IOM report calls for cultural transformation of attitudes toward pain and its prevention and management

Every year, at least 116 million adult Americans experience chronic pain, a condition that costs the nation between $560 billion and $635 billion annually, says a new report from the Institute of Medicine. Much of this pain is preventable or could be better managed, added the committee that wrote the report.

29 june 2011--The committee called for coordinated, national efforts of public and private organizations to create a cultural transformation in how the nation understands and approaches pain management and prevention. Some of the recommended changes can be implemented by the end of 2012 while others should be in place by 2015 and maintained as ongoing efforts.

"Given the large number of people who experience pain and the enormous cost in terms of both dollars and the suffering experienced by individuals and their families, it is clear that pain is a major public health problem in America," said committee chair Philip Pizzo, dean, Carl and Elizabeth Naumann Professor of Pediatrics, and professor of microbiology and immunology, Stanford University School of Medicine, Stanford, Calif. "All too often, prevention and treatment of pain are delayed, inaccessible, or inadequate. Patients, health care providers, and our society need to overcome misperceptions and biases about pain. We have effective tools and services to tackle the many factors that influence pain and we need to apply them expeditiously through an integrated approach tailored to each patient."

A new analysis undertaken as part of the study finds that the medical costs of pain care and the economic costs related to disability days and lost wages and productivity amount to at least $560 billion to $635 billion annually. Because the range does not include costs associated with pain in children or military personnel, it is a conservative estimate.

Health care providers, insurers, and the public need to understand that although pain is universal, it is experienced uniquely by each person and care –which often requires a combination of therapies and coping techniques — must be tailored, the report says. Pain is more than a physical symptom and is not always resolved by curing the underlying condition. Persistent pain can cause changes in the nervous system and become a distinct chronic disease. Moreover, people's experience of pain can be influenced by genes, cultural attitudes toward hardships, stress, depression, ability to understand health information, and other behavioral, cultural, and emotional factors.

Successful treatment, management, and prevention of pain requires an integrated, approach that responds to all the factors that influence pain, the committee concluded. The majority of care and management should take place through primary care providers and patient self-management with specialty care services reserved for more complex cases. Health care organizations should take the lead in developing innovative approaches and materials to coach and empower patients in self-management.

Training programs for dentists, nurses, physicians, psychologists, and other health professionals should include pain education in their curricula and promote interdisciplinary learning, the report says. Many health care professionals are not adequately prepared to provide the full range of pain care or to guide patients in self-managing chronic pain. For example, a recent study found that only five of the nation's 133 medical schools have required courses on pain and just 17 offer elective courses. Licensing and certification exams should include assessment of pain-related knowledge and capabilities. Programs that train specialists or offer training in advanced pain care need to be expanded.

The report calls on Medicare, Medicaid, workers' compensation programs, and private health plans to find ways to cover interdisciplinary pain care. Individualized care requires adequate time to counsel patients and families, consultation with multiple providers, and often more than one form of therapy, but current reimbursement systems are not designed to efficiently pay for this kind of approach and health care organizations are not set up for integrated patient management.

Due to its significant toll on individuals and society, pain warrants a higher level of attention and resources within the National Institutes of Health. The report recommends that NIH designate a lead institute to move pain research forward and increase the scope and resources of its existing Pain Consortium. NIH, academic researchers, and other public organizations should collaborate with private firms to advance research and development of new and improved therapies.

Provided by National Academy of Sciences

Case of mistaken identity: Study questions role of A-beta molecules in Alzheimer's disease pathology

Confocal microscope image of neurons in the 3xTgAD mice stained for the amyloid-ß (Aß) precursor protein (APP) showing APP (green) within these nerve cells which were not labeled by antibodies that detect free Aß, the peptide cleavage product of APP that, when released from APP by proteases will be secreted and for Alzheimer plaques outside nerved cells in the brain of these mice similar to Alzheimer patients. Credit: Edward B. Lee, Perelman School of Medicine at the University of Pennsylvania

Increasingly, researchers are suggesting that amyloid plaques and neurofibrillary tangles may be relatively late manifestations in the course of Alzheimer's disease (AD) pathology. Identifying earlier events in the development of AD remains a challenge. The laboratory of Virginia M.-Y. Lee, PhD, director of the Center for Neurodegenerative Disease Research, Perelman School of Medicine at the University of Pennsylvania, was the first, in 1993, to demonstrate unequivocally the presence of A-beta peptides -- a hallmark of AD -- inside neurons. But their role in Alzheimer's disease remained unclear.

28 june 2011--"It was exciting when a 'triple transgenic' mouse model of AD was reported in 2003 to show robust staining of cells interpreted as A-beta peptides inside neurons," says Edward Lee, MD, PhD, assistant professor of Pathology and Laboratory Medicine, co-author on a study just out in the Journal of Neuroscience that questions the role of A-beta peptides in AD pathology.

The triple transgenic mouse has since become a popular model in AD studies, says Edward Lee. In these mice, A-beta molecules were detected before amyloid-plaque and neurofibrillary-tangle pathology showed up, suggesting that intraneuronal A-beta peptides lead to amyloid plaques, which then lead to neurofibrillary tangles inside neurons.

The Penn researchers examined the trajectory of neuronal inclusions over time using rigorous biochemical and genetic methods. Virginia Lee's group discovered a case of mistaken identity: The intraneuronal molecules appear not to be A-beta peptides themselves, but rather the A-beta amino acid sequence nested within its parent protein, the A-beta precursor protein. What's more, blocking A-beta peptides from forming in the triple transgenic mice had no effect on the formation of neurofibrillary tangles.

According to Virginia Lee, this finding is significant for Alzheimer drug development because it underlines the need for tau-focused drug discovery for AD since the idea that intracellular A-beta drives tangle formation was not substantiated. Therapies aimed at blocking A-beta production may not have any effect on tangle formation, which is consistent with human clinical trial data to date.

The role of intraneuronal A-beta in AD is still unclear, but these results have profound implications for studies of mechanisms of AD and for AD drug discovery since mouse models of presumptive intracellular A-beta are widely used, state the authors.

Please take a look at the Alzforum webinar about the debate on intraneuronal A-beta as a potential instigator of Alzheimer's disease: www.alzforum.org/res/for/journal/detail.asp?liveID=193

More information: Paper: http://www.jneuros … 691.abstract

Provided by University of Pennsylvania School of Medicine

Premature aging caused by some HIV drugs, study shows

A class of anti-retroviral drugs commonly used to treat HIV, particularly in Africa and low income countries, can cause premature ageing, according to research published today in the journal Nature Genetics. The study shows that the drugs damage DNA in the patient's mitochondria – the 'batteries' which power their cells.

27 june 2011--The findings may explain why HIV-infected people treated with antiretroviral drugs sometimes show advanced signs of frailty and age-associated diseases such as cardiovascular disease and dementia at an early age.

Nucleoside analogue reverse-transcriptase inhibitors (NRTIs) – of which the most well known is Zidovudine, also known as AZT – were the first class of drug developed to treat HIV. They were a major breakthrough in the treatment of the disease, greatly extending lifespan and leading the condition to be seen as a chronic, rather than terminal, condition.

In high income countries, such as Europe and North America, the older NRTIs are used less commonly now due to concerns over toxicity and side-effects when taken over a long period of time. However, as they are now off-licence and hence relatively cheap, the drugs have proved to be an important lifeline for people infected with HIV in Africa and low income countries.

Professor Patrick Chinnery, a Wellcome Senior Fellow in Clinical Science from the Institute of Genetic Medicine at Newcastle University, says: "HIV clinics were seeing patients who had otherwise been successfully treated but who showed signs of being much older than their years. This was a real mystery. But colleagues recognised many similarities with patients affected by mitochondrial diseases – conditions that affect energy production in our cells – and referred them to our clinic."

Mitochondria are the 'batteries' in our cells which provide them with the energy to carry out their functions. During natural human ageing, these mitochondria acquire mutations, though it is unclear whether these mutations are a cause of ageing or a consequence.

In an attempt to understand what was happening at a cellular level, Professor Chinnery and colleagues studied muscle cells from HIV-infected adults, some of whom had previously been given NRTIs.

The researchers found that patients who had been treated with NRTIs – even as long ago as a decade previously – had damaged mitochondria which resembled that of a healthy aged person.

"The DNA in our mitochondria gets copied throughout our lifetimes and, as we age, naturally accumulates errors," explains Professor Chinnery. "We believe that these HIV drugs accelerate the rate at which these errors build up. So over the space of, say, ten years, a person's mitochondrial DNA may have accumulated the same amount of errors as a person who has naturally aged twenty or thirty years. What is surprising, though, is that patients who came off the medication many years ago may still be vulnerable to these changes."

Co-author and HIV specialist, Dr Brendan Payne, a Medical Research Council fellow from the Department of Infection and Tropical Medicine at the Royal Victoria Infirmary, Newcastle, believes that despite the side effects caused by NRTIs, they are still important drugs and the risks are relative.

"These drugs may not be perfect, but we must remember that when they were introduced they gave people an extra ten or twenty years when they would otherwise have died," he says. "In Africa, where the HIV epidemic has hit hardest and where more expensive medications are not an option, they are an absolute necessity."

Provided by Wellcome Trust

Lithium profoundly prevents brain damage associated with Parkinson's disease

Lithium profoundly prevents the aggregation of toxic proteins and cell loss associated with Parkinson's disease (PD) in a mouse model of the condition.

26 june 2011--Preclinical research is now underway at the Buck Institute for Research on Aging to determine correct dosages for a drug that continues to be the gold standard for the treatment of bipolar disorder. The Buck is currently working toward initiating a Phase IIa clinical studies of lithium in humans in conjunction with standard PD drug therapy. The research appears in the June 24 online edition of the Journal of Neuroscience Research.

"This is the first time lithium has been tested in an animal model of PD," said lead author and Buck Professor Julie Andersen, PhD. "The fact that lithium's safety profile in humans is well understood greatly reduces trial risk and lowers a significant hurdle to getting it into the clinic."

According to Andersen, lithium has recently been suggested to be neuroprotective in relation to several neurodegenerative conditions including Alzheimer's disease, Huntington's disease and amyotrophic lateral sclerosis and has been touted for its anti-aging properties in simple animals. "We fed our mice levels of lithium that were at the low end of the therapeutic range," said Andersen. "The possibility that lithium could be effective in PD patients at subclinical levels is exciting, because it would avoid many side effects associated at the higher dose range." Overuse of lithium has been linked to hyperthyroidism and kidney toxicity.

PD is a progressive, incurable neurodegenerative disorder that affects 1 million Americans and results in tremor, slowness of movement and rigidity. It is the second most common neurodegenerative disease after Alzheimer's. Between 50,000 and 60,000 new cases are diagnosed each year. Age is the largest risk factor for the PD. Onset usually begins between the ages of 45 and 70 years.

Andersen's research focuses on lithium as a potential treatment for PD as well as its efficacy in combination with drugs currently used to control the symptoms of the disease. An internet search reveals stories from PD patients who are using lithium "off label" as part of their treatment regime; others report benefits from low dose lithium salts which are available as a supplement in some health food stores. "This finding gives us an opportunity to explore lithium as a recognized therapeutic for PD, in doses that are safe and effective" said Andersen.

More information: Lithium protects against oxidative stress-mediated cell death in alpha-synuclein over-expressing in vitro and in vivo models of Parkinson's disease. JNR: 852471-744204

Provided by Buck Institute for Age Research

Alzheimer's may cause global cash crunch: experts

Alzheimer's disease could cause a global cash crunch in coming generations -- as people begin to regularly live to 100 -- and must be considered a serious fiscal danger, experts said Thursday.

25 june 2011--Already 24-37 million people worldwide live with the incurable form of dementia, and that number is projected to reach 115 million by 2050, a panel of Alzheimer's disease experts told the US House Committee on Foreign Affairs.

As women bear fewer children and the population ages, the world will become increasingly ill-prepared to cope with large numbers of dependent elderly people and must begin investing more in research to prevent the disease, they said.

Places like Russia, Europe, the United States and parts of Asia are experiencing "declining populations, fewer workers and more people dependent upon public health systems for their support," said George Vradenburg, founder of an advocacy group called USAgainstAlzheimer's.

"That is producing fiscal stress on our health systems around the world and it is producing the risk that the developed world -- particularly the Asian rim and particularly western Europe -- are going to be declining in their economic growth and prosperity in the coming years."

According to the London-based Alzheimer's Disease International, the total estimated worldwide cost of the disease in 2010 was 604 billion dollars, or nearly one percent of global GDP.

"If Alzheimer's were a country, it would be the 18th largest economy based on GDP," said Daisy Acosta, the chair of ADI, describing Alzheimer's as "the single most important health and social crisis of the 21st century."

"The impact of this disease today is massive and will accelerate with the years to come," she said.

And yet, compared to other major health woes such as cancer and HIV/AIDS, the amount of research money being spent on preventing it is minimal.

"We invest six billion a year for cancer, four billion dollars a year for heart disease, two billion dollars a year for AIDS," said Bill Thies, chief scientific officer at the Alzheimer's Association.

"We are at about 450 million a year for Alzheimer's disease," he said.

"Without increasing that significantly we are going to see the peak of this epidemic and we are going to see the worst possibilities of it."

The experts acknowledged that the strain of caring for an Alzheimer's patient usually falls on the family, but in the years to come nations as a whole could prepare themselves better by considering how to run an aging economy.

"My grandchildren, aging experts tell me, will live to 110 or 120," said Vradenburg, noting that after age 85 one in two people is diagnosed with dementia.

"We are going to see increasingly a physically able population but a cognitively disabled population."

In order to prevent the older set from consuming a nation's economic resources for health care, countries must think about how to put dementia patients to work in order to keep their economies from collapsing, he said.

"We need to change our aging populations from people who are taking a public benefit... and turn them into productive taxpayers who are participants in the workforce," Vradenburg said.

"Those countries that get it right and figure out how to support their aging populations -- keeping them healthy and keeping them productive -- are going to be winners in the 21st century."

Those who do not will be "losers," he added.

"It is critical for the world to begin to recognize this not just as a health issue but as a fiscal issue."

Eric Hall, president of the Alzheimer's Foundation of America, called for a global meeting early next year to compare notes among nations on how to best approach the problem and formulate a global action plan.

House Representative Ed Markey, a Democrat from Massachusetts, said the world must come together to find a solution.

"We are in a race against time here... and that is across the whole planet," said Markey.

"It is imperative for us to have an action plan that does work, because failure is not an option here."

Common drugs linked to cognitive impairment and possibly to increased risk of death

A large, long-term study confirms that medications with anticholinergic activity, which include many drugs frequently taken by older adults, cause cognitive impairment. The research is also the first to identify a possible link between these drugs – which include over-the-counter and prescription sleep aids and incontinence treatments – and risk of death.

24 june 2011--The two-year study of the impact of these medications on 13,000 men and women aged 65 and older is part of the Medical Research Council (UK) Cognitive Function and Ageing Studies (CFAS), a large UK-based longitudinal multi-center study initiative looking at health and cognitive function in older adults. Results of the study of anticholinergics appear June 24, 2011 in an advanced online publication of the Journal of the American Geriatrics Society.

Anticholinergics affect the brain by blocking acetylcholine, a nervous system neurotransmitter. Over-the-counter products containing diphenhydramine, sold under various brand names such as Benadryl, Dramamine, Excedrin PM, Nytol, Sominex, Tylenol PM, and Unisom, have anticolinergic activity. Other anticholinergic drugs, such as Paxil, Detrol, Demerol and Elavil are available by prescription.

"Our findings make it clear that clinicians need to review the cumulative anticholinergic burden in people presenting with cognitive impairment to determine if the drugs are causing decline in mental status," said co-author Malaz Boustani, M.D., Regenstrief Institute investigator, Indiana University School of Medicine associate professor of medicine, and research scientist with the IU Center for Aging Research.

"Physicians should review with older patients all the over-the-counter and prescription drugs they are taking to determine exposure," said Dr. Boustani a geriatrician who sees patients at Wishard Health Services' Healthy Aging Brain Center in Indianapolis.

The researchers, led by Chris Fox, M.D., of the University of East Anglia and Carol Brayne, M.D. of the University of Cambridge, used the Anticholinergic Cognitive Burden Scale developed by Dr. Boustani and colleagues at the Regenstrief Institute, Indiana University and in the United Kingdom to evaluate the link between anticholinergic activity and cognitive decline.

Medications with anticholinergic effects are used for many diseases including hypertension and congestive heart failure. The study found that older age, lower income, and greater number of health conditions increased use of medications with anticholinergic activity. Women were more likely to report taking anticholinergic medications, due to the greater number of health conditions reported by women than by men. Participants living in institutions were more likely to report taking anticholinergic medications.

"We looked at drugs with either moderate and severe anticholinergic activity. After adjusting for age, sex, baseline mental status, education, income level, number of non-anticholinergic medications and health conditions, we found that taking anticholinergic medications was linked to cognitive impairment and for the first time to death," said study corresponding author Dr. Fox, a psychiatrist. "We need follow-up to determine the degree to which anticholinergics are being prescribed for diseases with significant risk of death and the impact of that on our findings."

Authors of the study are Chris Fox, M.D., University of East Anglia; Carol Brayne, M.D., Kathryn Richardson, M.Sc. and George M. Savva, Ph.D, University of Cambridge; Ian D. Maidment, M.A., Kent and Medway NHS and Social Care Partnership Trust; Fiona E. Matthews, Ph.D., Medical Research Council Biostatistics Unit; David Smithard, M.D., Kent Community Health NHS Trust; Simon Coulton M.Sc., University of Kent; Cornelius Katona, M.D., University College London and Malaz Boustani, M.D., M.P.H., Regenstrief Institute, Indiana University School of Medicine and IU Center for Aging Research.

"The Anticholinergic Medication Use and Cognitive Impairment in the Older Population: The Medical Research Council Cognitive Function and Ageing Study (CFAS)" was funded by the Medical Research Council.

"The Medical Research Council invests in cohort studies like CFAS because they provide vital clinical information through observation. Such projects require long-term commitment to fulfill their potential but having supported cohort studies for well over half a century, MRC funding and collaborations have made us an international leader in this field," said Chris Kennard, MBBS, Ph.D., chairman of the MRC's Neuroscience and Mental Health Board.

Provided by Indiana University School of Medicine

New biomarker may help with early diagnosis of Alzheimer's disease

A new biomarker may help identify which people with mild memory deficits will go on to develop Alzheimer's disease, according to a new study published in the June 22, 2011, online issue of Neurology, the medical journal of the American Academy of Neurology. The biomarker may be more accurate than the currently established biomarkers.

23 june 2011--"Being able to identify who will develop Alzheimer's disease very early in the process will be crucial in the future," said study author Robert Perneczky, MD, of the Technical University Munich in Germany. "Once we have treatments that could prevent Alzheimer's disease, we could begin to treat very early and hopefully prevent the loss of memory and thinking skills that occurs with this devastating disease."

The study involved 58 people with slight memory problems, or mild cognitive impairment (MCI). Up to 15 percent of people with mild cognitive impairment develop Alzheimer's disease each year.

A sample of cerebrospinal fluid of the participants was taken at the beginning of the study through a lumbar puncture, or spinal tap. The concentrations in the cerebrospinal fluid of several proteins that are associated with Alzheimer's disease were measured.

The participants were followed for nearly three years on average. At that point, 21 people had developed Alzheimer's disease, 27 still had mild cognitive impairment and eight people had reverted back to their normal cognitive health. Two people had developed frontotemporal dementia, and their results were not included in the analysis.

Researchers found that the people who developed Alzheimer's disease had significantly higher levels of a protein called soluble amyloid precursor protein beta (sAPPβ) in their spinal fluid than those who did not develop Alzheimer's disease. Those who developed Alzheimer's disease had an average of 1,200 nanograms per milliliter, compared to 932 for those who did not develop the disease.

The researchers found that the best predictor of whether someone would develop Alzheimer's disease was a combination of sAPPβ, the tau protein (an established marker of brain cell damage) and the age of the individual. When these factors were combined, the results were roughly 80 percent accurate in predicting whether the disease would develop.

The protein amyloid beta1-42, or Aβ1-42, which has previously been considered a biomarker for Alzheimer's disease, was not a predictive factor in this study.

"These results suggest that sAPPβ as a biomarker may be useful and superior to the established marker Aβ1-42 in the early diagnosis of Alzheimer's disease," Perneczky said.

"One possible explanation is that Aβ1-42 measures events further downstream from the initial steps that lead to the production of the amyloid plaques that accumulate in the brains of people with Alzheimer's disease. sAPPβ is a measure of the first critical step in that process and may therefore provide more accurate information on the core pathological events."

Provided by American Academy of Neurology

Planning is key to a healthy and happy retirement, studies find

Retirement is often viewed as a time to relax, travel, participate in leisurely activities and spend time with family. However, for many older adults, chronic health problems and poor planning often hinder the enjoyment of retirement. Now, a University of Missouri researcher has found that planning for changes in lifestyle and health leads to better retirement for married couples.

22 june 2011--Angela Curl, an assistant professor in the School of Social Work, says it is important for couples to plan for retirement, both financially and socially and to consider the changes that may occur in their relationships and day-to-day activities.

Communication about retirement with each other and family members and friends makes it easier for couples to adjust to a new routine, Curl says.

"Any time a major life change happens, it is an opportunity for renegotiation of roles within a couple," Curl said. "If a couple wants positive changes to occur in retirement, it is important for spouses to be intentional in negotiating and planning for activities that match their ideals, finances and current health status."

In addition to planning for changes in routine and lifestyle in retirement, it is important to prepare for health problems that may occur later in life.

Curl examined the effects of retirement on self-rated health and cardiac health among couples and found gender differences in how husbands and wives rate their health after retirement. Wives rated their health worse during the first few years of retirement, but their ratings improved in the long run. In contrast, husbands continued to rate their health worse the longer they were retired.

Husbands reported improved health when their wives retired. Retirement also reduced the risk of cardiac health problems in men, but had no effect on cardiac health in women.

"When wives retire, they may monitor their husbands' health more closely, taking them to the doctor regularly and ensuring they lead a healthy lifestyle," Curl said. "Women traditionally put the needs of everyone else before themselves, a behavior that could put their own health at risk."

To ease the switch from full-time employment into retirement, Curl recommends a gradual transition to working less and maintaining some level of engagement in the workforce.
"There are a lot of health benefits to staying employed," Curl said. "Working just a few hours each week can facilitate better health."

Curl's research examined preparing for retirement through dialogue with friends, coworkers and family members. Her study, "Retirement and cardiac health: A longitudinal, dyadic analysis" was presented at the annual meeting of the Gerontological Society of America. The study was funded by the Hartford Geriatric Social Work Faculty Scholars Grant. Curl's study "A Multilevel Dyadic Study of the Impact of Retirement on Self-Rated Health: Does Retirement Predict Worse Health in Married Couples?" is under review.

More information: The study, “Retirement and cardiac health: A longitudinal, dyadic analysis,” was presented at the annual meeting of the Gerontological Society of America.

Provided by University of Missouri-Columbia

Researchers find new clues about aging

National Institutes of Health researchers have identified a new pathway that sets the clock for programmed aging in normal cells. The study provides insights about the interaction between a toxic protein called progerin and telomeres, which cap the ends of chromosomes like aglets, the plastic tips that bind the ends of shoelaces.

21 june 2011--The study by researchers from the National Human Genome Research Institute (NHGRI) appears in the June 13, 2011 early online edition of the Journal of Clinical Investigation.

Telomeres wear away during cell division. When they degrade sufficiently, the cell stops dividing and dies. The researchers have found that short or dysfunctional telomeres activate production of progerin, which is associated with age-related cell damage. As the telomeres shorten, the cell produces more progerin.

Progerin is a mutated version of a normal cellular protein called lamin A, which is encoded by the normal LMNA gene. Lamin A helps to maintain the normal structure of a cell's nucleus, the cellular repository of genetic information.

In 2003, NHGRI researchers discovered that a mutation in LMNA causes the rare premature aging condition, progeria, formally known as known as Hutchinson-Gilford progeria syndrome. Progeria is an extremely rare disease in which children experience symptoms normally associated with advanced age, including hair loss, diminished subcutaneous fat, premature atherosclerosis and skeletal abnormalities. These children typically die from cardiovascular complications in their teens.

"Connecting this rare disease phenomenon and normal aging is bearing fruit in an important way," said NIH Director Francis S. Collins, M.D., Ph.D., a senior author of the current paper. "This study highlights that valuable biological insights are gained by studying rare genetic disorders such as progeria. Our sense from the start was that progeria had a lot to teach us about the normal aging process and clues about more general biochemical and molecular mechanisms."

Collins led the earlier discovery of the gene mutation responsible for progeria and subsequent advances at NIH in understanding the biochemical and molecular underpinnings of the disease.

In a 2007 study, NIH researchers showed that normal cells of healthy people can produce a small amount of progerin, the toxic protein, even when they do not carry the mutation. The more cell divisions the cell underwent, the shorter the telomeres and the greater the production of progerin. But a mystery remained: What was triggering the production of the toxic progerin protein?

The current study shows that the mutation that causes progeria strongly activates the splicing of lamin A to produce the toxic progerin protein, leading to all of the features of premature aging suffered by children with this disease. But modifications in the splicing of LMNA are also at play in the presence of the normal gene.

The research suggests that the shortening of telomeres during normal cell division in individuals with normal LMNA genes somehow alters the way a normal cell processes genetic information when turning it into a protein, a process called RNA splicing. To build proteins, RNA is transcribed from genetic instructions embedded in DNA. RNA does not carry all of the linear information embedded in the ribbon of DNA; rather, the cell splices together segments of genetic information called exons that contain the code for building proteins, and removes the intervening letters of unused genetic information called introns. This mechanism appears to be altered by telomere shortening, and affects protein production for multiple proteins that are important for cytoskeleton integrity. Most importantly, this alteration in RNA splicing affects the processing of the LMNA messenger RNA, leading to an accumulation of the toxic progerin protein.

Cells age as part of the normal cell cycle process called senescence, which progressively advances through a limited number of divisions in the cell lifetime. "Telomere shortening during cellular senescence plays a causative role in activating progerin production and leads to extensive change in alternative splicing in multiple other genes," said lead author Kan Cao, Ph.D., an assistant professor of cell biology and molecular genetics at the University of Maryland, College Park.

Telomerase is an enzyme that can extend the structure of telomeres so that cells continue to maintain the ability to divide. The study supplied support for the telomere-progerin link, showing that cells that have a perpetual supply of telomerase, known as immortalized cells, produce very little progerin RNA. Most cells of this kind are cancer cells, which do not reach a normal cell cycle end point, and instead replicate out of control.

The researchers also conducted laboratory tests on normal cells from healthy individuals using biochemical markers to indicate the occurrence of progerin-generating RNA splicing in cells. The cell donors ranged in age from 10 to 92 years. Regardless of age, cells that passed through many cell cycles had progressively higher progerin production. Normal cells that produce higher concentrations of progerin also displayed shortened and dysfunctional telomeres, the tell-tale indication of many cell divisions.

In addition to their focus on progerin, the researchers conducted the first systematic analysis across the genome of alternative splicing during cellular aging, considering which other protein products are affected by jumbled instructions as RNA molecules assemble proteins through splicing. Using laboratory techniques that analyze the order of chemical units of RNA, called nucleotides, the researchers found that splicing is altered by short telomeres, affecting lamin A and a number of other genes, including those that encode proteins that play a role in the structure of the cell.

The researchers suggest that the combination of telomere fraying and loss with progerin production together induces cell aging. This finding lends insights into how progerin may participate in the normal aging process.

More information: Hutchinson-Gilford progeria syndrome: http://www.genome.gov/11007255

Provided by National Institutes of Health

Caregiver Support May Reduce Psychological Distress

Direct caregiver support was found to be more beneficial than providing patient care support

20 june 2011-- The psychological distress of caring for a friend or relative with a terminal disease may be reduced if informal caregivers receive direct support, although the quality of evidence is low, according to a review published in the June issue of the Cochrane Database of Systematic Reviews.

Bridget Candy, from the Royal Free & University College Medical School in London, and colleagues reviewed available literature until 2010 to investigate whether supportive interventions, either directly or through patient care, improved the psychological and physical health of informal caregivers of patients with a terminal disease. The analysis included 11 randomized controlled trials with 1,836 caregiver participants. Adverse effects were compared between participants who received intervention and those who did not.

The investigators found that interventions that directly supported the caregiver resulted in a significant reduction of short-term psychological distress with marginal improvements in coping skills and quality of life, but the quality of evidence was low. Only one study assessed physical outcomes and found no difference in sleep improvement. Although no study measured health service use or adverse outcomes, higher levels of family conflict were identified in a subgroup analysis from one study. Patient support did not significantly reduce caregivers' psychological distress, and its effect on caregivers' ability to cope, quality of life, service use, or adverse outcomes could not be assessed. Based on one study there was no difference in caregiver physical health when the patient received or did not receive additional care.

"These findings suggest that practitioners should inquire about the concerns of caregivers and should consider that they may benefit from additional support," the authors write.

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Lengthy TV Viewing Tied to Increased Morbidity, Mortality

Two hours of TV per day tied to elevated risk of type 2 diabetes, heart disease, and mortality

15 june 2011---- Prolonged television viewing is associated with an increased risk of developing type 2 diabetes, fatal or nonfatal cardiovascular disease, and all-cause mortality, according to a meta-analysis published in the June 15 issue of the Journal of the American Medical Association.

Anders Grøntved, M.P.H., from the University of Southern Denmark in Odense, and Frank B. Hu, M.D., Ph.D., from Harvard Medical School in Boston, reviewed available literature to assess the association between television viewing and the risk of developing type 2 diabetes, fatal or nonfatal cardiovascular disease, and all-cause mortality. A total of eight eligible studies were identified, with four studies reporting results for type 2 diabetes mellitus (6,428 incident cases out of 175,938 participants), four for fatal and nonfatal cardiovascular disease (1,052 incident cases out of 34,253 participants), and three for all-cause mortality (1,879 deaths out of 26,509 participants).

The investigators found that two hours of television viewing per day was associated with a significantly increased risk of type 2 diabetes, fatal and nonfatal cardiovascular disease, and all-cause mortality, with pooled relative risks of 1.20, 1.15, and 1.13, respectively. The risk of all-cause mortality increased even more with television viewing of more than three hours per day. Two hours of viewing per day was associated with an absolute risk of 176 cases of type 2 diabetes, 38 cases of fatal cardiovascular disease, and 104 deaths for all-cause mortality per 100,000 individuals per year.

"Prolonged TV viewing was associated with increased risk of type 2 diabetes, cardiovascular disease, and all-cause mortality," the authors write.

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Dietary changes appear to affect levels of biomarkers associated with Alzheimer's disease

Following a low–saturated fat and low–glycemic index diet appears to modulate the risk of developing dementia that proceeds to Alzheimer's disease (AD), although making a switch to this dietary pattern may not protect those already experiencing cognitive difficulty, according to a report in the June issue of Archives of Neurology.

15 june 2011--Previous research has suggested multiple links between diet and cognitive ability, the authors note as background information. Health conditions in which insulin resistance (the body's inability to use insulin effectively) is a factor—obesity, type 2 diabetes, cardiovascular disease and high cholesterol levels—have also been associated with "pathological brain aging." However, studies of specific foods have not found conclusive evidence of an influence on Alzheimer's risk. "Thus," the authors write, "a more promising approach to the study of dietary factors in AD might entail the use of whole-diet interventions, which have greater ecologic validity and preserve the nutritional milieu in which fat and carbohydrate consumption occurs."

Jennifer L. Bayer-Carter, M.S., from Veterans Affairs Puget Sound Health Care System, Seattle, and colleagues sought to compare a high–saturated fat/high–simple carbohydrate diet (a macronutrient pattern associated with type 2 diabetes and insulin resistance) with a low–saturated fat/low–simple carbohydrate diet; the interventions were named HIGH and LOW, respectively. The authors evaluated the effects of these diets in 20 older adults who were healthy and 29 older adults who had amnestic mild cognitive impairment (aMCI), meaning they experienced some memory problems; the latter condition is often considered a precursor to AD. In a four-week randomized, controlled trial, 24 participants followed the HIGH diet and 25 followed the LOW diet. The researchers studied participants' performance on memory tests as well as their levels of biomarkers (biological substances indicative of AD), such as insulin, cholesterol, blood glucose levels, blood lipid levels and components of cerebrospinal fluid (CSF).

Results of the study were different for the group that had aMCI and the group of healthy participants. In the latter group, the LOW diet decreased some CSF biomarkers of AD as well as total cholesterol levels. However, among individuals with aMCI, the LOW diet increased levels of these biomarkers. Some changes to biomarkers, such as CSF insulin levels, were observed in both groups. Additionally, the LOW diet improved performance on delayed visual recall tests for both healthy and memory-impaired participants, but did not affect scores on other cognitive measures.

The findings indicate that "for healthy adults, the HIGH diet moved CSF biomarkers in a direction that may characterize a presymptomatic stage of AD," explain the authors. They believe that the different results in participants with aMCI may show that dietary interventions are not as effective in later stages of cognitive impairment. "The therapeutic effects of longer-term dietary intervention may be a promising avenue of exploration," the authors conclude. "In addition, identification of the pathophysiologic changes underlying dietary effects may reveal important therapeutic targets that can be modulated through targeted dietary or pharmacologic intervention."

More information: Arch Neurol. 2011;68[6]:743-752

Provided by JAMA and Archives Journals

Moderate to intense exercise may protect the brain

Older people who regularly exercise at a moderate to intense level may be less likely to develop the small brain lesions, sometimes referred to as "silent strokes," that are the first sign of cerebrovascular disease, according to a new study published in the June 8, 2011, online issue of Neurology.

13 june 2011--"These 'silent strokes' are more significant than the name implies, because they have been associated with an increased risk of falls and impaired mobility, memory problems and even dementia, as well as stroke," said study author Joshua Z. Willey, MD, MS, of Columbia University in New York and a member of the American Academy of Neurology. "Encouraging older people to take part in moderate to intense exercise may be an important strategy for keeping their brains healthy."

The study involved 1,238 people who had never had a stroke. Participants completed a questionnaire about how often and how intensely they exercised at the beginning of the study and then had MRI scans of their brains an average of six years later, when they were an average of 70 years old.

A total of 43 percent of the participants reported that they had no regular exercise; 36 percent engaged in regular light exercise, such as golf, walking, bowling or dancing; and 21 percent engaged in regular moderate to intense exercise, such as hiking, tennis, swimming, biking, jogging or racquetball.

The brain scans showed that 197 of the participants, or 16 percent, had small brain lesions, or infarcts, called silent strokes. People who engaged in moderate to intense exercise were 40 percent less likely to have the silent strokes than people who did no regular exercise. The results remained the same after the researchers took into account other vascular risk factors such as high blood pressure, high cholesterol and smoking. There was no difference between those who engaged in light exercise and those who did not exercise.

"Of course, light exercise has many other beneficial effects, and these results should not discourage people from doing light exercise," Willey said.

The study also showed that the benefit of moderate to intense exercise on brain health was not apparent for people with Medicaid or no health insurance. People who exercised regularly at a moderate to intense level who had Medicaid or no health insurance were no less likely to have silent infarcts than people who did no regular exercise. "It may be that the overall life difficulties for people with no insurance or on Medicaid lessens the protective effect of regular exercise," Willey said.

Provided by American Academy of Neurology

Molecular imaging for Alzheimer's disease may be available in hospitals within a year

Researchers the world over are advancing positron emission tomography (PET) as an effective method of early detection for Alzheimer's disease, a currently incurable and deadly neurological disorder. Three studies presented at SNM's 58th Annual Meeting are providing new insights into the development of Alzheimer's disease while opening the door to future clinical screening and treatments.

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

10 june 2011--"The aging population around the world is escalating exponentially. From a macro perspective, amyloid imaging with PET scans can help to ascertain the likelihood that individuals will deteriorate cognitively within a few years, thereby enabling more efficient channeling of health care resources," says Kevin Ong, MD, lead author of a presented study and a research scientist at Austin Hospital, Melbourne, Australia. "From a micro perspective, planning and lifestyle modifications are possible for individuals who seek screening for Alzheimer's disease."

Molecular imaging of Alzheimer's disease is focused on detecting and analyzing the formation of a naturally occurring protein in the brain called beta-amyloid, which researchers now say is directly involved in the pathology of Alzheimer's.

"It turns out that increased amyloid is bad for cognition even in the healthy elderly," says Michael Devous, Sr., PhD, director of neuroimaging for the Alzheimer's Disease Center at UT Southwestern Medical Center, Dallas, Texas. "If you look at working memory, processing speed or fluent reasoning, three critical general domains of cognition, the more amyloid you have the worse your performance, and that's after correcting for age."

Not only is this important for imaging the disease, but it may also prove to be the key to amyloid-associated therapies and vaccines. Investigators warn that the beginning stages of the disease can precede symptoms of dementia as much as a decade or more. Imaging patients when they first show signs of mild cognitive impairment could be essential to determining their risk of future disease.

"For individuals who have already developed a measurable memory decline, a positive scan for amyloid is the most accurate predictor of progression to Alzheimer's disease," said Christopher Rowe, MD, a lead investigator for the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging and professor of nuclear medicine at Austin Hospital, Victoria, Australia. "Amyloid imaging with PET scans is expected to be widely available soon for clinical practice. It will be an important new tool in the assessment of cognitive decline."

Beta-amyloid accumulates as neurotoxic plaque in individuals preceding the onset of Alzheimer's disease, and as a result, extensive neural tissues that control major mental and physical functioning—including memory, language and motor function—are decimated. In time the disease becomes debilitating and has a devastating impact on individuals' quality of life.

Three ongoing studies presented at this year's meeting involve several years of research based on hundreds of participants ranging widely in age, cognitive ability and stage of disease. Results of these studies show that amyloid plaques build up very slowly, by an estimated two to three percent per year, and that they are often already present in healthy older individuals—12 percent of those in their 60s, 30 percent of those in their 70s and 55 percent in those over the age of 80. In one study, about 25 percent of subjects over the age of 60 had amyloid plaques. The presence of significant amyloid buildup is linked to quicker memory decline and brain atrophy.

One of the major questions in Alzheimer's imaging has been which imaging agent is best for amyloid plaque screening. Several studies have been conducted using 11C Pittsburgh Compound-B (11C-PIB), a PET imaging agent that binds to beta-amyloid in neural tissues, but two of the current studies are gauging the benefit of using F-18 labeled tracers (F-18 Florbetaben and F-18 Florbetapir), designed for routine clinical use. Both F-18 Florbetaben and F-18 Florbetapir are proving to be good predictors of progression to Alzheimer's disease, and F-18 amyloid imaging agents are the likeliest agents to move forward into clinical practice in the near future.

Researchers estimate that amyloid imaging agents will be available for clinical use in fewer than 12 months. These and further studies will continue to amass data about the development of Alzheimer's disease, and potential treatments could eventually stop and perhaps even prevent or reverse damage in the brain caused by Alzheimer's disease.

More information: Scientific Paper 119: K. Rodrigue, K. Kennedy, M. Devous, D. Park, UT Southwestern Medical Center, Dallas, TX; "Beta-amyloid in healthy aging: Regional distribution and cognitive consequences," SNM's 58th Annual Meeting, June 4-8, 2011, San Antonio, TX.

Scientific Paper 121: C. Rowe, K. Ellis, B. Brown, P. Bourgeat, R. Head, R. Martins, O. Salvado, C. Masters, D. Ames, V. Villemagne, Austin Hospital, Melbourne, Australia; University of Melbourne, Melbourne, Australia; Edith Cowan University, Perth, Australia; Australian e-Health Research Centre, CSIRO, Brisbane, Australia; National Ageing Research Institute, Melbourne, Australia; Mental Health Research Institute, Melbourne, Australia; "The consequences of Aβ deposition in ageing and Alzheimer's disease: Results from 366 elderly subjects," SNM's 58th Annual Meeting, June 4-8, 2011, San Antonio, TX.

Scientific Paper 170: K. Ong, V. Villemagne, A. Bahar-Fuchs, F. Lamb, G. Chételat, C. Reininger, B. Putz, B. Rohde, C. Masters, C. Rowe. Austin Hospital, Melbourne, Australia; Bayer Schering Pharma, Berlin, Germany; Mental Health Research Institute, Melbourne, Australia; "Conversion from mild cognitive impairment to Alzheimer's disease over 12 months: Predictive value of Aβ imaging with 18F-Florbetaben," SNM's 58th Annual Meeting, June 4-8, 2011, San Antonio, TX.

Provided by Society of Nuclear Medicine

Older age does not cause testosterone levels to decline in healthy men

A decline in testosterone levels as men grow older is likely the result—not the cause—of deteriorating general health, say Australian scientists, whose new study finds that age, in itself, has no effect on testosterone level in healthy older men.

09 june 2011--The results, to be presented Tuesday at The Endocrine Society's 93rd Annual Meeting in Boston, are the first findings released from the Healthy Man Study, according to principal investigator David Handelsman, MD, PhD, professor and director of the ANZAC Research Institute at the University of Sydney.

"Some researchers believe that an age-related testosterone deficiency contributes to the deteriorating health of older men and causes nonspecific symptoms, such as tiredness and loss of libido," he said.

Handelsman and his team, however, found that serum (blood) testosterone levels did not decline with increasing age in older men who reported being in excellent health with no symptoms to complain of.

"We had originally expected age to have an effect on serum testosterone, so the findings were a bit of a surprise," Handelsman said.

Two study centers in Australia recruited 325 men over the age of 40 (median age, 60) who had self-reported excellent health and no symptom complaints. To test blood testosterone levels, the researchers took blood samples from the men nine times over three months. They excluded men from the study who took medications that affect testosterone.

Obesity caused a mild and clinically unimportant lowering of blood testosterone levels, the investigators reported. Age had no effect on testosterone level.

"The modest decline in blood testosterone among older men, usually coupled with nonspecific symptoms, such as easy fatigue and low sexual desire, may be due to symptomatic disorders that accumulate during aging, including obesity and heart disease," he said. "It does not appear to be a hormone deficiency state."

The message for patients and their doctors, Handelsman said, is "older men with low testosterone levels do not need testosterone therapy unless they have diseases of their pituitary or testes."

Provided by The Endocrine Society

Active social, spiritual and physical life helps prevent health decline in seniors

Small, healthy lifestyle changes and involvement in meaningful activities—going beyond just diet and exercise—are critical to healthy aging, according to a new USC study.

08 june 2011--Guided by lifestyle advisors, seniors participating in the study made small, sustainable changes in their routines (such as visiting a museum with a friend once a week) that led to measurable gains in quality of life, including lower rates of depression and better reported satisfaction with life.

The study validates the current trend in public health strategies to focus on preventing illness and disability, as opposed to treating issues once they have already begun to negatively impact health, according to lead investigator Florence Clark.

"What is critical is that, as we age, we continue to be engaged in life through a sustainable mix of productive, social, physical and spiritual activities. This goal of prevention and wellness is really a key to health care reform, and results in cost savings to society," said Clark, professor and associate dean of the Division of Occupational Science and Occupational Therapy at the Herman Ostrow School of Dentistry of USC, and president of the American Occupational Therapy Association.

"The emphasis now is prevention," she said. "There are non-pharmacologic interventions that work."

The Well Elderly 2 trial was performed between 2004 and 2009, with the write-up appearing in the June 2 issue of the Journal of Epidemiology and Community Health.

During six-month periods, licensed occupational therapists assisted more than 200 individuals aged 60 and older to develop sustainably healthy lifestyles and see if they improved the participants' overall quality of life.

"The key to the individualized plans was to make them sustainable," Clark said.

For example, some people like going to the gym to stay physically healthy, but others find the thought of slaving away in a room indoors for three times a week utterly abhorrent—so much so that, no matter what good intentions they have, they will not wind up going. For such individuals, a more effective and longer-lasting strategy to improve physical health may be to instead walk for an hour around their neighborhood in the evenings.

The occupational therapists also provided guidance for using public transportation, getting the participants off of the couch and out into the world.

"You're able to go to a museum, you're able to go to a park… it can open up a whole world of opportunities," Clark said. In one instance, the therapists helped a woman who had taken a nasty fall while boarding a bus to work up enough confidence to ride again. Eventually, she was able to take the bus to go do volunteer work—a fulfilling pastime that she had sorely missed, Clark said.

"Being engaged in a social life has a positive effect on health," she said, "but the public is not sufficiently aware of how key this is to successful aging."

The older adult participants were described as "well" because they were living in the community, not in a skilled nursing facility or other institutional setting.

To determine the results of the trial, quality of life was measured using a variety of indicators, including physical health, mental health, social well-being and life satisfaction. The program participants were compared to a control group that did not receive the intervention.

Though the two groups started out roughly equivalent, the intervention group showed significant improvement in lessening bodily pain and depression while improving vitality, social function, mental health and overall life satisfaction.

Lesser, though still measurable, gains were made in general health and physical abilities.

At the end of the first phase of the trial, the control group was provided with the same treatment that had been given to the intervention group—and made identical progress.

The study findings replicate the outcomes of the influential Well Elderly 1 trial, but extend them to a more ethnically diverse population living in a wide range of community settings, demonstrating the lifestyle program's value for the general public.

The results of the Well Elderly 1 trial, conducted in 1997, were used by the London-and-Manchester-based National Institute for Health and Clinical Excellence (NICE) to develop recommendations for British public health policies.

"Although people are living longer, it is important that they also live better. This intervention results in improved quality of life and provides a vehicle for maintaining health as we age," Clark said.

The Well Elderly 2 trial demonstrated that, compared with other interventions, this lifestyle intervention was cost-effective. For every dollar spent, there was a significant enough gain in health outcomes to justify the expenditure, according to Clark.

"The American public needs to know about this," she said. "Making positive changes in how we live each day, and sustaining those changes over the long term, is critical for maintaining independence and healthy aging."

Provided by University of Southern California

Experts recommend screening for vitamin D deficiency in at-risk populations

Today, The Endocrine Society released "Evaluation, Treatment, and Prevention of Vitamin D Deficiency: An Endocrine Society Clinical Practice Guideline." The clinical practice guideline (CPG) is published in the July 2011 issue of the Journal of Clinical Endocrinology & Metabolism (JCEM), a publication of The Endocrine Society.

07 june 2011--The major source of vitamin D for children and adults is exposure to natural sunlight as very few foods naturally contain or are fortified with vitamin D. Vitamin D deficiency is common throughout the world and results in abnormalities of calcium, phosphorus and bone metabolism which can lead to muscle weakness, osteomalacia, osteopenia and osteoporosis. In children, vitamin D deficiency can result in skeletal deformities known as rickets.

"Vitamin D deficiency is very common in all age groups and it is important that physicians and health care providers have the best evidence-based recommendations for evaluating, treating and preventing vitamin D deficiency in patients at highest risk," said Michael F. Holick, PhD, MD, of the Boston University School of Medicine and chair of the task force that authored the CPG. "The Society's new Clinical Practice Guideline was developed by experts in the field who carefully reviewed the current literature and features the latest and most comprehensive recommendations available on the prevention and treatment of vitamin D deficiency."

Recommendations from the CPG include:

• Screening for vitamin D deficiency in individuals at risk for deficiency;
  
• Measurement of vitamin D level by a reliable assay as the initial diagnostic test in patients at risk for deficiency; and
  
• Treatment with either vitaminD2 or vitamin D3 for deficient patients.

The CPG also features recommendations for dietary intake of vitamin D in patients at risk for vitamin D deficiency. These recommendations include:

• Infants and children ages 0-1 year require at least 400 IU/day (IU=25 ng) of vitamin D and children 1 year and older require at least 600 IU/day to maximize bone health. To raise the blood level of vitamin D consistently above 30 ng/ml may require at least 1,000 IU/day of vitamin D;
  
• Adults aged 19-50 years require at least 600 IU/day of vitamin D to maximize bone health and muscle function and at least 1,500-2,000 IU/day of vitamin D may be needed to maintain blood level of vitamin D above 30 ng/ml;
  
• Adults aged 50-70 years and adults older than 70 years require at least 600 IU/day and 800 IU/day respectively of vitamin D. At least 1,500-2,000 IU/day of vitamin D may be needed to maintain blood level of vitamin D above 30 ng/ml; and
  
• Pregnant and lactating women require at least 600 IU/day of vitamin D and at least 1,500 IU/day of vitamin D may be needed to maintain blood level of vitamin D above 30 ng/ml.

"At the present time, there is not sufficient evidence to recommend screening individuals who are not at risk for deficiency or to prescribe vitamin D to attain the non-calcemic benefit for cardiovascular protection," said Holick.

Provided by The Endocrine Society

All the lonely people

UC Irvine psychologist Karen Rook can trace her interest in how loneliness affects the elderly to her childhood, when she saw a much-loved, once-robust grandmother decline markedly after losing her husband.

06 jun 2011--Unable to manage the family farm on her own, her grandmother moved into an apartment. After breaking her hip in a fall, she ended up frail and forlorn in a nursing home, away from the life and friends she had once known.

"The sadness and loneliness of many nursing home residents is simply heartbreaking," Rook says. "Family members can do only so much. We visited my grandmother every week, but at the end of each visit, she would become very quiet and struggle to fight back tears. It tore my father apart. Because of these experiences, my first life's goal was to build better nursing homes." But she chose a different path.

Through her research, Rook is working to draw attention to seniors' social needs and prevent them from spending their last days in painful isolation. The UCI associate dean of research in social ecology and professor of psychology & social behavior has studied relationships and their effect on people's health and well-being for 30 years.

"My work — and that of many other researchers — shows there's something fundamentally important about having relationships," she says. "Without them, there's a risk to our mental health, our longevity and our quality of life."

Social connections are important to all age groups, but Rook focuses on older adults because they're frequently coping with the death of loved ones as well as increased physical limitations.

"I was drawn to this field because a great deal of change occurs in people's social networks when they reach their 70s and 80s. The loss of a spouse and the loss of close friends are common. Declining health and mobility also can make it more difficult to get together with others," Rook says. "It's important to question how seniors' social needs are met when such losses and declines occur."

She wondered, for instance, whether making new friends or reviving existing relationships improved the mental outlook of recently widowed older women. Findings from the 2004 study surprised her.

"We asked to what extent new or rekindled social ties helped alleviate loneliness," Rook says. "We found little evidence of benefits. It takes time for new relationships to gel, of course, but it also may be inherently difficult for them to offer psychological benefits comparable to those of a decades-long marital relationship."

Even when adult children provide a great deal of emotional and practical support, widowed seniors may still feel lonely. "They continue to miss the companionship and unique connection supplied by the spouse," she says.

"Companionship is important to our well-being. It's not just who you can count on for support in times of stress but who you spend time with on a day-to-day basis."

Friendship is a topic Rook has explored among all age groups. Whether you're 25 or 85, she notes, "getting together with good friends is restorative, because it provides a respite from daily stresses and worries. It's also affirming. It signals, without needing to be spoken, that you're valued enough by others that they just want to spend time with you."

Still, being lonely isn't always enough to motivate people to try to meet others and risk rejection.

"Lonely people want companionship but sometimes fear that their overtures may not be reciprocated. Their hesitation can cause loneliness to persist," Rook says. "Making friends later in life isn't easy. When you're younger, you can meet people through school or work who have things in common with you. The elderly usually are retired from the workforce and don't have the ready access to peers with similar interests that schools provide."

In a current study of more than 900 older people, she's finding that the loneliest individuals are reluctant to forge relationships, but if they can overcome that initial resistance and make new friends, their happiness increases.

"We're fortunate to have Professor Rook shedding light on some of the mysteries of aging in a way that better prepares us to respond to some of its challenges," says Valerie Jenness, dean of social ecology.

"Understanding the nexus among aging, changing social relations and health is not only important to further our knowledge of developmental psychology, it's an imperative first step toward creating policies sensitive to the needs and desires of an aging population."

Rook is frequently moved by seniors' stories and struggles. "Later life is a time when there's not just vulnerability but also incredible fortitude," she says. "Older adults often exhibit truly impressive resilience."

She hopes her research will facilitate interventions to help alleviate loneliness and enhance well-being in the elderly — which could lead to better nursing homes after all.

Provided by University of California, Irvine

What can we do about death? Reinventing the American medical system

03 jun 2011-- In a feature article in The New Republic, Daniel Callahan and Sherwin Nuland propose a radical reinvention of the American medical system requiring new ways of thinking about living, aging, and dying. They argue that a sustainable -- and more humane -- medical system in the U.S. will have to reprioritize to emphasize public health and prevention for the young, and care not cure for the elderly.

An interesting twist on their argument, which would aim to bring everyone's life expectancy up to an average age of 80 years but give highest priority for medical treatment to those under 80, is that Callahan and Nuland are themselves 80 years old. Daniel Callahan, Ph.D., is cofounder and president emeritus of The Hastings Center and author most recently of Taming the Beloved Beast: How Medical Technology Costs Are Destroying Our Health Care System. Sherwin Nuland, M.D., is a retired Clinical Professor of Surgery at the Yale School of Medicine and author of How We Die and the Art of Aging. He is also a Hastings Center Fellow and Board member.

"The real problem is that we have medicine excessively driven by progress, which aims to rid us of death and disease and treats them as the targets of unlimited medical warfare," said Callahan and Nuland. "That warfare, however, has come to look like the trench warfare of World War I: great human and economic cost for little progress. Neither infectious disease nor the chronic diseases of an aging society will soon be cured. Cancer, heart disease, stroke, and Alzheimer's disease are our fate for the foreseeable future. Medicine and the public must adapt it to that reality, one that has mainly brought us lives that end poorly and expensively in old age."

The article notes that the Affordable Care Act might ease the financial burden of this system, but not eliminate it. It reports, for example, that the cost of Alzheimer's disease is projected to rise from $91 billion in 2005 to $189 billion in 2015, and to $1 trillion in 2025 – twice the cost of Medicare expenditures for all diseases now.

"We need to change our priorities for the elderly. Death is not the only bad thing that can happen to an elderly person," the authors write. "An old age marked by disability, economic insecurity, and social isolation are also great evils." They endorse a culture of care, not cure, for the elderly, with a stronger Social Security program and a Medicare program weighted toward primary care that supports preventative measures and independent living.

Callahan and Nuland point the way to a more sustainable path that reprioritizes the entire system. Among their recommendations:

• improve medicine at the level of public health and primary care, while reducing its use for expensive high-tech end-of-life care;
  
• shift resources for the elderly to greater economic and social security and away from more medical care;
  
• subsidize the education of physicians, particularly those who go into primary care, and decrease medical subspecialization;
  
• train physicians better to tell the truth to patients about the way excessively aggressive medicine can increase the likelihood of a poor death;
  
• shift the emphasis in chronic disease to care rather than cure;
  
• conduct a top-down, bottom-up, long-range study of the entire American system of health care, including the training of physicians, with a view toward reconstituting it along systematic lines that take science, humanistic concerns, economics, and social issues into account.

Provided by The Hastings Center

Arrowing in on Alzheimer's disease

Recently the number of genes known to be associated with Alzheimer's disease has increased from four to eight, including the MS4A gene cluster on chromosome 11. New research published in BioMed Central's open access journal Genome Medicine has expanded on this using a genome-wide association study (GWAS) to find a novel location within the MS4A gene cluster which is associated with Alzheimer's disease.

02 jun 2011--Alzheimer's disease is the most common cause of dementia in the developed world. It irrevocably destroys cells in the brain that are responsible for intellectual ability and memory. Despite continued investigation, the causes of Alzheimer's disease are not yet fully understood but they are thought to be a mixture of genetic and environmental factors. Several studies have used GWAS to search the entire human genome for genes which are mutated in Alzheimer's sufferers in the hope of finding a way to treat or slow down the disease.

A team of researchers across Spain and USA sponsored by non-profit Fundación Alzheimur (Comunidad Autónoma de la Región de Murcia) and Fundació ACE Institut Català de Neurociències Aplicades performed their own GWAS study using patients with Alzheimer's disease, and non-affected controls, from Spain and then combined their results with four public GWAS data sets. Dr Agustín Ruiz said, "Combining these data sets allowed us to look more accurately at small genetic defects. Using this technique we were able to confirm the presence of mutations (SNP) known to be associated with Alzheimer's disease, including those within the MS4A cluster, and we also found a novel site."

Dr Ruiz continued, "Several of the 16 genes within the MS4A cluster are implicated in the activities of the immune system and are probably involved in allergies and autoimmune disease. MS4A2 in particular has been linked to aspirin-intolerant asthma. Our research provides new evidence for a role of the immune system in the progression of Alzheimer's disease."

More information: The membrane-spanning 4-domains, subfamily A (MS4A) gene cluster contains a common variant associated with Alzheimer's disease. Carmen Antunez, et al. , Genome Medicine (in press)

Provided by BioMed Central

Experts say cellphones are 'possibly carcinogenic'

A man uses a cell phone in New York. The use of cell phones and other wireless communication devices are "possibly carcinogenic to humans", the World Health Organisation's cancer research agency said Tuesday.

01 jun 2011 -- A respected international panel of scientists says cellphones are possible cancer-causing agents, putting them in the same category as the pesticide DDT, gasoline engine exhaust and coffee.

The classification was issued Tuesday in Lyon, France, by the International Agency for Research on Cancer after a review of dozens of published studies. The agency is an arm of the World Health Organization and its assessment now goes to WHO and national health agencies for possible guidance on cellphone use.

Classifying agents as "possibly carcinogenic" doesn't mean they automatically cause cancer and some experts said the ruling shouldn't change people's cellphone habits.

"Anything is a possible carcinogen," said Donald Berry, a professor of biostatistics at the M.D. Anderson Cancer Center at the University of Texas. He was not involved in the WHO cancer group's assessment. "This is not something I worry about and it will not in any way change how I use my cellphone," he said - speaking from his cellphone.

The same cancer research agency lists alcoholic drinks as a known carcinogen and night shift work as a probable carcinogen. Anyone's risk for cancer depends on many factors, from genetic makeup to the amount and length of time of an exposure.

After a weeklong meeting on the type of electromagnetic radiation found in cellphones, microwaves and radar, the expert panel said there was limited evidence cellphone use was linked to two types of brain tumors and inadequate evidence to draw conclusions for other cancers.

"We found some threads of evidence telling us how cancers might occur, but there were acknowledged gaps and uncertainties," said Jonathan Samet of the University of Southern California, the panel's chairman.

"The WHO's verdict means there is some evidence linking mobile phones to cancer but it is too weak to draw strong conclusions from," said Ed Yong, head of health information at Cancer Research U.K. "If such a link exists, it is unlikely to be a large one."

Last year, results of a large study found no clear link between cellphones and cancer. But some advocacy groups contend the study raised serious concerns because it showed a hint of a possible connection between very heavy phone use and glioma, a rare but often deadly form of brain tumor. However, the numbers in that subgroup weren't sufficient to make the case.

The study was controversial because it began with people who already had cancer and asked them to recall how often they used their cellphones more than a decade ago.

In about 30 other studies done in Europe, New Zealand and the U.S., patients with brain tumors have not reported using their cellphones more often than unaffected people.

Because cellphones are so popular, it may be impossible for experts to compare cellphone users who develop brain tumors with people who don't use the devices. According to a survey last year, the number of cellphone subscribers worldwide has hit 5 billion, or nearly three-quarters of the global population.

People's cellphone habits have also changed dramatically since the first studies began years ago and it's unclear if the results of previous research would still apply today.

Since many cancerous tumors take decades to develop, experts say it's impossible to conclude cellphones have no long-term health risks. The studies conducted so far haven't tracked people for longer than about a decade.

Cellphones send signals to nearby towers via radio frequency waves, a form of energy similar to FM radio waves and microwaves. But the radiation produced by cellphones cannot directly damage DNA and is different from stronger types of radiation like X-rays or ultraviolet light. At very high levels, radio frequency waves from cellphones can heat up body tissue, but that is not believed to damage human cells.

Some experts recommended people use a headset or earpiece if they are worried about the possible health dangers of cellphones. "If there is a risk, most of it goes away with a wireless earpiece," said Otis Brawley, chief medical officer of the American Cancer Society.

Brawley said people should focus on the real health hazards of cellphones. "Cellphones may cause brain tumors but they kill far more people through automobile accidents," he said. Brawley added it was also reasonable to limit children's use of cellphones since their brains are still developing.

Earlier this year, a U.S. National Institutes of Health study found that cellphone use can speed up brain activity, but it is unknown whether that has any dangerous health effects.

The cellphone industry trade group, CTIA-The Wireless Association, pointed to two U.S. agencies that have found no evidence cellphones are linked to cancer - the Food and Drug Administration and the Federal Communications Commission.

The WHO's cancer research agency has reviewed more than 900 occupational exposures, chemicals and other agents since 1971, classifying their link to cancer by labeling them from carcinogenic to probably not carcinogenic. The American Cancer Society has estimated that only about 6 percent of cancers are related to environmental causes and most of that is on-the-job occupational exposure.