Posts tagged dementia
Articles and news from the latest research reports.
Acting Out Dreams Linked to Development of Dementia
The strongest predictor of whether a man is developing dementia with Lewy bodies — the second most common form of dementia in the elderly — is whether he acts out his dreams while sleeping, Mayo Clinic researchers have discovered. Patients are five times more likely to have dementia with Lewy bodies if they experience a condition known as rapid eye movement (REM) sleep behavior disorder than if they have one of the risk factors now used to make a diagnosis, such as fluctuating cognition or hallucinations, the study found.
The findings were being presented at the annual meeting of the American Academy of Neurology in San Diego. REM sleep behavior disorder is caused by loss of the normal muscle paralysis that occurs during REM sleep. It can appear three decades or more before a diagnosis of dementia with Lewy bodies is made in males, the researchers say. The link between dementia with Lewy bodies and the sleep disorder is not as strong in women, they add.
"While it is, of course, true that not everyone who has this sleep disorder develops dementia with Lewy bodies, as many as 75 to 80 percent of men with dementia with Lewy bodies in our Mayo database did experience REM sleep behavior disorder. So it is a very powerful marker for the disease," says lead investigator Melissa Murray, Ph.D., a neuroscientist at Mayo Clinic in Florida.
The study’s findings could improve diagnosis of this dementia, which can lead to beneficial treatment, Dr. Murray says.
"Screening for the sleep disorder in a patient with dementia could help clinicians diagnose either dementia with Lewy bodies or Alzheimer’s disease," she says. "It can sometimes be very difficult to tell the difference between these two dementias, especially in the early stages, but we have found that only 2 to 3 percent of patients with Alzheimer’s disease have a history of this sleep disorder."
Once the diagnosis of dementia with Lewy bodies is made, patients can use drugs that can treat cognitive issues, Dr. Murray says. No cure is currently available.
Researchers at Mayo Clinic in Minnesota and Florida, led by Dr. Murray, examined magnetic resonance imaging, or MRI, scans of the brains of 75 patients diagnosed with probable dementia with Lewy bodies. A low-to-high likelihood of dementia was made upon an autopsy examination of the brain.
The researchers checked the patients’ histories to see if the sleep disorder had been diagnosed while under Mayo care. Using this data and the brain scans, they matched a definitive diagnosis of the sleep disorder with a definite diagnosis of dementia with Lewy bodies five times more often than they could match risk factors, such as loss of brain volume, now used to aid in the diagnosis. The researchers also showed that low-probability dementia with Lewy bodies patients who did not have the sleep disorder had findings characteristic of Alzheimer’s disease.
"When there is greater certainty in the diagnosis, we can treat patients accordingly. Dementia with Lewy bodies patients who lack Alzheimer’s-like atrophy on an MRI scan are more likely to respond to therapy — certain classes of drugs — than those who have some Alzheimer’s pathology," Dr. Murray says.
(Source: mayoclinic.org)
New target for Alzheimer’s disease treatment
Researchers have found new evidence that insulating cells, the cells that protect our nerves, can be made and added to the central nervous system throughout our lifetime.
Chief investigator on the paper, Menzies Research Institute Tasmania’s Dr Kaylene Young, says there is now evidence that these cells may not be the passive by-standers to brain function that we once thought.
“Previously it was thought that most insulating cells in an adult brain were born before reaching adulthood,” Dr Young said.
“This research shows that new insulating cells are made from an immature cell type found in our brains, called oligodendrocyte precursor cells (OPCs).
“In fact, new insulation is added to brain circuits every day, which changes the way the circuits function.
“This process is likely to be very important for learning, memory, vision and co-ordination.”
“This finding may have important implications for sufferers of Alzheimer’s Disease, multiple sclerosis and other neurological disorders.
Alzheimer’s disease is the most common form of dementia. There are over 321,600 Australians living with dementia and without a medical breakthrough, the number of people with dementia is expected to be almost 900,000 by 2050. (Alzheimer’s Australia)
In Alzheimer’s Disease (AD) many nerve cells die. This causes patients with AD to progressively lose their ability to think clearly and remember things, and they can also experience problems with movement and co-ordination.
A single insulating cell in the brain supports the health and function of many nerve cells.
We know from diseases like multiple sclerosis that losing insulation makes nerve cells extremely vulnerable to damage and death.
This may also be true for AD, and there is an increasing amount of evidence that supports the idea that insulating cells are damaged before nerve cells and could contribute directly to nerve cell loss.
By studying brain scans from patients with AD, researchers previously found that the amount of insulation that is damaged matched the level of the patient’s dementia. The more damaged the insulation, the worse the person’s memory problems.
Dr Young’s research team are now investigating ways to hijack the natural ability of OPCs to make new insulating cells, and repair the insulation damage that is seen in the brains of AD patients.
“Stimulating OPCs in the brain is an appealing possibility since they are found throughout all brain regions, meaning that they are already where they need to be to make new insulating cells!
“We expect that increasing brain insulation, to re-wrap the nerve cells, will prevent more nerve cells from dying. Protecting nerve cells would prevent the rapid mental deterioration seen in people after they are diagnosed with AD,” Dr Young said.
This work was published this month, in the international journal, Neuron and involved collaboration with researchers in the United Kingdom and Japan.
(Source: utas.edu.au)
Improved Detection of Frontotemporal Degeneration May Aid Clinical Trial Efforts
A series of studies demonstrate improved detection of the second most common form of dementia, providing diagnostic specificity that clears the way for refined clinical trials testing targeted treatments. The new research is being presented by experts from the Perelman School of Medicine at the University of Pennsylvania at the American Academy of Neurology’s 65th Annual Meeting in San Diego March 16-23, 2013.
Frontotemporal degeneration, the most common dementia in people under 60, can be hereditary or sporadic in nature and caused by one of two different mutated proteins (tau or TDP-43). The disease results in damage to the anterior temporal and/or frontal lobes of the brain. As the disease progresses, it becomes increasingly difficult for people to plan or organize activities, behave appropriately in social or work settings, interact with others, and care for oneself, resulting in increasing dependency.
In one study, the team confirmed that a novel multimodal imaging approach was more accurate (88 percent) than using either MRI (72 percent) or DTI (81 percent) alone to detect FTD versus Alzheimer’s disease. The two imaging techniques integrate measures of white matter and grey matter, providing a statistically powerful method for predicting underlying pathology in order to screen patients for clinical trials.
“We are moving forward on our biomarker work to optimize our ability to identify the specific cause of an individual’s difficulties during life, said senior author Murray Grossman, MD, EdD, professor of Neurology and director of the Penn FTLD Center. “We use a novel multi-modality approach involving behavioral, imaging and biofluid biomarker measures.”
In a second study, researchers found that a brief series of neuropsychological tests of memory, word generation and conceptual flexibility (needed for creative problem-solving) helped differentiate people with very mild behavioral variant FTD (bvFTD) and those with mild cognitive impairment (MCI). The combination of tests correctly classified 85.7 percent of bvFTD cases and 83.3 percent of MCI cases at early stages of disease.
“This is particularly important because treatment trials with disease-modifying agents are emerging, often based on animal studies, yet we still don’t have all the tools we need to identify who is most appropriate to participate in one of these trials. Moreover, we can use this information we ascertain to help determine who is responding to a treatment in a clinical trial.”
The third study being presented at the meeting showed that hereditary forms of FTD appear to have more rapid cognitive decline and differing tau profiles compared with sporadic forms of the disease. For clinical trials testing whether a drug can delay damage caused by tau, any known differences in the speed of disease progression could interfere with trial results.
(Image courtesy: University of Pennsylvania)
Dynamic new software improves care of aging brain
Innovative medical records software developed by geriatricians and informaticians from the Regenstrief Institute and the Indiana University Center for Aging Research will provide more personalized health care for older adult patients, a population at significant risk for mental health decline and disorders.
A new study published in eGEMs, a peer-reviewed online publication recently launched by the Electronic Data Methods Forum, unveils the enhanced Electronic Medical Record Aging Brain Care Software, an automated decision-support system that enables care coordinators to track the health of the aging brain and help meet the complex biopsychosocial needs of patients and their informal caregivers.
The eMR-ABC captures and monitors the cognitive, functional, behavioral and psychological symptoms of older adults suffering from dementia or depression. It also collects information on the burden placed on patients’ family caregivers.
Utilizing this information, the software application provides decision support to care coordinators, who, working with physicians, social workers and other members of the health care team, create a personalized care plan that includes evidence-based non-pharmacological protocols, self-management handouts and alerts of medications with potentially adverse cognitive effects. The software’s built-in engine tracks patient visits and can be used to generate population reports for specified indicators such as cognitive decline or caregiver burnout.
"The number of older adults is growing rapidly. Delivering personalized care to this population is difficult and requires the ability to track a large number of mental and physical indicators," said Regenstrief Institute investigator Malaz Boustani, M.D., MPH, associate director of the IU Center for Aging Research and associate professor of medicine at the IU School of Medicine. He is senior author of the new study. "The software we have developed will help care coordinators measure the many needs of patients and their loved ones and monitor the effectiveness of individualized care plans."
In clinical trials over the past decade, Regenstrief and the IU Center for Aging Research investigator-clinicians developed and demonstrated the efficacy of an Alzheimer’s disease collaborative care model called the Aging Brain Care Medical Home. A hallmark of the ABC-MedHome is the employment of care coordinators who help clinicians identify and manage processes and protocols for Alzheimer’s patients who receive care in local primary care physician offices. The ABC-MedHome has been shown to improve the quality of Alzheimer’s care and decrease its burden on the health care system.
Within the ABC-MedHome program, Dr. Boustani and colleagues have now developed, tested, implemented and improved software that is sensitive to the clinical needs of a multispecialty team of professionals who provide care to complex patients across a variety of settings. The new software allows tracking of individual patient health outcomes as well as the ability to follow the status of an entire patient population with key quality, health and cost metrics.
"Integration of the eMR-ABC program within Wishard-Eskenazi Health was pivotal to our receipt in 2012 of a Health Care Innovation Challenge award from the Centers for Medicare & Medicaid Services to expand from care of 250 patients to 2,000 patients plus caregivers," said Dr. Boustani, who is medical director of the Wishard Healthy Aging Brain Center and also an IU Health geriatrician. "New models of care, supported by population health management tools, are needed if we are to provide improved quality of care and encourage better health outcomes for our patients and be cost sensitive. We are using health information technology to manage high-risk populations while achieving the triple aim of better health and better care at lower cost."
(Source: eurekalert.org)
Mutations in VCP gene implicated in a number of neurodegenerative diseases
New research, published in Neuron, gives insight into how single mutations in the VCP gene cause a range of neurological conditions including a form of dementia called Inclusion Body Myopathy, Paget’s Disease of the Bone and Frontotemporal Dementia (IBMPFD), and the motor neuron disease Amyotrophic Lateral Sclerosis (ALS).
Single mutations in one gene rarely cause such different diseases. This study shows that these mutations disrupt energy production in cells shedding new light on the role of VCP in these multiple disorders.
In healthy cells VCP helps remove damaged mitochondria, the energy-producing engines of cells. The mutant protein can’t do this and as a result, the dysfunctional mitochondria build up.
The new study led by Dr Fernando Bartolome, Dr Helene Plun-Favreau and Dr Andrey Abramov of the UCL Institute of Neurology, found that mitochondria are damaged in cells from patients with mutant VCP. Mitochondria generate a cell’s energy, and the study found these damaged mitochondria are less efficient, burning more nutrients but producing less energy. This reduction in available energy makes cells more vulnerable, which could explain why mutations in the VCP gene lead to neurological disorders.
Lead author Dr Fernando Bartolome said, “We have found that VCP mutations are associated with mitochondrial dysfunction. VCP had previously been shown to be important in the removal of damaged mitochondria and proteins, accumulation of which is potentially very toxic to cells. A single mutation in the VCP gene could cause multiple neurological diseases because a different type of protein is accumulating in each disorder”.
In the study, the researchers used live imaging techniques to examine the functioning of mitochondria in patient cells carrying three independent VCP mutations, and in nerve cells in which the amount of VCP has been reduced.
“The next step will be to find small molecules able to correct the mitochondrial dysfunction in the VCP deficient cells”, added Dr Bartolome .
Dr Brian Dickie, the Motor Neuron Disease Association’s Director of Research Development says: “Neurons - and motor neurons in particular - are incredibly energy hungry cells. These new findings from the team at UCL show that there is a significant interruption of energy supply in this hereditary form of MND, which has strong implications for understanding the degenerative process underpinning all forms of the disease.”
Sleep loss precedes Alzheimer’s symptoms
Sleep is disrupted in people who likely have early Alzheimer’s disease but do not yet have the memory loss or other cognitive problems characteristic of full-blown disease, researchers at Washington University School of Medicine in St. Louis report March 11 in JAMA Neurology.
The finding confirms earlier observations by some of the same researchers. Those studies showed a link in mice between sleep loss and brain plaques, a hallmark of Alzheimer’s disease. Early evidence tentatively suggests the connection may work in both directions: Alzheimer’s plaques disrupt sleep, and lack of sleep promotes Alzheimer’s plaques.
“This link may provide us with an easily detectable sign of Alzheimer’s pathology,” says senior author David M. Holtzman, MD, the Andrew B. and Gretchen P. Jones Professor and head of Washington University’s Department of Neurology. “As we start to treat people who have markers of early Alzheimer’s, changes in sleep in response to treatments may serve as an indicator of whether the new treatments are succeeding.”
Sleep problems are common in people who have symptomatic Alzheimer’s disease, but scientists recently have begun to suspect that they also may be an indicator of early disease. The new paper is among the first to connect early Alzheimer’s disease and sleep disruption in humans.
(Image: iStockphoto)
Scientists Identify Buphenyl as a Possible Drug for Alzheimer’s disease
Buphenyl, an FDA-approved medication for hyperammonemia, may protect memory and prevent the progression of Alzheimer’s disease. Hyperammonemia is a life-threatening condition that can affect patients at any age. It is caused by abnormal, high levels of ammonia in the blood.
Studies in mice with Alzheimer’s disease (AD) have shown that sodium phenylbutyrate, known as Buphenyl, successfully increases factors for neuronal growth and protects learning and memory, according to neurological researchers at the Rush University Medical Center.
Results from the National Institutes of Health funded study, recently were published in the Journal of Biological Chemistry.
“Understanding how the disease works is important to developing effective drugs that protect the brain and stop the progression of Alzheimer’s disease,” said Kalipada Pahan, PhD, the Floyd A. Davis professor of neurology at Rush and lead investigator of this study.
A family of proteins known as neurotrophic factors help in survival and function of neurons. Past research indicates that these proteins are drastically decreased in the brain of patients with Alzheimer’s disease (AD).
“Neurotrophic factor proteins could be increased in the brain by direct injection or gene delivery,” said Pahan. “However, using an oral medication to increase the level of these protein may be the best clinical option and a cost effective way to increase the level of these proteins directly in the brain.”
“Our study found that after oral feeding, Buphenyl enters into the brain, increases these beneficial proteins in the brain, protects neurons, and improves memory and learning in mice with AD-like pathology,” said Pahan.
In the brain of a patient with AD, two abnormal structures called plaques and tangles are prime suspects in damaging and killing nerve cells. While neurons die, other brain cells like astroglia do not die.
The study findings indicate that Buphenyl increases neurotrophic factors from astroglia. Buphenyl stimulates memory-related protein CREB (cyclic AMP response element-binding protein) using another protein known as Protein Kinase C (PKC) and increases neurotrophic factors in the brain.
"Now we need to translate this finding to the clinic and test Buphenyl in Alzheimer’s disease patients,” said Pahan. “If these results are replicated in Alzheimer’s disease patients, it would open up a promising avenue of treatment of this devastating neurodegenerative disease.”
Drugs targeting blood vessels may be candidates for treating Alzheimer’s
University of British Columbia researchers have successfully normalized the production of blood vessels in the brain of mice with Alzheimer’s disease (AD) by immunizing them with amyloid beta, a protein widely associated with the disease.
While AD is typically characterized by a build-up of plaques in the brain, recent research by the UBC team showed a near doubling of blood vessels in the brain of mice and humans with AD.
The new study, published online last week in Scientific Reports, a Nature journal, shows a reduction of brain capillaries in mice immunized with amyloid beta – a phenomenon subsequently corroborated by human clinical data – as well as a reduction of plaque build-up.
“The discovery provides further evidence of the role that an overabundance of brain blood vessels plays in AD, as well as the potential efficacy of amyloid beta as basis for an AD vaccine,” says lead investigator Wilfred Jefferies, a professor in UBC’s Michael Smith Laboratories.
“Now that we know blood vessel growth is a factor in AD, if follows that drugs targeting blood vessels may be good candidates as an AD treatment.”
AD accounts for two-thirds of all cases of dementia. The number of Canadians living with dementia is expected to reach 1.4 million by 2013, according to the Alzheimer’s Society of Canada.
Worming Our Way to New Treatments for Alzheimer’s Disease
According to a 2012 World Health Organization report, over 35 million people worldwide currently have dementia, a number that is expected to double by 2030 (66 million) and triple by 2050 (115 million). Alzheimer’s disease, the most common form of dementia, has no cure and there are currently only a handful of approved treatments that slow, but do not prevent, the progression of symptoms.
New drug development, no matter the disease, is a slow, expensive, and risky process. Thus, innovative techniques to study and assess the possibilities of already-existing drugs for different diseases can be used to alleviate the traditional burdens of cost and time. Detailed in their new article in Biological Psychiatry, researchers from the University of Washington, led by Dr. Brian Kraemer, have developed an exciting new approach to screening potential new treatments for Alzheimer’s disease using C. elegans, a small transparent worm.
Their focus was on tau, a protein involved in maintaining brain cell structure. In Alzheimer’s disease and related disorders, tau protein becomes abnormally modified and forms clumps of protein called aggregates. These aggregates are a hallmark of the dying nerve cells in Alzheimer’s disease and other related disorders. Diseases with abnormal tau are called tauopathies.
Dr. Kraemer’s lab previously developed a worm model for tauopathy by expressing human tau in C. elegans nerve cells. This model has behavioral abnormalities, accumulates abnormal tau protein, and exhibits loss of nerve cells—all of which are general features of Alzheimer’s disease.
Using their worm model for this study, they screened a library of 1,120 drugs approved for human use and tested each at three different concentrations to identify compounds that suppress the effects of abnormal tau aggregation.
“We have identified six compounds capable of reliably alleviating tau induced behavioral abnormalities in our C. elegans model for tauopathy. In a human cultured cell model for abnormal tau protein, we have also seen that azaperone treatment can decrease the amount of abnormal tau,” said Kraemer.
Azaperone, an antipsychotic drug, normally binds to certain dopamine receptors found in nerve cells. They demonstrated that removing those receptors in either C. elegans or human cells has the same effect as azaperone treatment, indicating that azaperone and related drugs should alter abnormal tau accumulation. Other antipsychotic drugs also have a similar effect to azaperone.
Tests of these compounds for anti-tau properties are now underway in existing mouse models of Alzheimer’s disease.
“This study is an exemplary instance of how a simple C. elegans model system may be used to rapidly screen drugs for diseases and evaluate mechanism of action,” said Drs. Sangeetha Iyer and Jonathan Pierce-Shimomura, authors of a commentary that accompanies this article.
Dr. John Krystal, Editor of Biological Psychiatry, agrees and added: “Studying the worm, C. elegans, has already provided us with fundamental insights into how the brain develops. The new approach described by McCormick and colleagues suggests that this animal model may be a powerful new approach to studying novel treatments that prevent its decline.”
(Source: elsevier.com)
"Use it or lose it." The saying could apply especially to the brain when it comes to protecting against Alzheimer’s disease. Previous studies have shown that keeping the mind active, exercising and social interactions may help delay the onset of dementia in Alzheimer’s disease.
Now, a new study led by Dennis Selkoe, MD, co-director of the Center for Neurologic Diseases in the Brigham and Women’s Hospital (BWH) Department of Neurology, provides specific pre-clinical scientific evidence supporting the concept that prolonged and intensive stimulation by an enriched environment, especially regular exposure to new activities, may have beneficial effects in delaying one of the key negative factors in Alzheimer’s disease.
The study will be published online on March 6, 2013 in Neuron.
Alzheimer’s disease occurs when a protein called amyloid beta accumulates and forms “senile plaques” in the brain. This protein accumulation can block nerve cells in the brain from properly communicating with one another. This may gradually lead to an erosion of a person’s mental processes, such as memory, attention, and the ability to learn, understand and process information.
The BWH researchers used a wild-type mouse model when evaluating how the environment might affect Alzheimer’s disease. Unlike other pre-clinical models used in Alzheimer’s disease research, wild-type mice tend to more closely mimic the scenario of average humans developing the disease under normal environmental conditions, rather than being strongly genetically pre-disposed to the disease.
Selkoe and his team found that prolonged exposure to an enriched environment activated certain adrenalin-related brain receptors which triggered a signaling pathway that prevented amyloid beta protein from weakening the communication between nerve cells in the brain’s “memory center,” the hippocampus. The hippocampus plays an important role in both short- and long-term memory.
The ability of an enriched, novel environment to prevent amyloid beta protein from affecting the signaling strength and communication between nerve cells was seen in both young and middle-aged wild-type mice.
"This part of our work suggests that prolonged exposure to a richer, more novel environment beginning even in middle age might help protect the hippocampus from the bad effects of amyloid beta, which builds up to toxic levels in one hundred percent of Alzheimer patients," said Selkoe.
Moreover, the scientists found that exposing the brain to novel activities in particular provided greater protection against Alzheimer’s disease than did just aerobic exercise. According to the researchers, this observation may be due to stimulation that occurred not only physically, but also mentally, when the mice moved quickly from one novel object to another.
"This work helps provide a molecular mechanism for why a richer environment can help lessen the memory-eroding effects of the build-up of amyloid beta protein with age," said Selkoe. "They point to basic scientific reasons for the apparent lessening of AD risk in people with cognitively richer and more complex experiences during life."