Age-proof diet for longevity

By studying the molecular mechanism of food nutrients from a Mediterranean diet in an elderly population, scientists hope to help countering their physical and mental decline.

28 feb 2013--We are what we eat. However, little is known on how a specific dietary regime can impact the life of the elderly. Now, researchers from an EU funded project called NU-AGE are investigating the effects of the Mediterranean diet on older people. Their aim is to get clues on how to counteract physical and cognitive decline through diet changes.

Starting in July 2013, the project will study how the Mediterranean diet regime affects people over 65 years old by focusing on 1,250 volunteers; the largest study of its kind to date. Half of them will constitute a control group. The other half will receive the classic Mediterranean diet, rich in olive oil, fresh fruits and vegetables. At different stages during this year-long study on diet change, researchers will collect blood samples to investigate its effects at the cellular and molecular level. 

"The Mediterranean diet is well known for being balanced", says Aurelia Santoro, immunologist at the University of Bologna, Italy, and NU-AGE scientific manager, "but we do not exactly know how micro-nutrients, such as vitamins and phenols, affect molecular mechanisms". Until now, scientists knew that nutrients such as polyphenols or carotenoids, contained in vegetables, have antioxidant properties, but did not know exactly how these bringing health benefits at the molecular level. 

Some experts welcome this much needed project in the context of an ageing European population, prone to neuronal degeneration and its devastating cognitive consequences. "More work is needed on nutrition in the elderly, in term of needs assessment, potentially identifying nutrient imbalances that are involved in neuro-degeneration", says Francesco Branca, Director of the Department of Nutrition for Health and Development at World Health Organization in Geneva. This means this project may be one of many more future studies that may be required before effective solutions to tackle the needs of the elderly become available. 

Once further work on molecular level mechanisms bring answers, the project will also attempt to design new functional food focused on the specific needs of the elderly. This will be done in collaboration with the food industry. Such functional food could help to counteract the lack of specific micro-nutrients. 

But functional food supplements are not the only option. Indeed, some experts do not believe that providing food supplements are the way to go. Instead, home cooking sometimes provides all the nutrients that are needed. Gianna Ferretti from the Nutrition Science School of Università Politecnica delle Marche, in Ancona, Italy, tells youris.com: "[previous] research has showed that traditional food, especially from Mediterranean diet, have positive effects on psychological and physical health and can help in protecting from several diseases." 

More information: www.nu-age.eu/

Source: Youris.com

USPSTF: Vitamin D, calcium supplements don't prevent fx

For non-institutionalized postmenopausal women, the U.S. Preventive Services Task Force recommends against daily supplementation with ≤400 IU of vitamin D₃ and ≤1,000 mg of calcium for primary prevention of fractures, and a lack of evidence impairs the provision of recommendations for other populations, according to a statement published online Feb. 26 in the Annals of Internal Medicine.

27 feb 2013—For non-institutionalized postmenopausal women, the U.S. Preventive Services Task Force (USPSTF) recommends against daily supplementation with ≤400 IU of vitamin D₃ and ≤1,000 mg of calcium for primary prevention of fractures, and a lack of evidence impairs the provision of recommendations for other populations, according to a statement published online Feb. 26 in the Annals of Internal Medicine.

Using data from two systematic evidence reviews and a meta-analysis, Virginia A. Moye, M.D., M.P.H., and colleagues on behalf of the USPSTF in Rockville, Md., examined the effects of vitamin D supplementation, with or without calcium, on bone health outcomes in community-dwelling adults. Adverse effects of supplementation were also considered.

The USPSTF found that, regarding premenopausal women and men, the current evidence was insufficient to support an evaluation of the benefits and harms of combined vitamin D and calcium supplementation on the primary prevention of fractures. For non-institutionalized postmenopausal women, insufficient evidence was available to examine the balance of benefits and harms for supplementation with >400 IU of vitamin D₃ and >1,000 mg of calcium for primary prevention of fractures. For non-institutionalized postmenopausal women, the USPSTF recommends against daily supplementation with ≤400 IU of vitamin D₃ and ≤1,000 mg of calcium.

"While we wait for the results of further research, the USPSTF's cautious, evidence-based advice should encourage clinicians to think carefully before advising calcium and vitamin D supplementation for healthy individuals," write the authors of an accompanying editorial.

More information: Abstract 
Full Text 
Editorial

For Alzheimer's caregivers, patience and compassion are key

Expert advice for those facing the challenges brought on by the disease.

24 feb 2013—The picture isn't necessarily pretty when it comes to Alzheimer's disease.

More than 5 million Americans currently have the degenerative brain condition, there's no sure way to prevent it and current treatment options don't work for everyone. Even more millions are tasked with the sometimes difficult and frustrating daily care of those stricken with the memory-robbing disease, often with little experience or training.

But as the number of Americans with Alzheimer's has risen in the past few decades and continues to spiral upward, anecdotal and research evidence has accumulated on ways to make everyday life more bearable for those with the disease and to help those caring for them. It includes expanded knowledge of what works and what doesn't in areas of medication, living situations, everyday contact and more, and ranges from complex to simple solutions.

"There are times that it can be difficult to handle someone with Alzheimer's, but you have to have patience, and you have to put yourself in their shoes," said Teresa Dinau, a caregiver for Home Care Assistance, based in Palo Alto, Calif. "It's important to try to understand what they're going through."

Dr. Jacobo Mintzer, chairman of the Medical and Scientific Advisory Board for the Alzheimer's Foundation of America, said that the biggest initial problem for caregivers is often that "they're trying to preserve the person they knew as long as possible."

"That's usually where they get themselves into trouble," he said. "Because of this desperate need to try to preserve the person, caregivers will put themselves in dangerous situations, like letting the person with Alzheimer's drive because it has always been important to them."

Not pushing someone with Alzheimer's to be who they used to be makes some caregivers feel like they've given up on their loved one, added Mintzer, who's also a physician at the Ralph H. Johnson VA Medical Center in Charleston, S.C.

But he said that's not the case and that there are plenty of safe ways to keep a connection. If someone with Alzheimer's used to like to swing dance, for instance, and you put on music and swing dance with them, it will often be calming, he said. Or, people with Alzheimer's usually enjoy looking at photos from the past, according to the Alzheimer's Association.

Mintzer said there are no treatments currently available to alter the course of the disease. However, two types of medications have been approved in the United States to help with memory loss: a group of drugs called cholinesterase inhibitors (brand names include Aricept, Exelon, Razadyne and Cognex) and memantine (brand name Namenda). However, the Alzheimer's Association reports that these medications don't work for everyone and, on average, delay worsening of symptoms only by about six to 12 months.

Also, antidepressants, anti-anxiety and antipsychotic medications are used to ease some of the behavioral symptoms that can be a part of Alzheimer's disease, including agitation and anxiety. None of these medications have been specifically approved to treat Alzheimer's, however, so the Alzheimer's Association recommends discussing the risks and the benefits of any medication with a doctor.

Despite the limitations of existing medications, problem behaviors can sometimes be overcome with the right type of stimulation and care.

"We need to see ourselves as a therapeutic agent," said Mintzer. "Patients have needs. When social stimulation is diminished, patients tend to get agitated." He noted that sundowning—increased confusion and agitation that some people with Alzheimer's experience later in the day—"may occur because the amount of care goes down in the evening, whether at home or in a nursing home."

"Sit down and talk with them for five minutes every hour," Mintzer suggested. "Talk with them in a non-threatening manner. Share a meal, or even sit down and split a cookie. It may not meet your needs for a social interaction, but that's not the purpose of it."

Using a calm voice is always important, and it's often easier to redirect attention than to try to get your friend or loved one to change a behavior. It's important to acknowledge any questions or requests, even though it may be the fifth time in 10 minutes that you've been asked what the time is. Each request is new to them.

Dinau said that she tries to keep routines as normal as possible. Instead of letting someone have dinner in bed, she guides them to the table to eat and then has a conversation with them during dinner. "A little activity here and there really helps," she said.

Mintzer also said it's important to have routine structure. Things can change within a day, but try to keep activities similar. For example, if Tuesday is the day you go out to lunch together, make a doctor's appointment for Tuesday. Then, while you're on your way to lunch, you can say something like, "Do you mind if we stop at the doctor on our way?" That way, he said, you're not changing the routine but just adding an element to it.

An array of devices also exist now that can help make a home safer for someone with Alzheimer's. He said these range from the very simple drawer and cabinet locks used to keep young children away from dangerous items to more high-tech safety devices like motion sensors for the stove and tracking devices that can be worn by people with Alzheimer's in case they wander.

But there does come a time when the disease ravages the brain so significantly that someone with Alzheimer's can't consistently control their behavior, Mintzer said. "When they get this impaired, they lack the ability to understand reality and suffer from delusions," he said, adding that medications that treat symptoms can be helpful at this point.

Though people with Alzheimer's can often stay in their homes, Mintzer said that if that's no longer safe, it's time to start looking into long-term care.

"When this time comes may be very different for different patients," he said. "If you live in the middle of New York City and you have a grocery store downstairs, it's irrelevant that your loved one can't drive anymore. If you're loved one lives in rural North Carolina and can't drive anymore, they will starve and need assistance or long-term care earlier."

More information: Learn more about caring for someone with Alzheimer's on a special website for caregivers set up by the U.S. Department of Health and Human Services.

Antidepressants alone are not enough

We should reconsider how we use antidepressants more effectively. The latest studies have shown that antidepressants restore the capacity of certain areas of the brain to repair abnormal neural pathways. According to neuroscientist Eero Castrén, the recipient of EUR 2.5 million of ERC funding, recovery requires redirection of these pathways through practice, rehabilitation or therapy.

23 feb 2013--This is a surprisingly blunt view, even for a respected neuroscientist such as Eero Castrén. After all, millions of people throughout the world have been prescribed antidepressants, and pharmaceutical companies have made a billion-dollar business out of selling them. Surely the system cannot be entirely wrong?

Recent studies suggest that this may be the case. Research on animal models demonstrates that antidepressants are not a cure as such. Rather, their role is to restore plasticity in the adult brain. Antidepressants reopen a window of brain plasticity, which allows the formation and adaptation of brain connections through the patient's own activities and observations, similarly to a young child whose brain and experiences about the world develop in response to environmental stimuli.   

Correcting abnormal pathways

When cerebral plasticity is reopened, problems caused by false connections in the brain can be addressed. Such problems can be manifested, for example, as phobias. Studies conducted on animal models by Professor Eero Castrén's research group at the University of Helsinki show that therapy helps to reduce fears for a time, but an antidepressant alone provides no relief. By combining the two, however, long-term effects can be achieved.

"Simply taking drugs is not enough. We must also show the brain what the desired connections should be," Professor Castrén of the Neuroscience Centre explains.

The need for both therapy and medical treatment may also explain why antidepressants sometimes seem to have no effect. If the patient's environment and situation remain unchanged, the drug-induced capacity of the brain to change will not make the patient feel better.

Reaching this point is the result of years of research. Scientists discovered as early as the 1960s that antidepressants affect neurotransmitters in the brain, such as serotonin. Later, antidepressants were found to increase neurotrophins and their ability to transmit signals in the brain. Only recently have scientists begun to explore the effects of drugs on plasticity of brain networks.

Enhancing the plasticity of the adult human brain through antidepressants has opened a whole new field of research for Eero Castrén. He has received a five-year grant of EUR 2.5 million from the European Research Council (ERC) to investigate mechanisms related to adult brain plasticity.

More information: Karpova, N. et al. Fear erasure in mice requires synergy between antidepressant drugs and extinction training. Science. 2011 Dec 23;334(6063):1731-4

Provided by University of Helsinki

Simple measures to promote sleep can reduce delirium in intensive care patients

A hospital is not the best place to get a good night's sleep, especially in a noisy intensive care unit. It's a cause for concern because studies have shown that a lack of sleep can cause patients to experience delirium—an altered mental state that may delay their recovery and lead to short and long-term confusion and memory problems.

22 feb 2013--A team of doctors, nurses, psychologists and pharmacists in the medical intensive care unit (MICU) at The Johns Hopkins Hospital implemented a project to see if by taking simple steps to reduce nighttime noise, light,and staff interruptions, as well as stopping certain medications for insomnia, they could reduce delirium and improve patient perceptions about the quality of their sleep. Their findings are described in an article posted online by Critical CareMedicine that will be printed in the journal's March issue.

"With our interventions, we were able to improve a patient's odds of being free of delirium in the ICU by 54 percent, even after taking into account the diagnosis, need for mechanical ventilation, age and other factors," says Biren Kamdar, M.D., M.B.A, M.H.S., a Johns Hopkins pulmonary and critical care fellow who led the initiative. "In addition, many patients said that the ICU was quiet and comfortable enough for them to get a good night's sleep," he says.

Three sets of interventions were introduced in stages. The first was a 10-item environmental checklist that included turning off televisions, room and hallway lights, safely consolidating the number of staff visits to patient rooms overnight for drawing blood and giving medications to reduce interruptions, reducing overhead pages and minimizing unnecessary equipment alarms.

In the second stage, patients also were offered eye masks, ear plugs and tranquil music. In the final stage, a new medication guideline was introduced that discouraged giving patients certain commonly prescribed drugs for sleep, such as benzodiazepines, that are known to cause delirium.

Before all of the interventions had been instituted, the researchers did a baseline assessment of 122 patients in the intensive care unit over an eight-week period. After all of the measures were in place, another 178 patients were evaluated.

"Each patient was evaluated twice a day for delirium using the Confusion Assessment Method for the ICU (CAM-ICU), a widely used delirium screening tool. After 13 weeks, during which all of the interventions had been in place, we saw a substantial reduction in patient delirium compared to the baseline group," Kamdar says.

The researchers also measured patient perception of their sleep quality with a questionnaire given to each patient by MICU nurses every morning. While there were positive findings in that measure, the improvement overall was not statistically significant.

"This is a unique study in terms of the number of patients involved and the three stages of interventions," says Dale M.Needham, M.D., Ph.D., associate professor of pulmonary and critical care medicine at Johns Hopkins who is the senior author of the study article.

"Delirium is a syndrome of confused thinking and lack of attention. It typically comes on quickly with illness, and it's a marker for the health of the brain," says Needham. "We put together a common-sense approach to change how care is provided to see if by improving sleep, we could reduce patients' confused thinking, and it was effective."

Needham also says that physical rehabilitation is important for the recovery of intensive care patients, and if they're sleepy or delirious during the day, they can't appropriately participate in their therapy.

"Up to 80 percent of ICU patients may experience delirium during their stay. The longer they have it, the higher their risk of long-lasting problems with memory and other cognitive functions. With advances in medicine and technology, many ICU patients can now recover and go home, so reducing their risk of delirium in the hospital is very important," Needham says.

Provided by Johns Hopkins University School of Medicine

Antioxidants in your diet may not reduce risk of stroke or dementia

Contrary to other research, a new study found that the total level of antioxidants in people's diets is not related to their risk of developing stroke or dementia. The study is published in the February 20, 2013, online issue of Neurology, the medical journal of the American Academy of Neurology. Antioxidants such as lycopene, beta-carotene and vitamins C and E are found in many foods.

21 feb 2013--"These results are interesting because other studies have suggested that antioxidants may help protect against stroke and dementia," said study author Elizabeth E. Devore, ScD, of Harvard Medical School in Boston and Erasmus Medical Center in Rotterdam, Netherlands. "It's possible that individual antioxidants, or the main foods that contribute those antioxidants—rather than the total antioxidant level in the diet—contribute to the lower risk of dementia and stroke found in earlier studies."

The study involved 5,395 people age 55 and older who had no signs of dementia at the start of the study. Participants completed questionnaires about how often they ate 170 foods over the past year at the start of the study. Then the participants were followed for an average of nearly 14 years.

Participants were divided into three groups: low, moderate and high levels of antioxidants in the diet. About 600 people developed dementia during the study and about 600 people had a stroke. But researchers found that people with high levels of antioxidants were no more or less likely to develop brain disease than people with low levels of antioxidants.

Devore noted that about 90 percent of the difference in antioxidant levels in the study was due to the amount of coffee and tea people drank. Coffee and tea contain high levels of nontraditional antioxidants such as flavonoids.

"This differed from an Italian study that found the higher total antioxidant levels were associated with a lower risk of stroke, where the variation from coffee and tea was lower, and the contribution from alcoholic beverages, fruits and vegetables was higher," Devore said.

Provided by American Academy of Neurology

Study examines family struggles with anger and forgiveness when relative is dying

Watching a loved one die tests some family members' relationships with God or the higher being of one's faith. And the spiritual anger and resentment grow with the level of pain and suffering their family member endures, according to researchers at Case Western Reserve University.

20 feb 2013--Psychologist Julie Exline and palliative care advanced practice nurse Maryjo Prince-Paul surveyed 147 family members with a hospice patient under home care.

More than four of every 10 respondents reported at least some level of anger with God, a major source of which was watching a loved one suffering great pain. Resentment was strongest among family members of cancer patients and weakest among family members of heart disease patients.

A family member's level of spirituality was also a factor. The less religious or spiritual family members said they were, the more anger they reported toward God. Family members also reported more anger toward God if they could not see any deeper meaning in the suffering that the patient and family were experiencing.

Exline, associate professor of psychological sciences in the College of Arts and Sciences, and Maryjo Prince-Paul, assistant professor at the Frances Payne Bolton School of Nursing at Case Western Reserve and research scientist at Hospice of the Western Reserve, published their findings in the current Journal of Palliative Medicine article, "The Spiritual Struggle of Anger Toward God: A Study with Family Members of Hospice Patients."

A related study by the researchers in a recent Journal of Palliative Medicine article (volume 15, issue 10, 2012), "Forgiveness, Depressive Symptoms, and Communication at the End of Life: A Study with Family Members of Hospice Patients," explored the importance of forgiveness-related communications between hospice patients and family members. Many family members reported that they saw seeking and granting forgiveness as very important in their relationships with loved ones who were dying.

The forgiveness study showed that if family members saw forgiveness issues as important but had not completed the process, these unresolved conflicts were linked with greater depressive symptoms. Building on these findings, the new study showed that anger toward God was also linked with higher levels of depressive symptoms among family members.

Respondents in the new study were asked about which coping strategies they would prefer if they were feeling angry toward God. The most popular strategy was prayer. Other common strategies included reading sacred texts, handling feelings on their own and discussions with friends, family, clergy or hospice team members. Self-help resources and therapies were less popular, respondents said.

Exline concludes that finding ways to overcome anger with God—and being able to seek and grant forgiveness in relationships with family members— can be important for both families and patients in the dying process.

"People have difficulties when they struggle to find meaning in their lives during stressful events," explains Exline. "If people feel guilty about mistakes they have made, or if they feel alienated from God or a family member, these issues can make it more difficult for them to cope." Such issues may loom especially large in end-of-life contexts, when repair of close relationships can take on great importance.

In the forgiveness study, family members wrote about the significance of expressing love and gratitude, but also felt that clearing up unresolved issues was important before the patient died.

These two articles continue Exline's research on the many anger-related issues that people can experience when they are facing stressful life events. The research also adds to understanding of the many emotional, social and spiritual strains faced by family members of dying patients.

Provided by Case Western Reserve University

Pioneering study reveals association of chronic pain and broad epigenetic changes

Injuries that result in chronic pain, such as limb injuries, and those unrelated to the brain are associated with epigenetic changes in the brain which persist months after the injury, according to researchers at McGill University. Epigenetics explores how the environment – including diet, exposure to contaminants and social conditions such as poverty – can have a long-term impact on the activity of our genes.

19 feb 2013--The team led by Prof. Laura Stone, a professor at the Faculty of Dentistry and the Alan Edwards Centre for Research on Pain, and Prof. Moshe Szyf, a professor at the Faculty of Medicine's Department of Pharmacology and Therapeutics, have discovered a mechanism that embeds the memory of an injury in the way the DNA is marked in the brain by a chemical coating called methyl groups or DNA methylation. The researchers report in the journal PLOS One, that if the symptoms of chronic pain are attenuated, the abnormal changes in DNA methylation could be reversed.

Research pioneered at McGill has previously shown that experiences and not solely chemicals alter the way genes are marked epigenetically, impacting our behavior and well-being. DNA methylation, an epigenetic mark on the gene itself, can therefore serve as a "memory" of an experience that will alter the way the gene functions long after the original experience is gone. The crucial difference between "genetic" and "epigenetic" causes for disease is that genetic changes are inherited and fixed, while epigenetic changes in contrast are possibly reversible.

The McGill research is the first to link chronic pain to genome-wide epigenetic changes in the brain. "Injury results in long-term changes to the DNA markings in the brain; our work shows it might be possible to reverse the effects of chronic pain by interventions using either behavioral or pharmacological means that interfere with DNA methylation, says Prof. Szyf. "Our findings have the potential to completely alter the way we treat chronic pain."

In this study, the researchers show that behavioral interventions that reverse chronic pain also remove differences in DNA methylation in the brain.

The team report alterations in global DNA methylation are observed in the prefrontal cortex (PFC) and amygdala of mice many months following injury to a nerve, and that environmental enrichment reduces both the pain and the pathological changes in PFC global methylation. They also found that the total amount of global methylation in the PFC significantly correlates with pain severity.

"These results suggest that epigenetic modulation mediates chronic pain-related alterations in the central nervous system (CNS), forming a "memory trace" for pain in the brain that can be targeted therapeutically, says Stone. Sinceepigenetics respond to environmental changes, these mechanisms represent a mind-body link between chronic pain and the brain at the genomic level. "The implications of this work are wide reaching and may alter the way we think about chronic pain diagnosis, research and treatment".

Provided by McGill University

Low-protein diet slows Alzheimer's in mice

Mice with many of the pathologies of Alzheimer's Disease showed fewer signs of the disease when given a protein-restricted diet supplemented with specific amino acids every other week for four months.

18 feb 2013--Mice at advanced stages of the disease were put on the new diet. They showed improved cognitive abilities over their non-dieting peers when their memory was tested using mazes. In addition, fewer of their neurons contained abnormal levels of a damaged protein, called "tau," which accumulates in the brains of Alzheimer's patients.

Dietary protein is the major dietary regulator of a growth hormone known as IGF-1, which has been associated with aging and diseases in mice and several diseases in older adults.

Upcoming studies by USC Professor Valter Longo, the study's corresponding author, will attempt to determine whether humans respond similarly – while simultaneously examining the effects of dietary restrictions on cancer, diabetes and cardiac disease.

"We had previously shown that humans deficient in Growth Hormone receptor and IGF-I displayed reduced incidence of cancer and diabetes. Although the new study is in mice, it raises the possibility that low protein intake and low IGF-I may also protect from age-dependent neurodegeneration," said Longo, who directs the Longevity Institute of the USC Davis School of Gerontology and has a joint appointment the USC Dornsife College of Letters, Arts and Sciences.

Longo worked with Pinchas Cohen, dean of the USC Davis School, as well as USC graduate students Edoardo Parrella, Tom Maxim, Lu Zhang, Junxiang Wan and Min Wei; Francesca Maialetti of the Istituto Superiore di Sanità in Rome; and Luigi Fontana of Washington University in St. Louis.

"Alzheimer's Disease and other forms of neurodegeneration are a major burden on society, and it is a rising priority for this nation to develop new approaches for preventing and treating these conditions, since the frequencies of these disorders will be rising as the population ages over the next several decades," said Cohen, who became dean of the School of Gerontology in summer 2012. "New strategies to address this, particularly non-invasive, non-pharmacological approaches such as tested in Dr. Longo's study are particularly exciting."

The results of their study were published online by Aging Cell last month.

The team found that a protein-restricted diet reduced levels of IGF-1 circulating through the body by 30 to 70 percent, and caused an eight-fold increase in a protein that blocks IGF-1's effects by binding to it.

IGF-1 helps the body grow during youth but is also associated with several diseases later in life in both mice and humans. Exploring dietary solutions to those diseases as opposed to generating pharmaceuticals to manipulate IGF-1 directly allows Longo's team to make strides that could help sufferers today or in the next few years.

"We always try to do things for people who have the problem now," Longo said. "Developing a drug can take 15 years of trials and a billion dollars.

"Although only clinical trials can determine whether the protein-restricted diet is effective and safe in humans with cognitive impairment, a doctor could read this study today and, if his or her patient did not have any other viable options, could consider introducing the protein restriction cycles in the treatment – understanding that effective interventions in mice may not translate into effective human therapies," he said.

Many elderly individuals may have already be frail, have lost weight or may not be healthy enough to eat a protein-restricted diet every other week. Longo strongly insisted that any dieting be monitored by a doctor or registered dietician to make sure that patients do not become amino acid deficient, lose additional weight or develop other side effects.

Provided by University of Southern California

Gene is marker only for mild cognitive impairment

Credit: Jennifer Infante

Defying the widely held belief that a specific gene is the biggest risk factor for Alzheimer's disease, two Cornell developmental psychologists and their colleagues report that people with that gene are more likely to develop mild cognitive impairment—but not Alzheimer's.

17feb 2013--The study suggests that older adults with healthy brain function can get genetic tests to predict increased risk of future mild cognitive impairment. However, once they are impaired cognitively, the tests won't predict their likelihood of developing Alzheimer's.

"Right now, genetic tests are used in exactly the opposite way. That is, healthy people don't get the tests to predict their risk of mild cognitive impairment, but impaired people get them to predict their risk of Alzheimer's disease," said Charles Brainerd, professor of human development and the study's lead co-author with Valerie Reyna, professor of human development. "So, impaired people think that tests will tell them if they are at increased risk of Alzheimer's, which they won't. And healthy people think that tests won't tell them whether they are at increased risk of cognitive impairment, which they will."

The researchers describe their findings in the January issue of Neuropsychology.

The work builds on previous research by Brainerd and associates that suggested the ε4 allele of the APOE genotype increases the risk of mild cognitive impairment as well as Alzheimer's.

The researchers analyzed data from the only nationally representative dataset of its kind, the National Institute on Aging's Aging, Demographics and Memory Study. They looked at data from 418 people over age 70 to see if those who carried the allele were more likely to develop mild cognitive impairment compared with those who did not have the allele. They also looked at whether ε4 carriers with mild cognitive impairment were more likely to develop Alzheimer's disease compared with non-carriers with mild cognitive impairment.

They found that healthy ε4 carriers were nearly three times—58 percent—more likely to develop mild cognitive impairment compared with non-carriers. However, ε4 carriers with mild cognitive impairment developed Alzheimer's at the same rate as non-carriers.

While previous studies showed that the ε4 allele was more common in people with Alzheimer's disease, this study shows that it does not increase the risk that healthy or impaired people will become demented. Rather, ε4 increases the risk that healthy people will become cognitively impaired, and impaired people are the primary source of new Alzheimer's diagnoses, Brainerd explained. "The reason ε4 is a risk factor for mild cognitive impairment, but not for progression from mild cognitive impairment to Alzheimer's disease, is that this allele is a marker of initial cognitive declines—for example, memory and executive function—that are associated with mild cognitive impairment but not of subsequent declines in cognition or in daily functioning that are associated with forms of Alzheimer's disease."

Brainerd also noted that the effects of ε4 in healthy adults can be detected by the mid-20s. While ε4 is not a risk factor for the severe cognitive declines that signal dementia, it is risk factor for the weaker declines that eventually produce mild cognitive impairment.

Provided by Cornell University

Study suggests link between regular aspirin use, increased risk of age-related macular degeneration

Regular aspirin use appears to be associated with an increased risk of neovascular age-related macular degeneration (AMD), which is a leading cause of blindness in older people, and it appears to be independent of a history of cardiovascular disease and smoking, according to a report published Online First by JAMA Internal Medicine.

16 feb 2013--Aspirin is one of the most widely used medications in the world and is commonly used in the prevention of cardiovascular disease, such as myocardial infarction (heart attack) and ischemic stroke. While a recent study suggested that regular aspirin use was associated with AMD, particularly the more visually devastating neovascular (wet) form, other studies have reported inconsistent findings. Smoking is also a preventable risk factor for AMD, the authors write in the study background.

Gerald Liew, Ph.D., of the University of Sydney, Australia, and colleagues examined whether regular aspirin use (defined as once or more per week in the past year) was associated with a higher risk of developing AMD by conducting a prospective analysis of data from an Australian study that included four examinations during a 15-year period. Of 2,389 participants, 257 individuals (10.8 percent) were regular aspirin users.

After the 15-year follow-up, 63 individuals (24.5 percent) developed incident neovascular AMD, according to the results.

"The cumulative incidence of neovascular AMD among nonregular aspirin users was 0.8 percent at five years, 1.6 percent at 10 years, and 3.7 percent at 15 years; among regular aspirin users, the cumulative incidence was 1.9 percent at five years, 7 percent at 10 years and 9.3 percent at 15 years, respectively," the authors note. "Regular aspirin use was significantly associated with an increased incidence of neovascular AMD."

The authors note that any decision concerning whether to stop aspirin therapy is "complex and needs to be individualized."

"Currently, there is insufficient evidence to recommend changing clinical practice, except perhaps in patients with strong risk factors for neovascular AMD (e.g., existing late AMD in the fellow eye) in whom it may be appropriate to raise the potentially small risk of incident neovascular AMD with long-term aspirin therapy," the authors conclude.

In an invited commentary, Sanjay Kaul, M.D., and George A. Diamond, M.D., of Cedars-Sinai Medical Center, Los Angeles, write: "This study has important strengths and limitations. It provides evidence from the largest prospective cohort with more than five years of longitudinal evaluation reported to date using objective and standardized ascertainment of AMD."

"The key limitation is the nonrandomized design of the study with its potential for residual (unmeasured or unobserved) confounding that cannot be mitigated by multivariate logistic regression or propensity score analysis," the authors continue.

"From a purely science-of-medicine perspective, the strength of evidence is not sufficiently robust to be clinically directive. These findings are, at best, hypothesis-generating that should await validation in prospective randomized studies before guiding clinical practice or patient behavior," the authors conclude. "However, from an art-of-medicine perspective, based on the limited amount of available evidence, there are some courses of action available to the thoughtful clinician. In the absence of definitive evidence regarding whether limiting aspirin exposure mitigates AMD risk, one obvious course of action is to maintain the status quo."

More information: JAMA Intern Med. Published online January 21, 2013. doi:10.1001/jamainternmed.2013.1583 
JAMA Intern Med. Published online January 21, 2013. doi:10.1001/jamainternmed.2013.2530

Provided by JAMA and Archives Journals

Risk of cardiovascular death doubled in women with high calcium intake

High intakes of calcium (corresponding to diet and supplements) in women are associated with a higher risk of death from all causes, but cardiovascular disease in particular, compared with women with lower calcium intake, a study published on bmj.com suggests.

15 feb 2013--Experts recommend a high calcium intake (as it plays a pivotal role in human physiology) and as such, more than 60% of middle-aged and older women in the USA now take supplements.

However, recent trials have indicated a higher risk of ischemic heart disease and stroke with calcium supplements but this was not observed in another trial and few studies have examined this association.

Researchers from Uppsala University in Sweden therefore studied 61,443 Swedish women (born between 1914 and 1948) for an average of 19 years to test this association.

Data were taken from the Swedish Cause of Death Registry and data on diet were taken from the Swedish Mammography Cohort. Total calcium intake included supplemental calcium. The mean intake in the lowest quartile was 572mg/day (the equivalent of five slices of cheese ) and in the highest 2137mg/day.

Information was obtained from the women on menopausal status, postmenopausal oestrogen therapy, parity information, weight and height, smoking habits, leisure-time physical activity and educational level.

Results showed that during 19 years of follow-up, 11,944 women (17%) died: 3,862 of these (32%) died from cardiovascular disease, 1932 (16%) heart disease and 1100 (8%) from stroke. Highest rates of all-cause, cardiovascular and heart disease were observed among those with a dietary calcium intake higher than 1400mg/day.

In addition, researchers observed higher death rates among women with an intake below 600mg/day.

Women who had a higher dietary intake of calcium exceeding 1400mg/day and also used supplements had a higher death rate compared to those not taking supplements. Women with a high dietary calcium intake (>1400 mg/day) were more than twice as likely to die compared with women with a 600-999mg/day calcium intake.

The researchers explain their findings by suggesting that diets very low or very high in calcium can override normal homeostatic control causing changes in blood levels of calcium.

The researchers conclude that high calcium is associated with "higher all-cause and cardiovascular mortality rates" and so to prevent fractures in the elderly emphasis should be placed on individuals with a low intake of calcium rather than increasing the intake of those already consuming satisfactory amounts.

Provided by British Medical Journal

A neural basis for benefits of meditation

Magnetoencephalographic studies show that people who have been trained in mindfulness have quicker and larger changes in alpha wave amplitude when they shift focus. 

Why does training in mindfulness meditation help patients manage chronic pain and depression? In a newly published neurophysiological review, Brown University scientists propose that mindfulness practitioners gain enhanced control over sensory cortical alpha rhythms that help regulate how the brain processes and filters sensations, including pain, and memories such as depressive cognitions.

14 feb 2013--The proposal, based on published experimental results and a validated computer simulation of neural networks, derives its mechanistic framework from the intimate connection in mindfulness between mind and body, since standardized mindfulness meditation training begins with a highly localized focus on body and breath sensations. This repeated localized sensory focus, the scientists write, enhances control over localized alpha rhythms in the primary somatosensory cortex where sensations from different body are "mapped" by the brain.

In effect, what the researchers propose in their paper in Frontiers in Human Neuroscience, is that by learning to control their focus on the present somatic moment, mindfulness meditators develop a more sensitive "volume knob" for controlling spatially specific, localized sensory cortical alpha rhythms. Efficient modulation of cortical alpha rhythms in turn enables optimal filtering of sensory information. Meditators learn not only to control what specific body sensations they pay attention to, but also how to regulate attention so that it does not become biased toward negative physical sensations such as chronic pain. The localized attentional control of somatosensory alpha rhythms becomes generalized to better regulate bias toward internally focused negative thoughts, as in depression.

"We think we're the first group to propose an underlying neurophysiological mechanism that directly links the actual practice of mindful awareness of breath and body sensations to the kinds of cognitive and emotional benefits that mindfulness confers," said lead author Catherine Kerr, assistant professor (research) of family medicine at the Alpert Medical School and director of translational neuroscience for the Contemplative Studies Initiative at Brown.

Experimental evidence

In experiments that Kerr and neuroscientist co-authors Stephanie Jones and Christopher Moore have published over the last few years, the team has used a brain imaging technology called magnetoencephalography (MEG) to show that alpha rhythms in the cortex correlate with sensory attention and that the ability to regulate localized alpha brainwaves on a millisecond scale is more distinct in people who have had standardized mindfulness training than in those who have not. The trio led these experiments at the Massachusetts Institute of Technology, Harvard, and Massachusettes General Hospital before they all came to Brown in 2011.

In one experiment published in the Journal of Neuroscience in 2010, they observed that when people focused their attention on sensations in the left hand, the corresponding "map" for the hand in the cortex showed a marked drop in alpha wave amplitude (as if to reduce filtering there). When the subjects' attention shifted away from that body part, the alpha rhythm amplitude in the corresponding brain map went back up (as if restoring the alpha filter). Other research groups have shown this to be the case for other kinds of attention-related tasks including focusing spatial attention and working memory.

Then in 2011 in Brain Research Bulletin, the team published another paper. They randomized subjects to eight weeks of mindfulness training versus a control group. In MEG, they asked members of each group to focus attention on sensations in their hand and then to switch their attention to their foot. The people trained in mindfulness displayed quicker and larger changes in alpha wave amplitude in their brain's hand map when they made the attentional shift than the six people who did not have mindfulness training.

Mindful computational model

In addition to the emerging experimental evidence, the research framework is also informed by a computer model that Jones has developed to simulate the alpha brainwaves through reciprocal interactions between the cortex, which processes information and thoughts, and the thalamus, which is like a switchboard that mediates information flow from the rest of the brain to the cortex. The model is well validated in that it produces alpha rhythms that closely match those observed in live MEG scans of real subjects.

Jones, assistant professor (research) of neuroscience, did not originally develop the model to aid meditation research.

"We were investigating what are the brain mechanisms that can create this prominent alpha rhythm and mediate its impact on sensory processing," Jones said. "The model simulates the electrical activity of neural networks and makes very specific predictions about how this rhythm is generated. Once we understand the brain processes regulating alpha rhythm expression, we can better understand how it can be modulated with mindfulness practice and why this is beneficial."

Among the most important predictions is one that could explain how gaining control of alpha rhythms not only enhances sensory focus on a particular area of the body, but also helps people overcome persistent competing stimuli, such as depressive thoughts or chronic pain signals.

To accomplish this, the model predicts, meditators must achieve proper control over the relative timing and strength of alpha rhythms generated from two separate regions of the thalamus, called thalamic nuclei, that talk to different parts of the cortex. One alpha generator would govern the local "tuning in," for instance of sensations in a hand, while the other would govern the broader "tuning out" of other sensory or cognitive information in the cortex.

It's a bit like focusing a telescope by precisely aligning the position of two different lenses. The authors' framework hypothesizes that experienced meditators gain the ability to turn that proverbial focus knob to align those different rhythms.

Working with the framework

In the new paper the authors propose that training chronic pain patients in the standardized mindfulness techniques of focusing on and then focusing away from pain, should result in MEG-measurable, testable improvements in alpha rhythm control.

"By this process of repeatedly engaging and disengaging alpha dynamics across the body map, according to our alpha theory, subjects are re-learning the process of directly modulating localized alpha rhythms," they wrote. "We hypothesize that chronic pain patients trained in mindfulness will show increased ability to modulate alpha in an anticipatory tactile attention paradigm similar to that used in [the 2011 study]."

Many such experiments are yet to be done, Kerr acknowledges, and her group can only do so many.

"There are a number of hypotheses in this framework that can be tested," Kerr said. "That's one of the reasons we wanted to put this out as a framework. It is beyond our ability to test all of these ideas. We wanted to make this available to the scientific field and present this unified view."

Provided by Brown University

Stress symptoms in midlife predict old-age disability, study finds

Nearly 30% of adult workers suffer from work-related stress, and it is commonly acknowledged that stress has damaging effects on individual's health. Recently published prospective cohort study by Dr. Jenni Kulmala and co-workers from the Gerontology Research Center (GEREC) at the University of Jyväskylä, Finland, provides strong evidence that perceived work-related stress in midlife predicts functional limitations and disability later in old age.

13 feb 2013--Previously stress has been described as a rather uniform entity in all individuals, with more or less consistent symptoms, but this study shows that dominant stress symptoms in middle age may vary between persons. The study involved more than 5,000 persons who were followed up for almost thirty years from working age to old age.

"We were able to identify four different stress profiles among occupationally active persons aged from 44 to 58 years: negative reactions to work and depressiveness; perceived decrease in cognition; sleep disturbances; and somatic symptoms. Some people suffered from occasional symptoms, but in some cases these symptoms were observed in several time points and thus were considered as continuous," says Dr. Jenni Kulmala.

All kinds of stress symptoms in midlife correlated with disability 28 years later. Persons who had reported long-term stress symptoms in midlife had more difficulties in the basic activities of daily living, such as bathing and dressing, and also in more demanding instrumental daily activities, such as shopping, coping with light housework, handling financial matters, taking medication and using the telephone at the mean age of 78 years. Additionally, the risk for inability to walk two kilometres was 2–3 times higher for those with constant stress symptoms in midlife. Occasional stress symptoms in midlife also increased the severity of disability, but less than constant symptoms.

"Stress symptoms are associated with chronic conditions and a maladaptive lifestyle, which may partly explain the found association. However, in our study, the association was not completely explained by such mediators. Therefore, it is also possible that the chronic activation of stress responses may result in the "wear and tear" of the human body and thus increase the risk of old age disability," says Dr. Kulmala.

The results obtained in this study offer targets for interventions aimed at preventing the decline of physical functioning, and promoting healthy aging.

More information: Kulmala J. et al. Perceived stress symptoms in midlife predict disability in old age. A 28-year prospective cohort study. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 2013; doi: 10.1093/gerona/gls339

Provided by Academy of Finland