Study shows Alzheimer's disease may spread by 'jumping' from one brain region to another

For decades, researchers have debated whether Alzheimer's disease starts independently in vulnerable brain regions at different times, or if it begins in one region and then spreads to neuroanatomically connected areas. A new study by Columbia University Medical Center (CUMC) researchers strongly supports the latter, demonstrating that abnormal tau protein, a key feature of the neurofibrillary tangles seen in the brains of those with Alzheimer's, propagates along linked brain circuits, "jumping" from neuron to neuron.

02 feb 2012--The findings, published today in the online journal PloS One, open new opportunities for gaining a greater understanding of Alzheimer's disease and other neurological diseases and for developing therapies to halt its progression, according to senior author Karen E. Duff, PhD, professor of pathology (in psychiatry and in the Taub Institute for Research on Alzheimer's Disease and the Aging Brain) at CUMC and at the New York State Psychiatric Institute.

Alzheimer's disease, the most common form of dementia, is characterized by the accumulation of plaques (composed of amyloid-beta protein) and fibrous tangles (composed of abnormal tau) in brain cells called neurons. Postmortem studies of human brains and neuroimaging studies have suggested that the disease, especially the neurofibrillary tangle pathology, begins in the entorhinal cortex, which plays a key role in memory. Then as Alzheimer's progresses, the disease appears in anatomically linked higher brain regions.

"Earlier research, including functional MRI studies in humans, have also supported this pattern of spread," said study coauthor Scott A. Small, MD, professor of neurology in the Sergievsky Center and in the Taub Institute for Research on Alzheimer's Disease and the Aging Brain at CUMC. "But these various findings do not definitively show that Alzheimer's spreads directly from one brain region to another."

To look further into this issue, the CUMC researchers developed a novel transgenic mouse in which the gene for abnormal human tau is expressed predominantly in the entorhinal cortex. The brains of the mice were analyzed at different time points over 22 months to map the spread of abnormal tau protein.

The researchers found that as the mice aged, the abnormal human tau spread along a linked anatomical pathway, from the entorhinal cortex to the hippocampus to the neocortex. "This pattern very much follows the staging that we see at the earliest stages of human Alzheimer's disease," said Dr. Duff.

The researchers also found evidence suggesting that the abnormal tau protein was moving from neuron to neuron across synapses, the junctions that these cells use to communicate with each other.

The findings of the study have important implications for therapy.

"If, as our data suggest, tau pathology starts in the entorhinal cortex and emanates from there, the most effective approach may be to treat Alzheimer's the way we treat cancer—through early detection and treatment, before it has a chance to spread," said Dr. Small. "The best way to cure Alzheimer's may be to identify and treat it when it is just beginning, to halt progression. It is during this early stage that the disease will be most amenable to treatment. That is the exciting clinical promise down the road."

Treatments could conceivably target tau during it extracellular phase, as it moves from cell to cell, added Dr. Duff. "If we can find the mechanism by which tau spreads from one cell to another, we could potentially stop it from jumping across the synapses — perhaps using some type of immunotherapy. This would prevent the disease from spreading to other regions of the brain, which is associated with more severe dementia."

More information: The paper is titled, "Trans-synaptic Spread of Tau Pathology in vivo."

Provided by Columbia University Medical Center

Women report feeling pain more intensely than men: study

Women report more-intense pain than men in virtually every disease category, according to Stanford University School of Medicine investigators who mined a huge collection of electronic medical records to establish the broad gender difference to a high level of statistical significance.

01 feb 2012--Their study, to be published online Jan. 23 in the Journal of Pain, suggests that stronger efforts should be made to recruit women subjects in population and clinical studies in order to find out why this gender difference exists.

The study also shows the value of EMR data mining for research purposes. Using a novel database designed especially for research, the Stanford scientists examined more than 160,000 pain scores reported for more than 72,000 adult patients. From these, they extracted cases where disease-associated pain was first reported, and then stratified these findings by disease and gender.

"None of these data were initially collected for research, but this study shows that we can use it in that capacity," said Atul Butte, MD, PhD, the study's senior author.

The medical literature contains numerous reports indicating that women report more pain than men for one or another particular disease, noted Butte, a professor of systems medicine in pediatrics. "We're certainly not the first to find differences in pain among men and women. But we focused on pain intensity, whereas most previous studies have looked at prevalence: the percentage of men vs. women with a particular clinical problem who are in pain. To the best of our knowledge, this is the first-ever systematic use of data from electronic medical records to examine pain on this large a scale, or across such a broad range of diseases."

The study's first authors were Butte's graduate student Linda Liu and postdoctoral scholar David Ruau, PhD, who splits his time between Butte's group and that of co-author Martin Angst, MD, professor of anesthesia. David Clark, MD, PhD, a professor of anesthesia, was another co-author.

Electronic medical records are deployed in about 1-2 percent of hospitals now, but that should approach 100 percent within the next few years as the United States continues to move toward EMRs, Butte said. Thus, large-scale research using clinically collected data will become increasingly feasible.

In this case, the scientists tapped an existing data archive that has been designed specifically for ease of research: the Stanford Translational Research Integrated Database Environment, or STRIDE. Pioneered by the medical school's chief information officer, Henry Lowe, MD (who is also an associate professor of systems medicine in pediatrics and director of Stanford's Center for Clinical Informatics), STRIDE aggregates clinical data on patients cared for at Stanford Hospital & Clinics and Lucile Packard Children's Hospital, making this data searchable for approved research projects.

Butte's team selected only adult records and looked for gender-related differences in pain intensity as reported on 1-to-10 scales, in which a zero stands for "no pain" and 10 for "worst imaginable." Their search algorithm combed through de-identified EMR data for more than 72,000 patients, and came up with more than 160,000 instances, ranging across some 250 different disease categories, in which a pain score had been reported.

"If someone's reporting that they're in pain, they're probably going to be given medication, which might reduce any subsequently measured pain score," said Butte. To get pain estimates that weren't as confounded by subsequent pain-relief medications or procedures, his group analyzed only the first pain-intensity score reported by a patient per encounter with a hospital-associated health professional.

The search identified 47 separate diagnostic categories for which there were more than 40 pain reports for each gender. The sample included more than 11,000 individual adult patients, of which 56 percent were women and 51 percent of them white. The researchers were able to further analyze these 47 categories by condensing them into 16 disease clusters: "musculoskeletal and connective tissue" (in which the biggest gender differences in reported pain intensity were observed), "circulatory" and so forth.

"We saw higher pain scores for female patients practically across the board," said Butte. Those reported differences were not only statistically significant, but also clinically significant. "In many cases, the reported difference approached a full point on the 1-to-10 scale. How big is that? A pain-score improvement of one point is what clinical researchers view as indicating that a pain medication is working."

While the overall results tended to confirm previous clinical findings — for example, that female fibromyalgia or migraine patients report more pain than their male counterparts — the search also unearthed previously unreported gender differences in pain intensity for particular diseases, for example acute sinusitis and "cervical spine disorders," more commonly known as neck pain.

The study's results come with a few caveats. First, the investigators made the assumption that patients' pain hadn't already been treated—for example, that they hadn't already self-medicated with over-the-counter painkillers — by the time they showed up in the emergency room, doctor's office or neighborhood health clinic (or, equivalently, that the men and women were equally likely to have done so).

Other possible confounders include the setting in which pain was reported, Butte said. "Will an 18-year-old male report the same pain intensity with or without his mom present, or in the presence of a male vs. a female nurse? We can't be sure." But the sheer size of the study probably washes these concerns out at least to some extent, he said.

The third caveat is perhaps the most controversial. "It's still not clear if women actually feel more pain than men do," said Butte. "But they're certainly reporting more pain than men do. We don't know why. But it's not just a few diseases here and there, it's a bunch of them — in fact, it may well turn out to be all of them. No matter what the disease, women appear to report more-intense levels of pain than men do."

To get to the bottom of this, Butte's team plans to search EMRs to see if they can find some objective measurement — an already commonly measured blood-test variable, for instance — that correlates highly with reported pain. "We want to find a biomarker for pain," he said.

Provided by Stanford University Medical Center

Two-arm blood pressure check indicator for risk from heart disease or death

A systematic review and meta-analysis carried out by researchers at the University of Exeter Peninsula College of Medicine and Dentistry (PCMD) has found that differences in systolic blood pressure between arms could be a useful indicator of the likelihood of vascular risk and death.

31 jan 2012--The findings add support to the calls for both-arm blood pressure checks to be performed as standard.

The review is published in The Lancet online today and the study is supported by the Royal College of General Practitioners, the South West GP Trust and the National Institute for Health Research Peninsula Collaboration for Leadership in Applied Health Research and Care.

The study reviewed 28 papers covering difference in systolic blood pressure between arms. It found significant evidence to suggest that a difference of 15mm Hg or more was associated with increased risk of: peripheral vascular disease (the narrowing and hardening of the arteries that supply blood to the legs and feet); pre-existing cerebrovascular disease (affecting the blood supply to the brain and often associated with cognitive issues such as dementia); and mortality, both as a result of cardiovascular problems and generally.

The risk of peripheral vascular disease was also increased at a difference of 10mm Hg or more.

The findings further support the need for both-arm blood pressure checks to be the norm – not least because most cases are 'clinically silent' and such checks would better identify those at risk.

Dr. Christopher Clark, Clinical Academic Fellow at PCMD and a GP in Witheridge, Devon, led the study. He said: "We set out to investigate whether there was an association between differences in systolic blood pressure between arms and vascular disease and mortality. Our findings indicate a strong association, and that differences of 10mm Hg or 15mm Hg or more might help to identify patients who are at risk and who need further vascular assessment. More research is required in order to transfer our findings to clinical practice, but in the meanwhile we will be flagging the results of our review to the UK Vascular Check programme."

More information: Paper online: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61710-8/abstract

Provided by The Peninsula College of Medicine and Dentistry

Study: Men at higher risk for mild memory loss than women

Men may be at higher risk of experiencing mild cognitive impairment (MCI), or the stage of mild memory loss that occurs between normal aging and dementia, than women, according to a study published in the January 25, 2012, online issue of Neurology.

30 jan 2012--"These results are surprising, given that women generally have higher rates of dementia than men," said study author R.O. (Rosebud) Roberts, MB ChB, MS, of the Mayo Clinic in Rochester, Minn., and a member of the American Academy of Neurology. "The risk of MCI in men and women combined was high in this age group of elderly persons. This is disturbing given that people are living longer, and MCI may have a large impact on health care costs if increased efforts at prevention are not used to reduce the risk."

For the study, a group of 1,450 people from Olmsted County, Minn., between the ages of 70 and 89 and free of dementia at enrollment underwent memory testing every 15 months for an average of three years. Participants were also interviewed about their memory by medical professionals. By the end of the study period, 296 people had developed MCI.

The study found that the number of new cases of dementia per year was higher in men, at 72 per 1,000 people compared to 57 per 1,000 people in women and 64 per 1,000 people in men and women combined. MCI with memory loss present was more common at 38 per 1,000 people than MCI where memory loss was not present, which affected 15 per 1,000 people. Those who had less education or were not married also had higher rates of MCI.

"Our study suggests that risk factors for mild cognitive impairment should be studied separately in men and women," said Roberts.

Another finding of interest in the study showed that among people who were newly diagnosed with MCI, 12 percent per year were later diagnosed at least once with no MCI, or reverted back to what was considered "cognitively normal." Roberts said the majority of people with MCI, about 88 percent per year, continue to have MCI or progress to dementia.

Provided by American Academy of Neurology

Food fried in olive or sunflower oil is not linked to heart disease

Eating food fried in olive or sunflower oil is not linked to heart disease or premature death, finds a paper published in the British Medical Journal today.

29 jan 2012--The authors stress, however, that their study took place in Spain, a Mediterranean country where olive or sunflower oil is used for frying and their results would probably not be the same in another country where solid and re-used oils were used for frying.

In Western countries, frying is one of the most common methods of cooking. When food is fried it becomes more calorific because the food absorbs the fat of the oils.

While eating lots of fried food can increase some heart disease risk factors such as high blood pressure, high cholesterol and obesity, a link between fried food and heart disease has not been fully investigated.

So the authors, led by Professor Pilar Guallar-Castillón from Autonomous University of Madrid, surveyed the cooking methods of 40,757 adults aged 29 to 69 over an 11-year period. None of the participants had heart disease when the study began.

Trained interviewers asked participants about their diet and cooking methods. Fried food was defined as food for which frying was the only cooking method used. Questions were also asked about whether food was fried, battered, crumbed or sautéed.

The participants' diet was divided into ranges of fried food consumption, the first quartile related to the lowest amount of fried food consumed and the fourth indicated the highest amount.

During the follow-up there were 606 events linked to heart disease and 1,134 deaths.

The authors conclude: "In a Mediterranean country where olive and sunflower oils are the most commonly used fats for frying, and where large amounts of fried foods are consumed both at and away from home, no association was observed between fried food consumption and the risk of coronary heart disease or death."

In an accompanying editorial, Professor Michael Leitzmann from the University of Regensburg in Germany, says the study explodes the myth that "frying food is generally bad for the heart" but stresses that this "does not mean that frequent meals of fish and chips will have no health consequences." He adds that specific aspects of frying food are relevant, such as the type of oil used.

Provided by British Medical Journal

Study finds exercise reduces anxiety symptoms in women

Approximately 3 percent of the U.S. population suffers from excessive, uncontrollable worry that reduces their health and quality of life. The condition, known as Generalized Anxiety Disorder, is difficult to overcome and is accompanied by a host of physical symptoms, including fatigue, muscle tension, irritability and poor sleep. However, a new University of Georgia study shows that regular exercise can significantly reduce anxiety symptoms in patients with GAD.

28 jan 2011--In a study published online in the Nov. 22 edition of Psychotherapy and Psychosomatics, researchers randomly assigned 30 sedentary women, ages 18-37 who were diagnosed with GAD, to either a control group or six weeks of strength or aerobic exercise training. Women in the exercise conditions completed two weekly sessions of either weight lifting or leg cycling exercise. Remission of the disorder, determined by psychologists who were unaware of the treatment each client received, was higher among exercisers and best among those who performed weight lifting exercise. Worry symptoms, the primary problem among individuals with GAD, were significantly reduced among the exercisers, and moderate-to-large improvements in other symptoms, such as irritability, feelings of tension, low energy and pain, were found.

Matthew Herring, now a research associate in the department of epidemiology at the University of Alabama, Birmingham, led the study during his dissertation research as a doctoral student in the UGA College of Education's department of kinesiology. The team also included Patrick O'Connor and Rodney Dishman, co-directors of the UGA exercise psychology laboratory, psychology professor Cynthia Suveg and doctoral student Marni Jacob.

"Our findings add to the growing body of evidence of the positive effects of exercise training on anxiety," said Herring. "Our study is the first randomized controlled trial focused on the effects of exercise training among individuals diagnosed with GAD. Given the prevalence of GAD and drawbacks of current treatments, including expense and potential negative side effects, our findings are particularly exciting, because they suggest that exercise training is a feasible, well-tolerated potential adjuvant therapy with low risk that can reduce the severity of signs and symptoms of GAD. Future research should confirm these findings with large trials and explore potential underlying mechanisms of exercise effects among individuals with GAD."

The study also examined potential interactions between exercise and drugs used to treat GAD. Half of the participants in each group were taking a medication to treat GAD during the exercise program. Exercise training lessened anxiety symptoms to the same degree among those taking medication compared to those not taking medication.

"The large improvements found in this small investigation show that regular exercise has the power to help calm women suffering from GAD, even among those who appear to be resistant to treatment using medication," said O'Connor.

"The results of this research are very exciting because exercise is available to everyone, is relatively inexpensive and has beneficial effects beyond the reduction of anxious and depressive symptoms," said Suveg. "For individuals suffering from impairing symptoms, these preliminary findings suggest that exercise may offer another potential treatment option that has few, if any, negative side effects. Future research needs to explore the long-term benefits of exercise as well as the conditions under which exercise may be most beneficial and for whom."

More information: For more information about the study, see http://content.kar … f&doi=327898

Provided by University of Georgia

Alzheimer's neurons induced from pluripotent stem cells

Stem-cell-derived neurons, made from patients with Alzheimer's disease, provide a new tool for unraveling the mechanisms underlying the neurodegenerative disease. In this image, DNA is shown in blue, dendrites and cell bodies in red and endosomal markers Rab5 and EEA1 in green and orange, respectively. Credit: UC San Diego School of Medicine

Led by researchers at the University of California, San Diego School of Medicine, scientists have, for the first time, created stem cell-derived, in vitro models of sporadic and hereditary Alzheimer's disease (AD), using induced pluripotent stem cells from patients with the much-dreaded neurodegenerative disorder.

26 jan 2012--"Creating highly purified and functional human Alzheimer's neurons in a dish – this has never been done before," said senior study author Lawrence Goldstein, PhD, professor in the Department of Cellular and Molecular Medicine, Howard Hughes Medical Institute Investigator and director of the UC San Diego Stem Cell Program. "It's a first step. These aren't perfect models. They're proof of concept. But now we know how to make them. It requires extraordinary care and diligence, really rigorous quality controls to induce consistent behavior, but we can do it."

The feat, published in the January 25 online edition of the journal Nature, represents a new and much-needed method for studying the causes of AD, a progressive dementia that afflicts approximately 5.4 million Americans. More importantly, the living cells provide an unprecedented tool for developing and testing drugs to treat the disorder.

"We're dealing with the human brain. You can't just do a biopsy on living patients," said Goldstein. "Instead, researchers have had to work around, mimicking some aspects of the disease in non-neuronal human cells or using limited animal models. Neither approach is really satisfactory."

Goldstein and colleagues extracted primary fibroblasts from skin tissues taken from two patients with familial AD (a rare, early-onset form of the disease associated with a genetic predisposition), two patients with sporadic AD (the common form whose cause is not known) and two persons with no known neurological problems. They reprogrammed the fibroblasts into induced pluripotent stem cells (iPSCs) that then differentiated into working neurons.

The iPSC-derived neurons from the Alzheimer's patients exhibited normal electrophysiological activity, formed functional synaptic contacts and, critically, displayed tell-tale indicators of AD. Specifically, they possessed higher-than-normal levels of proteins associated with the disorder.

With the in vitro Alzheimer's neurons, scientists can more deeply investigate how AD begins and chart the biochemical processes that eventually destroy brain cells associated with elemental cognitive functions like memory. Currently, AD research depends heavily upon studies of post-mortem tissues, long after the damage has been done.

"The differences between a healthy neuron and an Alzheimer's neuron are subtle," said Goldstein. "It basically comes down to low-level mischief accumulating over a very long time, with catastrophic results."

The researchers have already produced some surprising findings. "In this work, we show that one of the early changes in Alzheimer's neurons thought to be an initiating event in the course of the disease turns out not to be that significant," Goldstein said, adding that they discovered a different early event plays a bigger role.

The scientists also found that neurons derived from one of the two patients with sporadic AD exhibited biochemical changes possibly linked to the disease. The discovery suggests that there may be sub-categories of the disorder and that, in the future, potential therapies might be targeted to specific groups of AD patients.

Though just a beginning, Goldstein emphasized the iPSC-derived Alzheimer's neurons present a huge opportunity in a desperate fight. "At the end of the day, we need to use cells like these to better understand Alzheimer's and find drugs to treat it. We need to do everything we can because the cost of this disease is just too heavy and horrible to contemplate. Without solutions, it will bankrupt us – emotionally and financially."

More information: A patent application has been filed on this technology by the University of California, San Diego. For more information, go to: http://techtransfe … D/22199.html

Provided by University of California - San Diego

Researchers find negative social interactions can lead to increased amounts of internal inflammation

25 jan 2012--Researchers from the University of California have found that negative social interactions can cause internal inflammation that may over time lead to possible health consequences. In the study, the results of which the team has published in the Proceedings of the National Academy of Sciences, the team writes that stressful events can lead to increased production of cytokines, molecules that are produced when inflammation occurs.

To find out if cytokines are produced from everyday stressful events, the team recruited 122 young adults (69 women and 53 men) as volunteers to take part in a study. Each participant was asked to keep a very detailed diary describing the events of their day, for eight consecutive days, focusing most specifically on personal or social conflicts. Each volunteer also had a saliva sample taken each day, followed by a stress test followed by another saliva test to check for cytokine levels.

Following the completion of the study, the research team compared cytokine levels against diary entries and found that cytokine levels rose predictably during those periods when the volunteers were reporting negatively stressful events, such as arguing with a roommate. Interestingly, they found that positive stress factors, such as participating in team sports did not cause any increase.

Inflammation occurs, the authors explain, in response to stressful situations. It is believed it happens as our immune systems prepare to deal with the possibility of injury or disease, which is of course a good thing. Problems creep in however, when inflammation and the increased production of cytokines occurs over long periods of time. Prior research has shown it can lead to hypertension, cardiovascular disease, cancer, diabetes and mental disorders.

The team also notes that it is unlikely that short term negatively stressful events such as those experienced by the volunteer group would cause health problems, it’s only when such conditions persist for many years that people begin showing symptoms of stress induced diseases.

The authors suggest that their findings indicate that people would be wise to remove themselves from long term relationships that continually cause negative stresses and instead pursue supportive relationships that foster harmony and good will.

More information: Negative and competitive social interactions are related to heightened proinflammatory cytokine activity, PNAS, Published online before print January 23, 2012, doi: 10.1073/pnas.1120972109

Abstract
Research has consistently documented that social relationships influence physical health, a link that may implicate systemic inflammation. We examined whether daily social interactions predict levels of proinflammatory cytokines IL-6 and the soluble receptor for tumor necrosis factor-α (sTNFαRII) and their reactivity to a social stressor. One-hundred twenty-two healthy young adults completed daily diaries for 8 d that assessed positive, negative, and competitive social interactions. Participants then engaged in laboratory stress challenges, and IL-6 and sTNFαRII were collected at baseline and at 25- and 80-min poststressor, from oral mucosal transudate. Negative social interactions predicted elevated sTNFαRII at baseline, and IL-6 and sTNFαRII 25-min poststressor, as well as total output of sTNFαRII. Competitive social interactions predicted elevated baseline levels of IL-6 and sTNFαRII and total output of both cytokines. These findings suggest that daily social interactions that are negative and competitive are associated prospectively with heightened proinflammatory cytokine activity.

Lifelong brain-stimulating habits linked to lower Alzheimer's protein level

A new study led by researchers at the University of California, Berkeley, provides even more reason for people to read a book or do a puzzle, and to make such activities a lifetime habit.

24 jan 2012--Brain scans revealed that people with no symptoms of Alzheimer's who engaged in cognitively stimulating activities throughout their lives had fewer deposits of beta-amyloid, a destructive protein that is the hallmark of the disease.

While previous research has suggested that engaging in mentally stimulating activities – such as reading, writing and playing games – may help stave off Alzheimer's later in life, this new study identifies the biological target at play. This discovery could guide future research into effective prevention strategies.

"These findings point to a new way of thinking about how cognitive engagement throughout life affects the brain," said study principal investigator Dr. William Jagust, a professor with joint appointments at UC Berkeley's Helen Wills Neuroscience Institute, the School of Public Health and Lawrence Berkeley National Laboratory. "Rather than simply providing resistance to Alzheimer's, brain-stimulating activities may affect a primary pathological process in the disease. This suggests that cognitive therapies could have significant disease-modifying treatment benefits if applied early enough, before symptoms appear."

An estimated 5.4 million Americans live with Alzheimer's disease, but the numbers are growing as baby boomers age. Between 2000 and 2008, deaths from Alzheimer's increased 66 percent, making it the sixth-leading killer in the country. There is currently no cure, but a draft of the first-ever National Alzheimer's Plan, released this week, revealed that the U.S. government is aiming for effective Alzheimer's treatments by 2025.

The new study, to be published Monday, Jan. 23, in the Archives of Neurology, puts the spotlight on amyloid – protein fibers folded into tangled plaques that accumulate in the brain. Beta-amyloid is considered the top suspect in the pathology of Alzheimer's disease, so finding a way to reduce its development has become a major new direction of research.

The researchers note that the buildup of amyloid can also be influenced by genes and aging – one-third of people age 60 and over have some amyloid deposits in their brain – but how much reading and writing one does is under each individual's control.

"This is the first time cognitive activity level has been related to amyloid buildup in the brain," said study lead author Susan Landau, research scientist at the Helen Wills Neuroscience Institute and the Berkeley Lab. "Amyloid probably starts accumulating many years before symptoms appear. So it's possible that by the time you have symptoms of Alzheimer's, like memory problems, there is little that can be done to stop disease progression. The time for intervention may be much sooner, which is why we're trying to identify whether lifestyle factors might be related to the earliest possible changes."

The researchers asked 65 healthy, cognitively normal adults aged 60 and over (average age was 76) to rate how frequently they participated in such mentally engaging activities as going to the library, reading books or newspapers, and writing letters or email. The questions focused on various points in life from age 6 to the present.

The participants took part in extensive neuropsychological testing to assess memory and other cognitive functions, and received positron emission tomography (PET) scans at the Berkeley Lab using a new tracer called Pittsburgh Compound B that was developed to visualize amyloid. The results of the brain scans of healthy older individuals with various levels of lifetime cognitive activity were compared with those of 10 patients diagnosed with Alzheimer's disease and 11 healthy people in their 20s.

The researchers found a significant association between higher levels of cognitive activity over a lifetime and lower levels of beta-amyloid in the PET scans. They analyzed the impact of other factors such as memory function, physical activity, self-rated memory ability, level of education and gender, and found that lifelong cognitive engagement was independently linked to amyloid deposition.

Notably, the researchers did not find a strong connection between amyloid deposition and levels of current cognitive activity alone.

"What our data suggests is that a whole lifetime of engaging in these activities has a bigger effect than being cognitively active just in older age," said Landau.

The researchers are careful to point out that the study does not negate the benefits of kicking up brain activity in the later years.

"There is no downside to cognitive activity. It can only be beneficial, even if for reasons other than reducing amyloid in the brain, including social stimulation and empowerment," said Jagust. "And actually, cognitive activity late in life may well turn out to be beneficial for reducing amyloid. We just haven't found that connection yet."

More information: Arch Neurol. Published online January 23, 2012. doi:10.1001/archneurol.2011.2748

Provided by University of California - Berkeley

Is it the alcohol or polyphenols in red wine that decreases cardiovascular disease?

Observational epidemiologic studies relating wine and alcohol to health all suffer from the fact that they, of necessity, compare people who prefer certain beverages, but not the beverages themselves. While there have been many intervention trials in animals, randomized trials in humans are less common. Randomized crossover trials, in which each subject receives all interventions in sequence, can be especially important as they tend to avoid baseline differences among subjects and can detect effects of different interventions with smaller numbers of subjects.

23 jan 2012--This study by Chiva-Blanch G et al, just published in the American Journal of Clinical Nutrition, included 67 male volunteers in Spain who were considered to be at "high-risk" of cardiovascular disease on the basis of increased BMI, smoking, diabetes, hypertension, or other risk factors. About one half of the individuals were taking ACE inhibitors, statins, aspirin, and/or oral hypoglycemic drugs, so the results of this study may be especially relevant for patients in the real world.

The subjects agreed to not consume any alcohol for a baseline period, then for three one-month periods consumed 30 g/day of alcohol as red wine or as gin, or an equivalent amount of phenolics from dealcoholized red wine. The polyphenol contents of the RW and the DRW interventions were the same. A very high degree of compliance of the subjects with the assigned interventions is evidenced by results of counting numbers of empty bottles of the intervention beverage returned, dietary records, urinary metabolites, etc. Further, there is good evidence that there were no important changes between periods in diet or exercise habits. The effects of each intervention on a large number of adhesion molecules and chemokines that affect inflammation and relate to the development of vascular disease were evaluated.

The key results of the study were that both ethanol and nonalcoholic compounds in red wine have potentially protective effects that may reduce the risk of vascular disease. Specifically, the authors conclude that "the phenolic content of red wine may modulate leukocyte adhesion molecules, whereas both ethanol and polyphenols of red wine may modulate soluble inflammatory mediators in patients at high risk of cardiovascular disease."

Specific comments on the study: Most reviewers considered this to be a well-done, comprehensive study. As one reviewer commented: "This is an excellent paper. The results strongly indicate an effect of wine polyphenols on inflammation (in broad and modern terms) and this is just what we expect from the biochemistry and nutritional effects of fruits and vegetables. The effect of ethanol, on the other hand, likely fits a hormetic mechanism, where low doses regularly supplied are protective while high doses in a single shot are worsening the progression of disease." Another reviewer added: "We need more information on separating the effects of beer, wine, and various types of spirits. Some spirits like brandy and whisky can have useful antioxidant effects, so distinguishing effects among different types of beverages may be informative."

Another Forum reviewer commented: "This is a very interesting paper that goes a way towards answering the question whether it is the alcohol or polyphenols in red wine that confer the health benefits. The trial was well conducted and controlled, with very detailed analyses. It would have been interesting to analyse any changes in conventional risk factors after the interventions. It would also have been interesting in the study to determine the effects on vascular function by, for example, brachial artery activity (flow mediated dilatation)."

Given that the effects of both alcohol and polyphenols on physiologic factors (e.g., platelet function, fibrinolysis) are transient, generally lasting for no more than 24 hours, it was appropriate that the subjects in this study were instructed to consume the intervention substance (RW, gin, DRW) on a daily basis. When drinking is moderate, there is no evidence that having "alcohol-free days" is beneficial to health. Indeed, most epidemiologic studies show better health effects from daily consumption rather than from drinking on a few days per week.

Concerns about the present study: One Forum reviewer stated: "This appears to be a carefully designed and well executed study, but I have four concerns: (1) The study has been undertaken in high-risk individuals, more than half of whom are hypertensive, a quarter dyslipidaemic, and a quarter diabetic. It is not described what happened to the conventional risk factors during the interventions. (For example, any improvement in inflammatory markers may have come at the cost of higher blood pressure with the alcohol interventions.) (2) Was there any weight change that could have confounded any of the outcomes? (3) Both polyphenol and alcohol biomarkers were measured – did the change in these biomarkers correlate with the changes in any of the inflammatory markers; i.e., any suggestion of a dose response relationship? (4) Even though at least 30 outcome variables were assessed, the authors do not describe any correction for multiple comparisons."

Another Forum reviewer: "This is a well conducted study, and adds to our understanding of the potential cardiovascular benefits of alcohol and the non-alcoholic compounds of alcoholic beverages. However, in this study more than one-half of the high-risk subjects consumed drugs with known anti-inflammatory effects, which could be a confounding factor. The anti-inflammatory effects of these pharmaceuticals may be responsible for the beneficial results, and may not be related to the RW, DRW and gin interventions." However, others think that this concern is unlikely to be important since this was a crossover study, and there were no changes in lifestyle or medication use between the intervention periods.

The key results of the study were that both ethanol and nonalcoholic compounds in red wine have potentially protective effects that may reduce the risk of vascular disease. Specifically, the authors conclude that "the phenolic content of red wine may modulate leukocyte adhesion molecules, whereas both ethanol and polyphenols of red wine may modulate soluble inflammatory mediators in patients at high risk of cardiovascular disease." Thus, this study provides important new mechanistic evidence that the reduced risk of cardiovascular disease among red wine drinkers observed in most epidemiologic studies may result from a combination of both the alcohol and the polyphenols in the wine.

More information: Chiva-Blanch G, Urpi-Sarda M, Llorach R, Rotches-Ribalta M, Guillèn M, Casas R, Arranz S, Valderas-Martinez P, Portoles O, Corella D, Tinahones F, Lamuela-Raventos RM, Andres-Lacueva C, Estruch R. Differential effects of polyphenols and alcohol of red wine on the expression of adhesion molecules and inflammatory cytokines related to atherosclerosis: a randomized clinical trial. Am J Clin Nutr 2012. doi: 10.3945/ajcn.111.022889

Provided by Boston University Medical Center

Older women with normal T-scores may not need bone mineral density screening for 15 years

The U.S. Preventive Services Task Force and other organizations have recommended that women ages 65 and older be routinely screened for osteoporosis using bone mineral density (BMD) screening. However, how often women should be screened is a topic that remains controversial and undecided, with no definitive scientific evidence to provide guidance.

22 jan 2012--Now a new study led by Margaret L. Gourlay, MD, MPH of the University of North Carolina at Chapel Hill School of Medicine finds that women aged 67 years and older with normal bone mineral density scores may not need screening again for 15 years.

"If a woman's bone density at age 67 is very good, then she doesn't need to be re-screened in two years or three years, because we're not likely to see much change," Gourlay said. "Our study found it would take about 15 years for 10 percent of women in the highest bone density ranges to develop osteoporosis."

"That was longer than we expected, and it's great news for this group of women," Gourlay said.

Gourlay, an assistant professor in UNC's Department of Family Medicine, presented these results in a study published in the Jan. 19, 2012 issue of The New England Journal of Medicine.

In the study, Gourlay and study co-authors analyzed data from 4,957 women aged 67 years and older that were collected as part of the longest-running osteoporosis study in the U.S., the Study of Osteoporotic Fractures. These women were enrolled in the study from 1986 to 1988 when they were 65 years or older, and had bone mineral density (BMD) testing starting about two years later. All had bone mineral density testing at least twice during the study period; some were tested up to five times over a period of 15 years.

For the analysis, women were categorized by BMD T-scores, which compare a person's bone mineral density to the expected bone density of a healthy young adult (about age 30). Women with osteoporosis (those with a T-score of -2.5 or lower) or past hip or clinical vertebral (spine) fractures were excluded because current guidelines recommend treatment for all women in those groups. Women who had already received treatment for osteoporosis were also excluded. The remaining women were placed in three groups according to their baseline BMD T-scores at the hip. The high risk group was women with T-scores ranging from -2.49 to -2.00, while the moderate risk group had T-scores from -1.99 to -1.50. The low risk group included two T-score ranges: T-scores -1.49 to -1.01, and normal BMD (those with T-scores of -1.00 or higher).

The researchers calculated estimated times for 10 percent of the women in each T-score group to transition to osteoporosis. For the high risk group, the estimated time was 1.1 years, while it was about 5 years for the moderate risk group and slightly over 15 years for the low risk group. They found that in those same time periods, only 2 percent or less of women had hip or clinical vertebral fractures, which are the most important fractures doctors try to prevent by screening for osteoporosis.

The study concluded that baseline BMD is the most important factor for doctors to consider in determining how often a patient should be screened. It also suggests that older postmenopausal women with a T-score -2.0 and below will transition to osteoporosis more rapidly, while women with T-scores higher than -2.0 may not need screening again for 5 to 15 years, Gourlay said. "Doctors may adjust these time intervals for a number of reasons, but our results offer an evidence-based starting point for this clinical decision."

Provided by University of North Carolina School of Medicine

Sexual activity is safe for most heart, stroke patients

If you have stable cardiovascular disease, it is more than likely that you can safely engage in sexual activity, according to an American Heart Association scientific statement.

21 jan 2012--The statement, published online in Circulation: Journal of the American Heart Association, contains recommendations by experts from various fields, including heart disease, exercise physiology and sexual counseling.

"Sexual activity is a major quality of life issue for men and women with cardiovascular disease and their partners," said Glenn N. Levine, M.D., lead author of the statement and a professor of medicine at Baylor College of Medicine in Houston, Texas. "Unfortunately, discussions about sexual activity rarely take place in the clinical context."

The recommendations include:

• After a diagnosis of cardiovascular disease, it is reasonable for patients to be evaluated by their physician or healthcare provider before resuming sexual activity.
• Cardiac rehabilitation and regular physical activity can reduce the risk of cardiovascular complications related to sexual activity in people who have had heart failure or a heart attack.
• Women with cardiovascular disease should be counseled on the safety and advisability of contraceptive methods and pregnancy based on their patient profile.
• Patients with severe heart disease who have symptoms with minimal activity or while at rest should not be sexually active until their cardiovascular disease symptoms are stabilized with appropriate treatment.
• Patients should be assessed to see if their sexual dysfunction is related to underlying vascular or cardiac disease, anxiety, depression or other factors.
• Drugs that can improve cardiovascular symptoms or survival should not be withheld due to concerns that such drugs may impact sexual function.
• Drugs to treat erectile dysfunction are generally safe for men who have stable cardiovascular disease. These drugs should not be used in patients receiving nitrate therapy for chest pains due to coronary artery disease (blockages in the arteries that supply the heart with blood), and nitrates should not be administered to patients within 24-48 hours of using an erectile dysfunction drug (depending on the drug used).
• It is reasonable for post-menopausal women with cardiovascular disease to use estrogen that's topically or vaginally inserted for the treatment of painful intercourse.

Decreased sexual activity and function — common in men and women with cardiovascular diseases — is often related to anxiety and depression.

The absolute rate of cardiovascular events during sexual activity, such as heart attacks or chest pain caused by heart disease, is miniscule because sexual activity is usually for a short time.

"Some patients will postpone sexual activity when it is actually relatively safe for them to engage in it," said Levine, who is also director of the Cardiac Care Unit at the Michael E. DeBakey Medical Center in Houston. "On the other hand, there are some patients for whom it may be reasonable to defer sexual activity until they're assessed and stabilized."

Provided by American Heart Association

Cell senescence does not stop tumor growth

Since cancer cells grow indefinitely, it is commonly believed that senescence could act as a barrier against tumor growth and potentially be used as a way to treat cancer. A collaboration between a cancer biologist from the University of Milano, Italy, and two physicists, from the National Research Council of Italy and from Cornell University, has shown that cell senescence occurs spontaneously in melanoma cells, but does not stop their growth, which is sustained by a small population of cancer stem cells. The results, published in the open-access journal PLoS Computational Biology on January 19 explain why it is difficult to treat cancer cells by inducing senescence alone.

20 jan 2011--The work explores the relationship between melanoma and senescence, the normal process where cells decline and eventually stop duplicating after reaching maturity. The investigators followed the long-term evolution of melanoma cell populations, monitoring the number of senescent cells. After three months, growth slowed and most of the cells turned senescent, however growth did not stop and eventually resumed its initial rate until the senescent cells had almost disappeared.

The authors mathematically modeled the experimental data using the cancer stem cell hypothesis, where a sub-group of cancer cells replicate indefinitely, and are thus unaffected by senescence. These cancer stem cells give rise to a larger population of cancer cells that can duplicate only a finite number of times. The model yielded an indirect confirmation of the presence of cancer stem cells in melanoma, an issue that is still controversial in the cancer research community.

Although a large fraction of cancer cells are susceptible to senescence, the researchers conclude that inducing senescence is unlikely to provide a successful therapeutic strategy because these cells are irrelevant for tumor growth. However, the indirect evidence of cancer stem cells in melanoma may enable the development of new methods to treat specific kinds of cancer. The challenge will be in the strong resistance to drug induced senescence that would be found in the cancer stem cells. Along this line of research, treatment of tumors would focus on targeting only these cancer stem cells, rather than every single cancerous cell.

More information: La Porta CAM, Zapperi S, Sethna JP (2012) Senescent Cells in Growing Tumors: Population Dynamics and Cancer Stem Cells. PLoS Comput Biol 8(1): e1002316. doi:10.1371/journal.pcbi.1002316

Provided by Public Library of Science

Metastasis of pancreatic cancer in action

Pancreatic cells spread by blending in. The left panel shows an inflammed pancreatic duct surrounded by what appear to be fibroblasts (blue arrow). Lineage tagging allowed the researchers to see that some of these fibroblast-like cells are actually invading pancreatic epithelial cells in disguise (left panel, white arrow). Such cells have undergone a process of epithelial-to-mesenchymal transition and are able to enter the bloodstream. Credit: Andrew Rhim, PhD, Perelman School of Medicine, University of Pennsylvania; Cell Press

Ben Stanger, MD, PhD, assistant professor of Medicine in the Division of Gastroenterology at the Perelman School of Medicine, University of Pennsylvania, and Andrew Rhim, MD, a Gastroenterology Fellow in the Stanger lab, discovered that pancreatic cancer cells in an animal model begin to spread before clinically obvious tumor tissue is detected. What's more, they showed that inflammation enhances cancer progression in part by facilitating a cellular transformation that leads to entry of cancer cells into the circulation. They report their findings this week in Cell.

19 jan 2012--Metastasis has been difficult to study because it involves a series of unpredictable events. To capture these events, the team developed a sensitive method to tag and track pancreatic epithelial cells in a mouse model of pancreatic cancer. Tagged cells invaded and entered the bloodstream unexpectedly early, before overt malignancy could be detected by rigorous analysis of tissue slides.

Pancreatic cancer is among the most lethal of cancers, with no real treatments, and at the time of diagnosis up to three-quarters of patients have metastatic disease, says Stanger. Little is known about how pancreatic cancer cells spread, "What leads to this are rare events that are hard to catch in tissues. Small numbers of cells break off tumors and move, but how can we find them?"

These wandering cells are associated with a phenomenon called the epithelial-to-mesenchymal transition (EMT). This change in cell motility is an important process during the development of embryos. But when the transition is aberrantly reactivated in adults it can have dire physiological consequences, leading to cancer metastasis as well as other disease processes. Epithelial cells form a covering or lining of a body surface and are the type of cell from which most solid tumors arise. However, when a molecular switch is turned off or absent, epithelial cells acquire characteristics of another cell type, called mesenchymal cells, and gain the ability to migrate and move away from the primary tumor site.

Using a mouse model of pancreatic cancer developed at Penn in 2005, the team delivered mutations in an oncogene and a tumor suppressor protein, K-ras and p53 respectively, in the pancreas. A green marker was also induced in the embryos' still-forming pancreas. At about one to two months, the juvenile mice developed pre-malignant lesions, and at about four to five months full blown pancreatic cancer.

During this time, the mouse pancreatic epithelial cells lost their epithelial characteristics and became more like mesenchymal cells, blending in and making their way to the bloodstream. True epithelial cells are sticky, keeping linings tightly connected, but these imposter epithelial cells changed identity, becoming less sticky.

With the green stain, the researchers were able to detect the transition from epithelial cell to mesenchymal cell in a tissue slide, showing many green cells that had undergone EMT. "We are now able to see what was before before unseeable – the pancreas cells that have taken on a disguise," says Stanger.

What spurs the EMT in first place? The team surmised that it was inflammation, so they blocked inflammation with an immunosuppressant, and at about eight to ten weeks, the green cells undergoing EMT disappeared. Conversely, when they induced pancreatitis- associated inflammation, the EMT green cells increased.

In trying to relate these findings to metastasis, they looked for green EMT cells outside of the pancreas and found them in the blood and distinct tissues such as the liver at eight to ten weeks of age, long before a pathologist would recognize it as cancer.

"These results provide new insight into the earliest events of cellular invasion and suggest that inflammation enhances cancer progression by giving cells increased access to the bloodstream," says Stanger.

The team plans to use the methodology used in this study to enhance the detection of spreading cells in human patients at an early timepoint, when therapy could have a greater impact.

Both the development of the pancreatic cancer mouse model and Dr. Stanger's current work were partially funded by research grants from the Pancreatic Cancer Action Network. "We are highly encouraged by Dr. Stanger's recent results," said Lynn Matrisian, PhD, vice president of Scientific and Medical Affairs at the Pancreatic Cancer Action Network. "A deeper understanding of the disease biology, and in particular metastasis, will move us closer to our goal of doubling the survival rate of pancreatic cancer by the year 2020."

Provided by University of Pennsylvania School of Medicine

Exercise triggers beneficial cellular recycling: study

The cross-sections of tibialis anterior muscle shown above are from transgenic mice expressing GFP-LC3, a fluorescent green indicator of autophagy. Muscle from a resting animal is shown at left. The muscle on the right shows the increase in autophagy after 80 minutes of running on a treadmill.

Everyone knows exercise is good for you. We’re told time spent on the treadmill can reduce our risk of diabetes, cancer, and cardiovascular disorders. But exactly how exercise provides this protection is a bit of a mystery. A new study finds that exercise prompts cells to break down unwanted proteins and other cellular junk to produce more energy. The process, called autophagy, may explain how exercise fends off metabolic disorders like diabetes and protects against other diseases.

19 jan 2012--Autophagy is like a “cellular garbage disposal,” says Howard Hughes Medical Institute investigator Beth Levine, a physician at the University of Texas Southwestern Medical School in Dallas who has been studying the process for more than a decade. The process works like this: First, a double membrane forms around the unwanted cargo inside the cell, enveloping it. This membrane then fuses with an organelle called a lysosome, which contains enzymes that rush in and break down the contents. The bits and pieces created by this process get recycled, providing raw materials for new structures or a burst of energy.

Autophagy keeps cells healthy by “getting rid of all of the obsolete and abnormal structures,” Levine explains. It also helps cells survive lean times. By cannibalizing unwanted proteins and other junk, the cells can get nutrients.

Scientists have long known that starvation can trigger a boost in autophagy. Levine and her colleagues suspected that exercise, because it increases cells’ energy demands, might have a similar effect. To test the idea, she and her colleagues used transgenic mice whose cells produce a glowing green protein whenever autophagy occurs. Then they placed these mice on treadmills. After 30 minutes of running, the rodents’ muscle and heart cells were speckled with green dots, evidence of increased autophagy. “That was a brand new finding,” she says. In a paper published January 18, 2012, in the journal Nature, the researchers report that exercise also sparked an increase in autophagy in cells in the liver and pancreas, organs involved in the metabolism of glucose.

Next, Levine and her colleagues set out to determine what purpose the autophagy serves. The team engineered mice that could undergo normal autophagy, but due to a mutation in a gene called B-cell lymphoma 2 (Bcl-2), lacked the ability to ramp up autophagy during exercise or starvation. Bcl-2 is known to inhibit cell death and plays a key role in regulating autophagy.

When the researchers placed these mutant mice on the treadmill, they found that they couldn’t run as long as normal mice. A closer look revealed that the mice weren’t metabolizing sugar properly. When a normal mouse runs on a treadmill, its muscle cells kick into overdrive, increasing their uptake of sugar. Consequently, the amount of sugar in the blood plummets. But this didn’t happen in the mutant mice. The enzyme that helps cells take in more sugar, called AMP kinase, did not get activated. As a result, the blood sugar levels of the mice stayed unnaturally high and the mice showed less endurance.

Levine thought that these mutant mice might not derive any long-term benefit from exercise either. To test the hypothesis, the researchers fed both mutant and normal mice a high-fat diet for four weeks. Not surprisingly, the mice gained weight and developed a disorder akin to type 2 diabetes, a disease in which sugar doesn’t move efficiently from the blood into cells.

Next, they put the mice on a stringent exercise regimen for eight weeks while still feeding them a high fat diet. The normal mice lost weight and their diabetes disappeared. Their muscle cells regained the ability to take up sugar. The mutant mice that exercised on the treadmill also lost weight, but they didn’t get any of the metabolic benefits; their blood sugar levels stayed high. The data suggest that, to get the benefits, “autophagy really was necessary,” Levine says.

The findings suggest that increased autophagy may be the reason why exercise protects against type 2 diabetes and other metabolic disorders. Several oral drugs used to treat type 2 diabetes work by activating AMP kinase. Autophagy induced by exercise appears to do the same thing.

The team’s next step will be to investigate whether autophagy could also explain why regular exercise protects against cancer, neurodegenerative disorders, and aging. For cancer, the mechanism may be similar, Levine speculates. Studies have shown that diabetics who take AMP kinase activators have a lower incidence of cancer than diabetics with similar blood sugar levels who don’t take the drugs.

In the meantime, Levine plans to get more exercise herself. She recently invested in a treadmill. “If it’s good enough for my mice,” she says, “it’s good enough for me.”

More information: Study: DOI:10.1038/nature10758

Provided by Howard Hughes Medical Institute

Researchers identify genetic signatures of exceptional longevity in re-published study

While environment and family history are factors in healthy aging, genetic variants play a critical and complex role in conferring exceptional longevity, according to researchers from the Boston University Schools of Public Health and Medicine, Boston Medical Center, IRCCS Multimedica in Milan, Italy, and Yale University.

19 jan 2012--Published in PLoS ONE, after peer review, the research findings are the corrected version of work originally published in Science in July 2010. The revised publication includes additional authors who independently assessed and helped to produce a valid genotype data set, for which the same analysis as in the original paper was performed. It also contains an additional replication data set of subjects with an average age of 107.

Centenarians are a model of healthy aging, as the onset of disability in these individuals is generally delayed until they are well into their mid-90s. Because exceptional longevity can run strongly in families, and numerous animal studies have suggested a strong genetic influence on life span, the researchers set out to determine which genetic variants play roles in human survival beyond 100 years of age. They used a well-established Bayesian statistical method for determining which single nucleotide polymorphisms (SNPs, or genetic variants) could, as a group, be used to categorize subjects as centenarians versus controls, based solely upon the genetic information. The predictive sensitivity of the model they developed, which contains 281 SNPs, increased with the age of the subject, supporting the hypothesis that genes play an increasingly strong role in survival in centenarians. The model was able to predict exceptional longevity with 60 to 85 percent accuracy, depending on the average age of the replication sample that was used. The older the sample, the stronger the sensitivity. Many of the 130 known genes associated with the SNPs in the prediction model have been shown by other gerontologists to play roles in age-related diseases and aging, said the study's lead researchers, Paola Sebastiani, PhD, professor of biostatistics at the BU School of Public Health, and Thomas Perls, MD, MPH, associate professor of medicine at the BU School of Medicine.

"This is a useful step towards meaningful predictive medicine and personal genomics," said Dr. Perls, a geriatrician at Boston Medical Center. "When people can do this kind of analysis on whole genome sequences for traits that have important genetic components, the predictive value should be even better."

The new study differs from the earlier study, voluntarily retracted by the authors, in several ways: A select group of faulty SNPs was eliminated from this study ;an additional sample of extremely old study subjects was added; and researchers from Yale University were called in to independently validate the data and methodology. The corrected study, as did the original, found that subjects who shared the same profile of variations for genetic markers in the model appeared to share similar levels of risk for various traits or diseases associated with exceptional longevity -- most notably, in their ages of survival. "Further study of these genetic characteristics may yield a better understanding of the genetic and biological bases of delaying or escaping age-related diseases and achieving longer survival," Dr. Perls said."The novel approach to genetic data that is described here is likely applicable to other complex inherited traits, and we look forward to other research groups applying these methods to their data."

More information: The full study is available here: http://dx.plos.org … pone.0029848

Provided by Boston University Medical Center

US wants effective Alzheimer's treatment by 2025

The government is setting what it calls an ambitious goal for Alzheimer's disease: Development of effective ways to treat and prevent the mind-destroying illness by 2025.

18 jan 2012--The Obama administration is developing the first National Alzheimer's Plan to find better treatments for the disease and offer better day-to-day care for those afflicted.

A newly released draft of the overall goals sets the 2025 deadline, but doesn't provide details of how to fund the necessary research to meet that target date. Today's treatments only temporarily ease some dementia symptoms, and work to find better ones has been frustratingly slow.

A committee of Alzheimer's experts begins a two-day meeting Tuesday to help advise the government on how to finalize the plan.

An estimated 5.4 million Americans have Alzheimer's or similar dementias. It's the sixth-leading killer, and is steadily growing as the population rapidly ages. By 2050, 13 million to 16 million Americans are projected to have Alzheimer's, costing $1 trillion in medical and nursing home expenditures.

The national plan is supposed to tackle both the medical and social aspects of dementia, and advocacy groups had urged that it set a deadline for progress.

Among the draft's other goals:

-Improve timely diagnosis. A recent report found as many as half of today's Alzheimer's sufferers haven't been formally diagnosed, in part because of stigma and the belief that nothing can be done. Symptomatic treatment aside, a diagnosis lets families plan, and catching the disease earlier would be crucial if scientists ever find ways to slow the disease's progress.

-Improve support and training for families so they know what resources are available for patients and what to expect as dementia worsens.

Alzheimer's sufferers gradually lose the ability to do the simplest activities of daily life and can survive that way for a decade or more. In meetings around the country last summer and fall, families urged federal health officials to make sure the national plan addresses how to help patients live their last years at home without ruining their caregivers' own health and finances.

No walk in the park: Factors that predict walking difficulty in elderly

Yale School of Medicine researchers have found that the likelihood of becoming disabled with age increases with the following factors: having a chronic condition or cognitive impairment; low physical activity; slower gross motor coordination; having poor lower-extremity function; and being hospitalized. Women are also more likely than men to become disabled in their later years.

17 jan 2012--Based on 12 years of data, the findings are published in the Jan.17 issue of Annals of Internal Medicine by a research team led by Thomas Gill, M.D., the Humana Foundation Professor of Geriatric Medicine and professor of medicine, epidemiology, and public health at Yale School of Medicine.

With age, many people can no longer walk short distances or drive a car, and those with long-term loss of mobility have difficulty regaining independence.

"Losing the ability to walk independently not only leads to a poorer overall quality of life, but prolonged disability leads to higher rates of illness, death, depression and social isolation," said Gill, who followed a group of 641 people aged 70 or older who could walk a quarter mile unassisted or who were active drivers at the start of the study. All participants could perform essential activities of daily living, such as bathing and dressing.

Gill and his team assessed the participants for changes in potential disability risk factors every 18 months between 1998 and 2008. They also assessed the participants' mobility each month. Those who said they needed help from another person to walk a quarter mile were considered to be walking disabled. Those who said that they had not driven a car during the past month were considered driving disabled.

On a monthly basis, the research team also assessed the participants' exposure to potential causes of disability, including illnesses or injuries leading to hospitalization and restricted activity, which increased the likelihood of long-term disability by 6-fold.

The team found that multiple risk factors, together with subsequent illness and injury leading to hospitalization and restricted activity, are associated with an increased likelihood of developing long-term walking and driving disability. The team considered a disability to be long term if it persisted for at least six months.

"We've learned that targeted strategies are needed to prevent disability among older people living independently in the community," said Gill.

More information: Annals of Internal Medicine, Vol. 156, No. 2: 131-140 (January 17, 2012)

Provided by Yale University

Active lifestyle associated with less Alzheimer disease-related brain change among persons with APOE epsilon4 genotype

A sedentary lifestyle is associated with greater cerebral amyloid deposition, which is characteristic of Alzheimer’s disease (AD), among cognitively normal individuals with the ε4 allele of the apolipoprotein E (APOE) gene, according to a report published Online First by Archives of Neurology, one of the JAMA/Archives journals.

16 jan 2012--“The presence of an APOE ε4 allele is the most established genetic risk factor for Alzheimer disease (AD), with a higher percentage of individuals with AD having an ε4 allele in comparison with the general population,” the authors write as background information in the article. “It has been suggested that APOE status may modify associations between lifestyle factors such as exercise engagement and risk of cognitive decline and dementia.”

More information: Exercise Engagement as a Moderator of the Effects of APOE Genotype on Amyloid Deposition, Arch Neurol. Published online January 9, 2012. doi:10.1001/archneurol.2011.845

ABSTRACT

Objective. APOE 4 status has been associated with greater cortical amyloid deposition, whereas exercise has been associated with less in cognitively normal adults. The primary objective here was to examine whether physical exercise moderates the association between APOE genotype and amyloid deposition in cognitively normal adults.
Design APOE genotyping data and answers to a questionnaire on physical exercise engagement over the last decade were obtained in conjunction with cerebrospinal fluid (CSF) samples and amyloid imaging with carbon 11–labeled Pittsburgh Compound B ([11C]PiB) positron emission tomography. Participants were classified as either low or high exercisers based on exercise guidelines of the American Heart Association.
Setting. Knight Alzheimer's Disease Research Center at Washington University, St Louis, Missouri.
Participants. A total of 201 cognitively normal adults (135 of whom were women) aged 45 to 88 years were recruited from the Knight Alzheimer’s Disease Research Center. Samples of CSF were collected from 165 participants. Amyloid imaging was performed for 163 participants.
Results. APOE 4 carriers evidenced higher [11C]PiB binding (P < .001) and lower CSF Aβ42 levels (P < .001) than did noncarriers. Our previous findings of higher [11C]PiB binding (P = .005) and lower CSF Aβ42 levels (P = .009) in more sedentary individuals were replicated. Most importantly, we observed a novel interaction between APOE status and exercise engagement for [11C]PiB binding (P = .008) such that a more sedentary lifestyle was significantly associated with higher [11C]PiB binding for 4 carriers (P = .013) but not for noncarriers (P = .20). All findings remained significant after controlling for age; sex; educational level; body mass index; the presence or history of hypertension, diabetes mellitus, heart problems, or depression; and the interval between assessments.
Conclusion. Collectively, these results suggest that cognitively normal sedentary APOE 4–positive individuals may be at augmented risk for cerebral amyloid deposition.

Provided by Washington University in St. Louis

Over-65s are frequent binge drinkers: US study

Binge drinking is more common in the United States than previously thought, particularly among young adults, though the most frequent offenders are over 65, said a US government study on Tuesday.

14 jan 2011--One in six Americans, or 17.1 percent of the population, binge drinks, defined as consuming five or more alcoholic beverages in a sitting for men and four or more among women, said the Centers for Disease Control and Prevention.

The latest data for 2010 is an increase over the CDC's report on the same topic for 2009, which said about 15 percent of US adults, or 33 million Americans, binge drink, a rate that had stayed the same for more than 15 years.

While the most common age group among the 38 million American who binge drink was 18-34, those who reported doing it most often were over 65, said the CDC's Vital Signs report, which also warned of the health and safety risks of high alcohol use.

Seniors who binge drink reported doing so 5.5 times per month, compared to an average of four times a month among the rest of the binge-drinking population.

The 18-24 age group had the highest amount of binge drinkers (28.2 percent) in their ranks and tended to drink the most -- 9.3 drinks -- in each setting. The age group 25-34 was a close second (27.9 percent).

"Binge drinking by adults has a huge public health impact, and influences the drinking behavior of underage youth by the example it sets," said CDC substance abuse and mental health services administrator Pamela Hyde.

"We need to reduce binge drinking by adults to prevent the immediate and long-term effects it has on the health of adults and youth."

The data was collected by a randomized phone survey in 48 states and the US capital region. This year, it also included cell phones, which likely resulted in a higher number of young people's participation.

The survey found that binge drinking was most common among people who earned $75,000 or more a year in household income, but those who earned less than $25,000 a year went on binges more frequently.

Low-income binge drinkers tended to consume excessive alcohol five times per month and 8.5 drinks each time.

Whites and Hispanics were more likely to binge drink than blacks. Also, men were more likely to binge drink than women.

"Binge drinking causes more than half of the 80,000 deaths and three quarters of the $223.5 billion in economic costs caused by excessive drinking," said the report.

"Drinking too much contributes to over 54 different injuries and diseases, including car crashes, violence, and sexually-transmitted diseases."

The CDC said that raising the price of alcohol, limiting the days and hours when it can be sold, and restricting the number of liquor licenses offered in a given geographic area could help cut down on binge drinking.

More information: CDC report: http://www.cdc.gov/vitalsigns