Live longer with fewer calories

By consuming fewer calories, ageing can be slowed down and the development of age-related diseases such as cancer and type 2 diabetes can be delayed. The earlier calorie intake is reduced, the greater the effect. Researchers at the University of Gothenburg have now identified one of the enzymes that hold the key to the ageing process.

31 oct 2011--"We are able to show that caloric restriction slows down ageing by preventing an enzyme, peroxiredoxin, from being inactivated. This enzyme is also extremely important in counteracting damage to our genetic material," says Mikael Molin of the Department of Cell and Molecular Biology.

By gradually reducing the intake of sugar and proteins, without reducing vitamins and minerals, researchers have previously shown that monkeys can live several years longer than expected. The method has also been tested on everything from fishes and rats to fungi, flies and yeasts with favourable results. Caloric restriction also has favourable effects on our health and delays the development of age-related diseases. Despite this, researchers in the field have found it difficult to explain exactly how caloric restriction produces these favourable effects.

Using yeast cells as a model, the research team at the University of Gothenburg has successfully identified one of the enzymes required. They are able to show that active peroxiredoxin 1, Prx1, an enzyme that breaks down harmful hydrogen peroxide in the cells, is required for caloric restriction to work effectively.

The results, which have been published in the scientific journal Molecular Cell, show that Prx1 is damaged during ageing and loses its activity. Caloric restriction counteracts this by increasing the production of another enzyme, Srx1, which repairs Prx1. Interestingly, the study also shows that ageing can be delayed without caloric restriction by only increasing the quantity of Srx1 in the cell. Repair of the peroxiredoxin Prx1 consequently emerges as a key process in ageing.

"Impaired Prx1 function leads to various types of genetic defects and cancer. Conversely, we can now speculate whether increased repair of Prx1 during ageing can counteract, or at least delay, the development of cancer."

Peroxiredoxins have also been shown to be capable of preventing proteins from being damaged and aggregating, a process that has been linked to several age-related disorders affecting the nervous system, such as Alzheimer's and Parkinson's. The researchers are accordingly also considering whether stimulation of Prx1 can reduce and delay such disease processes.

More information: The article 'Life Span Extension and H2O2 Resistance Elicited by Caloric Restriction Require the Peroxiredoxin Tsa1 in Saccharomyces cerevisiae' has been published in the journal Molecular Cell.

Expert comments in the same issue "Translating a Low-Sugar Diet into a Longer Life by Maintaining Thioredoxin Peroxidase Activity of a Peroxiredoxin"

Provided by University of Gothenburg

New findings contradict dominant theory in Alzheimer's disease

For decades the amyloid hypothesis has dominated the research field in Alzheimer's disease. The theory describes how an increase in secreted beta-amyloid peptides leads to the formation of plaques, toxic clusters of damaged proteins between cells, which eventually result in neurodegeneration. Scientists at Lund University, Sweden, have now presented a study that turns this premise on its head.

30 oct 2011--The research group's data offers an opposite hypothesis, suggesting that it is in fact the neurons' inability to secrete beta-amyloid that is at the heart of pathogenesis in Alzheimer's disease.

The study, published in the October issue of the Journal of Neuroscience, shows an increase in unwanted intracellular beta-amyloid occurring early on in Alzheimer's disease. The accumulation of beta-amyloid inside the neuron is here shown to be caused by the loss of normal function to secrete beta-amyloid.

Contrary to the dominant theory, where aggregated extracellular beta-amyloid is considered the main culprit, the study instead demonstrates that reduced secretion of beta-amyloid signals the beginning of the disease.

The damage to the neuron, created by the aggregated toxic beta-amyloid inside the cell, is believed to be a prior step to the formation of plaques, the long-time hallmark biomarker of the disease.

Professor Gunnar Gouras, the senior researcher of the study, hopes that the surprising new findings can help push the research field in a new direction.

"The many investigators and pharmaceutical companies screening for compounds that reduce secreted beta-amyloid have it the wrong way around. The problem is rather the opposite, that it is not getting secreted. To find the root of the disease, we now need to focus on this critical intracellular pool of beta-amyloid.

"We are showing here that the increase of intracellular beta-amyloid is one of the earliest events occurring in Alzheimer's disease, before the formation of plaques. Our experiments clearly show a decreased secretion of beta-amyloid in our primary neuron disease model. This is probably because the cell's metabolism and secretion pathways are disrupted in some way, leading beta-amyloid to be accumulated inside the cell instead of being secreted naturally", says Davide Tampellini, first author of the study.

The theory of early accumulation of beta-amyloid inside the cell offers an alternate explanation for the formation of plaques. When excess amounts of beta-amyloid start to build up inside the cell, it is also stored in synapses.

When the synapses can no longer hold the increasing amounts of the toxic peptide the membrane breaks, releasing the waste into the extracellular space. The toxins released now create the seed for other amyloids to gather and start forming the plaques.

More information: "Impaired β-Amyloid Secretion in Alzheimer's Disease Pathogenesis" http://www.jneuros … 3/15384.full

Provided by Lund University

Yeast model connects Alzheimer's disease risk and amyloid beta toxicity

Using yeast cells, a team of Whitehead scientists in the lab of Whitehead Member Susan Lindquist investigated the harmful effects of amyloid beta (Aβ), a peptide whose accumulation in amyloid plaques is a hallmark of AD. Work by the lab indicates that Aβ disrupts normal cellular trafficking, with clathrin-mediated endocytosis being specifically vulnerable. Under normal conditions, the membrane bound receptor Ste3 (green) is subject to clathrin-mediated endocytosis and is trafficked to the cell’s vacuole (left). In Aβ expressing yeast cells, Ste3 is not localized to the vacuole, but is dispersed in foci throughout the cell, indicating that endocytic trafficking is perturbed (center). Expression of the yeast homolog of PICALM, one of the most highly validated human AD risk factors, restores normal trafficking in Aβ-expressing yeast, and Ste3 is again localized in the vacuole (right).

29 oct 2011--In a development that sheds new light on the pathology of Alzheimer's disease (AD), a team of Whitehead Institute scientists has identified connections between genetic risk factors for the disease and the effects of a peptide toxic to nerve cells in the brains of AD patients.

The scientists, working in and in collaboration with the lab of Whitehead Member Susan Lindquist, established these previously unknown links in an unexpected way. They used a very simple cell type—yeast cells—to investigate the harmful effects of amyloid beta (Aβ), a peptide whose accumulation in amyloid plaques is a hallmark of AD. This new yeast model of Aβ toxicity, which they further validated in the worm C. elegans and in rat neurons, enables researchers to identify and test potential genetic modifiers of this toxicity.

"As we tackle other diseases and extend our lifetimes, Alzheimer's and related diseases will be the most devastating personal challenge for our families and one the most crushing burdens on our economy," says Lindquist, who is also a professor of biology at Massachusetts Institute of Technology and an investigator of the Howard Hughes Medical Institute. "We have to try new approaches and find out-of the-box solutions."

In a multi-step process, the researchers were able to introduce the form of Aβ most closely associated with AD into yeast in a manner that mimics its presence in human cells. The resulting toxicity in yeast reflects aspects of the mechanism by which this protein damages neurons. This became clear when a screen of the yeast genome for genes that affect Aβ toxicity identified a dozen genes that have clear human homologs, including several that have previously been linked to AD risk by genome-wide association studies (GWAS) but with no known mechanistic connection.

With these genetic candidates in hand, the team set out to answer two key questions: Would the genes identified in yeast actually affect Aβ toxicity in neurons? And if so, how?

To address the first issue, in a collaboration with Guy Caldwell's lab at the University of Alabama, researchers created lines of C. elegans worms expressing the toxic form of Aβ specifically in a subset of neurons particularly vulnerable in AD. This resulted in an age-dependent loss of these neurons. Introducing the genes identified in the yeast that suppressed Aβ toxicity into the worms counteracted this toxicity. One of these modifiers is the homolog of PICALM, one of the most highly validated human AD risk factors. To address whether PICALM could also suppress Aβ toxicity in mammalian neurons, the group exposed cultured rat neurons to toxic Aβ species. Expressing PICALM in these neurons increased their survival.

The question of how these AD risk genes were actually impacting Aβ toxicity in neurons remained. The researchers had noted that many of the genes were associated with a key cellular protein-trafficking process known as endocytosis. This is the pathway that nerve cells use to move around the vital signaling molecules with which they connect circuits in the brain. They theorized that perhaps Aβ was doing its damage by disrupting this process. Returning to yeast, they discovered that, in fact, the trafficking of signaling molecules in yeast was adversely affected by Aβ. Here again, introducing genes identified as suppressors of Aβ toxicity helped restore proper functioning.

Much remains to be learned, but the work provides a new and promising avenue to explore the mechanisms of genes identified in studies of disease susceptibility.

"We now have the sequencing power to detect all these important disease risk alleles, but that doesn't tell us what they're actually doing, how they lead to disease," says Sebastian Treusch, a former graduate student in the Lindquist lab and now a postdoctoral research associate at Princeton University.

Jessica Goodman, a postdoctoral fellow in the Lindquist lab, says the yeast model provides a link between genetic data and efforts to understand AD from the biochemical and neurological perspectives.

"Our yeast model bridges the gap between these two fields," Goodman adds. "It enables us to figure out the mechanisms of these risk factors which were previously unknown."

Members of the Lindquist lab intend to fully exploit the yeast model, using it to identify novel AD risk genes, perhaps in a first step to determining if identified genes have mutations in AD patient samples. The work will undoubtedly take the lab into uncharted territory.

More information: "Functional Links Between Aβ Toxicity, Endocytic Trafficking and Alzheimer's Disease Risk Factors in Yeast" Science, October 28, 2011.

Provided by Whitehead Institute for Biomedical Research

Longevity's secrets sought in DNA of 100-year-olds

27 oct 2011-- George Eberhardt turned 107 last month, and scientists would love to know how he and other older folks like him made it that far. So he's going to hand over some of his DNA. He's one of 100 centenarians taking part in a project announced Wednesday that will examine some of the oldest citizens with one of the newest scientific tools: whole-genome sequencing, the deciphering of a person's complete collection of DNA.

Scientists think DNA from very old healthy people could offer clues to how they lived so long. And that could one day lead to medicines to help the rest of us stay disease-free longer.

By the time you reach, say, 105, "it's very hard to get there without some genetic advantages," says Dr. Thomas Perls, a geriatrics expert at Boston University.

Perls is helping find centenarians for the Archon Genomics X Prize competition. The X Prize Foundation, best known for a spaceflight competition, is offering $10 million in prize money to researchers who decipher the complete DNA code from 100 people older than 100. The contest will be judged on accuracy, completeness and the speed and cost of sequencing.

The contest is a relaunch of an older competition with a new focus on centenarians, and it's the second sequencing project involving the elderly to be announced this month.

Genome pioneer J. Craig Venter says the centenarian project is just a first step in revealing the genetic secrets of a long and healthy life.

"We need 10,000 genomes, not 100, to start to understand the link between genetics, disease and wellness," said Venter, who is co-chairing the X Prize contest.

The 107-year-old Eberhardt of Chester, N.J., played and taught tennis until he was 94. He said he's participating in the X Prize project because he's interested in science and technology. It's not clear his genes will reveal much. Nobody else in his extended family reached 100, and he thinks only a couple reached 90, he said in a telephone interview.

So why does he think he lived so long? He credits 70 years of marriage to his wife, Marie. She in turn cites his "intense interest in so many things" over a lifetime, from building radios as a child to pursuing a career in electronics research.

But scientists believe there's more to it, and they want to use genome sequencing to investigate. Dr. Richard Cawthon of the University of Utah, who is seeking longevity genes by other means, says it may turn up genetic features that protect against multiple diseases or that slow the process of aging in general.

Protective features of a centenarian's DNA can even overcome less-than-ideal lifestyles, says Dr. Nir Barzilai of the Albert Einstein College of Medicine in New York. His own study of how centenarians live found that "as a group, they haven't done the right things."

Many in the group he studied were obese or overweight. Many were smokers, and few exercised or followed a vegetarian diet. His oldest participant, who died this month just short of her 110th birthday, smoked for 95 years.

"She had genes that protected her against the environment," Barzilai said. One of her sisters died at 102, and one of her brothers is 105 and still manages a hedge fund.

Earlier this month, Scripps Health of San Diego announced a different genome project involving the elderly. The Scripps Wellderly Study will receive the complete genomes of 1,000 people age 80 and older from a sequencing company.

A complete genome reveals not only genes but also other DNA that's responsible for regulating genes. It's "the full monty," showing DNA elements that are key for illness and health, says Dr. Eric Topol, who heads the Wellderly Study.

Participants in that study have an average age of 87 and range up to 108, and they've never had diabetes, heart disease or cancer, or any neurological disease.

"Why are these people Teflon-coated?" Topol asked. "Why don't they get disease?"

The ability to turn out lots of complete genomes is "the new-new thing" in trying to find out, he said.

"There's been too much emphasis on disorders per se and not enough on the people who are exceptionally healthy," to learn from their genomes, Topol said. "Now we have the powerful tools to do that."

More information: X Prize competition: http://genomics.xprize.org/

Many Alzheimer's patients get drugs with opposing effects

You wouldn't brake your car while stepping on the gas—or wash down a sleeping pill with espresso. Yet many people taking common Alzheimer's disease medications—cholinesterase inhibitors—are given medications with anticholinergic properties, which oppose their effects. Group Health Research Institute scientists investigated how often that happens and reported on the consequences in an "Early View" study e-published in the Journal of the American Geriatrics Society.

26 oct 2011--"Cholinesterase inhibitors are today's primary therapy for slowing Alzheimer's disease," said study leader Denise Boudreau, PhD, RPh, an associate scientific investigator at Group Health Research Institute. "Anticholinergic properties are often found in drugs commonly used to treat gastrointestinal disorders, allergies, urinary incontinence, depression, and Parkinson's disease, and they can have negative effects on cognition and function in the elderly. There's concern that if someone is taking both types of drugs—cholinesterase inhibitors and anticholinergic medications—they will antagonize each other, and neither will work."

In clinical trials, cholinesterase inhibitors show modest effects against the functional and cognitive decline of people with Alzheimer's disease. These medications, such as donepezil (Aricept) work by inhibiting the breakdown of acetylcholine, which sends signals in the nervous system. By contrast, anticholinergics—such as diphenhydramine (Benadryl) and oxybutynin (Ditopan)—block the action of acetylcholine. Since the two types of drugs have opposite effects, it makes sense not to give both kinds of drugs to an individual person. But until Dr. Boudreau's study, few researchers had explored how often patients are prescribed both types of medications and which harms this might cause.

Dr. Boudreau and colleagues conducted a retrospective cohort study of 5,625 people aged 50 or older who received a new prescription for cholinesterase inhibitors between 2000 and 2007. The researchers used electronic pharmacy records of Group Health Cooperative and Kaiser Permanente Colorado, nonprofit health care systems that together provide care to more than a million people. The research team found patients who also had a prescription for anticholinergics from the year before their cholinesterase prescription until the analysis ended on December 31, 2008, or the patient left the health care system or died. The study was the first to use state death records and insurance claims for nursing home care to look for effects of taking both drug types.

The researchers found:

• Of the cholinesterase inhibitor users, 37 percent were also taking at least one anticholinergic drug, and more than 11 percent took two or more. This was similar to other studies of Medicare beneficiaries.
• For those using both medication types, dual use generally lasted three to four months, but 25 percent used both classes of drugs for more than a year.
• Anticholinergics were already being used in 23 percent of people receiving a new cholinesterase inhibitor prescription, and 77 percent continued, even after starting the cholinesterase inhibitor.
• Subjects using both medication types were not more likely to enter a nursing home or to die than those taking only cholinesterase inhibitors.

"It's reassuring that we did not observe an association between simultaneous use of the two types of drugs and increased risk of death or nursing home placement," said Dr. Boudreau. "But concomitant use of these drugs is, at the very least, not optimal clinical practice." Preventing concurrent use of opposing drugs could also be a chance to reduce waste in health care spending, since a month of donepezil treatment costs approximately $180.

One reason that health care providers might prescribe conflicting medications is that dementia patients often have multiple medical conditions. Also, anticholinergics are often given to counteract the side effects of cholinesterase inhibitors, which are one of the few available treatments for people with Alzheimer's. Dr. Boudreau hopes the study raises awareness about the potential inappropriateness of prescribing both types of drugs—and stimulate discussions about the best way to make therapeutic decisions for people with Alzheimer's.

"Providers, families, and patients should carefully consider the extent to which demonstrated benefits or harms in an individual patient justify long-term use of these drugs," said Dr. Boudreau. "A good first step is to have clearly agreed-upon goals for therapy and a plan to monitor for effects and side effects." Now Group Health Research Institute scientists have started to work with Group Health Cooperative on steps like these to improve the quality of care.

Provided by Group Health Research Institute

Structure of Parkinson's disease protein identified

erial view of computer generated alpha-synuclein bundle.

A team of researchers from the Petsko-Ringe and Pochapsky laboratories at Brandeis have produced and determined the structure of alpha-synuclein, a key protein associated with Parkinson’s disease.

25 oct 2011--Their findings, recently published in Proceedings of the National Academy of Sciences (PNAS), provide information that may someday be used to produce a new kind of treatment for the incurable degenerative brain disorder.


While people with Parkinson’s diseases exhibit many obvious symptoms such as tremors and weakness of face and throat muscles, definitive diagnosis of Parkinson’s comes post mortem, when alpha-synuclein proteins become denatured and form clumps called Lewy bodies in the brain.

“We don’t really know whether this is a side effect or whether it’s the cause of Parkinson’s disease, but we do know that the clumps of proteins are always there,” says Thomas C. Pochapsky, professor of chemistry and one of the authors of the paper. Pochapsky’s lab was responsible for examining the protein using nuclear magnetic resonance, a sort of MRI for molecules, housed at the Landsman Research Facility.

Alpha-synuclein is found in large quantities in the brain. Its association with Parkinson’s disease has stirred curiosity since it was discovered in 1997. 


“Nobody knows what it does, but there’s a lot of it,” says Pochapsky. “The question is whether the unfolded or coagulated Lewy body protein just represents the pathological form of something that’s normally doing something.”

To explore that question, the scientists wanted to find out what the form alpha-synuclein is in before it turns into Lewy body clumps, figuring that if it is possible to stabilize, the progression of Parkinson’s disease could be either slowed or reversed.

“Even if we don’t know what it is, we at least want to know in what form alpha-synuclein protein should be under normal conditions,” says Pochapsky.

Gregory Petsko, professor of biochemistry, compares alpha-synuclein to an origami bird that is benign when intact but dangerous if it unfolds. This knowledge could someday lead to the development of therapies that act like glue, helping the protein keep its shape. While some drugs perform in this manner in the treatment of other diseases, the possibility of one for Parkinson’s has not been investigated because, until now, scientists thought the Parkinson’s protein had no structure. The possibility that the protein actually has a structure and that this form of the protein is benign, means that such an approach can now be considered.

The research has the potential to create a paradigm shift, a dramatic change in how science views a given phenomenon.

More than half a million Americans suffer from Parkinson's disease and, according to the National Institutes of Health, about 50,000 new cases are reported annually. The altering of alpha-synuclein is also believed to be involved in Lewy Body Dementia, a relative of Parkinson’s that affects another one million Americans.

Quyen Q. Hoang, who was a post-doctoral researcher in the Petsko-Ringe lab, and is continuing with the research in his own lab at Indiana University School of Medicine, played a key role in developing the methodology for producing this protein.

Jeffrey Agar’s lab then used mass spectrometric studies, a method of determining molecule composition. Last, using nuclear magnetic resonance, Pochapsky’s lab examined the structure of the tetramer solution.

“We were able to establish that alpha-synuclein is actually a tetramer, meaning that four of these protein molecules stick together while moving around,” says Pochapsky. “We’ve found what we think is the normal form of alpha-synuclein, which no one has seen before it has clumped together in the form of Lewy bodies.”

Petsko points out that the ability to make this form of the protein may also shed light on its normal function.

“Synuclein makes up a sizeable percentage of the protein in neurons, but no one really understands what its role in the cell is,” Petsko says. “We hope that this form of the protein may be the form that has the benign function, so biochemists and cell biologists may now be able to figure out what it’s doing.”

Pochapsky explains that while researchers in other institutions have examined alpha-synuclein before, it has not been done with this ultra careful method, which maintains the structure.

Provided by Brandeis University

Study refutes testosterone as 'fountain of youth'

A new study of older Western Australian men has revealed that testosterone might not be the fountain of youth.

23 oct 2011--Published online this week in the Journal of Clinical Endocrinology and Metabolism, researchers from The University of Western Australia's Western Australian Centre for Health and Ageing set out to explore the association between testosterone levels and cause of death.

They confirmed earlier studies suggesting that men with low testosterone were more likely to die of cardiovascular disease.

But lead author and WA Centre for Health and Ageing researcher Zoë Hyde said low testosterone levels were not linked to death from other diseases, which was surprising.

"Previous studies suggested that men with low testosterone levels are likely to die earlier, and some researchers have argued that testosterone therapy might improve longevity," Ms Hyde said.

"However, our results suggest that low testosterone is a risk factor only for cardiovascular disease, and do not provide support for more widespread use of testosterone."

Testosterone therapy is available in Australia only for men whose levels have been found to be low on testing and are experiencing symptoms of testosterone deficiency.

Ms Hyde said it was premature to recommend testosterone therapy to prevent cardiovascular disease.

"Although our study suggests that preventing testosterone deficiency might have some health benefits, we need to first conduct clinical trials of testosterone therapy to see if these findings are real, and to also properly evaluate the risks of therapy," she said.

Ms Hyde said sex hormones played an important role in maintaining health and quality of life, particularly as their concentrations changed over time.

The research forms part of the Health In Men Study (HIMS) that has been following a group of men living in Perth, Western Australia since 1996 and is the largest study of ageing men in Australia. It involves community-dwelling men aged in their 70s and 80s but excludes men receiving hormonal therapy or men with prostate cancer.

Provided by University of Western Australia

Exceptional cognitive and physical health in old age leaves immunological fingerprint

Exceptional cognitive and physical function in old age leaves a tell-tale immunologic fingerprint, say researchers at the University of Pittsburgh and Children's Hospital of Pittsburgh of UPMC. Likewise, older adults who have mild impairments bear a distinct immunologic pattern, too, according to findings published today in the PLoS One.

22 oct 2011--Old age is not synonymous with impairment and disability, noted lead investigator Abbe N. de Vallejo, Ph.D., associate professor of pediatrics and immunology, University of Pittsburgh School of Medicine.

"Our study indicates that getting older does not necessarily mean that the immune system gets weaker, as many of us assumed," he said. "The immune system is dynamic, and the changes it undergoes over time very much influence function."

For the project, the team collected blood samples from 140 participants who had been followed in the Cardiovascular Health Study (CHS) for nearly two decades and were 78 to 94 years old. With only two participants younger than 82, the average age of the group was 86. The team also gathered information about the participants' health and function, medical history and hospitalizations, and self-rated health, and assessed their cognitive and physical function using standard tests.

Previous research has shown that with age, immune cells called T-cells become more like natural killer (NK) cells, which typically target tumor cells and virus-infected cells, Dr. de Vallejo said. A closer look in the new study shows that participants who were most physically and cognitively resilient had a dominant pattern of stimulatory NK receptors on the T-cell surface, and that these unusual T-cells can be activated directly through these NK receptors independently of the conventional ones. The functionally resilient elders also have a distinct profile of blood proteins called cytokines that reflect an immune-enhancing environment.

Conversely, the group that showed mild health impairment had a dominant pattern of inhibitory NK receptors on their T-cells, and they have a cytokine profile indicating a pro-inflammatory environment. Both of these immunologic features could suggest a greater susceptibility to illness.

"These findings indicate that there is remodeling or adaptation of the immune system as we age that can be either protective or detrimental," Dr. de Vallejo said. "Now we have an immunological fingerprint that can identify individuals who are more likely to stay physically and cognitively well."

He and his colleagues are now studying factors, such as genetics or traits developed during childhood that might influence the adaptation of the immune system with advancing age.

Provided by University of Pittsburgh Schools of the Health Sciences

Simple lifestyle changes can add a decade or more healthy years to the average lifespan

Vancouver − Health prevention strategies to help Canadians achieve their optimal health potential could add a decade or more of healthy years to the average lifespan and save the economy billions of dollars as a result of reduced cardiovascular disease, says noted cardiologist Dr. Clyde Yancy.

21 oct 2011--Dr. Yancy, who will deliver the Heart and Stroke Foundation of Canada Lecture at the opening ceremonies of the Canadian Cardiovascular Congress in Vancouver this Sunday, will tell delegates that people who follow seven simple steps to a healthy life can expect to live an additional 40 to 50 years after the age of 50.

"Achieving these seven simple lifestyle factors gives people a 90 per cent chance of living to the age of 90 or 100, free of not only heart disease and stroke but from a number of other chronic illnesses including cancer," says Dr. Yancy, a professor of medicine and chief of cardiology at the Northwestern University's Feinberg School of Medicine. He is also the past-president of the American Heart Association.

"By following these steps, we can compress life-threatening disease into the final stages of life and maintain quality of life for the longest possible time." He predicts that, if we act now, we can reverse the tide by 2020.

According to the Heart and Stroke Foundation, every year in Canada about 250,000 potential years of life are lost due to heart disease and stroke, which are two of the three leading causes of death in Canada.

Canadians can achieve optimal health, says Dr. Yancy, by following these steps:

1. GET ACTIVE: Inactivity can shave almost four years off a person's expected lifespan. People who are physically inactive are twice as likely to be at risk for heart disease or stroke.
2. KNOW AND CONTROL CHOLESTEROL LEVELS: Almost 40 per cent of Canadian adults have high blood cholesterol, which can lead to the build up of fatty deposits in your arteries − increasing your risk for heart disease and stroke.
3. FOLLOW A HEALTHY DIET: Healthy eating is one of the most important things you can do to improve your health – yet about half of Canadians don't meet the healthy eating recommendations.
4. KNOW AND CONTROL BLOOD PRESSURE: High blood pressure − often called a 'silent killer' because it has no warning signs or symptoms − affects one in five Canadians. By knowing and controlling your blood pressure, you can cut your risk of stroke by up to 40 per cent and the risk of heart attack by up to 25 per cent.
5. ACHIEVE AND MAINTAIN A HEALTHY WEIGHT: Almost 60 per cent of Canadian adults are either overweight or obese − major risk factors for heart disease and stroke. Being obese can reduce your life span by almost four years.
6. MANAGE DIABETES: By 2016 an estimated 2.4 million Canadians will live with diabetes. Diabetes increases the risk of high blood pressure, atherosclerosis (narrowing of the arteries), coronary artery disease, and stroke, particularly if your blood sugar levels are poorly controlled.
7. BE TOBACCO FREE: More than 37,000 Canadians die prematurely each year due to tobacco use, and thousands of non-smokers die each year from exposure to second-hand smoke. As soon as you become smoke-free, your risk of heart disease and stroke begins to decrease. After 15 years, your risk will be nearly that of a non-smoker.

A call for focused prevention strategies

While this goal of optimal health has been achieved by fewer than 10 per cent of the population, "it demonstrates the striking potential that prevention has if it is broadly embraced," says Dr. Yancy. "We know how to prevent heart disease and stroke – we now need to build the tools to empower our citizens to manage their risk and prevent heart disease."

Dr. Yancy calls on governments to invest in steady and focused prevention strategies. He says that necessary initiatives include a change in current sodium policies, continued progress in tobacco control initiatives, increased green space, and health education.

"Healthy living is key to preventing heart disease and stroke," says Bobbe Wood, president of the Heart and Stroke Foundation of Canada. "The Foundation is committed to raising awareness about heart health and to promoting public policies that facilitate healthy lifestyles and communities."

She says that the Foundation will continue to build on partnerships and policies that have led to a significant reduction of trans fats in the Canadian food supply; stronger tobacco control initiatives; healthy community design; and a continued reduction in the amount of salt in our food products, which has been achieved in part through Health Check™, the Foundation's flagship food information program.

Dr. Yancy adds that improved access to health care that focuses on prevention and control of important risk factors including high blood pressure, high cholesterol and diabetes is also key.

Raising the alarm over looming costs of treating heart disease

Dr. Yancy will also raise the alarm over the looming cost of treating heart disease now and in the future. With predictions that the direct medical cost of treating heart disease in the U.S. alone could climb to $818 billion in 2030, he says there is a health and economic imperative for governments and societies around the world to embrace prevention strategies.

Heart disease and stroke cost the Canadian economy more than $20.9 billion every year in physician services, hospital costs, lost wages and decreased productivity.

"The opportunity for prevention is not an unrealistic expectation," says Dr. Yancy. "Over the past 40 years the rates of heart disease and stroke have steadily declined." The rate has declined in Canada by 70 per cent since the mid-1950s. In the last decade alone, the rate has declined by 25 per cent.

Unfortunately, says Dr. Yancy, these benefits may be short-lived if the burden of risk, specifically obesity and diabetes, continues to grow, especially in children. "We need to act now."

Canadians can take a personalized My Heart&Stroke Risk Assessment™ to find out how their age, family history, and medical conditions affect their heart health at heartandstroke.ca/risk.

Provided by Heart and Stroke Foundation of Canada

Next-generation brain stimulation may improve treatment of Parkinson's disease

Parkinson's disease (PD) is a devastating and incurable disease that causes abnormal poverty of movement, involuntary tremor, and lack of coordination. A technique called deep brain stimulation (DBS) is sometimes used to improve motor symptoms in patients with advanced disease. Now, a study published by Cell Press in the October 20 issue of the journal Neuron describes a new and more effective DBS paradigm that makes real-time adjustments in response to disease dynamics and progression and may be better for managing symptoms of advanced PD.

20 oct 2011--DBS involves implantation of a medical device that functions as a "brain pacemaker." Essentially, this device sends electrical impulses to specific regions of the brain and alters brain activity in those regions in a controlled manner. Although the underlying principles are not entirely clear, DBS has provided significant therapeutic benefits for movement disorders like PD and for affective disorders like chronic pain and major depression.

After implantation of the DBS device, stimulation parameters, such as frequency and intensity of stimulation, must be programmed and adjusted over several months by a highly trained clinician. The goal is to maximize clinical improvement and minimize stimulation-induced side effects. Adjustments typically occur every 3 to 12 months when the patient visits the clinic, with the parameters remaining the same between visits. Unfortunately, this results in stimulation that does not keep up with the dynamic nature of PD.

"In recent years, the role of PD driven aberrant discharge patterns of neuronal activity have emerged as pivotal in the pathophysiology of the disease, and there is an urgent need for an automatic and dynamic system that can continually adjust the stimulus in response to ongoing pathological changes," explains Dr. Boris Rosin and Professor Hagai Bergman from The Hebrew University of Jerusalem. The authors tested several new paradigms for real-time adaptive DBS in a primate model of PD, in which the delivered stimulus was triggered by the ongoing brain activity.

The researchers discovered that real-time adaptive DBS paradigms alleviated PD motor symptoms and reduced abnormal neural activity more efficiently than standard DBS. The results provided new insight into brain activity underlying PD pathology and suggested that clinical improvement was achieved by disruption of a particular pattern from the variety of abnormal activity seen in the Parkinsonian brain. "It is our hope that in the near future we will see a new era of DBS strategies, based on real-time adaptive paradigms targeted at different pathological brain activity," conclude Dr. Rosin and Prof. Bergman. "Such strategies have potential not only for the treatment of PD, but perhaps other neurological disorders with a clear pathological pattern of brain activity."

Provided by Cell Press

New studies highlight risks of vitamin supplements

New research is prompting a fresh look at the value of vitamin supplements, with some surprising results indicating that taking too many supplements of some could be harmful.

18 oct 2011--The research is forcing scientists to rethink the use of supplements with antioxidants, which had been seen as beneficial in preventing cancer, heart disease and other ailments.

"Everybody is confused," admitted Toren Finkel, head of the Center for Molecular Medicine at the National Institutes of Health (NIH).

While logic would seem to dictate that taking vitamins and antioxidants should help fight illness and disease, Finkel said in an interview that the clinical data "are pretty consistently showing no benefit."

"So that means we have to go back and think about some of the assumptions we have made along the way in terms of what the mechanism for these diseases are and how things like oxidants play a role in those diseases," he told AFP.

Finkel explained that while it has long been believed that oxidants -- free radicals produced by the body or introduced through external sources such as pollution -- were unhealthy, the research paints a more complex picture.

"You have to go back to the lab and try to design experiments you can do a little simpler with cells or animals... to better understand the role of oxidants and vitamins," he said.

"For years, we were using these supplements without knowing the effects on the body."

A study published on October 11 in the United States indicates a 17 percent increase in the risk of developing prostate cancer among men who take high doses of vitamin E.

Another recent US study conducted among women and published on October 10 revealed that multivitamins -- commonly taken in the United States -- were useless and actually gradually contributed to a higher risk of mortality.

As far back as 2007, researchers had established a link between taking selenium supplements and an increased risk of adult diabetes.

For David Schardt, a nutritionist at the non-profit Center for Science in the Public Interest, the problem is that "people think more is better and that (supplements) are harmless."

"We are finding out that some of these vitamins taken alone in large amounts may have effects we did not predict, we did not understand and we did not anticipate," Schardt said.

He added that the country has "a lot of people who believe, almost like a religion, in their vitamins" -- a faith encouraged by an industry that generates $20 billion a year in the United States, where more than half of the population takes some kind of vitamin supplement.

Moreover, US manufacturers are "free to say almost anything they want" about the virtues of supplements, Schardt explained, adding: "The only thing the Food and Drug Administration does not let them make are claims about disease."

Patsy Brannon, a Cornell University professor who served on an NIH panel on multivitamins, mineral supplements and chronic diseases, said that those who take supplements are often those already getting nutrients from their food.

"So the people who are choosing supplements are maybe the people who don't need them," she said. "So they are not thinking about their total intake and that I think is a concern."

Experts agree that multivitamins and other supplements are useful for certain groups such as pregnant women and elderly people suffering from vitamin deficiencies.

But for the general population, a healthy balanced diet rich in fruits, vegetables and fiber as well as animal-based protein will provide the proper vitamins and nutrients needed, Brannon said.

A study published in late August in the Journal of Nutrition showed that a significant number of Americans did not eat well and did not take vitamin supplements.

Twenty-five percent of respondents had a vitamin C deficiency, 34 percent were not getting enough vitamin A and 60 percent needed more vitamin E. All three are found in fruits and vegetables.

Social media is mixed blessing in epidemics: WHO

A woman wears a protective mask in a street in Hong Kong in 2008. Facebook, Twitter and other social media websites boost public awareness of disease outbreaks but also make it more difficult to separate fact from fiction, world health officials say.

Facebook, Twitter and other social media websites boost public awareness of disease outbreaks but also make it more difficult to separate fact from fiction, world health officials said Thursday.

17 oct 2011--World Health Organization (WHO) director-general Margaret Chan said the Geneva-based UN body scans websites and online forums in different languages for indications of outbreaks across the world.

Any potential threat is analysed by experts and, if necessary, investigated, she told an international conference in Singapore on improving preparedness to fight disease outbreaks.

"I can assure you that with the rise of social media, the background noises for rumours have become much louder and making it so much harder to detect the really important segments," she said.

"But this development also makes it extremely hard for any country to hide a public health threat of international concern."

Chan, who was director of health in Hong Kong when a fatal outbreak of Severe Acute Respiratory Syndrome (SARS) effectively shut down the territory in 2003, did not elaborate.

China was heavily criticised by the international community during SARS for initially covering up the epidemic, which originated in the south of the country.

The flu-like disease eventually killed more than 800 people worldwide, according to the WHO.

WHO assistant director-general Keiji Fukuda said that during the H1N1 swine flu that swept the world in 2009/2010, the Internet was rife with rumours about how to build immunity against the disease.

"One of the rumours which started was that if you increase your salt intake it can help," Fukuda told reporters on the sidelines of the Singapore conference.

The agency had to counter the rumour, also using social media, by telling readers that taking too much salt "will be dangerous to your health", he added.

"The availability of information is better than in the past, and I think this is positive," Fukuda said.

"On the other hand, in social media anybody can say anything so it's also possible that you have a lot of miscommunication mixed in with correct information."

Herbal supplements may cause dangerous drug interactions in orthopaedic surgery patients

Complementary and alternative medical (CAM) treatments such as herbal supplements have become increasingly popular in the United States, especially among older patients and those with chronic pain. However, many of these products can have serious and potentially harmful side effects when combined with medications prescribed during and after surgery, according to a review article in the Journal of the American Academy of Orthopaedic Surgeons (JAAOS).

15 oct 2011--About 20 percent of prescription users also take an herbal supplement, and those rates are higher — studies suggest between 35 and 70 percent — among orthopaedic patients who are candidates for surgery.

"Herbal remedies are classified as dietary supplements, meaning they are exempt from the safety and efficacy regulations that the U.S. Food and Drug Administration (FDA) requires for prescription and over-the-counter medications," said David T. Rispler, MD, director of the Grand Rapids/Michigan State University Orthopedic Residency Program. "As a result, individual herbal remedies have not been thoroughly evaluated in large clinical trials, and little information is available on the interactions between drugs and herbs."

In addition, many herbal products are marketed as "natural" or "homeopathic," which may lead consumers to assume the products are safe, even when taken with prescription medicines, Dr. Rispler noted. "Herbal supplements can have a negative impact on patients both before and following surgery, and may interact with conventional medicines used to manage chronic conditions."

"Traditional physician-patient communications, like intake interviews, often do not include the subject of alternative medical products. As a result, patients may fail to report that they are using them and continue to take them along with any prescribed medicines and before surgery, thinking the herbal products pose no risk," said Dr. Rispler.

Many of the most popular herbal supplements used today can have serious side effects when combined with prescription medicines. For example:

• Feverfew (used for migraine prevention), ginger, cranberry, St. John's Wort and ginseng can interact with the anti-clotting drug warfarin;
• Feverfew, ginger, and gingko can interact with aspirin;
• Garlic can interfere with anti-clotting medications and the immunosuppressant drug cyclosporine (prevents transplant rejection);
• Valerian (used as a sedative) can intensify anesthetics; and
• St. John's Wort can interact with immunosuppressive drugs and potentially lead to transplant rejection.

Herbal products marketed for osteoarthritis also can pose serious risks when combined with prescription medications. For example:

• Glucosamine, chondroitin and flavocoxid can affect clotting agents;
• Black cohosh can interact with the cancer drug tamoxifen; and
• Cat's claw can interact with clotting agents, blood pressure medications and cyclosporine.

Most surgery-related side effects can be avoided by stopping the CAM product at least one to two weeks prior to surgery and during the postoperative period while prescription medications such as blood thinners or antibiotics are being used. The problem arises when physicians do not know that a patient is using a CAM product, Dr. Rispler said.

"One of the main reasons that patients do not disclose the use of a CAM product is that they may not believe it is important information to convey to the physician because they feel they are safe to use and all-natural," he said. "Patients may also decide not to report CAM product use if they are worried their physician may be prejudiced against the supplement's use, or believe their physician will not have an understanding of the supplement."

Although the use of herbal medicines should be monitored by patients' primary care physicians, Dr. Rispler said orthopaedic surgeons should have an understanding of the potential side effects of some of the most common CAM products used by their patients, and be able to guide them in suspending use prior to surgery.

To help ensure physicians are aware of the products their patients may be using, Dr. Rispler also recommends including CAM product-use questions on health/medical assessment forms to encourage patient disclosure.

"Physician-patient communication often does not include the use of CAM therapies, which results in underreporting of their use," he said. "To help avoid potential side effects, orthopaedists should develop questionnaires that can be used prior to surgery to help determine if their patients are using CAM products." Alternatively, patients should also report usage of any herbal products or other supplements they may be taking to all their physicians.

"By opening up a conversation on the use of herbal medications around the time of surgery and compiling a complete list of all prescribed and self-prescribed medications and supplements, patients and physicians may be able to work together to decrease the risk of complications that can occur during and following surgery," Dr. Rispler said.

More information: More information on understanding complementary and alternative medicine can be found at http://orthoinfo.a … topic=A00283

Provided by American Academy of Orthopaedic Surgeons

Researchers find first physical evidence bilingualism delays onset of Alzheimer's symptoms

Researchers at St. Michael's Hospital have found that people who speak more than one language have twice as much brain damage as unilingual people before they exhibit symptoms of Alzheimer's disease. It's the first physical evidence that bilingualism delays the onset of the disease.

14 oct 2011--"This is unheard of – no medicine comes close to delaying the onset of symptoms and now we have the evidence to prove this at the neuroanatomical level," said Dr. Tom Schweizer, a neuroscientist who headed the research.

Dr. Schweizer's team studied CT scans of patients who had been diagnosed with probable Alzheimer's disease and who had similar levels of education and cognitive skills, such as attention, memory, planning and organization. Half were fluently bilingual; the other half unilingual.

Despite the fact that both groups performed equivalently on all measures of cognitive performance, the scans of the bilingual patients showed twice as much atrophy in areas of the brain known to be affected by Alzheimer's.

The findings have been published on-line in the journal Cortex.

Dr. Schweizer said that bilingual people are constantly using their brain and keeping it active, which may contribute to overall brain health. That's why many physicians encourage older people to do crossword puzzles or Sudoku.

Dr. Schweizer said that because bilingual people constantly switch from one language to another or suppress one language to speak in the other, their brains may be better prepared to compensate through enhanced brain networks or pathways when Alzheimer's sets in.

Previous observational studies have found that bilingualism delays the onset of Alzheimer's symptoms by up to five years, but this is the first to find physical proof through CT scans.

Dr. Schweizer said the results are especially important in Canada, which is officially bilingual and has large numbers of immigrants for whom French and English are at least second languages. His study was conducted in Toronto, where the second language of many study participants was French, English or Chinese.

Dr. Schweizer noted that bilingualism does not prevent Alzheimer's. Once Alzheimer's symptoms appear in bilingual people, it is not clear whether the disease progresses at an accelerated rate.

He said the next steps would be to repeat the study in a larger sample of patients followed over time using more sophisticated MRIs. He said it wasn't clear from this study whether a second language had to be learned early in life to provide maximum benefit.

Provided by St. Michael's Hospital

Use of vitamin E associated with increased risk of prostate cancer

In a trial that included about 35,000 men, those who were randomized to receive daily supplementation with vitamin E had a significantly increased risk of prostate cancer, according to a study in the October 12 issue of JAMA.

12 oct 2011--Men who took 400 international units (I.U.) of vitamin E daily had more prostate cancers compared to men who took a placebo, according to an updated review of data from the Selenium and Vitamin E Cancer Prevention Trial (SELECT). The findings showed that, per 1,000 men, there were 76 prostate cancers in men who took only vitamin E supplements, vs. 65 in men on placebo over a seven-year period, or 11 more cases of prostate cancer per 1,000 men. This represents a 17 percent increase in prostate cancers relative to those who took a placebo. This difference was statistically significant and therefore is not likely due to chance. The results of this update appeared Oct. 12, 2011, in the Journal of the American Medical Association.

SWOG, an international network of research institutions, carried out SELECT at more than 400 clinical sites in the United States, Puerto Rico, and Canada. SELECT was funded by the National Cancer Institute (NCI) and other institutes that comprise the National Institutes of Health.

"Based on these results and the results of large cardiovascular studies using vitamin E, there is no reason for men in the general population to take the dose of vitamin E used in SELECT as the supplements have shown no benefit and some very real risks," said Eric Klein, M.D., a study co-chair for SELECT, and a physician at the Cleveland Clinic. "For now, men who were part of SELECT should continue to see their primary care physician or urologist and bring these results to their attention for further consideration."

The SELECT study began in 2001 and included over 35,000 men. It was started because earlier research had suggested that selenium or vitamin E might reduce the risk of developing prostate cancer. However, based on an independent safety monitoring review in autumn 2008, participants were told to stop taking their study supplements because it had become clear that the trial would never produce the 25 percent reduction in prostate cancer the study was designed to show with the use of these supplements. In 2010, the study sites were closed and over half of the participants consented to have their health monitored via mail questionnaires. Now, because of this latest finding, researchers are encouraging all participants to consider taking part in long-term study follow-up so investigators can continue to track outcomes.

SELECT was undertaken to substantiate earlier, separate findings from studies in which prostate cancer risk was not the primary outcome. A 1998 study of male smokers in Finland who took 50 I.U. of vitamin E daily to prevent lung cancer, showed 32 percent fewer prostate cancers in men who took the supplement. A 1996 study of men and women with a history of skin cancer who took selenium for prevention of disease recurrence showed that men who took the supplement had 52 percent fewer prostate cancers than men who did not take the supplement.

Based on these and other findings, men were recruited to participate in SELECT. They were randomly assigned to take one of four sets of supplements or placebos, with more than 8,000 men in each group. One group took both selenium and vitamin E; one took selenium and a placebo that looked similar to vitamin E; one took vitamin E and a placebo that looked similar to selenium; and the final group received placebos of both supplements. Men who took selenium alone or vitamin E and selenium together were also more likely to develop prostate cancer than men who took a placebo, but those increases were small and possibly due to chance.

"SELECT has definitively shown a lack of benefit from vitamin E and selenium supplements in the prevention of prostate cancer and has shown there is the potential for harm," said Lori Minasian, M.D., study co-author and acting director of NCI's Division of Cancer Prevention. "Nevertheless, this type of research has been critically important to understanding the potential benefits and risks from supplements."

SELECT researchers are now measuring the amount of vitamin E, selenium, and other nutrients in the blood of participants when they joined the trial, to see if the effect of the supplements depended upon this baseline level of micronutrient. Other researchers are looking at single nucleotide polymorphisms, which are DNA changes known as SNPs, to see if a change in one or more genes could affect cancer risk or perhaps increase a man's risk of developing prostate cancer while taking vitamin E.

The participant samples come from the study biorepository of blood and toe nail clippings which, when coupled with the extensive clinical information on participants, is a vital resource for further study. "SWOG is soliciting proposals from researchers nationwide to use the SELECT biorepository to help answer the biological question of why vitamin E increased risk instead of decreasing it," said Laurence Baker, D.O., study co-author and chairman of SWOG. "There are many more questions raised by these study results than we have answers for, and thus the need for further investigation."

Except for skin cancer, prostate cancer is the most common type of cancer in men in the United States. The current lifetime risk of prostate cancer for American men is 16 percent. In 2011, there will be an estimated 240,890 new cases of prostate cancer and 33,720 deaths from this disease in the United States.

More information: JAMA. 2011;306[14]:1549-1556

Provided by JAMA and Archives Journals

Certain dietary supplements associated with increased risk of death in older women

Consuming dietary supplements, including multivitamins, folic acid, iron and copper, among others, appears to be associated with an increased risk of death in older women, according to a report in the October 10 issue of Archives of Internal Medicine, one of the JAMA/Archives journals. The article is part of the journal's Less Is More series.

11 oct 2011--The use of dietary supplements in the United States has increased considerably over the last decade, according to background information in the article. "At the population level, dietary supplements contributed substantially to the total intake of several nutrients, particularly in elderly individuals," the authors write.

Jaakko Mursu, Ph.D., of the University of Eastern Finland, Kuopio, Finland, and the University of Minnesota, Minneapolis, and colleagues used data collected during the Iowa Women's Health Study to examine the association between vitamin and mineral supplements and mortality (death) rate among 38,772 older women (average age 61.6 years). Supplement use was self-reported in 1986, 1997 and 2004 via questionnaires.

Among the 38,772 women who started follow-up with the first survey in 1986, 15,594 deaths (40.2 percent) occurred over an average follow-up time of 19 years. Self-reported supplement use increased substantially between 1986 and 2004, with 62.7 percent of women reporting use of at least one supplement daily in 1986, 75.1 percent in 1997 and 85.1 percent in 2004.

The authors found that use of most supplements was not associated with reduced total mortality in older women, and many supplements appeared associated with increased mortality risk. After adjustment, use of multivitamins, vitamin B6, folic acid, iron, magnesium, zinc and copper, were all associated with increased risk of death in the study population. Conversely, calcium supplements appear to reduce risk of mortality. The association between supplement intake and mortality risk was strongest with iron, and the authors found a dose-response relationship as increased risk of mortality was seen at progressively lower doses as women aged throughout the study.

Findings for both iron and calcium supplements were replicated in separate, short-term analyses with follow-up occurring at four years, six years and 10 years.

"Based on existing evidence, we see little justification for the general and widespread use of dietary supplements," the authors conclude. "We recommend that they be used with strong medically based cause, such as symptomatic nutrient deficiency disease."

In an invited commentary, Goran Bjelakovic, M.D., D.M.Sc., of the University of Nis, Nis, Serbia, and Christian Gluud, M.D., D.M.Sc., of Copenhagen University Hospital, Copenhagen, Denmark, discuss the findings of Mursu and colleagues saying they "add to the growing evidence demonstrating that certain antioxidant supplements, such as vitamin E, vitamin A, and beta-carotene, can be harmful."

"Dietary supplementation has shifted from preventing deficiency to trying to promote wellness and prevent disease," the authors write. "Until recently, the available data regarding the adverse effects of dietary supplements has been limited and grossly underreported. We think the paradigm 'the more the better' is wrong. One should consider the likely U-shaped relationship between micronutrient status and health."

"We cannot recommend the use of vitamin and mineral supplements as a preventive measure, at least not in a well-nourished population," the authors conclude. "Older women (and perhaps men) may benefit from intake of vitamin D3 supplements, especially if they have insufficient vitamin D supply from the sun and from their diet. The issue of whether to use calcium supplements may require further study."

More information: Arch Intern Med. 2011;171[18]:1625-1633

Provided by JAMA and Archives Journals

Study shows increased Alzheimer's biomarkers in patients after anesthesia and surgery

10 oct 2011-- The possibility that anesthesia and surgery produces lasting cognitive losses has gained attention over past decades, but direct evidence has remained ambiguous and controversial. Now, researchers at the Perelman School of Medicine at the University of Pennsylvania provide further evidence that Alzheimer's pathology may be increased in patients after surgery. The new research is published in the October 2011 issue of the journal Anesthesiology.

"We have long sought a clearer picture of the true impact of anesthesia and surgery on the central nervous system," said lead study author Roderic Eckenhoff, MD, Austin Lamont Professor of Anesthesia at Penn. "Although not definitive, this human biomarker study gives some credibility to the notion that anesthesia and surgery produce an inflammatory insult on the brain and accelerate chronic neurodegenerative diseases like Alzheimer's."

Clinical observation of postoperative cognitive dysfunction in patients and studies in animals have long suggested that anesthetics could interact with Alzheimer neuropathology, but the decades-long refractory period, when Alzheimer pathology is developing in the absence of detectable cognitive symptoms, has made research difficult.

With advances in diagnostic tests led by Penn Medicine's Leslie Shaw, PhD, professor of Pathology and Laboratory Medicine, there is now a validated biomarker test that is able to detect the presence of Alzheimer's disease (AD) biomarkers found in cerebral spinal fluid (CSF). This 'signature' combination of Alzheimer's disease indicators – amyloid beta and tau protein – can find disease markers before Alzheimer's symptoms appear and reliably predicts which patients will progress from mild cognitive impairment to full blown Alzheimer's disease. Generally speaking, highly increased CSF tau protein and decreased beta-amyloid are indicative of AD pathology.

To further examine the impact of anesthesia and surgery on CSF in real time, Dr. Eckenhoff and colleagues at Penn set out to analyze the 'signature' indicators of Alzheimer's disease by collecting CSF from patients undergoing routine surgical procedures. A total of 11 patients, all undergoing endoscopic nasal surgery, were included in the study.

At the beginning of the study, there was no evidence of cognitive impairment and infection, and no patients were taking central nervous system (CNS)-active medications. The first, or baseline, CSF sample was taken at the beginning of the procedure. Another CSF sample was taken at the end of the procedure, and additional samples were taken at 6, 24, and 48 hours after that.

Mean CSF amyloid beta concentrations fluctuated by less than 10 percent in either direction and were statistically unchanged throughout the 48 hour postoperative period. However, total tau was significantly increased after 6 hours, and was still increasing at 48 hours when most of the spinal catheters were removed. An injury biomarker, S100B, and inflammatory biomarkers Interleukin-10, IL-6, and tumor necrosis factor, were also significantly increased over time after surgery suggesting neuroinflammation as a possible mechanism.

These findings together suggest significant changes in CSF biomarkers in a direction that is consistent with Alzheimer's disease progression and enhanced neuroinflammation.

The researchers also found that the use of the inhaled volatile anesthetic sevoflurane was associated with significantly higher CSF concentrations of inflammatory biomarkers than was associated with injectable anesthetics such as propofol and remifentanil. Although this suggests anesthetic management might make a difference in post-surgery neuroinflammation, the authors caution the study was too small to make a definitive connection; larger studies are needed to examine this concept.

"The evidence for anesthesia per se being responsible for the changes we saw in this study is not definitive – in fact, our work in animal models of Alzheimer's is beginning to suggest that the surgical procedure itself produces a larger effect than anesthesia," said Dr. Eckenhoff. "The next step in this line of research is to determine whether anesthetic management can modulate the neuroinflammation caused by surgery, whether this brief inflammatory insult can actually change the trajectory of something like AD, and given that surgery is usually not strictly elective, development of a strategy to reduce the inflammatory insult to the brain.

More information: http://journals.lw … default.aspx

Provided by University of Pennsylvania School of Medicine

Ability to ride a bike can aid differential diagnosis of Parkinson's disease in any setting

In a new study published today in the Journal of Parkinson's Disease, Japanese researchers report that the ability to ride a bike can differentiate between atypical parkinsonism and Parkinson's disease, regardless of the environment or situations for bicycling.

09 oct 2011--Atypical parkinsonisms are disorders that look similar to Parkinson's disease, but respond differently to treatments. The "bicycle sign" can help clinicians differentiate between the two. Patients with atypical parkinsonism lose their ability to cycle during the early phase of the illness, while patients with Parkinson's disease continue to ride well. Actual environments or situations for biking differ from one country to another, raising the question of whether the "bicycle sign" could be universally applicable. Hideto Miwa and Tomoyoshi Kondo, of the Department of Neurology at Wakayama Medical University, in Wakayama, Japan, set out to determine if the "bicycle sign" would be reliable in Japan, where the roads are hilly, narrow, and crowded with automobiles.

The study found that 88.9% of Japanese patients with atypical parkinsonism had ceased bicycling during the few years around the onset of their illness, as compared with only 9.8% of the patients with Parkinson's disease. In fact, the prevalence of the "bicycle sign" may be much higher in Japan than in The Netherlands (51.5%), which is known as one of the world's most bicycle-friendly countries. This may be because the tough bicycle environment in Japan makes it more difficult for atypical parkinsonism patients to bike.

"Although bicycling cultures may differ between countries, it is possible that the 'bicycle sign' could contribute to earlier and better differential diagnosis of parkinsonism during the diagnostic interview. When we see patients with parkinsonism without a definitive diagnosis, it is a simple thing to ask the question, 'Can you still ride a bicycle?'" commented Dr. Miwa.

More information: The article is "Bicycle Sign for Differential Diagnosis of Parkinsonism: Is It of Use in a Hilly Country Like Japan?" by Hideto Miwa and Tomoyoshi Kondo, Journal of Parkinson's Disease. 1(2). DOI 10.3233/JPD-2011-11039

Provided by IOS Press

Pancreatic cancer declining, but among most deadly

In this Jan. 6, 2004 , Apple CEO Steve Jobs displays the iPod mini at the Macworld Conference and Expo in San Francisco. Jobs, the Apple founder and former CEO who invented and masterfully marketed ever-sleeker gadgets that transformed everyday technology, from the personal computer to the iPod and iPhone, died Wednesday. He was 56.

07 oct 2011-- There are almost as many deaths from it each year as there are new cases. The deaths this week of Apple founder Steve Jobs and Nobelist Ralph Steinman bring unusual attention to this less-well-known type of cancer that has actually been declining despite no big advances in treatment or finding it early.

A decline in smoking, one of the top risk factors for the disease, may be behind the drop in cases.

Jobs lived more than seven years after being diagnosed with a neuroendocrine tumor - a less common, slower-growing and more treatable type of pancreatic cancer than the kind that killed Steinman a week ago and actor Patrick Swayze two years ago.

The Apple chief kept details of his illness behind a firewall and declared he was cured after cancer surgery in 2004. However, five years later, gaunt and having lost a lot of weight, Jobs had a liver transplant. Experts said it was likely because his cancer had returned or spread.

A liver transplant sometimes can cure the type of cancer that Jobs had. But if it comes back, "it's usually in one to two years," said Dr. Michael Pishvaian of Georgetown University's Lombardi Comprehensive Cancer Center.

In January, Jobs announced his third and final leave of absence. He resigned in August and died on Wednesday.

Part of what makes pancreatic cancer so deadly is that the pancreas is as vital as the heart. You can live with just part of a liver or a colon, or only one kidney or lung. But the pancreas is a fish-shaped organ that makes digestive enzymes and insulin and other hormones that enable the body to make energy from food.

In the United States, pancreatic cancer is the fourth leading cause of cancer deaths. About 44,030 people will be diagnosed with it and about 37,660 people will die of it this year in the U.S., the American Cancer Society estimates.

Possible symptoms are fatigue, back pain, abdominal pain, unexplained weight loss, loss of appetite, jaundice and nausea, according to the Lustgarten Foundation, a private group that finances research on the disease.

This cancer often is not found until it is advanced or has spread, and overall survival is dismal: 20 percent after one year and only 4 percent after five years.

However, with a neuroendocrine tumor like the one Jobs had, "people can live a longer time; median survival is five to eight years," said Dr. Alan Venook, a pancreatic cancer specialist at the University of California, San Francisco.

The lifetime risk of developing pancreatic cancer is about 1 in 71, according to the cancer society. Men and blacks account for more cases than women and whites, possibly because of differences in smoking rates. Smokers have two to three times more risk of developing the disease. Use of smokeless tobacco also raises the risk.

Obese people, those who don't exercise much and diabetics also have more risk for pancreatic cancer. Alcohol use might play a role: Most studies haven't tied it to pancreatic cancer, but heavy drinking can lead to diabetes and liver and pancreas problems that pose a cancer risk, the cancer society says.

The best hope for a patient is that the tumor is operable. That was the case in February 2009, when U.S. Supreme Court Justice Ruth Bader Ginsburg had a small, early-stage pancreatic tumor removed at New York's Memorial Sloan-Kettering Cancer Center.

On the horizon are immune system treatments - research that Steinman, the Nobel recipient from Rockefeller University in New York, was studying in the lab and trying on his own pancreatic cancer.

The immune system has a hard time recognizing and fighting cancer because the enemy is not an invading germ but our own cells gone rogue. Treatments called therapeutic cancer vaccines are ways to modify cells to help the immune system recognize the risk.

One such vaccine by NewLink Genetics, a small biotech firm in Ames, Iowa, is in late-stage testing now for pancreatic cancer. The company website says the larger study was initiated after a mid-stage test suggested improvement in survival.

Dr. Roderich Schwarz, chief of surgical oncology at the University of Texas Southwestern Medical Center in Dallas, has enrolled a few patients in some immune therapy studies, which have not paid off in the past.

"Vaccines are coming along," and last year's approval of one for advanced prostate cancer suggests researchers may be learning to overcome some of the drawbacks of the past, he said.

"It's quite possible that vaccines will claim their territory in the treatment of these challenging tumors," Schwarz said. "It's still in the development stage rather than the proven stage."

More information:
Cancer Institute: http://www.cancer.gov/cancertopics/types/pancreatic

Cancer Society: http://www.cancer.org/Cancer/PancreaticCancer/index

Survival rates: http://bit.ly/oAxKl5

Research and support: http://www.curePC.org and http://www.lustgarten.org

Vaccine study: http://www.linkp.com/products/hyperacute-pancreas.html

Alzheimer's might be transmissible in similar way as infectious prion diseases: study

The brain damage that characterizes Alzheimer's disease may originate in a form similar to that of infectious prion diseases such as bovine spongiform encephalopathy (mad cow) and Creutzfeldt-Jakob, according to newly published research by The University of Texas Health Science Center at Houston (UTHealth).

06 oct 2011--"Our findings open the possibility that some of the sporadic Alzheimer's cases may arise from an infectious process, which occurs with other neurological diseases such as mad cow and its human form, Creutzfeldt-Jakob disease," said Claudio Soto, Ph.D., professor of neurology at The University of Texas Medical School at Houston, part of UTHealth. "The underlying mechanism of Alzheimer's disease is very similar to the prion diseases. It involves a normal protein that becomes misshapen and is able to spread by transforming good proteins to bad ones. The bad proteins accumulate in the brain, forming plaque deposits that are believed to kill neuron cells in Alzheimer's."

The results showing a potentially infectious spreading of Alzheimer's disease in animal models were published in the Oct. 4, 2011 online issue of Molecular Psychiatry, part of the Nature Publishing Group. The research was funded by The George P. and Cynthia W. Mitchell Center for Research in Alzheimer's Disease and Related Brain Disorders at UTHealth.

Alzheimer's disease is a form of progressive dementia that affects memory, thinking and behavior. Of the estimated 5.4 million cases of Alzheimer's in the United States, 90 percent are sporadic. The plaques caused by misshapen aggregates of beta amyloid protein, along with twisted fibers of the protein tau, are the two major hallmarks associated with the disease. Alzheimer's is the sixth leading cause of death in the United States, according to the Alzheimer's Association.

Researchers injected the brain tissue of a confirmed Alzheimer's patient into mice and compared the results to those from injected tissue of a control without the disease. None of the mice injected with the control showed signs of Alzheimer's, whereas all of those injected with Alzheimer's brain extracts developed plaques and other brain alterations typical of the disease.

"We took a normal mouse model that spontaneously does not develop any brain damage and injected a small amount of Alzheimer's human brain tissue into the animal's brain," said Soto, who is director of the Mitchell Center. "The mouse developed Alzheimer's over time and it spread to other portions of the brain. We are currently working on whether disease transmission can happen in real life under more natural routes of exposure."

More information: "De novo Induction of amyloid-B Deposition in vivo," Molecular Psychiatry.

Provided by University of Texas Health Science Center at Houston

Calorific controversy for intensive care patients

Patients who are fed more calories while in intensive care have lower mortality rates than those who receive less of their daily-prescribed calories, according to a recent study of data from the largest critical care nutrition database in the world.

05 oct 2011--"Our finding is significant as there have been a number of previous studies in the area of critical care nutrition that have produced conflicting clinical recommendations and policy implications," says study lead Daren Heyland, a professor of Medicine at Queen's, director of the Clinical Evaluation Research Unit at Kingston General Hospital, and scientific director of the proposed Technology Evaluation in the Elderly Network. "Since caloric delivery is essential for improving the chances of these critically ill patients, it's vital that we know what the optimal level is."

Dr. Heyland's team examined the records of 7872 mechanically ventilated, artificially fed patients in 352 ICUs in 33 countries. They found that patients receiving at least two-thirds of their prescribed calorie intake had reduced mortality rates when compared with patients receiving less than one-third of their prescribed calorie intake. The researchers identified that the optimal caloric intake was about 80 to 85 per cent of total prescribed calorie intake.

World-wide, patients in ICUs typically receive 50 to 60 per cent of their prescribed calories so efforts to improve caloric delivery are important to improve the chances of critically ill patients surviving their illness.

In a further study, Dr Heyland and his research team examined the use of supplemental intravenous nutrition, in addition to the traditional use of feeding tubes. They concluded that efforts to improve the delivery of nutrition delivered via a feeding tube into the stomach are more important than the use of supplemental intravenous nutrition.

More information: These respective findings were both recently published in Critical Care Medicine, a leading US-based ICU journal.

Provided by Queen's University

Older people are happier in Brazil and South Africa

Contrary to belief, older people in South Africa and Brazil become happier as they age. New research suggests that, with the right policies in place, a developing country can significantly improve the wellbeing of its older citizens.

04 oct 2011--The average levels of wellbeing experienced by older people in South Africa and Brazil improved between 2002 and 2008, due to a combination of economic growth and enlightened social policies, according to a study from the New Dynamics of Ageing Programme, a unique collaboration between five UK Research Councils.

"Our work contradicts many of the assumptions people have about the fate of older people in developing countries," said Professor Armando Barrientos, Research Director at Manchester University's Brooks World Poverty Institute. "It's often assumed that people will become poorer and increasingly unhappy with life as they become old, but in South Africa and Brazil the opposite seems to have happened," he said.

The research explored the factors that influence wellbeing among the elderly populations of the two countries. Brazil and South Africa were chosen because of their far-reaching social policies. "They are leading countries in their respective regions, with innovative social policies addressing poverty and vulnerability, such as child and disability benefits, low interest loans for the elderly and non-contributory pension schemes," explained Professor Barrientos.

This large study included a survey of around 1000 households. When the new data was compared with data collected in 2002, it suggested wellbeing had improved and that the majority of older people in the two countries felt satisfied or very satisfied with their lives. A majority of older people in each country also said they were satisfied with their relationships with other family members and with the respect they received from others.

The improvement in wellbeing was strongly influenced by economic performance and labour market conditions, but social policy also played a significant role. For low-income families, the pension income received by elderly people was essential to both their objective standard of living and their feeling that that life was getting better.

"The research has important lessons for policymakers in the developing world", says Professor Barrientos. "Populations in the developing world are growing much faster than they did in the countries that we now consider as developed" he said. "That means governments in these nations have far less time to deal with the challenge of an ageing population, and they cannot just copy the policies used in developed countries."

There are lessons for the developed world too, he believes. "Many countries in the developed world have been moving towards the idea that the state should provide only a minimal pension", he said. "But our research suggests governments might want to think more carefully about the wider social value of decent state pension provision."

Provided by Economic & Social Research Council

Finding key structural insights into the pathological hallmark of Parkinson's disease

Better understanding the structure of AS fibrils is a step toward finding a treatment for Parkinson’s disease.

A team of researchers from the University of Illinois and EMSL recently completed a detailed structural and dynamic characterization of full-length α-Synuclein (AS) fibrils.

03 oct 2011--AS fibrils are the major component of Lewy bodies, the pathological hallmark of Parkinson's disease, which affects approximately 1–2% of the population over age 65.

By applying state-of-the-art, solid-state nuclear magnetic resonance (NMR) capabilities at EMSL, including the 900-MHz NMR spectrometer, as well as improved sample preparation and labeling schemes, the researchers detected many previously unobserved residues in the fibrils and performed detailed analysis of the side chains as well as the backbone.

The team’s results show that the core extends with a repeated structural motif and that three single-point mutations associated with early-onset Parkinson's disease —A30P, E46K and A53T—are located in structured regions. Additionally, the researchers found that E46K and A53T mutations are associated with major and minor structural perturbations, respectively.

These results are a step toward the rational design of small molecules to diagnose and/or treat Parkinson's disease and present a new approach for discovering therapeutic targets.

More information: Comellas G, LR Lemkau, AJ Nieuwkoop, KD Kloepper, DT Ladror, R Ebisu, WS Woods, AS Lipton, JM George, and CM Rienstra. 2011. "Structured Regions of [Alpha]-Synuclein Fibrils Include the Early-Onset Parkinson's Disease Mutation Sites." Journal of Molecular Biology 411:881-895. DOI:10.1016/j.jmb.2011.06.026

Provided by Environmental Molecular Sciences Laboratory

End-of-life discussions do not affect survival rates, study shows

Discussing and documenting patients' preferences for care at the end of life does not cause them any harm, contrary to recent claims. A new study published today in the Journal of Hospital Medicine found that patients who talk with their physicians about end-of-life care and have an advance directive in their medical record have similar survival rates as patients who do not have these discussions and documents.

02 oct 2011--The study included 356 patients admitted at three different hospitals who had low or medium risks of dying within one year. Patients were followed from 2003 to 2009. During the study, there were no differences in survival for patients who had an end-of-life discussion and those who had not; there also were no survival differences for those who had a living will in their medical record and those who did not.

"Our findings are reassuring. They support health care providers, who can initiate these discussions, and policy makers, who seek to reimburse these time consuming discussions," said lead researcher Stacy M. Fischer, MD of the University of Colorado School of Medicine. "Most importantly, our findings are reassuring for patients and families who desire these discussions with their health care providers."

"The term 'death panels' has sparked considerable controversy recently. It has undermined the efforts of clinicians who provide end-of-life care by scaring patients into thinking that their lives may be cut short for their families' or society's best interest," added Fischer. "We hope our study provides data to help inform the national debate about advance directives for key stakeholders; health care providers, policy makers, and patients and families."

Provided by Wiley