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Is Sleep a Missing Piece in the Alzheimer’s Puzzle?


The link between sleep, beta-amyloid and Alzheimer’s is increasingly clear. Beta-amyloid deposition leads to a vicious cycle – it disturbs sleep and impairs memory, which trigger further deposition. Learn what it means for lowering Alzheimer’s risk and improving sleep habits.

Scientists at the University of California, Berkeley, have found compelling evidence that poor sleep — particularly a deficit of the deep, restorative slumber needed to hit the save button on memories — is a channel through which the beta-amyloid protein believed to trigger Alzheimer’s disease attacks the brain’s long-term memory. (Beta-amyloid is the protein that makes up the toxic plaque that is the most common suspect behind Alzheimer’s.)

“Our findings reveal a new pathway through which Alzheimer’s disease may cause memory decline later in life,” said UC Berkeley neuroscience professor Matthew Walker, senior author of the study to be published in the journalNature Neuroscience.

Excessive deposits of beta-amyloid are key suspects in the pathology of Alzheimer’s disease, a virulent form of dementia caused by the gradual death of brain cells. An unprecedented wave of aging baby boomers is expected to make Alzheimer’s disease, which has been diagnosed in more than 40 million people, one of the world’s fastest-growing and most debilitating public health concerns.

The Good News

The good news about the findings, Walker said, is that poor sleep is potentially treatable and can be enhanced through exercise, behavioral therapy and even electrical stimulation that amplifies brain waves during sleep, a technology that has been used successfully in young adults to increase their overnight memory.

“This discovery offers hope,” he said. “Sleep could be a novel therapeutic target for fighting back against memory impairment in older adults and even those with dementia.”

The study was co-led by UC Berkeley neuroscientists Bryce Mander and William Jagust, a leading expert on Alzheimer’s disease. The team has received a major National Institutes of Health grant to conduct a longitudinal study to test their hypothesis that sleep is an early warning sign or biomarker of Alzheimer’s disease.

Real People

While most research in this area has depended on animal subjects, this latest study has the advantage of human subjects recruited by Jagust, a professor with joint appointments at UC Berkeley’s Helen Wills Neuroscience Institute, the School of Public Health and the Lawrence Berkeley National Laboratory.

“Over the past few years, the links between sleep, beta-amyloid, memory, and Alzheimer’s disease have been growing stronger,” Jagust said. “Our study shows that this beta-amyloid deposition may lead to a vicious cycle in which sleep is further disturbed and memory impaired.”

Using a powerful combination of brain imaging and other diagnostic tools on 26 older adults who have not been diagnosed with dementia, researchers looked for the link between bad sleep, poor memory and the toxic accumulation of beta-amyloid proteins.

“The data we’ve collected are very suggestive that there’s a causal link,” said Mander, lead author of the study and a postdoctoral researcher in the Sleep and Neuroimaging Laboratory directed by Walker. “If we intervene to improve sleep, perhaps we can break that causal chain.”

A buildup of beta-amyloid has been found in Alzheimer’s patients and, independently, in people reporting sleep disorders. Moreover, a 2013 University of Rochester study found that the brain cells of mice would shrink during non-rapid-eye-movement (non-REM) sleep to make space for cerebrospinal fluids to wash out toxic metabolites such as beta-amyloid.

How It Works

“Sleep is helping wash away toxic proteins at night, preventing them from building up and from potentially destroying brain cells,” Walker said. “It’s providing a power cleanse for the brain.”

Specifically, the researchers looked at how the quantity of beta-amyloid in the brain’s medial frontal lobe impairs deep non-REM sleep, which we need to retain and consolidate fact-based memories.

In a previous study, Mander, Jagust and Walker found that the powerful brain waves generated during non-REM sleep play a key role in transferring memories from the hippocampus — which supports short-term storage for information — to longer-term storage in the frontal cortex. In elderly people, deterioration of this frontal region of the brain has been linked to poor-quality sleep.

For this latest study, researchers used positron emission tomography (PET) scans to measure the accumulation of beta-amyloid in the brain; functional Magnetic Resonance Imaging (fMRI) to measure activity in the brain during memory tasks; an electroencephalographic (EEG) machine to measure brain waves during sleep; and statistical models to analyze all the data.

The research was performed on 26 older adults, between the ages of 65 and 81, who showed no existing evidence of dementia or other neurodegenerative, sleep or psychiatric disorders. First, they each received PET scans to measure levels of beta-amyloid in the brain, after which they were tasked with memorizing 120 word pairs, and then tested on how well they remembered a portion of them.

The study participants then slept for eight hours, during which EEG measured their brain waves. The following morning, their brains were scanned using fMRI as they recalled the remaining word pairs. At this point, researchers tracked activity in the hippocampus, where memories are temporarily stored before they are transferred to the prefrontal cortex.

Memory & Sleep

“The more you remember following a good night of sleep, the less you depend on the hippocampus and the more you use the cortex,” Walker said. “It’s the equivalent of retrieving files from the safe storage site of your computer’s hard drive, rather than the temporary storage of a USB stick.”

Overall, the results showed that the study participants with the highest levels of beta-amyloid in the medial frontal cortex had the poorest quality of sleep and, consequently, performed worst on the memory test the following morning, with some forgetting more than half of the information they had memorized the previous day.

“The more beta-amyloid you have in certain parts of your brain, the less deep sleep you get and, consequently, the worse your memory,” Walker said. “Additionally, the less deep sleep you have, the less effective you are at clearing out this bad protein. It’s a vicious cycle.

“But we don’t yet know which of these two factors — the bad sleep or the bad protein — initially begins this cycle. Which one is the finger that flicks the first domino, triggering the cascade?” Walker added.

And that’s what the researchers will determine as they track a new set of older adults over the next five years.

“This is a new pathway linking Alzheimer’s disease to memory loss, and it’s an important one because we can do something about it,” Mander said.

Alzheimer’s Weekly Store


Journal Reference:

  1. Matthew P Walker et al. β-amyloid disrupts human NREM slow waves and related hippocampus-dependent memory consolidationNature Neuroscience, June 2015 DOI: 10.1038/nn.4035
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June 9, 2015 7:13 pm

early onset dementia wife sleeps much in my mind.any time.

Chuck Anastasia
Chuck Anastasia
June 10, 2015 12:02 am

Pauley, Too much sleep may be a sign of depression. It took me a long time to understand that depression is not just sadness or a blue disposition, Fatigue & low energy are symptoms of depression.

June 10, 2015 10:58 pm

I sleep about six hours a night – uh-oh! But I walk the dog a few times a day, live as close as possible to the Mediterranean diet… and rooted for the NY Rangers in their playoffs!

June 13, 2015 6:57 pm

This comment has been removed by the author.

June 14, 2015 4:10 am

One of the main causes of a "less deep sleep", or a "superficial and several times by night interrupted sleep" , is the well known sleep apnea, that have several causes (even nasal obstruction by allergic rhinitis), between dozens of others causes that can be controlled. The sleep apnea leads to chronic low levels of energy and oxigen (hypoxia) in the brain during sleep, as in the part of the text of the Mayo Clinic article about sleep apnea describes it consequences :
"Sudden drops in blood oxygen levels that occur during sleep apnea increase blood pressure and strain the cardiovascular system. The more severe your sleep apnea, the greater the risk of high blood pressure.
However, obstructive sleep apnea increases the risk of STROKE regardless of whether or not you have high blood pressure. If there's underlying heart disease, these multiple episodes of low blood oxygen (hypoxia or hypoxemia) can lead to sudden death from a cardiac event. Studies also show that obstructive sleep apnea is associated with increased risk of atrial fibrillation, congestive heart failure and other vascular diseases."(part of the text from the Mayo Clinic site).
My notes :
It is interesting that,in a vicious circle, atrial fibrillation and/or chronic heart failure (mainly congestive heart failure),lowers significantly the brain energy/oxigen levels, that worsens the consequences of the sleep apnea to the brain.As "UPSTREAMS" to the betamyloid accumulation,the interrupted sleep by sleep apnea,can leads to Chronic Vascular Brain Disorders and it consequences,as the brain hypoxemia (low levels of oxigen in the vessels of the brain) and neuroglycopenia ( low levels of energy in the brain in consequence of the vascular disorders caused by the sleep apnea), that leads still "upstreams" to peroxinitrites accumulation, mitochondrial disfunction, more brain energy disorders, that "downstreams" leads to tau and betamyloid accumulation.
Then as Mayo Clinic states, sleep apnea is a severe disorder that most the times can be controlled, leading to prevents and treat it consequences to the brain and to the whole body. 

February 6, 2016 1:06 pm

My mother is 89 and has always had a lot of exercise and she has done puzzles etc for years, she has never smoked or drank alcohol and has never ever had problems sleeping. She has had alzheimers for about 5 years but needed to be put into a nursing home 2 years ago because she wasn't eating and was depressed (which she had never been in her life) she also wasn't taking care of her personal hygiene because her shower had changed to help her but it actually confused her. She also had type 2 diabetes and high blood pressure for a number of years.
I just wanted to give you a general idea of her health (healthy all of her life) and let you know that she NEVER EVER HAD SLEEP PROBLEMS.
thank you for the information. I am 61 and know that I will get alzheimers because my mother's mother had it and so have a few of her sisters and brothers

Reply to  Lynne
February 8, 2016 4:32 am

Sorry for your mother to has dementia,Lynne.

Only to remember,but diabetes and high blood pressure are the two main triggers of dementias. We ,baby boomers ,have to try to control both,to have some protection against dementias.

Best wishes


January 22, 2018 6:13 am

My husband has normal pressure hydrocephalus, VP SHUNT INSERTED INTO the skull and stomach 2014, akso vascular dementia, and sleep apnea ,on a Bypap machine, 2litre of 02. Plus diabetic, and high blood pressure, and heart disease, 3 stents. Sleep is horrible, up every 2 hours. Since brain surgery 2014😕

December 10, 2019 12:59 pm

My husband lived an active healthy life and never had a problem falling asleep or staying asleep. He developed high blood pressure later in life, but no diabetes.
Alzheimer’s ran deep on his mothers side of the family, killing not only her, but her father, four of her six siblings and her children (my husband and his sister).
Convincing me that Alzheimer’s is genetic and not a product of our lifestyle or sleeping patterns.

B. Berger

B. Berger

This site was inspired by my Mom’s autoimmune dementia.

It is a place where we separate out the wheat from the chaffe, the important articles & videos from each week’s river of news. With a new post on Alzheimer’s or dementia appearing on the internet every 7 minutes, the site’s focus on the best information has been a help to many over the past 15 years. Thanks to our many subscribers for your supportive feedback.

The site is dedicated to all those preserving the dignity of the community of people living with dementia.

Peter Berger, Editor

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Why Aging Ups Alzheimer’s

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This site was inspired by my Mom’s autoimmune dementia.

It is a place where we separate out the wheat from the chaffe, the important articles & videos from each week’s river of news. With a new post on Alzheimer’s or dementia appearing on the internet every 7 minutes, the site’s focus on the best information has been a help to many over the past 15 years. Thanks to our many subscribers for your supportive feedback.

The site is dedicated to all those preserving the dignity of the community of people living with dementia.

Peter Berger, Editor

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