Lack Of Deep Sleep May Set The Stage For Alzheimer's

Jan 4, 2016
Originally published on January 4, 2016 9:25 pm

There's growing evidence that a lack of sleep can leave the brain vulnerable to Alzheimer's disease.

"Changes in sleep habits may actually be setting the stage" for dementia, says Jeffrey Iliff, a brain scientist at Oregon Health & Science University in Portland.

The brain appears to clear out toxins linked to Alzheimer's during sleep, Iliff explains. And, at least among research animals that don't get enough solid shut-eye, those toxins can build up and damage the brain.

Iliff and other scientists at OHSU are about to launch a study of people that should clarify the link between sleep problems and Alzheimer's disease in humans.

It has been clear for decades that there is some sort of link. Sleep disorders are very common among people with Alzheimer's disease.

For a long time, researchers thought this was simply because the disease was "taking out the centers of the brain that are responsible for regulating sleep," Iliff says. But two recent discoveries have suggested the relationship may be more complicated.

The first finding emerged in 2009, when researchers at Washington University in St. Louis showed that the sticky amyloid plaques associated with Alzheimer's develop more quickly in the brains of sleep-deprived mice.

Then, in 2013, Iliff was a member of a team that discovered how a lack of sleep could be speeding the development of those Alzheimer's plaques: A remarkable cleansing process takes place in the brain during deep sleep, at least in animals.

What happens, Iliff says, is "the fluid that's normally on the outside of the brain, cerebrospinal fluid — it's a clean, clear fluid — it actually begins to recirculate back into and through the brain along the outsides of blood vessels."

This process, via what's known as the glymphatic system, allows the brain to clear out toxins, including the toxins that form Alzheimer's plaques, Iliff says.

"That suggests at least one possible way that disruption in sleep may predispose toward Alzheimer's disease," he says.

To know for sure, though, researchers will have to study this cleansing process in people, which won't be easy.

Iliff studied the glymphatic system in living mice by looking through a window created in the skull. The system also involved a powerful laser and state-of-the-art microscope.

With people, "we have to find a way to see the same sort of function, but in a way that is going to be reasonably noninvasive and safe," he says.

The solution may involve one of the world's most powerful magnetic resonance imaging machines, which sits in a basement at OHSU. The MRI unit is so sensitive, it should be able to detect changes that indicate precisely when the glymphatic system gets switched on in a person's brain, says Bill Rooney, who directs the university's Advanced Imaging Research Center.

When humans enter deep sleep, and toxin removal begins, there should be a particular change in the signal coming from certain salt molecules. That would indicate that fluid has begun moving freely through the brain.

In young, healthy brains, the signal should be "robust," Rooney says, indicating that the toxin removal system is working well. In the brains of older people, and those who are likely to develop Alzheimer's, the signal should be weaker.

Rooney and Iliff have received funding from the Paul G. Allen Foundation to test their approach. They hope to begin scanning the brains of participants within a year.

One challenge, though, will be finding people able to fall asleep in the cramped and noisy tunnel of the magnetic resonance machine.

"It's a tricky thing because it's a small space," Rooney says. "But we'll make people as comfortable as possible, and we'll just follow them as they go through these natural stages of sleep."

If Rooney and Iliff are right, the experiment will greatly strengthen the argument that a lack of sleep can lead to Alzheimer's disease. It might also provide a way to identify people whose health is at risk because they aren't getting enough deep sleep, and it could pave the way to new treatments.

"It could be anything from having people exercise more regularly, or new drugs," Rooney says. "A lot of the sleep aids don't particularly focus on driving people to deep sleep stages."

Copyright 2016 NPR. To see more, visit http://www.npr.org/.

Transcript

RENEE MONTAGNE, HOST:

Today in Your Health, we'll hear about how to tell normal memory loss from dementia. But first, let's look at the link between Alzheimer's disease and sleep. NPR's Jon Hamilton reports on emerging evidence that a lack of sleep can make the brain more vulnerable to Alzheimer's.

JON HAMILTON, BYLINE: People with Alzheimer's often have trouble sleeping. And for a long time researchers thought that was simply because the disease can affect areas of the brain that regulate sleep. But Jeffrey Iliff, a brain scientist at Oregon Health and Science University in Portland, says there's another possibility.

JEFFREY ILIFF: The relationship may go the other way as well. Changes in sleep habits may actually be setting the stage for the development of Alzheimer's disease.

HAMILTON: Iliff says much of the evidence for this comes from mice, mice like the ones he studies here in his lab.

ILIFF: This is the room where we do most of our imaging. Warning sign here because there's a very powerful laser in here that can actually blind you if you look into it.

HAMILTON: The laser also allows Iliff to study the brains of living mice using a state-of-the-art microscope.

ILIFF: 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.

HAMILTON: Iliff says two recent discoveries support the idea that sleep problems might lead to Alzheimer's disease. The first came in 2009 from researchers at Washington University in St. Louis. They showed that the sticky plaques associated with Alzheimer's develop more quickly in the brains of sleep-deprived mice. Then in 2013, Iliff was part of a team that discovered how a lack of sleep might be speeding up the development of Alzheimer's plaques. The team showed that a remarkable cleansing process was taking place in the brain during deep sleep.

ILIFF: 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.

HAMILTON: Iliff says this process appears to clear out harmful toxins, including the toxins that form Alzheimer's plaques.

ILIFF: And so that suggests at least one possible way that sleep or disruption in sleep may predispose toward Alzheimer's disease.

HAMILTON: To know for sure, though, researchers will have to study this cleansing process in people. And Iliff says they won't be able to use the laser microscope approach he's used on mice. It's too dangerous.

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

HAMILTON: That's where Iliff's colleague Bill Rooney comes in. Rooney directs the Advanced Imaging Research Center at Oregon Health and Science University. This center includes one of the world's most powerful magnetic resonance machines. It sits in a basement a short walk from Iliff's lab.

BILL ROONEY: Down here the magnetic fields are a little bit less controlled than they are upstairs. So I'll ask if you have any medical implants?

HAMILTON: I don't, so we enter the control room. It's filled with the sound of compressors that help cool the machine's superconducting magnet. Rooney thinks this machine will allow researchers to watch human brains activate the toxin removal system during sleep. One challenge, he says, will be finding people able to fall asleep in the device's cramped and noisy tunnel.

ROONEY: It's a tricky thing because it's a small space. But we'll make people as comfortable as possible. And we'll just follow them as they go through these natural stages of sleep.

HAMILTON: Rooney says when people enter deep sleep, there should be a change in one particular signal coming from the brain.

ROONEY: Starting out with young, healthy people that have totally normal sleep, we would expect that they would have a robust response when they go into deep sleep.

HAMILTON: That would indicate that the brain's cleaning system is working properly. Rooney expects a weaker response in older people and people who are likely to develop Alzheimer's. If he's right, it would bolster the idea that sleep problems can contribute to the disease. And Rooney says it might also help doctors identify people who need some help getting more deep sleep.

ROONEY: And it could be anything from having people exercise more regularly or new drugs. A lot of the sleep aids don't particularly focus on driving people to deep sleep stages.

HAMILTON: Rooney hopes to have the first study participants sleeping in the big magnet within a year. Jon Hamilton, NPR News. Transcript provided by NPR, Copyright NPR.