Memory And The Brain

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0:44And even change you. I literally feel like I'm a different person. Yes. Do you feel that way? Ideas worth spreading. From TED and NPR. I'm Manoush Zomorodi. On the show today, memory and the brain. So it was a few years ago. I was somewhere in my mid-40s. And I drove from Cape Cod to Cambridge, Massachusetts to give a talk. This is neuroscientist and novelist Lisa Genova. And I parked my car in a parking garage. And I was a little bit late. I was running late. So I got out of the car quickly, ran off a couple of blocks to the venue, gave my one-hour talk, signed some books, and I was done within an hour and a half.

1:33I'm back at the parking garage and I could not remember where I parked my car. So I thought I had parked on level three, but I couldn't find it there. So maybe it was level four or could be level five. I wasn't sure. So I'm walking up and down the ramps. I'm in heels. I'm sweating. I'm anxious. I'm frustrated. I'm pressing the button on my car remote, hoping to see the flashing lights or hear a beep beep. I'm seeing nothing. I'm hearing nothing. I'm starting to panic. I'm thinking the only explanation left is my car has probably been stolen. And I'm about ready to call a friend who's a Boston police officer to ask what to do when I finally just randomly happen upon it exactly where I had parked it on level three.

2:19And so I'm frazzled and I'm so upset with myself and I want to blame this whole frustrating experience on my memory, but the neuroscientist in me stepped in and saved me. Maybe you've had a moment like this, losing your car, misplacing your keys, walking into a room and not remembering what you're there for. A lot of us in that moment might have a heart-stopping thought, something's wrong, this isn't normal. But Lisa says actually it is. Not remembering where I parked my car actually didn't involve my memory at all. It was an issue of distraction. Because I didn't pay attention to where I parked, I never formed a memory of where I parked in the first place.

3:09There's this misconception out there, this expectation that memory is supposed to be perfect, that we're supposed to remember everything. And so that when we forget anything, people think it's a sign of aging or impairment or impending Alzheimer's. But no, this is the price of owning a human brain and you're okay. So today on the show, a conversation with neuroscientist and author Lisa Genova on memory and what's normal and not normal in the brain and what we can do to keep our brains healthy throughout our lives. So Lisa was in the lab researching the brain for years. But in 2007, she veered in a completely different direction, at least for a scientist.

3:55She wrote a novel called Still Alice. It's a book about early onset Alzheimer's. Still Alice became a bestseller and was later adapted into a movie starring Julianne Moore. Since then, Lisa has written four more novels, each about a person living and coping with a different neurological condition. Her latest book, though, is a foray into nonfiction. It's called Remember, the Science of Memory and the Art of Forgetting. You know, I have a lot of empathy for folks out there who, you know, don't know the owner's manual to their own brains and their memory and how it works. And so I wanted this book to feel really gentle and conversational about, okay, here's how your memory works.

4:42Here's what it's great at and amazing. It's really, you know, an incredible superpower and it's highly fallible. And here's what it's not good at. So what can we reasonably expect of it and how can we help support it? In your book, you write this sentence that I underlined, which is of all the complex and wondrous miracles that your brain executes, memory is king. And that took me like for a minute, I was like, wait a minute, really? Like, what about the part that can make my body move its limbs? And what about breathing? And what about all these other things that my brain can do? Yeah. Memory is essential to the functioning of almost everything we do.

5:26You need memory to walk, right? You learned how to walk. Everything you learned how to do is a memory. So we tend to think of muscle memory as something, maybe a lot of folks think muscle memory lives in your muscles. But no, this is the memorized choreography for how to type emails, how to drive the car, how to brush your teeth, tie your shoes, and so on. We need memory to recognize the people in our lives, the people we love, our family, our friends, our coworkers. We need memory to know who we are, the story of our lives, your biography, your narrative, what happened yesterday, 30 years ago.

6:06Without memory, we're really untethered to the life that we live. Let's talk about the basics because, as you say, very few of us even know how memory works. And you ask us in the book to picture a penny in your mind. And you had eight photos of pennies and they all look different. And you were like, which one is the right one? Which one really does look like the actual penny that you probably have in your wallet? And I was like, I don't know. I'm not sure. Yeah. And so it is astounding, right? And I want folks to know that at any age, your memory is limitless in what it can remember if it is given the right kinds of input, it if you support it with the right tools.

6:55But memory at any age, whether you're 20 or 70, is going to be highly fallible for certain things. And so we can't remember what we don't pay attention to. You can't remember what a penny looks like in detail unless you're a coin collector. Unless you've studied the coin and paid attention to the details, you probably don't really know which way Abe Lincoln's head faces or where the word liberty is. Because these details aren't essential for you to be able to use the penny and spend the penny, you never paid attention to it, so you never created a memory for those details. So let's talk about how memory functions.

7:37You say that there are sort of four steps that we have to go through to get memory to take something in and then hold on to it. Can you give us the basics? Yeah. So memory creation takes place in four basic steps. The first is that your brain takes in all of the sights, the sounds, the smells, the tastes, the emotion, the language, the meaning of whatever you perceived and paid attention to and translates all of that into neurological language. So what's out there gets into your brain. Then your brain takes all of that previously unrelated neural activity and weaves it into a single pattern of associated connections.

8:22So your brain links the information together into a neural circuit. Next, your brain then stores this information, this woven neural circuit, into lasting alterations in your brain. So your brain changes. It changes a neural architecture, changes a neural communication. chemistry that are stable over time. And then the last thing that happens, the fourth step, is that if you later activate this woven circuit, either tomorrow or next week or 30 years from now, you can then retrieve that woven information. You remember. I mean, it's really funny. It makes me think of the phrase that I've always hated.

9:05Let's make some memories. That's always seemed. But what you're saying is you can. Like, You say that there are ways, things that we can do to sort of better encode our memories. Definitely. So our human brains are designed to remember what is meaningful, emotional, surprising, new, and what we repeat and practice. And we forget what isn't. So, you know, our day, if you think about it that way, our day-to-day lives contain a lot of routine, inconsequential things, right? So you get up, you shower, you get dressed, you drink coffee, same old, same old day after day. We don't remember what same old, same old.

9:47Okay. So what did you have for lunch last Wednesday? Oh gosh. I don't know. I don't know. Right. You probably don't remember because it's like same old, same old. Can you tell me everyone you texted and everyone who texted you two days ago? Oh gosh, no. I can go look and scroll backwards. That'll remind me. Right. But this is okay. This is not a problem that we need to fix. Our brains don't keep what's same old, same old inconsequential. And so if we want to remember more of what happened in our lives, or if we want to remember if we're trying to memorize a speech, or remember if we're trying to learn information for a test, how can we make that information meaningful, emotional, surprising, or new?

10:27But day-to-day lives, we lose a lot. It makes me sad in some ways. You know, it's like, I mean, especially it makes me sad thinking that when I talk to my kids, they're not going to remember entire years of the time that I spent with them. Oh, I know. And that's maddening. Some of that has to do with the kinds of long-term memory that we have. We have muscle memory, which I've already talked about, and that's really stable over time. That's the expression, you know, it's just like riding a bike. Once you learn how to do something, that memory sticks with you, probably for life. Another kind of memory is semantic memory.

11:01This is the memory for facts and information. This is the Wikipedia of your brain. This is what's your birth date? Where do you live? What's six times six? Also really stable over time. Episodic memory is the memory for what happened in your life. So this is, you know, oh, remember when, the time when. And this, it turns out, like, to have a memory of what happened, you have to have language and the ability, because it's the story. Most of us don't remember much of what happened before the age of four, unless there was a death or a move or something very meaningful, emotional, surprising, or new.

11:38Because we don't have the language skills developed yet to be able to tell the story of what happened. So most of us will say, like, that starts to come online around, like, you know, seven, eight, like, nine, like, those memories start happening. But again, whether you're a kid or a grown up, you don't remember what happened on Wednesday, September 17th, 1986, because it was just a regular Wednesday. But if you were on vacation that day, right, or if that was your birthday, if it's special in some way, I mean, this is why we remember vacations so well. because they're not same old, same old. You're in a new place with new sights and sounds and tastes and new experiences.

12:20You're probably also taking pictures while you're there and those photos give you a chance to revisit what happened. And so now you're practicing and you're going over those neural pathways and making them stronger. But day to day, we don't take pictures of my Wednesday night dinner here with my kids. So we won't remember. And that's okay. So this is the thing. I want people to recognize that you don't have to freak out. Like when you said, oh, that's so sad. It's like, well, our brains are actually designed pretty well. If it's meaningful, emotional, surprising, or new, we keep it. And we can keep it for 70 years, 80 years.

12:58We can keep it for a lifetime if it's meaningful and emotional and important. But if it's not, it's okay to let it go. When we come back, Lisa talks about her bestselling book, Still Alice, and what to do when normal memory loss becomes abnormal. I'm Manoush Zomorodi, and you're listening to the TED Radio Hour from NPR. Stay with us.

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15:16It's the TED Radio Hour from NPR. I'm Anoush Zomorodi. On the show today, how our brains remember. We are spending the hour with Lisa Genova. She's a neuroscientist and an expert in memory and brain function. Thank you so much for being here, Lisa. Welcome back. It's my pleasure. So let's talk about one of the ways, very unique ways that you have found to make neurological disease really relatable novels. How would you describe your sort of niche genre that you've created? Yeah, it's, I'm a neuro novelist. Yes. I think that there's a special sort of taboo for anything going on with humans from the neck up.

16:06So if you've got a neurodegenerative disease, if you have autism, if you have bipolar disorder, if you have ALS, Alzheimer's, Huntington's, anything going on from the neck up, people get uncomfortable with you. I think society as a whole isn't really familiar with those issues. And so as humans, if we're not familiar with something, I don't have the language and the familiarity to understand what's going on with you. I get uncomfortable really fast. And the quickest way for me to relieve that discomfort is to look away. And so if we're talking about Alzheimer's and you have Alzheimer's and I don't quite understand what's going on with you, It's made me uncomfortable.

16:53And I look away. Well, I've just turned my back on you and 50 million people worldwide. Wow. And unless, if we're talking Alzheimer's, unless this impacts me or my family directly, certainly not going to read the Journal of Neuroscience, I'm not going to read a nonfiction book either. I'm not going to pick up a memoir. But I might read a novel, right? And even more so, I might see a movie. So I've just found that fiction and narrative, story, this is the way to reach the most people. So let's talk about for people who maybe – I feel like a lot of people are like, oh, yeah, she wrote that book.

17:34It's your first book that came out in 2007 called Still Alice, which was turned into a movie that won Julianne Moore an Oscar in 2015. and this is about a linguistics professor who has early onset Alzheimer's and she feels really alone in the illness because as you say it's like it's hard to explain what it feels like especially if you're starting to lose your language but there is a moment in the film version when her adult daughter asks Alice what these early symptoms are like. Like, what does it actually feel like?

18:19Well, it's not always the same. I have good days, bad days, and on my good days, I can, you know, almost pass for a normal person. But on my bad days, I feel like I can't find myself. I've always been so defined by my intellect, my language my articulation and now sometimes I can see the words hanging in front of me and I can't reach them and I don't know who I am and I don't know what I'm going to lose next Sounds horrible Thanks for asking That scene is just An amazing scene. I really appreciated hearing her describe how unpredictable the disease feels during those first stages. Was this scene based on something that someone told you?

19:20Yeah. When I was doing the research for Still Alice and I came to know 27 people living with Alzheimer's who were still in the earliest stages or early enough that they could communicate what it feels like to live with it. And people tend to think that it's, well, you start to lose access to your memories and your history and who you are. And it's like the flip of a switch and that it can never return. But it comes in and out. It's more like my friend Greg O 'Brien, who has Alzheimer's. He says it's like you're in the basement doing laundry and someone flicks the lights off because they don't realize you're down there and it goes dark.

19:57And you're waiting and you're waiting and you're hoping that someone will realize that you're down there and turn the lights back on. And someone does. And so that's when everything comes back online. But you don't know if someone's going to, you know, is someone going to realize you're down there or are the lights going to stay off for good? So what do we know now? Because we've been hearing about Alzheimer's for decades now. But what do we know in terms of how the disease works and what happens in the brain? Because we do know a lot more, right? We do. Okay, so we know that for many reasons, we can build up a protein called amyloid beta in your brain.

20:36A lot of things can lead to this buildup. Things like not getting enough sleep, a poor diet that leads to anything that is bad for your heart will also be bad for your brain and that it can also lead to increases in amyloid. So if you have – if amyloid is building up in your brain, it's a sticky protein. And if it binds to itself, it can form amyloid plaques. And we think it takes about 10 to 20 years of amyloid plaque accumulation in your brain that ultimately will lead to a tipping point. and it will trigger a molecular cascade that leads to something called neurofibrillary tangles, and these sort of choke off the highway transportation system of your neurons, and it will cause neuroinflammation where your brain is trying to solve the problem, but it can't, and then it leads to cell death.

21:26This is Alzheimer's. When it reaches the tipping point and it trips this molecular cascade, that's when we start to experience the symptoms of dementia. Can I just ask you, you just used the word dementia. Can we use those two things interchangeably, Alzheimer's and dementia? So they tend to be used interchangeably, but they're not the same thing. So dementia is a symptom. It's not a diagnosis. So dementia is a term that means you have an impairment with memory, language, and cognition that is out of proportion to your age and education level. Got it. And it can be a symptom due to many things.

22:04So you can experience dementia due to chronic sleep deprivation, to a B12 deficiency. It could be due to vascular dementia or a stroke. It could be due to frontotemporal lobe dementia. So there are lots of reasons why you can have symptoms of dementia. With Alzheimer's disease, dementia is the hallmark symptom. You talked about earlier what memory loss is normal. But what is not normal? What are some of the sort of signs that maybe this is worth getting checked out? Sure. So we all have the, where did I put my phone? Where did I put my keys or my glasses? If you find your keys and they're, you know, they're on the hallway table and you were in a rush and you, oh yeah, I was in a rush and I didn't pay attention to where I put them.

22:56So now all of you listening will have that moment of recognizing like, oh yes, I did not pay attention to where I put them. and this never even involved my memory. That's normal. But if you find your keys in a place that's strange, that doesn't make any sense, like you were actually thinking this is where keys go, like, oh, you find them in the refrigerator or you find them in the microwave, that's strange. If you find your keys and you're looking at them and think, I don't know what these are for, that could be a problem. If you drove your car and parked in a garage, and again, you didn't pay attention to where you parked because you were texting, you were talking, and then you get back to the garage and you're like, I can't remember if I'm parked on level three or level four.

23:36Well, that's normal. You weren't paying attention. If you have Alzheimer's, it will be, I can't remember how I got here. Or you could be standing in front of your car and you don't recognize it as yours because you don't remember what your car looks like. The words that go missing when you have Alzheimer's, it's going to be common nouns and dozens of times a day. So, you know, a 25-year-old might have three to four tip-of-the-tongue words a week, and that's totally normal. It does increase as we get older. I'm 52, and I notice that I have more tip-of-the-tongues. But for someone with Alzheimer's, it's going to be dozens of words a day that go missing.

24:16It's like, oh, the thing, the thing that, you know, you put in your mouth to wash the teeth. A toothbrush? Yes. Your first TED Talk, which you gave in 2017, it's called What You Can Do to Prevent Alzheimer's. But you say, don't be in denial. And you open your talk with a pretty terrifying statistic. Let's project out into the future, and let's imagine that we're all 85. Now, everyone look at two people. One of you probably has Alzheimer's disease.

24:57All right, all right. And maybe you're thinking, well, it won't be me. Then, okay, you are a caregiver.

25:11So if we're lucky enough to live long enough, Alzheimer's appears to be our brain's destiny. But maybe it doesn't have to be. What if I told you we could change these statistics, literally change our brain's destiny, without relying on a cure or advancements in medicine?

25:33the likelihood of developing alzheimer's is a combination of the genes that you inherited from your parents so nothing i can do about that and how you live whoa there's everything i can do about that so that how you live is it's sleep it's diet it's exercise it's managing stress it's staying socially and cognitively active those are the things that can help you clear away the amyloid, keep you from getting to that tipping point, keep you from developing Alzheimer's. And what about preventive medicine or medical intervention? What's the latest? So it's really hopeful. I mean, we're not there and everybody wants the home run right away.

26:17Everybody wants the magic pill yesterday. There are companies, lots of companies spending a lot of money and decades on developing a compound that targets amyloid that will clear this protein away so it doesn't develop into plaques and never reaches that tipping point. It's a great strategy. It's not simple. And there's mixed data on them. Some of it's really promising and some of it's not. But I would say overall, I'm really excited about the promising data because it's showing proof of concept that if you're at risk for developing Alzheimer's, if you have elevated levels of amyloid, that you can take a drug that will prevent your amyloid levels from, your amyloid plaques from becoming too high, and that will prevent you from developing Alzheimer's and symptoms of dementia.

27:10So you mentioned that lifestyle contributes to our likelihood of getting Alzheimer's, but there's also the genetic component. If you have a certain gene, ApoE4, it increases your risk. And that is something that we can now test for. And there's this scene in Still Alice where Alice is telling her children that she has the disease and warning them that one day they might develop it too. The thing is that the type of Alzheimer's I have is very rare. It's familial. It's passed on genetically. Oh, my God. We believe that she got it from her father, and, of course, we're very worried about the three of you.

27:58Now, there is a test you can take, but it's completely up to you whether you want to find out or not. I'm sorry. Lisa, what is the benefit of knowing you have this gene? Like, how does it change behavior? The reason to know, there's a few reasons. One is I can enroll in clinical trials if I have an APOE4 gene. The way to solve Alzheimer's is for people to be in clinical trials. And we want people who don't have the disease yet. Because if I already have Alzheimer's, I've already reached the tipping point. I've tripped the molecular cascade. So I've got tangles and neuroinflammation and cell death.