TorreyPines Therapeutics Initiates Second Phase I Study For NGX267, A Selective M1 Agonist For Treatment Of Alzheimer's Disease

TorreyPines Therapeutics, Inc. today
announced that it has initiated a Phase I single and multiple dose study in
healthy elderly volunteers for NGX267, a novel treatment for Alzheimer's
disease. This study follows successful completion of the company's first
Phase I study with this compound. In the first study, NGX267 was administered
as single doses to healthy adult males and it was shown to be well-tolerated.
In preclinical studies, NGX267, a selective muscarinic (M1) agonist, has shown
the potential to both reduce symptoms and slow disease progression.


Designed in two parts, this double-blind, placebo-controlled study is
being conducted at one center in the U.S. The study will enroll approximately
64 healthy men and women between the ages of 65 and 80, reflecting the age of
the primary Alzheimer's disease population. The first part of the study uses
a single, ascending dose, sequential cohort design followed by a multiple dose
phase. Investigators will evaluate the safety, tolerability and single and
multiple dose pharmacokinetics of NGX267, as well as pharmacodynamic measures
including effects on CSF levels of AB1-42 and neuropsychological tests. This
second Phase I study is scheduled to complete in mid-2006.


"We believe our M1 agonist has the potential to offer disease modification
as well as symptomatic relief without the level of side effects previously
found with other M1 agonists," said Neil Kurtz, M.D., President and Chief
Executive Officer of TorreyPines. "A therapy that targets both the cause and
symptoms of Alzheimer's disease would be a significant breakthrough in the
treatment of this devastating illness."


Preclinical data support a dual mechanism of action for NGX267. The
compound has been shown to stimulate M1 receptors in a fashion analogous to
acetylcholine, a neurotransmitter essential for memory and cognitive function
that is depleted when neurons, or brain cells, degenerate. In addition, in
studies in mice and rabbits, NGX267 lowered brain levels of AB1-42, a toxic
peptide that is the major component of amyloid plaques. The amyloid plaque is
considered to be the primary hallmark of Alzheimer's disease.


Currently approved Alzheimer's disease therapies treat symptoms of the
disease only. These therapies have not been shown to reduce AB1-42 levels in
man, nor treat the underlying cause of the disease. NGX267 data also suggest
a high level of pharmacological specificity, which may provide better
tolerability than other M1 agonists that have been studied.


About TorreyPines Therapeutics


TorreyPines Therapeutics, Inc. is a biopharmaceutical company that
discovers and develops breakthrough small molecule drugs to treat diseases and
disorders of the central nervous system. Led by an accomplished management
team, the company is leveraging novel drug targets and technologies to deliver
new therapies for Alzheimer's disease, severe migraine and neuropathic pain.
Its breakthrough therapies are intended to offer significant advantages over
current therapies. Further information is available at
torreypinestherapeutics.


This news release contains certain forward-looking statements that involve
risk and uncertainties. Such statements are only predictions and the
company's actual results may differ materially from those anticipated in these
forward-looking statements. Factors that may cause such differences include
the risk that products that appeared promising in early research and clinical
trials do not demonstrate safety or efficacy in larger-scale clinical trials
and the risk that the company will not obtain approval to market its products.


TorreyPines Therapeutics, Inc.

torreypinestherapeutics

Normal "Senior Moments," Or Alzheimer's Disease?

The recent passing of vibrant actor Charlton Heston from late-stage Alzheimer's disease makes us all stop and think about our own mortality. In particular, it is natural to wonder about your own memory, and what is 'normal' when it comes to memory loss as a result of aging.



Occasional memory lapses, such as forgetting why you walked into a room or having difficulty recalling a person's name, become more common as we approach our 50s and 60s. It's comforting to know that this minor forgetfulness is a normal sign of aging, not a sign of dementia.


But other types of memory loss, such as forgetting appointments or becoming momentarily disoriented in a familiar place, may indicate mild cognitive impairment.



In the most serious form of memory impairment -Alzheimer's and other forms of dementia -- people often find themselves disoriented in time and place and unable to name common objects or recognize once-familiar people.


Here are examples of the types of memory problems common in normal age-related forgetfulness, mild cognitive impairment, and dementia.


Memory Condition -- Normal Age-Related Forgetfulness:


- Sometimes misplaces keys, eyeglasses, or other items.

- Momentarily forgets an acquaintance's name.

- Occasionally has to "search" for a word.

- Occasionally forgets to run an errand.

- May forget an event from the distant past.

- When driving, may momentarily forget where to turn. Quickly orients self.

- Jokes about memory loss.


Memory Condition -- Mild Cognitive Impairment:


- Frequently misplaces items.

- Frequently forgets people's names and is slow to recall them.

- Finding words becomes more difficult.

- Begins to forget important events and appointments.

- May forget more recent events or newly learned information.

- May temporarily become lost more often.

- May have trouble understanding and following a map.

- Worries about memory loss. Family and friends notice the lapses.


Memory Condition -Alzheimer's Disease and Other Forms of Dementia:


- Forgets what an item is used for or puts it in an inappropriate place.

- May not remember knowing a person.

- Begins to lose language skills. May withdraw from social interaction.

- Loses sense of time. Doesn't know what day it is.

- Short-term memory is seriously impaired. Has difficulty learning and remembering new information.

- Becomes easily disoriented or lost in familiar places, sometimes for hours.

- May have little or no awareness of cognitive problems.


If you are concerned about memory loss in yourself or a loved one, there can be a variety of underlying causes too which can be treated, for example, temporary memory loss due to depression, or certain prescription or over the counter medications. You should discuss such concerns with your doctor.


There are a number of tests your doctor can administer right in the office which can help determine whether it is cognitive impairment or Alzheimer's Sisease or another form of dementia.


For more information on Memory Loss and Alzheimer's, please visit the Memory topic page at Johns Hopkins Health Alerts:
Johns Hopkins Health Alerts Memory Topic


The Johns Hopkins Guide To Memory Loss And Aging


Johns Hopkins Health Alerts has recently published a free special report, "The Johns Hopkins Guide to Memory Loss and Aging." It in you will learn more about the reasons for memory loss as we age, and how to distinguish between Alzheimer's disease and other forms of dementia, versus the normal changes in memory we can all expect as a result of the aging process.

This Special Report also offers 8 Memory Preserving Tips.


For a free copy The Johns Hopkins Guide to Memory Loss and Aging, please visit:
Johns Hopkins Guide to Memory Loss and Aging


Johns Hopkins Special Reports

Living With Dementia Demands Better Design, Says Kingston Professor

New research by Kingston University has revealed how design can improve the quality of life for people with dementia. The University hopes the new study will form a blueprint for future building, lay-out and management of care homes.


The project, called 'Living with Dementia: Can Design Make a Difference?' was led by Professor Hilary Dalke, Director of the Design Research Centre at Kingston University. "Design can contribute to the success or failure of a home and whether it provides the quality of life that we would want for our families, friends and ourselves," she said. The study was funded by the Audi Design Foundation, which supports inclusive and sustainable design initiatives.


After visiting nineteen care homes and studying their architecture, d?©cor, layout, gardens and lighting, the Kingston team has drawn up a blueprint for future care home design.


The proposals, currently being exhibited at the Building Centre in London, are likely to appeal to policy makers in light of the recent warning from spending watchdog, the Audit Commission, that the current nine billion pound social care bill will double by 2026 unless providers are "more imaginative". The new research suggested such cost-effective improvements as homes being laid out as small single storey 'villages' with a sense of neighbourhood.


The team from Kingston was impressed by homes that included shops, cafes and even, in one, a 'pub' and also came to the conclusion that gardens should be designed to encourage residents to keep active. Greenhouses needed to be accessible for wheelchair users, while raised beds allowed people with limited mobility to grow flowers and vegetables. Less mobile residents appreciated different types of bird feeders and even cats and chickens on site.


Entrances to care homes should be designed with visitors in mind, according to Professor Dalke. "It's important that the relatives feel positive, otherwise visiting drops off," she explained. "One lady told us she was disturbed by a very intense sensory room that her mother was encouraged to use. When the relative entered she said she was left feeling as if she had dementia herself."
more...


Staff in some homes had commented that children rarely visited. This might have been for safety or emotional reasons so intergenerational games and exercises -beneficial for residents and appealing to children - should be designed for sites, the researchers concluded.


Residents should be aware of ordinary activities such as cooking and laundry going on around them. Sam Cole, who is currently studying product and furniture design at Kingston and was one of four students who were involved in the project, designed a tea bar where visitors could sit with their relative and chat. "Things like making a cup of tea safely for a guest can help people with dementia remember a normal life," he said.


Design of stimulating activities is a priority. In one care home, the team observed old engine parts laid out on a table. "Some men appreciated the connections with their previous working life," Professor Dalke said. "Parts disappeared and staff found they had been taken back to their rooms." Elsewhere bookcases and televisions created a homely environment, even if the residents weren't able to read books or watch tv. The team urged developers to design spaces with plenty of natural light and sheltered outdoor seating.


Professor Dalke has been looking at how design can affect vulnerable people for more than 15 years. Her input is sought by architects and developers worldwide on healthcare, retail, transport and prisons.


She concluded: "Many care home professionals believe that a building with a lack of design for independent living can itself cause a rapid decline for residents with Alzheimer's disease. People who have been moved to a more stimulating home have shown significant improvement in their physical or mental condition that was not directly attributable to greater luxury or more staff."


Source: Kingston University

Variants In A Gene On The X Chromosome Are Associated With Increased Susceptibility To Alzheimer's Disease

Researchers at Mayo Clinic have discovered the first gender-linked susceptibility gene for late-onset Alzheimer's disease.



In the Jan. 11 online edition of Nature Genetics, they report the results of their two-stage genome-wide association study of patients with Alzheimer's disease. The research showed that women who inherited two copies of a variant in the PCDH11X gene, found on the X chromosome, are at considerably greater risk of developing Alzheimer's disease. Women with a variant on one of their two X chromosomes also had some increase in risk, as did men with the variant on their single X chromosome, but these effects were weaker than inheriting two variants.



Investigators caution that more study is required before assigning the definitive degree of risk the gene seems to carry, but they say it appears to be one of the stronger risk factors found to date.



"This is a very common genetic variant, and many women who had two copies of it did not have disease. But, overall, the odds were substantially greater that female patients with the disease did have two copies," says the study's senior investigator, Steven Younkin, M.D., Ph.D., a consultant-researcher at Mayo Clinic's campus in Florida and George M. Eisenberg, Professor of Neuroscience in the College of Medicine. "The results obtained do not imply that women are generally at increased risk for developing the disease than men."



The Mayo group first detected a variant in the gene PCDH11X, which associates with susceptibility to Alzheimer's disease, by scanning the entire genome of 844 patients affected with Alzheimer's disease and 1,255 unaffected control subjects. The association was confirmed by studying an additional 1,547 patients and 1,209 controls.



The variant was found in 79 percent of unaffected women; 50 percent had one copy and 29 percent had two. Since men have one X and one Y chromosome and women have two X chromosomes, the variant occurred in only 46 percent of unaffected men where a single copy was present. "When we compared Alzheimer's disease patients with unaffected controls, the largest and most significant difference was in women with two copies of the PCDH11X variant, who were found more frequently in the Alzheimer's disease group," Dr. Younkin says. "Compared to female non-carriers, the odds ratio was 1.75 for women with two copies of the variant and 1.26 for women with one copy. It was 1.18 for men with one copy compared to male non-carriers."



To put these findings in context, the odds ratio for two copies of the well-established, high-risk APOE 4 allele was 11.5 in the subjects assembled by the Mayo group, and it was 4.8 for one copy, Dr. Younkin says. APOE 4 is the highest-risk Alzheimer's disease susceptibility allele found to date. The association for women with one copy of the PCDH11X variant is similar to genetic associations now being reported for many diseases, but the strength of association when two copies were present is noteworthy particularly because the PCDH11X variant is so common, investigators say.
















"It is always exciting to identify a new Alzheimer's disease gene," says Minerva Carrasquillo, Ph.D., instructor of neuroscience and first author of the study. "The search for genes that influence the risk of common complex diseases such as Alzheimer's disease has proven extremely difficult, as most of the genes involved in the etiology of such diseases tend individually to have only modest effects on risk.



"When we set out to scan the genome for Alzheimer's disease susceptibility genes, we were not at all certain that we would find any gene other than the well-established APOE gene. Fortunately, the unbiased genome-wide scan that we undertook enabled us to identify PCDH11X, a previously unsuspected gene on the X chromosome that is the first to show gender-specific effects."



Dr. Younkin says, "Even though this is a large study showing highly significant association, it is important to analyze many additional Alzheimer's disease cases and controls before drawing any final conclusions about the strength of the association and the degree of risk it confers on developing Alzheimer's disease."



PCDH11X encodes a protocadherin that is included in a family of cadherin molecules that promote cell-cell adhesion and signaling in the central nervous system. Some evidence suggests that protocadherins are processed by presenilins linked to early-onset familial forms of Alzheimer's disease, the researchers say.



"The goal now will be to conduct further studies of this gene to determine the precise mechanism by which genetic variation in PCDH11X influences the risk of Alzheimer's disease and if the findings can be translated to improved diagnostics and therapeutics," Dr. Carrasquillo says.



This project was supported by the Robert and Clarice Smith Postdoctoral Fellowship; the Robert and Clarice Smith and Abigail Van Buren Alzheimer's Disease Research Program; and the Palumbo Professorship in Alzheimer's Disease Research. Samples from the National Cell Repository for Alzheimer's Disease, which receives government support under a cooperative agreement grant (U24 AG21886) awarded by the National Institute on Aging, were used in this study. The study was funded by grants from the National Institutes of Health, the Mayo Alzheimer's Disease Research Center, the Mayo Alzheimer's Disease Patient Registry, and the National Institute on Aging.







Source: Kevin Punsky


Mayo Clinic

Scientists Isolate A Toxic Key To Alzheimer's Disease In Human Brains

Scientists have long questioned whether the abundant amounts of amyloid plaques found in the brains of patients with Alzheimer's actually caused the neurological disease or were a by-product of its progress. Now, using new research techniques, scientists have shown that a two-molecule aggregate (or dimer) of beta-amyloid protein fragments may play a role in initiating the disease. The study, supported by the National Institutes of Health, suggests a possible new target for developing drug therapies to combat the irreversible and progressive disorder.


Ganesh M. Shankar, Ph.D., and Dennis J. Selkoe, M.D., of Brigham and Women's Hospital and Harvard Medical School, conducted the study in collaboration with other researchers at Harvard and in Ireland at University College Dublin, Beaumont Hospital and Royal College of Surgeons Ireland, and Trinity College Dublin. The National Institute on Aging (NIA), part of NIH, funded the study which appears online in the June 22, 2008, Nature Medicine.


Alzheimer's disease is marked by the build-up of plaques consisting of beta-amyloid protein fragments, as well as abnormal tangles of tau protein found inside brain cells. Early in the disease, Alzheimer's pathology is first observed in the hippocampus, the part of the brain important to memory, and gradually spreads to the cerebral cortex, the outer layer of the brain. In this study, researchers tested cerebral cortex extracts from brains donated for autopsy by people aged 65 and older with Alzheimer's and other dementias, as well as those without dementia. The extracts contained soluble one-molecule (monomer), two-molecule (dimer), three-molecule (trimer) or larger aggregates of beta-amyloid, as well as insoluble plaque cores. The researchers then injected the extracts into normal rats or added the extracts to slices of normal mouse hippocampus.


Shankar, Selkoe and colleagues discovered that both the soluble monomers and the insoluble plaque cores had no detectable effect on the hyppocampal slices. However, the soluble dimers induced certain key characteristics of Alzheimer's in the rats. The dimers impaired memory function, specifically the memories of newly learned behaviors. In the mouse hippocampal slices, the dimers also reduced by 47 percent the density of the dendrite spines that receive messages sent by other brain cells. The dimers seemed to be directly acting on synapses, the connections between neurons that are essential for communication between them.


To confirm this effect, the researchers then injected certain antibodies against beta-amyloid protein fragments. These latched onto and inactivated the dimers, preventing their toxic effects in the animal models. However, much work remains to be done before inactivation of dimers could move into the clinic.















"Scientists have theorized for many years that soluble beta-amyloid may be critical to the development and progression of this devastating disease. Now these researchers have isolated a candidate causative agent from brains of people with typical Alzheimer's and directly tested it in an animal model," said NIA Director Richard J. Hodes, M.D. "While more research is needed to replicate and extend these findings, this study has put yet one more piece into place in the puzzle that is Alzheimer's."


The animal findings were consistent with what the researchers found when they examined the brain tissues of people who had been clinically diagnosed with Alzheimer's and those without dementia. They detected soluble dimers and some trimers of amyloid in the brains of patients with Alzheimer's, but none or very low levels in those free of the disorder. Some people free of the disorder, however, did have insoluble amyloid plaques in their brains.


"These findings may help explain why people with normal cognitive function are sometimes found to have large amounts of amyloid plaques in their brains, which has been a puzzle for some time," said Marcelle Morrison-Bogorad, Ph.D., director of the NIA Division of Neuroscience. "Their findings noted that the brain of an individual who was never clinically diagnosed with dementia was found with abundant insoluble Alzheimer's plaques, but no soluble beta-amyloid."


Selkoe and Shankar noted that further insights into the early stages of this disease process may answer questions not only about Alzheimer's, but also about age-related memory impairments. "The approaches we used to isolate dimers and the widespread availability of tissues from brain banks, open new avenues of investigation into how these aggregates induce Alzheimer's disease," said Selkoe. "We still need to find out why dimers in particular are so destructive to neurons."


NIA leads the federal government effort conducting and supporting research on the biomedical and social and behavioral aspects of aging and the problems of older people. For more information on aging-related research and the NIA, please visit nia.nih. The NIA provides information on age-related cognitive change and neurodegenerative disease specifically at its Alzheimer's Disease Education and Referral (ADEAR) Center site at nia.nih/Alzheimers. To sign up for e-mail alerts about new findings or publications, please visit either Web site.


The National Institutes of Health (NIH) - The Nation's Medical Research Agency includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases.

National Institutes of Health

Advance Towards Early Alzheimer's Diagnosis

The leader of the team that made the discovery, Professor Christopher Rowe of the Austin Hospital in Melbourne, says early diagnosis and treatment presents medical practitioners with the best opportunity to delay the onset of Alzheimer's.



"While the discovery is at an experimental stage, this work places Australia at the forefront of neuro-imaging in Alzheimer's disease," Professor Rowe says.



A 2004 Access Economics report calculated that if the average age of onset of Alzheimer's was raised by just five months, cumulative savings of A$1.3 billion would be realised by 2020 rising to A$6.6 billion by 2040.



Alzheimer's disease is characterised by very high levels of a molecule called beta-amyloid in the brain. The project has demonstrated that a neuro-imaging scan called PiB PET can be used to identify individuals who will develop Alzheimer's disease up to 18 months earlier than all currently available diagnostics.



PiB PET can show the beta-amyloid in the brain which potentially allows clinicians to distinguish patients with early Alzheimer's disease from others without the disease, even before clear signs of memory loss are present.



The research was undertaken as part of the Australian Imaging, Biomarkers and Lifestyle (AIBL) Flagship



Study of Ageing.



The AIBL Flagship Study of Ageing is a collaboration initiated by the CSIRO Preventative Health National Research Flagship. AIBL is a joint activity between the University of Melbourne, Edith Cowan University - Western Australia, Neurosciences Australia, Mental Health Research Institute of Victoria and National Ageing Research Institute, and the Preventative Health Flagship.



The leader of the AIBL study, Professor David Ames, says the study has the potential to markedly reduce the burden this disabling illness places on both individuals and society.



"Early presymptomatic diagnosis is an essential development which will allow us to test new disease modifying therapies with the aim of delaying the onset of Alzheimer's disease in susceptible individuals," Professor Ames says.



The Director of CSIRO's Preventative Health National Research Flagship, Dr Richard Head, says the result highlights the value of a national collaborative team working together on one of Australia's biggest challenges.



Alzheimer's Australia has worked closely with AIBL to attract and co-ordinate the many volunteers who have made this study possible.



"Alzheimer's Australia is pleased to be part of this very exciting research and we look forward to its continuation," Alzheimer's Australia National Executive Director, Glenn Rees, says.



The findings were presented at international meetings in the USA on June 16 and will be presented in July at the International Conference on Alzheimer's disease in Chicago.



The AIBL Flagship Study of Ageing is a collaboration initiated by the CSIRO Preventative Health National Research Flagship. AIBL is a joint activity between the University of Melbourne, Edith Cowan University - Western Australia, Neurosciences Australia, Mental Health Research Institute of Victoria and National Ageing Research Institute, and the Preventative Health Flagship. The Biomedical Imaging Team from the Australian eHealth Research Centre is collaborating with the AIBL Study by developing image analysis methods to quantify disease progression with Magnetic Resonance and Positron Emission Tomography images.



National Research Flagships



CSIRO initiated the National Research Flagships to provide science-based solutions in response to Australia's major research challenges and opportunities. The nine Flagships form multidisciplinary teams with industry and the research community to deliver impact and benefits for Australia.



Source: Professor David Ames


CSIRO Australia

Physicists Study Behavior Of Enzyme Linked To Alzheimer's, Cancer

University of Houston (UH) physicists are using complex computer simulations to illuminate the workings of a crucial protein that, when malfunctioning, may cause Alzheimer's and cancer.



Margaret Cheung, assistant professor of physics at UH, and Antonios Samiotakis, a physics Ph.D. student, described their findings in a paper titled "Structure, function, and folding of phosphoglycerate kinase (PGK) are strongly perturbed by macromolecular crowding," published in a recent issue of the journal Proceedings of the National Academy of Sciences, one of the world's most-cited multidisciplinary scientific serials. The research was funded by a nearly $224,000 National Science Foundation grant in support of Samiotakis' dissertation.



"Imagine you're walking down the aisle toward an exit after a movie in a crowded theatre. The pace of your motion would be slowed down by the moving crowd and narrow space between the aisles. However, you can still maneuver your arm, stretch out and pat your friend on the shoulder who slept through the movie," Cheung said. "This can be the same environment inside a crowded cell from the viewpoint of a protein, the workhorse of all living systems. Proteins always 'talk' to each other inside cells, and they pass information about what happens to the cell and how to respond promptly. Failure to do so may cause uncontrollable cell growth that leads to cancer or cause malfunction of a cell that leads to Alzheimer's disease. Understanding a protein inside cells - in terms of structures and enzymatic activity - is important to shed light on preventing, managing or curing these diseases at a molecular level."



Cheung, a theoretical physicist, and Martin Gruebele, her experimental collaborator at the University of Illinois at Urbana-Champaign, led a team that unlocked this mystery. Studying the PGK enzyme, Cheung used computer models that simulate the environment inside a cell. Biochemists typically study proteins in water, but such test tube research is limited because it cannot gauge how a protein actually functions inside a crowded cell, where it can interact with DNA, ribosomes and other molecules.



The PGK enzyme plays a key role in the process of glycolysis, which is the metabolic breakdown of glucose and other sugars that releases energy in the form of ATP. ATP molecules are basically like packets of fuel that power biological molecular motors. This conversion of food to energy is present in every organism, from yeast to humans. Malfunction of the glycolytic pathway has been linked to Alzheimer's disease and cancer. Patients with reduced metabolic rates in the brain have been found to be at risk for Alzheimer's disease, while out-of-control metabolic rates are believed to fuel the growth of malignant tumor cells.



Scientists had previously believed that a PGK enzyme shaped like Pac-Man had to undergo a dynamic hinge motion to perform its metabolic function. However, in the computer models mimicking the cell interior, Cheung found that the enzyme was already functioning in its closed Pac-Man state in the jam-packed surrounding. In fact, the enzyme was 15 times more active in the tight spaces of a crowded cell. This shows that in cell-like conditions the function of a protein is more active and efficient than in a dilute condition, such as a test tube. This finding can drastically transform how scientists view proteins and their behavior when the environment of a cell is taken into account.



"This work deepens researchers' understanding of how proteins function, or don't function, in real cell conditions," Samiotakis said. "By understanding the impact of a crowded cell on the structure, dynamics of proteins can help researchers design efficient therapeutic means that will work better inside cells, with the goal to prevent diseases and improve human health."



Cheung and Samiotakis' computer simulations - performed using the supercomputers at the Texas Learning and Computation Center (TLC2) - were coupled with in vitro experiments by Gruebele and his team. Using the high-performance computing resources of TLC2 factored significantly in the success of their work.



"Picture having a type of medicine that can precisely recognize and target a key that causes Alzheimer's or cancer inside a crowded cell. Envision, then, the ability to switch a sick cell like this back to its healthy form of interaction at a molecular level," Cheung said. "This may become a reality in the near future. Our lab at UH is working toward that vision."



Source:

Lisa Merkl

University of Houston

Parental Dementia May Lead To Problems In Offspring

People who have parents diagnosed with Alzheimer's disease or dementia perform less well on formal memory testing when compared to people of the same age whose parents never developed Alzheimer's disease or other dementia. This is true even in middle-aged persons who do not have a diagnosis of clinical stroke or dementia, according to a Boston University School of Medicine (BUSM) study. This study has been selected to be presented at a Plenary Session at the American Academy of Neurology's 61st Annual Meeting in Seattle, Wash from April 25 - May 2.



Researchers from the Framingham Heart Study (FHS) are following three generations of participants to study the risk factors and earliest biomarkers of Alzheimer's disease, stroke and other cardiac and neurological diseases. The first generation has been followed since 1948. Since both the parental and offspring generation are enrolled as study participants, researchers could accurately identify which parents did or did not develop Alzheimer's disease or other dementia in their lifetime.



For this study, researchers studied 715 participants (372 women, 343 men) belonging to the second generation of FHS (average age 59) using standardized cognitive tests and MRI brain scans. One group of 282 persons had one or both parents fulfilling standardized criteria for a diagnosis of dementia, the other group of 433 persons had parents who were known to be free of dementia. The scientists also tested all these individuals for a gene thought to be a strong risk factor for dementia, called the ApoE ?µ4 gene.



Among persons who were carriers of the ApoE ?µ4 gene, those who had parents with Alzheimer's disease or other dementia scored significantly worse on tests of verbal memory and visual memory than persons who did not have parents with Alzheimer's dementia.



"Parental dementia and Alzheimer's disease were significantly associated with poorer performance in verbal and visual memory tasks," said senior author Sudha Seshadri, MD, associate professor of neurology and co-director of the Medical Education for Neurology Residency Program at Boston University School of Medicine.



Researchers further concluded that the result in persons with parents who have Alzheimer's disease is equivalent to approximately 15 years of brain aging. The effect was largely limited to those study participants who have the ApoE ?µ4 gene, which supports the idea that the gene is probably at least partially responsible for the transmission of Alzheimer's disease risk between generations.







This study was funded by the National Institute of Aging and other branches of the National Institutes of Health. The National Institute of Aging and the National Institutes of Health had no role in the design and conduct of the study, the collection, management, analysis and interpretation of the data, or the preparation, review and approval of the manuscript.



The American Academy of Neurology, an association of more than 21,000 neurologists and neuroscience professionals, is dedicated to promoting the highest quality patient-centered neurologic care. For more information about the American Academy of Neurology, visit aan.



For more information on Boston University School of Medicine, please visit bumc.bu/busm/.



Source: Michelle Roberts


Boston University

November Is National Alzheimer's Disease Awareness Month

Twenty five years ago, November was designated as National Alzheimer's Disease Awareness Month. At the time, fewer than 2 million Americans had Alzheimer's. Today, as many as 5.2 million Americans are living with Alzheimer's disease - 120,000 of them in Massachusetts. Alzheimer's can occur as young as age 35, and is currently the sixth leading cause of death in the country. By 2050, 11 to 16 million people will likely have Alzheimer's.


"While there is much we don't yet know about Alzheimer's disease, tremendous progress has been made since 1983," said James Wessler, President and CEO of the Alzheimer's Association MA/NH Chapter. "In November we focus on raising awareness of Alzheimer's disease and shedding light on the importance of finding breakthroughs in diagnosis, prevention, treatments and, eventually, a cure." The Alzheimer's Association will be offering educational programs throughout the state during the month of November. To find out what activities are planned in your area visit the Alzheimer's Association website at alz/MA


The Alzheimer's Association is the leading voluntary health organization in Alzheimer care, support and research. In Massachusetts, programs include a 24/7 Helpline, support groups, education offerings for families, and training for health care professionals. The Association has headquarters are in Watertown, and regional offices in Lowell, Raynham, Springfield, and Worcester, MA and Bedford, NH. alz

Potential Of Exelon® Patch As Promising Treatment Approach For Alzheimer's Disease Patients And Their Families

Results of a large-scale study published last week
in the International Journal of Geriatric Psychiatry show that Exelon®
Patch, the first skin patch in development for the treatment of Alzheimer's
disease, was well tolerated and provided benefits across a range of
symptoms 1.



Exelon Patch (rivastigmine transdermal patch) is designed to provide
smooth, continuous delivery of the drug through the skin. This maintains
steady drug levels in the bloodstream, improving tolerability and allowing
a higher proportion of patients to receive therapeutic doses of medication,
with potential improvements in efficacy.



During the 24-week IDEAL study of 1,195 patients with moderate Alzheimer's
disease 1, patients using once-daily Exelon Patch had improved memory and
thinking, and were better able to perform everyday activities than those on
placebo 1. In addition, the target dose of Exelon Patch 10 provided
equivalent efficacy to the highest doses of Exelon capsules with three
times fewer reports of nausea and vomiting 1. The patch showed a low level
of skin irritation and very good skin adhesion over 24 hours in a range of
everyday situations including bathing, and in hot weather 1.



In addition, more than 70 percent of caregivers in the IDEAL study
preferred the patch as a method of drug delivery for reasons including
aiding them to follow the treatment schedule, overall ease of use, and less
interference with daily life 2.



"In the IDEAL study, the Exelon Patch not only provided significantly
superior results compared to placebo, but also similar efficacy to the
highest dose of rivastigmine capsules, with dramatically improved
tolerability," said lead study investigator Professor Bengt Winblad of the
Karolinska Institute in Stockholm, Sweden. "These promising data indicate
that the Exelon Patch may provide an optimal way to deliver rivastigmine to
people with Alzheimer's disease."



Exelon (rivastigmine tartrate) is a dual cholinesterase inhibitor that is
already approved in oral form in many countries for the treatment of mild
to moderate Alzheimer's disease and dementia associated with Parkinson's
disease.



The IDEAL study results will support the regulatory submission of the
Exelon Patch to health authorities worldwide. If approved, the Exelon Patch
would be the first transdermal therapy for Alzheimer's disease, a
degenerative brain disorder that affects 24 million people worldwide 3.



About the IDEAL study


IDEAL (Investigation of Transdermal Exelon in Alzheimer's disease) was a
multi-center, randomized, double-blind, placebo- and active-controlled
trial to compare the efficacy, safety and tolerability of the once-daily
Exelon Patch with conventional twice-daily Exelon capsules in patients with
moderate Alzheimer's disease 1. The primary outcome measures were the
Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-cog) and
Alzheimer's Disease Cooperative Study - Clinical Global Impression of
Change (ADSC-CGIC).

IDEAL was conducted in 21 countries and involved 100 centers (23 in the US)
and 1,195 patients aged 50-85 years old with a score of 10-20 in the
Mini-Mental State Examination (MMSE), the most widely-used test for
assessing memory problems or dementia. Patients received Exelon either in
capsules (up to 6 mg twice-daily) or patches in two sizes, namely Patch 10
or Patch 20. Exelon Patch 10 provides equivalent exposure to the highest
doses of Exelon capsules (12 mg a day).
















Both patch sizes showed superior efficacy to placebo 1. The target dose of
Patch 10 showed similar efficacy to the highest doses of Exelon capsules
with three times fewer reports of nausea (7.2 percent vs. 23.1 percent) and
vomiting (6.2 percent vs. 17.0 percent), which are well-known side effects
of cholinesterase inhibitors. Patch 20 showed numerically, but not
statistically, improved cognitive scores versus capsules and similar
tolerability to capsules.



Local skin tolerability was good. The percentage of patients who reported
moderate or severe redness of the skin at any point of the study was only
7.6 percent and 6.2 percent of patients receiving Patch 10 and 20,
respectively 1.



About Exelon capsules and Alzheimer's disease


Since 1997, Exelon has been widely used to treat mild to moderate
Alzheimer's disease in more than 70 countries. Exelon belongs to a class of
drugs known as cholinesterase inhibitors, which increase the activity of
the neurotransmitter acetylcholine in the brain. Exelon is the only
cholinesterase inhibitor to be approved for both mild to moderate
Alzheimer's disease and Parkinson's disease dementia in Europe and the US.



Alzheimer's disease is a progressive disease that alters the brain, causing
impaired memory, thinking and behavior. Affecting two to six percent of
those over 65 years of age, it is the most common form of dementia and the
third leading cause of death in this age group behind cardiovascular
disease and cancer. The worldwide direct costs for dementia were estimated
at US$ 156 billion in 2003.



Disclaimer


This release contains certain forward-looking statements relating to the
Novartis Group's business, which can be identified by the use of
forward-looking terminology such as "may", "will", "could", "if approved",
"planned by", or similar expressions, or by express or implied discussions
regarding potential future regulatory submissions for Exelon or the Exelon
Patch, or regarding potential future revenue from Exelon or the Exelon
Patch. Such forward-looking statements involve known and unknown risks,
uncertainties and other factors that may cause actual results with Exelon
or the Exelon Patch to be materially different from any future results,
performance or achievements expressed or implied by such statements. There
can be no guarantee that any regulatory submissions regarding the Exelon
Patch will be made as planned or, if made, will be successful. Neither can
there be any guarantee regarding potential future revenue from Exelon or
the Exelon Patch. In particular, management's expectations regarding
commercialization of Exelon or the Exelon Patch could be affected by, among
other things, additional analysis of Exelon clinical data; new clinical
data; unexpected clinical trial results; unexpected regulatory actions or
delays in government regulation generally; the ability of Novartis to
obtain or maintain patent or other proprietary intellectual property
protection; competition in general; government, industry, and general
public pricing pressures; as well as factors discussed in Novartis AG's
Form 20-F filed with the U.S. Securities and Exchange Commission. Should
one or more of these risks or uncertainties materialize, or should
underlying assumptions prove incorrect, actual results may vary materially
from those described herein as anticipated, believed, estimated or
expected. Novartis is providing the information in this press release as of
this date and does not undertake any obligation to update any
forward-looking statements contained in this press release as a result of
new information, future events or otherwise.



About Novartis


Novartis AG (NYSE: NVS) is a world leader in offering medicines to protect
health, cure disease and improve well-being. Our goal is to discover,
develop and successfully market innovative products to treat patients, ease
suffering and enhance the quality of life. We are strengthening our
medicine-based portfolio, which is focused on strategic growth platforms in
innovation-driven pharmaceuticals, high-quality and low-cost generics,
human vaccines and leading self-medication OTC brands. Novartis is the only
company with leadership positions in these areas. In 2006, the Group's
businesses achieved net sales of USD 37.0 billion and net income of USD 7.2
billion. Approximately USD 5.4 billion was invested in R&D. Headquartered
in Basel, Switzerland, Novartis Group companies employ approximately
101,000 associates and operate in over 140 countries around the world. For
more information, please visit novartis.



References


1 Winblad B, Cummings J, et al. A 6-Month Double-blind, Randomized,
Placebo-Controlled Study of A Transdermal Patch in Alzheimer'd Disease -
Rivastigmine Patch versus Capsule. International Journal of Geriatric
Psychiatry. (In press)


2 Winblad B, Beusterien KM, et al. Caregivers prefer patches to
capsules: results from a 24-week placebo controlled study of rivastigmine
(IDEAL trial). Poster presented at the 10th International Congress of
Alzheimer's and Related Disorders (ICAD), Madrid, Spain, 19 July 2007.


3 World Health Organization. Neurological Disorders Affect Millions
Globally: WHO Report. Accessed online at:

who.int/mediacentre/news/releases/2007/pr04/en/index.html


View drug information on Exelon.

New Ebixa data - safe and effective treatment for Alzheimer's disease

New data highlights positive effects of Ebixa (memantine) treatment in Alzheimer's disease -


New results from a study assessing patients switched from an acetylcholinesterase inhibitor to Ebixa and results from an open
label naturalistic study -


Today, Lundbeck announced results from two independent studies demonstrating the efficacy and tolerability of Ebixa in the
treatment of Alzheimer's disease (AD) patients at the 7th International Conference on Alzheimer's and Parkinson's Disease
(AD/PD 2005) in Sorrento, Italy. The placebo controlled study results demonstrated that in moderate to severe Alzheimer's
patients for whom treatment was switched either abruptly or gradually from donepezil to Ebixa, the switch was found to be
well tolerated with the majority of patients maintained or improved in their global performance. The results from an open
label naturalistic study showed that Ebixa treatment led to clinical improvements in Alzheimer's disease patients.


"Previous data has indicated potential withdrawal reactions to the interruption of acetylcholinesterase inhibitor treatment
in Alzheimer's patients, characterised by global patient deterioration." said Anders Gersel Pedersen, head of drug
development at Lundbeck. "These results show that Alzheimer's patients, who were switched either abruptly or gradually to
Ebixa treatment from donepezil, did not experience tolerability problems and that the majority of these patients stabilised
or improved with Ebixa treatment. In addition, the open label study further supports Ebixa's efficacy and favourable
tolerability, as previously reported in randomised clinical studies."


Study 1: Switching to memantine in AD


Results from a double-blind, placebo controlled study in forty six patients with moderate to severe Alzheimer's disease (mean
MMSE < 14) conducted in Scandinavia, showed that switching from the acetylcholinesterase inhibitor donepezil to memantine is
well tolerated. Patients who appeared to be no longer benefiting from donepezil treatment, were randomised to either a
placebo group, with their current donepezil 10 mg therapy discontinued abruptly, or a gradual down-titration group, with
their current donepezil therapy discontinued in a stepwise programme, down-titrating donepezil from 10 mg to 5 mg for two
weeks before discontinuing. At the same time, memantine was up-titrated to 20mg/day over a three-week period for both patient
groups. The adverse events reported in either group were considered mild to moderate by the investigator and there were no
clinically relevant differences in tolerability between the abrupt and stepwise switching schedules respectively.


In addition, switching from donepezil to memantine appeared to maintain or improve patients' global performance, with 74% of
the patients either stabilising or improving as measured by Clinician's Global Impression of Change (CGI-C) after being
switched to memantine.















Study 2: Efficacy and tolerability of memantine in a naturalistic setting


Open label data from a large naturalistic study in 1,845 Alzheimer's disease patients in Germany were also presented at the
AD/PD conference today. Alzheimer's disease patients were treated for six months with memantine (20mg/day). Cognitive
function assessment as measured by the Mini Mental State Examination (MMSE), and other measures such as the Nurses'
Observation Scale for Geriatric Patients (NOSGER measure of behaviour and function), the Explorations Modul Demenz (EMD
measure of cognition, function and insight) and a rating of global efficacy by the clinician were recorded at baseline and at
six months.


After six months of open label treatment with memantine, patients' cognitive function was statistically significantly
improved by a mean of 2.5 MMSE points (p

A new analysis of a standard brain test may help predict dementia

Although Alzheimer's disease affects millions of people worldwide, there is no way to identify this devastating brain disease at its earliest stages when there still may be time to delay or even prevent the downward spiral into dementia. In research settings, scientists are using sophisticated tools like MRI and PET to distinguish characteristics of brain function and anatomy that indicate future problems, providing a sort of screening test for the brain.


Now a new study by a research group at NYU School of Medicine demonstrates that the earliest manifestations of Alzheimer's, when the first signs of memory loss appear, can be screened with a relatively inexpensive, painless, and easy-to-use tool called an EEG (electroencephalograph).


In the study, published in the upcoming on-line issue of the journal Neurobiology of Aging, the researchers demonstrate that a computer analysis of the EEG, which measures the brain's electrical activity, accurately predicted healthy people in their 60s and 70s who would develop dementia over the next 7 to 10 years. It also identified individuals who would remain virtually unchanged over the same time span. The EEGs were almost 95 percent accurate in identifying those who would decline cognitively and those who would not, according to the study.


"Our results suggest that quantitative analysis of the EEG is sensitive to the earliest signs of the dementing process," says Leslie S. Prichep, Ph.D., Associate Director of the Brain Research Laboratories of the Department of Psychiatry, who led the study. Some day she says it may be used as one of the tools to evaluate a person's propensity for developing Alzheimer's, the most common form of dementia affecting people over 65. But for now the results need to be replicated in and validated by much larger prospective studies before they can be applied to screen large populations.


It takes about 30 minutes to perform an EEG, which involves placing recording electrodes on the scalp. The test is perfomed with the patient seated comfortably. There are no injections and the scalp is not shaved.


The NYU researchers, led by Dr. Prichep and Roy John, Ph.D., Professor in the Department of Psychiatry, evaluated a group of 44 individuals between the ages of 64 and 79 who felt that their memories were faltering. These people enrolled voluntarily in a long-term study at NYU's Silberstein Aging and Dementia Research Center where they underwent a battery of neuropsychiatric and other tests, which revealed that their brain function was normal for their age.


At the beginning of the testing process each volunteer was also given a baseline EEG test at the Brain Research Laboratories at NYU School of Medicine. They were tested there several more times over the next 7 to 10 years. Over this period, 27 of the 44 subjects developed mild cognitive impairment or full-blown dementia, and 17 remained stable. Applying a mathematical algorhythm to the brain scans, Drs. Prichep and John showed that certain characteristics of the pattern of brain waves on the baseline EEG were associated with future cognitive deterioration.















To the untrained eye EEGs look like a confusing thicket of squiggly lines. But the lines are actually waves that have been described mathematically by their amplitude and frequency composition as a function of age, based on data collected over the last 30 years by Drs. Prichep and John. They and their NYU colleagues obtained this data from some 12,000 healthy people and psychiatric patients who had been given EEGs. About 3,500 of the EEGs were from aging and dementia patients.


"We probably have the largest electrophysiological database of this kind in the world," says Dr. Prichep. "Since we can compare each individual's quantitative EEG to age-expected normal values, we were able to describe which features reflected expected changes occurring with normal aging and which might be associated with future decline," she says.


A prominent feature associated with cognitive deterioration on the baseline EEG was a brain wave called theta, which was excessive in people who would eventually decline, according to the study. This band was particularly abnormal in the frontal regions, along the lateral regions and in the right posterior region of the brain in those people who went on to decline.


Another feature was a slowing in the mean frequency of the EEG, which is described in cycles per second. Yet another distinctive feature of those who decline was a change in the synchronization between the two sides of the brain. The source of the theta has been shown to be the hippocampus, a brain region demonstrated in imaging studies with MRI and PET to be impaired in dementia, notes Dr. Prichep.


The NYU researchers who contributed to this study are Drs. Prichep and John, Steven Ferris, Ph.D., Lawrence Rausch, PhD, Zeke Fang, PhD, Robert Cancro, M.D., Carol Torossian, Ph.D. and Barry Reisberg, M.D.


The study was supported by grants from National Institutes of Health, among other organizations.


Pamela McDonnell

Pamela.McDonnellnyumc

212-404-3555

New York University Medical Center and School of Medicine

med.nyu

Dementia Takes Away The Meaning Of Flavors

Flavour is literally the spice of life and for many people life without the pleasures of the table would be unthinkable. Yet just this aspect of everyday life is vulnerable in certain degenerative dementias, with patients developing abnormal eating behaviours including changes in food preferences, faddism and pathological sweet tooth. New research has revealed evidence that these behaviours are linked to a loss of meaning for flavours, as reported in the June 2010 issue of Elsevier's Cortex.



Dr Katherine Piwnica-Worms from Washington University in St Louis, Missouri, together with Dr Jason Warren and colleagues from University College London, investigated the processing of flavour information in patients with semantic dementia, a degenerative disease affecting the temporal lobes of the brain. Patients with this condition suffer a profound loss of the meaning of words and, ultimately, of things in the world at large; in addition, many develop a preference for unusual foods or food combinations.



The researchers tested patients' flavour processing using jelly beans: a convenient and widely available stimulus covering a broad spectrum of flavours. The abilities of patients to discriminate and identify flavours and to assess flavour combinations according to their appropriateness and pleasantness were compared with healthy people of the same age and cultural background. Patients were able to discriminate different flavours normally and to indicate whether they found certain combinations pleasant or not, but they had difficulty identifying individual flavours or assessing the appropriateness of particular flavour combinations (for example, vanilla and pickle).



These findings provide the first evidence that the meaning of flavours, like other things in the world, becomes affected in semantic dementia: this is a truly 'pan-modal' deficiency of knowledge. The research gives clues to the brain basis for the abnormal eating behaviours and the altered valuation of foods shown by many patients with dementia. More broadly, the results offer a perspective on how the brain organises and evaluates those commonplace flavours that enrich our daily lives.



Notes:


The article is "Flavour processing in semantic dementia" by Katherine E. Piwnica-Worms, Rohani Omar, Julia C. Hailstone, and Jason D. Warren, and appears in Cortex, Volume 46, Issue 6 (June 2010), published by Elsevier in Italy.



Source:

Valeria Brancolini


Elsevier

Alzheimer's Society Comment On Latest Report On Artificial Nutrition

A report by the Royal College of Physicians and British Society of Gastroenterology into artificial nutrician was published yesterday, 6 January 2010.


'People in the later stages of dementia have complex end of life needs and it is vital that the use of artificial nutrition or hydration is not used in place of good quality care. Alzheimer's Society maintains that quality of life should be considered a priority over length of life in the later stages of dementia


It is completely unacceptable that a lack of dementia training could be contributing to the current use of artificial nutrition. Training staff about dementia can drastically improve the care that people receive. It is essential that dementia training becomes a mandatory requirement for all care home staff. People with dementia should also make sure their wishes are communicated by making a lasting power of attorney.'


Neil Hunt

Chief Executive

Alzheimer's Society


Reference: Report by the Royal College of Physicians and British Society of Gastroenterology, entitled 'Oral feeding difficulties and dilemmas: A guide to practical care, particularly towards the end of life'


Source
Alzheimer's Society

Alzheimer's Disease: Finding Has Implications For Host Of Neurodegenerative Diseases

Researchers from the University of Pennsylvania School of Medicine have shown, in unprecedented detail, how a small molecule is able to selectively take apart abnormally folded protein fibers connected to Alzheimer's disease and prion diseases. The findings appeared online in the Proceedings of the National Academy of Sciences. Finding a way to dismantle misfolded proteins has implications for new treatments for a host of neurodegenerative diseases.



Abnormal accumulation of amyloid fibers and other misfolded forms in the brain cause neurodegenerative diseases. Similarly, build-up of abnormally folded prion proteins between neurons causes the human version of mad cow disease, Creutzfeldt-Jakob disease.



"Surprisingly, a small molecule called DAPH selectively targets the areas that hold fibers together, and converts fibers to a form that is unable to grow. Normally fibers grow from their ends, but the drug stops this activity," says senior author James Shorter, PhD, Assistant Professor of Biochemistry and Biophysics. "Our data suggest that it is possible to generate effective small molecules that can attack amyloid fibers, which are associated with so many devastating diseases."



The researchers are now working on how DAPH acts as a wedge to stop the fibers from growing. "Presumably DAPH fits very neatly into the crevices between fiber subunits," explains Shorter. "When we grow yeast cells with the prion in the presence of DAPH, they begin to lose the prion. We also saw this in the test tube using pure fibers. The small molecule directly remodels fiber architecture. We've really been able to get at the mechanism by which DAPH, or any small molecule, works for the first time." DAPH was originally found in a screen of small molecules that reduce amyloid-beta toxicity in the lab of co-author Vernon Ingram, Shorter's collaborator at the Massachusetts Institute of Technology (MIT).



In a test tube, if a small amount of amyloid or prion fiber is added to the normal form of the protein, it converts it to the fiber form. But when DPAH is added to the mix, the yeast prion protein does not aggregate into fibers. "It's essentially stopping fiber formation in its tracks," says Huan Wang, first author and research specialist in Shorter's lab. "We were surprised to see two very different proteins, amyloid-beta and Sup35, sensitive to this same small molecule."



The next step is to identify more potent DAPH variants with greater selectivity for deleterious amyloids. Since some amyloids may turn out to be beneficial - for example, one form may be involved in long-term memory formation - it will be necessary to find a drug that does not hit all amyloids indiscriminately. "We'd need one that hits only problem amyloids, and DAPH gives us a hint that such selectivity is possible" says Shorter.







This work was initiated in Susan Lindquist's lab at MIT and completed at Penn. The study was funded by the National Institute of General Medical Sciences, the Alzheimer's Association, the Kurt and Johanna Immerwahr Fund for Alzheimer Research, a DuPont-MIT alliance, the American Heart Association, and pilot grants from the University of Pennsylvania Alzheimer's Disease Core Center and Institute on Aging.



PENN Medicine is a $3.5 billion enterprise dedicated to the related missions of medical education, biomedical research, and excellence in patient care. PENN Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System.



Penn's School of Medicine is currently ranked #4 in the nation in U.S.News & World Report's survey of top research-oriented medical schools; and, according to most recent data from the National Institutes of Health, received over $379 million in NIH research funds in the 2006 fiscal year. Supporting 1,400 fulltime faculty and 700 students, the School of Medicine is recognized worldwide for its superior education and training of the next generation of physician-scientists and leaders of academic medicine.



The University of Pennsylvania Health System includes three hospitals - its flagship hospital, the Hospital of the University of Pennsylvania, rated one of the nation's "Honor Roll" hospitals by U.S.News & World Report; Pennsylvania Hospital, the nation's first hospital; and Penn Presbyterian Medical Center - a faculty practice plan; a primary-care provider network; two multispecialty satellite facilities; and home care and hospice.



Source: Karen Kreeger


University of Pennsylvania School of Medicine

Man's Memory Returns

"Scientists have accidentally discovered a key to unlocking memory, which could offer hope to thousands of Alzheimer's sufferers," according to The Daily Telegraph. The Independent also reported the case of an obese man who had "experimental brain surgery" in an attempt to control his appetite, but whose brain was instead accidentally stimulated to induce a "d?©j?  vu" like experience of an event from more than 30 years ago. In further experiments, the man was found to have improved memory and learning abilities when electrical current was applied to the same part of his brain.
The newspapers said that the researchers are now repeating the experiment in Alzheimer's patients to see if it is beneficial, and, if successful, could provide hope to the thousands of sufferers by "providing a pacemaker for the brain".


Deep brain stimulation, the technique that provoked the experience, is already widely used as a treatment for Parkinson's disease. It involves surgically inserting electrodes into patients' brains and stimulating parts of the brain with an electric current.


These findings will be of interest to doctors and scientists and will probably lead to further research and development in the field of deep brain stimulation. However, it is too early to say if this treatment could have any potential benefit in the improvement of memory or the management of Alzheimer's disease. The findings are the result of a case study in one man only, who was not himself a sufferer of Alzheimer's. Further research in Alzheimer's patients is needed before it is known if this could be used as a treatment for the disease.


Where did the story come from?


Dr Clement Hamani and colleagues from the Toronto Western Hospital and Research Institute, University of Toronto, Canada carried out the research. The study was published in the peer-reviewed medical journal: Annals of Neurology.


What kind of scientific study was this?


Animal studies have found that electrical stimulation of the hypothalamus, (the control centre of the brain that regulates hormone levels and certain body functions such as sleep, thirst and hunger), has an affect upon feeding behaviour and memory.


In this case report, an obese man received deep brain stimulation (DBS) to the hypothalamus, in an attempt to control his appetite. DBS is a surgical procedure that is widely used to treat the symptoms of neurological illnesses such as Parkinson's disease. The man was 50-years-old with a lifetime history of obesity that had been unresponsive to treatment. He also had several related medical problems including high blood pressure.















The patient was awake but anaesthetised during the procedure, during which DBS electrodes were implanted into both sides of his hypothalamus. The electrodes were moved to different positions to identify sites that affected the patient's appetite and where the electrodes would be best situated. Potential sites were identified by asking the patient to score between one and 10 how hungry he was when that site was stimulated. After testing was completed, the electrodes were secured in position, and a "pulse generator" that would provide the electrical stimuli was also implanted into the brain.


At the time of surgery, and after three weeks of continuous DBS, an in-depth neurological assessment was made using a variety of standardised intelligence, verbal and memory tests. At this point, further memory stimulation was also carried out, with the patient being unsure when electrodes were randomly switched on or off. The "on or off" tests each lasted two days and were one week apart. They involved presenting the patient with a series of 80 word pairs, and then later testing whether he could remember the words in the right combinations by presenting him with word pairs that were the same as before, recombined or new pairs.


A repeat experiment was carried out 12 months later, this time with the "on or off" tests being completed in the same day, and the man being given a series of 120 word pairs with which he had to construct a sentence.


Radiological testing was also carried out after one month of DBS to see which regions of the brain were being activated by hypothalamic stimulation.


What were the results of the study?


When the researchers placed the electrodes at one contact site on the left side of the hypothalamus, they found that the man unexpectedly reported a sensation he described as "d?©j?  vu". The experience was of a situation from about 30 years earlier, of being in a park with friends. As the voltage was increased (from three to five volts) the details of the scene became clearer to the man. When the experiment was repeated at different electrode positions (the man being unaware of which position was receiving the stimulation) the researchers found that specific situations could be recalled with each position.


When certain positions received more than five volts, the man experienced adverse effects including flushing and sweating. The patient also experienced flashes of light in one of his eyes when the front part of the hypothalamus - located where nerve tracts between the eyes and the brain cross over - was stimulated. During these experiences, the man reported no change in his feelings of hunger on the scale of one to 10.


Two weeks after the electrodes were fixed in place, repeat testing produced similar memories to those recalled in the operating room, although these were independent of the site of the hypothalamus being stimulated. The same findings that the memory increased in detail with increasing voltage and increased side effects were also repeated.


At the time of surgery, the man scored average to high-average on all verbal, memory and intelligence tests. At three weeks, there were significant improvements on two verbal and spatial learning tests, but not across the others (14 individual tests in total).


On both word pair tests, the researchers found that the patient was more likely to remember the correct word pairs when DBS was switched on.


Radiological testing demonstrated that when the electrodes in the hypothalamus were stimulated, there were signs of increased activity in parts of the temporal lobe of the brain that is involved with memory and recall.


Further details of the effects of DBS upon appetite were not published in this report.


What interpretations did the researchers draw from these results?


The authors conclude that deep brain stimulation to the hypothalamus causes activity in a region of the temporal lobe and that "it may be possible to apply electrical stimulation to modulate memory function".


What does the NHS Knowledge Service make of this study?


This study will be of interest to doctors and scientists and will probably lead to further research and development in the field of deep brain stimulation and the effects that it may have on memory. However, at the current time any practical applications of this treatment are a long way off.


It should be pointed out that these findings are the result of a case study in one man only and it is unclear whether the same effects would be witnessed in other people. There may also have been other hidden factors that affected the results.


The man in this study was not an Alzheimer's sufferer and the researchers do not make any mention of this as a potential treatment for Alzheimer's disease within the paper. It is too early to conclude from this research if this technique could be used as a treatment for Alzheimer's disease.


Links to the headlines


Deep stimulation 'boosts memory' BBC News, January 30 2008

Scientists discover way to reverse loss of memory. The Independent, January 30 2008

Discovery could make Alzheimer's a memory. The Daily Telegraph, January 30 2008


Links to the science


Memory enhancement induced by hypothalamic/fornix deep brain stimulation.
Hamani C, McAndrews MP, Cohn M, et al.

Ann Neurol; 63: 119-123


This news comes from NHS Choices

Antioxidant Therapy Shows Early Promise Against Alzheimer's Disease - Improved Blood Flow Boosted Cognition And Behavior In Mice With AD-Like Illness

For the first time, new research demonstrates that curbing harmful antioxidant processes in the brain's vasculature can reverse some of the cognitive decline associated with Alzheimer's disease. A natural enzyme of the immune system -- NADPH oxidase -- has been found to have toxic side effects, producing free radicals in the brains of mice. Identification of the enzyme's role in dementia might translate into a new drug target for Alzheimer's disease in humans, according to new findings published in a recent issue of the Proceedings of the National Academy of Sciences. After the offending enzyme was genetically "switched off," mice with a type of dementia mimicking Alzheimer's regained important cognitive abilities, even though the amount of Alzheimer's-linked amyloid plaques in their brains remained unchanged. These results suggest that the enzyme independently influences the progression of dementia.


The researchers, led by Dr. Costantino Iadecola, the George C. Cotzias Distinguished Professor of Neurology and Neuroscience at Weill Cornell Medical College and chief of the Division of Neurobiology at NewYork-Presbyterian Hospital/Weill Cornell Medical Center, also genetically engineered mice that produced a mutated form of NADPH enzyme that did not produce the toxic free radicals.



The result: The formerly "demented" mice regained their healthy, exploratory behaviors, just as non-demented mice do. According to the authors, the findings suggest that neurological damage from Alzheimer's may not be permanent and might even be reversed through antioxidant treatment.


NewYork-Presbyterian Hospital/Weill Cornell Medical Center


NewYork-Presbyterian Hospital/Weill Cornell Medical Center, located in New York City, is one of the leading academic medical centers in the world, comprising the teaching hospital NewYork-Presbyterian and Weill Cornell Medical College, the medical school of Cornell University. NewYork-Presbyterian/Weill Cornell provides state-of-the-art inpatient, ambulatory and preventive care in all areas of medicine, and is committed to excellence in patient care, education, research and community service. Weill Cornell physician-scientists have been responsible for many medical advances -- from the development of the Pap test for cervical cancer to the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., the first clinical trial for gene therapy for Parkinson's disease, the first indication of bone marrow's critical role in tumor growth, and, most recently, the world's first successful use of deep brain stimulation to treat a minimally-conscious brain-injured patient. NewYork-Presbyterian, which is ranked sixth on the U.S.News & World Report list of top hospitals, also comprises NewYork-Presbyterian Hospital/Columbia University Medical Center, Morgan Stanley Children's Hospital of NewYork-Presbyterian, NewYork-Presbyterian Hospital/Westchester Division and NewYork-Presbyterian Hospital/The Allen Pavilion. Weill Cornell Medical College is the first U.S. medical college to offer a medical degree oversees and maintains a strong global presence in Austria, Brazil, Haiti, Tanzania, Turkey and Qatar.

NewYork-Presbyterian Hospital
Weill Cornell Medical Center

Alzheimer's Society Comment - Care Quality Commission Survey Reveals Malnutrition In Hospitals

Around one in five hospital patients who have trouble feeding themselves do not get help with meals, according to the survey released by the Care Quality Commission (CQC).


'It's appalling that thousands of vulnerable people who rely on the help of others to eat are being denied vital support. One quarter of all hospital beds are occupied by people with dementia, who may have difficulty swallowing; forget how to eat or stop being able to recognise food.


Regular dementia training for nurses and social care staff can help tackle this issue and simple information sharing can illustrate how dementia affects everyday tasks. One in three people over 65 die with this devastating condition. Hospitals must act now and start making dementia a priority.'


Neil Hunt

Chief Executive

Alzheimer's Society


Source

Alzheimer's Society

Lower Dementia Drug Dose Boosts Brain Function, Cuts Side Effects

Sometimes less is more: Lower doses of an Alzheimer's drug delivered via skin patches improve cognition with fewer serious side effects than higher doses, researchers have found in an updated review.


"Is there any advantage of giving patients higher doses of rivastigmine? There doesn't seem to be any," said lead review author Jacqueline Birks, senior medical statistician for the University of Oxford, in England.


Previous studies had shown that high daily doses of rivastigmine (also known by its brand name, Exelon) of between 6 and 12 milligrams improved cognitive functions, such as memory, language and ability to perform simple daily living tasks, in patients with mild to moderate Alzheimer's disease.


However, adverse events often accompany high doses of rivastigmine.


Rivastigmine is part of the drug class called acetylcholinesterase inhibitors. These drugs work by improving transmission of electrical signals across certain areas of the brain.


Manufactured by Novartis, rivastigmine typically causes gastrointestinal side effects such as nausea, vomiting, diarrhea, abdominal pain and lack of appetite, as well as dizziness, fainting and weakness. In the United States, the drug costs about $160 per month.


Previous studies indicated that smaller, more frequent doses of rivastigmine might reduce the incidence of adverse events. Based on that evidence, a new study, the results of which are included in the update, began testing the safety and effectiveness of two strengths of the rivastigmine skin patch.


The review appears in the latest issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews like this one draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.


The current review examined nine studies involving 4,775 patients with Alzheimer's disease. Research in five of the studies took place in the United States.


"What I was really interested in was how the [smaller 9.6 milligram/day] patch compared to the [larger 17.4 milligram/day] patch. What I found was that there didn't seem to be any differences in efficacy, but the patch in higher doses has more adverse events associated with it," Birks said.


Patients taking the larger patch scored similarly on cognitive function tests, compared to those taking the smaller patch, but two-thirds of patients taking the larger patch had at least one adverse event, compared to only half of patients taking the smaller patch.















For example, 19 percent of those taking the larger patch reported vomiting, whereas only 6 percent of patients taking the smaller patch reported this side effect.


"Gastrointestinal adverse events are associated with acetylcholinesterase inhibitors, but we see fewer with the smaller patch compared with the larger patch," Birks noted.


Patients taking the smaller rivastigmine patch also had lower rates of adverse events when compared to patients taking a 6- to 12-milligram daily dose of rivastigmine capsules, Birks said.


"It seems to show that they have improved the method of administering rivastigmine. We seem to get the same efficacy but we have a better adverse event profile" with the smaller dose patch, Birks said.


"This review has confirmed what we knew about the drug that it provides cognitive improvements similar to other Alzheimer's medications, said Piero Antuono, M.D., a professor of neurology, pharmacology and toxicology at the Medical College of Wisconsin.


He has no affiliation with the review.


"Over a period of six months, people with Alzheimer's who take this drug improve by two points on a cognitive scale of zero to 70. If untreated, people with Alzheimer's lose an average of seven points per year," Antuono said.


Although acetylcholinesterase inhibitors such as rivastigmine do affect cognitive function in people with Alzheimer's, patients and their caregivers should understand that these drugs do not change the ultimate progression of this degenerative disease, he said.


"It's changing a little bit of the journey of the disease. You either take the expressway from point A to point B, or with this medication, you slow down and take the country road. It doesn't really make a difference long term, and it doesn't prolong life," Antuono said.


"Although these medications do provide symptomatic intervention for some time, they have to be used with non-pharmacological interventions, meaning that one needs to counsel the caregiver in managing the patient and provide social support so that the drug gets to work," Antuono said.


The Cochrane Collaboration is an international nonprofit, independent organization that produces and disseminates systematic reviews of health care interventions and promotes the search for evidence in the form of clinical trials and other studies of interventions


Birks J, et al. Rivastigmine for Alzheimer's disease. The Cochrane Database of Systematic Reviews 2009, Issue 2.


Source: Health Behavior News Service


View drug information on Exelon.

Alzheimer's Disease: Measuring Proteins In Spinal Fluid May Provide Early Clue

Early signs of the development of Alzheimer's disease can be seen in the cerebrospinal fluid of middle-aged adults who are genetically predisposed to the neurologic condition, according to a report in the July issue of Archives of Neurology, one of the JAMA/Archives journals.



The two strongest risk factors for Alzheimer's disease are aging and the presence of an allele (type of gene) known as apolipoprotein E*4 (APOE*4), according to background information in the article. Those with the APOE*4 allele develop clinical dementia about 10 to 15 years earlier than those who do not have the APOE*4 allele. Previous studies have shown that the plaques that form in the brain during Alzheimer's disease, which are made of proteins known as a-amyloids, begin forming years before affected individuals experience any symptoms of the disease. As a-amyloid proteins, predominately of a type known as Aa42, clump together, fewer are available to circulate through the nervous system. Therefore, lower levels of the Aa42 in the cerebrospinal fluid surrounding the brain and spinal cord serve as biomarkers or chemical indicators of the development of Alzheimer's disease.



Elaine R. Peskind, M.D., VA Puget Sound Health Care System and University of Washington School of Medicine, Seattle, and colleagues estimated the combined effect of aging and the APOE*4 allele on levels of Aa42 and another a-amyloid, Aa40, in 184 adults (94 men and 90 women, average age 50 years). The participants underwent clinical and laboratory screening and were found to be cognitively normal--that is, they had no difficulties with thinking, learning or memory. Researchers took samples of cerebrospinal fluid in the morning after an overnight fast and measured participants' Aa42 and Aa40 levels in addition to determining whether each individual had the APOE*4 allele.



Those who were older and who had the APOE*4 allele were more likely to have lower levels of Aa42. For those who did not have the APOE*4 allele, Aa42 levels rose slightly until about age 50 years then begin to decline slowly. On the other hand, those with the APOE*4 allele experienced a slight decline in Aa42 in their younger years and then a dramatic drop between ages 50 and 60 years. Levels of Aa42 were not associated with scores on any cognitive or memory tests. "In persons with the APOE*4 allele, decline in cerebrospinal fluid Aa42 concentration possibly begins in young adulthood, followed by marked acceleration of this decline beginning in midlife--decades before clinical manifestations of Alzheimer's disease," the authors write. The same relationship did not hold true for Aa40, which, although it is also found in amyloid plaques, is less prevalent there than Aa42; levels of Aa40 did not change with age in those with the APOE*4 allele and decreased with age in those without the APOE*4 allele.



"These findings have implications for the preclinical diagnosis of Alzheimer's disease, as well as for treatment," the authors conclude. "Therapeutic strategies aimed at prevention of Alzheimer's disease may need to be applied in early midlife or even younger ages to have maximal effect on amyloid deposition. Primary prevention trials for Alzheimer's disease targeting elderly persons may be too late to affect the early stages of disease pathology." (Arch Neurol. 2006;63:936-939.







Editor's Note: This study was supported by grants from the U.S. National Institute on Aging; the National Alzheimer's Coordinating Center; Friends of Alzheimer's Research; Alzheimer's Association of Western and Central Washington; and the Department of Veterans Affairs.



Editorial: Early Detection Needed to Treat Alzheimer's Disease



Research has indicated that the processes associated with Alzheimer's disease can be changed and even reversed--if they are detected in the early stages, writes Roger N. Rosenberg, M.D., University of Texas Southwestern Medical Center and editor, Archives of Neurology, in an accompanying editorial.



"???Peskind and colleagues offer an additional means to identify the earliest phase of Alzheimer's disease, when the effectiveness of future agents will have the most benefit," he writes. "Time matters in most issues, including treating the patient who has Alzheimer's disease."



Contact: Jeri Rowe


JAMA and Archives Journals

Positive Interim Results From Phase III Trial Of Amyloid Imaging Agent Florbetapir F18 Presented At American Academy Of Neurology Annual Meeting

Avid Radiopharmaceuticals, Inc. ("Avid") today announced the presentation of interim data from its landmark florbetapir "Image-to-Autopsy" Phase III study. These data come from the first cohort of subjects in the trial and are the first ever Phase III results for an agent designed to image Alzheimer's disease pathology. Today, Alzheimer's disease can only be definitely diagnosed by microscopic detection of beta-amyloid at autopsy. The goal of Avid's Phase III trial is to test the ability of florbetapir to image beta-amyloid in living patients.


The interim data showed that florbetapir PET imaging results in patients correlated with the levels of beta-amyloid pathology later found in their brains at autopsy. Dr. Adam Fleisher, Associate Director of Brain Imaging at Banner Alzheimer's Institute, presented the analysis at the 2010 Annual Meeting of the American Academy of Neurology in Toronto, ON.


Dr. Fleisher commented "These preliminary results are very encouraging for the field of amyloid imaging and the future management of Alzheimer's disease. The data suggest that florbetapir imaging may offer an opportunity to detect amyloid plaques in-life. Knowing if a patient has Alzheimer's pathology might lead to better patient management -- for example, if a patient has memory loss but no amyloid pathology, we could rule-out Alzheimer's disease, and instead focus on looking for other causes for their symptoms."


Dr. Fleisher reported the results from the analysis of the first six subjects of the florbetapir "Image-to-Autopsy" Phase III study. The data from this cohort demonstrated that the florbetapir PET images correlated strongly with the post mortem histopathology findings. The PET images not only correctly identified which subjects had beta-amyloid deposits, but also showed where in the brain the deposits had accumulated. The full trial data are expected to be available later this year.


Avid's florbetapir was the first beta-amyloid imaging compound to enter multi-center, IND clinical studies in the U.S., and has now been studied in more than a dozen trials in over 700 subjects ranging from cognitively normal individuals to those with Alzheimer's dementia. As well as the pivotal Phase III Image-to-Autopsy study, additional clinical studies in the E.U., South America, Australia and Asia are also being conducted.


About Alzheimer's Disease and Beta-Amyloid Plaque Deposits


Alzheimer's disease, a chronic neurodegenerative condition that currently affects over 5 million Americans1, cannot be definitively diagnosed until after death, when a brain autopsy is performed on a patient and evidence of beta-amyloid plaque deposits in the brain - which are a hallmark pathology of the disease - can be found. Accurate diagnosis during life can be challenging, particularly in the early stages of disease, when symptoms are mild and non-definitive and can be mistaken for those of other treatable conditions. Florbetapir, used with positron emission tomography (PET) technology is being assessed for the ability to detect beta-amyloid plaque deposits in-vivo, potentially offering clinically useful diagnostic insight at an early stage.


1 Source: Alzheimer's Association 2010 Alzheimer's Disease Facts and Figures


Source
Avid Radiopharmaceuticals, Inc.

Higher Folate Levels Linked To Reduced Risk For Alzheimer's Disease

Individuals who take in higher levels of the nutrient folate through both diet and supplements may have a reduced risk of developing Alzheimer's disease, according to a report in the January issue of Archives of Neurology, one of the JAMA/Archives journals.



By the year 2047, the prevalence of Alzheimer's disease is expected to quadruple, according to background information in the article. Delaying the onset of this neurodegenerative disease would significantly reduce the burden it causes. Researchers suspect that elevated levels of the amino acid homocysteine in the blood, which is linked to a higher risk for cardiovascular disease and stroke, may also increase the risk for Alzheimer's disease. Folate, vitamin B12 and vitamin B6, are important in the body's processing of homocysteine--therefore, deficiencies in these nutrients increase homocysteine levels and may contribute to cardiovascular disease, stroke and dementia.



Jos?© A. Luchsinger, M.D., Columbia University Medical Center, New York, and colleagues examined, interviewed and assessed the diets of 965 individuals without dementia between 1992 and 1994 and then followed them for an average of 6.1 years to see if they developed Alzheimer's disease. The participants had an average age of 75.8 and 70.2 percent were women, 32.6 percent African-American, 45.3 percent Hispanic and 22.1 percent white.



During the follow-up period, 192 of the participants developed Alzheimer's disease. When the individuals were divided into four groups based on the total level of folate they took in through food and supplements and the analysis was adjusted for patient characteristics, comorbid diseases and B12 and B6 intake, the risk of Alzheimer's disease was lower in the groups with higher intake. Neither dietary folate nor supplements alone were significantly linked to Alzheimer's disease risk; only the two in combination appeared to produce an effect. Levels of the vitamins B12 and B6 were not associated with Alzheimer's disease risk.



Higher folate intake was modestly correlated with lower homocysteine levels, "indirectly suggesting that a lower homocysteine level is a potential mechanism for the association between higher folate intake and a lower Alzheimer's disease risk," the authors write.



Definitive conclusions about the role of folate in the development of Alzheimer's disease cannot yet be made, they continue. The findings of this study are in contrast to those of some other research, and other compounds (such as hormones) perceived to reduce the risk for dementia in observational studies did not do so in randomized trials. "Thus, the decision to increase folate intake to prevent Alzheimer's disease should await clinical trials," they conclude.







(Arch Neurol. 2007;64:86-92.)


This study was supported by grants from the National Institutes of Health; a grant from the Charles S. Robertson Memorial Gift for research on Alzheimer's disease; the Blanchette Hooker Rockefeller Foundation; and the New York City Council Speaker's Fund for Public Health Research. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.



Contact: Craig LeMoult

JAMA and Archives Journals

Longevity Gene Also Protects Memory, Cognitive Function

A gene variation that helps people live into their 90s and beyond also protects their memories and ability to think and learn new information, according to a study published in the December 26, 2006, issue of Neurology, the scientific journal of the American Academy of Neurology.


The gene variant alters the cholesterol particles in the blood, making them bigger than normal. Researchers believe that smaller particles can more easily lodge themselves in blood vessel linings, leading to the fatty buildup that can cause heart attacks and strokes.


The study examined 158 people of Ashkenazi, or Eastern European, Jewish descent, who were 95 years old or older. Those who had the gene variant were twice as likely to have good brain function compared to those who did not have the gene variant. The researchers also validated these findings in a group of 124 Ashkenazi Jews who were between age 75 and 85 and found similar results.


???It??™s possible that this gene variant also protects against the development of Alzheimer??™s disease,??? said study author Nir Barzilai, MD, the director of the Institute for Aging Research at Albert Einstein College of Medicine in Bronx, NY.


Barzilai noted that many studies have identified risk factors associated with developing age-related diseases. ???But little effort has been made to identify the reasons for longevity in exceptionally old people, and why they don??™t develop disease. In studying these centenarians, we hope to learn what factors lessen their risk for diseases that affect the general population at a much younger age. Our results bring us a step closer to understanding the role that genes play in longevity.???


Work is being done to develop drugs that can mimic the effect of this gene variation, Barzilai said.


Approximately one in 10,000 people in the general population lives to the age of 100.


The study was supported by grants from the Einstein Aging Study, the Paul Beeson Physician Faculty Scholar in Aging Award, the Ellison Medical Foundation Senior Scholar Award, the National Institutes of Health, the Albert Einstein College of Medicine, and the Baltimore VA Geriatric Research and Education Clinical Center.


The American Academy of Neurology, an association of more than 20,000 neurologists and neuroscience professionals, is dedicated to improving patient care through education and research. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as stroke, Alzheimer??™s disease, epilepsy, Parkinson disease, and multiple sclerosis.


For more information about the American Academy of Neurology, visit aan.


American Academy of Neurology (AAN)

1080 Montreal Ave.

St. Paul, MN 55116

United States

neurology

'Abusive Behaviour' Towards People With Dementia By Family Carers Is Common

Half of family carers of people with dementia report some abusive behaviour towards the person they are caring for and one third report 'significant' levels of abuse, according to new research from UCL (University College London) published today in the British Medical Journal (BMJ).



The paper authors feel that this is unsurprising, as most people with dementia are being cared for by dedicated family or friends, often with little support.



Dr Claudia Cooper, UCL Department of Mental Health Sciences and lead author of the study, said: "Many people think about elder abuse in terms of "lashing out" and other similar acts, but abuse as defined by government guidelines* can be as simple as shouting or swearing at the person being cared for."



The UK government is currently consulting about a revision of their policy for safeguarding vulnerable adults. This focuses entirely on preventing abuse by paid carers, but in light of their clinical experience the authors wanted to find out how common abusive behaviour is and highlight that policy on abuse will be ineffective unless it is realistic about the problems that family carers are facing.



The researchers conducted a survey of 220 family carers of people with dementia newly referred to psychiatric services and living at home. 115 (52.3 per cent) of the carers reported some abusive behaviour, such as very occasionally screaming or yelling, and 74 (33.6 per cent) reported significant levels of abuse, such as more frequent insulting or swearing at the person for whom they care. Only 1.4 per cent reported significant physical abuse.



The measure used by the researchers in the study is known as the Modified Conflict Tactics Scale (MCTS). Carers answered questions about how often in the last three months they had acted in five psychologically and five physically abusive ways on a scale of 0-4 (never - all the time). A score of more then two on one question is defined by this scale as 'significant' abuse.



Dr Cooper added: "This is the first representative survey to ask family carers about abuse. It shows that abusive behaviour towards people with dementia from family carers is common according to the scale used, with a third reporting 'significant' levels of abuse, and half some abusive behaviour. We found few cases of physical or frequent abuse, although those with the most abusive behaviour may have been reluctant to report it, or take part in the study in the first place."



Co-author Professor Gill Livingston added: "Our findings suggest that any strategy for safeguarding vulnerable adults must be directed towards families who provide the majority of care for older people, rather than exclusively at paid carers. The UK government is currently revising its policy in this area, but unfortunately their review is entirely focused on preventing abuse by paid carers, suggesting that abuse is confined to the formal care system whereas our research suggests this is not the case.
















"The vast majority of family carers do a fantastic job under very difficult circumstances and although levels of minor abuse seem high according to the scale used, there may need to be a redefinition. Healthcare professionals can be reluctant to ask about abuse by family carers, but this attitude can be very unhelpful to carers who are worried about their own actions and want to talk about them and get help. Considering elder abuse as a spectrum of behaviours rather than an "all or nothing" phenomenon could help professionals to ask about it and therefore offer assistance."



-- * No secrets: guidance on developing and implementing multi-agency policies and procedures to protect vulnerable adults from abuse. March 2000, 1-42.


-- The paper 'The CARD study - abuse of people with dementia by family carers' is published online ahead of print in the British Medical Journal at 00.01 on Friday 23 January. Advance copies can be obtained by journalists from the UCL Media Relations office using the contact details above.


-- This research was funded by a research training fellowship awarded to Dr Cooper by the Medical Research Council. The author's work was carried out independently of the funders.




About UCL



Founded in 1826, UCL was the first English university established after Oxford and Cambridge, the first to admit students regardless of race, class, religion or gender, and the first to provide systematic teaching of law, architecture and medicine. UCL is the seventh-ranked university in the 2008 THES-QS World University Rankings, and the third-ranked UK university in the 2008 league table of the top 500 world universities produced by the Shanghai Jiao Tong University. UCL alumni include Marie Stopes, Jonathan Dimbleby, Lord Woolf, Alexander Graham Bell, and members of the band Coldplay. UCL currently has over 12,000 undergraduate and 8,000 postgraduate students. Its annual income is over ??600 million.

UCL