Is there a relation between Alzheimer's and sleep?

Caregivers, and healthcare professionals,here is some great information

Here is a great dementia resource for caregivers and healthcare professionals,

Follow alzheimersideas on twitter
The Dementia Caregiver's Little Book of Hope [Kindle Edition]

Your residents will love the Amazon Kindle Fire

Here is information on being the best caregiver you can be

Here is a way for nurses administrators, social workers and other health care  professionals to get an easyceu or two

• University of California - Berkeley

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.

Source:

• University of California - Berkeley

---

Journal Reference:

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

Alzheimer's study

Caregivers, and healthcare professionals,here is some great information

Here is a great dementia resource for caregivers and healthcare professionals,

Your residents will love the Amazon Kindle Fire

Here is information on being the best caregiver you can be

Here is a way for nurses administrators, social workers and other health care  professionals to get an easyceu or two

Follow alzheimersideas on twitter

The Dementia Caregiver's Little Book of Hope [Kindle Edition

Kenneth S. Kosik, MD, is professor of neuroscience and codirector of the Neuroscience Research Institute

It’s easy to think that the mysteries of Alzheimer’s disease will be revealed in the high-tech hallways of US medical centers and research institutes. But new discoveries are coming from far-off places like Medellín, Colombia, which may be ground zero for finding the genetic basis of this dreaded neurodegenerative disease that strips people of memories and destroys personalities.

For more than 25 years, I have worked with Dr. Francisco Lopera of Medellín’s University of Antioquia in studying the largest known family with inherited Alzheimer’s disease. Its family tree goes back 300 hundred years. Hundreds of individuals in this family are fated to get the disease. Their symptoms usually develop between the ages of 45 and 50.

Studying this community has given us a clear picture of Alzheimer’s in this genetic microcosm. We now know the gene, called presenilin 1 (PSEN1), that is responsible for this family’s disease. Knowing the gene mutation means we can predict which family members will get Alzheimer’s. Knowing whom the disease will strike, and when, offers a powerful basis for finding a treatment and determining if it is effective. The Colombian family is now part of a large prevention trial.

While most of the family members with the PSEN1 variant develop Alzheimer’s disease before age 50, a few develop it later. We have recently discovered that these individuals carry a different genetic variant that provides some protection against the disease. This modifier gene can delay Alzheimer’s onset by as much eight to 10 years. But it doesn’t provide complete protection — we haven’t seen anyone with the PSEN1 mutation who escapes Alzheimer’s disease.

In a surprisingly improbable happenstance, another large family with a different genetic mutation that also causes Alzheimer’s at an early age lives in a nearby village. This gives us an opportunity to put our findings of a modifier gene to the test in a different genetic setting.

Obstacles remain

Despite more than 100 years of research, relatively little is known about Alzheimer’s disease. Experts still don’t have a fundamental understanding of the underlying biological and physiological changes of the disease or what drives them.

The scope of the problem is daunting. Around the world, more than 40 million people are currently suffering from Alzheimer’s; more than 5 million of them live in the United States, and that number is projected to double as baby boomers age over the next 20 years. The disease already burdens our communities and our country: 15 million Americans provide care for a loved one with the disease, while Alzheimer’s health care costs exceed $200 billion a year in the US and are projected to surpass $1 trillion as the population ages.

READ MORE

Leading Alzheimer’s group splinters over claims of misplaced priorities and lavish spending

The drug development process for Alzheimer’s disease is riddled with challenges. One issue for clinical trials is the inclusion of individuals misdiagnosed with Alzheimer’s disease. Including individuals with vascular dementia, Lewy body dementia, or even poorly understood forms of cognitive impairment — all of which can look like Alzheimer’s — can easily throw off a trial’s results. On the other hand, including those with advanced Alzheimer’s may also skew results because they may have lost too many brain cells to measurably respond to the therapy.

Researchers also face challenges when measuring trial outcomes, since they must quantify changes in the way a person thinks (cognition). Directly measuring cognition can be hard to do, so stand-ins such as brain imaging are often used to interpret whether a therapy is effective. Unfortunately, such stand-ins don’t always correlate with changes in cognition or quality of life.

A path forward

Lopera and other colleagues are now conducting a clinical trial in Colombia to test an antibody directed against a type of protein called amyloid, which collects in the brain plaques associated with Alzheimer’s disease.

Regardless of the outcome of this trial, additional research and trials in Medellín and other parts of the world may help us better identify the underlying physiology of the disease, information the global scientific community desperately needs. Expanding the scope of our understanding can help expand the pipeline for drugs to target Alzheimer’s. There are likely many ways into this problem, but one thing is certain: The only way out of it is research.

Altered sleep patterns 'early sign' of Alzheimer’s

Caregivers, and healthcare professionals, here is some great information

Here is a great dementia resource for caregivers and healthcare professinals,

Your residents will love the Amazon Kindle Fire

Here is information on being the best caregiver you can be

Here is a way for nurses administrators, social workers and other health care  professionals to get an easyceu or two

Follow alzheimersideas on twitter

The Dementia Caregiver's Little Book of Hope [Kindle Edition

Nursing Times

Bad sleep may predict Alzheimer’s,” the BBC has reported, saying that “problems sleeping may be an early sign of Alzheimer’s if a study in mice also applies to people”.

This news is based on research into the association between sleep patterns and accumulation of plaques in the brains of mice. These plaques, which are made up of clumps of small proteins in the brain, are a sign of Alzheimer’s disease. They are reported to start to form in the brain 10 to 15 years before symptoms such as memory problemsappear.

The researchers investigated whether the early stages of plaque development were associated with changes to the sleeping patterns of mice. They found that as plaques began to develop, the mice spent more time awake and less time asleep.

The researchers concluded that further research in humans is needed to determine whether or not this association is also seen in people with Alzheimer’s disease, and whether changes in sleep behaviour may be a sign of early Alzheimer’s.

If researchers confirm a similar association in humans, then the findings may provide an additional warning sign for early-stage Alzheimer’s. However, sleep problems in themselves are not evidence that a person is developing Alzheimer’s.

Many things can cause difficulty sleeping (insomnia), including normal ageing, stress, medications and physical or mental health conditions. Read more about the causes of insomnia.

Where did the story come from?

The study was carried out by researchers from Washington University School of Medicine in the USA and was funded by the American Academy of Neurology, the Ellison Medical Foundation and the Cure Alzheimer’s Fund.

The study was published in the peer-reviewed journal Science Translational Medicine.

The media coverage of this research was quite appropriate. The BBC emphasised that we will have to wait to see whether or not the results of this animal study apply to humans before concluding that sleep troubles are an early sign of Alzheimer’s.

What kind of research was this?

This was an animal study into the association between the accumulation of amyloid-β peptide and sleep patterns. The research used mice that had been bred with a genetic mutation similar to those seen in a mainly inherited form of the disease in humans.

In people, this particular mutation is associated with the early development of Alzheimer’s, often in young adulthood.

Previous research in both mice and healthy people has shown that amyloid-β levels vary naturally with the sleep–wake cycle, with levels increasing while people are awake, and dropping during sleep.

The early stages of Alzheimer’s (before symptoms such as memory and thinking problems are apparent) are marked by the accumulation of amyloid-β into clumps of proteins known as plaques. Given that higher amyloid-β levels are associated with wakefulness, the researchers thought that sleep patterns may be an early behavioural sign of plaque development.

Animal studies are often used in the early stages of clinical research, but it is not appropriate to assume that the results from such studies can be generalised to human disease. Studies using mouse models for Alzheimer’s can give us a general idea of the associations and causes that may underlie the illness. Further research in humans is required to be sure that the results are applicable to Alzheimer’s in humans.

What did the research involve?

The researchers used two groups of mice, one with a genetic mutation similar to that seen in some people with an inherited form of Alzheimer’s, and one without the mutation (the control mice). Within each group, they examined differences in the sleep–wake cycle before and after the development of amyloid-β plaques.

Before the plaques developed, they measured the amount of time the mice were awake each hour throughout the day, as well as the amount of sleep time spent in rapid eye movement (REM) sleep. REM sleep is a marker of the quality of sleep – people experience REM sleep when they are in deep sleep and, often, while dreaming. Once the plaques started forming, the researchers once again measured these two factors and determined whether or not any changes to sleep patterns had occurred.

What were the basic results?

The researchers found that before the plaques developed the mice with the genetic mutation spent an average of 30 minutes each hour awake during a 24-hour period. After three months, plaques began to form and the mice spent significantly more time awake, on average. After six months the mice were awake for an average of 40 minutes each hour. The control mice were spending approximately 30 minutes awake each hour after six months, similar to the amount of time seen before the development of plaques in the Alzheimer’s model mice.

The researchers also found that as the amount of time spent asleep decreased, the quality of the sleep deteriorated as well, with the mice spending fewer minutes each hour in REM sleep.

How did the researchers interpret the results?

The researchers concluded that the accumulation of amyloid-β plaques was associated with getting less, as well as poorer quality, sleep in mice.

Conclusion

This study suggests that, in mice, the amount and quality of sleep decreases as amyloid-β plaques accumulate. Further research in humans will be needed before we know whether this is also the case in people with Alzheimer’s.

The researchers say that the relationship between changes in the sleep cycle and amyloid-β accumulation is not well understood. They say that previous research has shown that “sleep disruption and disorders might be a risk factor for the development” of amyloid-β deposits and possibly Alzheimer’s. Yet their research found that the development of these plaques led to the disruption of sleep.

They suggest that this may not be a straightforward cause-and-effect relationship, but may represent a cycle in which an initial increase in the amount of time spent awake initiates the clumping of amyloid-β, which leads to further disruption of the sleep–wake cycle, which leads to further clumping of amyloid-β, and so on.

Several factors should be considered when interpreting this research. First, the mouse model used is intended to mirror only one type of Alzheimer’s that arises due to a specific genetic mutation, and often results in the development of the disease earlier in life. Thus, research will need to confirm whether the findings hold in people with this genetic mutation, and whether they can be further generalised to people who do not have this mutation and develop Alzheimer’s later in life.

If similar disruptions to sleep patterns are found in humans, the researchers suggest that changes in sleep patterns may be a useful indicator of the early stages of Alzheimer’s, or as a way to measure responsiveness to “new disease-modifying therapies as they become available”.

However, the usefulness of recognising changes in sleep patterns in terms of identifying people in the early stages of the disease may be limited, as difficulty sleeping is fairly common, especially as people age.

Getting less and poorer quality sleep may not be a specific enough sign to be clinically useful, as such problems may result from a number of factors.

At this stage, this study can serve as a useful addition to the body of knowledge surrounding Alzheimer’s, but does not offer a practical ‘early-warning sign’ for the disease.

• Roh JH, Huang Y, Bero AW, et al. Disruption of the Sleep-Wake Cycle and Diurnal Fluctuation of β-Amyloid in Mice with Alzheimer’s Disease Pathology.