Abstract
Social Security announces new Compassionate Allowances conditions
Fast Track Disability Process Will Now Include 200 Conditions
Michael J. Astrue, Commissioner of Social Security, today announced 35 additional Compassionate Allowances conditions are in effect, bringing the total number of conditions in the expedited disability process to 200. Compassionate Allowances are a way to quickly identify diseases and other medical conditions that, by definition, meet Social Security’s standards for disability benefits. The program fast-tracks disability decisions to ensure that Americans with the most serious disabilities receive their benefit decisions within days instead of months or years. These conditions primarily include certain cancers, adult brain disorders, and a number of rare disorders that affect children.
“We have achieved another milestone for the Compassionate Allowances program, reaching 200 conditions,” Commissioner Astrue said. “Nearly 200,000 people with severe disabilities nationwide have been quickly approved, usually in less than two weeks, through the program since it began in October 2008.”
By definition, these conditions are so severe that Social Security does not need to fully develop the applicant’s work history to make a decision. As a result, Social Security eliminated this part of the application process for people who have a condition on the list.
Social Security has held seven public hearings and worked with experts to develop the list of Compassionate Allowances conditions. The hearings also have helped the agency identify ways to improve the disability process for applicants with Compassionate Allowances conditions.
For more information on the Compassionate Allowances initiative, please visit www.socialsecurity.gov/compassionateallowances.
Early onset Alzheimer’s disease, Creutzfeld-Jacob disease, Frontotemporal dementia, Lewy body dementia, Fatal Familial Insomnia and other less common dementia subtypes.
Hunting neuron killers in Alzheimer's and TBI
Sanford-Burnham researchers discovered that the protein appoptosin prompts neurons to commit suicide in several neurological conditions—giving them a new therapeutic target for Alzheimer's disease and traumatic brain injury
Dying neurons lead to cognitive impairment and memory loss in patients with neurodegenerative disorders–conditions like Alzheimer's disease and traumatic brain injury. To better diagnose and treat these neurological conditions, scientists first need to better understand the underlying causes of neuronal death.
Enter Huaxi Xu, Ph.D., professor in Sanford-Burnham's Del E. Webb Neuroscience, Aging, and Stem Cell Research Center. He and his team have been studying the protein appoptosin and its role in neurodegenerative disorders for the past several years. Appoptosin levels in the brain skyrocket in conditions like Alzheimer's and stroke, and especially following traumatic brain injury.
Appoptosin is known for its role in helping the body make heme, the molecule that carries iron in our blood (think “hemoglobin,” which makes blood red). But what does heme have to do with dying brain cells? As Xu and his group explain in a paper they published October 31 in the Journal of Neuroscience, excess heme leads to the overproduction of reactive oxygen species, which include cell-damaging free radicals and peroxides, and triggers apoptosis, the carefully regulated process of cellular suicide. This means that more appoptosin and more heme cause neurons to die.
Not only did Xu and his team unravel this whole appoptosin-heme-neurodegeneration mechanism, but when they inhibited appoptosin in laboratory cell cultures, they noticed that the cells didn't die. This finding suggests that appoptosin might make an interesting new therapeutic target for neurodegenerative disorders.
What's next? Xu and colleagues are now probing appoptosin's function in mouse models. They're also looking for new therapies that target the protein.
“Since the upregulation of appoptosin is important for cell death in diseases such as Alzheimer's, we're now searching for small molecules that modulate appoptosin expression or activity. We'll then determine whether these compounds may be potential drugs for Alzheimer's or other neurodegenerative diseases,” Xu explains.
Putting a stop to runaway appoptosin won't be easy, though. That's because we still need the heme-building protein to operate at normal levels for our blood to carry iron. In a previous study, researchers found that a mutation in the gene that encodes appoptosin causes anemia. “Too much of anything is bad, but so is too little,” Xu says.
New therapies that target neurodegenerative disorders and traumatic brain injury are sorely needed. According to the CDC, approximately 1.7 million people sustain a traumatic brain injury each year. It's an acute injury, but one that can also lead to long-term problems, causing epilepsy and increasing a person's risk for Alzheimer's and Parkinson's diseases. Not only has traumatic brain injury become a worrisome problem in youth and professional sports in recent years, the Department of Defense calls traumatic brain injury “one of the signature injuries of troops wounded in Afghanistan and Iraq.” (Source: EurekAlert! A service of AAAS and Sanford-Burnham Medical Research Institute).
Looking for the anti-Alzheimer's molecule -- A new approach to treating a devastating disease
‘In silico search for an endogenous anti-Alzheimer's molecule -- Screening amino acid metabolic pathways' published today in the Canadian Journal of Chemistry
Ottawa, Canada (November 7, 2012) – Researchers at Dalhousie University have discovered a new technique using “computer-aided” drug design that may lead to an entirely new approach in the treatment of Alzheimer's disease (AD).
“Alzheimer's is a devastating disease for which no truly disease-modifying drugs are available. Our approach is completely novel. We explore how the human body attempts to protect itself from Alzheimer's, and then we exploit this to develop an entirely new approach to therapeutics,” explained Dr. Weaver, a professor at Dalhousie University, clinical neurologist at Capital Health and IWK Health Centre, Canada Research Chair in Clinical Neuroscience, and the DMRF Irene MacDonald Sobey Chair in Curative Approaches to Alzheimer's Disease. “We are extremely excited about the results presented in this paper and believe that this may represent a new approach to the treatment of AD.”
Weaver says that he and his fellow researchers have successfully identified molecules that are able to prevent the disease-producing aggregation of both beta-amyloid and tau – the two proteins whose misfolding is implicated in the causation of Alzheimer's.
“Using ‘in silico’ (i.e. computer-aided) drug design, we have discovered new lead molecules that may aid in the future development of disease-modifying drugs for Alzheimer's disease,” said Dr. Autumn Meek whose research into Alzheimer's has been funded by the Dalhousie Medical Research Foundation's “Gunn Family Graduate Studentship in Alzheimer's Disease”. She works with co-authors Dr. Weaver and Mr. Gordon Simms in the Department of Chemistry at Dalhousie.
According to the Alzheimer's Society publication “Rising Tide: The Impact of Dementia on Canadian Society”, Alzheimer's disease is an ever-growing concern in Canadian society, and as the population trends toward the aged it will place an increased strain on healthcare and families alike. It is believed that within a generation, the numbers of Canadians with Alzheimer's disease will more than double, and the cost of caring for individuals afflicted with dementia will increase from $15 billion annually to $153 billion annually. (Source: EurekAlert! A service of AAAS and Canadian Science Publishing (NRC Research Press)).
New cell type developed for possible treatment of Alzheimer's and other brain diseases
UCI discovery accelerates efforts at Sue & Bill Gross Stem Cell Research Center
Irvine, Calif., Nov. 7, 2012 — UC Irvine researchers have created a new stem cell-derived cell type with unique promise for treating neurodegenerative diseases such as Alzheimer's.
Dr. Edwin Monuki of UCI's Sue & Bill Gross Stem Cell Research Center, developmental & cell biology graduate student Momoko Watanabe and colleagues developed these cells –called choroid plexus epithelial cells – from existing mouse and human embryonic stem cell lines.
CPECs are critical for proper functioning of the choroid plexus, the tissue in the brain that produces cerebrospinal fluid. Among their various roles, CPECs make CSF and remove metabolic waste and foreign substances from the fluid and brain.
In neurodegenerative diseases, the choroid plexus and CPECs age prematurely, resulting in reduced CSF formation and decreased ability to flush out such debris as the plaque-forming proteins that are a hallmark of Alzheimer's. Transplant studies have provided proof of concept for CPEC-based therapies. However, such therapies have been hindered by the inability to expand or generate CPECs in culture.
“Our method is promising, because for the first time we can use stem cells to create large amounts of these epithelial cells, which could be utilized in different ways to treat neurodegenerative diseases,” said Monuki, an associate professor of pathology & laboratory medicine and developmental & cell biology at UCI.
The study appears in today's issue of The Journal of Neuroscience.
To create the new cells, Monuki and his colleagues coaxed embryonic stem cells to differentiate into immature neural stem cells. They then developed the immature cells into CPECs capable of being delivered to a patient's choroid plexus.
These cells could be part of neurodegenerative disease treatments in at least three ways, Monuki said. First, they're able to increase the production of CSF to help flush out plaque-causing proteins from brain tissue and limit disease progression. Second, CPEC “superpumps” could be designed to transport high levels of therapeutic compounds to the CSF, brain and spinal cord. Third, these cells can be used to screen and optimize drugs that improve choroid plexus function.
Monuki said the next steps are to develop an effective drug screening system and to conduct proof-of-concept studies to see how these CPECs affect the brain in mouse models of Huntington's, Alzheimer's and pediatric diseases. (Source: EurekAlert! A service of AAAS and University of California - Irvine).
Controlling vascular disease may be key to reducing prevalence of Alzheimer's disease
International experts review the latest thinking in a special issue of Journal of Alzheimer's Disease
Amsterdam, NL, November 5, 2012 – Over the last 15 years, researchers have found a significant association between vascular diseases such as hypertension, atherosclerosis, diabetes type 2, hyperlipidemia, and heart disease and an increased risk of Alzheimer's disease. In a special issue of the Journal of Alzheimer's Disease, leading experts provide a comprehensive overview of the pathological, biochemical, and physiological processes that contribute to Alzheimer's disease risk and ways that may delay or reverse these age-related abnormalities.
“Vascular risk factors to Alzheimer's disease offer the possibility of markedly reducing incident dementia by early identification and appropriate medical management of these likely precursors of cognitive deterioration and dementia,” says Guest Editor Jack C. de la Torre, MD, PhD, of the University of Texas, Austin. “Improved understanding coupled with preventive strategies could be a monumental step forward in reducing worldwide prevalence of Alzheimer's disease, which is doubling every 20 years.”
The issue explores how vascular disease can affect cerebral blood flow and impair signaling, contributing to Alzheimer's disease (AD). The diagnostics of cardiovascular risk factors in AD are addressed, as are potential therapeutic approaches.
Paradoxically, the presence of vascular risk factors in middle age is associated with the development of AD more strongly than late-life vascular disease. In fact, some research suggests that vascular symptoms later in life may have a protective effect against the development of the disease. The physiopathological mechanisms that may underlie this phenomenon are discussed.
To date, trials that target major cardiovascular risk factors in the prevention of AD remain inconclusive but have become an important focus of international research as described by contributors of this special volume in their overviews. The multifactorial nature of AD and the need to identify the proper time window for intervention when designing possible interventions, and methodological issues that will have to be addressed to achieve an optimal design of new randomized controlled trials, are discussed. Promising avenues for treatment, such as the potential of low-level light therapy to increase the rate of oxygen consumption in the brain and enhance cortical metabolic capacity, and the possibility that some antihypertensive drug classes reduce the risk and progression of AD more than others, are discussed.
Dr. de la Torre notes that the presence of vascular risk factors is not an absolute pathway to dementia, and it may be as important to study how or why individuals who are cognitively normal but have vascular risk are able to avoid dementia. “Reducing Alzheimer's disease prevalence by focusing right now on vascular risk factors to Alzheimer's disease, even with our limited technology, is not a simple or easy task. But the task must begin somewhere and without delay because time is running out for millions of people whose destiny with dementia may start sooner rather than later,” he concludes. (Source: EurekAlert! A service of AAAS and IOS Press).
LSUHSC research identifies new therapeutic target for Alzheimer's disease
New Orleans, LA – Research led by Chu Chen, PhD, Associate Professor of Neuroscience at LSU Health Sciences Center New Orleans, has identified an enzyme called Monoacylglycerol lipase (MAGL) as a new therapeutic target to treat or prevent Alzheimer's disease. The study was published online November 1, 2012 in the Online Now section of the journal Cell Reports.
The research team found that inactivation of MAGL, best known for its role in degrading a cannabinoid produced in the brain, reduced the production and accumulation of beta amyloid plaques, a pathological hallmark of Alzheimer's disease. Inhibition of this enzyme also decreased neuroinflammation and neurodegeneration, and improved plasticity of the brain, learning and memory.
“Our results suggest that MAGL contributes to the cause and development of Alzheimer's disease and that blocking MAGL represents a promising therapeutic target,” notes Dr. Chu Chen, who is also a member of the Department of Otolaryngology at LSU Health Sciences Center New Orleans.
The researchers blocked MAGL with a highly selective and potent inhibitor in mice using different dosing regimens and found that inactivation of MAGL for eight weeks was sufficient to decrease production and deposition of beta amyloid plaques and the function of a gene involved in making beta amyloid toxic to brain cells. They also measured indicators of neuroinflammation and neurodegeneration and found them suppressed when MAGL was inhibited. The team discovered that not only did the integrity of the structure and function of synapses associated with cognition remain intact in treated mice, but MAGL inactivation appeared to promote spatial learning and memory, measured with behavioral testing.
Alzheimer's disease is a neurodegenerative disorder characterized by accumulation and deposition of amyloid plaques and neurofibrillary tangles, neuroinflammation, synaptic dysfunction, progressive deterioration of cognitive function and loss of memory in association with widespread nerve cell death. The most common cause of dementia among older people, more than 5.4 million people in the United States and 36 million people worldwide suffer with Alzheimer's disease in its various stages. Unfortunately, the few drugs that are currently approved by the Food and Drug Administration have demonstrated only modest effects in modifying the clinical symptoms for relatively short periods, and none has shown a clear effect on disease progression or prevention.
“There is a great public health need to discover new therapies to prevent and treat this devastating disorder,” Dr. Chen concludes. The research was supported by grants from the National Institutes of Health. In addition to scientists from LSU Health Sciences Center New Orleans, the research team also included investigators from the Massachusetts Institute of Technology. (Source: EurekAlert! A service of AAAS and Louisiana State University Health Sciences Center).
Plaque build-up in your brain may be more harmful than having Alzheimer's gene
MINNEAPOLIS – A new study shows that having a high amount of beta amyloid or “plaques” in the brain associated with Alzheimer's disease may cause steeper memory decline in mentally healthy older people than does having the APOE ε4 allele, also associated with the disease. The study is published in the October 16, 2012, print issue of Neurology®, the medical journal of the American Academy of Neurology.
“Our results show that plaques may be a more important factor in determining which people are at greater risk for cognitive impairment or other memory diseases such as Alzheimer's disease,” said study author Yen Ying Lim, MPsych, with the University of Melbourne in Victoria, Australia. “Unfortunately, testing for the APOE genotype is easier and much less costly than conducting amyloid imaging.”
For the study, 141 people with an average age of 76 who were free of any problems in memory and thinking underwent PET brain scans and were tested for the APOE gene. Their memory and thinking was then tracked over the following year and a half, using a set of computer-based cognitive assessments that were based on playing card games and remembering word lists.
The study found that after a year and a half, people who had more brain plaques at the start of the study had up to 20 percent greater decline on the computer based assessments of memory than did those who had fewer brain plaques. The study also found that while carriers of the APOE ∊4 allele also showed greater decline on the memory assessments than those who did not have the allele, carrying the ∊4 allele did not change the decline in memory related to the plaques.
“Our finding that brain plaque-related memory decline can occur while people still have normal memory and thinking shows that these plaque-related brain changes can be detected and measured while older people are still healthy. This provides an enormous opportunity for understanding the development of early Alzheimer's disease and even a sound basis for the assessment of plaque-targeting therapies,” said Lim. (Source: EurekAlert! A service of AAAS and American Academy of Neurology).
New tools for Alzheimer's may aid early diagnosis and treatment
Nanotechnology, brain imaging, and new mouse strains aiding quest for detection and therapy
NEW ORLEANS — Curtailing the imminent rise in Alzheimer's disease (AD) will require early, accurate diagnostic tests and treatments, and researchers are closer to achieving these two goals. New findings in medical imaging, molecular analysis of neurological diseases, and development of treatments using mouse models were presented at Neuroscience 2012, the annual meeting of the Society for Neuroscience and the world's largest source of emerging news about brain science and health.
AD is the most common cause of dementia and currently affects 5 million people in the United States. By 2015, this number could increase to 13 million people.
Today's new findings show that:
Changes in brain function occur many years before symptoms in people with AD; these changes could be detected by PET scans and might one day be used to identify people at risk for developing the disease (Lori Beason-Held, PhD, abstract 545.22, see attached summary).
A new drug that targets biochemical changes in proteins improved symptoms and increased survival in a mouse model of AD, but just how it works is a mystery (Fred Van Leuven, PhD, abstract 416.08, see attached summary).
An antibody-based probe that uses nanotechnology and magnetic resonance imaging can distinguish between diseased and non-diseased brain tissue and could lead to a test for early detection of AD (William Klein, PhD, abstract 753.21, see attached summary).
AD, Parkinson's disease, and Dementia with Lewy Bodies have specific molecular signatures caused by epigenetics — mechanisms that determine how and when DNA is expressed — that could assist in accurate diagnosis and earlier treatment (Paula Desplats, PhD, abstract 50.17, see attached summary).
A new mouse model for AD gives researchers more control over an Alzheimer's-related protein in mice, and could lead to better research on effective treatments (Alena Savonenko, MD, PhD, abstract 416.04, see attached summary).
“Being able to detect AD early — perhaps even before symptoms begin — is an essential pre-condition if we are to develop effective treatments that slow or stop the changes that occur in the brain during Alzheimer's. Our studies in mice already tell us this,” said press conference moderator Sam Gandy, PhD, MD, of the Mount Sinai School of Medicine in New York City, an expert on AD and dementia. “Being able to distinguish AD from other neurodegenerative diseases will help us give the right treatments to the right patients.” (Source: EurekAlert! A service of AAAS and the Society for Neuroscience).
Alzheimer's sufferers may function better with less visual clutter
TORONTO, ON – Psychologists at the University of Toronto and the Georgia Institute of Technology – commonly known as Georgia Tech – have shown that an individual's inability to recognize once-familiar faces and objects may have as much to do with difficulty perceiving their distinct features as it does with the capacity to recall from memory.
A study published in the October issue of Hippocampus suggests that memory impairments for people diagnosed with early stage Alzheimer's disease may in part be due to problems with determining the differences between similar objects. The research contributes to growing evidence that a part of the brain once believed to support memory exclusively – the medial temporal lobe – also plays a role in object perception.
“Not only does memory seem to be very closely linked to perception, but it's also likely that one affects the other,” said Morgan Barense of the University of Toronto's Department of Psychology. “Alzheimer's patients may have trouble recognizing a loved one's face not just because they can't remember it but also because they aren't able to correctly perceive its distinct combination of features to begin with.”
The research team tested patients with mild cognitive impairment (MCI) – a disorder commonly thought to be a precursor to Alzheimer's disease – on their ability to determine whether two rotated side-by-side pictures were different or identical.
In one set of trials, many pairs of photos of blob-like objects were shown. These were classified as high-interference trials as the photos varied only slightly when they weren't a perfect match, either by shapes or fill pattern. As expected, MCI patients struggled greatly to identify identical pairings.
In low-interference trials, the blob-like objects were interspersed with photos in which non-matches were more extreme and varied widely. For example, a picture of a butterfly was shown next to a photo of a microwave. Interspersing the very similar blob-like objects with photos of dissimilar objects greatly reduced the amount of interference.
“Minimizing the degree of perceptual interference improved patients' object perception by reducing the number of visually similar features,” said lead author of the study Rachel Newsome, a PhD candidate in U of T's Department of Psychology.
The findings suggest that, under certain circumstances, reducing “visual clutter” could help MCI patients with everyday tasks. For example, buttons on a telephone tend to be the same size and color. Only the numbers are different – a very slight visual difference for someone who struggles with object perception. One solution could be a phone with varying sized buttons and different colors.
The researchers, which also included Georgia Tech psychology professor Audrey Duarte, administered the same tests to people at risk for MCI who had previously shown no signs of cognitive impairment.
“They performed the same as those with MCI, suggesting that the perception test could be used as an early indicator of cognitive impairment,” said Barense. “It provides further support for the idea that any damage to a small area of the medial temporal lobe – especially the perirhinal cortex – affects perception as much as it does memory.” (Source: EurekAlert! A service of AAAS and the University of Toronto).
Use of anti-psychotic drugs by people with dementia ‘under reported’
The scale of the challenge to reduce the use of anti-psychotic drugs by people with dementia may be under-estimated, according to researchers from Aston University and the University of East Anglia, working with NHS Kent and Medway
The scale of the challenge to reduce the use of anti-psychotic drugs by people with dementia may be under-estimated, according to researchers from Aston University and the University of East Anglia, working with NHS Kent and Medway.
There is a key public health challenge to reduce the prescribing of anti-psychotic drugs to people with dementia as they are thought to be associated with up to 1,800 deaths a year.
Ian Maidment, corresponding author and a Senior Lecturer in Clinical Pharmacy from Aston University has worked in medication management in dementia for 20 years.
He said: “The true scale of anti-psychotic usage in dementia may be under-estimated. Usage may be up to 46 per cent greater than official figures suggest.”
The researchers compared the results of the government's National Dementia and Anti-Psychotic Prescribing Audit with research, led by Anne Child, an experienced senior clinical pharmacist for NHS Kent and Medway cluster of primary care trusts (PCTs).
They found that 15.3 per cent of people with dementia received an anti-psychotic, compared to the national audit, which found 10.5 per cent. However, only 48.9 per cent of GP practices across the country participated in the national audit compared with 98.3 per cent of practices in Medway which took part in the detailed local study.
The Medway project, carried out from January to December 2011, and analyzed by researchers from Aston University and the University of East Anglia, identified that:
People with dementia living in care homes were nearly 3.5 times more likely to receive a low-dose anti-psychotic than people living at home (25.5 per cent compared to 7.3 per cent)
It was possible to reduce or withdraw low-dose anti-psychotics for more than 60 per cent of patients with dementia (43 out of 70) whose medication was initiated by their GP.
Clinical trials need to be commissioned as a matter of urgency to confirm the effectiveness of pharmacist medication reviews.
The paper, which appears in the BioMed Central's open access journal BMC Psychiatry, also sets out the detailed process undertaken before and during withdrawal of anti-psychotics from patients.
Anne Child, primary author, who is now head of Pharmaceutical Care at Avante Care said: “We have demonstrated that a multi-disciplinary approach to dementia care, involving a pharmacy-led medication review, GPs, and care homes, can produce a positive outcome for patients, in one region of the country. More work is now needed.”
Dr Chris Fox, co-author, from UEA's Norwich Medical School said: “Another issue with the national audit is it fails to report the usage of the drug lorazepam, which is sometimes used instead of anti-psychotics. It is potentially equally dangerous. Until we capture the true level of usage of all these drugs we cannot truly understand the issue.”
Ian Maidment added: “Whilst the national audit is an important first step, it presents a partial picture. If we rely on it, exclusively we are doing a disservice to people with dementia, their careers and their families.” (Source: EurekAlert! A service of AAAS and University of East Anglia).