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 Spira’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.
Nelly A. Papalambros
Giovanni Santostasi
Roneil G. Malkani
Rosemary Braun
Sandra Weintraub4, 
Ken A. Paller
Phyllis C. Zee