New research suggests that obesity and diabetes are a downside of human evolution

As if the recent prediction that half of all Americans will have diabetes or pre-diabetes by the year 2020 isn't alarming enough, a new genetic discovery published online in the FASEB Journal (http://www.fasebj.org) provides a disturbing explanation as to why: we took an evolutionary "wrong turn." In the research report, scientists show that human evolution leading to the loss of function in a gene called "CMAH" may make humans more prone to obesity and diabetes than other mammals.

28 feb 2011--"Diabetes is estimated to affect over 25 million individuals in the U.S., and 285 million people worldwide," said Jane J. Kim, M.D., a researcher involved in the work from the Department of Pediatrics at the University of California, San Diego in La Jolla, CA. "Our study for the first time links human-specific sialic acid changes to insulin and glucose metabolism and therefore opens up a new perspective in understanding the causes of diabetes."

In this study, which is the first to examine the effect of a human-specific CMAH genetic mutation in obesity-related metabolism and diabetes, Kim and colleagues show that the loss of CMAH's function contributes to the failure of the insulin-producing pancreatic beta cells in overweight humans, which is known to be a key factor in the development of type 2 diabetes. This gene encodes for an enzyme present in all mammalian species except for humans and adds a single oxygen atom to sialic acids, which are sugars that coat the cell surface.

To make their discovery, the researchers used two groups of mice. The first group had the same mutant CMAH gene found in humans. These mice demonstrated that the CMAH enzyme was inactive and could not produce a sialic acid type called NeuSGc at the cell surface. The second group had a normal CMAH gene. When exposed to a high fat diet, both sets of mice developed insulin resistance as a result of their obesity. Pancreatic beta cell failure, however, occurred only in the CMAH mutant mice that lacked NeuSGc, resulting in a decreased insulin production, which then further impaired blood glucose level control. This discovery may enhance scientific understanding of why humans may be particularly prone to develop type 2 diabetes. Results may also suggest that conventional animal models may not accurately mirror the human situation.

"The diabetes discovery is an important advance in its own right. It tells us a lot about what goes wrong in diabetes, and where to aim with new treatments," said Gerald Weissmann, M.D., Editor-in-Chief of the FASEB Journal, "but its implications for human evolution are even greater. If this enzyme is unique to humans, it must also have given us a survival advantage over earlier species. Now the challenge is to find the function of CMAH in defending us against microbes or environmental stress or both. This evolutionary science explains how we can win some and lose some, to keep our species ahead of the extinction curve."

More information: Sarah Kavaler, Hidetaka Morinaga, Alice Jih, WuQiang Fan, Maria Hedlund, Ajit Varki, and Jane J. Kim. Pancreatic β-cell failure in obese mice with human-like CMP-Neu5Ac hydroxylase deficiency. FASEB J. fj.10-175281; doi:10.1096/fj.10-175281

Provided by Federation of American Societies for Experimental Biology

Elderly patients admitted with high glucose levels are more likely to die in hospital

A two-country hospital study of 808 elderly patients found a strong association between high, undiagnosed blood glucose in non-diabetic patients and increased hospital death rates, according to the March issue of IJCP, the International Journal of Clinical Practice.

27 feb 2011--Researchers are now calling for routine blood glucose testing of elderly patients when they are admitted to hospital. The Spanish team looked at 447 consecutive patients admitted to a geriatric unit, while the Italian team studied 361 patients over 60 admitted to an internal medicine department.

They found that, when they excluded the 206 patients already diagnosed with diabetes, 25% of the remaining 602 patients had a fasting glucose level of 126 mg/dl or more, which is the threshold used to diagnose the disease, with just under a fifth of those exceeding 180 mg/dl.

Mortality rates in patients with a fasting glucose level of less than 126 mg/dl was just over 8% for both the total sample and the patients admitted without a diagnosis of diabetes. But when the researchers looked at the undiagnosed patients whose fasting glucose levels were 126 mg/dl to 180mg/dl, the death rate rose to 18% and, in patients whose levels exceeded 180mg/dl, the rate increased to 31%.

These levels were much higher than the 14% and 23% recorded for diabetic patients with fasting glucose levels exceeding 126 mg/dl and 180 mg/dl respectively.

"This is the first multi-centre prospective study to assess the relationship between fasting serum glucose levels and in-hospital mortality in a large cohort of elderly patients" says lead author Dr Pedro Iglesias from the Department of Endocrinology at Hospital Ramon y Cajal in Madrid, Spain.

"Our findings clearly show that fasting glucose is a significant risk factor for death during hospitalisation, especially in patients who have not been diagnosed with diabetes."

Other key findings of the study included:

• The average age of the total cohort was 84 years and 57% were female, but the Spanish geriatric cohort was older than the Italian internal medicine cohort (86 versus 80 years), with a higher percentage of women (62% versus 50%).
  
• There was a higher incidence of high blood pressure, lower systolic and diastolic blood pressure, higher serum glucose and creatinine and lower total cholesterol concentrations in the Spanish cohort.
  
• The five most common reasons for hospital admission in the total cohort were: congestive heart failure (19%), respiratory tract infection (12.5%), acute cerebrovascular disease (12%), exacerbation of chronic obstructive pulmonary disease (9%) and cancer (8%). However, there were significant variations between the two cohorts.
  
• 25% of the total cohort had a pre-existing diagnosis of diabetes, with 2% more patients in the Spanish cohort than the Italian cohort having the disease.
  
• Median fasting glucose rates for the total cohort were more than 20% higher in patients who died (127 mg/dl) than those who survived (105 mg/dl).
  
• Hospital stays averaged 10.5 days for the total cohort and the average time from admission to death was 11.3 days. The Italian internal medicine cohort had a lower death rate (8% versus 14%) and lower average hospital stay (nine days versus 12 days) than the Spanish geriatric group, but the intervals from admission to death were similar in both groups.

"Our study shows a high mortality rate and short hospital survival in non-diabetic elderly patients with a high baseline fasting glucose level of more than 180 mg/dl" concludes co-author Professor Fabio Monzani from the Department of Internal Medicine at the University of Pisa, Italy.

"It underlines the importance of testing elderly patients for fasting glucose levels on admission to hospital for acute illnesses and suggests that a blood glucose level of 180 mg/dl or less might be an appropriate target in people who have not been diagnosed with diabetes.

"These findings should help us to identify those patients at high risk during hospitalisation, so that they can be offered intensive therapy to reduce their risk of death and improve their prognosis."

More information: Fasting hyperglycaemia and in-hospital mortality in elderly population. Iglesias et al. IJCP. 65.3, pp308-313. (March 2011). DOI: 10.1111/j.1742-1241.2010.02514.x

Using amphetamines may increase risk of Parkinson's disease

New research shows people who have used amphetamines such as benzedrine and dexedrine appear to be at an increased risk of developing Parkinson's disease, according to a study released today that will be presented at the American Academy of Neurology's 63rd Annual Meeting in Honolulu April 9 to April 16, 2011.

26 feb 2011--Benzedrine and Dexedrine are amphetamines often prescribed to increase wakefulness and focus for people with attention deficit hyperactivity disorder and narcolepsy, a disorder that can cause excessive daytime sleepiness and sudden attacks of sleep. They are also used to treat traumatic brain injuries.

The study involved 66,348 people in northern California who had participated in the Multiphasic Health Checkup Cohort Exam between 1964 and 1973 and were evaluated again in 1995. The average age of the participants at the start of the study was 36 years old. Of the participants, 1,154 people had been diagnosed with Parkinson's disease by the end of the study.

Exposure to amphetamines was determined by two questions: one on the use of drugs for weight loss and a second question on whether people often used Benzedrine or Dexedrine. Amphetamines were among the drugs commonly used for weight loss when this information was collected.

According to the study, those people who reported using Benzedrine or Dexedrine were nearly 60 percent more likely to develop Parkinson's than those people who didn't take the drugs. There was no increased risk found for those people who used drugs for weight loss.

"If further studies confirm these findings, the potential risk of developing Parkinson's disease from these types of amphetamines would need to be considered by doctors before prescribing these drugs as well as be incorporated into amphetamine abuse programs, including illicit use," said study author Stephen K. Van Den Eeden, PhD, with the Division of Research at Kaiser Permanente Northern California in Oakland, Calif.

Van Den Eeden explained that amphetamines affect the release and uptake of dopamine, the key neurotransmitter involved in Parkinson's disease. He explained that more research needs to be completed to confirm the association and learn more about possible mechanisms.

Provided by American Academy of Neurology

Aging, interrupted

The current pace of population aging is without parallel in human history but surprisingly little is known about the human aging process, because lifespans of eight decades or more make it difficult to study. Now, researchers at the Salk Institute for Biological Studies have replicated premature aging in the lab, allowing them to study aging-related disease in a dish.

25 feb2011--In the February 23, 2011 advance online edition of the journal Nature, Juan Carlos Izpisúa Belmonte, Ph.D. a professor in the Salk Institute's Gene Expression Laboratory, and his team report that they have successfully generated induced pluripotent stem (iPS) cells from skin cells obtained from patients with Hutchinson-Gilford Progeria Syndrome—who age eight to 10 times faster than the rest of us—and differentiated them into smooth muscle cells displaying the telltale signs of vascular aging.

"The slow progression and complexity of the aging process makes it very hard to study the pathogenesis of cardiovascular and other aging-related disorders," says Izpisúa Belmonte. "Having a human model of accelerated aging will facilitate the development of treatments and possibly a cure for Progeria and give us new insights into how we age. It may also help prevent or treat heart disease in the general aging population."

Progeria's striking features resemble the aging process put on fast-forward and afflicted people rarely live beyond 13 years. Almost all of the patients die from complications of arteriosclerosis—the clogging or hardening of arteries or blood vessels caused by plaques—which leads to heart attack and stroke.

Scientists are particularly interested in Progeria in the hopes that it might reveal clues to the normal human aging process. However, the disease is exceedingly rare and only 64 children living with progeria are known making access to patients very difficult.

Hutchinson-Gilford Progeria Syndrome is caused by a single point mutation in the gene encoding lamin A, which forms a protein scaffold on the inner edge of the nucleus that helps maintain chromatin structure and organize nuclear processes such as RNA and DNA synthesis. The mutation creates an alternative splice site that leads to the production of a truncated version of the protein known as progerin. Unlike the full-length protein, progerin does not properly integrate into the nuclear lamina, which disrupts the nuclear scaffold and causes a host of problems.

"There is also evidence that defective lamin A accumulates during the normal aging process via the sporadic use of the alternative splice site, " explains Izpisua Belmonte. "Therefore we are very keen on using our in vitro iPS cell-based model to identify new aging markers and explore other aspects of human premature and physiological aging."

Compared to normal skin fibroblasts, cells from Progeria patients have misshapen nuclei and a range of other nuclear defects, including a disorganized nuclear lamina, loss of super-condensed DNA, telomere shortening and genomic instability. Yet, despite their "old" appearance and characteristics, these cells could be readily converted into iPS cells.

"The reprogramming process erased all nuclear and epigenetic defects and the rejuvenated pluripotent cells looked and acted like perfectly normal healthy cells," says first author Guang-Hui Liu, Ph.D., a postdoctoral researcher in the Belmonte lab.

Since lamin A is only expressed in differentiated cells but is absent from embryonic stem cells, he wondered whether iPS cells produce lamin A and/or progerin, which should follow the same expression pattern as lamin A. In his experiments, he couldn't detect either one. "The biological clock is reset in these cells because lamin A is silenced," explains Liu.

As soon as the Salk researchers differentiated Progeria-derived iPS cells, progerin expression was reactivated. "This reversible suppression of progerin expression by reprogramming and subsequent reactivation during differentiation, provides a unique model system to study human premature aging pathologies," says Izpisúa Belmonte.

Progerin accumulates mainly in smooth muscle cells found within the walls of arterial blood vessels, and vascular smooth muscle cells degeneration is one of the hallmarks of Hutchinson-Gilford Progeria Syndrome-associated arteriosclerosis. In fact, vascular smooth muscle cell senescence also plays a role in advanced arteriosclerosis within the normal aging population.

Upon directed differentiation of Progeria-derived iPS cells into smooth muscle cells the premature aging phenotype, including misshapen nuclei, the loss of gene silencing marks and compromised proliferation, reappeared. Genetically modifying progeria-derived iPS cells to shut down the expression of progerin staved off the premature appearance of aging phenotypes after differentiation. "Transplantation of the progenitor cells derived from the "corrected" progeria iPS cells might hold the promise to treat these progeria children in the future." says Liu.

Provided by Salk Institute

Alzheimer's disease may be easily misdiagnosed

New research shows that Alzheimer's disease and other dementing illnesses may be easily misdiagnosed in the elderly, according to early results of a study of people in Hawaii who had their brains autopsied after death. The research is being released today and will be presented as part of a plenary session at the American Academy of Neurology's 63rd Annual Meeting in Honolulu April 9 to April 16, 2011.

24 feb 2011--"Diagnosing specific dementias in people who are very old is complex, but with the large increase in dementia cases expected within the next 10 years in the United States, it will be increasingly important to correctly recognize, diagnose, prevent and treat age-related cognitive decline," said study author Lon White, MD, MPH, with the Kuakini Medical System in Honolulu.

For the study, researchers autopsied the brains of 426 Japanese-American men who were residents of Hawaii, and who died at an average age of 87 years. Of those, 211 had been diagnosed with a dementia when they were alive, most commonly attributed to Alzheimer's disease.

The study found that about half of those diagnosed with Alzheimer's disease did not have sufficient numbers of the brain lesions characterizing that condition to support the diagnosis. Most of those in whom the diagnosis of Alzheimer's disease was not confirmed had one or a combination of other brain lesions sufficient to explain the dementia. These included microinfarcts, Lewy bodies, hippocampal sclerosis or generalized brain atrophy.

However, diagnoses of Lewy body dementia and vascular dementia were more accurate. Misdiagnoses increased with older age. They also reflected non-specific manifestations of dementia, a very high prevalence of mixed brain lesions, and the ambiguity of most neuroimaging measures.

"Larger studies are needed to confirm these findings and provide insight as to how we may more accurately diagnose and prevent Alzheimer's disease and other principal dementing disease processes in the elderly," said White.

More information: This research will be presented as part of the Contemporary and Clinical Issues and Case Studies Plenary Session on Wednesday, April 13, 2011, at the 2011 American Academy of Neurology's Annual Meeting in Honolulu.

Provided by American Academy of Neurology

The association between unhealthy behaviors and socioeconomic status differs between countries

According to a study by Silvia Stringhini and colleagues from INSERM, (U1018 Centre for Research in Epidemiology and Population Health) and University College London, (Department of Epidemiology and Public Health), published in this week's PLoS Medicine, although socioeconomic status and health behaviors are strong predictors of mortality, there are major differences in the social patterning of unhealthy behaviors in different countries.

23 feb 2011--The authors investigated whether health behaviours are equally important mediators of the association between socio-economic status and health in different cultural settings. They compared recent findings of the British Whitehall II study with those of another European cohort, the French GAZEL study. Both large cohort studies have comparable designs and have a similar age range and follow-up period. The Whitehall II study started in 1985, with the aim of examining the socioeconomic gradient in health among 10308 London-based civil servants (6895 men and 3413 women) aged 35-55. The GAZEL study started in 1989 among employees of the French national gas and electricity company totalling 20625 employees (15011 men and 5614 women), aged 35-50.

The authors found that the socioeconomic gradient in smoking and unhealthy diet was greater in Whitehall II than in GAZEL. Socioeconomic differences in mortality were similar in the two cohorts, a hazard ratio of 1.62 in Whitehall II and 1.94 in GAZEL for lowest versus highest occupational position. Health behaviours weakened the association between socio-economic status and mortality substantially in Whitehall II (by 75%) but only by 19% in GAZEL. The supplementary analysis the researchers conducted using education and income as socio-economic markers gave similar results.

These findings are important as they show that health behaviours are only likely to be major contributors towards socioeconomic differences in health in settings with a marked social characterisation of those behaviours. The authors conclude that in order to identify the common and unique determinants of social inequalities in health in different populations, "there needs to be further comparative research on the relative importance of different pathways linking socioeconomic status to health."

More information: Stringhini S, Dugravot A, Shipley M, Goldberg M, Zins M, et al. (2011) Health Behaviours, Socioeconomic Status, and Mortality: Further Analyses of the British Whitehall II and the French GAZEL Prospective Cohorts. PLoS Med 8(2): e1000419. doi:10.1371/journal.pmed.1000419

Provided by Public Library of Science

High cholesterol and blood pressure in middle age tied to early memory problems

Middle-age men and women who have cardiovascular issues, such as high cholesterol and high blood pressure, may not only be at risk for heart disease, but for an increased risk of developing early cognitive and memory problems as well. That's according to a study released today that will be presented at the American Academy of Neurology's 63rd Annual Meeting in Honolulu April 9 to April 16, 2011.

22 feb 2011--For the study, 3,486 men and 1,341 women with an average age of 55 underwent cognitive tests three times over 10 years. The tests measured reasoning, memory, fluency and vocabulary. Participants received a Framingham risk score that is used to predict 10-year risk of a cardiovascular event. It is based on age, sex, HDL cholesterol, total cholesterol, systolic blood pressure and whether they smoked or had diabetes.

The study found people who had higher cardiovascular risk were more likely to have lower cognitive function and a faster rate of overall cognitive decline compared to those with the lowest risk of heart disease. A 10-percent higher cardiovascular risk was associated with poorer cognitive test scores in all areas except reasoning for men and fluency for women. For example, a 10 percent higher cardiovascular risk was associated with a 2.8 percent lower score in the test of memory for men and a 7.1 percent lower score in the memory test for women.

Higher cardiovascular risk was also associated with a 10-year faster rate of overall cognitive decline in both men and women compared to those with lower cardiovascular risk.

"Our findings contribute to the mounting evidence for the role of cardiovascular risk factors, such as high cholesterol and blood pressure, contributing to cognitive problems, starting in middle age," said study author Sara Kaffashian, MSc, with INSERM, the French National Institute of Health & Medical Research in Paris. "The study further demonstrates how these heart disease risk factors can contribute to cognitive decline over a 10-year period."

Provided by American Academy of Neurology

Study reinforces link between obesity, high-fat meals and heart disease

The effect of a high-fat meal on blood vessel walls can vary among individuals depending on factors such as their waist size and triglyceride levels, suggests new research at UC Davis.

21 feb 2011--The new research reinforces the link between belly fat, inflammation and thickening of the arterial linings that can lead to heart disease and strokes.

Triglycerides are types of fat molecules, commonly associated with "bad cholesterol," known to increase risk of inflammation of the endothelium, the layer of cells that lines arteries.

"The new study shows that eating a common fast food meal can affect inflammatory responses in the blood vessels," said Anthony Passerini, assistant professor of biomedical engineering at UC Davis, who led the project.

"Our techniques allowed us to measure the inflammatory potential of an individual's lipids outside of the body and to correlate that with easily measured characteristics that could be used to help better understand a person's risk for vascular disease," Passerini said.

Passerini collaborated with Scott Simon, professor of biomedical engineering at UC Davis, to develop cell culture models to mimic the properties of blood vessels. They wanted to learn how triglyceride levels can cause endothelial inflammation, and find a way to assess an individual's inflammatory potential.

They recruited 61 volunteers with high and normal fasting triglyceride levels and a range of waist sizes, then measured levels of triglyceride particles in their blood after they ate a typical fast food breakfast from a major fast food franchise: two breakfast sandwiches, hash browns and orange juice.

Passerini's team found that after eating the high-fat meal, the size of a type of a particle called triglyceride-rich lipoprotein (TGRL) varied directly with the individual's waist size and preexisting blood triglyceride level. These particles can bind to the endothelium, triggering inflammation and an immune response that brings white blood cells to repair the damage. Over time, this leads to atherosclerosis.

The researchers tested whether TGRL particles from the volunteers' blood could cause cultured endothelial cells in the laboratory to express markers for inflammation.

There was a mixed response: individuals with both a waist size over 32 inches (not terribly large by most standards) and high triglyceride levels had large lipoprotein particles that bound easily to the endothelial cells and caused inflammation in response to an immune chemical "trigger."

The TGRLs only caused inflammation when exposed to this immune molecule, which suggests that people with existing low-grade inflammation may be more susceptible to endothelial dysfunction related to triglyceride "spikes" that occur after eating high-fat meals, Passerini said.

In people who are predisposed, repeated episodes of inflammation could lead to atherosclerosis. Passerini's lab is continuing to investigate how abdominal obesity, high triglyceride levels and inflammation can lead to atherosclerosis.

More information: The findings are published online in the journal American Journal of Physiology - Heart and Circulatory Physiology.

Provided by University of California - Davis

Expecting the best, fearing the worst with placebo effect

(20 feb 2011) -- Poor expectations of treatment can override all the effect of a potent pain-relieving drug, a brain imaging study at Oxford University has shown.

In contrast, positive expectations of treatment doubled the natural physiological or biochemical effect of the opioid drug among the healthy volunteers in the study.

The study of the placebo effect – and its opposite the nocebo effect – is published in Science Translational Medicine. The findings suggest that doctors may need to consider dealing with patients’ beliefs about the effectiveness of any treatment, as well as determining which drug might be the best for that patient.

"Doctors shouldn’t underestimate the significant influence that patients' negative expectations can have on outcome," says Professor Irene Tracey of the Center for Functional Magnetic Resonance Imaging of the Brain at Oxford University, who led the research.

"For example, people with chronic pain will often have seen many doctors and tried many drugs that haven’t worked for them. They come to see the clinician with all this negative experience, not expecting to receive anything that will work for them. Doctors have almost got to work on that first before any drug will have an effect on their pain."

The placebo effect describes the improvements seen when patients – unknowingly – are given dummy pills or sham treatments but believe it will do them good. This is a very real physiological effect; it is not just about patients ‘feeling’ better. The nocebo effect is the opposite: patients see poorer outcomes as the result of doubts about a medical treatment.

Previous studies have investigated the basis of the placebo effect, when using sugar pills or saline injections for example, and confirmed it can elicit a real response.

This new research, funded by the Medical Research Council and German research funders, goes a step further by examining how manipulating participants’ expectations can influence their response to an active drug.

The Oxford University team, along with colleagues from the University Medical Center Hamburg-Eppendorf in Germany, Cambridge University, and the Technische Universität München, set out to investigate these effects among 22 healthy adult volunteers by giving them an opioid drug and manipulating their expectations of the pain relief they might receive at different points.

The volunteers were placed in an MRI scanner and heat applied to the leg at a level where it begins to hurt – set so that each individual rated the pain at 70 on a scale of 1 to 100. An intravenous line for administration of a potent opioid drug for pain relief was also introduced.

After an initial control run, unknown to the participants, the team started giving the drug to see what effects there would be in the absence of any knowledge or expectation of treatment. The average initial pain rating of 66 went down to 55.

The volunteers were then told that the drug would start being administered, although no change was actually made and they continued receiving the opioid at the same dose. The average pain ratings dropped further to 39.

Finally, the volunteers were led to believe the drug had been stopped and cautioned that there may be a possible increase in pain. Again, the drug was still being administered in the same way with no change. Their pain intensity increased to 64. That is, the pain was as great as in the absence of any pain relief at the beginning of the experiment.

The researchers used brain imaging to confirm the participants’ reports of pain relief. MRI scans showed that the brain’s pain networks responded to different extents according to the volunteers’ expectations at each stage, and matching their reports of pain.

This showed the volunteers really did experience different levels of pain when their expectations were changed, although the administration of pain relief remained constant.

Professor Tracey notes that these results have been seen in a small, healthy group of volunteers, and that these are short-term, not sustained, manipulations of the participants’ beliefs about the treatment.

But she says it’s important not to underestimate the strength of the effect of such expectations on any treatment, and that clinicians need to know how to manage that.

Professor Tracey says there may also be lessons for the design of clinical trials. These are often carried out comparing a candidate drug against a dummy pill to see if there is any effect of a drug above and beyond that of the placebo.

"We should control for the effect of people’s expectations on the results of any clinical trial. At the very least we should make sure we minimise any negative expectations to make sure we’re not masking true efficacy in a trial drug."

More information: http://stm.science … a14.abstract

Provided by Oxford University

Speaking 2 languages may delay getting Alzheimer's

Mastering a second language can pump up your brain in ways that seem to delay getting Alzheimer's disease later on, scientists said Friday.

19 feb 2011--Never learned to habla or parlez? While the new research focuses mostly on the truly long-term bilingual, scientists say even people who tackle a new language later in life stand to gain.

The more proficient you become, the better, but "every little bit helps," said Ellen Bialystok, a psychology professor at York University in Toronto.

Much of the study of bilingualism has centered on babies, as scientists wondered why simply speaking to infants in two languages allows them to learn both in the time it takes most babies to learn one. Their brains seem to become more flexible, better able to multitask. As they grow up, their brains show better "executive control," a system key to higher functioning - as Bialystok puts it, "the most important part of your mind."

But does that mental juggling while you're young translate into protection against cognitive decline when you're old?

Bialystok studied 450 Alzheimer's patients, all of whom showed the same degree of impairment at the time of diagnosis. Half are bilingual - they've spoken two languages regularly for most of their lives. The rest are monolingual.

The bilingual patients had Alzheimer's symptoms and were diagnosed between four and five years later than the patients who spoke only one language, she told the annual meeting of the American Association for the Advancement of Science.

Being bilingual does nothing to prevent Alzheimer's disease from striking. But once the disease does begin its silent attack, those years of robust executive control provide a buffer so that symptoms don't become apparent as quickly, Bialystok said.

"They've been able to cope with the disease," she said.

Her work supports an earlier study from other researchers that also found a protective effect.

What is it about being bilingual that enhances that all-important executive control system?

Both languages are essentially turned on all the time, but the brain learns to inhibit the one you don't need, said psychology professor Teresa Bajo of the University of Granada in Spain. That's pretty constant activity.

That's not the only area. University of British Columbia psychologist Janet Werker studies infants exposed to two languages from birth to see why they don't confuse the two, and says bilingual babies learn very early to pay attention better.

Werker tested babies in Spain who were growing up learning both Spanish and Catalan. She showed the babies videos of women speaking languages they'd never heard - English and French - but with the sound off. By measuring the tots' attention span, Werker concluded that babies could distinguish between English and French simply by watching the speakers' facial cues. It could have been the different lip shapes.

"It looks like French people are always kissing," she joked, while the English "th" sound evokes a distinctive lip-in-teeth shape.

Whatever the cues, monolingual babies couldn't tell the difference, Werker said Friday at the meeting.

But what if you weren't lucky enough to be raised bilingual? Scientists and educators know that it becomes far harder to learn a new language after puberty.

Partly that's because adults' brains are so bombarded with other demands that we don't give learning a new language the same attention that a young child does, Bialystok said.

At the University of Maryland, scientists are studying how to identify adults who would be good candidates to master a new language, and then what types of training are best. Having a pretty strong executive control system, like the lifelong bilinguals have, is among the good predictive factors, said Amy Weinberg, deputy director of the university's Center for Advanced Study of Language.

But people don't have to master a new language to benefit some, Bialystok said. Exercising your brain throughout life contributes to what's called cognitive reserve, the overall ability to withstand the declines of aging and disease. That's the basis of the use-it-or-lose-it advice from aging experts who also recommend such things as crossword puzzles to keep your brain nimble.

"If you start to learn at 40, 50, 60, you are certainly keeping your brain active," she said.

More information: Science meeting: http://www.aaas.org/meetings/

Increasing brain enzyme may slow Alzheimer's disease progression

Increasing puromycin-sensitive aminopeptidase, the most abundant brain peptidase in mammals, slowed the damaging accumulation of tau proteins that are toxic to nerve cells and eventually lead to the neurofibrillary tangles, a major pathological hallmark of Alzheimer's disease and other forms of dementia, according to a study published online in the journal, Human Molecular Genetics.

18 feb 2011--Researchers found they could safely increase the puromycin-sensitive aminopeptidase, PSA/NPEPPS, by two to three times the usual amount in animal models, and it removed the tau proteins in the neurons. Removing the tau proteins restored neuronal density and slowed down disease progression. Researchers detected no abnormalities caused by the increase in PSA/NPEPPS, suggesting that elevating PSA/NPEPPS activity may be a viable approach to treat Alzheimer's disease and other forms of dementia, known a tauopathies.

"Our research demonstrated that increasing the brain enzyme known as PSA/NPEPPS can effectively block the accumulation of tau protein that is toxic to nerve cells and slow down the progression of neural degeneration without unwanted side effects," said Stanislav L. Karsten, PhD, the corresponding author for the study and a principal investigator at Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center (LA BioMed). "These findings suggest that increasing this naturally occurring brain peptidase, PSA/NPEPPS, may be a feasible therapeutic approach to eliminate the accumulation of unwanted toxic proteins, such as tau, that cause the neural degeneration associated with the devastating effects of Alzheimer's disease and other forms of dementia."

Alzheimer's disease affects 2 million to 4 million Americans, and their ranks are expected to grow to as many as 14 million by the middle of the 21st century as the population ages.

The potential for PSA/NPEPPS to protect neurons from degeneration was first reported in a 2006 issue of the journal, Neuron. At that time, researchers hypothesized that PSA/NPEPPS may be a natural mechanism for protecting neurons. Dr. Karsten, who was the lead author of the 2006 study, said the new study is the first to provide the data confirming the neuroprotective role of PSA/NPEPPS in mammals.

More information: The research paper may be accessed at http://hmg.oxfordj … ull.pdf+html

Provided by Los Angeles Biomedical Research Institute at Harbor

Obesity is heart disease killer in its own right, irrespective of other risk factors

Obesity is a killer in its own right, irrespective of other biological or social risk factors traditionally associated with coronary heart disease, suggests research published online in Heart.

17 feb 2011--Increasing weight is associated with a higher prevalence of known risk factors for coronary artery disease, such as diabetes, high blood pressure and cholesterol. And it has been assumed that these have been responsible for the increased risk of heart disease seen in obesity, say the authors.

The research team tracked the health of more than 6,000 middle aged men with high cholesterol, but no history of diabetes or cardiovascular disease, for around 15 years.

After excluding men who had cardiovascular problems or died within two years of the start of monitoring, to correct for any bias, 214 deaths and 1,027 non-fatal heart attacks/strokes occurred during the whole period.

The risk of a heart attack was compared across categories of increasing body mass index (BMI), using two different approaches.

One simply corrected for any differences in the age or smoking status of the men, while the second corrected for cardiovascular risk factors such as high cholesterol and blood pressure, deprivation and any medications the men were taking.

Not unexpectedly, the results showed that the higher a man's weight, the higher was his likelihood of having other risk factors for cardiovascular disease. And there was no increased risk of a non-fatal heart attack with increasing BMI, (when using either approach)

But the risk of death was significantly higher in men who were obese - a BMI of 30 to 39.9 kg/m².

In the model simply correcting for age and smoking, this risk was 75% higher. And despite correcting for known cardiovascular risk factors, medication, and deprivation in the second model, the risk was still 60% higher.

Inflammation is a strong factor in fatal cardiovascular disease, and obesity is increasingly being recognised as an inflammatory state, which may partly explain how obesity is linked to heart disease, say the authors. This has implications for treatment and prevention, they add.

In an accompanying podcast, which expands on the findings, lead author Dr Jennifer Logue, of the British Heart Foundation Cardiovascular Research Centre, at the University of Glasgow, cautions that the number of obese men in the sample was small, so the results need to be replicated elsewhere.

But she says, this is mainly because when the study started 20 years ago, the prevalence of obesity was low. But all that has now changed.

"The obesity generation is coming of age. We are going to see more and more complications from obesity, and coming at an earlier age," she warns.

Provided by British Medical Journal

Hearing loss associated with development of dementia

Older adults with hearing loss appear more likely to develop dementia, and their risk increases as hearing loss becomes more severe, according to a report in the February issue of Archives of Neurology.

16 feb 2011--By the year 2050, an estimated 100 million people or nearly one in 85 individuals worldwide will be affected by dementia, according to background information in the article. Interventions that could delay the onset of dementia by even one year could lead to a more than 10 percent decrease in the prevalence of dementia in 2050, the authors note. "Unfortunately, there are no known interventions that currently have such effectiveness," they write. "Epidemiologic approaches have focused on the identification of putative risk factors that could be targeted for prevention based on the assumption that dementia is easier to prevent than to reverse. Candidate factors include low involvement in leisure activities and social interactions, sedentary state, diabetes mellitus and hypertension."

To assess another potential risk factor, hearing loss, Frank R. Lin, M.D., Ph.D., of Johns Hopkins Medical Institutions, Baltimore, and colleagues studied 639 individuals age 36 to 90 without dementia. Participants initially underwent cognitive and hearing testing between 1990 and 1994 and were followed for the development of dementia and Alzheimer's disease through May 31, 2008.

Of the participants, 125 had mild hearing loss (25 to 40 decibels), 53 had moderate hearing loss (41 to 70 decibels) and six had severe hearing loss (more than 70 decibels). During a median (midpoint) follow-up of 11.9 years, 58 individuals were diagnosed with dementia, including 37 who had Alzheimer's disease.

The risk of dementia was increased among those with hearing loss of greater than 25 decibels, with further increases in risk observed among those with moderate or severe hearing loss as compared with mild hearing loss. For participants age 60 and older, more than one-third (36.4 percent) of the risk of dementia was associated with hearing loss.

The risk of developing Alzheimer's disease specifically also increased with hearing loss, such that for every 10 decibels of hearing loss, the extra risk increased by 20 percent. There was no association between self-reported use of hearing aids and a reduction in dementia or Alzheimer's disease risk.

"A number of mechanisms may be theoretically implicated in the observed association between hearing loss and incident dementia," the authors write. Dementia may be overdiagnosed in individuals with hearing loss, or those with cognitive impairment may be overdiagnosed with hearing loss. The two conditions may share an underlying neuropathologic process. "Finally, hearing loss may be causually related to dementia, possibly through exhaustion of cognitive reserve, social isolation, environmental deafferentation [elimination of sensory nerve fibers] or a combination of these pathways."

"If confirmed in other independent cohorts, the findings of our study could have substantial implications for individuals and public health. Hearing loss in older adults may be preventable and can be practically addressed with current technology (e.g., digital hearing aids and cochlear implants) and with other rehabilitative interventions focusing on optimizing social and environmental conditions for hearing. With the increasing number of people with hearing loss, research into the mechanistic pathways linking hearing loss with dementia and the potential of rehabilitative strategies to moderate this association are critically needed."

More information: Arch Neurol. 2011;68[2]:214-220.

Provided by JAMA and Archives Journals

Fiber intake associated with reduced risk of death

Dietary fiber may be associated with a reduced risk of death from cardiovascular, infectious and respiratory diseases, as well as a reduced risk of death from any cause over a nine-year period, according to a report posted online today that will be published in the June 14 print issue of Archives of Internal Medicine.

15 feb 2011--Fiber, the edible part of plants that resist digestion, has been hypothesized to lower risks of heart disease, some cancers, diabetes and obesity, according to background information in the article. It is known to assist with bowel movements, reduce blood cholesterol levels, improve blood glucose levels, lower blood pressure, promote weight loss and reduce inflammation and bind to potential cancer-causing agents to increase the likelihood they will be excreted by the body.

Yikyung Park, Sc.D., of the National Cancer Institute, Rockville, Md., and colleagues analyzed data from 219,123 men and 168,999 women in the National Institutes of Health-AARP Diet and Health Study. Participants completed a food frequency questionnaire at the beginning of the study in 1995 and 1996. Causes of death were determined by linking study records to national registries.

Participants' fiber intake ranged from 13 to 29 grams per day in men and from 11 to 26 grams per day in women. Over an average of nine years of follow-up, 20,126 men and 11,330 women died. Fiber intake was associated with a significantly decreased risk of total death in both men and women—the one-fifth of men and women consuming the most fiber (29.4 grams per day for men and 25.8 grams for women) were 22 percent less likely to die than those consuming the least (12.6 grams per day for men and 10.8 grams for women).

The risk of cardiovascular, infectious and respiratory diseases was reduced by 24 percent to 56 percent in men and 34 percent to 59 percent in women with high fiber intakes. Dietary fiber from grains, but not from other sources such as fruits, was associated with reduced risks of total, cardiovascular, cancer and respiratory disease deaths in men and women.

"The findings remained robust when we corrected for dietary intake measurement error using calibration study data; in fact, the association was even stronger with measurement error correction," the authors write.

"The current Dietary Guidelines for Americans recommend choosing fiber-rich fruits, vegetables and whole grains frequently and consuming 14 grams per 1,000 calories of dietary fiber," the authors conclude. "A diet rich in dietary fiber from whole plant foods may provide significant health benefits."

More information: Arch Intern Med. Published online February 14, 2011. doi:10.1001/archinternmed.2011.18

More candor urged in care of dying cancer patients

14 feb 2011-- Patients don't want to hear that they're dying and doctors don't want to tell them. But new guidance for the nation's cancer specialists says they should be upfront and do it far sooner.

The American Society of Clinical Oncology says too often, patients aren't told about options like comfort care or even that their chemo has become futile until the bitter end.

To help families broach the topic, too, the group developed an easy-to-read booklet about those choices, from standard care to symptom relief, and advice about what to ask to maximize remaining time.

"This is not a 15-minute conversation, and it should not happen in the back of the ambulance on the way to the ICU at 3 in the morning," says ASCO chief executive Dr. Allen Lichter. "When everyone is well and has their wits about them, it's time to start the process."

The guidance and booklet - available at http://www.cancer.net - mark an unusually strong push for planning end-of-life care, in a profession that earns more from attacking tumors than from lengthy, emotional discussions about when it's time to stop.

"This is a clarion call for oncologists . to take the lead in curtailing the use of ineffective therapy and ensuring a focus on palliative care and relief of symptoms throughout the course of illness," the guidance stresses.

But it's part of a slowly growing movement to deal with a subject so taboo that Congress' attempt to give such planning a nudge in 2009 degenerated into charges of "death panels."

Now consider a program in Pittsburgh named Closure. In so-called "community conversations," the program teaches families how to talk with each other and their doctors about what they want - and want to avoid - in their final days. Created by the Jewish Healthcare Foundation, sessions have spread to hospitals, religious centers and neighborhoods around the city, and a website opened last month at http://www.closure.org .

The sessions are frank. Doctors tell of entering hospital rooms late at night asking for resuscitation preferences should a very ill patient worsen only to find relatives didn't know their loved one was that sick.

"There is going to be, over the next few years, a groundswell of people telling physicians, `I don't want to go out in excruciating pain, short of breath, alone, surrounded by lights and sirens and people pounding on my chest,'" predicts Dr. Jonathan Weinkle, a primary care physician who advises the program.

"Everybody wants a good death but not a moment too soon, but they don't have the language to ask for it."

Closure participant Pearl Moore, a retired Pittsburgh oncology nurse, urges people to start planning before they're ever sick, when it's easier to discuss.

Moore's mother died of stomach cancer without health workers or family ever discussing the inevitable. Haunted, she returned to college to specialize in cancer nursing. She helped her patients discuss quality of life, "to be able to live until they died, is the way I put it," Moore says.

And years ago she prepared her own living will and other health care directives, giving copies to her daughter, Cheryl, as soon as she was grown.

"Remembering my mother, we had the discussion," says Moore.

It's not clear how often the still healthy like Moore do that kind of advance planning.

But the oncology society says it isn't happening enough with the very sick. Fewer than 40 percent of advanced cancer patients have what it calls a "realistic conversation" with their doctors about what to expect and their choices of care.

The consequences: Patients increasingly are receiving aggressive chemotherapy in the last two weeks of life. They're spending more of their last months hospitalized. They're not told that a lot of expensive, side effect-prone therapies buy at best a few more months.

They think palliative care - specialized care for pain, nausea, shortness of breath - means giving up when it should be offered with standard anti-tumor care.

And they're not referred to hospice until their final days. Lichter tells of a lung cancer patient who spent his last days on a ventilator, unable to say goodbye and incurring $25,000 in hospital bills, because his family called 911 when he became short of breath. Hospice care could have eased that symptom at home.

The society plans by summer to issue detailed guidelines to help doctors conduct those tough conversations. Meanwhile, among its advice for patients:

-Ask your doctor about pros and cons of different treatment options, and discuss your priorities, including quality of life, with the doctor and family. You can change your mind later.

-Ask about palliative care for symptom relief along with your chemo. A major study last summer found that combination helped advanced lung cancer patients live a few months longer, because people who feel better can tolerate more anti-cancer treatment.

-A living will ensures health workers and family know your choices when you cannot communicate, including whether you would want such things as a feeding tube.

-Most clinical trials for experimental treatments won't admit people who've already undergone multiple treatments, so consider that option early.

More information:
Cancer group: http://www.cancer.net

Closure: http://www.closure.org

State advance directives: http://www.caringinfo.org/PlanningAhead

Non-dopaminergic drug preladenant reduces motor fluctuations in patients with Parkinson's disease

Preladenant, a non-dopaminergic medication, reduces off time in patients with Parkinson's disease receiving standard dopamine therapy, an international study led by the University of South Florida found.

12 feb 2011--Results of the double-blind, randomized clinical trial are reported online today in the journal Lancet Neurology. The findings suggest that preladenant may offer a new supplemental treatment for Parkinson's disease without some of the complications of levodopa and other standard dopamine treatments.

"The goal of treatment is to provide the best possible function and quality of life to patients over time," said lead author Dr. Robert A. Hauser, director of the Parkinson's Disease and Movement Disorders Center at USF. "After a few years, many patients find that their traditional Parkinson's disease medications wear off after a few hours leading to a re-emergence of symptoms. In this study, preladenant was shown to reduce off time, thereby affording patients more time through the day with better function."

Dr. Hauser and colleagues evaluated the safety and effectiveness of a range of doses of preladenant in 253 patients experiencing "wearing off" symptoms from their levodopa therapy. The patients were also receiving other available anti-parkinsonian drugs, such as dopamine agonists and/or entacapone.

The 12-week study found that the addition of 5 and 10 mg of preladenant twice daily significantly reduced "off time" -- the re-emergence of troublesome motor symptoms such as slowness, stiffness, tremors, and immobility – when compared to patients receiving similar doses of placebo. Futhermore, preladenant significantly increased "on time" – the period during which patients' Parkinson's symptoms were adequately controlled --.without significantly worsening dyskinesia (involuntary twisting, turning movements). The doses were well tolerated, and the incidence of treatment-related adverse effects was similar for patients receiving preladenant and placebo.

In Parkinson's disease, the brain's dopamine-producing cells falter and die, leading to movement-related or motor symptoms such as tremors, stiffness, slowness, and balance problems.

Levodopa, a compound converted into dopamine in the brain, is still the gold standard therapy for Parkinson's, but as the disease advances this standard drug works for increasingly shorter time periods. As a result, patients begin to experience impaired movement before their next scheduled dose of medication. The re-emergence of symptoms accompanying this "off-time" can make it difficult for patients to perform even the most basic functions, such as walking and dressing. In addition, over time patients tend to develop a sensitivity to levodopa therapy during "on-time" resulting in involuntary twisting, turning movements known as dyskinesia.

Currently available drugs widely used to treat Parkinson's disease correct for the loss of the neurotransmitter dopamine – either by boosting available dopamine in the brain or directly stimulating dopamine receptors. New ways to treat the disease that better address motor fluctuations without adverse side effects continue to be sought. Preladenant is a non-dopaminergic medication that targets adenosine A2A receptors in the motor control areas of the brain. It may offer advantages over dopamine medications, possibly including fewer side effects.

The clinical trial was conducted at 44 sites in 15 countries. Preladenant is an investigational medicine and is not approved for use.

Provided by University of South Florida

Stroke rehab doesn't have to be high-tech to help

12 feb 2011-- The largest study ever on stroke rehabilitation found that doing physical therapy at home improved walking just as well as a high-tech treadmill program.

More surprising, patients who started rehab late - six months after their strokes - still improved. It's long been thought that there was little to gain from rehab after half a year.

"We now have evidence, for the first time, that a prolonged course of therapy will have benefits," said Dr. Jeffrey Saver, director of the stroke center at the University of California, Los Angeles. "For virtually everyone, we should be doing more intensive therapy than we are."

He had no role in the federally funded study, which was led by Duke University researchers and discussed Friday at an American Stroke Association conference in Los Angeles.

Each year, nearly 800,000 Americans suffer a stroke, and up to two-thirds of survivors have problems walking. Sophisticated machines like robots and weight-supporting treadmills increasingly are being used, but there's limited research on how well they work compared to more traditional therapy.

Such equipment is popular in high-end rehab hospitals like the one in Houston where Rep. Gabrielle Giffords is being treated after her gunshot wound to the head.

The new study included 408 stroke survivors who had trouble walking. On average, they took 1,700 steps a day; normal is 10,000 steps a day. They either traveled to a facility to get high-tech rehab or received physical therapy at home. Some began therapy two months after a stroke; others started six months after the stroke to see if there was a difference.

In high-tech rehab, patients exercised on a treadmill while their weight was supported by an overhead harness. As they gained speed and endurance, they could practice walking on their own.

In the home program, a physical therapist helped patients do exercises to improve strength and balance, and to walk every day.

After a year, both groups made similar improvements in how far and how fast they could walk. However, the treadmill exercisers were more likely to feel dizzy or faint during training, and had a higher risk of falling.

What's more, fewer patients dropped out of the home therapy - 3 percent compared to 13 percent in high-tech rehab.

"There's a tendency in our country to go to high-tech machines," but this study shows they're not always better, said Dr. Walter Koroshetz, deputy director of the National Institute of Neurological Disorders and Stroke, the study's main sponsor.

The bigger message, said study leader Pamela Duncan of Duke University, is that longer treatment and more treatment is best. She said many insurance companies allow 20 visits, while this study gave 36.

The care that stroke victims usually get now - less intense therapy for three to six months - "does not get them to the point where they could be," Koroshetz said.

Doctors are working on a cost comparison, but believe the home program is much cheaper. High-tech rehab requires expensive equipment and two to three therapists per patient; the home program needs only one.

Also at the conference:

Doctors may be missing "silent strokes" in a small but significant number of children with severe anemia, who may be unfairly labeled as slow learners when in fact they have a medical problem.

Strokes have long been known to be a risk for kids with sickle cell anemia, an inherited blood disease that mostly affects blacks. The new study found they also were occurring undetected in children with other conditions that can cause anemia, such as cancer, kidney failure or blood loss from trauma such as a car crash.

"I don't think there's any reason to panic," but doctors need to consider the possibility of stroke when treating any child with severe anemia, said Dr. Michael Dowling of the University of Texas Southwestern Medical Center in Dallas.

Dowling led the study involving 52 children at Children's Medical Center Dallas - 22 with sickle cell and 30 with other causes of severe anemia. MRI scans revealed fresh strokes were occurring in four of the 22 children with sickle cell, and two of the other 30 kids. "Silent strokes" - evidence of damage but no obvious symptoms - were found in three of the 22 sickle cell patients and seven of the other 30.

More information:
Stroke meeting: http://www.strokeconference.org

Sickle cell: http://www.cdc.gov/ncbddd/sicklecell/index.html

Stroke info: http://www.ninds.nih.gov

Limited lymph node removal for certain breast cancer does not appear to result in poorer survival

Among patients with early-stage breast cancer that had spread to a nearby lymph node and who received treatment that included lumpectomy and radiation therapy, women who just had the sentinel lymph node removed (the first lymph node to which cancer is likely to spread from the primary tumor) did not have worse survival than women who had more extensive axillary lymph node dissection (surgery to remove lymph nodes found in the armpit), according to a study in the February 9 issue of JAMA.

11 feb 2011--Axillary lymph node dissection (ALND) has been part of breast cancer surgery since the use of radical mastectomy and reliably identifies nodal metastases. "Sentinel lymph node dissection (SLND) accurately identifies nodal metastasis of early breast cancer, but it is not clear whether further nodal dissection [removal] affects survival," the authors write. "ALND, as a means for achieving local disease control, carries an indisputable and often unacceptable risk of complications such as seroma [a mass or swelling caused by the localized accumulation of serum within a tissue or organ], infection, and lymphedema [condition in which excess fluid called lymph collects in tissues and causes swelling]."

Armando E. Giuliano, M.D., of the John Wayne Cancer Institute at Saint John's Health Center, Santa Monica, Calif., and colleagues conducted a study to determine the effects of ALND on overall survival in patients with SLN metastases treated with lumpectomy (surgical removal of a tumor without removing much of the surrounding tissue or lymph nodes) and radiation therapy. The trial was conducted at 115 sites and enrolled patients from May 1999 to December 2004. Patients were women with T1-T2 (stage of tumor) invasive breast cancer, no palpable adenopathy (enlarged lymph nodes), and 1 to 2 SLNs containing metastases.

Patients with SLN metastases identified by SLND were randomized to undergo ALND or no further axillary treatment. Those randomized to ALND underwent dissection of 10 or more nodes. Of 891 patients, 445 were randomly assigned to the ALND group and 446 to the SLND-alone group.

As expected, there was a difference between ALND and SLND-alone treatment groups in total number of removed lymph nodes and total number of tumor-involved nodes; the median (midpoint) total number of nodes removed was 17 in the ALND group and 2 in the SLND-alone group. At a median follow-up of 6.3 years, there were 94 deaths (SLND-alone group, 42; ALND group, 52). The use of SLND alone compared with ALND did not appear to result in statistically inferior survival, with the 5-year over all survival rates being 92.5 percent in the SLND-alone group and 91.8 percent in the ALND group. Disease-free survival did not differ significantly between treatment groups, with 5-year disease-free survival being 83.9 percent for the SLND-alone group and 82.2 percent for the ALND group.

The rate of wound infections, axillary seromas, and paresthesias (prickly, tingling sensations) among patients in the trial was higher for the ALND group than for the SLND-alone group (70 percent vs. 25 percent).

The authors note that these results suggest that breast cancer patients, such as those in this study, do not benefit from the addition of ALND in terms of local control, disease-free survival, or overall survival, and that ALND may no longer be justified for certain patients. "Implementation of this practice change would improve clinical outcomes in thousands of women each year by reducing the complications associated with ALND and improving quality of life with no diminution in survival."

More information: JAMA. 2011;305[6]:569-575.

Provided by JAMA and Archives Journals

Diet soda may raise odds of vascular events; salt linked to stroke risk

Even if you drink diet soda — instead of the sugar variety — you could still have a much higher risk of vascular events compared to those who don't drink soda, according to research presented at the American Stroke Association's International Stroke Conference 2011.

10 feb 2011--In findings involving 2,564 people in the large, multi-ethnic Northern Manhattan Study (NOMAS), scientists said people who drank diet soda every day had a 61 percent higher risk of vascular events than those who reported no soda drinking.

"If our results are confirmed with future studies, then it would suggest that diet soda may not be the optimal substitute for sugar-sweetened beverages for protection against vascular outcomes," said Hannah Gardener, Sc.D., lead author and epidemiologist at the University of Miami Miller School of Medicine in Miami, Fla.

In separate research using 2,657 participants also in the Manhattan study, scientists found that high salt intake, independent of the hypertension it causes, was linked to a dramatically increased risk of ischemic strokes (when a blood vessel blockage cuts off blood flow to the brain).

In the study, people who consumed more than 4,000 milligrams (mg) per day of sodium had more than double the risk of stroke compared to those consuming less than 1,500 mg per day.

At the start of both studies, researchers assessed diet by a food frequency questionnaire.

NOMAS is a collaboration of investigators at Columbia University in New York and Miami's Miller School of Medicine, launched in 1993 to examine stroke incidence and risk factors in a multi-ethnic urban population. A total of 3,298 participants over 40 years old (average age 69) were enrolled through 2001 and continue to be followed. Sixty-three percent were women, 21 percent were white, 24 percent black and 53 percent Hispanic.

In the soda study, researchers asked subjects at the outset to report how much and what kind of soda they drank. Based on the data, they grouped participants into seven consumption categories: no soda (meaning less than one soda of any kind per month); moderate regular soda only (between one per month and six per week), daily regular soda (at least one per day); moderate diet soda only; daily diet soda only; and two groups of people who drink both types: moderate diet and any regular, and daily diet with any regular.

During an average follow-up of 9.3 years, 559 vascular events occurred (including ischemic and hemorrhagic stroke, which is caused by rupture of a weakened blood vessel). Researchers accounted for participants' age, sex, race or ethnicity, smoking status, exercise, alcohol consumption and daily caloric intake. And even after researchers also accounted for patients' metabolic syndrome, peripheral vascular disease and heart disease history, the increased risk persisted at a rate 48 percent higher.

In the sodium research, 187 ischemic strokes were reported during 9.7 years of follow-up. Stroke risk, independent of hypertension, increased 16 percent for every 500 mg of sodium consumed a day, the scientists calculated. Those figures included adjustment for age, sex, race/ethnicity, education, alcohol use, exercise, daily caloric intake, smoking status, diabetes, high cholesterol, high blood pressure and previous heart disease.

Only a third of participants met the current U.S. Dietary Guidelines for Americans that recommend daily sodium intake fall below 2,300 mg, or about a teaspoon of salt, Gardener said. Only 12 percent of subjects met the American Heart Association's recommendations to consume less than 1,500 mg a day. Average intake was 3,031 milligrams.

"The take-home message is that high sodium intake is a risk factor for ischemic stroke among people with hypertension as well as among those without hypertension, underscoring the importance of limiting consumption of high sodium foods for stroke prevention," Gardener said.

Participants' reporting their dietary behavior is a key limitation of both studies, Gardener said.

In the soda study, investigators also lacked data on types of diet and regular drinks consumed, preventing analysis of whether variations among brands or changes over time in coloring and sweeteners might have played a role.

Provided by American Heart Association

Combining brain imaging, genetic analysis may help identify people at early risk of Alzheimer's

A new study from the Centre for Addiction and Mental Health (CAMH) has found evidence suggesting that a variation of a specific gene may play a role in late-onset Alzheimer's, the disease which accounts for over 90% of Alzheimer's cases. This innovative study has combined genetics and brain imaging to determine who may be at risk for developing late-onset Alzheimer's disease long before symptoms appear.

09 feb 2011--The gene, which is called brain-derived neurotrophic factor (BDNF), is crucial to maintaining healthy function of the brain, primarily the brain's memory centre of the hippocampus and entorhinal cortex, and is responsible for learning and memory function. Past research has found that less BDNF is present in the memory centre of those diagnosed with Alzheimer's disease. However genetic association studies alone have not produced definite findings regarding this gene. Instead, a combination of genetics and brain imaging were used to demonstrate clear effects of this gene in the brain.

In the study published today in the Archives of General Psychiatry, a variation of the BDNF gene called val66met, was tracked and examined in healthy individuals to see what effect it had on the brain. Genotyping was used to determine which study participants carried the gene variation. Then two types of brain imaging -- high-resolution magnetic resonance imaging (MRI) cortical thickness mapping and diffusion tensor imaging (DTI) (an MRI-based technique that measures key structural connections in the brain)-- were applied to measure the physical structures of the brain in each individual. This combination of genetic screening and imaging found that BDNF val66met gene variation influenced exactly those brain structures and connections that deteriorate at the earliest phases of Alzheimer's disease.

"Our sample consisted of healthy adults who passed all cognitive testing and displayed no clinical symptoms of Alzheimer's disease, yet the brains of those who carried the gene variation had differences in their brain structures consistent with changes we see in people at the earliest stages of Alzheimer's disease," said Dr. Aristotle Voineskos, physician and scientist at CAMH, and principal investigator of the study.

Participants who carried the variation were more likely to have thinner temporal lobe structures and disrupted white matter tract connections leading into the temporal lobe - the same structures and neural networks that have deteriorated in the brains of Alzheimer's patients when their brains are examined post-mortem.

"In the past, Alzheimer's disease could only be diagnosed and treated once outward symptoms became present," added Dr. Voineskos. "Early identification is key because, in addition to seeking therapeutic treatments early to reduce suffering, delaying Alzheimer's onset by only two years has the potential of saving the Canadian health care system nearly $15 billion over the next 10 years. The combination of brain imaging and genetics is a key approach that may help us to identify people at risk for Alzheimer's disease."

This breakthrough in image-genetics research can be valuable in the research of other brain diseases and will enable researchers to examine how a gene affects the brain and possibly intervene before a person develops an illness.

Provided by Centre for Addiction and Mental Health

Lifestyle affects life expectancy more than genetics

How long your parents lived does not affect how long you will live. Instead it is how you live your life that determines how old you will get, reveals research from the University of Gothenburg recently published in the Journal of Internal Medicine.

08 feb 2011--It is often assumed that people with parents who lived to be very old are more likely to live to a grand old age themselves.

"But that's just not true – our study shows that hereditary factors don't play a major role and that lifestyle has the biggest impact," says professor emeritus Lars Wilhelmsen, referring to the 1913 Men study that formed the basis of the current research.

Those who did not smoke, consumed moderate amounts of coffee and had a good socio-economic status at the age of 50 (measured in terms of housing costs), as well as good physical working capacity at the age of 54 and low cholesterol at 50 had the greatest chance of celebrating their 90th birthday.

"We're breaking new ground here," says Wilhelmsen. "Many of these factors have previously been identified as playing a role in cardiovascular disease, but here we are showing for the first time that they are important for survival in general."

He believes that it is significant that the research illustrates so clearly that we do not "inherit" mortality to any great extent, but instead that it is the sum of our own habits that has the biggest impact.

"The study clearly shows that we can influence several of the factors that decide how old we get," says Wilhelmsen. "This is positive not only for the individual, but also for society as it doesn't entail any major drug costs."

The study has been published in the Journal of Internal Medicine.

The study of men born in 1913

The 1913 Men epidemiological study started up in 1963. A third of all male 50-year-olds in Gothenburg were called for a check-up that focused on cardiovascular health. Every ten years since, a new group of 50-year-olds has been called in and those who were already taking part in the study have been given another check-up. This has enabled researchers to follow the development of illnesses in a specific age group, and to compare the health of 50-year-olds in 2003 with that of 50-year-olds in 1963, for example. Women have also been included in the study since 2003. Several variables have been studied over the years, including BMI, smoking habits, cholesterol, exercise habits and blood pressure.

The men born in 1913 were examined when they were 50, 54, 60, 67, 75 and 80. Of the 855 men who took part in the study from the start, 111 (13%) were still alive at the age of 90.

Over the years the material has generated many research articles and doctoral theses. An interesting result came in 2008 when researchers were able to show that the drop in the number of smokers, combined with lower cholesterol levels and lower blood pressure, between 1963 and 2003 could offer an explanation for the marked downturn in the number of heart attacks during this 40-year period.

Provided by University of Gothenburg

Physical exercise helps keeps cancer at bay: WHO

The World Health Organisation is advising people engage in at least 150 minutes of "moderate" physical exercise a week to reduce the risk of breast and colon cancers, in new recommendations published Friday.

07 feb 2011--"Cancer is preventable and many cancers are avoidable," said Eduardo Cazap, president of the Union for International Cancer Control (UICC) and one of the authors of the joint "Global Recommendations on Physical Activity for Health".

UICC and WHO experts estimate based on scientific evidence that around 25 percent of breast and colon cancers could be prevented by undertaking physical activity, while exercise can also affect other types of cancers.

"The dose of physical activity required is 150 minutes a week," WHO health promotion expert Tim Armstrong told journalists.

"Most individuals can accomplish it, it's 30 minutes of moderate effort like walking on five days of the week," he explained.

The WHO ranks lack of physical activity alongside tobacco, diabetes and high blood pressure as a health risk, leading to the deaths of 3.2 million people a year.

"Physical inactivity is the fourth leading risk factor for all global deaths, with 31 percent of the world's population not physically active," said Dr Ala Alwan, WHO assistant director-general for non-communicable diseases and mental health.

Some 460,000 women died as a result of breast cancer in 2008 while about 610,000 died of colorectal cancers, according to UN health agency data.

Cazap underlined that one person in two is likely to have a cancer in their lifetime, and the probability grows with ageing.

The UICC believes that the problem of physical inactivity is now extending beyond industralised nations to emerging nations where the population is becoming wealthier.

The recommendations were released for World Cancer Day on Friday.

Report says economic development could change worldwide face of cancer

A new American Cancer Society report says cancers associated with lifestyles and behaviors related to economic development, including lung, breast, and colorectal cancers, will continue to rise in developing countries if preventive measures are not widely applied. The finding comes from the second edition of Global Cancer Facts & Figures and its academic publication, Global Cancer Statistics, published in CA: A Cancer Journal for Clinicians. Both publications are being released on World Cancer Day, Feb. 4, 2011. The latest edition of Global Cancer Facts & Figures includes a special section on cancer in Africa, where according to the International Agency for Research on Cancer (IARC) about 681,000 new cancer cases and 512,400 cancer deaths occurred in 2008, numbers that are projected to nearly double by 2030 due to growth and aging of the population.

06 feb 2011-- According to estimates from IARC, there were approximately 12.7 million new cancer cases worldwide in 2008, 5.6 million of which occurred in economically developed countries and 7.1 million in economically developing countries. There were approximately 7.6 million cancer deaths worldwide in 2008, 2.8 million of which occurred in economically developed countries and 4.8 million in economically developing countries. By 2030, the global cancer burden is expected to nearly double, growing to 21.4 million cases and 13.2 million deaths. And while that increase is the result of demographic changes – a growing and aging population – it may be compounded by the adoption of unhealthy lifestyles and behaviors related to economic development, such as smoking, poor diet, and physical inactivity.

An accompanying editorial (appearing in CA:) by Otis W. Brawley, M.D., chief medical officer of the American Cancer Society, says about 2.6 million of the 7.6 million cancer deaths that occurred in 2008, or about 7300 cancer deaths per day, were potentially avoidable through the prevention of known risk factors, including tobacco use, dietary factors, certain infections, and alcohol use. "The worldwide application of existing cancer control knowledge according to the capacity and economic development of countries or regions could lead to the prevention of even more cancer deaths in the next 2 to 3 decades," writes Dr. Brawley. "In order to achieve this, however, national and international public health agencies, governments, donors, and the private sectors must play major roles in the development and implementation of national or regional cancer control programs worldwide."

A comparison of cancer rates reveals differences in cancer causation between economically developed and economically developing countries. In economically developed countries, the three most commonly diagnosed cancers in 2008 were prostate, lung, and colorectal cancers in men and breast, colorectal, and lung cancers in women. In economically developing countries, cancers of the lung, stomach, and liver were most frequently diagnosed in men while breast, cervical, and lung cancers were the most commonly diagnosed in women. Two of the three leading cancers in men (stomach and liver) and one of the three leading cancers in women (cervix) in developing countries are related to infection. Overall, about one in four cancers in developing countries are related to infection compared to fewer than one in ten in developed countries.

The report also outlines shifts in cancer trends that point to the increasing impact that unhealthy behaviors are beginning to have in developing countries. While male lung cancer death rates are decreasing in most Western countries, they are increasing in China and several other countries in Asia and Africa where the tobacco epidemic is in earlier stages and smoking prevalence has not begun to drop, or even continues to increase. Lung cancer rates in women, which have plateaued in the US, are also increasing in many countries, notably in Spain, France, Belgium, and the Netherlands, where rates are increasing among younger women suggesting that lung cancer in females in these countries will likely increase for several decades barring major interventions.

Breast cancer is now the leading cause of cancer death among females in economically developing countries, a shift from previous decades during which cervical cancer was the most common cause of cancer death. Colorectal cancer incidence rates, which have been decreasing in the US, are rapidly increasing in several countries historically at low risk, including Spain and a number of countries within Eastern Asia and Eastern Europe.

Special Section: Cancer in Africa

Global Cancer Facts & Figures 2nd edition includes a special section on cancer in Africa, where the disease is an emerging public health problem. According to IARC, about 681,000 new cancer cases and 512,400 cancer deaths occurred in 2008 in Africa. These numbers are projected to nearly double (1.28 million new cancer cases and 970,000 cancer deaths) by 2030 due to the aging and growth of the population, with the potential to be even higher due to the adoption of behaviors and lifestyles associated with economic development and urbanization such as smoking, unhealthy diet, and physical inactivity.

The report says despite this growing burden, cancer continues to receive low public health priority in Africa, largely because of limited resources and other pressing public health problems, including communicable diseases such as AIDS/HIV infection, malaria, and tuberculosis.

Cancers related to infectious agents (cervix, liver, Kaposi sarcoma, urinary bladder) are among the dominant forms of cancer in Africa. In 2008, cervical cancer accounted for 21 percent of the total newly diagnosed cancers in females and liver cancer accounted for 11 percent of the total cancer cases in males.

A majority of cancers in Africa are thought to be diagnosed at advanced stage of the disease largely because of lack of screening and early detection services as well as limited awareness of the early signs and symptoms of cancers among the public and health care providers. Stigma associated with a diagnosis of cancer also plays a role in late stage presentation in most parts of Africa.

Survival after a diagnosis of cancer is much poorer in Africa than in the developed world for most cancer types, especially those cancers affected by screening and treatment. For example, the five-year survival rate for breast cancer is less than 50 percent in The Gambia, Uganda, and Algeria, compared to nearly 90 percent in the United States.

While tobacco use is the most preventable cause of cancer death worldwide, accounting for 20 percent of cancer deaths, it accounts for only about 6 percent of cancer deaths in Africa. The smaller contribution of tobacco use to cancer deaths in Africa reflects the early stage of the tobacco epidemic and low smoking prevalence, especially in women. However, cigarette consumption is increasing in many African countries due to the adoption of behaviors associated with economic growth and increased marketing by tobacco companies. The smoking pattern among teens is even more disturbing. According to the Global Youth Tobacco Survey, in some African countries, the smoking prevalence among boys is higher than that among adults. Although a majority of African countries have ratified the Framework Convention on Tobacco Control, few have implemented or enforced tobacco control programs according to the guidelines.

This September, the United Nations will hold a high-level meeting to develop a global response to the growing threat of non-communicable diseases, including cancer, heart disease, and diabetes. This meeting, supported by the United States government, is only the second meeting the United Nations has held on a global health issue.

Provided by American Cancer Society

Obesity has doubled since 1980, major global analysis of risk factors reveals

The worldwide prevalence of obesity has nearly doubled since 1980, according to a major study on how three important heart disease risk factors have changed across the world over the last three decades. The study, published today in three papers in the Lancet, looked at all available global data to assess how body mass index, blood pressure and cholesterol changed between 1980 and 2008.

05 feb 2011-- The study shows that in 2008, more than one in ten of the world's adult population was obese, with women more likely to be obese than men. An estimated 205 million men and 297 million adult women were obese - a total of more than half a billion adults worldwide.

The proportion of the world's population with high blood pressure, or uncontrolled hypertension, fell modestly between 1980 and 2008. However, because of population growth and ageing, the number of people with uncontrolled hypertension rose from 600 million in 1980 to nearly 1 billion in 2008. High-income countries achieved large reductions in uncontrolled hypertension, with the most impressive progress seen in women in Australasia and men in North America. Uncontrolled hypertension is defined as a systolic blood pressure higher than 140 mmHg or diastolic blood pressure higher than 90 mmHg.

Average levels of total blood cholesterol fell in Western countries of North America, Australasia and Europe, but increased in East and Southeast Asia and the Pacific region.

Professor Majid Ezzati, the senior author of the study from the School of Public Health at Imperial College London, said: "Our results show that overweight and obesity, high blood pressure and high cholesterol are no longer Western problems or problems of wealthy nations. Their presence has shifted towards low and middle income countries, making them global problems."

Beyond global trends, the studies reveal how different countries compare in terms of each risk factor. The results show that:

BMI:

• In 2008, 9.8 per cent of men and 13.8 per cent of women in the world were obese (with a BMI above 30 kg/m2), compared with 4.8 per cent for men and 7.9 per cent for women in 1980.
  
• Pacific island nations have the highest average BMI in the world, reaching 34-35 kg/m2, up to 70 per cent higher than some countries in Southeast Asia and sub-Saharan Africa.
  
• Among high income countries, USA has the single highest BMI (over 28 kg/m2 for men and women), followed by New Zealand. Japan has the lowest BMI (about 22 kg/m2 for women and 24 kg/m2 for men), followed by Singapore.
  
• Among high-income countries, between 1980 and 2008, BMI rose most in USA (by more than 1 kg/m2/decade), followed by New Zealand and Australia for women and followed by UK and Australia for men. Women in a few Western European countries had virtually no rise in BMI.
  
• The UK has the sixth highest BMI in Europe for women and ninth highest for men (both around 27 kg/m2).
  
• Turkish women and Czech men have the highest BMI in Europe (both around 28 kg/m2). Swiss women had the lowest BMI in Europe (around 24 kg/m²).

Blood pressure:

• Systolic blood pressure levels are highest in Baltic and East and West African countries, reaching 135 mmHg for women and 138 mmHg for men. These levels were seen in some Western European countries in the 1980s before their impressive declines.
  
• South Korea, Cambodia, Australia, Canada and USA had some of the lowest blood pressures for both men and women, below 120 mmHg for women and below 125 mmHg for men.
  
• Among high income countries, Portugal, Finland and Norway have the highest blood pressure.
  
• Men had higher blood pressure than women in most world regions.

Cholesterol:

• Western European countries like Greenland, Iceland, Andorra, and Germany have the highest cholesterol levels in the world, with mean serum total cholesterols of around 5.5 mmol/L.
  
• African countries have the lowest cholesterol, some as low as 4 mmol/L.
  
• Among western high-income countries, Greece has the lowest cholesterol for both men and women (below 5 mmol/L). USA, Canada, and Sweden also had low cholesterol.
  
• The UK's cholesterol is ninth highest in the world, slightly below 5.5 mmol/L.

The review was carried out by an international collaboration of researchers, led by Professor Majid Ezzati from Imperial College London and co-led by Dr. Goodarz Danaei from the Harvard School of Public Health, in collaboration with The World Health Organization and a number of other institutions.

Professor Ezzati added: "It's heartening that many countries have successfully reduced blood pressure and cholesterol despite rising BMI. Improved screening and treatment probably helped to lower these risk factors in high-income countries, as did using less salt and healthier, unsaturated fats.

"The findings are an opportunity to implement policies that lead to healthier diets, especially lower salt intake, at all levels of economic development, as well as looking at how we improve detection and control through the primary healthcare system. Policies and targets for cardiovascular risk factors should get special attention at the High-level Meeting of the United Nations General Assembly on Non-Communicable Diseases in September 2011."

Dr. Goodarz Danaei, from the Harvard School of Public Health, said: "This is the first time that anyone has tried to estimate trends in these major risk factors in every country in the world. The amount of data we collected is unprecedented and vast, and allows us to draw robust conclusions."

Dr. Gretchen Stevens, from the World Health Organization, said: "Our study helps track the obesity problem in individual countries and regions. We know that changes in diet and in physical activity have contributed to the worldwide rise in obesity, but it remains unclear which policies would effectively reduce obesity. We need to identify, implement, and rigorously evaluate policy interventions aimed at reversing the trends, or limiting their harmful effects."

Provided by Imperial College London