Infection risk up for seniors with rheumatoid arthritis

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

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

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

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

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

More information: Abstract 

Clinicians can unintentionally prompt nocebo effect

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

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

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

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

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

Two authors disclosed financial ties to the pharmaceutical industry.

More information: Full Text

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

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

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

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

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

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

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

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

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

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

Provided by The Mount Sinai Hospital

Alzheimer's cognitive decline slows in advanced age

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

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

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

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

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

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

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

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

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

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

Provided by University of California - San Diego

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

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

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

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

First Encouraging Results after Removal of Autoantibodies by Immunoadsorption

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

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

Provided by Helmholtz Association of German Research Centres

What would happen without PSA testing?

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

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

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

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

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

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

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

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

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

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

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

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

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

Provided by Wiley

Blocking the effects of amyloid b in Alzheimer's disease

During Alzheimer's disease, 'plaques' of amyloid beta (Ab) and tau protein 'tangles' develop in the brain, leading to the death of brain cells and disruption of chemical signaling between neurons. This leads to loss of memory, mood changes, and difficulties with reasoning. New research published in BioMed Central's open access journal Alzheimer's Research & Therapy, has found that up-regulating the gene Hes1 largely counteracted the effects of Ab on neurons, including preventing cell death, and on GABAergic signaling.

31 july 2012--The exact mechanism behind how Ab contributes to Alzheimer's disease is not yet fully understood, however researchers from Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER) in Spain recently discovered that Ab interferes with the normal activity of nerve growth factor (NGF). One of the actions of NGF is activating the protein Hes1, a transcription factor required to turn on other genes. Without this factor GABAergic signaling within the brain decreases.

Using gene therapy techniques, Pedro Chacón and Alfredo Rodríguez-Tébar augmented the amount of Hes1 in cultured neurons. Increasing the amount of Hes1, directly or by activating the protein NF-kB (which in turn up-regulate the cell's own Hes1), abolished the effect of Ab and prevented neuron death. Additionally another growth factor, TGFb, which can also activate NF-kB, was able to prevent the effects of Ab on neurons by improving levels of Hes1.

Pedro Chacón explained, "Ab usually decreases the length of dendrites and GABAergic connectivity of neurons, however these effects were completely reversed by Hes1, NF-kB, and TGFb. When we grew neurons in a concentration of Ab which normally kills most cells, 50% of the neurons with extra Hes1 were able to survive."

These results demonstrate that neurons can be protected from the effects of Ab by increasing the amount of Hes1 in the cells. By clarifying the roles of NGF or TGFb in Hes1 protection this research provides strategies for limiting the effects of Alzheimer's disease.

More information: Increased expression of the homologue of Enhancer-of-split 1 protects neurons from beta amyloid neurotoxicity and hints at an alternative role for transforming growth factor beta1 as a neuroprotector Pedro J Chacon and Alfredo Rodriguez-Tebar Alzheimer's Research & Therapy (in press)

Provided by BioMed Central

Shortened telomere length tied to dementia, mortality risk

30 july 2012-- Shortened telomere length (TL) is associated with risks for dementia and mortality in a population of older adults, according to a study published online July 23 in the Archives of Neurology.

Lawrence S. Honig, M.D., Ph.D., from the Columbia University College of Physicians and Surgeons in New York City, and colleagues used real-time polymerase chain reaction analysis to determine TL in stored leukocyte DNA from 1,983 participants in a community-based study of aging. Participants were 65 years or older and blood was drawn at a mean age of 78.3 years. Participants were followed for a median of 9.3 years for mortality, and 9.6 percent developed incident dementia.

The researchers found that TL correlated inversely with age and was shorter in men than women. TL was significantly shorter in persons dying during follow-up compared with survivors, even after adjusting for age, sex, education, and apolipoprotein E genotype. TL was significantly shorter in the participants with incident and prevalent dementia, compared with those who remained dementia-free. Shorter TL correlated with earlier onset of dementia but this association was significant in women only.

"Our results show an association between shortened TL and mortality, and more specifically an association of shortened TL with Alzheimer's disease, and are consistent with but not indicative of the possibility that TL may be a factor indicative of biological age," the authors conclude.

More information: Abstract
Full Text

Japanese women fall behind Hong Kong in longevity

29 july 2012— Japanese women are no longer the world's longest living, their longevity pushed down in part by last year's devastating earthquake and tsunami, according to a government report Thursday. The top of the global life expectancy rankings now belongs to Hong Kong women.

The annual report by Japan's health ministry said the expected lifespan for Japanese women slipped to 85.90 years in 2011 from 86.30 the year before, mainly due to disease and other natural causes of death. The life expectancy for men also declined slightly, from 79.55 to 79.44.

The report said that the earthquake and tsunami, which killed nearly 20,000 people, contributed to pushing the statistics down. It noted that if deaths related to the disaster were not included, the life expectancies would be higher for both men, at 79.70 years, and women, at 86.24.

But the official life expectancy for women in Hong Kong — 86.70 years in 2011 — would still be longer than Japan's even without the disaster deaths, the report said.

It said suicides among Japanese women have been on the rise, and that was a contributing factor, although disease and other natural causes remained the most important issues.

Officials said it was the first time since 1985 that Japan's women had ranked second.

The ministry's report, which uses statistics supplied by other countries or the U.N. for its comparisons, noted that international statistics are hard to compare because of differences in calculation methods.

What's that symptom? Experts warn of self-diagnosis via the web

Many people prone to leap to worst-case conclusions when investigating own ailments, study finds.

28 july 2012-- Got a weird ache or pain? A rash that's hung around too long? With the wealth of information now available at the click of a mouse, it's common to search the Web to figure out what may be wrong with you.

But a new study suggests that when the symptoms are your own, "self-diagnosis" via the Internet -- or anywhere but a doctor's office -- too often leads to inaccurate, worst-case conclusions.

Research suggests that people tend to overestimate their own risk for serious ailments, in a way that they wouldn't do if they were thinking about someone else's symptoms.

"This is particularly true when the disease is rare," said study co-author Dengfeng Yan, a doctoral student at the Hong Kong University of Science and Technology. "That is, given the same set of symptoms, people will overestimate their own likelihood of getting such rare (often serious) diseases than that of other people."

The study was published online recently in the Journal of Consumer Research and will appear in the journal's February 2013 print issue.

In a series of six experiments, Yan and co-researcher Jaideep Sengupta gave nearly 250 college students information about such diseases as flu, HIV, osteoporosis and breast cancer.

In the experiment on flu, for example, the students were told they were simply being tested on what they knew about the illness. But the researchers then told them to imagine that they had a number of symptoms -- cough, fever, runny nose, headache -- and then asked whether they thought they had "regular" flu or the (at the time) rarer and scarier H1N1 "swine" flu. They were also asked to diagnose a hypothetical "someone else" with these symptoms.

According to the researchers, when referring to their own symptoms people were much quicker to diagnose the rarer H1N1 strain of flu compared to if they thought the symptoms were someone else's. In other words, their accuracy in correctly gauging the likelihood of H1N1 infection dropped if they were thinking about their own symptoms.

Why the difference? "We explain these effects using the concept of psychological distance," Yan said. With distancing -- in other words, thinking about someone else rather than yourself -- people tend to rely more on broader information such as statistics (that is, the likelihood any one person will get disease X) and less on information specific to the individual, such as the symptoms he or she is having.

"Consumers often fear the worst when it comes to their own health, while maintaining a calm objectivity with regard to others," Yan said. If you've got pain in the chest, you think: heart attack. If a friend of a friend has the same symptoms, you say: probably indigestion.

But this type of thinking can have downsides, the authors write, often leading "to mistakenly diagnosing oneself as possessing a serious disease, causing both unnecessary anxiety and wasteful medical expenditure." They add that, "mistaken self-diagnoses of this sort are particularly likely given the ease of information access on the Internet, which frequently leads consumers to engage in 'symptom-matching' exercises."

The findings ring true with Dr. Peter Galier, an internal medicine specialist at Santa Monica-UCLA Medical Center, who reviewed the findings.

"I think it's human nature," he said. People are much more likely to worry about themselves and family members, he said, than about strangers.

Getting information via the Web can also make it difficult to decide what symptoms mean in the absence of a doctor's analysis. "When people are able to access a lot of information that isn't filtered, and they don't have expertise in the field, they don't know how to prioritize the information," Galier explained.

That's true whether you're investigating that strange knocking noise in your car but have no clue about mechanics, he said, or whether you've just spotted a lump in your thigh and have no medical expertise.

For instance, a healthy young man may have just drank a very cold soda and then has crushing chest pain. If he looks that up online, he is likely to see that the symptoms may point to a heart attack, Galier said. But that information doesn't take vital facts such as the man's age and medical history into account, he said. "Chest pain in a 55-year-old guy is looked at much differently than in a 25-year-old guy," he said.

Instead of doing amateur diagnosing on their own, Yan said, "We advise people to see a real doctor."

And as the new study points out, ''The advantage of seeing a real doctor isn't just because he or she is an expert," he said. "It's also that they aren't you."

For that reason, they will take into account less "emotional" information, such as how many people in the population actually get the condition you worry that you might have.

And what about that worrying time before you can get to your doctor's office? "People may simply tell the situation to their colleagues," Yan said, since they're likely to put those symptoms into a less panicked perspective.

Lower vitamin D could increase risk of dying, especially for frail, older adults

Milk is one of the sources of vitamin D. About 70 percent of Americans, and up to a billion people worldwide, have insufficient levels of vitamin D. 

A new study concludes that among older adults – especially those who are frail – low levels of vitamin D can mean a much greater risk of death.

27 july 2012--The randomized, nationally representative study found that older adults with low vitamin D levels had a 30 percent greater risk of death than people who had higher levels.

Overall, people who were frail had more than double the risk of death than those who were not frail. Frail adults with low levels of vitamin D tripled their risk of death over people who were not frail and who had higher levels of vitamin D.

"What this really means is that it is important to assess vitamin D levels in older adults, and especially among people who are frail," said lead author Ellen Smit of Oregon State University.

Smit said past studies have separately associated frailty and low vitamin D with a greater mortality risk, but this is the first to look at the combined effect. This study, published online in the European Journal of Clinical Nutrition, examined more than 4,300 adults older than 60 using data from the Third National Health and Nutrition Examination Survey.

"Older adults need to be screened for vitamin D," said Smit, who is a nutritional epidemiologist at OSU's College of Public Health and Human Sciences. Her research is focused on diet, metabolism, and physical activity in relation to both chronic disease and HIV infection.

"As you age, there is an increased risk of melanoma, but older adults should try and get more activity in the sunshine," she said. "Our study suggests that there is an opportunity for intervention with those who are in the pre-frail group, but could live longer, more independent lives if they get proper nutrition and exercise."

Frailty is when a person experiences a decrease in physical functioning characterized by at least three of the following five criteria: muscle weakness, slow walking, exhaustion, low physical activity, and unintentional weight loss. People are considered "pre-frail" when they have one or two of the five criteria.

Because of the cross-sectional nature of the survey, researchers could not determine if low vitamin D contributed to frailty, or whether frail people became vitamin D deficient because of health problems. However, Smit said the longitudinal analysis on death showed it may not matter which came first.

"If you have both, it may not really matter which came first because you are worse off and at greater risk of dying than other older people who are frail and who don't have low vitamin D," she said. "This is an important finding because we already know there is a biological basis for this. Vitamin D impacts muscle function and bones, so it makes sense that it plays a big role in frailty."

The study divided people into four groups. The low group had levels less than 50 nanograms per milliliter; the highest group had vitamin D of 84 or higher. In general, those who had lower vitamin D levels were more likely to be frail.

About 70 percent of Americans, and up to a billion people worldwide, have insufficient levels of vitamin D. And during the winter months in northern climates, it can be difficult to get enough just from the sun. OSU's Linus Pauling Institute recommends adults take 2,000 IU of supplemental vitamin D daily. The current federal guidelines are 600 IU for most adults, and 800 for those older than 70.

"We want the older population to be able to live as independent for as long as possible, and those who are frail have a number of health problems as they age," Smit said. "A balanced diet including good sources of vitamin D like milk and fish, and being physically active outdoors, will go a long way in helping older adults to stay independent and healthy for longer."

Provided by Oregon State University

More testosterone increases prostate cancer risk in older men: study

26 july 2012-- Older men - those in their 70s and 80s - with higher levels of testosterone, including those who undergo hormone replacement therapy, are at an increased risk of prostate cancer, according to new research.  

Results from Australia's largest healthy ageing study, The Health in Men Study (HIMS), published online today in the peer reviewed journal, Cancer Epidemiology Biomarkers & Prevention, have confirmed this link.

Lead author from The University of Western Australia's Centre for Health and Ageing, Dr Zoë Hyde, said while higher levels of testosterone were unlikely to cause cancer, they might make an existing cancer grow faster. 

However, Dr Hyde cautioned that this did not prove a cause-and-effect relationship.

"We need to conduct large-scale long-term trials of testosterone therapy to see if this risk applies to men receiving testosterone," she said.

The research is timely because the use of testosterone therapy is growing, and prostate cancer is very common in old age, Dr Hyde said.

Low testosterone in older men can cause loss of muscle mass, decreased sexual function, fatigue, mood changes, depression and impaired cognition. Hormone replacement therapy may seem the best approach to relieve the symptoms, but scientists now believe more research is needed on this treatment to determine if it does help patients.

They say the possibility that high levels of testosterone could make prostate cancer grow faster is concerning.  A cancer that would have gone undetected and never caused any problems might now affect health.

"While some men can benefit from testosterone therapy, we still don't fully understand all of the benefits and risks of treatment," Dr Hyde said.

"There is no need for men who are currently taking testosterone to stop but in light of our findings, prostate health should be monitored closely during treatment."

This research is part of the Health In Men Study that has been following a group of men living in Perth, Western Australia, since 1996 and is the largest study of ageing men in Australia.  The study involved community-dwelling men in their 70s and 80s but excluded those receiving hormonal therapy or men with prostate cancer.

More information: cebp.aacrjournals.… .EPI-12-0129

Provided by University of Western Australia

A quarter of our very elderly have undiagnosed treatable heart problems, research reveals

The very oldest in our society are missing out on simple heart treatments which can prolong and improve their quality of life, Newcastle heart experts say.

25 july 2012--Studying a group of people aged 87 to 89 years old, the team of researchers at Newcastle University found that a routine test in the home revealed that around a quarter of them had undiagnosed heart problems which could be treated with established and cost-effective treatments.

In the study, funded by the British Heart Foundation (BHF), the team visited the homes of 376 people aged 87 to 89 years old and carried out echocardiograms -heart scans- using portable instruments.

Publishing today in Heart, they reveal that around a quarter (26%) of the people involved had a previously undiagnosed heart problem, in particular, impairment of left ventricular systolic function. Affected people's hearts do not contract strongly enough, which can leave them breathless and lead to heart failure. The condition is treatable with established drugs such as beta-blockers and ACE inhibitors.

BHF Professor Bernard Keavney, a cardiologist at Newcastle University who led the study, admits to being taken aback at the extent of the problem: "We were surprised to discover just how many older people have heart problems. Many of these people could be treated with drugs that we know work, if their condition were recognised.

"Our research suggests that it might be practical to offer people over 85 who are breathless, an echocardiogram at home which would reveal these problems. Because this heart problem occurs so often at this age, home checks are likely to be cost-effective, whereas they wouldn't be in younger people In those people found to have hearts that were not pumping strongly enough on a home scan, medication could be considered. This would improve their quality of life and it's likely to slow their progression to heart failure.

"With heart failure, prevention is definitely a priority. Older patients coming into hospital with worsening heart failure is one of the largest sources of expenditure for the NHS. The number of people over 85 is already soaring, and this will continue for the foreseeable future. So anything we can do to improve the heart health of our oldest old is likely to have a big impact."

Taking part in the research were people involved in the Newcastle 85+ study, a unique study of the health of more than one thousand people from Newcastle and North Tyneside born in 1921.

"This is a group of people who are routinely excluded from trials of treatment on the grounds of their age," adds Dr. Joanna Collerton, Senior Clinical Research Associate at Newcastle's Institute for Ageing and Health and the study's co-lead author. "What we have discovered is that very many more people in this age group have heart problems compared to those in younger age groups so we need to think about more inclusive trials or trials focusing exclusively on older groups to ensure that as we face a growing older population we offer them the healthiest future."

Dr Shannon Amoils, Research Advisor at the BHF, said: "This study suggests that there are probably many more very elderly people in the community with heart problems than we previously supposed and many have symptoms like breathlessness that limits their daily activities. Despite this, their heart condition is often not recognised."

This research builds on Newcastle University's work as part of the Newcastle Initiative on Changing Age and the Newcastle institute for Social Renewal. This the University's response to the societal challenges including ageing, seeking new ways to make the most of the extensive opportunities associated with increasing human longevity, while at the same time solving some of the problems.

Provided by Newcastle University

Meta-analysis: Interventions improve depression in cancer patients

Despite guidelines recommending screening for depression in cancer patients, it's been unclear whether interventions designed to treat this depression are effective. A study by the University of Colorado Cancer Centerand other institutions, published in the Journal of the National Cancer Institute, changes that. This meta-analysis of 10 studies encompassing 1362 patients shows that especially cognitive behavioral therapy and pharmacologic interventions decrease depressive symptoms in cancer patients.

24 july 2012--"In the past, we had looked at interventions as a whole – most of which were designed to help cancer patients cope generally with stress but not specifically with depression – and found moderate effects. This study shows not only that interventions specific to depression in cancer patients can improve symptoms, but shows which interventions are likely to offer the most benefit," says Kristin Kilbourn, PhD, CU Cancer Center investigator and assistant professor of psychology at the University of Colorado Denver.

The recent study is the culmination of a five-year effort during which Kilbourn and collaborators combed the literature for studies that met stringent criteria specifying that studies were randomized control trials in which cancer patients reported a significant number of depressive symptoms prior to starting the intervention.

"Still, many questions exist," Kilbourn says. "For example, which interventions are best in early cancers versus metastatic disease? Do we find similar effectiveness if patients were diagnosed with depression before their cancer? And which interventions are most effective with different cultural and ethnic subpopulations?" Likewise, Kilbourn hopes further study will explore the durability of gains patients experience with these interventions.

Finally, "This study supports the notion that screening for depression in cancer patients is important because if we could identify people early in the process and intervene, we now know definitively that we can affect the trajectory of this depression," Kilbourn says.

Provided by University of Colorado Denve

Exposure to light could help Alzheimer's patients sleep better

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23 july 2012 -- Individuals with Alzheimer’s disease and related dementias (ADRD) often sleep during the day and are awake at night. The situation can turn life-threatening if they leave their homes and wander around outside. This irregular sleep schedule and night wandering, and the consequent burden on their caretakers, is a primary reason individuals with ADRD are placed in more controlled environments such as nursing homes. A new study from the Lighting Research Center (LRC) at Rensselaer Polytechnic Institute lays the foundation for the importance of tailored light exposures as a viable treatment option for the reduction of sleep disturbances in older adults and those with ADRD.

Funded by a grant from the National Institute on Aging (NIA), the study is the first to collect circadian light exposures in individuals with ADRD. Results of the quantitative study show that individuals with ADRD experienced lower light levels, exhibited lower activity levels, and had greater disruption to their natural circadian rhythms than healthy older adults. The findings also show that people with ADRD experience lower levels of light exposure and greater levels of circadian disruption during the winter.

“We used light/dark and activity/rest patterns to assess circadian disruption and our results are consistent with previous studies. However, this is the first field study to examine the synchrony between the circadian light pattern and the activity response pattern to assess circadian disruption,” said Mariana Figueiro, associate professor at Rensselaer and director of the Light and Health Program at the LRC, who led the study. “Measurements revealed that those with ADRD experienced more circadian disruption than healthy older adults.”

Results of the study, titled “Field Measurements of Light Exposures and Circadian Disruption in Two Populations of Older Adults,” will appear in the Journal of Alzheimer’s Disease. Figueiro presented the research team’s findings at the Alzheimer’s Association International Conference in Vancouver on July 17.

Along with Figueiro, co-authors of the study are LRC Director and Professor Mark S. Rea, LRC Research Specialist Robert Hamner, along with Patricia Higgins and Thomas Hornick, clinicians at Case Western Reserve University and Louis Stokes Cleveland VA Medical Center in Cleveland, Ohio.

Growing evidence indicates that circadian disruption by irregular light/dark patterns is associated with reduced quality of life and increased risk of disease. Circadian rhythms are governed by the human body’s master clock in what is known as the suprachiasmatic nuclei (SCN), which has an intrinsic period slightly longer than 24 hours. On average, the SCN runs with a period of 24.2 hours. Light/dark patterns on the retina, the photosensitive part of the eye, synchronizes the SCN to the 24-hour solar day, regulating biological rhythms such as when we are active and when we sleep. Without exposure to a regular, daily pattern of light and dark, circadian rhythms can become irregular.

“Biology is driven by circadian rhythms at every level, and light is the main stimulus for synchronizing the circadian system to the solar day. By quantifying an individual’s light/dark exposure pattern, we can prescribe ‘light treatments’ promoting circadian entrainment, thereby improving health and well-being,” said Figueiro.

To collect data for the study, the research team used a Dimesimeter, a dime-sized device developed by the LRC, to record how much photopic and circadian light an individual is exposed to and whether they are active or resting. The data-logging device records these light and activity levels continuously over many days, and can be easily attached to shirt collars, lapels, hats, wristbands, or eyeglasses. The Dimesimeter enables researchers to examine light/dark and activity/rest patterns in those experiencing circadian sleep disorders, such as Alzheimer’s patients. Data from the device can be downloaded to a computer and processed to calculate a cross-correlation of the activity/rest and light/dark exposure data, a measure of circadian entrainment/disruption.

“The Dimesimeter system allows researchers to accurately measure light/dark exposure and activity/rest patterns to quantify circadian disruption. In this way, we can collect ecological data on populations who suffer from circadian sleep disorders,” said Rea. “This new study using the Dimesimeter is a major step toward the goal of better understanding the impact of circadian disruption on human health.”

For the new NIA-funded study, the research team enlisted 16 healthy older adults and 21 adults with ADRD to wear a Dimesimeter on their wrists for one week. The research team in Cleveland collected data from those with ADRD and the research team in Troy collected the data from healthy older adults. From the resulting data, the researchers calculated two metrics for each subject: relative activity (RA) to measure activity, and phasor magnitude to measure both light exposure and activity. The analysis revealed that during winter, those with ADRD exhibited more circadian disruption than healthy adults as reflected by their significantly shorter phasor magnitudes and lower RA values. Those with ADRD studied in winter also had significantly shorter phasor magnitudes than those studied in summer. ADRD adults were less active during waking hours than healthy adults, and ADRD adults studied in winter were exposed to less light than healthy adults in winter and ADRD adults in summer. The research team is currently delivering a lighting intervention to those with ADRD and their caretakers and measuring its impact on their sleep efficiency and circadian disruption.

Looking forward, the Dimesimeter could one day allow physicians to predict the optimum timing of the light therapy necessary to resynchronize the circadian phase with the solar day. Such treatments could range from going outdoors for 15 minutes to sitting in front of a light box fitted with blue LEDs for a prescribed amount of time, according to Figueiro.

Last year, international magazine The Scientist named the LRC’s Dimesimeter as one of the “ Top 10 Innovations of 2011.”

Provided by Rensselaer Polytechnic Institute

New study evaluates link between physical activity in middle age and onset of dementia in later life

22 july 2012-- Dementia and cognitive impairment are important public health issues, due to the morbidity associated with deteriorating memory, and the cost of caring for patients by both families and health services.

Previous studies have suggested that physical activity may be protective against dementia and cognitive impairment; however results have been conflicting. Many studies in this area have been limited by small sample sizes and short follow-up times.

New research, which aimed to measure the association between physical activity and onset of dementia and cognitive impairment, has found no association.

The cohort study, published in the Journal of Alzheimer’s Disease and led by academics from the University of Bristol and Cardiff University, analysed data from 1,005 middle-aged, and mostly manual-class, men in order to identify whether physical activity in mid-life is a risk factor for dementia and cognitive impairment.

Using data from The Caerphilly Prospective Study, the researchers carried out analyses using data on levels of leisure-time and work-related physical activity (collected when the men were aged 48-66 years) and cognitive function measured an average 16 years later. 

The study’s results did not provide any convincing evidence of an association between either leisure-time or work-related physical activity in mid-life and dementia or cognitive impairment in later life.

Dr. Gemma Morgan, lead researcher from Bristol’s School of Social and Community Medicine, said: “Although our results show no protective effect of mid-life physical activity for cognitive decline in later life, there is good evidence that physical activity prevents other health problems. It is important that the health benefits of physical activity continue to be promoted by the public health community. However our study suggests that the protective effects on dementia and cognitive impairment may be overly optimistic.”

Data presented in this study are from a considerably longer follow-up period than many other studies in this area, and this may partially explain the lack of association. The researchers undertook further analysis of the findings from other published studies, and found that some of the differences in findings could be explained by the different follow-up periods. Studies with shorter follow-up periods were more likely to show a protective association between physical activity and cognitive impairment compared to studies with longer follow-up periods.

Professor Yoav Ben-Shlomo from Bristol’s School of Social and Community Medicine, added: “This study represents an important addition to the literature on physical activity and cognitive disease as few studies have data with more than 15-years follow-up. It is possible that previous studies have shown protective effects due to a tendency for the literature to preferentially publish positive studies and the phenomenon known as “reverse causation”.  Hence subjects with very early disease, before any clinical diagnosis, reduce physical activity levels as a secondary effect of the disease rather than physical activity itself being protective. We are discovering that the pathology leading to dementia may have a long latency period before diagnosis so this is a possibility.”

An early online version of this paper detailing the findings has been published and is scheduled for publication in the August issue of the Journal of Alzheimer’s Disease.

More information: Physical activity in middle-age and dementia in later life: findings from a prospective cohort of men in Caerphilly, South Wales and a Meta-Analysis by Gemma Morgan, et al. JAD Volume 31/Issue 3 (August 2012), DOI: 10.3233/JAD-2012-112171

Provided by University of Bristol

Anti-tau drug improves cognition, decreases tau tangles in Alzheimer's disease models

While clinical trial results are being released regarding drugs intended to decrease amyloid production - thought to contribute to decline in Alzheimer's disease - clinical trials of drugs targeting other disease proteins, such as tau, are in their initial phases.

21 july 2012--Penn Medicine research presented today at the 2012 Alzheimer's Association International Conference (AAIC) shows that an anti-tau treatment called epithilone D (EpoD) was effective in preventing and intervening the progress of Alzheimer's disease in animal models, improving neuron function and cognition, as well as decreasing tau pathology.

By targeting tau, the drug aims to stabilize microtubules, which help support and transport of essential nutrients and information between cells. When tau malfunctions, microtubules break and tau accumulates into tangles.

"This drug effectively hits a tau target by correcting tau loss of function, thereby stabilizing microtubules and offsetting the loss of tau due to its formation into neurofibrillary tangles in animal models, which suggests that this could be an important option to mediate tau function in Alzheimer's and other tau-based neurodegenerative diseases," said John Trojanowski, MD, PhD, professor of Pathology and Laboratory Medicine in the Perelman School of Medicine at the University of Pennsylvania. "In addition to drugs targeting amyloid, which may not work in advanced Alzheimer's disease, our hope is that this and other anti-tau drugs can be tested in people with Alzheimer's disease to determine whether stabilizing microtubules damaged by malfunctioning tau protein may improve clinical and pathological outcomes."

The drug, identified through Penn's Center for Neurodegenerative Disease Research (CNDR) Drug Discovery Program, was previously shown to prevent further neurological damage and improve cognitive performance in animal models*. The Penn research team includes senior investigator Bin Zhang, MD, and Kurt Brunden, PhD, director of Drug Discovery at CNDR.

More information: Bristol-Myers Squibb, who developed and owns the rights to the drug, has started enrolling patients into a phase I clinical trial in people with mild Alzheimer's disease.

Presentation: "Microtubule Stabilizing Drugs for Abrogation and Prevention of Alzheimer's Disease," during symposium on "Insights into Non-Alzheimer's Disease Dementia Also Inform Us About Alzheimer's Disease"

*Brunden, K.R., Zhang, B., Carroll, J., Yao, Y., Poduzak, J.S., Hogan, A.M., Iba, M., James, M.J., Xie, S., Ballatore, C., Smith, A.B., III, Lee, V.M-Y., and Trojanowski, J.Q. Epothilone D improves microtubule density, axonal integrity and cognition in a transgenic mouse model of tauopathy. J. Neurosci., 30: 13861-13866, 2010.

Provided by University of Pennsylvania School of Medicine

Research identifies link between Alzheimer's disease and diabetes

(Medical Xpress) -- Researchers from the University of Medicine and Dentistry of New Jersey (UMDNJ), collaborating with scientists from Northwestern University in Illinois, have provided direct experimental evidence that diabetes is linked to the onset of Alzheimer's disease. The study, published online this week in the Journal of Alzheimer's Disease, used an experimental model that shows potential as an important new tool for investigations of Alzheimer’s disease and of drugs being developed to treat Alzheimer’s.

20 july 2012--UMDNJ researchers Peter Frederikse, PhD, and Chinnaswamy Kasinathan, PhD, collaborated with William Klein, PhD, at Northwestern University, to build on prior studies from the Klein lab and others that indicated close links between Alzheimer’s disease and diabetes. Working with Claudine Bitel and Rajesh Kaswala, students at UMDNJ, the researchers tested whether untreated diabetes would provide a physiological model of Alzheimer neuropathology.

“The results were striking,” Frederikse said. “Because we used diabetes as an instigator of the disease, our study shows – for the first time directly – the link between Alzheimer’s and diabetes.”

The researchers found substantial increases in amyloid beta peptide pathology – a hallmark of Alzheimer’s disease – in the brain cortex and hippocampus concurrent with diabetes. They also found significant amyloid beta pathology in the retina and by contrast, when diabetes is not present, no observable pathology was detected in either the brain or the retina.

“Second, our study examined the retina, which is considered an extension of the brain, and is more accessible for diagnostic exams,” Frederikse added. “Our findings indicate that scientists may be able to follow the onset and progression of Alzheimer’s disease through retinal examination, which could provide a long sought after early-warning sign of the disease.”

This experimental model replicated spontaneous formation of amyloid beta “oligomer” assemblies in brain and retina which may help to explain one of the most widely recognized symptoms of Alzheimer’s. “This is exciting,” Klein said. “Oligomers are the neurotoxins now regarded as causing Alzheimer’s disease memory loss. What could cause them to appear and buildup in late-onset Alzheimer’s disease has been a mystery, so these new findings with diabetes represent an important step.”

Previous research indicated that insulin plays an important role in the formation of memories. Once attached to neurons, oligomers cause insulin receptors to be eliminated from the surface membranes, contributing to insulin resistance in the brain. This launches a vicious cycle in which diabetes induces oligomer accumulation which makes neurons even more insulin resistant.

“In light of the near epidemic increases in Alzheimer’s disease and diabetes today, developing a physiological model of Alzheimer neuropathology has been an important goal,” Kasinathan added. “It allows us to identify a potential biomarker for Alzheimer’s disease and may also make important contributions to Alzheimer drug testing and development.”

The current research was supported by a grant from the National Eye Institute of the National Institutes of Health, the National Institute of Aging, and the Neuroscience Research and Education Foundation. Drs. Kasinathan and Frederikse have applied for patent protection regarding this novel experimental model of Alzheimer neuropathology.

Provided by University of Medicine and Dentistry of New Jersey

Alzheimer's drug shows promise in early trial

Experimental agent similar to medicines already used to ease symptoms, but more study needed.

19  july 2012--Researchers say an investigational drug helped improve memory, language, attention and other mental skills in people with early Alzheimer's disease.

The study was funded by EnVivo Pharmaceuticals, which is developing the drug, dubbed EVP-6124. The results are to be presented Wednesday at the annual meeting of the Alzheimer's Association in Vancouver.

The study involved 409 patients with mild to moderate Alzheimer's disease who were either being treated with the drugs donepezil (Aricept) or rivastigmine (Exelon) or were receiving no treatment.

During the six-month, phase 2 trial, patients took either a placebo or one of three different doses of EVP-6124.

After 23 weeks of treatment, the patients in the high-dose group showed statistically significant benefits on tests of mental function compared to those taking the dummy pill. Some patients in the medium- and high-dose groups did experience mild to moderate gastrointestinal side effects, the team added.

"In our study, EVP-6124 provided significant benefits for people with mild to moderate Alzheimer's whether they were on currently approved therapy or not," Dr. Dana Hilt, senior vice president of clinical development and chief medical officer of EnVivo, said in an Alzheimer's Association news release.

The authors explain that EVP-6124 belongs to a family of drugs called alpha-7 nicotinic agonists, which amplify the effects of acetylcholine, a brain chemical that's essential for normal brain and memory function. People with Alzheimer's disease have greatly reduced levels of acetylcholine.

Currently, there are no effective treatments to fight Alzheimer's disease, although certain drugs may temporarily ameliorate symptoms.

For that reason, the new study "is potentially interesting, as there is a need for better symptomatic treatment of Alzheimer's disease," said Peter Davies, director of the Litwin Zucker Research Center for the Study of Alzheimer's Disease at the Feinstein Institute for Medical Research in New Hyde Park, N.Y.

He pointed out that the mechanism behind the new drug is not altogether novel. "Treating the deficiency of acetylcholine is the basis for the already approved drugs Aricept, Exelon and Razodyne," Davies said. "This drug does the same thing, but in a different way. The other drugs act to reduce the breakdown of acetylcholine: this drug mimics the effect of acetylcholine at one of the receptors for this compound."

He said that there are hints that this approach might do more than just ease symptoms, and might attack the underlying illness. But that remains speculative and "further studies do seem to be warranted," Davies said.

Another expert agreed.

"These promising effects are 'symptomatic' (the drug does not slow progression of disease), and the study is relatively small in size," noted Stephen Ferris, director of the Alzheimer's Disease Center and the clinical trials program at NYU Langone Medical Center's Comprehensive Center on Brain Aging in New York City.

Like Davies, Ferris stressed that "if the results can be confirmed in a larger trial, the drug would be an important addition to current Alzheimer treatments."

Findings presented at medical meeting are typically considered preliminary until published in a peer-reviewed journal.