really need the social outcry and the urgency and the interest to get this done, which is one of the reasons why XPRIZE feels really timely right now.

The other is that if people aren’t talking about it, folks get excluded from community. We, as human beings, don’t like to be around something that’s unfamiliar. It makes us really uncomfortable and we don’t like to feel uncomfortable. So, we’re going to look the other way if we don’t know what something is.

So, I write these books to help people become familiar with the unfamiliar and, so, the stories are about Alzheimer’s or ALS or Huntington’s or autism or brain injury. But they really all are about a human experience, so the experience has to be despite this disease or this crisis or this condition that is very unusual or different, how are we all connected? How ids my identity as a human being not erased by a disease like Alzheimer’s? How can I still matter? Who am I if I can’t remember who I am, if I can’t remember my children or what I used to do? These books are all a chance at seeing yourself in the other and understanding that the human spirit is quite resilient, that despite any of these diseases that they don’t take away our ability to matter and love and be loved.

Kathy Smith:                   Yeah. And be loved. I think that’s a key factor – this unconditional love that you write about your books where people really step up or just are profound in the way that they give in these kinds of situations. I think starting to develop that empathy for people that are going through different phases in their life, whether they’re these neurological diseases or just–not just–but things like addiction or other issues that people have where a lot of times we can’t relate. I think as we start to feel through your stories in our beings of how people deal with families, with children, with grandparents, it brings everybody closer together. It brings the community together.

And the more you talk–I know in my family, we have depression, and until we started shining a light on that, it was very scary. It was a very scary place and all the things you mentioned. There’s embarrassment, there’s fear, there’s the unknown. Once you shine a light on it and people laugh about our family situation, because there’s humor around it, there is acceptance, there’s all these things and it just becomes an easier process. So, for that I thank you. But let’s talk about your next book that’s coming out in March.

Lisa Genova:                   Yes. It’s called Every Note Played, and it’s about a concert pianist with ALS. I chose to write about ALS next because one of the two directors of Still Alice was diagnosed with ALS just before he read the book. So, he co-directed that film, unable to speak and paralyzed in one of his arms. I asked him shortly after the film premiered if I could write about ALS in his honor and he, of course, generously said, “Yes.”

So, this book is about ALS and I want in part–and not only his honor–but also in part, I think most folks in this country have heard of those three letters. They’ve dumped a bucket of ice water over their heads and maybe they’re familiar with Steven Hawking and his story. Maybe they saw The Theory of Everything with Eddie Redmayne, which is phenomenal. But I think that might be it. There’s sort of a surface level of familiarity with it but not an understanding of what it feels like to live and die with that disease.

So, again, I wanted to shed a light on what that’s like. And story-wise, it became obvious to me that this is a disease that paralyzes you. So, your motor neurons and your brain and spinal cord start to degenerate, and the muscles that they feed become paralyzed. So, eventually your entire body becomes paralyzed, which includes your diaphragm so you can’t breathe anymore. So, if you don’t get a tracheostomy surgery and go on 24/7 life support, your average life expectancy with ALS is about three years. So, it’s really fast.

While that’s an experience that hopefully most of us don’t experience directly, how many of us are paralyzed in some way in our lives where we don’t allow ourselves to do or be what we really want? We have fears or excuses or blame or self-imposed limitations for reasons why we can’t strive for something or try for something or do something. Or how many of us feel paralyzed, trapped in relationships or a job that’s unfulfilling but we have reasons why we think we need to stay or we have shoulds in our lives that keep us stuck.

This idea of communications, eventually people with ALS can’t speak anymore. And today, in 2018, there are lots of amazing augmentative communication devices that allow people to speak with their eyes so they can look at letters on a keyboard and string together words that can, then, be spoken through the computer. It’s painstaking and difficult, but it’s still an amazing advancement for folks who are dealing with ALS.

But for the rest of us who can speak and say anything we want, how many of us actually say the things that need to be said while we’re still here? So, how many of us apologize when we need to, forgive when we need to, say “I love you,” to the people who we love? So, the book is a chance to explore all the ways that we might communicate better, that we might live a more fulfilled and free life.

Kathy Smith:                   So fascinating, and I’m actually heading to a silent retreat in about a week. I do it every year where I spend four to five days not talking.

To your point, when you don’t have the ability to talk, how you start, then, to develop your other senses including your intuition. But you sit and you’re present with people, not feeling that you have to comment on everything or talk out of boredom, out of fear, out of not liking the silence and it allows you to be in the silence. You discover another aspect of yourself. I know that’s not what you’re talking about, but I do feel that when I go to these retreats, I start to look at people more, start to understand people more. I start to think about how I am communicating when I do communicate. So, I can imagine what this book’s going to be like and I can imagine for somebody like myself. I cannot wait to read it. I cannot wait until its launch date, which is March 20? Is that correct?

Lisa Genova:                   Yes, it is. Yes. And I’m glad you mentioned that because for the folks with ALS who begin not to be able to speak–actually with all the books. When someone has a disease that’s fatal and that can’t be cured, I always try to look for the ways that there can be healing and growth despite all of the compromise and the fact that it can’t be cured. Like, we can’t heal the disease, but in what ways can maybe through that stillness and a chance to be quiet and a chance to face mortality, where can there be growth and healing? I’ve definitely witnessed that over and over again. It’s incredibly humbling and inspiring.

Kathy Smith:                   Well, you’re an incredible woman. I just have to say everything you do inspires me. I thank you for being a guest today.

It sounds like from our talk today that you’re hopeful that there is a future where we might be wiping this mind-blowing disease of Alzheimer’s. Are you hopeful?

Lisa Genova:                   Absolutely. Yeah, we didn’t have the technology 10, 20 years ago to really do this yet. I think that the sense of urgency is reaching enough people with Bill Gates throwing his hat in the ring, with our Alzheimer’s team at the XPRIZE summit winning and getting funding, so we’re launching that this year. I just think–I’m not discouraged. We’ve seen advancements in–we have cancer survivors, we have HIV survivors. People don’t get polio because we have vaccinations. There’s no reason to think that we can’t wipe this disease out. We have to, so we will.

Kathy Smith:                   With people like you working on it, I’m sure we will. For everybody listening, be sure to check out Lisa’s upcoming book Every Note Played which, as she mentioned, comes out on March 20. And you can learn more about everything she’s doing at LisaGenova.com. Lisa, thank you so much.

Lisa Genova:                   Thank you so much, Kathy.

Kathy Smith:                   Ok. Bye-bye.

Lisa Genova:                   Alright. Thank you so much. Bye.