Psychiatry debates whether the pain of loss is really depression

The pain of losing a loved one can be a searing, gut-wrenching hurt and a long-lasting blow to a person's mood, concentration and ability to function. But is grief the same as depression?

18 feb 2012--That's a lively debate right now, as the psychiatric profession considers a key change in the forthcoming rewrite of its diagnostic "Bible." That proposed modification - one of many - would allow mental health providers to label the psychic pain of bereavement a mood disorder and act quickly to treat it, in some cases, with medication. With the Diagnostic and Statistical Manual's fifth edition set for completion by the end of this year, the editors of the British journal The Lancet have come out in strong opposition to the new language, calling grief a natural and healthy response to loss, not a pathological state.

"Grief is not an illness. It is more usefully thought of as part of being human, and a normal response to the death of a loved one," writes the editor of The Lancet. "Most people who experience the death of someone they love do not need treatment by a psychiatrist or indeed by any doctor. For those who are grieving, doctors would do better to offer time, compassion, remembrance, and empathy, than pills."

The change under consideration would expunge any reference to the passage of time since a loved one's death before a diagnosis of depression could be considered. The current edition of the diagnostic manual states that if a patient's low mood and energy, sleep difficulties and appetite changes persist for more than two months following bereavement, a diagnosis of depression might be considered. An earlier edition of the manual had established a year as the period during which mourning should not be confused with depression.

"Putting a time frame on grief is inappropriate," The Lancet's lead editorial states simply. And in a "Perspectives" essay also published Thursday in Lancet, Harvard University medical anthropologist Dr. Arthur Kleinman agrees, eloquently exploring what's at stake.

"Is grief something we can or should no longer tolerate?" asks Kleinman, who describes his own grief after his wife of 46 years died last March from Alzheimer's Disease. "Is this existential source of suffering like any dental or back pain unwanted and unneeded?"

Kleinman calls the current two-month time period allowed for grief a "shockingly short expectation" that no religion or society would support. To allow grief to be redefined as depression with no allowance at all for the passage of time not only spells "the loss of grief": it risks redefining vast numbers of Americans who are taking their time to adjust to the loss of a loved one as sick, he writes. And it powerfully rewrites cultural values about how we understand and mark the loss of a fellow human being.

Proponents of the change have argued that it would allow the bereaved to seek help for their suffering. And they add that it would not define all who grieve as depressed. They argue there is often no difference, but for the recent death of a loved one, between the behaviors that define depression and those that define grief.

The Lancet's editors note there is no evidence that antidepressant medications improve the moods of people who are healthy to begin with. Citing fellow critics of the proposed move, Kleinman suggests that it might have been inevitable once the financial interests of pharmaceutical manufacturers collided with psychiatry's loose definitions of mental illness and the profession's tendency to expand its patient base.

"Its ubiquity makes grief a potential profit centre for the business of psychiatry," writes Kleinman.

Study: Weight training improves Parkinson's symptoms

New research suggests weight training for two years significantly improves the motor symptoms of Parkinson's disease compared to other forms of exercise such as stretching and balance exercises. The clinical trial, which compared two forms of exercise for Parkinson's disease, was released today and will be presented at the American Academy of Neurology's 64th Annual Meeting in New Orleans April 21 to April 28, 2012.

17 feb 2012--"While we have known that many different types of exercise can benefit Parkinson's patients over short time periods, we did not know whether exercise improves the motor symptoms of Parkinson's over the long term," said study author Daniel Corcos, PhD, with the University of Illinois at Chicago.

For the study, 48 people with Parkinson's disease were randomized to progressive resistance exercise, known as weight training, or they were assigned to the exercise known as fitness counts, which includes flexibility, balance and strengthening exercises. The groups exercised for one hour, twice a week for two years.

The severity of motor symptoms, including tremors, was measured using the Unified Parkinson's Disease Rating Scale (UPDRS) after six, 12, 18 and 24 months of exercise. Scores were taken when the participants were not taking their medication.

While both forms of exercise reduced motor symptoms at six months of exercise, participants who did weight training saw a 7.3 point improvement in their UPRDS score after two years while the fitness counts group returned to the same scores they had at the start of the study.

"Our results suggest that long-term weight training could be considered by patients and doctors as an important component in managing Parkinson's disease," said Corcos.

Provided by American Academy of Neurology

Stem cell treatments improve heart function after heart attack

Stem cell therapy moderately improves heart function after a heart attack, according to a systematic review published in The Cochrane Library. But the researchers behind the review say larger clinical trials are needed to establish whether this benefit translates to a longer life.

16 feb 2012--In a heart attack, the blood supply to parts of the heart is cut off by a blocked artery, causing damage to the heart tissue. The cells in the affected area start to die. This is called necrosis and in the days and weeks that follow, the necrotic area may grow, eventually leaving a large part of the heart unable to contract and increasing the risk of further heart problems. Stem cell therapy uses cells from the patient's own bone marrow to try to repair and reduce this damage. Currently, the treatment is only available in facilities with links to scientific research.

The authors of the review drew together all the available evidence to ask whether adult bone marrow stem cells can effectively prevent and repair the damage caused by a heart attack. In 2008, a Cochrane review of 13 stem cell therapy clinical trials addressed the same question, but the new review adds 20 more recent trials, drawing its conclusions from all 33. By incorporating longer follow up, the later trials provide a better indication of the effects of the therapy several years after treatment.

The total number of patients involved in trials was 1,765. All had already undergone angioplasty, a conventional treatment that uses a balloon to open the blocked artery and reintroduce the blood supply. The review's findings suggest that stem cell therapy using bone marrow-derived stem cells (BMSCs) can produce a moderate long-term improvement in heart function, which is sustained for up to five years. However, there was not enough data to reach firm conclusions about improvements in survival rates.

"This new treatment may lead to moderate improvement in heart function over standard treatments," said lead author of the study, Enca Martin-Rendon, of the Stem Cell Research laboratory, NHS Blood and Transplant at the John Radcliffe Hospital in Oxford, UK. "Stem cell therapy may also reduce the number of patients who later die or suffer from heart failure, but currently there is a lack of statistically significant evidence based on the small number of patients treated so far."

It is still too early to formulate guidelines for standard practice, according to the review. The authors say further work is required to establish standard methods, including cell dosage, timing of cell transplantation and methods to measure heart function. "The studies were hard to compare because they used so many different methods," said Martin-Rendon. "Larger trials with standardised treatment procedures would help us to know whether this treatment is really effective.

Recently, the task force of the European Society of Cardiology for Stem Cells and Cardiac Repair received funding from the European Union Seventh Framework Programme for Research and Innovation (EU FP7-BAMI) to start such a trial. Principal Investigator for the BAMI trial, and co-author of this Cochrane review, Anthony Mathur, said, ''The BAMI trial will be the largest stem cell therapy trial in patients who have suffered heart attacks and will test whether this treatment prolongs the life of these patients."

More information: Clifford DM, Fisher SA, Brunskill SJ, Doree C, Mathur A, Watt S, Martin-Rendon E. Stem cell treatment for acute myocardial infarction. Cochrane Database of Systematic Reviews 2012, Issue 2. Art. No.: CD006536. DOI: 10.1002/14651858.CD006536.pub3

Cognitive impairment in older adults often unrecognized in the primary care setting

A new study published in the Journal of the American Geriatrics Society reveals that brief cognitive screenings combined with offering further evaluation increased new diagnoses of cognitive impairment in older veterans two to three fold.

15 feb 2012--Led by J. Riley McCarten, MD, of the Minneapolis VA Health Care System and the University of Minnesota, researchers assessed the effect of screening on diagnosing cognitive impairment in patients who were seen in VA primary care clinics and had no indiction of memory loss. Veterans aged 70 and older who failed the brief cognitive screen at a routine primary care visit were offered a further, comprehensive evaluation.

Of the 8,342 Veterans offered screening, 8,063 (97%) accepted, 2,081 (26%) failed the screen, and 580 (28%) agreed to further evaluation.

Among those accepting further evaluation, 93% were documented to have cognitive impairment, including 75% with dementia.

Additionally, 118 patients who passed the initial screen still requested further evaluation, and 87% were found to have cognitive impairment, including 70% with dementia.

"Our study demonstrates that proactive strategies such as routine screening are well-accepted and effective in diagnosing cognitive impairment, and that primary care providers value the diagnostic and management services involved," McCarten notes. "This project has implications for strategies that seek to improve care and contain costs in dementia."

The findings of this study run counter to the current standard recommendations by the American College of Physicians, U.S. Preventive Health Task Force, and Alzheimer's Association, which discourage routine cognitive impairment/dementia screening on all older patients at a certain age. Screening is only recommended if a person comes to a provider with some type of complaint that could be due to dementia.

Provided by Wiley

Overeating may double risk of memory loss

New research suggests that consuming between 2,100 and 6,000 calories per day may double the risk of memory loss, or mild cognitive impairment (MCI), among people age 70 and older. The study was released today and will be presented at the American Academy of Neurology's 64th Annual Meeting in New Orleans April 21 to April 28, 2012. MCI is the stage between normal memory loss that comes with aging and early Alzheimer's disease.

14 feb 2012--"We observed a dose-response pattern which simply means; the higher the amount of calories consumed each day, the higher the risk of MCI," said study author Yonas E. Geda, MD, MSc, with the Mayo Clinic in Scottsdale, Arizona and a member of the American Academy of Neurology.

The study involved 1,233 people between the ages of 70 and 89 and free of dementia residing in Olmsted County, Minn. Of those, 163 had MCI. Participants reported the amount of calories they ate or drank in a food questionnaire and were divided into three equal groups based on their daily caloric consumption. One-third of the participants consumed between 600 and 1,526 calories per day, one-third between 1,526 and 2,143 and one-third consumed between 2,143 and 6,000 calories per day.

The odds of having MCI more than doubled for those in the highest calorie-consuming group compared to those in the lowest calorie-consuming group. The results were the same after adjusting for history of stroke, diabetes, amount of education, and other factors that can affect risk of memory loss. There was no significant difference in risk for the middle group.

"Cutting calories and eating foods that make up a healthy diet may be a simpler way to prevent memory loss as we age," said Geda.

Provided by American Academy of Neurology

Exercise triggers stem cells in muscle

University of Illinois researchers determined that an adult stem cell present in muscle is responsive to exercise, a discovery that may provide a link between exercise and muscle health. The findings could lead to new therapeutic techniques using these cells to rehabilitate injured muscle and prevent or restore muscle loss with age.

13 feb 2012--Mesenchymal stem cells (MSCs) in skeletal muscle have been known to be important for muscle repair in response to non-physiological injury, predominantly in response to chemical injections that significantly damage muscle tissue and induce inflammation. The researchers, led by kinesiology and community health professor Marni Boppart, investigated whether MSCs also responded to strain during exercise, and if so, how.

"Since exercise can induce some injury as part of the remodeling process following mechanical strain, we wondered if MSC accumulation was a natural response to exercise and whether these cells contributed to the beneficial regeneration and growth process that occurs post-exercise," said Boppart, who also is affiliated with the Beckman Institute for Advanced Science and Technology at the U. of I.

The researchers found that MSCs in muscle are very responsive to mechanical strain. They witnessed MSC accumulation in muscle of mice after vigorous exercise. Then, they determined that although MSCs don't directly contribute to building new muscle fibers, they release growth factors that spur other cells in muscle to fuse and generate new muscle, providing the cellular basis for enhanced muscle health following exercise.

A key element to the Illinois team's method was in exercising the mice before isolating the cells to trigger secretion of beneficial growth factors. Then, they dyed the cells with a fluorescent marker and injected them into other mice to6 see how MSCs coordinated with other muscle-building cells.

In addition to examining the cells in vivo, the researchers studied the cells' response to strain on different substrates. They found that MSC response is very sensitive to the mechanical environment, indicating that conditions of muscle strain affect the cells' activity.

"These findings are important because we've identified an adult stem cell in muscle that may provide the basis for muscle health with exercise and enhanced muscle healing with rehabilitation/movement therapy," Boppart said. "The fact that MSCs in muscle have the potential to release high concentrations of growth factor into the circulatory system during exercise also makes us wonder if they provide a critical link between enhanced whole-body health and participation in routine physical activity."

Next, the group hopes to determine whether these cells contribute to the decline in muscle mass over a person's lifetime. Preliminary data suggest MSCs become deficient in muscle with age. The team hopes to develop a combinatorial therapy that utilizes molecular and stem-cell-based strategies to prevent age-related muscle loss.

"Although exercise is the best strategy for preserving muscle as we age, some individuals are just not able to effectively engage in physical activity," Boppart said. "Disabilities can limit opportunities for muscle growth. We're working hard to understand how we can best utilize these cells effectively to preserve muscle mass in the face of atrophy."

The team published its findings in the journal PLoS One. The Illinois Regenerative Medicine Institute, the Ellison Medical Foundation and the Mary Jane Neer Foundation supported this work.

More information: The paper, "Eccentric Exercise Facilitates Mesenchymal Stem Cell Appearance in Skeletal Muscle," is available online on PLoS ONE site.

Provided by University of Illinois at Urbana-Champaign

Cognitive problems common among non-demented elderly

Both subjective and objective cognitive impairment are highly common among non-demented elderly Swedes, with an overall prevalence of 39 percent and 25 percent respectively, according to a nationwide twin study by researchers at the Aging Research Center of Karolinska Institutet, Sweden. The study confirms higher education as a major protective factor and stresses the importance of environmental aspects over genes in mild cognitive disorders in old age.

12 feb 2012--In the current study, which is published in the Journal of Alzheimer's Disease, the researchers investigated the distribution and heritability of subjective and objective cognitive impairment in the population by using data from 11,926 twins aged 65 and above in the Swedish Twin Registry. Objective cognitive impairment involves a reduced performance on tests measuring different cognitive abilities, such as memory and attention, while subjective cognitive impairment involves the same type of problems but experienced only at the subjective level. The researchers then found, that together subjective and objective cognitive impairment affect the majority of non-demented Swedish elderly (joint prevalence 64 percent), suggesting that mild cognitive disorders may represent a major public health concern even in the absence of dementia.

The study also highlights that subjective and objective cognitive impairment has distinct socio-demographic profiles. Specifically, when compared with people with objective cognitive impairment, elderly with subjective complaints only were more educated, more likely to be married, and to have higher socio-economic status – pointing to a possible protective effect of this favorable life conditions. Co-twin control analysis showed that the detrimental effect of lower educational level on cognitive functioning is largely independent by genetic background and early life environment.

"This underlies the relevance of adult life educational achievements for preserved cognitive functioning in older life", says Dr Barbara Caracciolo, who led the study at the Aging Research Center in Stockholm.

Regarding the heritability of subjective and objective cognitive impairment, the researchers observed concordance rates of 63 percent and 52 percent in monozygotic twins, 63 percent and 50 percent in dizygotic same-sex twins, and 42 percent and 29 percent in dizygotic unlike-sex twins. The lack of substantial differences in concordance rates between genetically identical (monozygotic) and or non-identical (dizygotic) twins suggests that environmental influences rather than genetic background play the major role in the occurrence of mild cognitive disorders in non-demented elderly.

More information: 'Differential Distribution of Subjective and Objective Cognitive Impairment in the Population: A Nation-Wide Twin-Study', Caracciolo B, Gatz M, Xu W, Pedersen NL, Fratiglioni L., Journal of Alzheimer's Disease, epub ahead of print 10 January 2012, doi:10.3233/JAD-2011-111904

Provided by Karolinska Institutet

News of plaque-clearing drug tops week of major advances against Alzheimer's disease

In the last eight days, scientists have delivered a powerful one-two punch in the fight to defeat Alzheimer's disease. At the same time, the White House and members of Congress are proposing increases in Alzheimer's research funding. This has been a big week for all who seek to end this disease, says the CEO of the American Health Assistance Foundation.

11 feb 2012--"In the last eight days, scientists have delivered a powerful one-two punch in the fight to defeat Alzheimer's disease," said Stacy Pagos Haller, President and CEO of the American Health Assistance Foundation (AHAF), a nonprofit that identifies and funds exceptionally high-impact research worldwide through its Alzheimer's Disease Research program.

"We are excited about today's announcement by Case Western University researchers that a cancer drug, used in mice studies, appears to help clear out the excess plaque found in the Alzheimer's-disease brain and it does this by enhancing the body's natural defense mechanisms," noted Haller. "This follows last week's announced discovery of how Alzheimer's disease spreads in the brain. The timing of these findings coincides with new proposals in Congress and the White House to increase federal funding for Alzheimer's research. This has been a big week for all who seek to end this disease."

In a study of mice, a research team headed by Case Western University scientist Gary Landreth, Ph.D., found that bexarotene—a drug currently used to combat T cell lymphoma— helped the body clear out amyloid beta proteins. Alzheimer's disease arises in large part from the body's inability to clear these naturally occurring proteins. As amyloid beta levels increase they tend to aggregate and contribute to the so-called brain "plaques" found in Alzheimer's disease.

Bexarotene appeared to improve brain function in these mice. Study results were published in the journal Science.

"Although this is a mouse study, the results are encouraging, and the drug did its job with unprecedented speed, by targeting ApoE, the primary genetic risk factor for Alzheimer's disease," said AHAF Vice President for Scientific Affairs Guy Eakin, Ph.D.

"This announcement is particularly exciting because bexarotene achieved regulatory approval by the U.S. Food and Drug Administration more than a decade ago for the treatment of cancer. That earlier approval could speed up the prospects for human clinical trials of the drug as an Alzheimer's treatment."

AHAF, which had also supported Landreth earlier in his career, started funding the preliminary work leading to this line of research in 2007. Currently, AHAF is funding follow-up studies in which the Landreth team is testing the latest findings on other "mouse models" that may better represent the human form of Alzheimer's disease. Positive findings could help pave the way towards human clinical studies.

"While it is still too early to make predictions, if these findings can be replicated in additional preclinical studies, and then later in human clinical trials, we may have a powerful new weapon in the battle to halt this disease," noted Eakin.

This latest news comes only one week after an AHAF-funded research team in Boston and another team in New York announced a major breakthrough in understanding how Alzheimer's disease spreads in the brain. By learning that toxic "tau" proteins jump from nerve cell to nerve cell, scientists can now focus on ways to target and stop this cell-to-cell spread.

Although these reports are coming in rapid succession, the overall progress of Alzheimer's disease research has been slower than that of other major diseases, due in part to comparatively meager financial support for Alzheimer's disease research. "We hope this funding scenario will improve, as promising study results stimulate our national resolve to defeat this disease," said Haller.

This week the Obama Administration announced it will provide an additional $130 million in Alzheimer's research funding over the next two years. Last week a bipartisan group in Congress unveiled the Spending Reductions through Innovations in Therapies (SPRINT) Agenda Act of 2012. The legislation, introduced by Senators Barbara Mikulski (D-MD) and Susan Collins (R-ME) and Representatives Chris Smith (R-NJ) and Ed Markey (D-MA), would spur public and private research funding and streamline the regulatory review of treatments.

More information: http://www.science … ence.1217697

Provided by AHAF-American Health Assistance Foundation

FDA-approved drug rapidly clears amyloid from the brain, reverses Alzheimer's symptoms in mice

Neuroscientists at Case Western Reserve University School of Medicine have made a dramatic breakthrough in their efforts to find a cure for Alzheimer's disease. The researchers' findings, published in the journal Science, show that use of a drug in mice appears to quickly reverse the pathological, cognitive and memory deficits caused by the onset of Alzheimer's. The results point to the significant potential that the medication, bexarotene, has to help the roughly 5.4 million Americans suffering from the progressive brain disease.

10 feb 2012--Bexarotene has been approved for the treatment of cancer by the U.S. Food and Drug Administration for more than a decade. These experiments explored whether the medication might also be used to help patients with Alzheimer's disease, and the results were more than promising.

Alzheimer's disease arises in large part from the body's inability to clear naturally-occurring amyloid beta from the brain. In 2008 Case Western Reserve researcher Gary Landreth, PhD, professor of neurosciences, discovered that the main cholesterol carrier in the brain, Apolipoprotein E (ApoE), facilitated the clearance of the amyloid beta proteins. Landreth, a professor of neurosciences in the university's medical school, is the senior author of this study as well.

Landreth and his colleagues chose to explore the effectiveness of bexarotene for increasing ApoE expression. The elevation of brain ApoE levels, in turn, speeds the clearance of amyloid beta from the brain. Bexarotene acts by stimulating retinoid X receptors (RXR), which control how much ApoE is produced.

In particular, the researchers were struck by the speed with which bexarotene improved memory deficits and behavior even as it also acted to reverse the pathology of Alzheimer's disease. The present view of the scientific community is that small soluble forms of amyloid beta cause the memory impairments seen in animal models and humans with the disease. Within six hours of administering bexarotene, however, soluble amyloid levels fell by 25 percent; even more impressive, the effect lasted as long as three days. Finally, this shift was correlated with rapid improvement in a broad range of behaviors in three different mouse models of Alzheimer's.

One example of the improved behaviors involved the typical nesting instinct of the mice. When Alzheimer's-diseased mice encountered material suited for nesting – in this case, tissue paper – they did nothing to create a space to nest. This reaction demonstrated that they had lost the ability to associate the tissue paper with the opportunity to nest. Just 72 hours after the bexarotene treatment, however, the mice began to use the paper to make nests. Administration of the drug also improved the ability of the mice to sense and respond to odors.

Bexarotene treatment also worked quickly to stimulate the removal of amyloid plaques from the brain. The plaques are compacted aggregates of amyloid that form in the brain and are the pathological hallmark of Alzheimer's disease. Researchers found that more than half of the plaques had been cleared within 72 hours. Ultimately, the reduction totaled 75 percent. It appears that the bexarotene reprogrammed the brain's immune cells to "eat" or phagocytose the amyloid deposits. This observation demonstrated that the drug addresses the amount of both soluble and deposited forms of amyloid beta within the brain and reverses the pathological features of the disease in mice.

This study identifies a link between the primary genetic risk factor for Alzheimer's disease and a potential therapy to address it. Humans have three forms of ApoE: ApoE2, ApoE3, and ApoE4. Possession of the ApoE4 gene greatly increases the likelihood of developing Alzheimer's disease. Previously, the Landreth laboratory had shown that this form of ApoE was impaired in its ability of clear amyloid. The new work suggests that elevation of ApoE levels in the brain may be an effective therapeutic strategy to clear the forms of amyloid associated with impaired memory and cognition.

"This is an unprecedented finding," says Paige Cramer, PhD candidate at Case Western Reserve School of Medicine and first author of the study. "Previously, the best existing treatment for Alzheimer's disease in mice required several months to reduce plaque in the brain."

Added Professor Landreth: "This is a particularly exciting and rewarding study because of the new science we have discovered and the potential promise of a therapy for Alzheimer's disease. We need to be clear; the drug works quite well in mouse models of the disease. Our next objective is to ascertain if it acts similarly in humans. We are at an early stage in translating this basic science discovery into a treatment."

Daniel Wesson, PhD, assistant professor of neurosciences at Case Western Reserve School of Medicine and co-author of the study agreed.

"Many often think of Alzheimer's as a problem of remembering and learning, but the prevalent reality is this disease spreads throughout the brain, resulting in serious insults to numerous functions," he said. "The results of this study, showing the preservation of behaviors across a wide spectrum, and accompanying brain function, are tremendously exciting and suggest great promise in the utility of this approach in treatment of Alzheimer's disease."

Bexarotene has a good safety and side-effect profile. The Case Western Reserve researchers hope these attributes will help speed the transition to clinical trials of the drug.

Professor Landreth said modest resources funded this self-described "far-fetched idea." Crucial support came from the Blanchette Hooker Rockefeller Foundation, the Thome Foundation, and the National Institutes of Health.

Provided by Case Western Reserve University

Tai Chi program helps Parkinson's disease patients

An Oregon Research Institute (ORI) exercise study conducted in four Oregon cities has shown significant benefits for patients with mild-to-moderate Parkinson's disease. In an original article published in the February 9, 2012 issue of the New England Journal of Medicine (NEJM), ORI scientist Fuzhong Li, Ph.D. and colleagues report that a tailored program of twice-weekly Tai Chi training resulted in improved postural stability and walking ability, and reduced falls in the participants.

09 feb 2012--"These results are clinically significant because they suggest that Tai Chi, a low-to-moderate impact exercise, may be used, as an add-on to current physical therapies, to address some of the key clinical problems in Parkinson's disease, such as postural and gait instability. Since many training features in the program are functionally oriented, the improvements in the balance and gait measures that we demonstrated highlight the potential of Tai Chi-based movements in rehabilitating patients with these types of problems and, consequently, easing cardinal symptoms of Parkinson's disease and improving mobility, flexibility, balance, and range of motion," noted Dr. Li.

In the 4-year project funded by the National Institute of Neurological Disorders and Stroke, the investigators randomly assigned 195 patients to one of three exercise groups: Tai Chi, resistance training, or stretching. The patients participated in 60-minute exercise sessions twice weekly for 24 weeks.

The results of the study showed that the Tai Chi group performed consistently better than the stretching group in how far they could lean in any direction without losing balance as well as demonstrating better levels of directional control of the body and walking ability (i.e., longer stride length). Tai Chi participants also outperformed those in the resistance training group on the balance and stride length measures. Finally, Tai Chi training was shown to significantly lower the incidence of falls compared to stretching and to be as equally effective as resistance training in reducing falls.

Impaired movement, especially the loss of ability to maintain standing balance, adversely affects function and quality of life in patients with Parkinson's disease. With progression of the disease, patients lose stability and have trouble walking, difficulty managing activities of daily living, and experience frequent falls. Exercise is an important part of the management of Parkinson's disease because physical activity has been shown to retard the deterioration of motor function and to prolong functional independence. However, research on alternative forms of exercise, such as Tai Chi, that could improve balance, gait, and function in patients with Parkinson's disease is scarce.

The Tai Chi program developed by Dr. Li consisted of six Tai Chi movements integrated into an eight-form routine that focused on weight-shifting, controlled-displacement of the center of gravity over the base of support, ankle sway, and front-to-back and sideways stepping. Natural breathing was integrated into the training routine.

"There are a number of practical advantages to using Tai Chi to improve motor dysfunction of Parkinson's disease - it is a low cost activity that does not require equipment, it can be done anywhere, at any time, and the movements can be easily learned. It can also be incorporated into a rehabilitation setting as part of existing treatment. Similarly, because of its simplicity, certain aspects of this Tai Chi program can also be prescribed to patients as a self-care/home activity," Dr. Li added.

Provided by Oregon Research Institute

Mild cognitive impairment is associated with disability and neuropsychiatric symptoms

In low- and middle-income countries, mild cognitive impairment—an intermediate state between normal signs of cognitive aging, such as becoming increasingly forgetful, and dementia, which may or may not progress—is consistently associated with higher disability and with neuropsychiatric symptoms but not with most socio-demographic factors, according to a large study published in this week's PLoS Medicine.

08 feb 2012--The established 10/66 Dementia Research Group interviewed approximately 15 000 people over 65 years of age who did not have dementia in eight low- and middle-incomes countries: Cuba, Dominican Republic, Peru, Mexico, Venezuela, Puerto Rico, China, and India.

Participants also completed standardized assessments of their mental and physical health and cognitive function and the researchers also interviewed relatives and carers for further details about any memory loss or other declines in cognitive function or the presence of any neuropsychiatric symptoms.

Then, using a clinical framework and a statistical model, the authors found that mild cognitive impairment with related memory problems was associated with disability, anxiety, apathy, and irritability but not with depression.

Increasing age or former education level did not seem to be linked but the authors found that men had a slightly higher prevalence of mild cognitive impairment than women. Furthermore, the prevalence of this type of mild cognitive impairment ranged from 0.8% in China to 4.3% in India.

The authors say: "This is one of the first studies, to our knowledge, to investigate the prevalence of [mild cognitive impairment with related memory problems] in [low- and middle-income countries], where the large majority of older people and people with dementia currently live."

They continue: "Differences in prevalence between countries were marked and ranged from 0.8% (China) to 4.3% (India), that is, greater than fivefold variation. After direct standardization for age, gender, and education, using the whole population as the reference, these differences were not markedly attenuated."

The authors conclude: "Further evaluation is needed of the associations with disability and neuropsychiatric symptoms since our findings do suggest higher than expected comorbidity and there are large absolute numbers of older people with [mild cognitive impairment with related memory problems] in these rapidly ageing and populous world regions."

More information: Sosa AL, Albanese E, Stephan BCM, Dewey M, Acosta D, et al. (2012) Prevalence, Distribution, and Impact of Mild Cognitive Impairment in Latin America, China, and India: A 10/66 Population-Based Study. PLoS Med 9(2): e1001170. doi:10.1371/journal.pmed.1001170

Provided by Public Library of Science

Revised criteria could reclassify many with mild Alzheimer dementia

Many patients currently diagnosed with very mild or mild Alzheimer disease dementia could potentially be reclassified as having mild cognitive impairment (MCI) under revised criteria for that condition, according to a report published Online First by Archives of Neurology.

07 feb 2012--The National Institute on Aging and the Alzheimer's Association convened a work group to update criteria for MCI, and the revised criteria allow "considerable latitude" as to what represents functional independence, writes the study's sole author, John C. Morris, M.D., of Washington University School of Medicine in St. Louis. For example, "mild problems" performing daily activities such as shopping, paying bills and cooking are permissible, as is dependency on aids or assistance to complete those tasks.

In this study, the functional ratings of patients enrolled at federally funded Alzheimer's Disease Centers with clinical and cognitive data maintained by the National Alzheimer's Coordinating Center were evaluated. A total of 17,535 people with normal cognition, MCI or AD dementia met eligibility requirements. The mean (average) age of the total sample was 74.6 years.

The study suggests that 99.8 percent of patients currently diagnosed with very mild AD dementia and 92.7 percent of those diagnosed with mild AD dementia could be reclassified as having MCI based on the revised criteria.

The difference between MCI and AD dementia in its earliest symptomatic stages has largely been based on whether cognitive impairment disrupts the activities of daily living. The revised criteria "now obscure this distinction," Morris notes.

"The elimination of the functional boundary between MCI and AD dementia means that their distinction will be based solely on the individual judgment of clinicians, resulting in nonstandard and ultimately arbitrary diagnostic approaches to MCI," Morris comments. "This recalibration of MCI moves its focus away from the earliest stages of cognitive decline, confounds clinical trials of individuals with MCI where progression to AD dementia is an outcome, and complicates diagnostic decisions and research comparisons with legacy data."

The author suggests that the revised criteria for MCI "laudably recommend" an etiologic (origins) diagnosis, "MCI due to AD," when the physician's judgment is that AD is responsible for an individual's cognitive dysfunction.

"The diagnostic overlap for MCI with milder cases of AD dementia is considerable and suggests that any distinction is artificial and arbitrary," Morris concludes. "Already, many individuals with MCI are treated with pharmacological agents approved for symptomatic AD, indicating that clinicians often do not distinguish the two conditions when faced with issues of medical management. It now is time to advance AD patient care and research by accepting that 'MCI due to AD' is more appropriately recognized as the earliest symptomatic stage of AD."

More information: Arch Neurol. Published online February 6, 2012. doi:10.1001/archneurol.2011.3152

Provided by JAMA and Archives Journals

New study to assess 3 simple, cost-effective strategies to promote healthy aging

In Europe, the number of seniors aged 70 and over will increase by 40% in the next 20 years, while those aged 80 and over will more than double. Health authorities and the medical community expect a corresponding increase in the number of people suffering costly and debilitating age-related chronic diseases such as osteoporosis, arthritis, heart and lung diseases and dementia. The significant increase in the numbers of people suffering age-related chronic diseases is expected to have serious social and health-economic repercussions across Europe – unless effective prevention strategies are put in place.

06 feb 2012--A new international study announced today by the University of Zurich hopes to provide definitive evidence that three effective, affordable and safe measures can be taken to significantly reduce the burden of chronic diseases in the elderly. The DO-HEALTH study (VitaminD3-Omega3-Home Exercise-Healthy Ageing and Longevity Trial) will be Europe's largest healthy ageing study. It expects to provide solid evidence for the efficacy and safety of three simple preventive interventions: vitamin D, omega-3 fatty acids and a simple home exercise programme.

Professor Heike Bischoff-Ferrari, Director of the Centre on Aging and Mobility of Zurich University and DO-HEALTH Principal Investigator said "Various studies have shown that vitamin D and simple targeted exercise programmes can significantly improve functional mobility and reduce falls and fractures in seniors, even by up to 30%. As well Omega 3 provides significant health benefits to seniors. DO-HEALTH hopes to provide definitive evidence that the three interventions, alone or combined, are able to reduce the number of fractures, the functional and cognitive decline, the risk of hypertension and the risk of infections in the senior population".

Additionally, the study will measure several other important parameters, such as the severity of knee pain in patients with osteoarthritis, the ability to carry out daily life activities and the participants' general quality of life.

DO-HEALTH will start recruiting seniors in five European countries as of May 2012 and will observe more than 2,000 healthy-at-start community-dwelling seniors, aged 70 and older, for three years. Participants' follow-up will be in-person and in quarterly intervals, including yearly clinical visits. Participants will be recruited at the University of Zurich, Basel, Geneva, Toulouse, Innsbruck, Nuremberg, Coimbra and the Charité in Berlin.

Professor René Rizzoli, Board Member of the International Osteoporosis Foundation and Head of the Division of Bone Diseases, Department of Medical Specialties, Geneva University Hospitals and Faculty of Medicine, stated, "The findings of this important new study may provide the critical evidence that will result in the implementation of simple, cost-effective strategies and medical recommendations to help tackle the growing burden of chronic diseases in Europe's senior population. Health authorities must do all they can to ensure that senior citizens remain physically independent and active members of the community".

More information: http://europa.eu/r … iLanguage=en

Provided by International Osteoporosis Foundation

Same genes linked to early- and late-onset Alzheimer's disease

The PET image of the brain shows a build up of amyloid deposits (highest amounts in yellow and red) in a patient with Alzheimer's disease.

The same gene mutations linked to inherited, early-onset Alzheimer's disease have been found in people with the more common late-onset form of the illness.

05 feb 2012--The discovery by researchers at Washington University School of Medicine in St. Louis may lead doctors and researchers to change the way Alzheimer's disease is classified.

They report their findings Feb. 1 in the online journal PLoS One.

"We probably shouldn't think of early-onset disease as inherited and late-onset as sporadic because sporadic cases and familial clustering occur in both age groups," says senior investigator Alison M. Goate, DPhil. "I think it's reasonable to assume that at least some cases among both early- and late-onset disease have the same causes. Our findings suggest the disease mechanism can be the same, regardless of the age at which Alzheimer's strikes. People who get the disease at younger ages probably have more risk factors and fewer protective ones, while those who develop the disease later in life may have more protective factors, but it appears the mechanism may be the same for both."

The researchers used next-generation DNA sequencing to analyze genes linked to dementia. They sequenced the APP (amyloid precursor protein) gene, and the PSEN1 and PSEN2 (presenilin) genes. Mutations in those genes have been identified as causes of early-onset Alzheimer's disease. They also sequenced the MAPT (microtubule associated protein tau) gene and GRN (progranulin) gene, which have been associated with inherited forms of another illness involving memory loss called frontotemporal dementia.

For several years, scientists have known that genetic mutations are linked to inherited forms of early-onset Alzheimer's disease. But now researchers at Washington University School of Medicine in St. Louis have found that some of the same genes also play a role in more common late-onset forms of Alzheimer's. Credit: Washington University BioMed Radio

"We found an increase in rare variants in the Alzheimer's genes in families where four or more members were affected with late-onset disease," says Goate, the Samuel and Mae S. Ludwig Professor of Genetics in Psychiatry, professor of neurology, of genetics and co-director of the Hope Center Program on Protein Aggregation and Neurodegeneration. "Changes in these genes were more common in Alzheimer's cases with a family history of dementia, compared to normal individuals. This suggests that some of these gene variants are likely contributing to Alzheimer's disease risk."

The study also found mutations in the MAPT and GRN genes in some Alzheimer's patients, suggesting they had been incorrectly diagnosed as having Alzheimer's disease when they instead had frontotemporal dementia.

Goate and her colleagues studied the five genes in members of 440 families in which at least four individuals per family had been diagnosed with Alzheimer's disease. They found rare variants in key Alzheimer's-related genes in 13 percent of the samples they analyzed.

"Of those rare gene variants, we think about 5 percent likely contribute to Alzheimer's disease," says first author Carlos Cruchaga, PhD, assistant professor of psychiatry. "That may not seem like a lot, but so many people have the late-onset form of Alzheimer's that even a very small percentage of patients with changes in these genes could represent very large numbers of affected individuals."

Goate, who in 1991 was the first scientist to identify a mutation in the APP gene linked to inherited, early-onset Alzheimer's disease, now wants to look closely at families with multiple cases of Alzheimer's but no mutations in previously identified Alzheimer's genes. She says it's likely they carry mutations in genes that scientists don't yet know about. And she believes that new sequencing techniques could speed the discovery of these genes. In fact, the researchers say a study like this would have been impossible only a few years ago.

"With next-generation sequencing technology, it's now possible to sequence all of these genes at the same time," Cruchaga says. "One reason we didn't do this study until now is that 15 to 20 years ago when these genes were first identified, it would have taken years to sequence each gene individually."

Cruchaga and Goate say the new technology and their new findings suggest that it may be worthwhile to sequence these genes in people with a strong family history of Alzheimer's disease.

"We would like to see physicians who treat patients with late-onset disease ask detailed questions about family history," Goate says. "I'm sure many probably do that already, but in those families with very strong histories, it's not unreasonable to think about screening for genetic mutations."

She says such screenings also may weed out people thought to have Alzheimer's disease who actually have changes in genes related to frontotemperal dementia.

Both Goate and Cruchaga agree that one result of their discovery that the same genes can be connected with both early- and late-onset forms of Alzheimer's disease may be changes in the way the disease is classified.

"It's always been somewhat arbitrary, figuring out where early-onset ends and late-onset begins," Goate says. "So I no longer look at early- and late-onset disease as being different illnesses. I think of them as stages along a continuum."

More information: Cruchaga C, et al, Rare variants in APP, PSEN1 and PSEN2 increase risk for AD in late-onset Alzheimer's disease families. PLoS One, Feb. 1, 2012. http://dx.plos.org … pone.0031039

Provided by Washington University School of Medicine

Why two new studies represent important breakthrough in Alzheimer's disease research

Two different research groups have independently made the same important discoveries on how Alzheimer's disease spreads in the brain. The groups' findings have the potential to give us a much more sophisticated understanding of what goes wrong in Alzheimer's disease and, more importantly, what can be done to prevent or repair damage in the brain.

04 feb 2012--The Times reported on the research teams of Bradley T. Hyman, MD, Ph.D., at Massachusetts General Hospital in Boston, and Karen E. Duff, Ph.D., of Columbia University Medical Center in New York.

Each research group found that the Alzheimer's disease protein called tau can apparently spread from one part of the brain to other connected areas by effectively "jumping" from one nerve cell (neuron) to another. This is good news for scientists exploring pathways for treating Alzheimer's disease, which is now a growing epidemic with the aging of the Baby Boomer generation and the sixth leading cause of death in the U.S. If scientists can determine how tau jumps from neuron to neuron, Alzheimer's disease can potentially be stopped from spreading.

Results of Dr. Hyman's AHAF-funded research will be published later this month in the journal Neuro. Dr. Duff's research was published this week in PLoS ONE.

The two research groups also made similar advances in how to study the development of the disease in mice, by making new "mouse models" that better represent the human form of Alzheimer's at later stages of the disease. This will allow scientists to develop a much more detailed understanding of what goes awry with the spread of Alzheimer's disease over time, and what can be done to stop it.

It is important to note that these scientists' findings build on an idea studied by a number of others over the years—the idea that cells can infect neighboring cells. This concept—now significantly advanced by the work of Hyman and Duff—was previously pursued by several scientists including AHAF grantees Joanna Jankowsky, Ph.D., of Baylor College of Medicine in Houston, and Marc Diamond, M.D., of Washington University School of Medicine in St. Louis.

The announcement this week reminds us why early-stage basic research is so crucial to fighting costly and devastating diseases. Only with solid investment in this type of research will solutions ultimately be developed that improve the lives of people affected by this disease.

On that front, important bipartisan legislation was unveiled this week by Senators Barbara Mikulski (D-MD) and Susan Collins (R-ME) and Representatives Chris Smith (R-NJ) and Ed Markey (D-MA). The Spending Reductions through Innovations in Therapies (SPRINT) Agenda Act of 2012 would ultimately reduce America's healthcare costs, by spurring public and private research funding and streamlining the regulatory review of treatments needed for Alzheimer's and other costly diseases. Read more information from Sen. Mikulski, and Sen. Collins. Provided by American Health Assistance Foundation

Study of Alzheimer's-related protein in healthy adults may shed light on earliest signs of disease

These are positron emission tomography scans of the brains of healthy adults showing low (left) and high (right) levels of beta-amyloid protein. Credit: Image courtesy of the Center for Vital Longevity, The University of Texas at Dallas

Researchers from the Center for Vital Longevity at the University of Texas at Dallas and UT Southwestern Medical Center have completed a large-scale neuroimaging study of healthy adults from age 30 to 90 that measured beta-amyloid protein—a substance whose toxic buildup in the brain is a diagnostic marker for Alzheimer's disease.

03 feb 2012--The findings, published in the February 1, 2012 online issue of Neurology, the medical journal of the American Academy of Neurology, mark a crucial step toward being able to predict who may be at risk for developing Alzheimer's disease long before symptoms appear.

Relatively few studies have looked at levels of beta-amyloid in healthy living adults, as until recently, beta-amyloid levels could only be measured at autopsy. Few, if any, studies have looked at beta-amyloid levels in middle-aged and younger adults. Many investigators now believe that the beginning stages of Alzheimer's disease can precede symptoms of dementia by a decade or more, so data on middle-aged adults is critically important to understanding the transition from a healthy brain to a diseased brain.

In the new study, researchers measured levels of beta-amyloid protein in the brains of 137 cognitively healthy adults between the ages of 30 and 89 using an amyloid imaging agent. The researchers found that beta-amyloid levels increased with age across the entire age span and that about 20% of adults aged 60 and older had particularly high levels of beta-amyloid.

"We found that this high-amyloid group showed deficits in cognitive performance even though the individuals were well educated and scored normally on our standard tests of cognition," said Dr. Karen Rodrigue, a postdoctoral fellow at the Center for Vital Longevity and lead author of the study. On tests of processing speed, working memory, and reasoning ability—three major aspects of cognition—higher levels of beta-amyloid correlated with lower test scores.

That beta-amyloid burden has detectable effects on cognitive function even in adults with apparently good cognitive health underscores the need to better understand the recently proposed preclinical phase of Alzheimer's disease, which suggests that beta-amyloid deposits in healthy adults do not exert a strong effect on cognition for some time.

"Our findings suggest that subtle effects on cognition occur early," said principal investigator Dr. Denise Park, co-director of the Center for Vital Longevity and Distinguished University Chair in the School of Behavioral and Brain Sciences at UT Dallas. "These are important findings because imaging patients when they first show signs of very mild cognitive impairment could be essential to determining their risk of future disease."

Long-term follow-up studies led by Dr. Park as part of the Dallas Lifespan Brain Study, one of the nation's largest projects examining neural and cognitive aging across the entire adult lifespan, are already underway to help researchers determine whether high beta-amyloid burden in healthy people necessarily predetermines occurrence of Alzheimer's disease later in life.

"Knowing this information will help us determine at what stage potential interventions, once available, may be most critical and most effective," said Park. Many researchers believe that interventions to slow or halt the progression of Alzheimer's will be most effective during middle age, before irreparable damage to the brain is done. "Just as many adults take aspirin to lower their risk of heart disease or stroke, one day we may be able to help protect our brains and cognitive health by starting a treatment in our 40s or 50s," Park said.

Another of the study's interesting findings was that some people well into their 60s, 70s, and even 80s, had beta-amyloid levels as low or lower than people at middle age or younger.

"Another avenue of our future work will be to investigate what factors enable these individuals to maintain cognitive health well into old age, whether they be genetic factors, lifestyle factors, or environmental issues," said Park.

"Understanding how the brain and mind stay healthy and vital over the long term will help guide our efforts to delay or even prevent the devastation caused by diseases like Alzheimer's."

Provided by University of Texas at Dallas

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

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

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

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

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

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

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

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

The findings of the study have important implications for therapy.

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

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

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

Provided by Columbia University Medical Center

Women report feeling pain more intensely than men: study

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Provided by Stanford University Medical Center

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

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

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

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

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

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

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

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

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

Provided by The Peninsula College of Medicine and Dentistry

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

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

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

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

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

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

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

Provided by American Academy of Neurology

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

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

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

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

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

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

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

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

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

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

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

Provided by British Medical Journal

Study finds exercise reduces anxiety symptoms in women

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

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

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

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

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

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

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

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

Provided by University of Georgia

Alzheimer's neurons induced from pluripotent stem cells

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

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

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

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

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

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

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

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

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

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

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

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

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

Provided by University of California - San Diego

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

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

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

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

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

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

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

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

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