Obesity, metabolic factors linked to faster cognitive decline

People who are obese and also have high blood pressure and other risk factors called metabolic abnormalities may experience a faster decline in their cognitive skills over time than others, according to a study published in the August 21, 2012, print issue of Neurology, the medical journal of the American Academy of Neurology.

25 aug 2012--Metabolic abnormality was defined as having two or more of the following risk factors: high blood pressure or taking medication for it; low HDL or "good" cholesterol; high blood sugar or taking diabetes medication; and high triglycerides (a type of fat found in the blood) or taking medication to lower cholesterol.

The study involved 6,401 people with an average age 50 at the start of the study. Information on body mass index (BMI) and the risk factors was gathered at the beginning of the study. The participants took tests on memory and other cognitive skills three times over the next 10 years.

A total of 31 percent of the participants had two or more metabolic abnormalities. Nine percent were obese and 38 percent were overweight. Of the 582 obese people, 350, or 60 percent, met the criteria for metabolic abnormality. The metabolically normal obese individuals also experienced more rapid decline.

Over the 10 years of the study, people who were both obese and metabolically abnormal experienced a 22.5 percent faster decline on their cognitive test scores than those who were of normal weight without metabolic abnormalities.

"More research is needed to look at the effects of genetic factors and also to take into account how long people have been obese and how long they have had these metabolic risk factors and also to look at cognitive test scores spanning adulthood to give us a better understanding of the link between obesity and cognitive function, such as thinking, reasoning and memory," said study author Archana Singh-Manoux, PhD, of INSERM, the French research institute in Paris and University College London in England.

Singh-Manoux said the study also provides evidence against the concept of "metabolically healthy obesity" that has suggested that obese people without metabolic risk factors do not show negative cardiac and cognitive results compared to obese people with metabolic risk factors.

Provided by American Academy of Neurology

First evidence from humans on how alcohol may boost risk of cancer

Almost 30 years after discovery of a link between alcohol consumption and certain forms of cancer, scientists are reporting the first evidence from research on people explaining how the popular beverage may be carcinogenic. The results, which have special implications for hundreds of millions of people of Asian descent, were reported here today at the 244^th National Meeting & Exposition of the American Chemical Society.

24 aug 2012--Silvia Balbo, Ph.D., who led the study, explained that the human body breaks down, or metabolizes, the alcohol in beer, wine and hard liquor. One of the substances formed in that breakdown is acetaldehyde, a substance with a chemical backbone that resembles formaldehyde. Formaldehyde is a known human carcinogen. Scientists also have known from laboratory experiments that acetaldehyde can cause DNA damage, trigger chromosomal abnormalities in cell cultures and act as an animal carcinogen.

"We now have the first evidence from living human volunteers that acetaldehyde formed after alcohol consumption damages DNA dramatically," Balbo said. She is a research associate in the laboratory of Stephen Hecht, Ph.D., a noted authority on cancer prevention at the University of Minnesota. "Acetaldehyde attaches to DNA in humans ― to the genetic material that makes up genes - in a way that results in the formation of a 'DNA adduct.' It's acetaldehyde that latches onto DNA and interferes with DNA activity in a way linked to an increased risk of cancer."

Balbo pointed out that people have a highly effective natural repair mechanism for correcting the damage from DNA adducts. Most people thus are unlikely to develop cancer from social drinking, although alcohol is associated with a risk of other health problems and accidents. In addition, most people have an enzyme called alcohol dehydrogenase, which quickly converts acetaldehyde to acetate, a relatively harmless substance.

However, about 30 percent of people of Asian descent ― almost 1.6 billion people ― have a variant of the alcohol dehydrogenase gene and are unable to metabolize alcohol to acetate. That genetic variant results in an elevated risk of esophageal cancer from alcohol drinking. Native Americans and native Alaskans have a deficiency in the production of that same enzyme.

To test the hypothesis that acetaldehyde causes DNA adducts to form in humans, Balbo and colleagues gave 10 volunteers increasing doses of vodka (comparable to one, two and three drinks) once a week for three weeks. They found that levels of a key DNA adduct increased up to 100-fold in the subjects' oral cells within hours after each dose, then declined about 24 hours later. Adduct levels in blood cells also rose.

"These findings tell us that alcohol, a lifestyle carcinogen, is metabolized into acetaldehyde in the mouth, and acetaldehyde is forming DNA adducts, which are known major players in carcinogenesis," said Balbo.

Provided by American Chemical Society

Many medications for elderly are prescribed inappropriately

Approximately one in five prescriptions to elderly people is inappropriate, according to a study published Aug. 22 in the open access journal PLOS ONE.

23 aug 2012--The authors of the study, led by Dedan Opondo of the Academic Medical Center in Amsterdam, conducted a systematic review of English-language studies of medication use in the elderly and found that the median rate of inappropriate prescriptions was 20.5%.

Some of the medications with the highest rates of inappropriate use were the antihistamine diphenhydramine, the antidepressant amitriptyline, and the pain reliever propoxyphene.

More information: Opondo D, Eslami S, Visscher S, de Rooij SE, Verheij R, et al. (2012) Inappropriateness of Medication Prescriptions to Elderly Patients in the Primary Care Setting: A Systematic Review. PLoS ONE 7(8): e43617.doi:10.1371/journal.pone.0043617

Provided by Public Library of Science

Common treatment for mild hypertension challenged

Doctors often prescribe drugs for people with mild high blood pressure with the hope of preventing cardiovascular disease (CVD). However, a new review from The Cochrane Library has found that this treatment does not reduce death rates, heart attacks or strokes.

22 aug 2012--Current guidelines in the U.S., Europe and Canada support drug treatment for people with mild hypertension, the majority of hypertension patients, even when they have no history of cardiovascular events. Consequences of such treatment include potential side effects, cost, and inconvenience.

“In people with no cardiovascular events and mild elevations in resting blood pressure ( 140 – 159/90 – 89 mmHg), it is not known whether the benefits of drug therapy exceed the harms,” said Diana Diao, M.D., resident physician at the University of British Columbia. To answer this concern, the research team combined findings from 4 clinical trials done between 1976 and 2000, which together included data on 8,912 study participants followed for up to 5 years.

The researchers found that 400 people with mild hypertension would have to be treated for five years to prevent one death and 128 people would have to be treated for five years to prevent one cardiovascular event, such as aheart attack. However, treated patients had a nine percent risk of an adverse effect that would force them to stop taking the prescribed drug.

These findings might prompt physicians to emphasize non-drug treatment approaches, including changes in diet and exercise, said the authors. They note that many physicians have been prescribing medications for patients with mild hypertension thinking that the approach is based on evidence from randomized clinical trials.

Luci Belnick, M.D., an Orlando-based physician with over 25 years experience questioned the new findings’ validity. She said that the patients should have been followed for longer than five years as that is a short time in terms of accumulating vascular damage due to hypertension; that the studies included concerned many drugs that are now seldom used; and that the studies included too few African-Americans, who have elevated risks of kidney damage and strokes from even mild hypertension.

“Before you diagnose and treat a patient, it’s important to make sure that they really have hypertension, that their particular patient group has a meaningful risk of hypertension complications, even long-term, and that you select a medication with a known benefit in that group,” she said.

More information: Diao D, Wright JM, Cundiff DK, Gueyffier F. Pharmacotherapy for mild hypertension. Cochrane Database of Systematic Reviews 2012, Issue 8. Art. No.: CD006742. DOI: 10.1002/14651858.CD006742.pub2

Provided by Center for Advanced Healing

Cocoa compounds may reduce blood pressure

Compounds in cocoa may help to reduce blood pressure, according to a new systematic review in The Cochrane Library. The researchers reviewed evidence from short-term trials in which participants were given dark chocolate or cocoa powder daily and found that their blood pressure dropped slightly compared to a control group.

21 aug 2012--Cocoa contains compounds called flavanols, thought to be responsible for the formation of nitric oxide in the body. Nitric oxide causes blood vessel walls to relax and open wider, thereby reducing blood pressure. The link between cocoa and blood pressure stems from the discovery that the indigenous people of San Blas Island in Central American, who drink flavanol-rich cocoa drinks every day, have normal blood pressure regardless of age. However, flavanol concentrations in cocoa and chocolate products vary according to cocoa processing procedures and types of chocolate, so it is difficult to establish the optimal dosage for an effect.

To investigate the effect of flavanols on blood pressure, the researchers reviewed data from trials in which people consumed dark chocolate or cocoa powder containing between 30-1080 mg of flavanols in 3-100 g of chocolate each day. Altogether, 856 people were involved in 20 trials lasting 2-8 weeks, or in one case, 18 weeks. Flavanol-rich chocolate or cocoa powder reduced blood pressure on average by 2-3 mm Hg.

"Although we don't yet have evidence for any sustained decrease in blood pressure, the small reduction we saw over the short term might complement other treatment options and might contribute to reducing the risk of cardiovascular disease," said lead researcher Karin Ried of the National Institute of Integrative Medicine in Melbourne, Australia, who worked with colleagues at the University of Adelaide.

In a subset of trials, when chocolate or cocoa powder was compared to flavanol-free-products as controls, the beneficial effects were more pronounced (3-4 mm Hg), whereas the researchers found no significant effect on blood pressure in the second subset with low-flavanol products as control. It is possible that low-flavanol products also have a small effect on blood pressure, so that it was harder to observe differences between high and low-flavanol products in these trials. However, results of these subsets of trials may have been influenced by trial length and blinding of participants, as trials using flavanol-free control products tended to be of shorter duration with participants knowing their allocated group.

"We'll also need to see long term trials, including effects on the risk of stroke and cardiovascular disease, before we can come to conclusions regarding clinical outcomes and potential side effects of long-term consumption," said Ried. "These trials should use flavanol-free products in the control groups to eliminate any potential effects of low-dose flavanol on blood pressure."

More information: Ried K, Sullivan TR, Fakler P, Frank OR, Stocks NP. Effect of cocoa on blood pressure. Cochrane Database of Systematic Reviews 2012, Issue 8. Art. No.: CD008893. DOI: 10.1002/14651858.CD008893.pub2

Provided by Wiley

Egg yolk consumption almost as bad as smoking when it comes to atherosclerosis

Newly published research led by Dr. David Spence of Western University, Canada, shows that eating egg yolks accelerates atherosclerosis in a manner similar to smoking cigarettes. Surveying more than 1200 patients, Dr. Spence found regular consumption of egg yolks is about two-thirds as bad as smoking when it comes to increased build-up of carotid plaque, a risk factor for stroke and heart attack. The research is published online in the journalAtherosclerosis.

20 aug 2012--Atherosclerosis, also called coronary artery disease, is a disorder of the arteries where plaques, aggravated by cholesterol, form on the inner arterial wall. Plaque rupture is the usual cause of most heart attacks and many strokes. The study looked at data from 1231 men and women, with a mean age of 61.5, who were patients attending vascular prevention clinics at London Health Sciences Centre's University Hospital. Ultrasound was used to establish a measurement of total plaque area and questionnaires were filled out regarding their lifestyle and medications including pack-years of smoking (number of packs per day of cigarettes times the number of years), and the number of egg yolks consumed per week times the number of years consumed (egg yolk-years).

The researchers found carotid plaque area increased linearly with age after age 40, but increased exponentially with pack-years of smoking and egg yolk-years. In other words, compared to age, both tobacco smoking and egg yolk consumption accelerate atherosclerosis. The study also found those eating three or more yolks a week had significantly more plaque area than those who ate two or fewer yolks per week.

"The mantra 'eggs can be part of a healthy diet for healthy people' has confused the issue. It has been known for a long time that a high cholesterol intake increases the risk of cardiovascular events, and egg yolks have a very high cholesterol content. In diabetics, an egg a day increases coronary risk by two to five-fold," says Dr. Spence, a Professor of Neurology at Western's Schulich School of Medicine & Dentistry and the Director of its Stroke Prevention and Atherosclerosis Research Centre (SPARC) at the Robarts Research Institute. "What we have shown is that with aging, plaque builds up gradually in the arteries of Canadians, and egg yolks make it build up faster - about two-thirds as much as smoking. In the long haul, egg yolks are not okay for most Canadians."

Dr. Spence adds the effect of egg yolk consumption over time on increasing the amount of plaque in the arteries was independent of sex, cholesterol, blood pressure, smoking, body mass index and diabetes. And while he says more research should be done to take in possible confounders such as exercise and waist circumference, he stresses that regular consumption of egg yolk should be avoided by persons at risk of cardiovascular disease.

Provided by University of Western Ontario

Mediterranean diet enriched with olive oil may protect bone

A study to be published in the Endocrine Society's Journal of Clinical Endocrinology and Metabolism (JCEM) shows consumption of a Mediterranean diet enriched with olive oil for two years is associated with increased serum osteocalcin concentrations, suggesting a protective effect on bone.

19 aug 2012--Age-related bone mass loss and decreased bone strength affects women and men alike are an important determinant of osteoporosis and fracture risk. Studies have shown that the incidence of osteoporosis in Europe is lower in theMediterranean basin. The traditional Mediterranean diet, rich in fruits and vegetables, with a high intake of olives and olive oil could be one of the environmental factors underlying this difference.

"The intake of olive oil has been related to the prevention of osteoporosis in experimental and in vitro models," said José Manuel Fernández-Real, MD, PhD, of Hospital Dr. Josep Trueta in Girona, Spain and lead author of the study. "This is the first randomized study which demonstrates that olive oil preserves bone, at least as inferred by circulating bone markers, in humans."

The participants in this study were 127 community-dwelling men aged 55 to 80 years randomly selected from one of the Prevencion con Dieta Mediterranea (PREDIMED) study centers who had at least two years of follow-up. The PREDIMED study is a large, parallel group, randomized, controlled trial aimed to assess the effect of the Mediterranean diet on the prevention of cardiovascular diseases.

For this study, subjects were elderly without prior cardiovascular disease but having a diagnosis of type 2 diabetes or harboring at least three cardiovascular risk factors, namely hypertension, dyslipidemia, or a family history of premature cardiovascular disease. Participants were randomly assigned to three intervention groups: Mediterranean diet with mixed nuts, Mediterranean diet with virgin olive oil, and a low-fat diet.

Biochemical measurements of osteocalcin, glucose, total cholesterol, HDL-cholesterol and triglycerides were performed at baseline and after two year follow-up on fasting blood samples. Researchers found that only consumption of the Mediterranean diet with olive oil was associated with a significant increase in the concentrations of total osteocalcin and other bone formation markers. There were also no significant changes in serum calcium in subjects taking olive oil whereas serum calcium decreased significantly in the other two groups.

"It's important to note that circulating osteocalcin was associated with preserved insulin secretion in subjects taking olive oil," added Fernández-Real. "Osteocalcin has also been described to increase insulin secretion in experimental models."

More information: The article, "A Mediterranean Diet Enriched with Olive Oil is Associated with Higher Serum Total Osteocalcin Levels in Elderly Men at High Cardiovascular Risk," will appear in the October 2012 issue of JCEM.

Provided by The Endocrine Society

Fit over-fifties are lowering heart disease odds

18 aug 2012-- Even a moderate increase in exercise when you are in your fifties can help your heart health according to a study published today by researchers from UCL Epidemiology and Public Health.

The study shows inflammation in the body – which is thought to contribute to heart disease – remains lower in people in the transition to retirement who embrace an active lifestyle, with at least 2.5 hours a week of moderate physical activity (enough to raise your heart rate), than in those who stay less active. This is great news for retirees, who often celebrate their new-found freedom with a whole range of activities, from gardening to DIY to countryside walks.

In the study, over 4,000 people from the Whitehall II cohort were quizzed on their exercise routines and had levels of inflammation measured to gauge their heart health over a ten year period.

Dr Mark Hamer, UCL Epidemiology and Public Health, said: “Previous studies looking at how exercise protects the heart have only been carried out for short periods of time. Our ten year study reveals for the first time the long-term effects of leading an active lifestyle on inflammation and heart disease.

“It’s great news that people who spring into retirement and become more active are actually making a big difference in helping their hearts grow old healthily.”

British Heart Foundation Senior Cardiac Nurse Maureen Talbot said: “Donning your gardening gloves, or picking up a paint brush, can still go a long way to help look after your heart health, as exercise can have a big impact on how well your heart ages.

“This research highlights the positive impact changing your exercise habits can have on the future of your heart health – and that it’s never too late to re-energise your life. However it’s important not to wait until you retire to get off the couch, as being active for life is a great way to keep your heart healthy.”

Jack Oldman, aged 87, who plays table tennis through the BHF Hearty Lives Hull project, said: “I play at my club twice a week and still compete in my local league. If I couldn’t play sport I don’t know what I‘d do.

“The worst thing you could do when you retire is to sit down and watch telly all day. I keep busy with sports and my vegetable patch and it seems to be keeping me going well - doctors have told me I’ve got a great heart for my age.”

More information: circ.ahajournals.o… 879.abstract

Provided by University College London

Resistance to dementia may run in the family

People who are free of dementia and have high levels of a protein that indicates the presence of inflammation have relatives who are more likely to avoid the disease as well, according to a new study published in the August 15, 2012, online issue of Neurology, the medical journal of the American Academy of Neurology.

17 aug 2012--"In very elderly people with good cognition, higher levels of C-reactive protein, which is related to inflammation, are associated with better memory," said study author Jeremy M. Silverman, PhD, with Mount Sinai School of Medicine in New York. "Our results found that the higher the level of this protein in the study participant, the lower the risk for dementia in their parents and siblings."

For the study, researchers identified 277 male veterans age 75 and older and free of dementia symptoms. They were given a test that measured levels of the protein. Next, the group was interviewed about 1,329 parents and siblings and whether they had dementia. A total of 40 relatives from 37 families had dementia. A secondary, independent group of 51 men age 85 and older with no dementia symptoms were given an interview about 202 relatives for dementia. Nine of the relatives had dementia.

Study investigators found that participants who had higher amounts of the protein were more than 30 percent less likely to have relatives with dementia. Similar results were found in the secondary group. Since the protein levels were not associated with years of education, marital status, occupation and physical activity, these factors could not account for the lower risks seen.

"This protein is related to worse cognition in younger elderly people. Thus, for very old people who remain cognitively healthy, those with a high protein level may be more resistant to dementia," said Silverman. "Our study shows that this protection may be passed on to immediate relatives."

Provided by American Academy of Neurology

Study adds to evidence daily aspirin linked to lower cancer mortality

A large new observational study finds more evidence of an association between daily aspirin use and modestly lower cancer mortality, but suggests any reduction may be smaller than that observed in a recent analysis. The study, appearing early online in the Journal of the National Cancer Institute (JNCI), provides additional support for a potential benefit of daily aspirin use for cancer mortality, but the authors say important questions remain about the size of the potential benefit.

16 aug 2012--A recent analysis pooling results from existing randomized trials of daily aspirin for prevention of vascular events found an estimated 37% reduction in cancer mortality among those using aspirin for five years or more. But uncertainty remains about how much daily aspirin use may lower cancer mortality, as the size of this pooled analysis was limited and two very large randomized trials of aspirin taken every other day found no effect on overall cancer mortality.

For the current study, American Cancer Society researchers led by Eric J. Jacobs, Ph.D., analyzed information from 100,139 predominantly elderly participants in the Cancer Prevention Study II Nutrition Cohort who reported aspirin use onquestionnaires, did not have cancer at the start of the study, and were followed for up to 11 years. They found daily aspirin use was associated with an estimated 16% lower overall risk of cancer mortality, both among people who reported taking aspirin daily for at least five years and among those who reported shorter term daily use. The lower overall cancer mortality was driven by about 40% lower mortality from cancers of the gastrointestinal tract (such as esophageal, stomach, and colorectal cancer) and about 12% lower mortality from cancers outside the gastrointestinal tract.

The reduction in cancer mortality observed in the current study is considerably smaller than the 37% reduction reported in the recent pooled analysis of randomized trials. The authors note that their study was observational, not randomized, and therefore could have underestimated or overestimated potential effects on cancer mortality if participants who took aspirin daily had different underlying risk factors for fatal cancer than those who did not. However, the study's large size is a strength in determining how much daily aspirin use might lower cancer mortality.

"Expert committees that develop clinical guidelines will consider the totality of evidence about aspirin's risks and benefits when guidelines for aspirin use are next updated," said Dr. Jacobs. "Although recent evidence about aspirin use and cancer is encouraging, it is still premature to recommend people start taking aspirin specifically to prevent cancer. Even low-dose aspirin can substantially increase the risk of serious gastrointestinal bleeding. Decisions about aspirin use should be made by balancing the risks against the benefits in the context of each individual's medical history. Any decision about daily aspirin use should be made only in consultation with a health care professional."

More information: Daily Aspirin Use and Cancer Mortality in a Large US Cohort, Eric J. Jacobs, Christina C. Newton, Susan M. Gapstur, Michael J. Thun. Journal of the National Cancer Institute; Published early online: August 10, 2012,DOI:10.1093/jnci/djs318

Provided by American Cancer Society

Thinking about giving, not receiving, motivates people to help others

 We’re often told to ‘count our blessings’ and be grateful for what we have. And research shows that doing so makes us happier. But will it actually change our behavior towards others?

15 aug 2012--A new study published in Psychological Science, a journal of the Association for Psychological Science, suggests that thinking about what we’ve given, rather than what we’ve received, may lead us to be more helpful toward others.

Researchers Adam Grant of The Wharton School of the University of Pennsylvania and Jane Dutton of The Ross School of Business at the University of Michigan wanted to understand how reflection, in the form of expressive writing, might influence prosocial behavior. They observed that when we reflect on what we’ve received from another person, we might feel an obligation to help that person, but the motivation to help doesn’t necessarily extend to other people. And reflecting on what we’ve received from others may even cause us to feel dependent and indebted.

The researchers wondered whether thinking about times when we have given to others might be more effective in promoting helping. They hypothesized that reflecting on giving could lead a person to see herself as a benefactor, strengthening her identity as a caring, helpful individual and motivating her to take action to benefit others.

In their first experiment, the researchers studied fundraisers whose job was to solicit alumni donations to support various programs at a university. The researchers randomly split the fundraisers into two groups: one group wrote journal entries about recent experiences of feeling grateful for receiving a benefit and the other group wrote journal entries about recent experiences in which they made a contribution that enabled other people to feel grateful.

Grant and Dutton then measured how many calls each fundraiser made per hour in the two weeks before and the two weeks after the week that they spent journaling. Because the fundraisers were paid a fixed hourly rate, with no fundraising goals or incentives, the number of calls they made reflected voluntary effort to help raise funds for the university.

As the researchers hypothesized, the fundraisers who wrote about giving for just two or three days increased their hourly calls by more than 29% in the following two weeks. The fundraisers who wrote about receiving, however, showed no change in the number hourly calls made.

In a second experiment, the researchers randomly assigned college students to one of three groups, requiring them to list three ways they had recently given help, list three ways they had recently received help, or list three different foods they had eaten in the last week.

When the participants came to the university’s behavioral lab a few weeks later to pick up their payment for participating in the study, they were given a form describing the March 11, 2011 earthquake and tsunami in Japan. On the form, the participants were asked whether they would like to donate any portion of their $5 payment to an earthquake relief fund.

Overall, 26% of the participants donated some amount of money. Similar to the results of the first experiment, participants who reflected on giving were significantly more likely to donate (46.15%) than those in either the beneficiary (21.43%) or control condition (13.33%).

Grant and Dutton believe that the findings from these two experiments have important real-world implications.

“Helping, giving, volunteering, and other actions undertaken to benefit others play a critical role in protecting health, promoting education, fighting poverty and hunger, and providing disaster relief,” the researchers write.

This new research suggests that self-reflection about giving can be a powerful tool for motivating helping and volunteering behaviors that benefit individuals and communities. When we reflect on positive experiences, it may be worthwhile to think about what we’ve given to others—not only what we’ve received.

Provided by Association for Psychological Science

Should doctors treat lack of exercise as a medical condition? Mayo expert says 'yes'

A sedentary lifestyle is a common cause of obesity, and excessive body weight and fat in turn are considered catalysts for diabetes, high blood pressure, joint damage and other serious health problems. But what if lack of exercise itself were treated as a medical condition? Mayo Clinic physiologist Michael Joyner, M.D., argues that it should be. His commentary is published this month in The Journal of Physiology.

14 aug 2012--Physical inactivity affects the health not only of many obese patients, but also people of normal weight, such as workers with desk jobs, patients immobilized for long periods after injuries or surgery, and women on extended bed rest during pregnancies, among others, Dr. Joyner says. Prolonged lack of exercise can cause the body to become deconditioned, with wide-ranging structural and metabolic changes: the heart rate may rise excessively during physical activity, bones and muscles atrophy, physical endurance wane, and blood volume decline.

When deconditioned people try to exercise, they may tire quickly and experience dizziness or other discomfort, then give up trying to exercise and find the problem gets worse rather than better.

"I would argue that physical inactivity is the root cause of many of the common problems that we have," Dr. Joyner says. "If we were to medicalize it, we could then develop a way, just like we've done for addiction, cigarettes and other things, to give people treatments, and lifelong treatments, that focus on behavioral modifications and physical activity. And then we can take public health measures, like we did for smoking, drunken driving and other things, to limit physical inactivity and promote physical activity."

Several chronic medical conditions are associated with poor capacity to exercise, including fibromyalgia, chronic fatigue syndrome and postural orthostatic tachycardia syndrome, better known as POTS, a syndrome marked by an excessive heart rate and flu-like symptoms when standing or a given level of exercise. Too often, medication rather than progressive exercise is prescribed, Dr. Joyner says.

Texas Health Presbyterian Hospital Dallas and University of Texas Southwestern Medical Center researchers found that three months of exercise training can reverse or improve many POTS symptoms, Dr. Joyner notes. That study offers hope for such patients and shows that physicians should consider prescribing carefully monitored exercise before medication, he says.

If physical inactivity were treated as a medical condition itself rather than simply a cause or byproduct of other medical conditions, physicians may become more aware of the value of prescribing supported exercise, and more formal rehabilitation programs that include cognitive and behavioral therapy would develop, Dr. Joyner says.

For those who have been sedentary and are trying to get into exercise, Dr. Joyner advises doing it slowly and progressively.

"You just don't jump right back into it and try to train for a marathon," he says. "Start off with achievable goals and do it in small bites."

There's no need to join a gym or get a personal trainer: build as much activity as possible into daily life. Even walking just 10 minutes three times a day can go a long way toward working up to the 150 minutes a week of moderate physical activity the typical adult needs, Dr. Joyner says.

Provided by Mayo Clinic

Why do older adults display more positive emotion? It might have to do with what they're looking at

Research has shown that older adults display more positive emotions and are quicker to regulate out of negative emotional states than younger adults. Given the declines in cognitive functioning and physical health that tend to come with age, we might expect that age would be associated with worse moods, not better ones.

09* auig 2012--So what explains older adults' positive mood regulation?

In a new article in the August issue of Current Directions in Psychological Science, a journal of the Association for Psychological Science, researcher Derek Isaacowitz of Northeastern University explores positive looking as one possible explanation: older adults may be better at regulating emotion because they tend to direct their eyes away from negative material or toward positive material.

Isaacowitz presents evidence indicating that, compared to younger adults, older adults prefer positive looking patterns and they show the most positive looking when they are in bad moods, even though this is when younger adults show the most negative looking.

Research conducted by Isaacowitz and colleagues indicates that there is actually a causal relationship between positive looking and mood: for adults with good attentional abilities, positive looking patterns can help to regulate their mood.

Although older adults prefer to focus on positive stimuli, the research shows that they aren't necessarily missing any salient or important information.

Provided by Association for Psychological Science

Delirium increases risk of developing new dementia eight-fold in older patients

Older people who have experienced episodes of delirium are significantly more likely to develop dementia, according to new research. The study is published in the journal Brain today.

09 aug 2012--When in hospital, older people sometimes become acutely confused and disorientated. This condition, known as delirium, affects at least 15 per cent of older people in hospitals and has long thought to be simply a temporary side effect of other illness (such as an infection, a reaction to a medication or an operation). However, the new research shows that episodes of delirium can have long term effects - increasing the future risk of dementia eight-fold.

Dr Daniel Davis, lead author of the paper from the University of Cambridge, said: "This means that delirium, or the acute causes of delirium, could be a newly discovered cause of dementia. This is important, because although delirium is extremely common, less than a quarter of cases are actually diagnosed in hospitals."

Scientists at the University of Cambridge and the University of Eastern Finland recruited 553 people aged 85 and over, and assessed their memory and thinking over 10 years. Of the patients who had previously experienced at least one episode of delirium prior to the study, 77 per cent also had dementia. In comparison, only 33 per cent of the patients who had no previous history of delirium had dementia. They also recorded the number of episodes of delirium throughout the study.

In people without pre-existing dementia, experiencing delirium resulted in an eight-fold increase in the risk of dementia. In individuals with existing dementia, delirium was associated with an acceleration of dementia severity, loss of independence in physical functioning, and higher mortality.

Dr Davis added: "Worsening confusion and disorientation in older persons does not attract much attention among clinical staff and many believe that delirium is simply an inconvenient consequence of illness. However, this research suggests the possibility that delirium, or the problems giving rise to delirium, may be actually causing brain damage.

"Because some delirium is preventable, it is plausible that delirium prevention may lead to dementia prevention. We now urgently need to test if better delirium care can prevent dementia, or prevent further decline in patients who already have dementia."

The Wellcome Trust-funded study also found, for the first time, that there may be differences in the brains of people who have had delirium compared to those without delirium. Dementia is known to result from a several different pathological processes (e.g. accumulation of abnormal proteins, or blockages in blood vessels). However, this study found that when individuals had both delirium and dementia, these standard neuropathological markers were not enough to explain the dementia. This raises the important possibility that dementia occurring after delirium had alternative pathological processes causing the dementia.

Professor Clive Ballard, Director of Research at Alzheimer's Society, said: "Scientists have believed there could be a link between delirium and dementia for many years. This robust study adds weight to this knowledge. With hospitalisation thought to be a cause of delirium, it's vital that healthcare professionals recognise the potential long term impact of delirium and are aware that older people who experience episodes could be susceptible to developing dementia."

Dr Karin Neufeld, President-Elect of the American Delirium Society and Director of General Hospital Psychiatry at Johns Hopkins Hospital, commented: "Research on delirium has repeatedly highlighted the association between cognitive impairment, and dementia and the development of delirium in the hospital setting in elderly individuals.

"This important research suggests that preventing delirium might be an important way to decrease the onset and progression of dementia in some people. The implication is that we, as healthcare professionals, need to redouble our efforts to detect and prevent delirium in hospitalised patients."

More information: The paper 'Delirium is a strong risk factor for dementia in the oldest old: a population-based cohort study' will be published in the 09 August 2012 edition of Brain.

Provided by University of Cambridge

Balance and strength training can prevent falls in older people

Balance and strength training is known to reduce falls in older adults. However, less than 10% of older people routinely engage in strength training and it is likely that this is much lower for activities that challenge balance.

08 aug 2012--It has been suggested that integrating exercise into everyday activities may help people stick to it, but this approach has never been investigated in frail older people at risk of falls.

So a team of researchers at the University of Sydney designed and tested the Lifestyle integrated Functional Exercise (LiFE) programme, which involves embedding balance and lower limb strength training into daily routines, such as walking, stepping over objects and moving from sitting to standing.

They then compared this approach with a structured exercise programme (performed three times a week using ankle cuff weights) and gentle 'sham' exercises that acted as the study control.

They recruited 317 men and women aged 70 or older, living in the community and having two or more falls, or one injurious fall, in the past year.

Participants were split into the three treatment arms and recorded any falls over 12 months using daily calendars. Other measures like static and dynamic balance, ankle, knee and hip strength, daily living activities, and quality of life were also measured recognised scales.

They found a significant (31%) reduction in the rate of falls for participants in the LiFE programme compared with the control group. The overall incidence of falls in the LiFE programme was 1.66 per person years, compared with 1.90 in the structured programme and 2.28 in the control group.

There was a non-significant reduction in the rate of falls for participants in the structured programme compared to the control group.

Compared with control patients, LiFE participants showed improvements in both static and dynamic balance, ankle strength, and in function and participation in daily life, suggesting that this programme improves both fall risk and frailty.

Adherence was significantly better in the LiFE programme and control group compared with the structured exercise programme.

The authors conclude that the LiFE programme "provides an alternative to traditional exercise for older people to reduce falls, to improve function in doing activities and to enhance participation in daily life."

In an accompanying editorial, Professor Meg Morris from the University of Melbourne says that for fall prevention programmes in older people to be effective, "therapeutic exercises, education, and physical activities need to be sustainable, enjoyable, and effective over the long term."

She adds: "The belief that falls should be accepted and tolerated as part of the ageing process is a myth that needs dispelling. Many falls can and should be prevented."

More information: 
www.bmj.com/cgi/do… 36/bmj.e4547 
www.bmj.com/cgi/do… 36/bmj.e4919

Provided by British Medical Journal

Infection risk up for seniors with rheumatoid arthritis

Elderly adults with rheumatoid arthritis have a considerable risk of serious infection, with antirheumatic drug use increasing the risk, according to a study published online July 25 in Arthritis Care & Research.

07 aug 2012-- Elderly adults with rheumatoid arthritis have a considerable risk of serious infection, with antirheumatic drug use increasing the risk, according to a study published online July 25 in Arthritis Care & Research.

Jessica Widdifield, Ph.D., of University of Toronto, and associates examined the risk and risk factors for serious infection in a cohort of 86,039 patients with rheumatoid arthritis, aged 66 years or older, from Ontario health administrative data across 1992 to 2010.

The researchers identified 20,575 infections, for a rate of 46.4 per 1,000 person-years, with respiratory infection, herpes zoster, and skin/soft tissue infection being the most common. Factors that correlated with infection included higher comorbidity, rural residence, markers of disease severity, and history of prior infection. There was a several-fold increase in infection noted with the use of anti-tumor necrosis factor agents and disease modifying antirheumatic drugs (adjusted odds ratio ranging from 1.2 to 3.5), with the greatest effect seen for glucocorticosteroids (odds ratio ranging from 4.0 at low doses to 7.6 at high doses).

"While the relative risk of serious infection was elevated across all antirheumatic treatments, the message should not be that non-use is the way to reduce infection risk in seniors," the authors write. "Rather, seniors with rheumatoidarthritis have significant morbidity related to serious infections and require enhanced vigilance in the management of their pharmacotherapy and comorbidities."

More information: Abstract 

Clinicians can unintentionally prompt nocebo effect

The nocebo effect, or induction of a symptom perceived as negative by sham treatment and/or the suggestion of negative expectation, may arise from suggestions by doctors and nurses, according to a study published in Deutsches Ärzteblatt International.

05 aug 2012-- The nocebo effect, or induction of a symptom perceived as negative by sham treatment and/or the suggestion of negative expectation, may arise from suggestions by doctors and nurses, according to a study published in Deutsches Ärzteblatt International.

Winfried Häuser, M.D., from Technische Universität München, and colleagues conducted a literature review to investigate nocebo phenomena in clinical practice.

The researchers found that the underlying mechanisms behind nocebo responses included learning by Pavlovian conditioning and reaction to expectations induced by verbal information or suggestion. Unintentional negative suggestion on the part of physicians and nurses was found to trigger nocebo responses. The patients' negative expectations, along with being given information about possible complications, increased the likelihood of adverse effects. A nocebo effect was found to cause adverse events under treatment with medications.

"Physicians face an ethical dilemma, as they are required not just to inform patients of the potential complications of treatment, but also to minimize the likelihood of these complications, i.e., to avoid inducing them through the potential nocebo effect of thorough patient information," the authors write. "Possible ways out of the dilemma include emphasizing the fact that the proposed treatment is usually well tolerated, or else getting the patient's permission to inform less than fully about its possible side effects."

Two authors disclosed financial ties to the pharmaceutical industry.

More information: Full Text

Aurka-to-p53 signaling: A link between stem cell regulation and cancer

Researchers at Mount Sinai School of Medicine, the University of Manchester, and the MD Anderson Cancer Center have found a new role for an oncogenic signaling pathway in embryonic stem cell (ESC) self-renewal and in reprogramming adult cells into an ESC-state, which will aid in the development of future cancer therapies.

04 aug 2012--The findings promote the understanding of the self-renewal mechanism in embryonic stem cells and provide insight into the role of Aurka, an oncoprotein that is amplified in several human cancers. The research is published in the August 3rd issue of the journal Cell Stem Cell.

Embryonic stem cells (ESCs) and, more recently, induced pluripotent stem cells (iPSCs) hold great promise for biomedicine as a major source of differentiated cells for developing new ways to study disease etiology, the development of more effective drugs and diagnostic methodologies, and for future transplantation-based therapies. Cancer cells and ESCs can both proliferate indefinitely and show some similarities.

The researchers, a team at Mount Sinai School of Medicine led by Ihor Lemischka, PhD, Director of the Black Family Stem Cell Institute, in collaboration with groups at the University of Manchester and the MD Anderson Cancer Center, applied a functional genomics strategy and identified the protein kinase Aurora A (Aurka) as an essential component of ESC function.

These studies showed that Aurka functions by inactivating the well-known tumor suppressor gene p53. The p53 protein acts as the "guardian of the genome" and mutations as well as deletions of the p53 gene are associated with a wide range of tumors.

In the absence of Aurka, up-regulated p53 signaling causes ESCs to differentiate and thus lose their stem cell state. By connecting the loss of Aurka to re-activation of p53 it was shown that Aurka adds a phosphate group (a process called phosphorylation) to a single amino acid in p53, thus shifting ESCs from a differentiation-prone state to self-renewal.

"These studies are exciting not only from a basic science point-of-view, but also because they suggest that stem cell research may impact the development of novel treatments for cancer. Conversely, cancer research may facilitate the realization of the biomedical potential of stem cells," said Dr. Lemischka.

Interestingly, in contrast to the low p53 levels in mature cells, this protein is highly expressed in ESCs and iPSCs. In addition, p53 has a limited role in promoting apoptosis – the process of programmed cell death – and cell cycle inhibition in pluripotent cells. The present findings provide a possible explanation to an unsolved mystery.

The study will aid in developing future cancer therapies and support the science underlying multiple clinical trials using Aurka inhibitors that are currently used to treat cancers.

Provided by The Mount Sinai Hospital

Alzheimer's cognitive decline slows in advanced age

The greatest risk factor for Alzheimer's disease (AD) is advancing age. By age 85, the likelihood of developing the dreaded neurological disorder is roughly 50 percent. But researchers at the University of California, San Diego School of Medicine say AD hits hardest among the "younger elderly" – people in their 60s and 70s – who show faster rates of brain tissue loss and cognitive decline than AD patients 80 years and older.

03 aug 2012--The findings, reported online in the August 2, 2012 issue of the journal PLOS One, have profound implications for both diagnosing AD – which currently afflicts an estimated 5.6 million Americans, a number projected to triple by 2050 – and efforts to find new treatments. There is no cure for AD and existing therapies do not slow or stop disease progression.

"One of the key features for the clinical determination of AD is its relentless progressive course," said Dominic Holland, PhD, a researcher at the Department of Neurosciences at UC San Diego and the study's first author. "Patients typically show marked deterioration year after year. If older patients are not showing the same deterioration from one year to the next, doctors may be hesitant to diagnose AD, and thus these patients may not receive appropriate care, which can be very important for their quality of life."

Holland and colleagues used imaging and biomarker data from participants in the Alzheimer's Disease Neuroimaging Initiative, a multi-institution effort coordinated at UC San Diego. They examined 723 people, ages 65 to 90 years, who were categorized as either cognitively normal, with mild cognitive impairment (an intermediate stage between normal, age-related cognitive decline and dementia) or suffering from full-blown AD.

"We found that younger elderly show higher rates of cognitive decline and faster rates of tissue loss in brain regions that are vulnerable during the early stages of AD," said Holland. "Additionally cerebrospinal fluid biomarker levels indicate a greater disease burden in younger than in older individuals."

Holland said it's not clear why AD is more aggressive among younger elderly.

"It may be that patients who show onset of dementia at an older age, and are declining slowly, have been declining at that rate for a long time," said co-author Linda McEvoy, PhD, associate professor of radiology. "But because of cognitive reserve or other still-unknown factors that provide 'resistance' against brain damage, clinical symptoms do not manifest till later age."

Another possibility, according to Holland, is that older patients may be suffering from mixed dementia – a combination of AD pathology and other neurological conditions. These patients might withstand the effects of AD until other adverse factors, such as brain lesions caused by cerebrovascular disease, take hold. At the moment, AD can only be diagnosed definitively by an autopsy. "So we do not yet know the underlying neuropathology of participants in this study," Holland said.

Clinical trials to find new treatments for AD may be impacted by the differing rates, researchers said. "Our results show that if clinical trials of candidate therapies predominately enroll older elderly, who show slower rates of change over time, the ability of a therapy to successfully slow disease progression may not be recognized, leading to failure of the clinical trial," said Holland. "Thus, it's critical to take into account age as a factor when enrolling subjects for AD clinical trials."

The obvious downside of the findings is that younger patients with AD lose more of their productive years to the disease, Holland noted. "The good news in all of this is that our results indicate those who survive into the later years before showing symptoms of AD will experience a less aggressive form of the disease."

Provided by University of California - San Diego

Autoantibodies damage blood vessels in the brain -- important factor in development of dementia

The presence of specific autoantibodies of the immune system is associated with blood vessel damage in the brain. These findings were made by by Marion Bimmler, a graduate engineer of medical laboratory diagnostics at the Max Delbrück Center for Molecular Medicine Berlin-Buch and Dr. Peter Karczewski of the biotech company E.R.D.E.-AAK-Diagnostik GmbH in studies on a rat model. Their results suggest that autoimmune mechanisms play a significant role in the pathogenesis and progression of Alzheimer’s and vascular dementia. The MR Angiography shows that antibodies damage blood vessels in the brain of rats (see arrow in image B). Eight months after the rats were administered an antibody against a surface protein (alpha1-adrenergic receptor) in the vascular cells, the blood vessels are hardly recognizable, because the blood flow has been interrupted. Image A shows the blood vessels (white) in the brain of healthy animals with no antibodies. These findings are important for understanding the pathogenesis and progression of Alzheimer’s disease and vascular dementia.

The presence of specific autoantibodies of the immune system is associated with blood vessel damage in the brain. These findings were made by Marion Bimmler, a graduate engineer of medical laboratory diagnostics at the Max Delbrück Center for Molecular Medicine Berlin-Buch and Dr. Peter Karczewski of the biotech company E.R.D.E.-AAK-Diagnostik GmbH in studies on a rat model. The researchers' results suggest that autoimmune mechanisms play a significant role in the pathogenesis and progression of Alzheimer's and vascular dementia.

02 aug 2012--Antibodies are the defense molecules of the body's immune system against foreign invaders. If the antibodies cease to distinguish between "foreign" and "self", they attack the cells of the own body, and are thus referred to as autoantibodies. These can trigger autoimmune diseases. Using MR angiography and other methods, Marion Bimmler and her colleagues have now shown that the autoantibodies bind to specific surface proteins (alpha1 andrenergic receptors) of vascular cells and thereby damage the blood vessels of the brain. The reason: The autoantibodies generate a continual stimulation of the receptor and at the same time trigger an increase in intracellular calcium ion levels. As a result, the blood vessel walls thicken, and blood flow to the brain is disturbed.

First Encouraging Results after Removal of Autoantibodies by Immunoadsorption

In earlier studies, Marion Bimmler and her research team examined blood samples of patients with Alzheimer's or vascular dementia and showed that half of them had comparable autoantibodies. A first clinical trial together with Charité – Universitätsmedizin Berlin is currently ongoing with a collective of patients with Alzheimer's or vascular dementia. The patients were divided into two groups – a small group whose autoantibodies were removed from the blood via immunoadsorption and a control group that did not receive this treatment. Until now, over an observation period of 6 and subsequently 12 months, the patient group who had undergone immunoadsorption improved in their memory performance and in their ability to cope with their everyday lives. In contrast, the condition of the patients who did not receive immunoadsorption treatment and continued to have autoantibodies in their blood deteriorated dramatically. Now the researchers are planning further clinical trials with larger numbers of patients.

More information: Antibodies to the 1-Adrenergic Receptor Cause Vascular Impairments in Rat Brain as Demonstrated by Magnetic Resonance Angiography, PloS ONE, doi:10.1371/journal.pone.0041602

Provided by Helmholtz Association of German Research Centres

What would happen without PSA testing?

Eliminating the PSA test to screen for prostate cancer would be taking a big step backwards and would likely result in rising numbers of men with metastatic cancer at the time of diagnosis, predicted a University of Rochester Medical Center analysis published in the journal, Cancer.

01 aug 2012--The URMC study suggests that the prostate-specific antigen (PSA) test and early detection may prevent up to 17,000 cases of metastatic prostate cancer a year. Data shows, in fact, that if age-specific pre-PSA era incidence rates were to occur in the present day, the number of men whose cancer had already spread at diagnosis would be three times greater.

"Our findings are very important in light of the recent controversy over PSA testing," said Edward M. Messing, M.D., study co-author, chair of Urology at URMC, and president of the Society of Urologic Oncology. "Yes, there are trade-offs associated with the PSA test and many factors influence the disease outcome. And yet our data are very clear: not doing the PSA test will result in many men presenting with far more advanced prostate cancer. And almost all men with metastasis at diagnosis will die from prostate cancer."

Prostate cancer usually occurs in older men, and is the second leading cause of cancer death in the male population. In 2012 an estimated 241,740 new cases will be diagnosed and 28,000 deaths will occur. Prognosis depends on whether the cancer has spread outside the prostate gland, and the degree to which the cancer cells are abnormal.

In 2011 the U.S. Preventative Services Task Force recommended against PSA screening in all men, prompting criticism from the medical community. The government panel reviewed scientific evidence and concluded that screening has little or no benefit, or that the harms of early detection outweigh the benefits. One major concern, for example, was that doctors are screening for, finding, and treating non-aggressive cancers that might have remained quiet, causing patients to needlessly suffer from serious treatment side effects such as incontinence or erectile dysfunction.

The U.S. Task Force recommendations against screening caused some confusion, and in response, a special panel of experts from the American Society of Clinical Oncology this month issued its own opinion. The ASCO panel decided that for men with a life expectancy of less than 10 years, general screening with the PSA test should be discouraged. For men with a longer life expectancy, though, it is recommended that physicians discuss with patients whether the PSA test is appropriate for them.

Messing's study looked back at the era prior to 1986, when no one was routinely screened for prostate cancer with a PSA test. To analyze the effect of screening on stage of disease at initial diagnosis, Messing and Emelian Scosyrev, Ph.D., assistant professor of Urology, reviewed data from 1983 to 2008 kept by the nation's largest cancer registry, Surveillance, Epidemiology and End-Results or SEER. They compared SEER data from the pre-PSA era (1983 to '85) to the current era of widespread PSA use (2006 to 2008), and adjusted for age, race, and geographic variations in the United States population.

Approximately 8,000 cases of prostate cancer with metastases at initial presentation occurred in the U.S. in 2008. Using a mathematical model to estimate the number of metastatic cases that would be expected to occur in 2008 in the absence of PSA screening, Scosyrev and Messing predicted the number would be 25,000.

The authors emphasized the study was observational and has some limitations. In particular it is impossible to know if the PSA test and early detection is solely responsible for the fewer cases of metastasis at diagnosis in 2008.

The potential lead-time of screening also should be considered when interpreting the study findings, Scosyrev said. For some people an earlier stage of cancer at diagnosis may not always translate into better survival. This may happen, for example, in cases when the cancer had already metastasized at the time of screening, but the metastasis remained undetected.

In general, however, the study concluded that massive screening and PSA awareness efforts during the 1990s and early 2000s resulted in substantial shifts toward earlier-stage disease and fewer cases of metastases at diagnosis.

In the United States over the most recent 20 years, Messing said, prostate cancer death rates have been reduced by close to 40%. This occurred without substantial changes in how men were treated (via surgery and radiation therapy). Other models published in the scientific literature have suggested that more than 50% of this reduction is due to early detection.

More information: “Prostate-specific antigen screening for prostate cancer and the risk of overt metastatic disease at presentation: analysis of trends over time.” Emil Scosyrev, Guan Wu, Supriya Mohile, and Edward Messing. CANCER; Published Online: July 30, 2012 (DOI: 10.1002/cncr.27503).

Provided by Wiley