Alzheimer’s Disease: Are You, Poor Sleeper, at Risk?

I talk quite a bit about dementia and Alzheimer’s disease with family and friends. Our parents are drifting into cognitive impairment, asking the same questions again and again and struggling to find words to express themselves, and we wonder if we’re destined for the same fate.

The concern may be justified in middle-aged adults with chronically poor sleep, according to new research on sleep and two proteins involved in Alzheimer’s disease. Here’s more about the study and its relevance to people with insomnia and other sleep disorders.

Proteins linked to Alzheimer's a function of insufficient deep sleepI talk quite a bit about dementia and Alzheimer’s disease with family and friends. Our parents are drifting into cognitive impairment, asking the same questions again and again and struggling to find words to express themselves, and we wonder if we’re destined for the same fate.

The concern may be justified in middle-aged adults with chronically poor sleep, according to new research on sleep and two proteins involved in Alzheimer’s disease. Here’s more about the study and its relevance to people with insomnia and other sleep disorders.

Poor Sleep and Cognitive Impairment

Previous research has shown that poor sleep increases the risk of cognitive impairment. And mild cognitive impairment—trouble thinking and memory loss—is one of the first signs of Alzheimer’s disease. The cognitive declines and memory problems gradually worsen as deposits of two proteins—amyloid beta and tau—grow thicker and thicker, causing brain tissue to atrophy and die. To date the disease is irreversible.

But “poor sleep” can take different shapes and forms:

  • Sleep apnea, or pauses in breathing that occur repeatedly throughout the night, leaving sleepers feeling unrested in the morning.
  • Restless legs syndrome, in which sleep is disrupted by involuntary leg movements in the first half of the night.
  • Insomnia, consisting of trouble falling asleep, staying asleep, or waking up early in the morning, and related daytime complaints

Which feature of some or all of these sleep disorders might hasten development of amyloid plaques in the brain? The researchers suspected the problem had to do with deep, or slow wave, sleep, which is associated with feeling rested and restored in the morning. So they set out to see if disrupted slow wave sleep would bring about increased levels of amyloid beta in the brain.

Who They Studied, What They Did

Seventeen healthy adults ages 35 to 65 participated in the study, none with sleep problems or cognitive impairment. Each participant wore a wrist watch-type device to monitor their sleep. After several nights of wearing the device, participants spent a night in a sleep lab. There, they underwent a sleep study that involved wearing headphones.

Half of the participants were allowed to sleep without interruption. The other half experienced sleep disruption. Every time they entered deep sleep, they were subjected to beeps that grew louder and louder until their slow waves disappeared and were replaced by brain waves characteristic of lighter sleep.

The participants subjected to the beeps reported feeling tired and unrefreshed in the morning although they slept as long as usual. Most did not recall awakening during the night. All participants underwent a spinal tap so researchers could test for levels of amyloid beta and tau in the spinal fluid.

The procedure was repeated a month later, when the participants originally allowed to sleep uninterruptedly were subjected to the beeps and the others were allowed to sleep without interruption. Another spinal tap was conducted in the morning to measure protein levels.

Disrupted Deep Sleep and Harmful Proteins in the Brain

The results supported researchers’ contention about the effects of disrupted slow wave sleep:

  1. Participants’ amyloid beta levels were up by 10 percent after a single night of disrupted slow wave sleep
  2. In addition, levels of tau were significantly higher in participants whose wrist monitors showed they’d slept poorly during the week before the spinal tap

So disrupted slow wave sleep increased amyloid beta levels after just one night and tau levels after several days of poor sleep. Evidently, one function of slow wave sleep is to help rid the brain of byproducts that collect there during the day. When deep sleep is compromised, amyloid beta and tau start to accumulate. Development of cognitive impairment and Alzheimer’s is then more likely to occur.

Alzheimer’s and Poor Sleep in Perspective

So does the overall risk of developing Alzheimer’s increase with every poor night’s sleep? Probably not. Lead author Yo-El S. Ju, cited in a Washington University press release, said it’s unlikely that a single night or even a week of poor sleep has much effect on overall risk of developing Alzheimer’s disease. Amyloid beta and tau levels probably go back down the next time the person has a good night’s sleep, she said.

It’s people with chronic, untreated sleep disorders who should be concerned. Here, too, a dose of perspective is in order. Slow wave sleep occurs during the first half of the night. People who suspect they have sleep apnea, which occurs throughout the night, or restless legs syndrome, which occurs during the first half of the night, would be wise to see a sleep specialist for diagnosis and treatment.

People with chronic insomnia may have cause for concern as well—and maybe not so much. These investigators did not find that excess amyloid beta and tau had anything to do with sleep duration or sleep efficiency. Further, it’s never been shown that the main problem for people with insomnia is insufficient slow wave sleep. Some insomniacs experience a reduced percentage of slow wave sleep. Yet in others, slow wave sleep is intact.

The underlying problem in insomnia may instead involve restless REM sleep, which typically occurs in the second half of the night. It may have nothing to do with the development of amyloid plaques in the brain.

In any event, chronic insomnia can be treated (although the causes remain largely unknown). Click on “insomnia treatment” in the tag cloud to the right for more information.

Pink Noise Enhances Sleep and Memory

An acoustic device may be able to accomplish for older adults what sleeping pills still cannot: enhance both sleep and memory.

Researchers at Northwestern University in Chicago conducted a study of 13 healthy older adults whose sleep deepened and whose recall of word pairs improved with timed acoustic stimulation at night. The discovery holds promise not just for older people with insomnia but also for everyone concerned about aging and memory impairment.

Sleep may be deeper and memory better by listening to timed exposure to pink noise at nightAn acoustic device may be able to accomplish for older adults what sleeping pills still cannot: enhance both sleep and memory.

Researchers at Northwestern University in Chicago conducted a study of 13 healthy older adults whose sleep deepened and whose recall of word pairs improved with timed acoustic stimulation at night. The discovery holds promise not just for older people with insomnia but also for everyone concerned about aging and memory impairment.

Older Research on Deep Sleep and Memory

Previous research has shown that memory consolidation for facts and events takes place mainly during deep, or slow wave, sleep. Overnight new memories are replayed in the brain and processed so they become more resistant to loss and deterioration. In this way, sleep actually improves our mental hold on learning that took place the day before.

Research has also shown that gentle sound stimulation at night—pink noise, specifically, which sounds like rushing water—can increase slow wave activity and improve the recall of words. Three prior studies were conducted on young adults, all with positive results. The Northwestern team wanted to see if older adults, who typically get less deep sleep and whose risk of memory impairment is greater, would reap the same benefits.

How They Conducted This Study

Thirteen adults ages 60 to 84 participated in this randomized controlled study. They spent two nights in a sleep lab spaced one to two weeks apart.

The procedure on both nights was identical in the eyes of the participants. They wore a device consisting in part of an electrode cap that would record their brain activity as they cycled through the different stages of sleep.

About 90 minutes before bedtime, participants were shown a series of 88 word pairs on a computer screen and told to memorize the pairs. Then, in random order, they were shown one word and asked to recall the other half of the pair (e.g., energy: oil). Then they put on soft headphones and went to sleep.

An hour after waking up, each participant was again shown the words, in random order, and asked to recall the paired word.

What participants did not know was on which of the two nights they were going to be exposed to several pulses of pink noise during slow wave sleep. The noise wasn’t loud enough to wake them up; nor was it faint enough for their brains to tune out. There was no noise exposure on the other night.

A Relationship Between Pink Noise, Sleep, and Memory

The results of the study were similar to results in the studies of young adults. Although participants’ overall sleep structure did not change,

  • When acoustic stimulation was delivered, it increased slow wave activity in the brain.
  • The acoustic stimulation improved participants’ morning recall of words. As predicted, they remembered more words in the morning than they had the night before. But after acoustic stimulation, on average they remembered 9 more words than they had the night before, as compared with recall on the morning following the night without noise, when on average they remembered only 3 more words.
  • The relative change in slow wave activity predicted the improvement in memory.

Tracking Brain Activity to Time Noise Exposure Right

This study might lead to the conclusion that older adults could sleep more soundly and smarten up by using pink noise sound apps at night. Maybe so and maybe not. Exposed to continuous low-level sound, the brain might decide to tune it out.

The beauty of this new device lies in the way it individualizes and maximizes the effects of treatment. It uses an automated algorithm to monitor slow waves produced in the brain and deliver acoustic stimuli at just the right time. This feature—called a phase-locked loop—was found in previous studies to increase slow wave activity and memory consolidation in young adults during daytime naps. So despite age-related changes in sleep and memory (and whether or not insomnia is involved), older adults stand to gain a lot if and when the device comes to market.

Northwestern University currently has a patent pending but researchers say more testing is needed before the device is ready for general use. Still, it’s nice to know that some researchers studying sleep and memory are thinking outside the box.

Deep Sleep for Insomniacs: Closer Than We Thought?

Could more deep sleep be the solution to insomnia? Investigators have toyed with the idea for years. People with insomnia tend not to get as much deep, or slow-wave, sleep as normal sleepers. Finding a way to prolong slow-wave sleep might make our sleep feel sounder and more restorative.

Last week’s discovery of a sleep node in the brainstem associated with the initiation of slow-wave sleep is promising news in this regard.

Sleep node in the brain could one day help insomnia sufferers sleep like babiesCould more deep sleep be the solution to insomnia? Investigators have toyed with the idea for years. People with insomnia tend not to get as much deep, or slow-wave, sleep as normal sleepers. Finding a way to prolong slow-wave sleep might make our sleep feel sounder and more restorative.

Last week’s discovery of a sleep node in the brainstem associated with the initiation of slow-wave sleep is promising news in this regard. Not only does it point to a new target for treatment. The procedure scientists at Harvard Medical School and University at Buffalo School of Medicine and Biomedical Sciences used to obtain their results suggests that the possibility of altering sleep via genetic modification may not be as remote as it sounds.

A Look at the Research

These researchers set out to study an area deep in the brainstem of humans and other mammals. It’s located in the medullary parafacial zone, or PZ. The PZ contains neurons that produce GABA, the main neurotransmitter responsible for calming the brain at night. These neurons are always active during normal slow-wave sleep.

They wanted to find out whether simply activating these neurons would induce slow-wave sleep in mice, and they used a novel protocol to find out. Rather than stimulating the GABA neurons with electrodes, a process that disturbs surrounding neurons, they targeted the GABA neurons by altering a gene.

“To get the precision required for these experiments,” said Patrick Fuller, senior author of the paper, “we introduced a virus into the PZ that expressed a ‘designer’ receptor on GABA neurons only but didn’t otherwise alter brain function.” Using innovative tools that enabled them to control the GABA neurons remotely, they turned the neurons on.

The result? The mice fell quickly into a deep sleep—as if they’d been knocked out with a sedative. But no sleep medication was involved.

The ability to induce slow-wave sleep by means of a single genetic modification is an encouraging development. “We are at a truly transformative point in neuroscience,” said Caroline E. Bass, co-author of the paper, “where the use of designer genes gives us unprecedented ability to control the brain.”

Other Treatments That Enhance Deep Sleep

Scientists have worked to develop other therapies that boost slow-wave sleep. But none are available for people with insomnia.

  • Development of sleep medications such as eplivanserin and pimavanserin was abandoned due to concerns about safety and side effects.
  • Transcranial magnetic stimulation (TMS)–a treatment in which an instrument sends a harmless magnetic signal through the scalp and skull into the brain, activating electrical impulses and inducing slow waves–is currently approved for the treatment of depression. Some studies have suggested that TMS is helpful in treating insomnia, and a clinical trial of TMS for insomnia is now under way at the University of Florida. But it hasn’t been approved as a therapy for insomnia yet.

Which brings us back to designer genes that modify sleep. I’ve always thought they were pie in the sky for my generation. But the results of this experiment suggest they may become a reality sooner than I thought.

 

"Sleep on It" Is Good Advice

Do you remember your dreams?

People who recall certain types of dreams—those in which they’re rehearsing a skill like riding a unicycle or skiing downhill—have a leg up on people who do not recall such dreams. They’re generally able to master skills faster.

Sleep helps you learn new tasks and skills more quicklyDo you remember your dreams?

People who recall certain types of dreams—those in which they’re rehearsing a skill like riding a unicycle or skiing downhill—have a leg up on people who do not recall such dreams. They’re generally able to master skills faster.

This is one of many fascinating bits of information I learned listening to Terry Gross’s interview of neuroscientist Penelope Lewis, whose new book, The Secret World of Sleep: The Surprising Science of the Mind at Rest, is set for release this month. (Click here to listen to the full interview on NPR’s Fresh Air.)

Lewis, who directs the Sleep and Memory Lab at the University of Manchester in England, is mainly interested in how sleep affects memory. “Memories evolve constantly,” she said, “and a lot of that evolution occurs when we’re asleep.”

Excerpts from the Interview

1)    Sleep helps to strengthen memories. “Supposing you are learning to play the piano,” Lewis said. “You’re moving your fingers a lot. That’s associated with responses in motor areas of your brain. . . . Those areas will become active again while you’re asleep, and that replay—or reactivation—is what we think is responsible for the strengthening. So it’s kind of like your brain is rehearsing stuff without you knowing, while you’re asleep.”

2)    But sleep doesn’t only strengthen memories. Sleep helps us synthesize information and understand what’s important and what’s not. “It’s about extracting out the gist or maybe the main points” of what you’ve learned, she said.

3)    At the same time as sleep serves to strengthen memories, it also enables us to forget. “Across the day while we’re busy doing things, experiencing things, seeing things, hearing things, learning things, processing different kinds of information, the connections between neurons in the brain get strengthened because they’re trying to retain all of this information,” Lewis said. “And an awful lot of it is garbage; it’s stuff you don’t want to remember or don’t care about—what you had for breakfast, or the color of a stain on the cover of a book or something. It’s really not useful or interesting.”

“And the problem is, if you keep storing all of this stuff, you reach capacity and you can’t keep storing more. And so what happens during sleep, and specifically during the deep stage of sleep that we call slow-wave sleep, is that all of those synapses get downscaled again. So where they’ve been strengthened up, they all get proportionally downscaled.”

These are just a few points Lewis touches on her interview, which, for those of us interested in what goes on in our heads at night, is well worth a listen. I’m guessing her book will make for a good read.

Memory Loss: What’s Sleep Got to Do with It?

We all know memory loss is part of aging, and that glimmerings of compromise start appearing in middle age.

A new study by sleep researchers in California suggests that age-related memory loss is caused by changes in sleep, and that remedies being developed to improve sleep may help us remember more.

memory-lossAll my friends are complaining about memory loss these days.

“Was I supposed to call you? I’m sorry. I can’t remember a thing unless I write it down.”

“It’s my Halfs-heimers. How long before I forget my name?”

All this talk about memory issues makes me feel a little less self-conscious about mine. Yes, I’m more and more prone to sounding like my mother, who gropes a lot for words. “She told me I had to—oh, you know—there’s something I have to fill out—you know—to get the money . . . She’s going to send it to me—what’s the word?” And how long before I also start repeating stories the way my mother does, who told me not once or twice but ten times that she suspected her missing checkbook fell into the trash?

Memory Loss and Sleep

We all know memory loss is part of aging, and that glimmerings of compromise start appearing in middle age. A new study by sleep researchers in California suggests that age-related memory loss is caused by changes in sleep, and that remedies being developed to improve sleep may help us remember more.

Short-term memory storage occurs in a brain region called the hippocampus. But for memories to become consolidated for long-term storage, they have to be transported to the front part of the brain, or the prefrontal cortex—a process that occurs during sleep. As people age, two things occur to interfere with this process.

  1. We lose gray matter in the prefrontal cortex, the region responsible for initiating the slow brainwaves that occur during deep sleep. Deep sleep is the kind of sleep that enables memory consolidation to occur. In turn,
  2.  We get less deep sleep—much less, in fact. While young adults spend about a quarter of their sleep time in deep sleep, the amount of deep sleep older adults get may be as little as 10 percent. So in older adults, some short-term memories in the hippocampus never get to migrate to the long-term storage area at the front of the brain.

“When we are young, we have deep sleep that helps the brain store and retain new facts and information,” said UC Berkeley sleep researcher Matthew Walker, commenting on the study in Medical News Today. “But as we get older, the quality of our sleep deteriorates and prevents those memories from being saved by the brain at night.” The result is that we have trouble remembering facts that we learned and events that occurred just a day or two before.

Remedies in the Pipeline

But hope is at hand, this same group of researchers says. Despite aged-related deterioration of the prefrontal cortex, new therapies under development now may help prevent memory loss. Weak electrical stimulation of the brain and new medications may help promote deep sleep and improve the memory of older adults.

“Can you jumpstart slow-wave sleep and help people remember their lives and memories better?” said Bryce Mander, a postdoctoral fellow in psychology at UC Berkeley and the lead author of the new study, published last month in the journal Nature Neuroscience. “It’s an exciting possibility.”

I don’t know how you feel, but I want access to these slow-wave sleep-promoting therapies RIGHT NOW.

Have you noticed that how soundly you sleep seems to affect your memory? The issue is near and dear to my heart, and I’ll share a more personal perspective in my blog on Thursday.

Boosting Slow-Wave Sleep Could Restore Memory

Disrupted Slow-Wave Sleep and Memory