One More Step Toward Solving The Sleep & Alzheimer's Puzzle : Short Wave We know that people with Alzheimer's often have sleep problems. But does it work the other way? Do problems with sleep set the stage for this degenerative brain disease?

NPR correspondent Jon Hamilton introduces us to some scientists looking into that connection in this updated report on the key role deep sleep may play in maintaining brain health and protecting the brain against Alzheimer's.

Follow host Maddie Sofia on Twitter @maddie_sofia. Email the show at

One More Step Toward Solving The Sleep & Alzheimer's Puzzle

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You're listening to SHORT WAVE from NPR. Maddie Sofia here with NPR science correspondent Jon Hamilton. Hi, Jon.


SOFIA: OK. So you are our in-house sleep reporter.

HAMILTON: I am. And I am here today with an update on that episode we did last year about sleep and Alzheimer's disease.

SOFIA: That's the episode about whether all of us sleep-deprived people are more likely to get Alzheimer's.

HAMILTON: That's the one. Yeah.

SOFIA: OK. Great. Our audience is going to love this update, Jon, because it is still one of our most popular episodes of all time. So are you saying that there's an answer to that question now?

HAMILTON: Well, maybe not a final answer, but there is some new research suggesting that bad sleep really does speed up some of the brain changes associated with Alzheimer's.

SOFIA: Jon, that sounds like bad news for insomniacs and podcast hosts.

HAMILTON: Yeah. Sorry, Maddie. But the sleep researchers tell me that even people who aren't getting enough sleep now, it's not too late for them to change their ways.

SOFIA: So today on the show, we revisit the connection between sleep and Alzheimer's and bring you the latest update.


SOFIA: OK. Jon, scientists have been looking at this connection between sleep and Alzheimer's for a while. And a lot of these studies started in mice.

HAMILTON: Right. So several years ago, I stopped by this lab where they're doing research on mouse brains. And I met up with a scientist named Jeffrey Iliff.


JEFFREY ILIFF: Come on in.

SOFIA: He's a brain scientist at the University of Washington now. But then he was studying mouse brains at Oregon Health and Science University.


ILIFF: Warning sign here because there's a very powerful laser in here that can actually blind you if you look into it.

SOFIA: Jon, doesn't that always make you want to look at it a little, like out of the side of your eye?

HAMILTON: Yeah. It's like the solar eclipse. And you just can't help yourself.

SOFIA: I'm glad you didn't, though.

HAMILTON: Anyway, the laser we were talking about made it possible for Jeff and his colleagues to study the brains of living mice using this state-of-the-art microscope.


ILIFF: So there's - black curtains surround this microscope because our microscope is very, very sensitive. And it's almost literally counting every single photon that comes up out of the mouse's brain.

SOFIA: Wow. So what are they using this fancy microscope to look at exactly?

HAMILTON: Well, to understand that, you kind of need to understand what happens in the brains of mice when they go to sleep.

SOFIA: All right. Mouse brain science. Here we go.

HAMILTON: Right. When mice sleep - or for that matter, when people sleep, when you sleep - the brain cells shrink, so it's easier for this fluid to flow through the entire brain.


ILIFF: So what happens is during sleep, the fluid that's normally on the outside of the brain, which is called cerebral spinal fluid - it's a clean, clear fluid. It actually begins to recirculate back into and through the brain along the outsides of blood vessels. So it uses the blood vessels as sort of a scaffold, allowing that CSF to exchange with the fluid between the brain cells.

HAMILTON: And that exchange between the CSF and brain fluid washes out all these toxins that build up during waking hours.

SOFIA: I've heard some scientists compare it to like how a dishwasher works, so getting rid of the dirty stuff that's accumulated on the plates, in the bowls and the silverware.

HAMILTON: It's not a bad comparison because that fluid can get going pretty fast. And by the way, the team that discovered it named it something. They call it the glymphatic system.

SOFIA: Sure. Love it. OK, Jon, what kind of toxins are we actually talking about?

HAMILTON: OK. So brain cells, like all cells, produce waste that they need to get rid of, stuff like carbon dioxide, ammonia. And the cells kind of excrete this stuff, and it would build up in the spaces between cells if there weren't some kind of system that took it away. So the scientists who discovered the system actually think these wastes are the reason that we can't think straight because we didn't get enough sleep.

SOFIA: That explains my brain since the launch of this podcast, Jon Hamilton.

HAMILTON: Oh, and animals and people eventually die without sleep.

SOFIA: Good to know (laughter).

HAMILTON: So at this point, you may be a highly functional zombie.

SOFIA: Yeah.

HAMILTON: But wait. Wait. There's more. By not sleeping, you also may be raising your risk for Alzheimer's. And the reason for that is that one of the waste products that builds up in the brain is something called beta amyloid.

SOFIA: Beta amyloid.

HAMILTON: Yeah. You've probably heard about the plaques and tangles that are associated with Alzheimer's disease. Well, beta amyloid is the plaque. It forms these sticky clumps in the brains of people who either have Alzheimer's or are likely to develop it. And the idea is that beta amyloid is part of a process that ultimately kills brain cells. So it was kind of alarming back in 2009, when scientists started finding evidence that a lack of sleep might actually be speeding up the development of these beta amyloid plaques.

SOFIA: So basically, scientists found evidence of a strong connection between sleep - like a lack of it - can make your brain more vulnerable to Alzheimer's.

HAMILTON: Right, at least in mice, which really don't get Alzheimer's without some genetic tinkering.


ILIFF: So we have to find a way to see the same sort of function but in a way that is going to be, you know, reasonably noninvasive and safe for a human.

SOFIA: So have scientists figured out how to test for it in humans?

HAMILTON: Yep. And most recently, scientists have figured out a way to study it in real time.


LAURA LEWIS: My name is Laura Lewis. I'm an assistant professor of biomedical engineering.

HAMILTON: At Boston University. And Laura and a team of researchers found a way to watch the glymphatic system at work. This was in about a dozen sleeping people. The whole thing was written up in the journal Science. And what they did was have people fall asleep inside an MRI scanner, so in this cramped, like, super noisy tube.

SOFIA: Yeah. Not an easy place to nap.

HAMILTON: And then while these people were asleep, they used all this cutting-edge technology to monitor things like brainwaves and blood flow.

SOFIA: What did they find out, Jon?

HAMILTON: I'm going to let Laura describe it.


LEWIS: And that's when we discovered that, during sleep, there are these really large, slow waves occurring maybe once every 20 seconds of CSF washing into the brain.

HAMILTON: So the fluid isn't just flowing steadily. It's kind of oscillating like a washing machine. And these researchers were watching this happen in a human brain. And then they saw something else, this other discovery.


LEWIS: Before each wave of fluid, we would actually see a wave of electrical activity in the neurons. This electrical wave always happens first, and the CSF wave always seems to follow seconds later.

SOFIA: So were the electrical waves triggering the washing cycle that flushed out these toxins?

HAMILTON: Well, that is the current hypothesis. Those electrical waves are called slow waves, and they show up when a person enters a state known as deep sleep. So, you know, everybody talks about REM sleep - right? - rapid eye movement. This is a different state, and it's one where a lot of brain systems seem to be shut down and people are a lot less likely to dream.

SOFIA: So the deep sleep thing is key here. The less somebody gets, the fewer slow waves. And the fewer the slow waves, the fewer the toxins flush out of the brain?

HAMILTON: That's what it looks like. And, of course, one of those toxins is beta amyloid, that plaque we were talking about that's linked to Alzheimer's. And it looks like there's this kind of vicious cycle. You don't get enough sleep, so more beta amyloid, you know, builds up in your brain. And when you build up beta amyloid, it disrupts the sleep.

SOFIA: OK, Jon, so that's where we left off last time. We know that toxins build up in the brains of mice that don't get enough sleep because they don't get enough of that dishwasher brain cleaning time, and that human brains have a similar detoxifying system. But we really only had circumstantial evidence that poor sleep increases risk factors for Alzheimer's in humans.

HAMILTON: Right, that was true, but now it looks like we do. A team of scientists at the University of California, Berkeley, have been looking at beta amyloid, you know, in the context of sleep. One of those scientists is Matthew Walker. He's been studying sleep for years, and he wanted to answer a simple question.

MATTHEW WALKER: Can I look into your future, and can I accurately estimate how much beta amyloid you're going to accumulate over the next two years, the next four years, the next six years, simply on the basis of your sleep tonight?

SOFIA: Wow. I mean, Jon, if he could, that would show a pretty strong link between sleep and Alzheimer's, right?

HAMILTON: Exactly.

SOFIA: But a study like that would take years - right? - because you have to kind of wait to see what happens in a person's brain.

HAMILTON: Yeah. And that's what the researchers did. They picked 32 older adults with healthy brains who had taken part in a sleep study that used brainwave patterns to track their sleep. Then the scientists looked to see how levels of beta amyloid changed in these people's brains over several years. And it turned out that the ones who had more fragmented sleep and the ones who got less deep sleep, they accumulated more beta amyloid. Here's what Walker told me.

WALKER: We have a specific sleep signature right now that seems to help us better understand where you may sit on the Alzheimer's disease risk trajectory in the future.

SOFIA: So, Jon, should I, an occasionally sleep deprived podcast host or other people like me be worried?

HAMILTON: Well, yeah, maybe. But Walker told me it's never too late for people like you and your sleep-deprived comrades.

WALKER: Even in mid-life, if I correct your sleep and I improve it here in the context of a sleep disorder, then I can actually sort of downgrade the likelihood of you developing cognitive impairment in later life and Alzheimer's disease.

HAMILTON: Of course, sleep is just one factor affecting your risk for Alzheimer's. Genetics is another one. And so are health problems like high cholesterol and high blood pressure.

SOFIA: All right, Jon Hamilton, thank you for this update. And good sleeping to you, sir.

HAMILTON: Thank you, Maddie.

SOFIA: Today's episode was produced by Brit Hanson, fact-checked by Ariela Zebede and edited by Gisel Grace (ph). I'm Maddie Sofia. Thanks for listening to SHORT WAVE from NPR.

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