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“It’s like the dishwasher turned on,” Nedergaard says. She named this phenomenon the “glymphatic system” because it appears to be controlled by glial cells, brain cells that help insulate neurons and perform much of the brain’s routine
maintenance work (SN: 8/22/15, p. 18).

Similar observations of cerebrospinal fluid circulation have been carried out in people, but with less invasive ways of measuring. In one, researchers from Oslo University Hospital, Rikshospitalet compared 15 patients who had a condition called normal
pressure hydrocephalus, a kind of dementia caused by buildup of cerebrospinal fluid in the cavities of the brain, with eight people who didn’t have the condition.

The researchers used a tracer for cerebrospinal fluid and magnetic resonance imaging to measure the flow over 24 hours. Immediately after a night’s sleep,
cerebrospinal fluid had drained in healthy people but lingered in the patients with dementia, the
researchers reported in Brain in 2017.

Go with the flow

One way the brain might clear out waste, including amyloid-beta, is via circulation of cerebrospinal and interstitial fluids. Fluid flows through the spaces in the brain, bathing neurons and eventually carrying debris out of the brain toward the liver.
Studies suggest that this “glymphatic” circulation increases during sleep.

E. OTWELL
Source: M. Nedergaard/Science 2013

Don’t snooze, you lose?

The central question — the one that doctors really want to answer — is whether better sleep could treat or even prevent Alzheimer’s. To try to figure this out, Bendlin and her Wisconsin colleagues are now studying people with sleep apnea. People
with that condition stop breathing during the night, which wakes them up and makes for a lousy night’s sleep. A machine called a CPAP, short for continuous positive airway pressure, treats the condition.

“Once people start treatment, what might we see in the brain? Is there a beneficial effect of CPAP on markers of Alzheimer’s?” Bendlin wonders. “I
think that’s a big question because the implications are so large.”

A study reported in Neurology in 2015 offers a reason to think CPAP might help.
Using data from almost 2,500 people in the Alzheimer’s Disease Neuroimaging Initiative, researchers at the New York University School of Medicine found that people with
sleep disorders like obstructive sleep apnea showed signs of mild cognitive problems and Alzheimer’s disease at younger ages than those who did not. But for those who used CPAP, onset of mild cognitive problems was delayed.

“If we find out that sleep problems contribute to brain amyloid — what that
really says is there may be a window to intervene,” Bendlin says. And the solution — more attention to sleep — is one prescription with no side effects.

This article appears in the July 21, 2018 issue of Science News with the headline, "The Clean Cycle: The body may use sleep as a time to wash away the waste that can cause Alzheimer's disease."

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According to the U.S. Centers for Disease Control and Prevention, more than 80 million American adults are chronically sleep deprived, meaning they sleep less
than the recommended minimum of seven hours a night. Fatigue contributes to more than a million
auto accidents each year, as well as to a significant number of medical errors.
Even small adjustments in sleep can be problematic. The Monday after a daylight
saving time change in the U.S., there’s a 24 percent increase in heart attacks, compared
with other Mondays, and a jump in fatal car crashes too.

During our lifetimes, about a third of us will suffer from at least one diagnosable sleep disorder. They range from chronic insomnia to sleep apnea to restless leg syndrome to much rarer and stranger conditions.

In exploding head syndrome, booming sounds seem to reverberate in your brain as
you try to sleep. A Harvard study found that sleep paralysis—the inability to
move for a few minutes after you’ve woken from dreaming—is the genesis of many alien
abduction stories. Narcoleptic attacks, uncontrollable episodes of sudden sleep
onset, often are triggered by strongly positive emotions, such as listening to a joke, being tickled, or tasting delicious food. People with Kleine-Levin syndrome will, every
few years, sleep nearly nonstop for a week or two. They return to regular cycles of consciousness without any discernible side effects.

Insomnia is by far the most common problem, the main reason 4 percent of U.S. adults take sleeping pills in any given month. Insomniacs generally take longer
to fall asleep, wake up for prolonged periods during the night, or both. If sleep is such a
ubiquitous natural phenomenon, refined across the eons, you might wonder, why do so many of us have such trouble with it? Blame evolution; blame the modern world. Or blame the mismatch between the two.

[THE POWER OF ARTIFICIAL LIGHT
The war on sleep began when incandescent bulbs first made it easy to banish night. Big cities such as Tokyo are now often illuminated with LED bulbs. They’re more energy efficient, but they tend to produce a lot of blue light, the most sleep-disrupting
kind.]

Evolution endowed us, like other creatures, with sleep that is malleable in its
timing and readily interruptible, so it can be subordinated to higher priorities. The brain has an override system, operating in all stages of sleep,
that can rouse us when
it perceives an emergency—the cry of a child, say, or the footfall of an approaching predator.

The problem is that in the modern world, our ancient, innate wake-up call is constantly triggered by non–life-threatening situations, like anxiety before an exam, worries about finances, or every car alarm in the neighborhood. Before
the industrial
revolution, which brought us alarm clocks and fixed work schedules, we could often counteract insomnia simply by sleeping in. No longer. And if you’re one
of those people who are proud of being able to fall asleep quickly just about anywhere, you can
stop gloating—it’s a distinct sign, especially if you’re less than 40 years old, that you’re acutely sleep deprived.

The first segment of the brain that begins to fizzle when we don’t get enough
sleep is the prefrontal cortex, the cradle of decision-making and problem-solving. Underslept people are more irritable, moody, and irrational. “Every cognitive function to
some extent seems to be affected by sleep loss,” says Chiara Cirelli, a neuroscientist at the Wisconsin Institute for Sleep and Consciousness. Sleep-deprived suspects held by the police, it’s been shown, will confess to anything in exchange for rest.

Anyone who regularly sleeps less than six hours a night has an elevated risk of
depression, psychosis, and stroke. Lack of sleep is also directly tied to obesity: Without enough sleep, the stomach and other organs overproduce ghrelin, the hunger hormone,
causing us to eat more than we need. Proving a cause-and-effect relationship in
these cases is challenging, because you can’t subject humans to the necessary
experiments. But it’s clear that sleeplessness undermines the whole body.

Power naps don’t solve the problem; nor do pharmaceuticals. “Sleep is not monolithic,” says Jeffrey Ellenbogen, a sleep scientist at Johns Hopkins University who directs the Sound Sleep Project, which counsels businesses on how their employees can
achieve better performance through healthier rest. “It’s not a marathon; it’s more like a decathlon. It’s a thousand different things. It’s tempting to manipulate sleep with drugs or devices, but we don’t yet understand sleep enough to risk
artificially manipulating the parts.”

Ellenbogen and other experts argue against shortcuts, especially the original one—the notion that we can mostly do without sleep. It was a glorious idea: If we could just cut the unnecessary parts of sleep, it’d be like adding decades to our life. In
the early days of sleep science, the 1930s and ’40s, the second half of the night was considered by some to be the doldrums of rest. Some thought we might not need it at all.

That period turns out, instead, to be the wellspring of a completely separate but just as essential form of sleep, practically another type of consciousness altogether.

REM
In a wild state of psychosis, we’re dreaming, we’re flying, and we’re falling—whether we remember it or not. we’re also regulating our mood and consolidating our memories.

Rapid eye movement, or REM, sleep was discovered in 1953—more than 15 years after stages 1 through 4 had been mapped—by Eugene Aserinsky and Nathaniel Kleitman at the University of Chicago. Before then, because of its unremarkable
pattern on early
EEGs, this period was usually thought of as a variant form of stage 1, and not particularly significant. But once the distinctive eye darting was documented, and the engorgement of sexual organs that always goes with it, and it was understood that
virtually all vivid dreaming takes place in this phase, the science of sleep was upended.

Generally, a healthy sleep begins with a spiral down to stage 4, a momentary return to wakefulness, and a five- to 20-minute REM session. With each ensuing cycle, REM time roughly doubles. Overall, REM sleep occupies about one-fifth of
total rest time in
adults. Yet stages 1 through 4 have been labeled as non-REM sleep, or NREM—80
percent of sleep is defined by what it’s not. Sleep scientists speculate that
specific sequences of NREM and REM sleep somehow optimize our physical and mental recuperation.
At the cellular level, protein synthesis peaks during REM sleep, keeping the body working properly. REM sleep also seems essential for regulating mood and consolidating memories.

Every time we experience REM sleep, we literally go mad. By definition, psychosis is a condition characterized by hallucinations and delusions. Dreaming, some sleep scientists say, is a psychotic state—we fully believe that we see what is not there,
and we accept that time, location, and people themselves can morph and disappear without warning.

From ancient Greeks to Sigmund Freud to back-alley fortune-tellers, dreams have
always been a source of enchantment and mystery—interpreted as messages from the gods or our unconscious. Today many sleep experts aren’t interested in the specific
images and events in our dreams. They believe that dreams result from the chaotic firing of neurons and, even if imbued with emotional resonance, are devoid of significance. It’s only after we wake that the conscious brain, seeking meaning, quickly
stitches together a whole cloth out of haphazard scraps.

Other sleep scientists strongly disagree. “The content of dreams,” says Stickgold of Harvard, “is part of an evolved mechanism for looking at the larger significance of new memories and how they could be useful in the future.”

Even if you never recall a single image, you still dream. Everyone does. Lack of dream recollection is actually an indication of a healthy sleeper. The action in dream sleep takes place too deep in the brain to register well on an EEG, but with newer
technology, we’ve inferred what’s going on, physically and chemically. Dreams also occur in NREM sleep, especially stage 2, but these are generally thought to be more like overtures. Only in REM sleep do we encounter the full potent force of our
nighttime madness.

Dreams, often falsely said to be just momentary flashes, are instead thought to
span almost all of REM sleep, typically about two hours per night, though this decreases as we age—perhaps because our less pliant brains are not learning as much while
awake and have fewer new memories to process as we sleep. Newborn infants sleep
up to 17 hours a day and spend about half of that in an active, REM-like condition. And for about a month in the womb, starting at week 26 of gestation,
it seems that fetuses
remain without pause in a state very similar to REM sleep. All this REM time, it has been theorized, is the equivalent of the brain testing its software, preparing to come fully on line. The process is called telencephalization. It’s nothing less than
the opening of the mind.

The body doesn’t thermoregulate in REM sleep; our internal temperature remains at its lowest setting. We are truly out cold. Our heart rate increases compared with other sleep stages, and our breathing is irregular. Our muscles, with a few exceptions—
eyes, ears, heart, diaphragm—are immobilized. Sadly, this doesn’t keep some
of us from snoring; this bane of the bed partner, impetus for hundreds of anti-snoring gadgets, is caused when turbulent airflow vibrates the relaxed tissues of the throat or
nose. It’s common in stages 3 and 4 too. In REM sleep, whether snoring or not, we’re completely incapable of physical response, slack-jawed, unable to regulate even our blood pressure. Yet our brain is able to convince us that we’re surfing on
clouds, slaying dragons.

Belief in the unbelievable happens because in REM sleep, stewardship of the brain is transferred away from the logic centers and impulse-control regions. Production of two specific chemicals, serotonin and norepinephrine, is completely shut off. Both are
essential neurotransmitters, permitting brain cells to communicate, and without
them, our ability to learn and remember is severely impaired—we’re in a chemically altered state of consciousness. But it’s not a coma-like state, as
in stage 4. Our
brain during REM sleep is fully active, guzzling as much energy as when we’re
awake.

REM sleep is ruled by the limbic system—a deep-brain region, the untamed jungle of the mind, where some of our most savage and base instincts arise. Freud was right, in effect, that dreams do tap our primitive emotions. The limbic system is home to our
sex drive, aggression, and fear, though it also allows us to feel elation and joy and love. While it sometimes seems as if we have more nightmares than pleasant dreams, this probably isn’t true. Frightening dreams are simply more
likely to trigger our
override system and wake us.

Down in the brain stem, a little bulge called the pons is supercharged during REM sleep. Electrical pulses from the pons often target the part of the brain that controls muscles in the eyes and ears. Our lids usually remain shut, but our eyeballs bounce
from side to side, possibly in response to the intensity of the dream. Our inner ears too are active while we dream.

So are the parts of the brain that generate motion—which is why there’s frequently a sense of flying or falling in dreams. We dream, as well, in full color, unless we’ve been blind from birth, in which case dreams do not have visual imagery but
remain emotionally intense. Men’s and women’s dreams seem to be similar in emotional content. Every time a man dreams, even if the content isn’t sexual,
he has an erection; in women, blood vessels in the vagina are engorged. And while we dream, no
matter how absurd, despite all transgressions against the laws of physics, we’re almost always convinced we’re awake. The ultimate virtual-reality machine resides inside our head.

Thank goodness we’re paralyzed. When you dream, your brain is actually trying
to produce movements, but a system in the brain stem completely shuts down the motor-neuron gate. There’s a parasomnia—a sleep abnormality that affects the nervous system�
��called REM behavior disorder in which the gate does not fully lower, and people act out their dreams in spectacular fashion, punching, kicking, swearing, all while their eyes are closed and they’re fully asleep. This often results in injuries to the
sleeper and his or her bedmate.

The end of a REM session, like the end of stage 4, is usually marked with a brief awakening. If we rest naturally, without an alarm clock, our last dream of the night often concludes our sleep. Though the amount of time we’ve been asleep helps
determine the optimal moment to wake, daylight has immediate alerting properties. When light seeps through our eyelids and touches our retinas, a signal is sent to a deep-brain region called the suprachiasmatic nucleus. This is the time, for many of us,
that our last dream dissolves, we open our eyes, and we rejoin our real life.

Or do we? Perhaps the most remarkable thing about REM sleep is that it proves the brain can operate independently of sensory input. Like an artist ensconced in a secret studio, our mind appears to experiment without inhibition, let loose on its own
personal mission.

When we’re awake, the brain is occupied with busy work — all those limbs to
control, the constant driving and shopping and texting and talking. The money-earning, the child-rearing.

But when we’re sleeping, and we commence our first REM session, the most elaborate and complex instrument known in the universe is free to do what it wishes. It self-activates. It dreams. This, one could say, is the playtime of the brain. Some sleep
theorists postulate that REM sleep is when we are our most intelligent, insightful, creative, and free. It’s when we truly come alive.

.

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