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.

New York Stem Cell Foundation scientists featured for new model of Alzheimer's disease

A team of scientists at The New York Stem Cell Foundation (NYSCF) Laboratory led by Scott Noggle, PhD, NYSCF–Charles Evans Senior Research Fellow for Alzheimer's Disease, has developed the first cell-based model of Alzheimer's disease (AD) by reprogramming skin cells of Alzheimer's patients to become brain cells that are affected in Alzheimer's. This will allow researchers to work directly on living brain cells suffering from Alzheimer's, which until now had not been possible.

18 july 2012--Andrew Sproul, PhD, a postdoctoral associate in Dr. Noggle's laboratory, will present this work on Thursday, July 19 at the Alzheimer's Association International Conference (AAIC) held in Vancouver.

Dr. Noggle and his team reprogrammed skin cell samples taken from twelve patients diagnosed with early-onset Alzheimer's and from healthy, genetically related individuals into induced pluripotent stem (iPS) cells, which can differentiate into any cell type. The team of scientists used these iPS cells to create cholinergic basal forebrain neurons, the brain cells that are affected in Alzheimer's. These cells recapitulate the features and cellular-level functions of patients suffering from Alzheimer's, a devastating disease that affects millions of people globally but for which there is currently no effective treatment.

NYSCF has pioneered the creation of disease models based on the derivation of human cells. Four years ago, a NYSCF-funded team created a cell-based model for ALS, or motor neuron disease, the first patient-specific stem cells created for any disease. The cell-based model for Alzheimer's builds on this earlier work.

"Patient derived AD cells will prove invaluable for future research advances, as they already have with patient-derived ALS cells," said NYSCF CEO Susan Solomon. "They will be a critical tool in the drug discovery process, as potential drugs could be tested directly on these cells. Although research on animals has provided valuable insight into AD, we aren't mice, and animals don't properly reflect the features of the disease we are trying to cure. As we work to find new drugs and treatments our research should focus on actual human sufferers of Alzheimer's disease," emphasized Ms. Solomon

This cell-based model has already led to important findings. Preliminary results of this NYSCF research, done in collaboration with Sam Gandy, MD, PhD, an international expert in the pathology of Alzheimer's at Mount Sinai School of Medicine, demonstrated differences in cellular function in Alzheimer's patients. Specifically, Alzheimer's neurons produce more of the toxic form of beta amyloid, the protein fragment that makes up amyloid plaques, than in disease-free neurons.

"iPS cell technology, along with whole genome sequencing, provide our best chance at unravelling the causes of common forms of Alzheimer's disease," noted Dr. Gandy.

"This collaboration is a great example of how NYSCF is bringing together experts in stem cell technology and clinicians to save and enhance lives by finding better treatments," Ms. Solomon explained.

The research to be reported at the AAIC by Andrew Sproul focused on stem cell models of individuals with presenilin-1 (PSEN1) mutations, a genetic cause of AD. As Dr. Sproul has said, this cell-based model could "revolutionize how we discover drugs to potentially cure Alzheimer's disease."

Provided by New York Stem Cell Foundation

Open access journals reaching the same scientific impact as subscription journals

BioMed Central's open access journal BMC Medicine adds scientific rigour to the debate about open access research, by publishing an article which compares the scientific impact of open access with traditional subscription publishing and has found that both of these publishing business models produce high quality peer reviewed articles.

17 july 2012--The debate about who should pay for scientific publishing is of continuing importance to the scientific community but also to the general public who not only often pay for the research though charitable contributions, their taxes, and by buying products, but are also affected by the results contained within these articles.

Many publically funded agencies, such as the Wellcome Trust and NIH require that scientific research sponsored by them is made freely available to the public. However the issues aren't as simple as just putting the results of your research on line. Scientific research goes through the quality control filter of peer review and journals act as gatekeepers performing quality-assuring peer review, and who provide web-based repositories. Scientists currently rely on publishing in peer reviewed high quality journals to show that their research itself is of good quality, is of importance to their field of research, and consequently improves their chances of obtaining funding to continue their work.

One way of measuring quality is by impact factors calculated from citation data (how many times other scientists have mentioned the research). Bo-Christer Björk from Hanken School of Economics, Helsinki, and David Solomon from Michigan State University compared the impact factors of 610 open access journals and over 7000 subscription journals.

The citation rate for subscription journals was overall 30% higher than for open access ones but this difference was largely due to a high share of older OA journals, particularly from regions like Latin America in the citation indexes. When like was compared with like, for instance, journals founded after 2000 from difference regions or disciplines, the differences disappeared.

Bo-Christer Björk, explained, The open access debate has included accusations from some traditional publishers and their lobbyists that Open Access publishing implies low scientific quality and endangers the quality assurance function of the peer review system that the academic community and publishers have built up over decades."

Explaining the results Prof Björk said, "If you take into account the journal discipline, location of publisher and age of publication the differences in impact between open access and subscription journals largely disappear. In medicine and health, open access journals founded in the last 10 years are receiving on average as many citations as subscription journals launched during the same time."

David Solomon continued, "It is easy to see why scientists might be sceptical of electronic, open access journals – after all they have their reputation to maintain. Open access journals that fund publishing with article processing charges (APCs), sometimes called gold open access, are on average cited more than other OA journals. Since the launch of professionally run high quality biomedical journals in 2000 gold OA has increased by 30% per year and many of these are on a par with their subscription counterparts."

More information: Open access versus subscription journals: a comparison of scientific impact Bo-Christer Björk and David Solomon BMC Medicine (in press)

Provided by BioMed Central

Mayo Clinic maps brain, finds Alzheimer's patients drive differently

Activity lingers longer in certain areas of the brain in those with Alzheimer's than it does in healthy people, Mayo Clinic researchers who created a map of the brain found. The results suggest varying brain activity may reduce the risk of Alzheimer's disease. The study, "Non-stationarity in the "Resting Brain's" Modular Architecture," was presented at the Alzheimer's Association International Conference and recently published in the journal PLoS One.

16 july 2012--Researchers compared brain activity to a complex network, with multiple objects sharing information along pathways.

"Our understanding of those objects and pathways is limited," says lead author David T. Jones, M.D. "There are regions in the brain that correspond to those objects, and we are not really clear exactly what those are. We need a good mapping or atlas of those regions that make up the network in the brain, which is part of what we were doing in this study."

Researchers examined 892 cognitively normal people taking part in the Mayo Clinic Study of Aging, and set out to create an active map of their brains while the people were "at rest," not engaged in a specific task. To do this, they employed task-free, functional magnetic resonance imaging to construct an atlas of 68 functional regions of the brain, which correspond to the cities on the road map.

Researchers filled in the roads between these regions by creating dynamic graphic representations of brain connectivity within a sliding time window.

This analysis revealed that there were many roads that could be used to exchange information in the brain, and the brain uses different roads at different times. The question to answer then, said Dr. Jones, is whether or not Alzheimer's patients used this map and these roads in a different way than their healthy peers.

"What we found in this study was that Alzheimer's patients tended to spend more time using some roads and less time using other roads, biasing one over the other," he says.

While more research is needed, the researchers say one implication is that how we use our brains may protect us from Alzheimer's. Dr. Jones says exercise, education, and social contacts may help balance activity in the brain.

"Diversifying the mental space that you explore may actually decrease your risk for Alzheimer's," he says.

Provided by Mayo Clinic

Cranberry products associated with prevention of urinary tract infections

Use of cranberry-containing products appears to be associated with prevention of urinary tract infections in some individuals, according to a study that reviewed the available medical literature and was published by Archives of Internal Medicine.

15 july 2012--Urinary tract infections (UTIs) are common bacterial infections and adult women are particularly susceptible. Cranberry-containing products have long been used as a "folk remedy" to prevent the condition, according to the study background.

Chih-Hung Wang, M.D., of National Taiwan University Hospital and National Taiwan University College of Medicine, and colleagues reviewed the available medical literature to reevaluate cranberry-containing products for the prevention of UTI.

"Cranberry-containing products tend to be more effective in women with recurrent UTIs, female populations, children, cranberry juice drinkers, and people using cranberry-containing products more than twice daily," the authors note.

The authors identified 13 trials, including 1,616 individuals, for qualitative analysis and 10 of these trials, including 1,494 individuals, were included in quantitative analysis. The random-effects pooled risk ratio for cranberry users vs. nonusers was 0.62, according to the study results.

"In conclusion, the results of the present meta-analysis support that consumption of cranberry-containing products may protect against UTIs in certain populations. However, because of the substantial heterogeneity across trials, this conclusion should be interpreted with great caution," the authors conclude.

More information: Arch Intern Med. 2012;172[13]:988-996.

Provided by JAMA and Archives Journals

'Natural' protection against Alzheimer’s disease

deCODE Genetics, together with their colleagues from the pharmaceutical company Genentech, reported today in the journal Nature the discovery of a variant of the amyloid precursor protein (APP) gene that confers protection against both Alzheimer's disease (AD) and cognitive decline in the elderly. The findings also indicate a linkage between age-related cognitive decline and late-onset forms of AD, the most common cause of dementia.

14 july 2012--"Our results suggest that late-onset Alzheimer's disease may represent the extreme of more general age-related decline in cognitive function," said study lead author Kari Stefansson, M.D., Dr. Med., CEO of deCODE Genetics. "Also important, these data support certain Alzheimer's disease drug development programs--some of which are already in human clinical trials."

Alzheimer's disease is a progressive neurodegenerative disease associated with the production and accumulation of beta-amyloid peptides produced by cleaving bits off the APP. While several mutant forms of the APP gene have been linked to early-onset, aggressive forms of AD, there is limited evidence supporting a role for mutations in the gene in the more common late-onset form of the disease.

In searching for low-frequency variants of the APP gene associated with AD, deCODE scientists found a significant association with a mutation in whole genome sequence data from 1,795 Icelanders. The research team showed that the mutation is significantly more common in the study's elderly control group than in those with AD, suggesting that the mutation confers protection against the disease.

The Genentech team then tested these findings using in vitro cellular assays with wild-type APP and APP enriched with A673T, the mutation allele. Importantly, they showed a significantly reduced production of amyloid beta in cells with A673T.

"Our genetic data indicate that the mutation is protective against Alzheimer's disease," said Stefansson. "Our findings and the in vitro work done by Genentech also provide a proof of principle for the idea that blocking BACE1 cleavage of APP may protect against Alzheimer's, offering greater confidence to pharmaceutical companies with active BACE1 inhibitor drug development programs."

To study the association of the protective mutation with general cognitive decline, the research team examined the frequency of the mutation in the original Icelandic control group of those cognitively intact at age 85. The team found an enrichment of the mutation in this group, consistent with its protective effect against AD.

Extending this work further, the team investigated cognitive function using a seven-category test in carriers of the mutation and non-carriers in the age range of 80 to 100 years old. The research team found a statistically significant difference between carriers and non-carriers, with the carriers of the mutation having a score indicative of better-conserved cognition. After removing known AD cases, the team again found that carriers had better cognitive function, suggesting that the mutation extends its protective effect to the elderly in general.

"The implication of these data is that general cognitive decline and late-onset Alzheimer's disease share biological pathways," said Stefansson. "It also suggests that approaches to treating Alzheimer's may have benefit to those elderly who do not carry the protective mutation, and do not suffer from AD."

Alzheimer's disease, a progressive neurodegenerative disorder, is the most common form of dementia that affects four to eight percent of the elderly population worldwide. The neuropathological features of AD are the presence of extracellular amyloid plaques and intracellular neurofibrillary tangles in the hippocampus and cortical grey matter of the AD brain.

Age-specific prevalence of AD nearly doubles after age 65, leading to a prevalence of greater than 25 percent in those over the age of 90.

More information: DOI: 10.1038/nature11283

Alzheimer's plaques in PET brain scans identify future cognitive decline

12 july 2012--Among patients with mild or no cognitive impairment, brain scans using a new radioactive dye can detect early evidence of Alzheimer's disease that may predict future decline, according to a multi-center study led by researchers at Duke University Medical Center.

The finding is published online July 11, 2012, in the journal Neurology, the medical journal of the American Academy of Neurology. It expands on smaller studies demonstrating that early detection of tell-tale plaques could be a predictive tool to help guide care and treatment decisions for patients with Alzheimer's disease.

"Even at a short follow-up of 18 months we can see how the presence of amyloid plaques affects cognitive function," said P. Murali Doraiswamy, M.D., professor of psychiatry at Duke who co-led the study with R. Edward Coleman, M.D., professor of radiology at Duke . "Most people who come to the doctor with mild impairment really want to know the short-term prognosis and potential long-term effect."

Doraiswamy said such knowledge also has some pitfalls. There is no cure for Alzheimer's disease, which afflicts 5.4 million people in the United States and is the sixth-leading cause of death among U.S. adults. But he said numerous drugs are being investigated, and identifying earlier disease would improve research into their potential benefits and speed new discoveries, while also enhancing care and treatment of current patients.

In the Neurology study, 151 people who had enrolled in a multi-center test of a new radioactive dye called florbetapir (Amyvid) were recruited to participate in a 36-month analysis. Of those participants, 69 had normal cognitive function at the start of the study, 51 had been diagnosed with mild impairment, and 31 had Alzheimer's dementia.

All completed cognitive tests and underwent a brain scan using Positron Emission Tomography, or PET imaging. The technology uses radioactive tracers designed to highlight specific tissue to create a three-dimensional picture of an organ or a biological function.

The dye used in the study, florbetapir, was recently approved by the U.S. Food and Drug Administration for PET imaging of the brain to estimate beta-amyloid plaque density in patients who are being evaluated for cognitive impairment. It binds to the amyloid plaques that characterize Alzheimer's disease, providing a window into the brain to see if the plaques have formed, and how extensively.

Patients in the study were reassessed with additional cognitive exams at 18 months and 36 months. At the 18-month point, patients with mild cognitive impairment who had PET evidence of plaque at the trial's start worsened to a great degree on cognitive tests than patients who had no evidence of plaque at the trial's start. Twenty-nine percent of the plaque-positive patients in this group developed Alzheimer's dementia, compared to 10 percent who started with no plaque.

Cognitively normal patients with a plaque-positive PET scan at the start of the study also showed more mental decline at 18 months compared to those who were negative for plaque.

The study additionally found that people with negative scans reversed from minimally impaired to normal more often than people with positive PET scan, suggesting test anxiety or concentration problems could have affected their initial performance.

"For the most part we have been blind about who would progress and who wouldn't, so this approach is a step toward having a biomarker that predicts risk of decline in people who are experiencing cognitive impairment," Doraiswamy said.

He said the study's results provide initial data that needs to be verified by additional research. Final, 36-month data from the study has been completed and will be presented at the Alzheimer's Association International Conference this week in Vancouver, Canada. Doraiswamy also cautioned that florbetapir is currently not approved to predict the development of dementia or other neurologic conditions and stressed that it should not be used as a screening tool in otherwise normal or minimally impaired people. Likewise, a positive scan is not necessarily diagnostic for Alzheimer's by itself.

Provided by Duke University Medical Center

Study examines quality of life factors at end of life for patients with cancer

Better quality of life at the end of life for patients with advanced cancer was associated with avoiding hospitalizations and the intensive care unit, worrying less, praying or meditating, being visited by a pastor in a hospital or clinic, and having a therapeutic alliance with their physician, according to a report published Online First by Archives of Internal Medicine.

11 july 2012--When treatments to cure a patient's cancer are no longer an option, the focus of care often shifts from prolonging life to promoting the quality of life (QOL) at the end of life (EOL). But researchers note in their study background that there has been a gap in data on the strongest predictors of higher QOL at the EOL.

"The aim of this study was to identify the best set of predictors of QOL of patients in their final week of life. By doing so, we identify promising targets for health care interventions to improve QOL of dying patients," the authors note.

The study by Baohui Zhang, M.S., formerly of the Dana-Farber Cancer Institute, Boston, and colleagues included 396 patients with advanced cancer and their caregivers as part of the Coping with Cancer study. The average age of patients was almost 59 years.

A set of nine factors explained the most variance in patients' QOL at the EOL: intensive care stays in the final week, hospital deaths, patient worry at baseline, religious prayer or meditation at baseline, site of cancer care, feeding tube use in the final week, pastoral care within the hospital or clinic, chemotherapy in the final week, and a patient-physician therapeutic alliance where the patient felt they were treated as a "whole person," according to the study.

"Two of the most important determinants of poor patient quality QOL at the EOL were dying in a hospital and ICU stays in the last week of life. Therefore, attempts to avoid costly hospitalizations and to encourage transfer of hospitalized patients to home or hospice might improve patient QOL at the EOL," the authors comment.

Patient worry at baseline also was "one of the most influential predictors of worse QOL at the EOL," the authors note.

"By reducing patient worry, encouraging contemplation, integrating pastoral care within medical care, fostering a therapeutic alliance between patient and physician that enables patients to feel dignified, and preventing unnecessary hospitalizations and receipt of life-prolonging care, physicians can enable their patients to live their last days with the highest possible level of comfort and care," the authors conclude.

In an invited commentary, Alan B. Zonderman, Ph.D., and Michele K. Evans, M.D., of the Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, Md., write: "The concept of quality of the EOL [end of life] in cancer patients has been under examined in cancer medicine in the quest to develop newer, more advanced, and effective modalities of interventional cytotoxic therapies. This study highlights the scarcity of research in an area that can give us important tools in further refining coherent treatment strategies for patients throughout the timeline of cancer treatment and disease trajectory."

"It is surprising at this stage in the development and implementation of complex multimodal cancer treatment strategies that the factors most critical in influencing the quality of the EOL are not clearly defined and considered along the entire timeline beginning with cancer diagnosis," they continue.

"This work, as well as the American Society of Clinical Oncology statement, support early introduction of palliative care for advanced cancer patients," the authors conclude.

More information: Arch Intern Med. Published online July 9, 2012. doi:10.1001/archinternmed.2012.2364 
Arch Intern Med. Published online July 9, 2012. doi:10.1001/archinternmed.2012.3169

Provided by JAMA and Archives Journals