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. 

Single brain trauma affects an enzyme associated with Alzheimer's disease

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

Tufts Now

By 

News Staff

A study, performed in mice and utilizing post-mortem samples of brains from patients with Alzheimer’s disease, found that a single event of a moderate-to-severe traumatic brain injury (TBI) can disrupt proteins that regulate an enzyme associated with Alzheimer’s. The paper, published in the Journal of Neuroscience, identifies the complex mechanisms that result in a rapid and robust post-injury elevation of the enzyme BACE1 in the brain. These results may lead to the development of a drug treatment that targets this mechanism to slow the progression of Alzheimer’s disease.

“A moderate-to-severe TBI, or head trauma, is one of the strongest environmental risk factors for Alzheimer’s disease. A serious TBI can lead to a dysfunction in the regulation of the enzyme BACE1. Elevations of this enzyme cause elevated levels of amyloid-beta, the key component of brain plaques associated with senility and Alzheimer’s disease,” says first author Kendall Walker, postdoctoral associate in the department of neuroscience at Tufts University School of Medicine (TUSM). 

Moderate-to-severe TBIs are caused most often by traumas such as severe falls or motor vehicle accidents that result in a loss of consciousness. Not all traumas to the head result in a TBI. According to the Centers for Disease Control and Prevention, each year 1.7 million people sustain a TBI. Concussions, the mildest form of a TBI, account for about 75 percent of all TBIs. Studies have linked repeated head trauma to brain disease, and some previous studies have linked single events of brain trauma to brain disease, such as Alzheimer’s. Alzheimer’s disease currently affects as many as 5.1 million Americans and is the most common cause of dementia in adults age 65 and over.

Building on her previous work, Giuseppina Tesco, an assistant professor of neuroscience in the School of Medicine, led a research team that first used an in vivo model to determine how a single episode of TBI could alter the brain. In the acute phase (first two days) following injury, levels of two intracellular trafficking proteins (GGA1 and GGA3) were reduced, and an elevation of BACE1 enzyme level was observed.

Next, in an analysis of post-mortem brain samples from patients with Alzheimer’s disease, the researchers found that GGA1 and GGA3 levels were reduced while BACE1 levels were elevated in the brains of Alzheimer’s disease patients compared to the brains of people without Alzheimer’s disease, suggesting a possible inverse association.

In an additional experiment using a mouse strain genetically modified to express the reduced level of GGA3 that was observed in the brains of Alzheimer’s disease patients, the team found that one week following traumatic brain injury, BACE1 and amyloid-beta levels remained elevated even when GGA1 levels had returned to normal. The research suggests that reduced levels of GGA3 were solely responsible for the increase in BACE 1 levels and therefore the sustained amyloid-beta production observed in the sub-acute phase, or seven days, after injury.

“When the proteins are at normal levels, they work as a clean-up crew for the brain by regulating the removal of BACE1 enzymes and facilitating their transport to lysosomes within brain cells, an area of the cell that breaks down and removes excess cellular material. BACE1 enzyme levels may be stabilized when levels of the two proteins are low, likely caused by an interruption in the natural disposal process of the enzyme,” said Tesco, who is also member of the neuroscience program faculty at the Sackler School of Graduate Biomedical Sciences at Tufts.

“We found that GGA1 and GGA3 act synergistically to regulate BACE1 post-injury. The identification of this interaction may provide a drug target to therapeutically regulate the BACE1 enzyme and reduce the deposition of amyloid-beta in Alzheimer’s patients,” she continued. “Our next steps are to confirm these findings in post-mortem brain samples from patients with moderate-to-severe traumatic brain injuries.”

Will the new Alzheimer's drugs work

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

Forbes


Michael Waldholz, 

In the coming months researchers will release results of several drug studies that will impact millions of Alzheimer’s victims and their families, as well as the fortunes of drugmakers,  Merck, Pfizer, Lilly and Johnson & Johnson  among others. Just as important, maybe even more so, the studies may finally provide evidence to support a controversial 20-year old theory of how the mind-robbing and lethal illness works.

But there’s plenty of reason to believe these studies tests will be inconclusive. The biggest worry is that even if the drugs work, the studies may show that to be effective, the medicines must be used much like anti-cholesterol pills, well  before the disease begins to show debilitating symptoms. If that’s true it will mean years of uncertainty about an effective treatment or cure. Alternately, the 

drugs may turn out to be complete busts, or only improve memory and thinking in a statistically negligible manner that will spark conflicting interpretations. And since there is nothing in drugmakers’ pipeline to replace the drugs being tested, negative results will force Alzheimer’s research back to square one for a disease that is already costing untold suffering and adding hundreds of millions of dollars a year in health costs that will explode as the population ages.

What follows is a review, a scorecard of sorts, of what is at stake. Much of this conversation will be front and center at an international research meeting beginning this weekend in Vancouver.

A primer: The experimental medicines all focus on attacking beta amyloid, a protein autopsies show masses in the brains of Alzheimer’s victims. According to the amyloid theory, these packets of plaque destroy brain cells over time, though exactly how they do this is still unknown. One school of scientists believes the plaques, which collect in small amounts in nearly all people as they reach old age, arise earlier and in much larger amounts in people with a predisposing genetic makeup. Another group argues that the clumping is merely the residue of some other unknown chain of events, so drugs designed to prevent or destroy amyloid will provide little if any benefit.

Alzheimer’s researchers, doctors and victims are literally holding their collective breath, hoping the studies will not only provide relief, but give scientists the kind of clear roadmap needed to fuel future investigations

A gene discovery backing the amyloid theory:  Just this week, a well-regarded research team in Icelandreported in the journal Nature that they had identified a gene that, when mutated, slows the body’s production an enzyme called beta secretase. This is a valuable discovery because beta secretase appears to play an important role in amyloid formation. Merck, Lilly and Esai are in advanced clinical studies of drugs that mimic the protective action of the gene by blocking the action of the enzyme. The Iceland group, under the direction of the gene-hunting company DeCode and its charismatic founder, Kari Stefansson, found that people with an unusual variant of the gene either don’t have the disease or don’t amass plaque in large amounts. Because the study involved a small number of people in Iceland, there is reason to be cautious about broader application.

• The garbage collectors:  Perhaps the most important advanced study, whose results will be reported in October, involves the drug bapineuzumab, being developed by Pfizer and Johnson & Johnson and a similar drug called solanezumab from Lilly. These medicines are laboratory produced antibodies that, given through infusions, have been shown to attack and clear amyloid from the brain. Early results of another drug, Gammagard from Baxter, a combination of plaque-clearing antibodies, will also be released at the week the Alzheimer’s Association International Conference. Even a slight increase in cognition from these drugs will likely result in FDA approval and annual sales of billions of dollars. The worry is that even there though the drugs can sterilize amyloid clumps from the brain, the patient population studied may be too far advanced in their disease to be helped, or the study not be sensitive enough to detect benefits.

Still another antibody, crenezumab, being developed by Roche’s Genentech unit, is being tested in a $100 million trial in a family in Colombia where an early-onset form of the disease is common. That trial, involving about 300 relatives, won’t be completed for years.

• The gatekeepers: Merck and Lilly are in the second of three phases of clinical trials of drugs called beta-secretase inhibitors, also referred to as BACE drugs. Unlike the antibody medicines, these drugs are being tested in pill form. The science underlying these drugs got a boost from the Iceland gene study. The idea behind these medicines is to inhibit the formation of amyloid plaque before it can cause havoc. As with the amyloid clearing drugs, there is concern that the studies underway involve patients too far into their disease.

• The takeaway: It is clear that all the drugs in development will be most effective if used early in the disease, meaning the ability to identify those at risk is critical. Even then, the health profession and policymakers will face a dilemma. Conducting population-wide screening will be enormously expensive. Giving these medicines as long-term preventive treatments will cost many billions of dollars more. This is just one of many example of why the nation’s health bill will continue to rise sharply, with or without success in battling Alzheimer’s disease.

Rock Creek Pharmaceuticals Announces First Study Using Anatabloc® Nutritional Supplementation in Alzheimer's Patients

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


You 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 Alzheimers1 on twitter


Market Watch


GLEN ALLEN, Va., PRNewswire via COMTEX/ -- Star Scientific, Inc. /quotes/zigman/80562/quotes/nls/cigx CIGX +5.90% through its wholly owned subsidiary, Rock Creek Pharmaceuticals, Inc., announces that it has received IRB approval of the first human clinical study of the safety and effects of nutritional supplementation with Anatabloc® in individuals with Alzheimer's disease. The study will be undertaken in conjunction with the Roskamp Institute of Sarasota, Florida, which has been acting as a research partner in assessing the impact of Anatabloc® on Alzheimer's