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‘A Rinsing of the Brain.’ New Research Shows How Sleep Could Ward Off Alzheimer's Disease

Alice Park

Each of us carts around a 3-lb. universe that orchestrates everything we do: directing our conscious actions of moving, thinking and sensing, while also managing body functions we take for granted, like breathing, keeping our hearts beating and digesting our food. It makes sense that such a bustling world of activity would need rest. Which is what, for decades, doctors thought sleep was all about. Slumber was when all the intricate connections and signals involved in the business of shuttling critical brain chemicals around went off duty, taking time to recharge. We’re all familiar with this restorative role of sleep for the brain–pulling an all-nighter or staying awake during a red-eye flight can not only change our mood, but also affect our ability to think clearly until, at some point, it practically shuts down on its own. When we don’t get enough sleep, we’re simply not ourselves.

Yet exactly what goes on in the sleeping brain has been a biological black box. Do neurons stop functioning altogether, putting up the cellular equivalent of a Do Not Disturb sign? And what if a sleeping brain is not just taking some well-deserved time off but also using the downtime to make sense of the world, by storing away memories and captured emotions? And how, precisely, is it doing that?

In the past five years, brain researchers have begun to expose a hidden world of chemical reactions, fluids flowing into and out of the brain, and the busy work of neurons that reveal the sleeping brain is as industrious as the waking one. Without good-quality sleep, those critical activities don’t take place, and as a consequence, we don’t just feel tired and cranky, but the processes that lead to certain diseases may even get seeded. One of the reasons we sleep, it now seems, might be to keep a range of illnesses–including cognitive diseases like Alzheimer’s and other dementias–at bay. As Adam Spira, a professor in the department of mental health at the Johns Hopkins Bloomberg School of Public Health, puts it, “Sleep really should not be seen as a luxury or waste of time. People joke that they’ll sleep when they’re dead, but they might end up dead sooner if they don’t sleep.”

Blame Polymath Benjamin Franklin, who averred, “There will be sleeping enough in the grave”; ever since, a culture of industry has rooted itself in the human psyche–embedding the idea that activity, even well into the night, is valued far more than daily rest.

In part that’s because while medical experts have long recommended seven to eight hours of sleep a night–including some time spent in deep, or non-REM, sleep–exactly what our bodies are doing during that time is less clear. Now, thanks to newer technologies for measuring and tracking brain activity, scientists have defined the biological processes that occur during good-quality sleep. That they seem to be essential for lowering the risk of brain disorders, from the forgetfulness of senior moments to the more serious memory loss and cognitive decline of dementia and Alzheimer’s disease, may convince the Franklins of the world that sleep is not for the lazy.

Experts in the field of Alzheimer’s are especially excited, since there are currently no treatments for the neurodegenerative disease, and sleep-based strategies might open new ways to slow its progression in some and even prevent it in others.

“There has been a real renaissance in research around the connection between sleep, sleep quality, sleep disturbance and dementia, especially Alzheimer’s dementia,” says Dr. Kristine Yaffe, professor of psychiatry, neurology and epidemiology at the University of California, San Francisco. The National Institutes of Health is currently funding at least half a dozen new studies exploring how sleep may impact dementia, and the Alzheimer’s Association created a committee to promote more research in the area.

For decades, researchers thought sleep disturbances were a symptom or a consequence of Alzheimer’s. They assumed that as clumps of amyloid proteins built up, then started to strangle and kill nerve cells–particularly in the memory regions of the brain–changes in sleep followed. Even older people without Alzheimer’s can experience changes in their sleep patterns, sleeping less and more lightly as they age. So experts didn’t initially take these shorter and more fragmented sleep cycles seriously.

But in the 1980s and 1990s, scientists began studying whether there was any causal relationship between sleep patterns and cognitive-test performance among older people without Alzheimer’s by studying them over longer periods of time. Those studies suggested that people with poor sleep habits tended to perform worse on cognitive tests over time. “That got people thinking about the possibility that sleep could be a risk factor in dementia,” says Spira.

Yaffe’s recent research, which focused on a group of healthy older women, supported the idea that what seemed to matter, in terms of dementia risk, was the quality as opposed to the quantity of sleep. Those who reported spending less time in bed actually sleeping, and more time tossing and turning and waking up throughout the night, were more likely to develop any type of dementia five to 10 years later than those who got better-quality sleep.

Others focused on explaining the biology behind the sleep-dementia connection. At this point, Alzheimer’s researchers knew that a buildup in the brain of amyloid and another protein called tau were key features of the disease. At Washington University School of Medicine in St. Louis, David Holtzman, chair of the department of neurology, launched studies to track exactly where in the brain this amyloid originated. His search led him to nerve cells, which release fragments of the protein as they go about their normal business. Typically, these protein by-products (sometimes called amyloid beta) are released into the circulatory system, where they float around without causing problems, but in some cases they remain in the brain, where they morph into a sort of molecular Velcro, sticking together to form amyloid plaques, which in turn damage neurons.

But what controls the production of amyloid beta? In a 2009 study on mice, Holtzman found that while the animals were awake, levels of the protein fragments circulating in their brains surged. When the mice slept, the levels dropped dramatically–especially during the deeper stages of non-REM sleep. And when he and his team deprived the mice of non-REM sleep, more amyloid built up in their brains over time than in mice who got regular nightly rest. He saw similar changes when he compared amyloid in the spinal fluid of people who were well rested vs. sleep-deprived.

It was a revelation for Alzheimer’s experts. “That showed experimentally for the first time that there was an effect of sleep deprivation on Alzheimer’s disease pathology,” says Spira. “That’s what really flipped everything on its head.” In 2013, to test whether the same effect occurred in people, Spira studied brain scans of 70 healthy adults with an average age of 76. Indeed, the scans of those who reported less or compromised sleep showed higher levels of amyloid plaques than the scans of those who slept better.

A year later, a biological explanation for why poor sleep might be linked to Alzheimer’s emerged. Dr. Maiken Nedergaard, co-director of the Center for Translational Neuromedicine at the University of Rochester, identified a previously ignored army of cells that is called to duty during sleep in the brains of mice and acts as a massive pump for sloshing fluid into and out of the brain. This plumbing system, which she dubbed the “glymphatic system” (it works in parallel to the lymph system that drains fluid from other tissues in the body), seemed to perform a neural rinsing of the brain, swishing out the toxic proteins generated by active neurons (including those amyloid fragments) and clearing the way for another busy daily cycle of connecting and networking.

Taken together with Holtzman’s discovery that levels of amyloid spiked during the day and dropped during sleep, Nedergaard’s findings gave further credence to the theory that sleep might perform a housekeeping function critical for warding off diseases like Alzheimer’s. “These results very much support the notion that one of the roles of sleep is to actually accelerate the clearance of beta amyloid from the brain,” says Nora Volkow, director of the U.S. National Institute on Drug Abuse.

Late last year, Laura Lewis, assistant professor of biomedical engineering at Boston University, built on Nedergaard’s work by matching up the ebb and flow of cerebrospinal fluid in the brain with brain-wave activity, which indicates different stages of sleep. She showed that in healthy adults, during the day when the brain is active, there is less fluid bathing neurons and tissues in the organ. During sleep–and especially during deeper sleep–this solution saturates the brain in a cleansing flood. The finding reinforced Nedergaard’s theory that sleeping may help clear the brain of toxic proteins that can eventually cause disease.

Still, while all these discoveries are strongly suggestive, they are not what scientists would call definitive. For that, researchers need two additional pieces of evidence: first, a clear correlation between disrupted sleep patterns and a higher risk for Alzheimer’s; and second, evidence that if these high-risk people improve their sleep, that risk falls.

They are currently working to build those data sets, and already the results are promising. For example, Volkow measured baseline amyloid levels in the brains of 20 healthy people ages 22 to 72 years, then scanned their brains again after each had a good night’s sleep and yet again after each was kept awake for about 31 hours straight. After a loss of sleep, levels of amyloid were 5% more than after adequate sleep; the spikes were concentrated in parts of the brain involved in memory and higher thinking, which are typically affected in Alzheimer’s.

But seeing levels of amyloid change with more or less sleep doesn’t necessarily mean sleep habits are contributing to Alzheimer’s. To make that case, researchers are studying people with disorders like sleep apnea, or those who work night shifts or keep irregular working hours, such as first responders, pilots and flight attendants. Studies already suggest that all of these groups are more vulnerable to Alzheimer’s. The next step is to see if treatment, or changes in sleep habits, matters. For people with sleep apnea, for example, doctors can prescribe devices to wear during sleep to keep oxygen flowing more consistently to the brain so they don’t wake up. In shift workers, researchers want to test the impact of resetting their biological clocks to a standard day-night schedule. If these efforts lower their likelihood of developing Alzheimer’s, that would make a strong case for a connection between lifelong sleep patterns and risk of dementia.

Researchers also need to better understand how sleep medications and treatments like melatonin affect the dementia process. While some sleep aids promote the deeper sleep that seems to be protective against brain decline, it’s not clear yet whether long-term dependence on such medications can maintain the benefit.

Even while these studies are being done, many experts believe the data are already strong enough to start educating at least older people, especially those at higher risk of developing Alzheimer’s, about improving their sleep habits. Yaffe, for one, already does that with her patients. “Even practical sleep-hygiene tips, where we teach people best practices like avoiding caffeine in the evening and darkening their room and staying off their phones, could help them sleep better,” she says. “I would love to see whether this low-cost and pragmatic approach could improve cognition or prevent decline in Alzheimer’s patients.”

She and others don’t believe sleep alone can fully prevent Alzheimer’s or halt its progression. But together with other therapies that could emerge to treat the disease, sleep may be a powerful way to help people lower their risk even further. It’s even possible that sleep could play an important role in keeping our brains healthy in other ways: by controlling metabolism and other cellular functions behind diseases like diabetes, hypertension and even cancer. As the latest research shows, a good night’s sleep isn’t a luxury–it’s critical for keeping the brain healthy.

 

Correction, Aug 6 The original version of this story misstated the researcher whose work showed amyloid spiked during the day and dropped during sleep. It was David Holtzman, not Adam Spira.