Music activates regions of the brain spared by Alzheimer's disease

Diagram of brain networks involved in processing attention. Credit: Brain Network Lab

30 april 2018--Ever get chills listening to a particularly moving piece of music? You can thank the salience network of the brain for that emotional joint. Surprisingly, this region also remains an island of remembrance that is spared from the ravages of Alzheimer's disease. Researchers at the University of Utah Health are looking to this region of the brain to develop music-based treatments to help alleviate anxiety in patients with dementia. Their research will appear in the April online issue of The Journal of Prevention of Alzheimer's Disease.
"People with dementia are confronted by a world that is unfamiliar to them, which causes disorientation and anxiety" said Jeff Anderson, M.D., Ph.D., associate professor in Radiology at U of U Health and contributing author on the study. "We believe musicwill tap into the salience network of the brain that is still relatively functioning."
Previous work demonstrated the effect of a personalized music program on mood for dementia patients. This study set out to examine a mechanism that activates the attentional network in the salience region of the brain. The results offer a new way to approach anxiety, depression and agitation in patients with dementia. Activation of neighboring regions of the brain may also offer opportunities to delay the continued decline caused by the disease.
For three weeks, the researchers helped participants select meaningful songs and trained the patient and caregiver on how to use a portable media player loaded with the self-selected collection of music.
"When you put headphones on dementia patients and play familiar music, they come alive," said Jace King, a graduate student in the Brain Network Lab and first author on the paper. "Music is like an anchor, grounding the patient back in reality."

The shaded areas of the brain were particularly activated by familiar music. This region is called the supplementary motor area, and is involved in processing attention in the brain. Credit: Brain Network Lab

Using a functional MRI, the researchers scanned the patients to image the regions of the brain that lit up when they listened to 20-second clips of music versus silence. The researchers played eight clips of music from the patient's music collection, eight clips of the same music played in reverse and eight blocks of silence. The researchers compared the images from each scan.
The researchers found that music activates the brain, causing whole regions to communicate. By listening to the personal soundtrack, the visual network, the salience network, the executive network and the cerebellar and corticocerebellar network pairs all showed significantly higher functional connectivity.
"This is objective evidence from brain imaging that shows personally meaningful music is an alternative route for communicating with patients who have Alzheimer's disease," said Norman Foster, M.D., Director of the Center for Alzheimer's Care at U of U Health and senior author on the paper. "Language and visual memory pathways are damaged early as the disease progresses, but personalized music programs can activate the brain, especially for patients who are losing contact with their environment."
However, these results are by no means conclusive. The researchers note the small sample size (17 participants) for this study. In addition, the study only included a single imaging session for each patient. It is remains unclear whether the effects identified in this study persist beyond a brief period of stimulation or whether other areas of memory or mood are enhanced by changes in neural activation and connectivity for the long term.
"In our society, the diagnoses of dementia are snowballing and are taxing resources to the max," Anderson said. "No one says playing music will be a cure for Alzheimer's disease, but it might make the symptoms more manageable, decrease the cost of care and improve a patient's quality of life."


Provided by University of Utah Health

Experimental drug extends survival in progeria

Credit: Progeria Research Foundation

A report from a clinical trial for a drug to treat the rapid-aging disorder progeria, published in this week's Journal of the American Medical Association, offers hope for families with the ultra-rare genetic condition.

Old Before Their Time

28 april 2018--Children with Hutchinson-Gilford Progeria Syndrome have a distinctive appearance, seemingly hurtling towards old age. After an outwardly normal infancy, weight gain slows, hair thins, joints stiffen, and bones weaken. The gums remain smooth, bereft of erupting teeth. Skin wrinkles as the child's chubbiness melts away too quickly, and a cherubic toddler begins to resemble a delicate bird.
Beneath the child's toughening skin, blood vessels stiffen with premature atherosclerosis, fat pockets shrink, and connective tissue hardens. Inside cells, chromosome tips – telomeres – whittle down at a frightening rate, marking time too quickly. But some organs remain healthy, and intellect is spared. The end comes, typically during adolescence, usually from heart failure.
The rapid aging disorder has puzzled physicians at least since the first case was described in 1886. It occurs in only 1 in 4 million births, affecting one in 20 million people.
The Progeria Research Foundation's International Progeria Registry has found 110 living children, and estimates at least 250 others worldwide are undiagnosed. Their work in identifying affected children made the clinical trial possible.
A dominant mutation causes this most serious form of progeria. It arises anew in an affected child. Or, it can affect siblings if a parent has a mosaic gonad and produces some eggs and sperm that have the mutant gene. But progeria isn't passed as an autosomal dominant trait from parent to child, as Huntington's disease is, because people with progeria don't live long enough to have children. Median age at death is 14.6 years.

An oversimplified view of a cell. Nuclear pores are actually complex structures built of many types of proteins.

The discovery of the gene behind progeria, and realization of how a mutation can contort the membrane surrounding a cell's nucleus, provided the critical clue to researchers that a failed pediatric brain cancer drug, lonafarnib, might slow or arrest the course of the rapid-aging illness. Could it extend survival?

Disorganization Inside the Nucleus

The DNA inside a nucleus is only neatly packaged into the familiar X-shaped chromosomes when the cell is on the brink of division. At other times, the 46 chromosomes remain intact, but unwind and rewind around quartets of globular proteins (histones).
The precise position of the DNA spooled around the histones, controlled by a fleet of small organic molecules, determines which genes are "expressed" – that is, transcribed into mRNA in the nucleus and the RNA sent out through nuclear pores into the cytoplasm, where yet other molecules translate the mRNA into a protein. The genetic material with all this other stuff – RNAs and proteins – is called chromatin.
Of course, the DNA must remain in the nucleus. But which parts of the genome contact the inner face of the nuclear membrane affects which genes are turned on or off.
Normally a scaffolding protein, lamin A, places threads of chromatin along the inner face of the nuclear membrane. But for lamin A to adhere DNA threads to the appropriate surfaces, a small organic molecule, farnesyl, must be jettisoned from one end of lamin A.
In progeria, a mutation that affects a specific part of the lamin A gene blocks farnesyl removal. The mutation changes only one DNA base, but that alteration creates a splice site, so that a hunk of the gene isn't represented in the mRNA. As a result, farnesyl stays on lamin A. The protein with the extra part is called progerin.

A cell from a child with progeria collapses in on itself. Credit: PRF

The drug lonafarnib blocks the enzyme that puts farnesyl onto lamin A protein. It was developed to block farnesyl transfer in certain pediatric brain tumors, but had been sidelined because it didn't work. The genius of repurposing the drug was in recognizing the connection between the two diseases at the molecular level.
We all have progerin; the protein slowly accrues as we age. But in progeria, the accumulation is accelerated. And as progerin builds up, it wrecks the cell, from the inside out.
The nucleus undulates and stiffens, affecting the pores that let molecular traffic in and out. DNA replication and RNA transcription go haywire, as the patterns of the molecules clinging to the chromatin change, altering epigenetics. Programmed cell death (apoptosis) hastens.
The trademark rapid cellular aging may emerge as abnormal infoldings of the crinkling nuclear membrane touch the telomeres, accelerating their shrinkage. (With each cell division, copies of the DNA sequence TTAGGG are removed.) It's easy to imagine that the chromosomal tips are the most vulnerable parts of chromatin, like the ends of a shoelace dangling from a hoodie.
This blog, DNA Science, began in 2012 with two posts about progeria. The first post interviewed NIH Director Dr. Francis Collins about his role in the gene's discovery in 2003, start of the Progeria Research Foundation, and the road to repurposing the drug. The gene discovery was key because the lamin A gene was already well-studied; mutations in different parts of the gene impair health in different ways.
The second post described how the drug works and its effects on the cardiovascular system and other symptoms, but not survival. The twice-daily pill stabilized weight loss, thinned arteries and made them more elastic, strengthened bones, and improved hearing.
By the time of the third post at DNA Science, in 2014, hints had begun to emerge that the drug may extend life, by on average of 1.6 years.

Lonafarnib (a farnesyltransferase inhibitor)

This week's report is more than a hint that the drug affects survival. Although the study is observational – the disease's rarity and ethical issues prevent designing a randomized controlled clinical trial – the findings are clear.
Of 63 progeria patients treated with the drug over 2.2 years, 4 died (6.3%). Among 63 untreated controls matched for age, gender, and home continent, 17 died (27%). Children in the untreated group couldn't receive the drug for various practical reasons – distance, or diagnosis after the study had begun. It wasn't denied to set up an experiment.
An accompanying editorial from Fuki Marie Hisama, MD and Junko Oshima, MD, PhD of the University of Washington concludes with a list of the reasons that the study is so compelling for the rare disease community. The progeria story illustrates the value of:

• basic research in understanding the cell and molecular basis of a disease
• patient registries (the one for progeria began in 1886)
• close involvement of patients and their families
• government (NIH) funding
• collaboration among scientists and clinicians in diverse fields

Leslie Gordon, MD, PhD, Medical Director for the Progeria Research Foundation, first author on the JAMA paper, led the team with researchers from Boston Children's Hospital and Brown University. Her son Sam passed away at age 17 in 2014 and brought progeria to the public, most notably in the HBO documentary Life According to Sam.
"This study published in JAMA shows evidence that we can begin to put the brakes on the rapid aging process for children with progeria. These results provide new promise and optimism to the progeria community," Dr. Gordon said in a news release.
It's wonderful to track progress in treating devastating genetic diseases, especially in children.

More information: Leslie B. Gordon et al. Association of Lonafarnib Treatment vs No Treatment With Mortality Rate in Patients With Hutchinson-Gilford Progeria Syndrome, JAMA (2018). DOI: 10.1001/jama.2018.3264

This story is republished courtesy of PLOS Blogs: blogs.plos.org.

Provided by Public Library of Science

Common class of drugs linked to dementia even when taken 20 years before diagnosis

Pill bottle. Credit: CDC/Public domain

The largest and most detailed study of the long-term impact of anticholinergic drugs, a class of drugs commonly prescribed in the United States and United Kingdom as antidepressants and incontinence medications, has found that their use is associated with increased risk of dementia, even when taken 20 years before diagnosis of cognitive impairment.

27 april 2018--An international research team from the US, UK and Ireland analyzed more than 27 million prescriptions as recorded in the medical records of 40,770 patients over age 65 diagnosed with dementia compared to the records of 283,933 older adults without dementia.
The researchers found greater incidence of dementia among patients prescribed anticholinergic antidepressants, anticholinergic bladder medications and anticholinergic Parkinson's disease medications than among older adults who were not prescribed these drugs.
Dementia increased with greater exposure to anticholinergic medications.
"Anticholinergic Medication and Risk of Dementia: Case-control Study" is published in BMJ (formerly the British Medical Journal) an international peer-reviewed medical journal.
"Anticholinergics, medications that block acetylcholine, a nervous system neurotransmitter, have previously been implicated as a potential cause of cognitive impairment," said Regenstrief Institute and Indiana University Center for Aging Research investigator Noll Campbell, PharmD, MS, a co-author of the new BMJ study. "This study is large enough to evaluate the long-term effect and determine that harm may be experienced years before a diagnosis of dementia is made." Dr. Campbell is also an assistant professor of pharmacy practice at Purdue University College of Pharmacy.
"These findings make it clear that clinicians need to carefully consider the anticholinergic burden of their patients and weigh other options," said study co-author Malaz Boustani, M.D., MPH, a Regenstrief Institute and IU Center for Aging Research investigator. Dr. Boustani is the founder of the Indiana Clinical and Translational Science Institute's IU Center for Health Innovation and Implementation Science and the Richard M. Fairbanks Professor of Aging Research at IU School of Medicine.
"Physicians should review all the anticholinergic medications - including over-the-counter drugs - that patients of all ages are taking and determine safe ways to take individuals off anticholinergic medications in the interest of preserving brain health," Dr. Boustani said.
The study, which was led by the University of East Anglia and funded by the Alzheimer's Society, both in the UK, utilized data from the Clinical Practice Research Datalink which includes anonymized diagnosis, referral and prescription records for more than 11 million patients from 674 primary care practices across the UK. The data is broadly representative of the UK population in terms of age, sex and ethnicity.
"This research is really important because there are an estimated 350 million people affected globally by depression. Bladder conditions requiring treatment are estimated to affect over 13 percent of men and 30 percent of women in the UK and US," said study lead researcher George Savva, PhD, visiting researcher at University of East Anglia's School of Health Sciences.
"We don't know exactly how anticholinergics might cause dementia," said study co-author Chris Fox, MD, professor of clinical psychiatry at UEA's Norwich Medical School and a consultant psychiatrist. "Further research is needed to understand possible reasons for this link. In the meantime, I strongly advise patients with any concerns to continue taking their medicines until they have consulted their doctor or pharmacist."
Study co-author Ian Maidment, PhD, senior lecturer in clinical pharmacy at Aston University in the UK, said: "With many medicines having some anticholinergic activity, one key focus should be de-prescribing. Clinical staff, patients and carers need to work together collaboratively to limit the potential harm associated with anticholinergics."

More information: Kathryn Richardson et al. Anticholinergic drugs and risk of dementia: case-control study, BMJ (2018). DOI: 10.1136/bmj.k1315

Editorial: Anticholinergic drugs and dementia in older adults, www.bmj.com/content/361/bmj.k1722


Provided by Regenstrief Institute

Drinking kefir may prompt brain-gut communication to lower blood pressure

Credit: CC0 Public Domain

Drinking kefir may have a positive effect on blood pressure by promoting communication between the gut and brain. Kefir is a fermented probiotic milk beverage known to help maintain the balance of beneficial bacteria in the digestive system. Researchers will present their findings today at the American Physiological Society (APS) annual meeting at Experimental Biology 2018 in San Diego.

26 april 2018--Previous research has shown that an imbalance in the gut's colony of bacteria (microbiota) may cause high blood pressure in some people. Similarly, probiotics—live bacteria supplements that are beneficial to the digestive system—have been found to lower blood pressure, but the mechanisms by which this occurs are unclear.
A research team from Auburn University in Alabama, in collaboration with the University of Vila Velha in Brazil, studied three groups of rats to determine how kefir reduces high blood pressure (hypertension):

• One group had hypertension and was treated with kefir ("treated").
• One group had hypertension and was not treated ("untreated").
• One group had normal blood pressure and was not treated ("control").

After nine weeks of kefir supplementation, the treated rats had lower levels of endotoxins (toxic substances associated with disruption in the cells), lower blood pressure and improved intestinal permeability when compared with the untreated group. Healthy intestines allow some substances to pass through, but generally act as a barrier to keep out harmful bacteria and other potentially dangerous substances. In addition, kefir supplementation restored the natural balance of four different bacteria in the gut and of an enzyme in the brain essential for normal nervous system function, suggesting that the nervous and digestive systems work together to reduce hypertension.
"Our data suggests that kefir antihypertensive-associated mechanisms involve gut microbiota-brain axis communication during hypertension," the researchers wrote.

More information: Mirian Silva-Cutini, of Auburn University, will present "Probiotic kefir antihypertensive effects in spontaneously hypertensive rats involve central and peripheral mechanisms" on Wednesday, April 25, in the Sails Pavilion of the San Diego Convention Center.


Provided by Experimental Biology 2018

Regular nut intake linked to lower risk of heart rhythm irregularity (atrial fibrillation)

Credit: CC0 Public Domain

Eating several servings of nuts every week may help lower the risk of developing the heart rhythm irregularity, atrial fibrillation, also known as heart flutter, finds research published online in the journal Heart.
This level of consumption may also lessen the risk of developing heart failure, although the findings are less consistent, the research indicates.

22 april 2018--Previous studies have suggested that eating nuts regularly is associated with a lower risk of heart disease/stroke and associated death, but it's not clear which particular aspects of cardiovascular disease nut consumption may be linked to.
To explore this in more depth, the researchers drew on the completed Food Frequency Questionnaire responses and lifestyle information from more than 61,000 Swedish 45-83 year olds. Their cardiovascular health was then tracked for 17 years (to the end of 2014) or until death, whichever came first.
People who ate nuts tended to be better educated and to have healthier lifestyles than those who didn't include nuts in their diet. They were less likely to smoke or to have a history of high blood pressure. And they were leaner, more physically active, drank more alcohol and ate more fruit and vegetables.
During the monitoring period, there were 4983 heart attacks, of which 917 were fatal; 3160 cases of heart failure; 7550 cases of atrial fibrillation; 972 cases of aortic valve narrowing; 983 abdominal aortic aneurysms (a bulge or swelling in the aorta, a major artery); and 3782 cases of stroke caused by a blood clot (ischaemic) and 543 caused by a brain bleed (intracerebral haemorrhage).
Nut consumption was associated with a lower risk of heart attack, heart failure, atrial fibrillation and abdominal aortic aneurysm, after taking account of age and sex.
But when several potentially influential known risk factors were accounted for, including lifestyle, general diet, diabetes, and family history, only associations with atrial fibrillation and with heart failure emerged.
The more often nuts were included in the diet, the lower was the associated risk of atrial fibrillation, the findings showed.
Eating a serving of nuts one to three times a month was associated with a lowered risk of just 3 percent, rising to 12 percent when eating them once or twice a week, and to 18 percent when eating them three or more times a week.
The findings for heart failure were less consistent: moderate, but not high, weekly nut consumption was associated with a 20 percent lower risk.
Each additional portion of nuts eaten during the week was associated with a 4 percent lowering in atrial fibrillation risk.
Eating nuts regularly was not associated with a lower risk of the narrowing of the valve serving the heart's largest artery, the aorta, or with the risk of stroke.
This is an observational study, and as such, cannot establish causation. And the researchers emphasise that those who ate nuts had fewer cardiovascular risk factors to start with, which may have affected the findings.
But the strength of the study lies in its large size and the large number of cardiovascular disease cases reported during the monitoring period, they say.
Nuts are a rich source of healthy fats, minerals, and antioxidants, all of which may aid cardiovascular health, they explain.
"Nut consumption or factors associated with this nutritional behaviour may play a role in reducing the risk of atrial fibrillation and possibly heart failure," they write.
And they suggest: "Since only a small proportion of this population had moderate (about 5%) or high (less than 2%) nut consumption, even a small increase in nut consumption may have large potential to lead to a reduction in incidence of atrial fibrillation and heart failure in this population."

More information: Nut consumption and incidence of seven cardiovascular diseases, Heart (2018). heart.bmj.com/lookup/oi/10.113 … heartjnl-2017-312819


Provided by British Medical Journal

Education, not income, the best predictor of a long life

Curve showing the relationship between income and life expectancy in 1970, 1990 and 2010. Credit: Lutz/Kebede

Rising income and the subsequent improved standards of living have long been thought to be the most important factors contributing to a long and healthy life. However, new research from Wolfgang Lutz and Endale Kebede, from IIASA and the Vienna University of Economics and Business (WU) has shown that instead, the level of education a person has is a much better predictor of life expectancy.

20 april 2018--In 1975, Samuel Preston developed the Preston Curve, which plotted the GDP per person on the horizontal axis against life expectancy on the vertical axis. The curve shows a clear but flattening upward trend in life expectancy with increasing GDP. The curves also shift upwards over time which has been explained by better healthcare.
In 1985, John Caldwell and Pat Caldwell suggested instead that lowered mortality resulted from better female education. In their new paper, Lutz and Kebede used global data from 174 countries from 1970-2015 to test the two hypotheses. Whether income or education is more important for improving health and life expectancy is an important question for policymakers deciding where to direct funding.
Lutz and Kebede also plotted life expectancy against the mean years of schooling of the adult population. The curve created is much more linear, suggesting that education is a much better predictor. There is no upward shift of the curve requiring explanation by other factors. Data was subject to multivariate analyses to validate the findings. The same link was found when the curves were adjusted for child mortality.

Curve showing the relationship between education and life expectancy in 1970, 1990 and 2010 Credit: Lutz/Kebede

The researchers point out that better education leads to improved cognition and in turn to better choices for health-related behaviours. Recent decades have seen a shift in the disease burden from infectious to chronic diseases, the latter of which are largely lifestyle-related. As time goes on, the link between education and better health choices, and therefore life expectancy, will become even more apparent.
"This paper is more radical than previous analyses in terms of challenging the ubiquitous view that income and medical interventions are the main drivers of health. It even shows that the empirical association between income and health is largely spurious," says Lutz.
Previous lines of research at the Wittgenstein Centre, a collaboration between IIASA, WU and the Vienna Institute of Demography, have emphasised the importance of improving education for poverty eradication and economic growth, as well as the ability to adapt to climate change. These findings further back up the call for improved access to education.
The apparent link between health and income found by Preston can be explained by the fact that better education results in both better health and higher incomes.
"The findings matter for the entire global health research community, and they matter for everybody in global development and deciding on funding allocations for the different aspects of development," says Lutz, adding that funding quality education for all around the world should be a much higher priority.

More information: Wolfgang Lutz et al, Education and Health: Redrawing the Preston Curve, Population and Development Review (2018). DOI: 10.1111/padr.12141


Provided by International Institute for Applied Systems Analysis

Preventing fractures and falls: Shedding light on the USPSTF's new recommendations

The U.S. Preventive Services Task Force (USPSTF) has released new recommendation statements on preventing fractures and falls in older adults, casting doubt on vitamin D and calcium supplements but advocating for exercise and other interventions. JoAnn Manson, MD, DrPH, chief of the Division of Preventive Medicine at BWH, and Shalender Bhasin, MD, director of the Research Program in Men's Health in the Division of Aging and Metabolism, are coauthors of an editorial published in JAMA accompanying the new guidelines.


18 april 2018--In this issue of JAMA, the USPSTF presents recommendation statements based on comprehensive reviews of the evidence. These include:

• Insufficient evidence to assess the benefit/harm of vitamin D and calcium supplementation for preventing primary fractures in men and postmenopausal women;
• Revision of an earlier, favorable assessment of vitamin D for fall prevention in 2012 to a current recommendation against vitamin D supplementation;
• Recommendation, with moderate evidence, of exercise interventions to prevent falls in adults 65 years and older;
• Recommendation, with lower level of evidence, for multi-factorial interventions, including targeting problems with balance, gait, vision, medication use, blood pressure and other factors that can contribute to increased risk of falls.

Manson and her co-authors provide important context for these recommendations, including the additional health benefits likely to be achieved by a renewed focus on physical activity: "The updated recommendations, which emphasize the importance of exercise, have the potential to prevent injurious falls, the cascade of health problems that often result from such falls, and should improve general health and well-being," commented Manson.
The new guidelines also call for more evidence about whether higher doses of vitamin D may help prevent falls and fractures. This is timely because two large-scale clinical trials, including VITAL, will be announcing findings on this very topic over the next year. In addition, large-scale randomized trials, including STRIDE, are evaluating the effectiveness of multi-factorial interventions in fall prevention.
Manson is a leading authority on women's health whose major research interests include the role of vitamin D in a variety of health conditions and the role of lifestyle factors and clinical interventions in chronic disease prevention. She has led several large-scale prospective cohort studies and randomized clinical trials, including VITAL.
Bhasin is an internationally recognized expert in human aging, clinical trials of function promoting therapies for older adults, functional decline in aging and testosterone biology. He also serves as the director of the NIA-funded Boston Claude D. Pepper Older Americans Independence Center for Function Promoting Therapies at BWH. Bhasin is a also a principal investigator of the STRIDE study.

More information: JAMA (2018). jamanetwork.com/journals/jama/ … .1001/jama.2018.3097


Provided by Brigham and Women's Hospital

In new anthology, experts look to future for managing dementia, mental health

In a newly published collection of research reports and essays , more than 20 experts in aging are looking to the future of science, professional education, clinical practice, and public policy to address two of America's fastest growing health concerns: Dementia and mental health in late life.

17 april 2018--Across 10 articles compiled as a supplement to the Journal of the American Geriatrics Society (JAGS) , field leaders in geriatrics, dementia, and mental health have traced the trajectory of everything from our knowledge of neurological systems contributing to dementia to the development of new interprofessional approaches to teaching and managing late life problems in mental health. In so doing, they hope to chart a course forward for bridging the gap between science and clinical practice, which could transform the prevention and treatment of dementia and mental illness for us all as we age.
"As longer lives become a reality for more and more Americans, so too do concerns about conditions like Alzheimer's disease and other dementias," said Christine Bradway, PhD, CRNP, FAAN, AGSF, Associate Professor of Gerontological Nursing at the School of Nursing, University of Pennsylvania, and Guest Editor for the JAGS supplement. "For those who worry about the impact of increased longevity on memory and mental health, it's important to see forward-facing progress that can give us the science and social supports we need to continue contributing to our communities for as long as possible," added Caroline E. Stephens, PhD, RN, GNP, Associate Professor at the UCSF School of Nursing who led the concept, design, and implementation for the supplement.
Compiled following a two-day summit convened by the National Hartford Center of Gerontological Nursing Excellence and supported by the National Institute on Aging, the new JAGS supplement takes stock of dementia and mental health research and care in its current state, identifies public and professional needs to accelerate change, and reveals promising avenues for moving forward in science, practice, health professions training, and public policy.
The series begins with a paper exploring dementia-associated apathy research (studies that explore how apathy, or a general lack of enthusiasm/concern, is tied to dementia), accompanied by commentary that points to the critical need for enhanced research using novel clinical trial designs and data-sharing platforms.
A second research report and corresponding commentary describe the role of the neural system (the complex connections linking your brain to the rest of your body) in late-life depression and how knowledge of its effects can better shape treatment options and health outcomes.
A third set of papers examines why health systems may be slow to adopt new and promising models of dementia and late-life mental health care and proposes solutions. A final research report and commentary included in the series reimagine collaboration in training multiple healthcare professionals to meet the needs of older Americans, more and more of whom are likely to live with dementia and/or mental health problems as our population continues to age.
The supplement concludes with an outline of critical policy priorities for research, reimbursement, models of care, and clinician/researcher training. Highlighting examples from the Health and Aging Policy Fellows Program—an initiative supported by The Atlantic Philanthropies and the John A. Hartford Foundation to help connect professionals in aging to the legislative processes that make their work possible—this final paper illustrates the essential roles health professionals and academic researchers must play in translating science into social and healthcare systems equipped to support our care, especially as more Americans manage dementia and mental health conditions.
Already impacting millions of Americans 65-years-old and older, forms of "dementia" (including Alzheimer's disease) are characterized by declining mental abilities and deteriorating memory skills severe enough to interfere with daily life. Dementia is also one of several mental health concerns we may face as we age. One in five older adults currently experience mental illnesses like depression, anxiety, or addictive disorders, for example, and the numbers of people affected with these conditions will likely continue to grow. Sadly, many individuals live with undiagnosed or untreated dementia or mental health disorders, which can take an added toll on physical well-being while also increasing the risk for emergency department visits, placement in a nursing home, and other health concerns. As the experts writing in JAGS observe, "Science has made much progress in increasing knowledge about dementia and mental health in later life," and this new anthology of research reports will do much to create "a solid theoretical base, clarity about meanings of mixed findings, and solutions to the challenges of conducting clinical trials, especially for nonpharmacological interventions [treatment/prevention options that do not involve the use of prescription medications]."

More information: Caroline E. Stephens et al, Challenges in Aging, Dementia, and Mental Health: New Knowledge and Energy to Inform Solutions, Journal of the American Geriatrics Society (2018). DOI: 10.1111/jgs.15271


Provided by American Geriatrics Society

Augmented reality app may aid patients with Parkinson's

Rice engineering students have designed an iPhone app to help patients overcome a symptom known as “freezing,” in which the legs temporarily refuse to follow the brain’s command to lift and move forward. In visual mode, the app places a circle or other object over what the camera sees in front of users and encourages them to step into the graphic. Credit: Jeff Fitlow

15 april 2018--It's appropriate that during Parkinson's Awareness Month, a team of Rice University seniors will show how augmented reality may help patients with the disease.
Six Rice engineering students have designed an iPhone app to help patients overcome a symptom known as "freezing," in which the legs temporarily refuse to follow the brain's command to lift and move forward.
For many of these patients, researchers have found that visual, audio or vibratory cues can help them overcome freezing. The Rice app may be the most elegant and comprehensive way to date to provide those cues, according to the students.
The app takes advantage of new programming tools that allow for the incorporation of augmented reality. In this case, the user can point the phone at the floor or sidewalk and trigger it to place the image of a block, circle or other object where his or her foot should land. That visual cue is often enough to allow patients to initiate their gait.
The app can also provide audio or sensory cues through the phone's sound and vibration capabilities. It should be adaptable to Android phones as well, according to the students.
"This is for patients who, in their day-to-day lives, experience freezing episodes," said team member Gaby Perez. "There are a couple of devices on the market to help them, but none of them incorporate all three kinds of cues."

Rice senior engineering student Jeremy David shows the user interface of an iPhone app intended to help patients with Parkinson’s disease maneuver. Credit: Jeff Fitlow

Perez and her Stairway to Stability teammates, Theresa Sonka, Kristen Smith, Keshav Rao, Jeremy David and Dan Burke, all bioengineering majors, took on the challenge as their capstone design project, required of most Rice engineering seniors. They were advised by bioengineering lecturer Eric Richardson with help from Dr. Eugene Lai, a neurologist at Houston Methodist, and sponsorship by Karen and Richard Whitney. The team said client and partial sponsor Nora Bynum was an influential adviser during development of the app.
Their creation is certainly smaller and cheaper than what they referred to as the state of the art for patients, a cane with a laser attachment. "Every time you place the cane down, the laser line pops up in front of you, cueing the user to step over it," Sonka said. "But a lot of the time, these laser solutions have trouble working outdoors."
"What's cool about our project is that the cheapest solutions available right now are about $200, with some solutions costing as much as $3,000," David said. "Our solution, however, has the potential to work more effectively and at a fraction of the cost."
Because some patients may also experience tremors in their hands, the team created a lanyard phone case a patient can wear to make the phone easier to manipulate.
The team worked with the Houston Area Parkinson Society to recruit patients who are helping them test the app at Rice's Oshman Engineering Design Kitchen, Burke said. "Our goal right now is to prove that the concept of augmented reality can be used in a therapeutic context while maintaining the user-friendly nature of smartphones."
"The patients we've talked to are a little on the milder end and are still able to walk, but each one of them has started to see instances of freezing, whether it be just for a few seconds or on the order of minutes," Rao said. "They've each talked about the mental gymnastics they go through to be able to move their feet again. They're very interested in anything that can reduce that burden."
The students appreciate the irony that their solution for people with Parkinson's would make them look like everybody else who walks down the street staring at a cellphone.
"Another big criterion was social comfort," Smith said. "We wanted it to be a very discreet solution."
The team plans to demonstrate the app at the annual George R. Brown School of Engineering Design Showcase April 12 at Rice's Tudor Fieldhouse. The event opens to the public at 4:30 p.m., with the winners of cash prizes announced at 6:30. As many as 80 teams are expected to compete this year.

More information: Follow the team at oedk.rice.edu/Sys/PublicProfile/41416142/4330110


Provided by Rice University

Polypharmacy linked to poorer cognitive, physical capability

Polypharmacy is associated with poorer cognitive and physical capability even after adjustment for disease burden, according to a study published online March 24 in the Journal of the American Geriatrics Society.

10 april 2018--Mark James Rawle, M.B.Ch.B., from University College London, and colleagues conducted a prospective birth cohort study to examine longitudinal correlations between polypharmacy and cognitive and physical capability. An eligible sample of 2,122 men and women with medication data at age 69 years participated.
The researchers found that 18.2 percent of the participants had polypharmacy (five to eight prescribed medications) and 4.7 percent had excessive polypharmacy (nine or more medications) at age 69 years. In models adjusted for sex, education, and disease burden, both polypharmacy and excessive polypharmacy were correlated with poorer cognitive and physical capability, with stronger associations seen for excessive polypharmacy. Stronger negative associations with cognitive and physical capability were seen for participants with polypharmacy at both age 60 to 64 and at age 69 years.
"Future research aiming to improve cognitive and physical capability should consider interventions to reduce the duration and level of polypharmacy at younger ages, in addition to optimizing disease control with appropriate medications," the authors write.

More information: Abstract/Full Text

Poverty increases risk of non-communicable diseases in lower income countries

Poverty increases the risk of death and disability from non-communicable diseases, such as cancer, heart disease, stroke and diabetes in low- and middle-income countries, a new systematic review shows. Researchers also found evidence that developing an NCD increases the risk of falling into poverty in these countries.

07 april 2018--Researchers conducted one of the first comprehensive systematic reviews to assess the relationship between poverty and non-communicable diseases (NCDs) in low- and middle-income countries. Globally, NCDs contribute to more than two-thirds of all deaths and the majority of all early deaths and disability—four-fifths of these deaths due to NCDs occur in low- and middle-income countries.
Published April 4 in The Lancet, the paper is one of five in the journal's Taskforce on NCDs and Economics special series. The research team for this paper was based at Johns Hopkins Bloomberg School of Public Health, icddr,b and the Liverpool School of Tropical Medicine.
For their study, researchers analyzed 283 peer-reviewed studies conducted in low- and middle-income countries in Africa, Asia and Latin America between 1968 and 2017. Their findings show that since 2000, populations with lower socioeconomic status are at an elevated risk of developing NCDs—diabetes, stroke, myocardial infarction (heart attack) and cancer. These populations were also at an elevated risk of NCD risk factors (high BMI, tobacco use, alcohol use and hypertension). Studies conducted before 2000 did not show a clear link between poverty and NCDs.
"Poorer and less educated people are suffering from what once were considered diseases of the rich. In higher income countries, we have known this was the case for some time. Relatively few resources, however, have been invested in this issue in lower income settings," says David Peters, MD, DrPH, MPH, senior author and Edgar Berman Professor and Chair of International Health at Johns Hopkins Bloomberg School of Public Health. "Our findings show that health inequalities have clearly become a double blow to poorer people in low- and middle-income countries. Lack of access to health care and disease prevention efforts puts them at a higher risk of dying from both tuberculosis and lung cancer, for example."
Researchers identified studies that measured both indicators of poverty, such as income and education, and NCDs or their risk factors.
They analyzed the study findings and assigned each study to one of four categories: (1) no association—no evidence of low socioeconomic status (SES) and an elevated NCD risk, (2) mixed or unclear—some results showed low SES elevated the risk of NCDs while others did not, (3) negative association–high SES was associated with higher NCD risk, or (4) positive association–low SES was associated with an elevated NCD risk. After 2000, an increasing majority of studies fell into category 4, showing a growing association between low SES and elevated risk for NCDs and NCD risk factors.
Researchers also found 19 studies that focused on how chronic disease can lead to poverty. These study results suggest that NCDs elevate the risk of becoming poor just as they have been shown to do in higher income countries. Without safety nets, such as insurance or large personal savings, chronic disease can quickly reduce individuals and households to poverty.
"International and national policies and programs, such as universal health coverage, must be implemented to address growing health inequalities," says Peters. "NCDs are an ever-increasing burden for poorer people across the world. Poverty must not be a barrier to access to care."

More information: Louis W Niessen et al. Tackling socioeconomic inequalities and non-communicable diseases in low-income and middle-income countries under the Sustainable Development agenda, The Lancet (2018). DOI: 10.1016/S0140-6736(18)30482-3


Provided by Johns Hopkins University Bloomberg School of Public Health

Regular stretching shown to improve muscles in elderly

Credit: CC0 Public Domain

Daily muscle stretching could bring health benefits to elderly people with reduced mobility, according to new research published today in the Journal of Physiology.

06april 2018--Despite the well-known beneficial effects of exercise, the proportion of elderly people participating in regular exercise programmes is low, often due to the strenuous nature of exercise training. In particular, elderly people with reduced mobility and weak muscles are often less likely to take part in exercise.
Muscle stretching is widely performed as a warm-up or cool-down and is low intensity compared to aerobic exercise. This means that even very old individuals can perform muscle stretching with minimal risk of injury.
Researchers from Florida State University, Kansas State University and the University of Electro-communications in Tokyo found that regular muscular stretching, when performed five times per week, for four weeks, increases blood flow to muscles of the lower leg. They also found that regular muscular stretching improves the function of arteries in the muscles of the lower legs, and increases the number of capillaries within stretched muscles.
This suggests that for individuals with limited mobility, regular muscular stretching could improve blood flow to muscles. This has particularly important implications for elderly people with lower leg problems for whom walking is difficult due to pain or lack of mobility. Additionally, patients with peripheral artery disease and patients with foot or leg problems related to conditions such as diabetes might be able to use muscular stretching to improve blood flow to their lower limbs and increase or regain walking function.
The team carried out the research by placing splints on the lower limb of aged rats so that the calf muscles were stretched while the splint was in place. Splints were placed on one leg for thirty minutes, five days per week, for four weeks. They compared blood flow, arterial function, and the number of capillaries in the muscles of the stretched lower limb to the unstretched, contralateral limb.
Lead researcher on the study, Dr Judy Muller-Delp, Professor of Biomedical Sciences at the Florida State University College of Medicine, said:
"The benefits of exercise are well known, but elderly people with limited mobility are often less likely to take part. Our research suggests that static muscle stretching performed regularly can have a real impact by increasing blood flow to muscles in the lower leg. This highlights that even individuals who struggle to walk due to pain or lack of mobility can undertake activity to possibly improve their health.
"We did not test a range of stretching or a different timeframe for the stretching intervention. It is possible that greater stretch or stretch that increases steadily over the four week period would have an even greater benefit. It is also possible that greater benefit would be seen if the stretching continued for longer than 4 weeks."

More information: Daily muscle stretching enhances blood flow, endothelial function, capillarity, vessel density and connectivity in aged skeletal muscle, Journal of Physiology (2018). DOI: 10.1113/JP275459


Provided by The Physiological Society

Study suggests pasta can be part of a healthy diet without packing on the pounds

Credit: CC0 Public Domain

Carbohydrates get a lot of bad press and blame for the obesity epidemic, but a new study suggests that this negative attention may not be deserved for pasta.
Unlike most 'refined' carbohydrates, which are rapidly absorbed into the bloodstream, pasta has a low glycemic index, meaning it causes smaller increases in blood sugar levels than those caused by eating foods with a high glycemic index.

04 april 2018--Researchers at St. Michael's Hospital undertook a systematic review and meta-analysis of all of the available evidence from randomized controlled trials, the gold standard of research design. They identified 30 randomized control trials involving almost 2,500 people who ate pasta instead of other carbohydrates as part of a healthy low-glycemic index diet. Their results were published today in the journal BMJ Open.
"The study found that pasta didn't contribute to weight gain or increase in body fat," said lead author Dr. John Sievenpiper, a clinician scientist with the hospital's Clinical Nutrition and Risk Modification Centre. "In fact analysis actually showed a small weight loss. So contrary to concerns, perhaps pasta can be part of a healthy diet such as a low GI diet."
The people involved in the clinical trials on average ate 3.3 servings of pasta a week instead of other carbohydrates. One serving equals about one-half cup of cooked pasta. They lost about one-half kilogram over a median follow-up of 12 weeks.
The study authors stressed that these results are generalizable to pasta consumed along with other low-glycemic index foods as part of a low-glycemic index diet. They caution more work is needed to determine if the lack of weight gain will extend to pasta as part of other healthy diets.
"In weighing the evidence, we can now say with some confidence that pasta does not have an adverse effect on body weight outcomes when it is consumed as part of a healthy dietary pattern," said Dr. Sievenpiper.
This work received funding from the Canadian Institutes of Health Research through the Canada-wide Human Nutrition Trialists' Network; the Diet, Digestive Tract and Disease Centre, funded through the Canadian Foundation for Innovation, and the Ministry of Research and Innovation's Ontario Research Fund, among other non-industry sponsors.
Some of the authors have received prior research grants, in-kind donations of pasta for a randomized controlled trial, and travel support from the pasta maker Barilla.


Provided by St. Michael's Hospital

Montreal Parkinson risk of dementia scale deemed accurate

The office-based, eight-item Montreal Parkinson Risk of Dementia Scale is a valid predictor of development of dementia, according to a study published online March 26 in JAMA Neurology.

03 april 2018--Benjamin K. Dawson, from McGill University in Montreal, and colleagues conducted a multicenter study using four diverse Parkinson's disease cohorts with a prospective 4.4-year follow-up to examine the predictive validity of the Montreal Parkinson Risk of Dementia Scale. A total of 717 patients with Parkinson's disease were recruited; 607 were dementia-free at baseline and followed for one year or more.
The researchers found that all eight items of the Montreal Parkinson Risk of Dementia Scale independently predicted the development of dementia (significant at the 5 percent level). In the high-risk group (score >5) the annual conversion rate to dementia was 14.9 percent, compared with 5.8 and 0.6 percent in the intermediate- (score, 4 to 5) and low-risk (score, 0 to 3) groups. Across all cohorts, the overall predictive validity by the area under the receiver operator characteristic curve was 0.877. Sensitivity was 77.1 percent and specificity 87.2 percent for a cut-off of 4 or greater, with positive and negative predictive values of 43.9 and 96.7 percent, respectively; positive and negative likelihood ratios were 5.94 and 0.26, respectively. There were correlations for scale results with makers of Alzheimer's pathology and neuropsychological test results.
"Future studies using head-to-head comparisons or refinement of weighting would be of interest," the authors write.
One author disclosed financial ties to the pharmaceutical industry.

More information: Abstract/Full Text (subscription or payment may be required)

Science Says: What we know about cancer risk and coffee

Trouble is brewing for coffee lovers in California, where a judge ruled that sellers must post scary warnings about cancer risks. But how frightened should we be of a daily cup of joe? Not very, some scientists and available evidence seem to suggest.

02 april 2018--Scientific concerns about coffee have eased in recent years, and many studies even suggest it can help health.
"At the minimum, coffee is neutral. If anything, there is fairly good evidence of the benefit of coffee on cancer," said Dr. Edward Giovannucci, a nutrition expert at the Harvard School of Public Health.
The World Health Organization's cancer agency moved coffee off the "possible carcinogen" list two years ago, though it says evidence is insufficient to rule out any possible role.
The current flap isn't about coffee itself, but a chemical called acrylamide (ah-KRILL-ah-mide) that's made when the beans are roasted. Government agencies call it a probable or likely carcinogen, based on animal research, and a group sued to require coffee sellers to warn of that under a California law passed by voters in 1986.
The problem: No one knows what levels are safe or risky for people. The U.S. Environmental Protection Agency sets acrylamide limits for drinking water, but there aren't any for food.
"A cup of coffee a day, exposure probably is not that high," and probably should not change your habit, said Dr. Bruce Y. Lee of Johns Hopkins Bloomberg School of Public Health. "If you drink a lot of cups a day, this is one of the reasons you might consider cutting that down."
Here's what's known about the risks.
THE CHEMICAL
Start with the biggest known risk factor for cancer—smoking—which generates acrylamide . In the diet, French fries, potato chips, crackers, cookies, cereal and other high-carbohydrate foods contain it as a byproduct of roasting, baking, toasting or frying.
Food and Drug Administration tests of acrylamide levels found they ranged from 175 to 351 parts per billion (a measure of concentration for a contaminant) for six brands of coffee tested; the highest was for one type of decaf coffee crystals. By comparison, French fries at one fast food chain ranged from 117 to 313 parts per billion, depending on the location tested. Some commercial fries had more than 1,000.
Even some baby foods contain acrylamide, such as teething biscuits and crackers. One brand of organic sweet potatoes tested as having 121 parts per billion.
WHAT'S THE RISK?
The "probable" or "likely" carcinogen label is based on studies of animals given high levels of acrylamide in drinking water. But people and rodents absorb the chemical at different rates and metabolize it differently, so its relevance to human health is unknown.
A group of 23 scientists convened by the WHO's cancer agency in 2016 looked at coffee—not acrylamide directly—and decided coffee was unlikely to cause breast, prostate or pancreatic cancer, and that it seemed to lower the risks for liver and uterine cancers. Evidence was inadequate to determine its effect on dozens of other cancer types.
THE CALIFORNIA LAW
Since 1986, businesses have been required to post warnings about chemicals known to cause cancer or other health risks—more than 900 substances are on the state's list today—but what's a "significant" risk is arguable.
Coffee sellers and other defendants in the lawsuit that spurred Thursday's ruling have a couple weeks to challenge it or appeal.
The law "has potential to do much more harm than good to public health," by confusing people into thinking risks from something like coffee are similar to those from smoking, Giovannucci said.
The International Food Information Council and Foundation, an organization funded mostly by the food and beverage industry, says the law is confusing the public because it doesn't note levels of risk, and adds that U.S. dietary guidelines say up to five cups of coffee a day can be part of a healthy diet.
Dr. Otis Brawley, the American Cancer Society's chief medical officer, said, "The issue here is dose, and the amount of acrylamide that would be included in coffee, which is really very small, compared to the amount from smoking tobacco. I don't think we should be worried about a cup of coffee."
Amy Trenton-Dietz, public health specialist at the University of Wisconsin-Madison, said the California ruling contrasts with what science shows.
"Studies in humans suggest that if anything, coffee is protective for some types of cancer," she said. "As long as people are not putting a lot of sugar or sweeteners in, coffee, tea and water are the best things for people to be drinking."