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

Hip fracture guidelines tackle 'considerable variations' in UK and Irish hospital care

All patients with hip fractures should be fast-tracked through hospital emergency departments and operated on within 48 hours of admission, according to new consensus guidelines developed by UK experts in anaesthesia, orthopaedics, geriatrics and emergency medicine and published in the January issue of Anaesthesia.

13 jan 2012--However, patients in one in five hospitals in England and Wales currently wait longer than two days, risking lengthier inpatient stays, increased health problems - such as pressure sores, pneumonia and blood clots - and even an increased chance of death if the delay is prolonged.

The Association of Anaesthetists of Great Britain and Ireland teamed up with a number of other organisations, including the Age Anaesthesia Association and British Orthopaedic Association, to develop the new ten-point plan for the Management of Proximal Femoral Fractures.

"Unlike existing guidelines, they review the current clinical evidence and also recommend best practice in numerous circumstances where evidence is controversial or incomplete, based on expert consensus" says consultant anaesthetist Dr Richard Griffiths, who chaired the working party.

"These are the first guidelines to cover some of the difficult clinical problems faced by anaesthetists on a daily basis.

"For example, we recommend that if any investigations need to be carried out on patients with systolic heart murmurs, this should be done as a matter of urgency to avoid delaying their operations.

"The management of patients on antiplatelet drugs to avoid blood clots forming is another controversial area. Evidence is incomplete, but the expert consensus is to proceed with surgery without stopping the drugs, as operating delays pose a greater risk to the patient."

Hip fractures present unique challenges for anaesthetists as they often occur in elderly patients with significant health problems, stresses Dr Griffiths.

"Despite the fact that guidance has been in place since the early 1990s concerning best practice management for these vulnerable patients, there remain considerable variations in models of post-operative care, rehabilitation and orthogeriatric input" he says.

"Bringing together experts in anaesthesia, orthopaedics, geriatrics and emergency medicine has enabled us to look at the journey of the hip fracture patients from admission to discharge and recommend how their care can be maximised by everyone involved."

Approximately 77,000 patients break their hips in the UK every year, spending an average of 16 days in hospital and costing the National Health Service £785 million. The majority (95 per cent) occur in people over 60 years of age and 75 per cent occur in females.

More than eight per cent of patients will die within 30 days of a hip fracture, especially if they are older, sicker or male, and this figure rises to up to 30 per cent within a year. It has been suggested that half of postoperative deaths are potentially preventable.

Only 44 per cent of UK patients admitted from home are discharged back to their home within 30 days of surgery. A further 22 per cent are discharged to a residential or nursing home and they can often spend a long time in hospital waiting for admission to these facilities, blocking much needed beds.

The ten-point action plan advises that:

1. There should be protocol-driven, fast-track admission of patients with hip fractures through the emergency department.
2. Patients with hip fractures require multidisciplinary care, led by orthogeriatricians.
3. Surgery is the best analgesic for hip fractures.
4. Surgical repair of hip fractures should occur within 48 hours of hospital admission.
5. Surgery and anaesthesia must be undertaken by appropriately experienced surgeons and anaesthetists.
6. There must be high-quality communication between clinicians and allied health professionals.
7. Early mobilisation is a key part of the management of patients with hip fractures.
8. Pre-operative management should take into consideration plans for the patient's discharge from hospital.
9. Measures should be taken to prevent secondary falls.
10. Continuous audit and targeted research is required in order to inform and improve the management of patients with hip fracture.

"We hope that our guidelines will address current variations in clinical practice so that patients can all benefit from a more consistent approach" concludes Dr Griffiths, who is also lead clinician for the National Health Service Hip Fracture Perioperative Group, an initiative started by anaesthetists, but with increasing membership from orthogeriatricians.

More information: Management of proximal femoral fractures 2011. Griffiths et al. Anaesthesia. 67, pp85-98. (2012). doi:10.1111/j.1365-2044.2011.06957.x

Provided by Wiley

New study supports view that Lewy bodies are not the primary cause of cell death in Parkinson's Disease

The pathology of Parkinson's disease is characterized by a loss of dopamine-producing neurons in the pars compacta of the substantia nigra (SN), an area of the brain associated with motor control, along with the development of α-synuclein (αS) protein in the form of Lewy bodies (LB) in the neurons that survive. The spread of LB pathology is thought to progress along with the clinical course of Parkinson's disease, although recent studies suggest that they are not the toxic cause of cell death. A new study published in The Journal of Parkinson's Disease finds no support for a primary pathogenic role of LBs, as neither their distribution nor density was associated with the severity of nigral cell loss.

12 jan 2011--"We investigated the relationship between nigral dopaminergic cell loss, distribution and density of α-synuclein immunoreactive LBs, and the duration of motor symptoms in 97 patients with Parkinson's disease," explains lead investigator Andrew J. Lees, MD, of Queen Square Brain Bank for Neurological Disorders and the Reta Lila Weston Institute for Neurological Studies, UCL Institute of Neurology, London, UK. "Despite the reasonably close correlation between neuronal density in SN and severity of bradykinesia and rigidity in Parkinson's disease, our results suggest that nigral cell loss is gradual and there is considerable variability, which may explain the clinical heterogeneity."

Researchers confirmed that both neuronal number and density in SN in Parkinson's disease decrease over time. The density of nigral neurons was estimated to decrease by 2% each year after confirmation of the clinical diagnosis of Parkinson's disease, but showed marked heterogeneity across patients. Some patients with longer duration of illness still had a significant number of preserved nigral neurons at the time of death. An average of 15% of surviving nigral neurons contained LBs and the age-adjusted proportion of LB-bearing neurons appeared relatively stable through the disease duration. "This could be explained by a passive 'one-pass' phenomenon where the LBs appear at the beginning of the disease and then decrease at the same rate as nigral neurons are lost, or alternatively that a dynamic 'turnover' occurs with some LBs continuously produced and destroyed at the same rate," explains Dr. Lees.

Nigral neuron density was unrelated to the Braak PD stage of the disease (i.e. distribution of LBs in the brain) or to cortical LB densities. "In our view, the fact that neither the widespread regional distribution of LBs nor increased cortical LB densities were found directly linked with pars compacta nigral cell loss lends support to the view that they are not the primary cause of the pathological process leading to cell death in vulnerable regions in the brain in Parkinson's disease," concludes Dr. Lees.

More information: The article is "Disentangling the Relationship between Lewy Bodies and Nigral Neuronal Loss in Parkinson's Disease" by Laura Parkkinen, Sean S O'Sullivan, Catherine Collins, Aviva Petrie, Janice L. Holton, Tamas Revesz, and Andrew J. Lees. Journal of Parkinson's Disease. 1(2011) 277-286. DOI 10.3233/JPD-2011-11046

Provided by IOS Press

Study finds nicotine patches may help improve memory loss in older adults

Wearing a nicotine patch may help improve memory loss in older adults with mild cognitive impairment, according to a study published today in Neurology, the medical journal of the American Academy of Neurology.

11 jan 2012--The study looked at individuals with mild cognitive impairment (MCI), the stage between normal aging and dementia when others begin to notice that an individual is developing mild memory or thinking problems. Many older adults with MCI go on to develop Alzheimer's disease.

The study looked at 74 non-smokers with MCI and an average age of 76. Half of the patients were given a nicotine patch of 15 mg a day for six months and half received a placebo. The study was designed so neither the participants nor the investigators knew which group received the nicotine patch.

Paul Newhouse, M.D., professor of Psychiatry and director of the Center for Cognitive Medicine at Vanderbilt University Medical Center, who authored the study, said the results of the study should not be viewed as an endorsement of smoking or of nicotine for normal individuals. "What we and others have shown is that nicotine doesn't do much for memory and attention in the normal population, but it does do something for those whose cognitive function is already impaired."

"People with memory loss should not start smoking or using nicotine patches by themselves because there are harmful effects of smoking and a medication such as nicotine should only be used with a doctor's supervision," Newhouse said. "But this study provides strong justification for further research into the use of nicotine for people with early signs of memory loss which may help us determine whether benefits persist over long periods of time and provide meaningful improvement."

Newhouse said nicotine is a "fascinating drug with interesting properties." The effects of nicotine are dependent on the initial state of a person's cognitive functioning, he said. "If you're already functioning fine, but slip down the hill, nicotine will push you back up toward the top. A little bit of the drug makes poor performers better. Too much, and it makes them worse again, so there's a range. The key issue is to find the sweet spot where it helps."

The study showed evidence of improvement across multiple cognitive tests for attention memory, speed of processing and consistency of processing. For example, after 6 months of treatment, the nicotine-treated group regained 46 percent of normal performance for age on long-term memory, whereas the placebo group worsened by 26 percent over the same time period. One area that didn't show significant improvement was that of "global impression," which means a health care provider didn't observe the patient was any better or any worse.

Newhouse said that future study is needed. "We need to do a much longer and larger study, to see if we can make a significant impact on the process of change. "

Nicotine stimulates receptors in the brain that are important for thinking and memory and may have neuroprotective effects. People with Alzheimer's disease lose some of those receptors.

Newhouse said the future of nicotinic treatment is to try to identify earlier stages at which treatment can be applied, to see if it changes the trajectory of those who already have evidence of memory loss. "I don't think it's going to become a treatment for Alzheimer's disease by itself. That would be like trying to rebuild a house after a fire when the fire's still going. You need to prevent the fire. The holy grail would be changing the deterioration curve."

Those in the study group receiving the nicotine patch experienced only minor side effects like nausea and dizziness, similar to what a person would experience when smoking a cigarette for the first time, Newhouse said. Those on the nicotine patch also experienced mild weight loss, not surprising since nicotine is an appetite suppressant. There were also no withdrawal symptoms reported when the study participants stopped using the nicotine patch.

Provided by Vanderbilt University Medical Center

Mass prostate cancer screening doesn't reduce deaths: study

There's new evidence that annual prostate cancer screening does not reduce deaths from the disease, even among men in their 50s and 60s and those with underlying health conditions, according to new research led by Washington University School of Medicine in St. Louis.

10 jan 2012--A longer follow-up of more than 76,000 men in a major U.S. study shows that six years of aggressive, annual screening for prostate cancer led to more diagnoses of tumors but not to fewer deaths from the disease.

The updated results of the Prostate, Lung, Cancer, Colorectal and Ovarian (PLCO) Cancer Screening Trial will be published online Jan. 6 in the Journal of the National Cancer Institute.

"The data confirm that for most men, it is not necessary to be screened annually for prostate cancer," says the study's lead author and principal investigator Gerald Andriole, MD, chief urologic surgeon at the Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine. "A large majority of the cancers we found are slow-growing tumors that are unlikely to be deadly."

The PLCO study involved men ages 55 to 74, who were randomly assigned to receive either annual PSA tests for six years and digital rectal exams for four years or "routine care," meaning they had the screening tests only if their physicians recommended them.

The new research updates an earlier report of the data published in 2009 in the New England Journal of Medicine. At that time, when nearly all men had been followed for seven years, Andriole and his colleagues did not find a mortality benefit from prostate cancer screening.

But because so few men in the study had died from any causes, the researchers said then that it would be premature to make broad generalizations about whether men should continue to be screened. However, they did recommend against prostate cancer screening for men with a life expectancy of seven to 10 years or less.

"Now, based on our updated results with nearly all men followed for 10 years and more than half for 13 years, we are learning that only the youngest men — those with the longest life expectancy — are apt to benefit from screening. We need to modify our current practices and stop screening elderly men and those with a limited life expectancy," says Andriole, who also is the Robert K. Royce Distinguished Professor. "Instead, we need to take a more targeted approach and selectively screen men who are young and healthy and particularly those at high risk for prostate cancer, including African-Americans and those with a family history of the disease."

Andriole recommends that men get a baseline PSA test in their early 40s because recent studies have indicated that elevated levels at that age can predict the risk of prostate cancer in later years. Men in their 40s with low PSA levels are very unlikely to develop lethal prostate cancer and could potentially avoid additional testing.

The researchers detected 12 percent more prostate tumors among men screened annually compared to those who received routine care (4,250 tumors in the screening arm vs. 3,815 tumors in the control arm).

But deaths from prostate cancer did not differ significantly between the groups. There were 158 deaths from prostate cancer in the screening group and 145 deaths in the routine-care group.

Annual screening tests also did not reduce deaths from prostate cancer among men in their 50s and 60s, as the researchers had hoped.

In addition, men diagnosed with prostate cancer who also had a history of heart attacks, strokes, diabetes, cancer or lung and liver disease were far more likely to die from causes other than prostate cancer – a finding that suggests that screening often finds tumors that are not likely to cause harm.

"Mass screening of all men on the basis of age alone is not the way to go, but screening can still be useful in select men," says Andriole, who acknowledges that widespread testing has lead many men with slow-growing tumors to be over-diagnosed and over-treated with surgery or radiation therapy, the possible side effects of which include incontinence and impotence. "We have to take a more nuanced approach to determine which men should be screened with PSA in the first place, how frequently they should be tested, the PSA level at which they should be biopsied and whether their cancer warrants aggressive therapy."

The study comes just months after a draft recommendation by the U.S. Preventive Services Task Force calling for an end to routine PSA testing for healthy men age 50 and older because of concerns that the test does not save lives and, when positive, often leads to invasive biopsies and aggressive treatments.

The researchers will continue to follow patients in the PLCO study for up to 15 years after they enrolled and evaluate the effects of prostate cancer screening on mortality.

More information: Andriole GL, Crawford ED, Grubb RL, Prorok PC et al. Prostate cancer screening in the randomized prostate, lung, colorectal and ovarian cancer screening trial: mortality results after 13 years of follow-up. Journal of the National Cancer Institute, published online Jan. 6, 2012.

Provided by Washington University School of Medicine

Low vitamin D levels linked to depression, psychiatrists report

Low levels of vitamin D have been linked to depression, according to UT Southwestern Medical Center psychiatrists working with the Cooper Center Longitudinal Study. It is believed to be the largest such investigation ever undertaken.

09 jan 2012--Low levels of vitamin D already are associated with a cavalcade of health woes from cardiovascular diseases to neurological ailments. This new study – published in Mayo Clinic Proceedings – helps clarify a debate that erupted after smaller studies produced conflicting results about the relationship between vitamin D and depression. Major depressive disorder affects nearly one in 10 adults in the U.S.

"Our findings suggest that screening for vitamin D levels in depressed patients – and perhaps screening for depression in people with low vitamin D levels – might be useful," said Dr. E. Sherwood Brown, professor of psychiatry and senior author of the study, done in conjunction with The Cooper Institute in Dallas. "But we don't have enough information yet to recommend going out and taking supplements."

UT Southwestern researchers examined the results of almost 12,600 participants from late 2006 to late 2010. Dr. Brown and colleagues from The Cooper Institute found that higher vitamin D levels were associated with a significantly decreased risk of current depression, particularly among people with a prior history of depression. Low vitamin D levels were associated with depressive symptoms, particularly those with a history of depression, so primary care patients with a history of depression may be an important target for assessing vitamin D levels. The study did not address whether increasing vitamin D levels reduced depressive symptoms.

The scientists have not determined the exact relationship – whether low vitamin D contributes to symptoms of depression, whether depression itself contributes to lower vitamin D levels, or chemically how that happens. But vitamin D may affect neurotransmitters, inflammatory markers and other factors, which could help explain the relationship with depression, said Dr. Brown, who leads the psychoneuroendocrine research program at UT Southwestern.

Vitamin D levels are now commonly tested during routine physical exams, and they already are accepted as risk factors for a number of other medical problems: autoimmune diseases; heart and vascular disease; infectious diseases; osteoporosis; obesity; diabetes; certain cancers; and neurological disorders such as Alzheimer's and Parkinson's diseases, multiple sclerosis, and general cognitive decline.

Investigators used information gathered by the institute, which has 40 years of data on runners and other fit volunteers. UT Southwestern has a partnership with the institute, a preventive medicine research and educational nonprofit located at the Cooper Aerobics Center, to develop a joint scientific medical research program aimed at improving health and preventing a wide range of chronic diseases. The institute maintains one of the world's most extensive databases – known as the Cooper Center Longitudinal Study – that includes detailed information from more than 250,000 clinic visits that has been collected since Dr. Kenneth Cooper founded the institute and clinic in 1970.

Provided by UT Southwestern Medical Center

Sexual satisfaction in women increases with age

A new study of sexually active older women has found that sexual satisfaction in women increases with age and those not engaging in sex are satisfied with their sex lives. A majority of study participants report frequent arousal and orgasm that continue into old age, despite low sexual desire. The study appears in the January issue of the American Journal of Medicine.

08 jan 2012--Researchers from the University of California, San Diego School of Medicine and the Veterans Affairs San Diego Healthcare System evaluated sexual activity and satisfaction as reported by 806 older women who are part of the Rancho Bernardo Study (RBS) cohort, a group of women who live in a planned community near San Diego and whose health has been tracked for medical research for 40 years. The study measured the prevalence of current sexual activity; the characteristics associated with sexual activity including demographics, health, and hormone use; frequency of arousal, lubrication, orgasm, and pain during sexual intercourse; and sexual desire and satisfaction in older women.

The median age in the study was 67 years and 63% were postmenopausal. Half the respondents who reported having a partner had been sexually active in the last 4 weeks. The likelihood of sexual activity declined with increasing age. The majority of the sexually active women, 67.1%, achieved orgasm most of the time or always. The youngest and oldest women in the study reported the highest frequency of orgasm satisfaction.

40% of all women stated that they never or almost never felt sexual desire, and one third of the sexually active women reported low sexual desire. Lead investigator Elizabeth Barrett-Connor, MD, Distinguished Professor and Chief, Division of Epidemiology, Department of Family and Preventive Medicine, University of California, San Diego School of Medicine, comments, "Despite a correlation between sexual desire and other sexual function domains, only 1 in 5 sexually active women reported high sexual desire. Approximately half of the women aged 80 years or more reported arousal, lubrication, and orgasm most of the time, but rarely reported sexual desire. In contrast with traditional linear model in which desire precedes sex, these results suggest that women engage in sexual activity for multiple reasons, which may include affirmation or sustenance of a relationship."

Regardless of partner status or sexual activity, 61% of all women in this cohort were satisfied with their overall sex life. Although older age has been described as a significant predictor of low sexual satisfaction, the percentage of RBS sexually satisfied women actually increased with age, with approximately half of the women over 80 years old reporting sexual satisfaction almost always or always. Not only were the oldest women in this study the most satisfied overall, those who were recently sexually active experienced orgasm satisfaction rates similar to the youngest participants. "In this study, sexual activity was not always necessary for sexual satisfaction. Those who were not sexually active may have achieved sexual satisfaction through touching, caressing, or other intimacies developed over the course of a long relationship," says first author Susan Trompeter, MD, Associate Clinical Professor of Medicine. Division of General Internal Medicine, Department of Medicine at the University of California, San Diego School of Medicine and Staff Physician at the VA San Diego Healthcare System.

"Emotional and physical closeness to the partner may be more important than experiencing orgasm. A more positive approach to female sexual health focusing on sexual satisfaction may be more beneficial to women than a focus limited to female sexual activity or dysfunction," Trompeter concludes.

More information: The article is "Sexual Activity and Satisfaction in Healthy Community-Dwelling Older Women," by Susan E. Trompeter, MD, Ricki Bettencourt, MS, and Elizabeth Barrett-Connor, MD. It appears in the American Journal of Medicine, Volume 125, Issue 1 (January 2012)

Provided by Elsevier

A decade of research proves PET effectively detects dementia

In a new review of imaging studies spanning more than ten years, scientists find that a method of positron emission tomography (PET) safely and accurately detects dementia, including the most common and devastating form among the elderly, Alzheimer's disease. This research is featured in the January issue of the Journal of Nuclear Medicine.

07 jan 2012--Researchers reviewed numerous PET studies to evaluate a molecular imaging technique that combines PET, which provides functional images of biological processes, with an injected biomarker called 18F-FDG to pinpoint key areas of metabolic decline in the brain indicating dementia. Having physiological evidence of neurodegenerative disease by imaging patients with PET could give clinicians the information they need to make more accurate diagnoses earlier than ever before.

"The new data support the role of 18F-FDG PET as an effective addition to other diagnostic methods used to assess patients with symptoms of dementia," says Nicolaas Bohnen, MD, PhD, lead author of the study and professor of radiology and neurology at the University of Michigan, Ann Arbor, Mich. "The review also identified new literature showing the benefit of this imaging technique for not only helping to diagnose dementia but also for improving physician confidence when diagnosing a patient with dementia. This process can be difficult for physicians, especially when evaluating younger patients or those who have subtle signs of disease."

Dementia is not a specific illness but a pattern of symptoms characterized by a loss of cognitive ability. These disorders can be caused by injury or progressive disease affecting areas of the brain that control attention, memory, language and mobility. While Alzheimer's is most commonly associated with progressive memory impairment, dementia with Lewy bodies, another form of the disease, can be associated with symptoms of Parkinson's and prominent hallucinations, while another disorder, called frontotemporal dementia, can be seen in patients showing uncharacteristic personality changes and difficulties in relating and communicating. Physicians can use FDG-PET with high accuracy to not only help diagnose dementia but also differentiate between the individual disorders. The role molecular imaging plays in the diagnosis of dementia has expanded enough that the official criteria physicians use to diagnose patients now includes evidence from molecular imaging studies.

"For the first time, imaging biomarkers of Alzheimer's disease are included in the newly revised clinical diagnostic criteria for the disease," says Bohnen. "This is a major shift in disease definition, as previously an Alzheimer's diagnosis was based mainly on a process of evaluating patients to exclude possible trauma, hemorrhage, tumor or metabolic disorder. Now it is becoming a process of inclusion based on biomarker evidence from molecular imaging."

The PET biomarker 18F-FDG comprises a radionuclide combined with fluorodeoxyglucose (FDG), which mimics glucose in the body. Cells metabolize FDG as fuel, and the variation in this uptake by cells throughout the body can then be imaged to detect a range of abnormalities. In the case of dementia, marked reductions in the metabolism of different lobes of the cerebral cortex can confirm a patient's disorder. Physicians can tell Alzheimer's disease apart from other dementias, depending on the specific cortices affected.

This review presents the most up-to-date and salient evidence of FDG-PET's usefulness for the evaluation of patients with suspected dementia. The objective of the study was to replace prior retrospective reviews that were performed as the technique was just emerging and that suggested methodological improvements. The new review includes studies with better methodology, including confirmation of diagnoses with autopsy, more expansive recruitment of subjects and use of multi-center studies. After reviewing 11 studies that occurred since the year 2000 and that met more stringent study review standards, researchers conclude that 18F-FDG is highly effective for detecting the presence and type of dementia.

"Using 18F-FDG PET in the evaluation of patients with dementia can improve diagnostic accuracy and lead to earlier treatment and better patient care," says Bohnen. "The earlier we make a diagnosis, the more we can alleviate uncertainty and suffering for patients and their families."

The biomarker 18F-FDG is among a variety of imaging agents being investigated for its efficacy in Alzheimer's imaging. As treatments for dementia become available for clinical use, PET will no doubt play an important role in not only the diagnosis of these diseases, but also the assessment and monitoring of future therapies.

According to the World Health Organization, an estimated 18 million people worldwide are currently living with Alzheimer disease. That number is projected to almost double by 2025.

More information: "Effectiveness and safety of FDG-PET in the evaluation of dementia: a review of the recent literature" Journal of Nuclear Medicine. http://jnm.snmjournals.org/

Provided by Society of Nuclear Medicine

Cognitive decline can begin as early as age 45: study

The brain's capacity for memory, reasoning and comprehension skills (cognitive function) can start to deteriorate from age 45, finds research published in the British Medical Journal today.

06 jan 2012--Previous research suggests that cognitive decline does not begin before the age of 60, but this view is not universally accepted.

Researchers, led by Archana Singh-Manoux from the Centre for Research in Epidemiology and Population Health in France and University College London in the UK, argue that "understanding cognitive ageing will be one of the challenges of this century," especially as life expectancy continues to rise.

They add that it is important to investigate the age at which cognitive decline begins because medical interventions are more likely to work when individuals first start to experience mental impairment.

Therefore the authors observed 5,198 men and 2,192 women over a 10-year period from 1997. They were all civil servants aged between 45 and 70 and were part of the Whitehall II cohort study established in 1985.

Participants' cognitive functions were assessed three times over the study period. Individuals were tested for memory, vocabulary and aural and visual comprehension skills. The latter include recalling in writing as many words beginning with "S" (phonemic fluency) and as many animal names (semantic fluency) as possible.

Differences in education level were taken into account.

The results show that cognitive scores declined in all categories (memory, reasoning, phonemic and semantic fluency) except vocabulary and there was faster decline in older people.

The findings also reveal that over the 10-year study period there was a 3.6% decline in mental reasoning in men aged 45-49 and a 9.6% decline in those aged 65-70. The corresponding figures for women were 3.6% and 7.4%.

The authors argue that robust evidence showing cognitive decline before the age of 60 has important ramifications because it demonstrates the importance of promoting healthy lifestyles, particularly cardiovascular health, as there is emerging evidence that "what is good for our hearts is also good for our heads."

They add that targeting patients who suffer from one or more risk factors for heart disease (obesity, high blood pressure and high cholesterol levels) could not only protect their hearts but also safeguard them from dementia in later life.

In an accompanying editorial, Francine Grodstein, Associate Professor of Medicine at Brigham and Women's Hospital in Boston, says the study "has profound implications for prevention of dementia and public health."

She adds that more creative research, perhaps using telephone and computer cognitive assessments, needs to be undertaken.

Provided by British Medical Journal

Another potential risk factor for developing dementia and Alzheimer's disease women

A hormone derived from visceral fat called adiponectin may play a role as a risk factor for development of all-cause dementia and Alzheimer disease (AD) in women, according to a study published Online First by the Archives of Neurology.

05 jan 2012--The number of people affected by dementia worldwide is estimated to double over the next 20 years from the current number of about 36 million people, the authors provide as background information in the article. AD is the most common form of dementia. The authors write that data suggest an association between insulin resistance and inflammation, hallmarks for type 2 diabetes, and development of dementia. "An additional potential factor that may contribute to the onset of AD and all-cause dementia is adiponectin. Adiponectin is a hormone derived from visceral fat, which sensitizes the body to insulin, has anti-inflammatory properties, and plays a role in the metabolism of glucose and lipids."

Thomas M. van Himbergen, Ph.D., from the Lipid Metabolism Laboratory, Human Nutrition Research Center on Aging, Tufts University, Boston, and colleagues measured levels of glucose, insulin, and glycated albumin, as well as C reactive protein, lipoprotein associated phospholipase A2, and adiponectin in the plasma of patients at the 19th biennial examination (1985 – 1988) of the Framingham Heart Study.

The 840 patients (541 women, median age of 76 years) were followed-up for an average of 13 years and evaluated for signs of the development of AD and all-cause dementia. During that time, 159 patients developed dementia, including 125 cases of AD. After adjustment for other dementia risk factors (age, apoE genotype, low plasma docosahexaenoic acid, weight change) only adiponectin in women was associated with an increased risk of all-cause dementia and AD.

"It is well established that insulin signaling is dysfunctional in the brains of patients with AD, and since adiponectin enhances insulin sensitivity, one would also expect beneficial actions protecting against cognitive decline," the authors write. "Our data, however, indicate that elevated adiponectin level was associated with an increased risk of dementia and AD in women."

"One of the main features of adiponectin is that it has been shown to play a role in the sensitization of insulin and therefore may become a therapeutic target for the treatment of T2D (type 2 diabetes). Surprisingly, a higher adiponectin level was found to be a predictor of all-cause and vascular mortality. In concurrence with the mortality findings, the current investigation shows that an elevated adiponectin level is also an independent predictor for all-cause dementia and AD in women," the authors conclude.

More information: Arch Neurol. Published online January 2, 2012. doi:10.1001/archneurol.2011.670

Provided by JAMA and Archives Journals

Genetic predisposition to disease common in two supercentenarians: study

The first-ever published whole-genome sequences of not just one, but two supercentenarians, aged more than 114 years, reveal that both unusual and common genetic phenomena contribute to the genetic background of extreme human longevity.

04 jan 2012--Data from the study led by researchers from the Boston University Schools of Public Health and Medicine and Boston Medical Center -- will be available to researchers around the world at the NIH data repository.

In the study, published Jan. 3 in the open-access journal Frontiers in Genetics, researchers at BU, the University of Florida, Gainesville, and The Scripps Research Institute report a comprehensive analysis of the whole genome sequences of a man and a woman, both of whom lived past the age of 114. Supercentenarians (age 110+ years) are very rare, occurring at a rate of one person per five million in developed countries, and there is growing evidence supporting a strong genetic influence in survival to such ages.

The study, led by Paola Sebastiani, professor of biostatistics at the BU School of Public Health, shows that the overall genomic architecture of these two subjects is comparable to that of other published full genomes, in terms of rates of novel variants, functional variants, and variants that predispose to common age-related diseases and common cancers. But while the two carried as many disease-associated genes as the general population, their longevity suggests other protective mechanisms at work.

For example, the male subject had 37 genetic mutations associated with increased risk for colon cancer -- indicating that he was in no way immune to that age-related disease. "In fact, he had presented with an obstructing colon cancer earlier in his life that had not metastasized and was cured with surgery. He was in phenomenal cognitive and physical shape near the time of his death," said Dr. Thomas Perls, director of the New England Centenarian Study and senior author of the article.

The female supercentenarian also had numerous genetic variations associated with age-related diseases, including those related to increased risks for Alzheimer's, cancer and heart disease. She did have congestive heart failure and mild cognitive impairment, but these diseases did not become evident until after the age of 108 years.

"The presence of these disease-associated variants is consistent with our and other researchers' findings that centenarians carry as many disease-associated genes as the general population," Perls said. "The difference may be that the centenarians likely have longevity-associated variants that cancel out the disease genes. That effect may extend to the point that the diseases don't occur -- or, if they do, are much less pathogenic or markedly delayed towards the end of life, in these individuals who are practically living to the limit of the human lifespan."

In support of this conjecture, Sebastiani and colleagues identified more than 50 putative longevity-associated variants in genes that determine two forms of progeria (an accelerated aging disease), and genes linked to cardiovascular disease and Alzheimer's disease. The authors highlighted the importance of performing follow-up studies to determine the impact and function of these genetic variants and their role in regulating health span, as well as life span.

The findings of the study suggest that unusual genetic phenomena and a combination of rare and common genetic variants contribute to the genetic background of extreme human longevity, the authors said.

"The study of these two supercentenarians is just the beginning, and genetic study of many more such subjects needs to be performed," said Perls. A number of such endeavors are underway, on a larger scale, including the Archon Genomics X Prize and a collaboration between Complete Genomics, Inc., The Scripps Translational Science Institute, and other institutions.

More information: http://www.frontie … 090/abstract

Provided by Boston University Medical Center

Changes seen in cerebrospinal fluid levels before onset of Alzheimer dementia

Cerebrospinal fluid levels of Aβ42 appear to be decreased at least five to 10 years before some patients with mild cognitive impairment develop Alzheimer disease (AD) dementia whereas other spinal fluid levels seem to be later markers of disease, according to a report in the January issue of Archives of General Psychiatry.

03 jan 2012--Hopefully, new therapies that can retard or even halt progression of the disease will soon be available. Together with an early and accurate diagnosis, such therapies could be initiated before neuronal degeneration is too widespread and patients are already demented," the authors conclude.

The researchers note as background in the study that disease-modifying therapies, such as immunotherapy, are more likely to be successful if started in the early stages of the disease so there is a need to identify patients with Alzheimer disease before neurodegeneration is not too severe.

Peder Buchhave, M.D., Ph.D, who is affiliated with Lund University and Skane University, Sweden, and colleagues conducted an extended follow-up of the cohort from a previous study of 137 patients with mild cognitive impairment (MCI) at baseline. The median follow-up was 9.2 years.

During the follow-up, 72 patients (53.7 percent) developed AD and 21 (15.7 percent) progressed to other forms of dementia. At the baseline, cerebrospinal fluid Aβ42 levels were reduced and other biomarkers T-tau and P-tau levels were elevated in patients who converted to AD during follow-up compared with levels in patients who did not develop AD.

The study indicates baseline CSF Aβ42 levels were equally reduced in patients with MCI who converted to AD within five years (the early converters) compared to those who converted later between five and 10 years. However, T-tau and P-tau levels were significantly higher in early converters compared to later ones.

Researchers suggest that "approximately 90 percent of patients with MCI and pathologic CSF biomarkers at baseline will develop AD within 9.2 years."

"Therefore, these markers can identify individuals at high risk for future AD least five to 10 years before conversion to dement

Provided by JAMA and Archives Journals

How to prevent, treat a New Year's hangover

01 jan 2012-- New Year’s Eve is fast approaching and many plan on ringing in the new year with a few drinks.

Dr. Aaron Michelfelder, a Loyola University Health System family physician, offers these tips on how to avoid the misery of a New Year's hangover:

Before the party:

• Plan to drink moderately -- a maximum of five drinks for men and three drinks for women during a minimum three-hour periode.

During the party:

• Eat first, and then drink, not the other way around. Food slows the absorption of alcohol.

• Drink slowly.

• To prevent dehydration, drink a glass of water after each alcoholic drink.

• Take a B vitamin supplement.

After the party:

• Do not drink and drive.

• Get as much sleep as possible.

• The morning after:

• Take another B vitamin.

• Drink lots of water.

• Exercise (if you can stand it). During vigorous exercise, blood circulates three times as fast as it does when you are sitting on the couch. And the faster you circulate blood through your liver and kidneys, the faster your body will remove the toxins.

What doesn't work:

• Coffee will make you more alert, but it won't prevent or help a hangover.

• Forget "hair of the dog" -- the notion that having a drink can relieve a hangover. It will only make you feel worse.

Provided by Loyola University Health System