From: david.j.worrell@gmail.com

The brain may clean out Alzheimer’s plaques during sleep

If sleep deprivation puts garbage removal on the fritz,
the memory-robbing disease may develop

Science News
BY LAURA BEIL JULY 15, 2018

http://tinyurl.com/ydcpnm4g

Neuroscientist Barbara Bendlin studies the brain as Alzheimer’s disease develops. When she goes home, she tries to leave her work in the lab. But one recent research project has crossed into her personal life: She now takes sleep
much more seriously.

Bendlin works at the University of Wisconsin–Madison, home to the Wisconsin Registry for Alzheimer’s Prevention, a study of more than 1,500 people who were ages 40 to 65 when they signed up. Members of the registry did not have symptoms of dementia
when they volunteered, but more than 70 percent had a family history of Alzheimer’s disease.

Since 2001, participants have been tested regularly for memory loss and other signs of the disease, such as the presence of amyloid-beta, a protein fragment that can clump into sticky plaques in the brain. Those plaques are a hallmark of Alzheimer’s,
the most common form of dementia.

Each person also fills out lengthy questionnaires about their lives in the hopes that one day the information will offer clues to the disease. Among the inquiries: How tired are you?

Some answers to the sleep questions have been eye-opening. Bendlin and her colleagues identified 98 people from the registry who recorded their sleep quality and had brain scans. Those who slept badly — measured by such things as being tired during the
day — tended to have more A-beta plaques visible on brain imaging, the researchers reported in 2015 in Neurobiology of Aging.

In a different subgroup of 101 people willing to have a spinal tap, poor sleep was associated with biological markers of Alzheimer’s in the spinal fluid, Bendlin’s team reported last year in Neurology. The markers included some related to A-beta
plaques, as well as inflammation and the protein tau, which appears in higher levels in the brains of people with Alzheimer’s.

Bendlin’s studies are part of a modest but growing body of research suggesting that a sleep-deprived brain might be more vulnerable to Alzheimer’s disease. In animal studies, levels of plaque-forming A-beta plummet during sleep. Other research
suggests that a snoozing brain runs the “clean cycle” to remove the day’s
metabolic debris — notably A-beta — an action that might protect against the disease. Even one sleepless night appears to leave behind an excess of the troublesome
protein fragment (SN Online: 7/10/17).

But while the new research is compelling, plenty of gaps remain. There’s not enough evidence yet to know the degree to which sleep might make a difference in the disease, and study results are not consistent.

A 2017 analysis combined results of 27 studies that looked at the relationship between sleep and cognitive problems, including Alzheimer’s. Overall, poor sleepers appeared to have about a 68 percent higher risk of these disorders than those who were
rested, researchers reported last year in Sleep. That said, most studies have a
chicken-and-egg problem. Alzheimer’s is known to cause difficulty sleeping. If Alzheimer’s both affects sleep and is affected by it, which comes first?

For now, the direction and the strength of the cause-and-effect arrow remain unclear. But approximately one-third of U.S. adults are considered sleep deprived (getting less than seven hours of sleep a night) and Alzheimer’s is expected to strike almost
14 million U.S. adults by 2050 (5.7 million have the disease today). The research has the potential to make a big difference.

Dream weavers

It would be easier to understand sleep deprivation if scientists had a better handle on sleep itself. The brain appears to use sleep to consolidate and process memories (SN: 6/11/16, p. 15) and to catalog thoughts from the day. But
that can’t be all.
Even the simplest animals need to sleep. Flies and worms sleep.

But mammals appear to be particularly dependent on sleep — even if some, like
elephants and giraffes, hardly nod off at all (SN: 4/1/17, p. 10). If rats are forced to stay awake, they die in about a month, sometimes within days.

And the bodies and brains of mice change when they are kept awake, says neurologist David Holtzman of Washington University School of Medicine in St. Louis. In one landmark experiment, Holtzman toyed with mice’s sleep right when the animals’ brain
would normally begin to clear A-beta. Compared with well-rested mice, sleep-deprived animals developed more than two times as many amyloid plaques over about a month, Holtzman says.

Losing sleep

Alzheimer’s disease disrupts sleep. And disrupted sleep itself might encourage Alzheimer’s by allowing buildup of amyloid-beta, or A-beta, which is thought to lead to the death of neurons. This cycle of sleep deprivation can
also affect levels of the
hormone melatonin, which helps the body to sleep, and can interfere with metabolism, a disruption that is also a risk factor for Alzheimer’s.

Source: Y. Saeed and S.M. Abbott/Current Neurology and Neuroscience Reports 2017

He thinks Alzheimer’s disease is a kind of garbage collection problem. As nerve cells, or neurons, take care of business, they tend to leave their trash lying around. They throw away A-beta, which is a leftover remnant of a larger protein that is
thought to form connections between neurons in the developing brain, but whose role in adults is still being studied. The body usually clears away A-beta.

But sometimes, especially when cheated on sleep, the brain doesn’t get the chance to mop up all the A-beta that the neurons produce, according to a developing consensus. A-beta starts to collect in the small seams between cells
of the brain, like
litter in the gutter. If A-beta piles up too much, it can accumulate into plaques that are thought to eventually lead to other problems such as inflammation and the buildup of tau, which appears to destroy neurons and lead to Alzheimer’s disease.

About a decade ago, Holtzman wanted to know if levels of A-beta in the fluid that bathes neurons fluctuated as mice ate, exercised, slept and otherwise did what mice do. It seemed like a run-of-the-mill question. To Holtzman’s surprise, time of day
mattered — a lot. A-beta levels were highest when the animals were awake but fell when the mice were sleeping (SN: 10/24/09, p. 11).

“We just stumbled across this,” Holtzman says. Still, it wasn’t clear whether the difference was related to the hour, or to sleep itself. So Holtzman
and colleagues designed an experiment in which they used a drug to force mice to stay awake or
fall asleep. Sure enough, the A-beta levels in the brain-bathing fluid rose and
fell with sleep, regardless of the time on the clock.

A-beta levels in deeply sleeping versus wide-awake mice differed by about 25 percent. That may not sound like a dramatic drop, but over the long term, “it
definitely will influence the probability [that A-beta] will aggregate to form amyloid plaques,”
Holtzman says.

The study turned conventional thinking on its head: Perhaps Alzheimer’s doesn’t just make it hard to sleep. Perhaps interrupted sleep drives the development of Alzheimer’s itself.

Published in Science in 2009, the paper triggered a flood of research into sleep and Alzheimer’s. While the initial experiment found that the condition worsens the longer animals are awake, research since then has found that the reverse is true, too,
at least in flies and mice.

Using fruit flies genetically programmed to mimic the neurological damage of Alzheimer’s disease, a team led by researchers at Washington University School of Medicine reversed the cognitive problems of the disease by simply forcing the flies to sleep (
SN: 5/16/15, p. 13).

Researchers from Germany and Israel reported in 2015 in Nature Neuroscience that slow-wave sleep — the deep sleep that occupies the brain most during a long snooze and is thought to be involved in memory storage — was disrupted in mice that had A-
beta deposits in their brains. When the mice were given low doses of a sleep-inducing drug, the animals slept more soundly and improved their memory and ability to navigate a water maze.

Gray matters

Even with these studies in lab animals indicating that loss of sleep accelerates Alzheimer’s, researchers still hesitate to say the same is true in people. There’s too little data. Human studies are harder and more complicated to do. One big hurdle:
The brain changes in humans that lead to Alzheimer’s build up over decades. And you can’t do a controlled experiment in people that forces half of the study’s volunteers to endure years of sleep deprivation.

Plus the nagging chicken-and-egg problem is hard to get around, although a study published in June in JAMA Neurology tried. Researchers from the Mayo Clinic in Rochester, Minn., examined the medical records of 283 people older than 70. None had dementia
when they enrolled in the Mayo Clinic Study of Aging. At the study’s start, participants answered questions about their sleep quality and received brain scans looking for plaque deposits.

People who reported excessive daytime sleepiness — a telltale sign of fitful sleep — had more plaques in their brains to start with. When checked again about two years later, those same people showed a more rapid accumulation than people who slept
soundly.

Other scientists have used brain scans to measure what happens to A-beta in people’s brains after a sleepless night. Researchers from the National Institutes of Health and colleagues completed a study involving 20 healthy people who had a brain scan
while rested and then again after they were forced to stay awake for 31 hours.

HARD DAY'S NIGHT Scientists measured accumulation of amyloid-beta in people who
were rested (left) and then again after 31 hours without sleep (right). In this
PET scan of one volunteer’s brain, levels of A-beta, which is linked to Alzheimer’s, rose
in the hippocampus (yellow at arrow) after sleep deprivation.

Nora Volkow, head of the National Institute on Drug Abuse in Bethesda, Md., led
the study. She is interested in sleep’s potential connections to dementia because people with drug addiction have massive disruptions of sleep. For the study, the
researchers injected people with a compound that latches onto A-beta and makes it visible under a PET scanner.

The sleep-deprived brains showed an increase in A-beta accumulation that was about 5 percent higher in two areas of the brain that are often damaged early in Alzheimer’s: the thalamus and hippocampus. Other regions had lesser buildup.

“I was surprised that it was actually so large,” says study coauthor Ehsan Shokri-Kojori, now at the National Institute on Alcohol Abuse and Alcoholism. “Five percent from one night of sleep deprivation is far from trivial.” And
while the brain
can likely recover with a good night’s sleep, the question is: What happens when sleep deprivation is a pattern night after night, year after year?

“It does highlight that sleep is indispensable for proper brain function,” Volkow says. “What we have to question is what happens when you are consistently sleep deprived.” The study was published April 24 in the Proceedings of the National
Academy of Sciences.

One bad night

Using PET scans to measure amyloid-beta markers, researchers compared levels of
A-beta in the brains of 20 healthy volunteers after one restful night and after
one night of sleep deprivation. Levels of the plaque-forming A-beta rose in most people tested.

As tantalizing as studies like this may seem, there are still inconsistencies that scientists are trying to resolve. Consider a study published in May in Sleep from a team of Swedish and British researchers. They set out to measure levels of A-beta in
cerebrospinal fluid and markers of neuron injury in 13 volunteers, sleep deprived and not.

The first measurements took place after five nights of sound sleep. Then participants were cut back to four hours of sleep a night, for five nights. Four participants even lasted eight days with only four hours of nightly sleep.
After good sleep versus
very little, the measurements did not show the expected differences.

“That was surprising,” says Henrik Zetterberg of the University Gothenburg in Sweden. Given the previous studies, including his own, “I would have expected a change.”

He notes, however, that the study participants were all healthy people in their
20s and 30s. Their youthful brains might cope with sleep deprivation more readily than those in middle age and older. But that’s just a hypothesis. “It shows why we have
to do further research,” he says.

Rinse cycle

Questions could be better answered if scientists could find a mechanism to explain how sleepless nights might exacerbate Alzheimer’s. In 2013, scientists revealed an important clue.

The lymphatic system flows through the body’s tissues to pick up waste and carry it away. All lymphatic vessels run to the liver, the body’s recycling plant for used proteins from each organ’s operation. But the lymphatic system
doesn’t reach the
brain.

“I found it weird because the brain is our most precious organ — why should
it be the only organ that recycles its own proteins?” asks Maiken Nedergaard,
a neuroscientist at the University of Rochester in New York. Maybe, she thought, the brain has
“a hidden lymphatic system.”

Nedergaard and colleagues decided to measure cerebrospinal fluid throughout the
brain. When mice were awake, there appeared to be little circulation of fluid in the brain. Then the team examined sleeping mice. “You take mice and train them to be quiet
under a microscope,” Nedergaard says. “The mice after a couple of days feel
very calm. Especially if you do it during the daytime when they are supposed to
be sleeping, and they are warm and you give them sugar water. They’re not afraid.”

The day of the experiment, the scientists made a hole in the mice’s skulls, placed a cover over it and injected a dye to measure cerebrospinal fluid in the
brain. During sleep, the spaces between the brain cells widened by about 60 percent and allowed
more fluid to wash through, taking the metabolic debris, including A-beta, with
it.


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From: david.j.worrell@gmail.com

While We Sleep, Our Mind Goes on an Amazing Journey

Our floodlit society has made sleep deprivation a lifestyle.
But we know more than ever about how we rest—and how it keeps us healthy.

[The World Health Organization has described night shift work as “probably carcinogenic to humans.”]

BY MICHAEL FINKEL

This story will appear in the August 2018 issue of National Geographic magazine.

http://tinyurl.com/y8y6snb6

Nearly every night of our lives, we undergo a startling metamorphosis.

Our brain profoundly alters its behavior and purpose, dimming our consciousness. For a while, we become almost entirely paralyzed. We can’t even shiver. Our eyes, however, periodically dart about behind closed lids as if seeing, and the tiny muscles in
our middle ear, even in silence, move as though hearing. We are sexually stimulated, men and women both, repeatedly. We sometimes believe we can fly. We
approach the frontiers of death. We sleep.

Around 350 B.C., Aristotle wrote an essay, “On Sleep and Sleeplessness,” wondering just what we were doing and why. For the next 2,300 years no one had a good answer. In 1924 German psychiatrist Hans Berger invented the electroencephalograph, which
records electrical activity in the brain, and the study of sleep shifted from philosophy to science. It’s only in the past few decades, though, as imaging machines have allowed ever deeper glimpses of the brain’s inner workings, that we’ve
approached a convincing answer to Aristotle.

Everything we’ve learned about sleep has emphasized its importance to our mental and physical health. Our sleep-wake pattern is a central feature of human biology—an adaptation to life on a spinning planet, with its endless wheel of day and night.
The 2017 Nobel Prize in medicine was awarded to three scientists who, in the 1980s and 1990s, identified the molecular clock inside our cells that aims to keep us in sync with the sun. When this circadian rhythm breaks down, recent research has shown, we
are at increased risk for illnesses such as diabetes, heart disease, and dementia.

[Light rich in blue wavelengths promotes alertness and is good in daytime, Lockley says. Redder light is best at night because it has less power to alert the brain or reset the biological clock.]

Yet an imbalance between lifestyle and sun cycle has become epidemic. “It seems as if we are now living in a worldwide test of the negative consequences of sleep deprivation,” says Robert Stickgold, director of the Center for Sleep and Cognition at
Harvard Medical School. The average American today sleeps less than seven hours
a night, about two hours less than a century ago. This is chiefly due to the proliferation of electric lights, followed by televisions, computers, and smartphones. In our
restless, floodlit society, we often think of sleep as an adversary, a state depriving us of productivity and play. Thomas Edison, who gave us light bulbs, said that “sleep is an absurdity, a bad habit.” He believed we’d eventually dispense with it
entirely.

A full night’s sleep now feels as rare and old-fashioned as a handwritten letter. We all seem to cut corners, fighting insomnia through sleeping pills, guzzling coffee to slap away yawns, ignoring the intricate journey we’re designed to take each
evening. On a good night, we cycle four or five times through several stages of
sleep, each with distinct qualities and purpose—a serpentine, surreal descent
into an alternative world.

[Light at night inhibits the production of melatonin, the hormone that helps regulate our daily biological rhythms.]

Stages 1-2

As we fall into sleep, our brain stays active and fires into its editing process—deciding which memories to keep and which ones to toss.

The initial transformation happens quickly. The human body does not like to stall between states, lingering in doorways. We prefer to be in one realm or another, awake or asleep. So we turn off the lights and lie in bed and shut our
eyes. If our
circadian rhythm is pegged to the flow of daylight and dark, and if the pineal gland at the base of our brain is pumping melatonin, signaling it’s nighttime, and if an array of other systems align, our neurons swiftly fall into step.

Neurons, some 86 billion of them, are the cells that form the World Wide Web of
the brain, communicating with each other via electrical and chemical signals. When we’re fully awake, neurons form a jostling crowd, a cellular lightning storm. When they
fire evenly and rhythmically, expressed on an electroencephalogram, or EEG, by neat rippled lines, it indicates that the brain has turned inward, away from the chaos of waking life. At the same time, our sensory receptors are muffled, and soon we’re
asleep.

Scientists call this stage 1, the shallow end of sleep. It lasts maybe five minutes. Then, ascending from deep in the brain, comes a series of electric sparks that zap our cerebral cortex, the pleated gray matter covering the outer
layer of the brain,
home of language and consciousness. These half-second bursts, called spindles, indicate that we’ve entered stage 2.

Our brains aren’t less active when we sleep, as was long thought, just differently active. Spindles, it’s theorized, stimulate the cortex in such a way as to preserve recently acquired information—and perhaps also to link it to established
knowledge in long-term memory. In sleep labs, when people have been introduced to certain new tasks, mental or physical, their spindle frequency increases that night. The more spindles they have, it seems, the better they perform the task the next day.

The strength of one’s nightly spindles, some experts have suggested, might even be a predictor of general intelligence. Sleep literally makes connections you might never have consciously formed, an idea we’ve all intuitively realized. No one says, “
I’m going to eat on a problem.” We always sleep on it.

The waking brain is optimized for collecting external stimuli, the sleeping brain for consolidating the information that’s been collected. At night, that
is, we switch from recording to editing, a change that can be measured on the molecular scale. We�
�re not just rotely filing our thoughts—the sleeping brain actively curates which memories to keep and which to toss.

It doesn’t necessarily choose wisely. Sleep reinforces our memory so powerfully—not just in stage 2, where we spend about half our sleeping time, but throughout the looping voyage of the night—that it might be best, for example, if exhausted
soldiers returning from harrowing missions did not go directly to bed. To forestall post-traumatic stress disorder, the soldiers should remain awake for six to eight hours, according to neuroscientist Gina Poe at the University of California, Los Angeles.
Research by her and others suggests that sleeping soon after a major event, before some of the ordeal is mentally resolved, is more likely to turn the experience into long-term memories.

Stage 2 can last up to 50 minutes during the night’s first 90-minute sleep cycle. (It typically occupies a smaller portion of subsequent cycles.) Spindles
can arrive every few seconds for a while, but when these eruptions taper off, our heart rate
slows. Our core temperature drops. Any remaining awareness of the external environment disappears. We commence the long dive into stages 3 and 4, the deep
parts of sleep.

[Finding the conditions that best trigger sleep could be the first step in curing insomnia.]

Stages 3-4
We enter a deep, coma-like sleep that is as essential to our brain as food is to our body. It’s a time for physiological housekeeping—not for dreaming.

Every animal, without exception, exhibits at least a primitive form of sleep. Three-toed sloths snooze about 10 hours a day, a disappointing display of languor, but some fruit bats manage 15 hours, and little brown bats have been reported to laze for 20.
Giraffes sleep less than five. Horses typically sleep part of the night standing up and part lying down. Dolphins sleep one hemisphere at a time—half
the brain sleeps while the other half is awake, allowing them to swim continuously. Great frigatebirds
can nap while gliding, and other birds may do the same. Nurse sharks rest in a pile on the ocean floor. Cockroaches lower their antennae while napping, and they’re also sensitive to caffeine.

Sleep, defined as a behavior marked by diminished responsiveness and reduced mobility that is easily disrupted (unlike hibernation or coma), exists in creatures without brains at all. Jellyfish sleep, the pulsing action of their bodies noticeably slowing,
and one-celled organisms such as plankton and yeast display clear cycles of activity and rest. This implies that sleep is ancient and that its original and
universal function is not about organizing memories or promoting learning but more about the
preservation of life itself. It’s evidently natural law that a creature, no matter the size, cannot go full throttle 24 hours a day.

“Being awake is demanding,” says Thomas Scammell, a neurology professor at Harvard Medical School. “You’ve got to go out there and outcompete every other organism to survive, and the consequences are that you need a period of rest to help cells
recuperate.”

For humans this happens chiefly during deep sleep, stages 3 and 4, which differ
in the percentage of brain activity that’s composed of big, rolling delta waves, as measured on an EEG. In stage 3, delta waves are present less than half the time; in
stage 4, more than half. (Some scientists consider the two to be a single deep-sleep stage.) It’s in deep sleep that our cells produce most growth hormone, which is needed throughout life to service bones and muscles.

There is further evidence that sleep is essential for maintaining a healthy immune system, body temperature, and blood pressure. Without enough of it, we can’t regulate our moods well or recover swiftly from injuries. Sleep may be more essential to us
than food; animals will die of sleep deprivation before starvation, says Steven
Lockley of Brigham and Women’s Hospital in Boston.

Good sleep likely also reduces one’s risk of developing dementia. A study done in mice by Maiken Nedergaard at the University of Rochester, in New York, suggests that while we’re awake, our neurons are packed tightly together, but
when we’re asleep,
some brain cells deflate by 60 percent, widening the spaces between them. These intercellular spaces are dumping grounds for the cells’ metabolic waste—notably a substance called beta-amyloid, which disrupts communication between neurons and is
closely linked to Alzheimer’s. Only during sleep can spinal fluid slosh like detergent through these broader hallways of our brain, washing beta-amyloid away.

[Sleep is crucial for childhood health and development; it’s when most growth
hormone and infection-fighting proteins are released... Poor sleep in kids has been linked to diabetes, obesity, and learning disabilities.]

While all this housekeeping and repair occurs, our muscles are fully relaxed. Mental activity is minimal: Stage 4 waves are similar to patterns produced by coma patients. We do not typically dream during stage 4; we may not even be able to feel pain. In
Greek mythology the gods Hypnos (sleep) and Thanatos (death) are twin brothers.
The Greeks may have been right.

“You’re talking about a level of brain deactivation that is really rather intense,” says Michael Perlis, the director of the Behavioral Sleep Medicine program at the University of Pennsylvania. “Stage 4 sleep is not far removed from coma or brain
death. While recuperative and restorative, it’s not something you’d want to
overdose on.”

At most, we can remain in stage 4 for only about 30 minutes before the brain kicks itself out. (In sleepwalkers at least, that shift can be accompanied by a
bodily jerk.) We often sail straight through stages 3, 2, and 1 into awakeness.

Even healthy sleepers wake several times a night, though most don’t notice. We drop back to sleep in a matter of seconds. But at this point, rather than repeating the stages again, the brain resets itself for something entirely new—a trip into the
truly bizarre.

[MASTER CLOCK
HOW LIGHT AFFECTS US

How perky we’re feeling at any moment depends on the interaction of two processes: “Sleep pressure,” which is thought to be created by sleep-promoting substances that accumulate in the brain during waking hours, and our circadian rhythm, the
internal clock that keeps brain and body in sync with the sun. The clock can be
set backward or forward by light. We’re particularly sensitive to blue (short-wavelength) light, the kind that brightens midday sunlight and our computer screens, but can
disrupt our cycle—especially at night, when we need the dark to cue us to sleep.

The pressure to sleep builds throughout the day.

INTERNAL TIMEKEEPER
The suprachiasmatic nucleus (SCN) spontaneously generates
a near 24-hour rhythm. Sunlight synchronizes it each day.

DAYTIME DOMINATOR
Metabolism, digestion, and hormones like the stress hormone cortisol
are tightly controlled by the SCN’s rhythm.

EVENING INFLUENCER
At dusk the SCN signals the pineal gland (via the spinal cord) to
release melatonin, a hormone that tells the body darkness has arrived.

LIGHT SETS OUR INTERNAL CLOCK  …
Some ganglion cells have blue-light-sensitive receptors that tell
our brain to set our circadian clock to night or day. They also
gather subtle light information from rods and cones.

… AND ARTIFICIAL LIGHT DISRUPTS IT
The bluer and brighter the light, the more likely it is to suppress
melatonin release and shift our sleep cycle — especially when
we’re exposed to it at night and up close on electronic screens.

Sleep Delay At Night:

Tablet - 96 mins
Smartphone - 67 mins
E-reader - with backlit display 58 mins
Incandescent - 55 mins
Candle - 0 mins]


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From: allreadydun@gmail.com

take a nap it works wonders.
100 million mexicans can't be wrong.
Not to mention the others who nap
on this planet. naping in the summer
is the best !

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