Is dementia on the decline? Research suggests it might be

Despite fears that the coming silver tsunami will trigger a dementia epidemic, a surprising new study suggests that it may be possible to delay - or even prevent - some kinds of dementia.

29 feb 2016--Dementia rates in the United States dropped by 44 percent from the late 1970s to 2010, according to the Boston University study.
In addition, the average age when people showed symptoms rose from 80 to 85, researchers discovered.
Their findings were published recently in the New England Journal of Medicine.
The report analyzed data from a long-running study of thousands of people in a small Massachusetts town.
While scientists don't know the exact reason for the decrease in dementia cases, they highlight two contributing factors: education level and heart health.
People in the study who earned at least a high school diploma had a much lower dementia risk than those with less education. Other studies have revealed a link between higher levels of education and better overall health.
The largest decrease was reported in dementia cases caused by stroke and other vascular diseases. People in the study who improved their heart health saw a reduction in their dementia risk.
Currently, about 5.3 million Americans have Alzheimer's disease, the most common form of dementia.

Older adults have their own perspectives on sadness, loneliness and serenity

In a recent study, Ready found that older adults report feeling more serenity than younger people, and have a richer concept of what it means to feel serene than younger people. Credit: UMass Amherst

28 feb 2016--A new study led by associate professor Rebecca Ready in the department of psychological and brain sciences at the University of Massachusetts Amherst has found that older adults have different, more positive responses than young adults about feelings such as serenity, sadness and loneliness.
Ready calls the findings "highly clinically significant" because the information could help caregivers, psychotherapists and workers at assisted living facilities, for example, better understand the emotions of older people in their care, which could lead to improved treatment and quality of interactions. Findings appear in the current online issue of Aging and Mental Health.
She says, "Older adults report feeling more serenity than younger persons. They also have a richer concept of what it means to feel serene than younger persons." In a word grouping task, older adults associated more positive emotional terms with serene, such as cheerful, happy and joyful, than did younger people. The authors speculate that "this broader conception of serene" is associated with the fact that older adults report more calming positive emotions than younger people.
She adds, "We were surprised to find that younger adults associated more self-deprecating terms with feeling sad and lonely, such as being ashamed or disgusted with themselves, than older persons." When grouping other emotion words with sadness, older adults included words such as droopy and sheepish, while younger adults included more self-deprecating terms with the word, such as dissatisfied with self, ashamed, angry and disgusted with self. A similar pattern was observed for lonely.
For this study, Ready and her graduate student Gennarina Santorelli recruited 32 older adults ages 60 to 92, and 111 younger adults ages 18 to 32, and asked them to judge 70 emotion terms on whether the words had a positive or negative connotation and if the words were activating or arousing. For example, excited is generally rated as a high activation word, while serene is associated with less activation. They then had participants group similar words together.
Ready and colleagues found the word groupings were similar between older and younger persons for many words but they noted systematic differences for sadness, loneliness and, as noted above, serenity. They also found that older adults perceive emotion terms as most positive and more active than younger persons. Emotions overall may be more stimulating for older than younger persons.
The older adults in this study reported fewer depressive symptoms than the younger participants. Controlling for age group differences in these symptoms, Ready says, "We gained a deeper appreciation of some relatively unknown benefits of aging, such as increased positive emotions and less shame associated with feeling sad or lonely."
As the percentage of older adults in the United States increases, Ready says, "It is imperative to determine how older adults define emotions differently than younger adults. These data ensure effective communication with older adults, accurate understanding of their emotion experiences, and appropriate access to psychological interventions."

More information: Rebecca E. Ready et al. Judgment and classification of emotion terms by older and younger adults, Aging & Mental Health (2016). DOI: 10.1080/13607863.2016.1150415


Provided by University of Massachusetts Amherst

People in their nineties reveal the secrets to ageing well

Never too old. Credit: www.shutterstock.com

27 feb 2016--There are many reasons why some people live long healthy lives while others don't, but one of them is undoubtedly genes. That doesn't mean we should be negative about our chances of ageing in good health. Although our genes are handed down from our parents, the hand that we are dealt seems to be influenced by our lifestyle, too. Food, physical activity and stress can change how genes function by adding "chemical tags" that act as on/off or dimmer switches, influencing our health and lifespan. The study of this process is known as epigenetics.
In a series of research studies with nonagenarians who were in robust health (the BELFAST studies), we found that participants carried fewer of the genes that are implicated in cardiovascular disease and showed some gene types which may have helped boost their immunity.
In the most recent BELFAST nonagenarians' study, we built on these findings and asked active nonagenarians why they thought they had lived for so long and in such good health. Family history and personal stories are powerful tools when used in parallel with genomic analyses. They can help us to understand how our beliefs, behaviour and lifestyle choices subtly fine-tune how our genes function in daily life.
By talking to nonagenarians about their lives, we identified how important they considered their genes to be, but they also told us about several other factors that they thought supported their long and healthy lives.
Genes and good health
Nonagenarian siblings recognised genes as important. Ellie, 99, said: "I suppose it was the family I was born into – my mother's female relatives all seemed to live into their 90s. I can remember cousins and aunts, all were over 90."

Socialising and exercising your brain – both important in ageing well. Credit: Zina Seletskaya/Shutterstock.com

She added: "The men didn't live so long."
In fact, Ellie had observed something scientists still don't understand: why women live longer than men. Evidence suggests that it may relate to male hormones in the womb leading to increased age-related disease.
Train body and mind
All of the people in our study spoke about the importance of keeping mentally and physically active. Robert, a shopkeeper, said: "Hard work all my life. I think that is the secret."
Norman, 95, one of two nonagenarian brothers, both railwaymen, said: "I left school at 16 and, yes, we had to go to work then. It wasn't like today when you can keep your education going until you are 23 or 24." His brother, Joyce, 96, agreed: "Yes we worked hard. There is no doubt about it."
Samuel, 95, but "going on 25", keeps mentally busy and told us that he had just finished writing his tenth book.
The health benefits of physical activity are hard to ignore. Regular exercise changes our epigenome, activating genes that improve muscle function. Exercise not only protects our muscles but also our brains with a possible dose-related effect – the more we do, the greater the effect. Exercise is good for everyone and it's never too late to start.
Eat well
Many of the study participants mentioned the importance of food in ageing well. Norman said: "I have always led a quiet life. Didn't smoke or drink to any extent and was always fed on good solid food. No junk food." His brother, Joyce, added: "We always had sensible food. Never smoked, except for a couple of months."
Eileen, 92, gave details of "good food, good healthy meals. Mama would have a big pot of broth for us."
There is truth in the saying: you are what you eat. Scientists have provided evidence that fruit and vegetablea may dampen cancer-causing genes, or may protect us from cancer by altering epigenetic markers.
Few participants smoked, avoiding the known epigenetic effects of cigarette smoke including lung damage, increased risk of dementia and cancer.
Be positive, stay social
Many of the participants described "being happy", "always cheerful", "never melancholy" and being content with a "rich life" and family relationships. Typical examples from siblings include Samuel, 95, who said he is "interested in people, interested in life". His sister Ethel, 93, added: "[I am] interested in things, and everything that's going on." Whilst Sarah, 95, one of two sisters, told us: "Oh, I am always happy" and her sister Mariah, 94, said: "I have just a happy disposition".
The ability or willingness to cope with difficulties was another common attitude we observed. As Eileen, 96, told us: " just take things as they come."
Successful ageing is considered to be more than the absence of disease and being able to live independently but involves being socially active. Friends and family are important factors in ageing well, making for good mental health, reduced risk of premature death and can help people deal with stressful events in their lives.
The epigenetic modification of our genes – and the life stories of healthy nonagenarians – offer explanations about how diet, physical activity, stress and exposure to toxins and infections can subtly alter our genes and our predisposition to disease.
The key to ageing well may not depend on choosing our parents wisely (even if we could), but making good lifestyle choices.

This article was originally published on The Conversation. 



Source: The Conversation

High levels of intense exercise may be unhealthy for the heart

Increased incidence of arrhythmias in the athlete's heart. There is a well demonstrated association between atrial fibrillation and/or flutter and endurance exercise training. There is also an increase in premature ventricular beats, although this tends to be benign in most athletes. Although there is some speculation that extreme exercise might cause serious arrhythmias in some cases, these events remain very uncommon. PPM, permanent pacemaker; RV, right ventricular. Credit: Canadian Journal of Cardiology

26 feb 2016--There is growing evidence that high levels of intense exercise may be cardiotoxic and promote permanent structural changes in the heart, which can, in some individuals, predispose them to experience arrhythmias (abnormal heart rhythm). A review published in the Canadian Journal of Cardiology explores current controversies and makes the case for investing in large prospective research studies into the effect of intense exercise on heart structure and function.

There are unquestionable benefits to "getting off the couch." However, there is already fairly compelling evidence supporting the association between long-term sports practice and increased prevalence of atrial fibrillation, and the fact that this relates to chronic altered atrial substrate. Without challenging the undeniable evidence supporting low and moderate intensity exercise, this review by sports cardiologist André La Gerche, MD, PhD, provides a balanced discussion of the available data for and against the concept that intense exercise, particularly endurance exercise, may cause adverse cardiac changes in some athletes.

"Much of the discussion regarding the relative risks and benefits of long-term endurance sports training is hijacked by definitive media-grabbing statements, which has fueled an environment in which one may be criticized for even questioning the benefits of exercise," explains Dr. La Gerche, who is Head of Sports Cardiology at the Baker IDI Heart and Diabetes Institute, Melbourne, Australia. "This paper discusses the often questionable, incomplete, and controversial science behind the emerging concern that high levels of intense exercise may be associated with some adverse health effects."

As Dr. La Gerche points out, all available therapies, pharmacological or otherwise, have a dose-response relationship whereby benefits diminish at high doses and the risk of adverse events increases. An open mind would consider that this may even be possible for exercise.

A commonly held view is that adverse clinical events in athletes are explained by exercise acting as a trigger in individuals who are susceptible because of an underlying abnormality. Dr. La Gerche excludes inherited conditions from this discussion, focusing instead on whether exercise may affect a change in the heart that may serve as a cause of arrhythmias in its own right. He reviews the following emerging controversies:

• Is there a non-linear dose-response relationship with exercise?
• Elite athletes tend to live longer but is this the effect of exercise or other factors such as the absence of smoking and alcohol consumption?
• Is endurance exercise in athletes associated with arrhythmias?
• What are the potential mechanisms that predispose athletes to arrhythmias?
• Is chronic cardiac remodelling a consequence of repeated bouts of injury?
• Why is there disproportionate right ventricular (RV) injury following an acute bout of intense exercise and are there any long-term consequences?
• Is the risk of ischemic heart disease increased with intense exercise?

Many of these controversies are based on small cross-sectional cohort studies and small mechanistic studies that are dwarfed by the large population studies supporting the benefits of exercise, albeit in doses of exercise less than those commonly practiced by elite sportspersons, notes Dr. La Gerche.

"The answers regarding the healthfulness of 'extreme' exercise are not complete and there are valid questions being raised," continues Dr. La Gerche. "Given that this is a concern that affects such a large proportion of society, it is something that deserves investment. The lack of large prospective studies of persons engaged in high-volume and high-intensity exercise represents the biggest deficiency in the literature to date, and, although such work presents a logistical and financial challenge, many questions will remain controversies until such data emege."

More information: "The potential cardiotoxic effects of exercise," by Andre La Gerche, MBBS PhD (DOI: dx.doi.org/10.1016/j.cjca.2015.11.010). Published online in advance of Volume 32/Issue 4 (April 2016) of the Canadian Journal of Cardiology. 

Provided by Elsevier

What are the benefits and harms of cancer screening? Most guidelines don't tell you

Screening for cancer has many obvious benefits - you're preventing cancer or catching it early. But each screening tool also comes with potential harms or risks.
A new study finds most cancer screening guidelines do not clearly spell out the benefits and harms of the recommended actions.

24 feb 2016--Researchers from the University of Michigan Health System examined 55 professional guideline recommendations for cancer screening or prevention. They found 69 percent did not quantify and present benefits and harms in comparable terms.
"Almost all medical interventions have tradeoffs between different types of benefits and harms," says Tanner J. Caverly, M.D., MPH, clinical lecturer of internal medicine at the University of Michigan Medical School and a research investigator at the VA Ann Arbor Healthcare System Center for Clinical Management Research.
"Patients rely on doctors to base screening recommendations on sound judgment as to whether, in their individual context, the benefits outweigh the harms. For this judgment, doctors need a clear understanding, in quantitative and comparable terms, about the degree of potential benefit and the degree of potential harm."
The study, published in the Journal of the National Cancer Institute, looked at guidelines such as mammography screening for breast cancer, PSA testing for prostate cancer, colonoscopy for colon cancer, HPV vaccination for cervical cancer and other screening tests. Guidelines were from agencies such as the U.S. Preventive Services Task Force, the American Cancer Society and the National Comprehensive Cancer Network.
The researchers found that 31 percent of guidelines recommending screening presented absolute effects for both benefits and harms. Meanwhile, 55 percent presented the tradeoffs unevenly, explaining the benefit but not the harm or presenting the numbers in different ways.
For example, some studies used relative risk reduction, often a larger number, to show benefit - people who were screened were twice as likely to survive. But they used absolute risk, often a much smaller number, to demonstrate harm - 1 percent of people screened had a false diagnosis.
"By unevenly presenting the statistics, guidelines can unintentionally give a false picture of the benefits and harms. The relative risk of "twice as likely" sounds significant, but in terms of absolute risk it might represent a very small difference," said senior author Angela Fagerlin, Ph.D., professor and chair at the University of Utah's Department of Population Health Sciences and a research scientist at the Salt Lake City VA.
The researchers suggest that guidelines should quantify and present all important benefit and harm information in a well-designed table or graphic, so that they can be easily compared.
"Improving how guidelines present the benefits and harms would help doctors better understand the trade-offs and facilitate informed discussions with patients. It would also help us to build better decision support tools for physicians," says Caverly, who is also a member of the U-M Institute for Healthcare Policy and Innovation.

More information: Journal of the National Cancer Institute, published online Feb. 24, 2016, DOI: 10.1093/jnci/djv436


Provided by University of Michigan Health System

Estrogen for vaginal symptoms OK for breast cancer survivors: experts

23 feb 2016—Women who've battled or survived an estrogen-dependent form of breast cancer often encounter vaginal symptoms linked to their treatment, especially around the time of menopause.
Now, new guidelines from the American College of Obstetricians and Gynecologists (ACOG) advise that the use of symptom-relieving estrogen therapy is warranted for these patients.
"These new recommendations are especially important and helpful because they provide the patient with the information needed to make an informed decision with the input of her health care provider," Dr. Diana Nancy Contreras, chair of ACOG's Subcommittee on Gynecologic Oncology, said in a college news release.
One expert in women's health explained that patients with an estrogen-dependent breast cancer often suffer vaginal symptoms linked to treatment.
"Many estrogen-dependent breast cancer treatments may bring about and exacerbate vaginal atrophy," said Dr. Jill Rabin, who's with Women's Health Programs-PCAP Services, Northwell Health, in New Hyde Park, N.Y.
"Vaginal and urologic symptoms range from mild to severe and can include vaginal dryness, pain, bleeding, bacterial infections and dyspareunia [painful sex]," she noted. "These symptoms—which may arise for many women in menopause—may be multiplied for these patients in treatment and can worsen over time.
"These symptoms can have a huge impact on a woman's quality of life—for all affected women and especially for breast cancer survivors," Rabin added. In fact, up to a fifth of breast cancer patients"terminate or consider terminating therapies due to the severe detrimental effect that vaginal atrophy poses on their quality of life," she said.
There's been a concern, however, about the safety of estrogen-based therapies for women who are battling or who have survived an estrogen-linked breast tumor.
Specifically, there have been concerns about a possible link between topical (cream or lotion) estrogen therapy and recurrence of estrogen-linked breast cancers. However, current research has not confirmed such a connection, the experts at ACOG stated.
So, in its new recommendations, the group recommends that non-hormonal therapies for vaginal symptoms still be the first choice for women with estrogen-dependent breast cancer or a history of such a cancer.
However, topical estrogen therapy can now also be considered for estrogen-dependent breast cancer survivors who do not respond to non-hormonal therapies, ACOG said.
Dr. Eva Chalas is chief of gynecological oncology at Winthrop-University Hospital, in Mineola, N.Y. She said she agreed with the new recommendation.
"Non-hormonal management should be the first course of action," Chalas said. "However, the most effective treatment remains estrogen.
"Quality of life, which includes an opportunity for sexual intimacy, is an important aspect of cancer survivorship," Chalas explained. "Women should address the severity of symptoms with their physicians and participate in selection of therapy which yields the best quality of life. This [ACOG] document provides safe guidelines which could enhance post-treatment sexual function in many breast cancer survivors."

The new guidelines will be published in the March issue of Obstetrics & Gynecology.
More information: The U.S. National Cancer Institute discusses menopausal hormone therapy and cancer.

Common problem for older adults: Losing the five key senses

Credit: Peter Griffin/public domain

It's a well-known fact that aging can lead to losing one's senses: vision, smell, hearing, touch, and taste. In previous studies, researchers have learned about the consequences of experiencing a decline in a single sense. For example, losing senses of smell, vision, and hearing have all been linked to cognitive decline, poor mental health, and increased mortality. Losing the sense of taste can lead to poor nutrition and even death in certain instances. However, until now little has been known about losing multiple senses. In a new study, researchers examined how often multisensory losses occur and what their impact on older adults might be.

21 feb 2016--In a study published in the Journal of the American Geriatrics Society, University of Chicago researchers analyzed data from the National Social Life, Health, and Aging Project (NSHAP), a population-based study of adults ages 57-85. The study collected information about the participants' senses of vision, touch, smell, hearing, and taste. The participants were also asked to rate their physical health.
The researchers reported several key findings:

• 94 percent of the participants experienced loss in at least one of their senses; 67 percent had two or more sensory losses. Of those with multisensory losses, 65 percent had substantial loss in at least one of their senses, and 22 percent experienced substantial loss in two or more senses.
• 74 percent of participants suffered impairment in their ability to taste, which was the most common sensory loss.
• 38 percent of participants had a sense of touch that was "fair;" 32 percent said it was "poor."
• 22 percent had smell impairment (19 percent fair/3 percent poor function).
• 14 percent had corrected distance vision that was "fair;" 6 percent said it was "poor."
• 13 percent rated their corrected hearing as "fair;" 5 percent said it was "poor."

Older age was linked to poorer function in all five senses; the largest differences were in hearing, vision, and smell. What's more, men had worse functioning for hearing, smell, and taste than did women—although men had better corrected vision than women. African Americans and Hispanics tended to have worse sensory function than Caucasians in all senses except hearing. Hispanics tended to have better function in taste than those from other groups.
The researchers said that losing more than one sense might explain why older adults report having a poorer quality of life and face challenges in interacting with other people and the world around them. The researchers suggested that further studies into multisensory loss hold promise for designing better programs to prevent or treat loss and to ease the suffering such losses cause.

More information: This summary is from "Global Sensory Impairment among Older Adults in the United States." It appears online ahead of print in the February 2016 issue of the Journal of the American Geriatrics Society.


Provided by American Geriatrics Society

Light-to-moderate drinking good for your heart, researchers say

People who drink wine, liquor or beer regularly are less prone to heart failure and heart attacks than those who rarely or never drink. Three to five drinks a week can be good for your heart.
Drinking a little alcohol every day may be part of a healthy lifestyle, according to Imre Janszky, a professor of social medicine at the Norwegian University of Science and Technology (NTNU). He says alcohol does more good than harm for your heart when consumed in moderation.

20 feb 2016--And, Janszky says, it doesn't matter much whether you drink wine, liquor or beer.
"It's primarily the alcohol that leads to more good cholesterol, among other things. But alcohol can also cause higher blood pressure. So it's best to drink moderate amounts relatively often," he says
.
Decreased risk with each additional serving

Along with a number of colleagues from NTNU and the Karolinska Institute in Stockholm, Janszky has published two studies regarding the relationship between alcohol and heart health. One, published in the January 15 issue of the International Journal of Cardiology, is about heart failure. The second, from September 2015, is on acute myocardial infarction (AMI), and has been published in the Journal of Internal Medicine.
In both cases, research shows that people who regularly drink alcohol have better cardiovascular health than those who consume little or no alcohol.
The studies showed that those who drank three to five drinks per week were 33 per cent less prone to heart failure than those who abstained or drank infrequently. In the case of heart attacks, the risk appears to be reduced by 28 percent with each additional one-drink increment.
This does not surprise the researchers at all.
A majority of researchers worldwide seem to think three to five drinks a week can be good for your heart.

Different drinking patterns

"The relationship between alcohol and heart health has been studied in many countries, including the USA and southern European nations. The conclusions have been the same, but the drinking patterns in these countries are very different than in Norway. In countries like France and Italy, very few people don't drink," says Janszky. "It raises the question as to whether earlier findings can be fully trusted, if other factors related to non-drinkers might have influenced research results. It may be that these are people who previously had alcohol problems, and who have stopped drinking completely," he says.
For this reason, the researchers wanted to examine the theory with a Norwegian population where a significant population drinks rarely or not at all. In the myocardial infarction study, 41 per cent of participants reported that they did not drink at all or that they consumed less than half of one alcoholic beverage per week.
Both studies are based on the longitudinal HUNT 2 Nord-Trøndelag Health Study conducted between 1995 and 1997.

The greater the drinking frequency, the lower the risk

The study, which looked at the relationship between heart failure and alcohol, followed 60,665 participants who enrolled in the HUNT study between 1995-1997 and who had no incidence of heart failure at that time. Of those, 1588 of them developed heart failure during the period of the study, which ended in 2008. The risk was highest for those who rarely or never drank alcohol, and for those who had an alcohol problem.
The more often participants consumed alcohol within normal amounts, the lower their risk of heart failure turned out to be. Those who drank five or more times a month had a 21 per cent lower risk compared to non-drinkers and those who drank little, while those who drank between one and five times a month had a two per cent lower risk.

Drinking isn't necessary for a healthy heart

"I'm not encouraging people to drink alcohol all the time. We've only been studying the heart, and it's important to emphasize that a little alcohol every day can be healthy for the heart. But that doesn't mean it's necessary to drink alcohol every day to have a healthy heart," says Janszky.
In the heart attack study, 58,827 participants were categorized by how much and how often they drank. 2966 of the participants experienced an acute myocardial infarction (AMI) between 1995 and the end of 2008. The adjusted analyses showed that each additional one-drink increment decreased the risk of AMI by 28 percent.

Alcohol may increase other problems

The researchers stressed that few participants in the study drank particularly much, so they cannot conclude that high alcohol intake protects against heart attack or heart failure. They also encourage looking at the findings in a larger context, since the risk of a number of other diseases and social problems can increase as a result of higher alcohol consumption.
For example, the researchers observed that the risk of dying from various types of cardiovascular disease increased with about five drinks a week and up, while those who drank more moderate amounts had the lowest risk. High alcohol consumption was also strongly associated with an increased risk of death from liver disease.

More information: Katalin Gémes et al. Light-to-moderate drinking and incident heart failure—the Norwegian HUNT study, International Journal of Cardiology (2016). DOI: 10.1016/j.ijcard.2015.10.179 K.

Gémes et al. Alcohol consumption is associated with a lower incidence of acute myocardial infarction: results from a large prospective population-based study in Norway, Journal of Internal Medicine(2015). DOI: 10.1111/joim.12428


Provided by Norwegian University of Science and Technology

Update on menopausal symptoms and treatment options published

Credit: Mary Ann Liebert, Inc., publishers

The vast majority of women going through the period of menopausal transition, or perimenopause, will seek medical help coping with symptoms that can significantly impact their health and quality of life, such as hot flashes, poor sleep, depression, and vaginal dryness. The pattern of common perimenopausal symptoms, how they often interact to worsen the effects of each, and current hormonal and non-hormonal therapeutic options are examined in a comprehensive Review article published in Journal of Women's Health.

18 feb 2016--In "Perimenopause: From Research to Practice"), Nanette Santoro, MD, University of Colorado School of Medicine, Denver, describes the stages of reproductive aging in women, linking common symptoms to the late reproductive stages, the early and late menopausal transition stages, and the early postmenopause. Dr. Santoro discusses strategies for treating multiple symptoms with a single medication when possible. For women who experience the four main menopausal symptoms, hormone therapy is the most effective way to improve their quality of life, as long as hormone use is not contraindicated.
"This outstanding review integrates research findings with the clinical presentations of symptomatic perimenopausal women and treatment options," says Susan G. Kornstein, MD, Editor-in-Chief of Journal of Women's Health, Executive Director of the Virginia Commonwealth University Institute for Women's Health, Richmond, VA, and President of the Academy of Women's Health.

More information: Nanette Santoro. Perimenopause: From Research to Practice, Journal of Women's Health (2015). DOI: 10.1089/jwh.2015.5556


Provided by Mary Ann Liebert, Inc

New guide from AGS, NHTSA a green light to promoting safe driving for older adults

A newly updated guide from the American Geriatrics Society (AGS) and the National Highway Traffic Safety Administration (NHTSA) is putting healthcare professionals on the road to success for assessing and counseling older drivers. With older adults accounting for 10 percent of all people injured in traffic crashes annually and 17 percent of annual traffic fatalities, the Clinician's Guide to Assessing and Counseling Older Drivers (3rd Edition) translates research findings and public health initiatives into practical, person-centered advice for safely navigating the open road.

17 feb 2016--"For all of us, but for Baby Boomers especially, driving is more than just a national pastime and a means for transportation. It's a reflection of independence, mobility, and freedom," explains Alice Pomidor, MD, MPH, AGSF, chair of the editorial board that developed the AGS-NHTSA guide. "The main goal of this guide is to help healthcare professionals promote health, independence, and quality of life by preventing crashes and injuries."
Added Nancy E. Lundebjerg, MPA, AGS CEO: "This guide reflects the fact that many individuals play a role in older adult well-being, and that expert-authored tools, tips, and recommendations can help all healthcare professionals support high-quality, person-centered care in a key focus area: driver safety."
Reviewed and edited by an interprofessional board of physicians, nurses, social workers, occupational therapists, and pharmacists, the updated guide walks through key issues, opportunities, and challenges faced by older drivers, theirhealthcare professionals, and their caregivers. Areas of emphasis include:

• Determining when an older person may be at an increased risk for unsafe driving. The AGS-NHTSA guide highlights certain "red lights" that clinicians should look for, such as impaired vision or hearing.
• Recognizing medical conditions, functional deficits, and medications that may affect driver safety. Increased longevity in the U.S. population coupled with the number of health conditions older adults manage mean that many older individuals may outlive their ability to drive safely.
• Understanding how to screen and assess functional abilities for driving. Motor skills, sensory perception, vision, and cognition are all important to driving. However, they may not be equally important for a particular older adult: one area of function may warrant greater attention than another on a case-by-case basis.
• Advising older adults about transitioning from driving. Proactively screening frail older adults for driving safety means knowing when to make strategic recommendations and planning for driving retirement beforehand.
• Considering ethical and legal issues affecting older drivers. Laws, regulations, and policies on driving vary not only by state but also by local jurisdiction.
• Meeting the future transportation needs of older adults. Coordination among clinicians, licensing agencies, and relevant state/community entities can help older adults and caregivers become aware of resources once independent driving is no longer an option.

More information: The full guide and collateral tools will be available on GeriatricsCareOnline.org, the online home for AGS resources. Public education materials also will be released by the Health in Aging Foundation onHealthinAging.org.


Provided by American Geriatrics Society

A new tool improves the diagnosis of frailty syndrome

The Telecommunications Engineer Millor-Muruzábal has designed a new measuring tool that provides objective, quantifiable data to improve the diagnosis of frailty syndrome, a set of symptoms that render elderly people more vulnerable. It has been described thus in her Ph.D. thesis, read at the NUP/UPNA-Public University of Navarre, in which she wrote about a novel technology: inertial sensors that she used to analyse the patients' movements.

16 feb 2016--"Experts insist that measuring the state of health of the elderly population needs to be done in terms of function and not disease. So it is crucial to know their functional capacity prior to the development of disability or dependence to be able to mitigate its effects," wrote Millor.
Millor chose frailty syndrome for her work because "those who suffer from it, in particular the elderly, face a greater risk of deterioration in their health and functional state. It is defined as a syndrome because it includes a set of symptoms that in this case render the person with them more vulnerable in the face of any factor," she explained. "Until now, one of the most common methods to diagnose it has been the Fried criterion, which is based on the presence of three or more of these components: slowness in walking, weakness, weight loss, fatigue and low physical activity. So the subjects are classified as frail if they meet three or more criteria; pre-frail if they meet one or two; and healthy if they don't meet any of them."
However, in the view of the new Ph.D. holder, the problem of assessments of this type is that "it is not easy to determine these components and, what is more, the experience of the person who makes the diagnosis plays a significant role, so the result tends to be more qualitative than quantitative."
In order to come up with some objective measurements, Millor studied the frailty syndrome taking as the basis one of the tests used in geriatrics to measure the state of the patients: the 30-second chair test. "Getting up from a chair is one of the activities in daily life that poses the greatest level of mechanical and muscular demand. A proportion of the elderly population has serious difficulties in being able to do this, so they spend more time sitting and their capacity to live independently is reduced," she said. The test is based on the number of times a person is capable of getting up from a chair and sitting down during the thirty seconds the test lasts.

Measuring by means of sensors

Millor used inertial sensors capable of providing information about how a specific moment has been carried out in a way that is "non-invasive, portable and economic." Specifically, they provide data on acceleration (the speed at which the movement varies) and angular speed (how fast a turn is made). "This not only provides data on the amount of movement, but also on how it has been made," said Millor, who received the grade of distinction cum laude.
Millor has specified new parameters from the analysis of the signals provided by the inertial sensors; clinical staff can now avail themselves of "a series of objective, quantifiable measurements to make their diagnoses. In the future, the results could be built into a user-friendly tool such as a mobile app," predicted Millor.


Provided by Elhuyar Fundazioa

Researchers identify 'neurostatin' that may reduce the risk of Alzheimer's disease

Diagram of the brain of a person with Alzheimer's Disease. Credit: Wikipedia/public domain.

Researchers have identified a drug that targets the first step in the toxic chain reaction leading to the death of brain cells, suggesting that treatments could be developed to protect against Alzheimer's disease, in a similar way to how statins are able to reduce the risk of developing heart disease.

13 feb 2016--The drug, which is an approved anti-cancer treatment, has been shown to delay the onset of Alzheimer's disease, both in a test tube and in nematode worms. It has previously been suggested that statin-like drugs - which are safe and can be taken widely by those at risk of developing disease - might be a prospect, but this is the first time that a potential 'neurostatin' has been reported.
When the drug was given to nematode worms genetically programmed to develop Alzheimer's disease, it had no effect once symptoms had already appeared. But when the drug was given to the worms before any symptoms became apparent, no evidence of the condition appeared, raising the possibility that this drug, or other molecules like it, could be used to reduce the risk of developing Alzheimer's disease. The results are reported in the journal Science Advances.
By analysing the way the drug, called bexarotene, works at the molecular level, the international team of researchers, from the University of Cambridge, Lund University and the University of Groningen, found that it stops the first step in the molecular cascade that leads to the death of brain cells. This step, called primary nucleation, occurs when naturally occurring proteins in the body fold into the wrong shape and stick together with other proteins, eventually forming thin filament-like structures called amyloid fibrils. This process also creates smaller clusters called oligomers, which are highly toxic to nerve cells and are thought to be responsible for brain damage in Alzheimer's disease.
"The body has a variety of natural defences to protect itself against neurodegeneration, but as we age, these defences become progressively impaired and can get overwhelmed," said Professor Michele Vendruscolo of Cambridge's Department of Chemistry, the paper's senior author. "By understanding how these natural defences work, we might be able to support them by designing drugs that behave in similar ways."
For the past two decades, researchers have attempted to develop treatments for Alzheimer's that could stop the aggregation and proliferation of oligomers. However, these attempts have all failed, in part because there was not a precise knowledge of the mechanics of the disease's development: Vendruscolo and his colleagues have been working to understand exactly that.
Using a test developed by study co-author Professor Tuomas Knowles, also from the Department of Chemistry, and by Professor Sara Linse, from Lund University, the researchers were able to determine what happens during each stage of the disease's development, and also what might happen if one of those stages was somehow switched off.
"In order to block protein aggregation, we need accurate understanding of exactly what is happening and when," said Vendruscolo. "The test that we have developed not only measures the rates of the process as a whole, but also the rates of its specific component sub-processes, so that we can reduce the toxicity of the aggregates rather than simply stopping them forming."
Johnny Habchi, the first author of the paper, and colleagues assembled a library of more than 10,000 small molecules which interact in some way with amyloid-beta, a molecule that plays a vital role in Alzheimer's disease.
Using the test developed by Knowles and Linse, the researchers first analysed molecules that were either drugs already approved for some other purpose, or drugs developed for Alzheimer's disease or other similar conditions which had failed clinical trials.
The first successful molecule they identified was bexarotene, which is approved by the US Food and Drug Administration for the treatment of lymphoma. "One of the real steps forward was to take a molecule that we thought could be a potential drug and work out exactly what it does. In this case, what it does is suppress primary nucleation, which is the aim for any neurostatin-type molecule," said Vendruscolo. "If you stop the process before aggregation has started, you can't get proliferation."
One of the key advances of the current work is that by understanding the mechanisms of how Alzheimer's disease develops in the brain, the researchers were able to target bexarotene to the correct point in the process.
"Even if you have an effective molecule, if you target the wrong step in the process, you can actually make things worse by causing toxic protein assemblies to build up elsewhere," said study co-author Professor Chris Dobson, Master of St John's College, University of Cambridge. "It's like traffic control - if you close a road to try to reduce jams, you can actually make the situation worse if you put the block in the wrong place. It is not necessarily the case that all the molecules in earlier drug trials were ineffective, but it may be that in some cases the timing of the delivery was wrong."
Earlier studies of bexarotene had suggested that the drug could actually reverse Alzheimer's symptoms by clearing amyloid-beta aggregates in the brain, which received a great deal of attention. However, the earlier results, which were later called into question, were based on a completely different mode of action - the clearance of aggregates - than the one reported in the current study. By exploiting their novel approach, which enables them to carry out highly quantitative analysis of the aggregation process, the researchers have now shown that compounds such as bexarotene could instead be developed as preventive drugs, because its primary action is to inhibit the crucial first step in the aggregation of amyloid-beta.
"We know that the accumulation of amyloid is a hallmark feature of Alzheimer's and that drugs to halt this build-up could help protect nerve cells from damage and death," said Dr Rosa Sancho, Head of Research at Alzheimer's Research UK. "A recent clinical trial of bexarotene in people with Alzheimer's was not successful, but this new work in worms suggests the drug may need to be given very early in the disease. We will now need to see whether this new preventative approach could halt the earliest biological events in Alzheimer's and keep damage at bay in in further animal and human studies."
Over the next 35 years, the number of people with Alzheimer's disease is predicted to go from 40 million to 130 million, with 70% of those in middle or low-income countries. "The only way of realistically stopping this dramatic rise is through preventive measures: treating Alzheimer's disease only after symptoms have already developed could overwhelm healthcare systems around the world."
The body has a number of natural defences designed to keep proteins in check. But as we get older, these processes can become impaired and get overwhelmed, and some proteins can slip through the safety net, resulting in Alzheimer's disease and other protein misfolding conditions. While neurostatins are not a cure for Alzheimer's disease, the researchers say that they could reduce its risk by acting as a backup for the body's natural defences against misfolding proteins.
"You wouldn't give statins to someone who had just had a heart attack, and we doubt that giving a neurostatin to an Alzheimer's patient who could no longer recognise a family member would be very helpful," said Dobson. "But if it reduces the risk of the initial step in the process, then it has a serious prospect of being an effective preventive treatment."
But is there hope for those already affected by the disease? The methods that have led to the present advance have enabled the researchers to identify compounds that, rather than preventing the disease, could slow down its progression even when symptoms have become evident. "The next target of our research is also to be able to treat victims of this dreadful disease," said Vendruscolo.

More information: An anticancer drug suppresses the primary nucleation reaction that produces the toxic Aβ42 aggregates linked with Alzheimer's disease , dx.doi.org/10.1126/sciadv.1501244


Provided by University of Cambridge

Relationships key to mental health recovery, says study

Mental health service users saw the relationships with their care coordinators as being central to their recovery and felt that care plans were largely irrelevant, according to mental health researchers at City University London.

12 feb 2016--The study, published in Health Services & Delivery Research, also found that care coordinators saw care plans as a useful record but also as an inflexible administrative burden that restricted time with service users.
The researchers hope that the research will help improve cumbersome and time consuming care planning processes while enabling mental health workers more time to create meaningful therapeutic relationships, which are currently valued but limited by the focus on bureaucracy.
The study also found that risk remains a significant concern for mental health workers but appeared to be rarely discussed with service users or their carers.
Care planning and coordination is at the heart of effective mental health service delivery and is increasingly required to be personalised and focused on recovery, yet there has been little research conducted that explores these key aspects.
To find out more about how community mental health care was planned and coordinated, the City University London team – in collaboration with Cardiff University and Swansea University - conducted a cross-national comparative study involving six NHS sites in England and Wales that included a survey of 449 service users and 205 care coordinators. They also conducted interviews with 117 managers, practitioners, service users and carers. As part of the process, service users were employed as researchers and advisors.
Speaking about the research, Alan Simpson, Professor of Collaborative Mental Health Nursing in the School of Health Sciences, said:
"Our study has highlighted two very important issues around the delivery of mental health care. Firstly, our study showed that while workers are acutely aware of the need to assess and manage risk, this is rarely discussed openly with service users or their families. This is a missed opportunity to learn from the patient's and family's perspective and to share responsibility in this important area.
"Secondly, there is clearly an issue between how service users see their relationship with care coordinators, and how this is managed. While managers and clinicians clearly see care plans as vital records of care, service users instead said that regular contact and therapeutic relationships with staff help them most in their recovery and time consuming care plans are rarely used.
"The challenge now is for us to work with clinicians and service users to test out new ways of working that maximise therapeutic contact, support collaborative working around risk and reduce the time spent completing lengthy care plan documentation that is rarely used."


Provided by City University London

Social Internet-based activities important for healthy ageing

A steadily increasing amount of everyday activities require access to the Internet, and to achieve increased participation in society, we need to pay attention to an increased inclusion of seniors according to study at Umeå University. Credit: Mostphotos

11 feb 2016--Meaningful and Internet-based activities promote experiences of participation in society and are important for healthy ageing. In a new dissertation at Umeå University in Sweden, occupational therapists are shown to promote participation, reduce experiences of loneliness and strengthen seniors' social network using an Internet-based intervention programme.
"Digitalisation is increasing the risk of excluding seniors who often can have limited experiences of Internet-based activities," says Ellinor Larsson, doctoral student at the Department of Community Medicine and Rehabilitation.
"A steadily increasing amount of everyday activities require access to the Internet, and to achieve increased participation in society, we need to pay attention to an increased inclusion of seniors. The senior citizen can also experience social change at the loss of loved ones, which makes the loneliness more evident. A joint effort focusing on how the well-being of the elderly can be promoted through meaningful Internet-based activities, is becoming more important in order to support the ageing population of today's society."
In her dissertation, which covers interviews and an evaluation of an Internet-based intervention programme, Ellinor Larsson describes how health-promoting efforts aimed at the seniors can be developed. To enable Internet-based social interventions for seniors, a collaboration between several parties in society is needed.
One of the studies showed that seniors who performed daily activities online also sensed a satisfying participation in society. According to the study, the participation in Internet-based activities can be promoted through support and encouragement from people in the person's surroundings, through greater access to technology and by identifying what online activities that are meaningful and important in the senior's everyday life.
The dissertation also shows how an individual and Internet-based occupational therapy intervention was drawn up to support the seniors in the introduction to social Internet-based activities. In an evaluation of the intervention, the participants showed a significant reduction in loneliness. A follow-up study shows that the online social activities constituted a compliment to other social activities and contacts both online and offline.

Provided by Umea University

AGS guidance on diversity proves 'seeing' older patients is about more than seeing age

New guidance from the American Geriatrics Society (AGS) aims to transform approaches to healthcare for our increasingly diverse older population. Developed by a committee of experts in ethnogeriatrics (the study of how ethnicity and culture impact the health and well-being of older people), "Achieving High-Quality Multicultural Geriatric Care" outlines present health disparities and the need for sensitivity to culture and health literacy when working with older individuals. As we look toward a not-so-distant future in 2050 when more than 80 million Americans will be 65-years-old or older, the factors outlined by AGS experts represent aspirational hallmarks of health care for a nation where 'minorities' will soon account for nearly 40 percent of all older adults. Credit: (c) 2016, American Geriatrics Society

10 feb 2016--New guidance from the American Geriatrics Society (AGS) aims to transform approaches to healthcare for our increasingly diverse older population. Developed by a committee of experts in ethnogeriatrics (the study of how ethnicity and culture impact the health and well-being of older people), "Achieving High-Quality Multicultural Geriatric Care" outlines present health disparities and the need for sensitivity to culture and health literacy when working with older individuals. As we look toward a not-so-distant future in 2050 when more than 80 million Americans will be 65-years-old or older, the factors outlined by AGS experts represent aspirational hallmarks of health care for a nation where "minorities" will soon account for nearly 40 percent of all older adults.
"With 10,000 people across the U.S. turning 65 every day, virtually all doctors, nurses, social workers, and other health professionals will soon be caring for older adults—and importantly, older adults who are more diverse than ever before," explains VJ Periyakoil, MD, Chair of the AGS Ethnogeriatrics Committee. "The AGS believes that providing high-quality care for older adults means helping healthcare professionals practice self-awareness, develop interpersonal skills, and become skilled in providing respectful care that meets the unique needs of our richly diverse older adult population," Dr. Periyakoil added.
While health inequities are already well-documented among older people, they are even more pronounced for multi-cultural older Americans. Minority individuals over age 65 have higher rates of disease and disability when compared with Caucasian men and women, for example. Furthermore, of the 36 percent of Americans who report limited health literacy (the ability to obtain, process, and understand basic health information), most are older, less educated, and not white. And as AGS researchers note, mistrust of medicine and medical research remains a persistent barrier to high-quality multicultural care.

New guidance from the American Geriatrics Society (AGS) aims to transform approaches to healthcare for our increasingly diverse older population. Developed by a committee of experts in ethnogeriatrics (the study of how ethnicity and culture impact the health and well-being of older people), 'Achieving High-Quality Multicultural Geriatric Care' outlines present health disparities and the need for sensitivity to culture and health literacy when working with older individuals. As we look toward a not-so-distant future in 2050 when more than 80 million Americans will be 65-years-old or older, the factors outlined by AGS experts represent aspirational hallmarks of health care for a nation where 'minorities' will soon account for nearly 40 percent of all older adults. Credit: (c) 2016, American Geriatrics Society

As outlined by experts in this new AGS position statement, delivering culturally effective care means exploring and being responsive to the unique care needs of each patient during every clinical encounter. Putting processes or systems in place to ensure that patients are asked about their ethnicity, their preferred language, their level of education, and their familiarity with helpful resources like interpreter services, for example, can go a long way toward incorporating an older person's identity into her or his care.
Healthcare professionals themselves also need to become skilled in communicating effectively with people from different backgrounds, particularly since a provider's personal values and beliefs might inadvertently impede care without a healthy dose of self-awareness. The new AGS position statement walks through several questions for self-reflection, each exploring an aspect of personal identity that can impact the complex, coordinated care that many older people need.
"Culturally sensitive care isn't just about language or helping 'someone else.' For a healthcare professional, it's also an honest and deeply personal reflection on the stigmas and health disparities attached to certain groups. It means looking at ways our own personal journeys influence perspective and how we might respond to older people who look different, sound different, need different resources, or approach well-being with unique values and beliefs," said Steven R. Counsell, MD, AGSF, AGS President. "As a tool for recognizing how we are different, this new guidance from the AGS also helps to uncover what we have in common: a desire for care that is high-quality, person-centered, and supportive of the values and expectations that inform who we are."
The new AGS position statement on high-quality multicultural geriatric care was published online ahead of print in the Journal of the American Geriatrics Society, and will be available for free from GeriatricsCareOnline.org, the online home for AGS resources and publications.

New guidance from the American Geriatrics Society (AGS) aims to transform approaches to healthcare for our increasingly diverse older population. Developed by a committee of experts in ethnogeriatrics (the study of how ethnicity and culture impact the health and well-being of older people), 'Achieving High-Quality Multicultural Geriatric Care' outlines present health disparities and the need for sensitivity to culture and health literacy when working with older individuals. As we look toward a not-so-distant future in 2050 when more than 80 million Americans will be 65-years-old or older, the factors outlined by AGS experts represent aspirational hallmarks of health care for a nation where 'minorities' will soon account for nearly 40 percent of all older adults. Credit: (c) 2016, American Geriatrics Society

More information: "Achieving High-Quality Multicultural Geriatric Care" onlinelibrary.wiley.com/doi/10.1111/jgs.13924/pdf


Provided by American Geriatrics Society

Zika virus: Five things to know

Transmission electron micrograph (TEM) of Zika virus. Credit: Cynthia Goldsmith/Centers for Disease Control and Prevention

09 feb 2016--A concise "Five things to know about.... Zika virus infection" article for physicians highlights key points about this newly emerged virus in CMAJ (Canadian Medical Association Journal)
Zika virus is transmitted by Aedes mosquitoes, which are active during the day. They also transmit dengue and chikungunya viruses. Physicians should be alert to symptoms in travellers returning from Central and South America, Mexico and the Caribbean. Zika virus may be linked to Guillain-Barré syndrome and microcephaly in babies born to women infected with Zika virus.
A blood test is used to diagnosis Zika virus infection. Acetaminophen may be used to alleviate pain and fever in affected patients.

More information: Canadian Medical Association Journal, www.cmaj.ca/lookup/doi/10.1503/cmaj.151486


Provided by Canadian Medical Association Journal

ACIP approves 2016 adult immunization schedule

The Advisory Committee on Immunization Practices (ACIP) has approved the recommended adult immunization schedule for 2016. The recommendations are published as a clinical guideline in the Feb. 2 issue of the Annals of Internal Medicine.

06 feb 2016--David K. Kim, M.D., from the U.S. Centers for Disease Control and Prevention in Atlanta, and colleagues present changes to the 2016 adult immunization schedule from the 2015 schedule, based on new ACIP recommendations.
The researchers note that the major changes to the schedule relate to human papillomavirus (HPV), pneumococcal, and serogroup B meningococcal (MenB) vaccines. The nine-valent HPV vaccine was added to the schedule, and can be used for routine vaccination against HPV for males and females. For immunocompetent adults aged 65 years and older, the vaccine interval for 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) was changed from "six to 12 months" to "at least one year." Immunocompromised adults, and those with anatomical or functional asplenia, cerebrospinal fluid leak, or cochlear implant, aged 19 years or older, should receive PPSV23 at least eight weeks after PCV13. All persons aged 10 years and older who are at increased risk for serogroup B meningococcal disease should have the MenB vaccine series.
"Only 29 percent of general internists and 32 percent of family physicians assess their patients' vaccination status at every visit," the authors write. "The health care provider is clearly the central figure in promoting vaccination among adults with high-risk conditions and adults in general."

More information: Full Text

The amyloid protein alpha-synuclein has been visualised in the cell for the first time

State of the protein α-synuclein in living, healthy cells: The central NAC region (grey) is well protected. The protein ensures that no interaction occurs with the cytoplasm (white) and other cell components. In the case of neurodegenerative changes, the grey areas would grow together and form amyloid structures. Credit: Philipp Selenko

03 feb 2016--The protein α-synuclein plays an important role in Parkinson's and other neurodegenerative diseases. Although a considerable amount is known about the structure of the protein within the Parkinson's-typical amyloid deposits, nothing was known about its original state in the healthy cell up to now. Scientists from the Leibniz-Institut für Molekulare Pharmakologie (FMP) in Berlin have now for the first time visualised the protein in healthy cells with the help of high resolution spectroscopic procedures. Surprisingly, they discovered an unstructured state. The new findings, which have appeared in Nature and Nature Communications, represent a milestone for research worldwide: It is now known that the structure of the protein changes dramatically over the course of the disease.
Neurodegenerative diseases such as Parkinson's, Alzheimer's or Huntington's have one thing in common: so-called amyloid aggregates are deposited in the brain. Amyloid is the umbrella term for protein fragments that are produced by the body and that ultimately lead to the demise of nerve cells. The protein α-synuclein is one of the main components of the amyloid aggregates and therefore plays a major role in the development of Parkinson's disease. Much is known about the structural aspects of these aggregates. For example, it is known that α-synuclein has a very concrete structure, which means that it is based on a blueprint that follows a specific pattern. And, in contrast to this, it is known that the isolated, purified protein has no structure whatsoever.
However, up to now, it was not known what α-synuclein looks like inside a healthy cell. And pathological changes can only be fully explained if the original state of the protein is known. Researchers  from the Leibniz-Institut für Molekulare Pharmakologie (FMP) in Berlin have therefore literally taken a closer look at the make-up of the protein in healthy cells. As the first research team worldwide, they succeeded in demonstrating – and visualising – α-synuclein in neuronal and non-neuronal cells. This was made possible by a combination of nuclear magnetic resonance spectroscopy (NMR) and electron paramagnetic resonance spectroscopy (EPR), two procedures that make it possible to characterise the structural configuration of a protein at atomic resolution.

"Now we know the starting point of α-synuclein"

"We discovered the unstructured state that the protein also has in the purified state," explains Dr. Philipp Selenko, Head of the In-cell NMR Spectroscopy research group, the research results published in the specialist journals Nature andNature Communications. "This is actually rather surprising, because it was inconceivable up to now that such an unstructured state can survive at all in a cellular milieu."
However, apparently cells can indeed deal with unstructured proteins. The images published in Nature show how the protein in the healthy cell protects the so-called NAC region from the penetration of foreign molecules. This central region plays a decisive role in the development of highly structured amyloid aggregates. Why the protective properties of the protein are lost in neurodegenerative diseases is one of the core questions with which research will be concerned in the future. "In the diseased state, this protein must change structurally to such an extent that the NAC region becomes accessible for other molecules, so that these regions can accumulate, start to grow and thus form the amyloid structures," suspects the biophysicist Selenko.

Watching the protein change its structure

The findings from Berlin provide the basis for an elucidation of these structural changes. The FMP researchers already have concrete plans for the coming months. With a few tricks, they will create artificially aged cells and introduce theamyloid protein and observe it using the same spectroscopic procedures. The age simulation is performed, because Parkinson's and other neurodegenerative diseases are age-related diseases. Ultimately, the researchers want to construct a state that corresponds to the origin of the disease. "We hope to watch the protein as the protection of the NAC region is gradually lost and how it begins to form amyloid-like structures," says research group leader Selenko.
In the study published in Nature Communications, the team of researchers had already made an exciting discovery in this respect. They had damaged the protein α-synuclein at several points in such a way as is normally the case in an aged cell. The proteinwas then introduced into a young, healthy cell. There, the researchers observed how the cell was able to repair the defects with amazing perfection in some regions, but not in others. The region that could not be repaired was the one that is immensely important for the function of the protein.

The discovery of the cause of the disease is getting closer

In the forthcoming study, the researchers want to gain a comprehensive insight into which defects cause the repair mechanisms to fail and thus prepare the ground for neurodegenerative processes. According to Philipp Selenko, this holds the key to at last finding the cause of the disease and thus one day intervening in the destructive process – with active substances that will then have to be developed on the basis of these findings. "With our discovery of the starting state of the protein, we have taken the decisive first step in this direction," says Selenko.

More information: Francois-Xavier Theillet et al. Structural disorder of monomeric α-synuclein persists in mammalian cells, Nature (2016). DOI: 10.1038/nature16531
Andres Binolfi et al. Intracellular repair of oxidation-damaged α-synuclein fails to target C-terminal modification sites, Nature Communications (2016). DOI: 10.1038/ncomms10251


Provided by Forschungsverbund Berlin e.V. (FVB)