Prediction of conversion to Alzheimer's disease with longitudinal measures and time-to-event data

Predicting the timing of Alzheimer's disease (AD) conversion for individuals with mild cognitive impairment (MCI) can be significantly improved by incorporating longitudinal change information of clinical and neuroimaging markers, in addition to baseline characteristics, according to projections made by investigators from The University of Texas Health Science Center at Houston.

 12 may 2017--In an article published in Journal of Alzheimer's Disease, the research team describes how their novel statistical models found that longitudinal measurements of ADAS-Cog was the strongest predictor for AD progression and the predictive utility was consistently significant with progression of disease.
"The growing public health threat posed by Alzheimer's disease has raised urgency to discover and assess prognostic markers for the early detection of the disease," says Sheng Luo, PhD, senior author of the report. "We assessed the comparative predictive utility of thirty-three longitudinal markers in determining the risk of AD conversion at future time points among individuals with MCI. We found that longitudinal measurements of common cognitive and functional tools can provide more accurate prediction regarding AD conversion than volumetric MRI markers for MCI patients, and markers would show different predictive values at different times in disease progression."
The data used for this study was from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study. It was very well suited for the tasks because of its large samples, long follow-up period, breadth of cognitive markers and biomarkers, and prospective nature. "We simultaneously modeled time-to-dementia as well as longitudinal change in the neuropsychological, neuroimaging, and functional/behavioral variables, using joint modelling for longitudinal and survival data. These longitudinal measures may be highly associated with time-to-dementia, and therefore statistical methods that can model both the longitudinal and the time-to-event components jointly are becoming increasingly essential in most observational studies and clinical trials of neurodegenerative disorders such as AD," remarked Dr. Luo.
"The main contribution of the study," according to the lead author Li, "is that it's the first attempt to comprehensively evaluate the comparative predictive ability of longitudinal markers, both clinical and biological, for timing of AD conversion under the joint model framework. We demonstrated that the imaging and other technology-intensive markers are less powerful than cognitive and functional assessments in the prediction of AD conversion. We expect the markers identified as strong predictors in this study along with the joint modeling approach can serve as a useful tool for continuous monitoring of AD progression and treatment effect in the clinical practice."


Provided by IOS Press

Personalized music may help nursing home residents with dementia

A new study suggests that personalized music has important psychiatric benefits for people with dementia living in nursing homes. 

11 may 2017--Across the country, nursing home employees and families are trying personalized music playlists to help seniors cope with the disorienting, anxious experience of living with Alzheimer's disease and related dementias. Now they can look to the results of the first national study to compare key outcomes in homes that implemented an individualized music program called MUSIC & MEMORY with similar homes that did not adopt the program.
The Brown University evaluation found that after homes adopted the program, residents with dementia became significantly more likely to discontinue antipsychotic and antianxiety medications and significantly less likely to engage in disruptive behaviors, compared to those residing in homes used for comparison. But the study of more than 25,000 residents in 196 nursing homes did not identify a significant improvement in mood.
"This is promising," said co-lead author Rosa Baier, an associate professor of practice at the Brown University School of Public Health. "It's a first step to understanding that there may be improvements that can be attributed to this intervention."
Baier noted that many gerontology experts and advocates for patients have called for ways to reduce the use of antipsychotic and antianxiety medications through a national campaign led by Medicare.
"Providers are looking for non-pharmacologic interventions to address dementia behaviors," she said. "This adds to the evidence base that can help improve patient care for these residents."
The study's findings also reinforce personal reports among caregivers and family members, including those presented in the documentary "Alive Inside," suggesting that personalized music helps patients even when their dementia is highly advanced, said co-lead author Kali Thomas, an assistant professor of health services, policy and practice at Brown. Thomas, who directed the study's evaluation, said her family tried a custom playlist with an uncle with dementia and saw him appear more at ease after listening to his favorite music, including from artists Merle Haggard and Johnny Cash.
"When we put the earphones on him, his breathing relaxed and his grimaced face relaxed," Thomas said.

Measures of music

To better understand how widespread such effects may be and how they might become clinically meaningful, Thomas, Baier and their co-authors designed the new evaluation, published in the American Journal of Geriatric Psychiatry, to test the program's effects with greater national breadth and statistical rigor than previous study designs. The work was part of the mission of Brown's Center for Long-Term Care Quality and Innovation, which tests interventions to improve post-acute and long-term care that appear promising, but haven't yet been rigorously evaluated, said Baier, the center's associate director.
To make their comparison, the team identified 98 nursing homes that had received formal training in the MUSIC & MEMORY program during 2013 and then assembled a list of similar nursing homes—accounting for Medicare quality rating, geography, the age mix of residents and other factors—that did not implement the program. The researchers included in the study all residents in each kind of home who had dementia and cognitive impairment, but who were not receiving hospice care and were not comatose. In all, 12,905 such residents lived in program homes, while 12,811 residents lived in non-program homes.
Using federal Medicare and nursing home data, the researchers then compared the before-2013-and-after changes among residents in each group on four metrics: ending antipsychotic medication, ending antianxiety medication, reductions in disruptive behavior and improvement in mood. While there were no significant differences in mood, here's what they found otherwise:
Antipsychotics: The rate of discontinuing these medications rose to 20.1 percent of program home residents after implementation in 2013 compared to 17.6 percent in a similar period before. By comparison, in non-program homes, the rate stayed flat: 15.2 discontinued after 2013 while 15.9 percent discontinued before.
Antianxiety: The discontinuation rate rose to 24.4 percent after MUSIC & MEMORY implementation in program homes, compared to 23.5 percent before, but in non-program homes the rate fell to 20.0 percent after 2013 compared to 24.8 percent before.
Behavior improvement: The rate of reduction in behavior problems increased to 56.5 percent in program homes from 50.9 percent before the program. In non-program homes the rate stayed flat at 55.9 percent after and 55.8 before.
Behavioral improvements not only help the individual patients, Thomas said, but also enhance quality of life for the residents around them and the morale of nursing home staff.
"Research suggests there is a relationship between nursing staff turnover and residents' behaviors," Thomas said.

The next step

Thomas and Baier acknowledged key limitations in their study. Because they did not track everything each nursing home might be doing to achieve these care improvements, they can't be sure that all the improvements resulted from MUSIC & MEMORY specifically.
On the other hand, because the team didn't know which or how many program home residents actually received the intervention, they had to assume that every eligible resident did. Since it might be that only a fraction of residents on average actually received the interventions in program homes, the results of the study might be understated because they are "diluted" by people who were assumed to receive the intervention but did not.
"In other words, the program may have an even greater impact than reported," Baier said.
To improve their evaluation, Baier, Thomas and their colleagues plan to conduct a second study in which they will randomize some homes to implement the program and some comparison homes to continue without it. By randomizing and collecting data about how the program is implemented, they'll be able to account for the current limitations. They have applied for funding to proceed.

More information: Kali S. Thomas et al, Individualized Music Program is Associated with Improved Outcomes for U.S. Nursing Home Residents with Dementia, The American Journal of Geriatric Psychiatry (2017). DOI: 10.1016/j.jagp.2017.04.008


Provided by Brown University

Lower incidence of chronic illness for centenarians

10 may 2017—Among elderly veterans, the incidence of chronic illness is lower for centenarians than octogenarians and nonagenarians, according to a study published online April 19 in the Journal of the American Geriatrics Society.

Raya Elfadel Kheirbek, M.D., M.P.H., from the Washington D.C. Veterans Affairs Medical Center, and colleagues conducted a retrospective study involving community-dwelling veterans born between 1910 and 1915 who survived to at least age 80 (31,121 octogenarians, 52,420 nonagenarians, and 3,351 centenarians). The authors examined the cumulative incidence of chronic conditions according to age group.
The researchers found that octogenarians had higher incidence rates of chronic illnesses than centenarians did (atrial fibrillation, 15 versus 0.6 percent; heart failure, 19.3 versus 0.4 percent; chronic obstructive pulmonary disease, 17.9 versus 0.6. percent; hypertension, 29.6 versus 3 percent; end-stage renal disease, 7.2 versus 0.1 percent; malignancy, 14.1 versus 0.6 percent; diabetes mellitus, 11.1 versus 0.4 percent; and stroke, 4.6 versus 0.4 percent). Nonagenarians also had higher incidence rates of chronic illnesses than did centenarians (atrial fibrillation, 13.2 versus 3.5 percent; heart failure, 15.8 versus 3.3 percent; chronic obstructive pulmonary disease, 11.8 versus 3.5 percent; hypertension, 27.2 versus 12.8 percent; end-stage renal disease, 11.9 versus 4.5 percent; malignancy, 8.6 versus 2.3 percent; diabetes mellitus, 7.5 versus 2.2 percent; and stroke, 3.5 versus 1.3 percent).
"Centenarians had a lower incidence of chronic illness than those in their 80s and 90s, demonstrating similar compression of morbidity and extension of health span observed in other studies," the authors write.

More information: Abstract
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'Silent seizures' discovered in patients with Alzheimer's disease

On the left is Dr. Alica Goldman and on the right is Dr. Jeffrey Noebels. 

Deep in the brains of two patients with Alzheimer's disease, the main memory structure, the hippocampus, displays episodic seizure-like electrical activity. These non-convulsive hippocampal seizures are the first signs of 'silent' brain electrical network dysfunction described in patients with Alzheimer's disease. 

08 may 2017--The discovery, published in the journal Nature Medicine, provides a better understanding of the condition and can potentially lead to new treatments for this devastating disease affecting more than 5 million people in the U.S.
"About 10 years ago, we were surprised to find 'silent seizures' in mouse models of Alzheimer's disease," said co-senior author Dr. Jeffrey L. Noebels, professor of neurology, neuroscience, and molecular & human genetics, and director of the Blue Bird Circle Developmental Neurogenetics Laboratory at Baylor College of Medicine. "When we measured the animal's brain electrical activity, we detected abnormal electrical discharges in the brain with a seizure-like pattern. The mice, however, did not present with convulsions. These 'clinically silent seizures' in the deep regions of the brain, we speculated, could lead to problems of memory."
It's been reported that in a group of patients with Alzheimer's disease, those that have a history of the disease in their families, convulsive seizures are common, especially in advanced cases. However, for most patients with Alzheimer's the condition does not run in the family. In this group of patients, which are said to present with the sporadic form of the disease, convulsive seizures are typically absent. "For this reason, measuring the brain's electrical activity with an electroencephalogram or EEG test is not required for diagnosis and rarely performed," Noebels said.
Even if the test was performed, previous studies in the epilepsy field had shown that seizures deep in the brain, such as the hippocampal region, cannot be detected with routine scalp EEG recordings. Detecting such brain activity requires placing electrodes deep in the brain.

From mouse model to patients

"My colleagues and I have been interested for years in determining whether 'silent seizures' are present in the hippocampus of patients with Alzheimer's disease," Noebels said. "We were able to answer this question when my colleague and senior co-author Dr. Andrew Cole, director of Massachusetts General Hospital Epilepsy Service and professor of neurology at Harvard Medical School, told me that he had two candidates for the procedure."
Cole and Dr. Alice Lam, first-author of the study and a fellow at Massachusetts General Hospital Epilepsy Service, led the team that performed the test in the patients. They used a minimally invasive recording technique involving fine wires inserted through a small natural opening in the skull. This allowed the researchers to monitor this deep region continuously for several days. Simultaneously, the researchers recorded scalp EEG readings.
In the two patients, who had been diagnosed with Alzheimer's disease and had no previous history of epilepsy or behaviorally obvious seizures, the hippocampal recordings showed clear clinically silent seizures. At the same time, the EEG recordings that had been taken simultaneously showed no abnormal brain activity, confirming that EEG tests do not register changes in deep brain activity.
"What was fascinating was that this activity was present at night when the patients were sleeping, a time thought to be critical for the consolidation of recent memories, a trait that is most impaired in early Alzheimer's disease," Noebels said.
"Based on our observations, we are particularly intrigued by the possibility that 'silent seizure' activity per se could contribute to or accelerate the degenerative process underlying Alzheimer's disease," Cole said.
In addition, Noebels and his Baylor colleague, Dr. Alica Goldman, co-author and associate professor of neurology and neurophysiology, performed genetic analysis on the patients' samples.
"We determined that these two patients did not have a gene known to cause epilepsy. So Alica and I, who have been studying epilepsy genes for a long time, sequenced the patients' samples for the three genes known to be linked to Alzheimer's disease," Noebels said. "It turned out that the patients didn't have those either; they present with the sporadic form of the disease."
"It is very exciting that we were able to move from an observation in genetically engineered mouse models of Alzheimer's to a demonstration of the same phenomenon in patients with verified Alzheimer's disease," said Cole. "This is a critical step toward a better understanding of network dysfunction in the disease and opens the window to novel therapeutic approaches for this common condition."
"From a physician's perspective, I think this work opened my eyes toward the need to look deeper into our patients' condition in order to improve the quality of their lives as well as that of their caregivers," Goldman said. "I think this work offers an opportunity for new investigations that could be relevant for moving forward the clinical practice of Alzheimer's disease."

The need for future studies

"This work with two patients proves the concept that 'silent seizures' can occur in patients with Alzheimer's disease," Noebels said.
"Next, we need to determine whether this finding is common in Alzheimer's disease, present in other types of progressive degenerative neurocognitive diseases, and when in the course of the disease it occurs," Cole said.

More information: Silent hippocampal seizures and spikes identified by foramen ovale electrodes in Alzheimer's disease, Nature Medicine (2017). nature.com/articles/doi:10.1038/nm.4330


Provided by Baylor College of Medicine

Stroke prevention may also reduce dementia

Dr. Vladimir Hachinski is a neurologist at Western University and a scientist at Lawson Health Research Institute in Ontario, Canada. 

05 may 2017--Ontario's stroke prevention strategy appears to have had an unexpected, beneficial side effect: a reduction also in the incidence of dementia among older seniors.
A new paper by researchers at Western University, Lawson Health Research Institute and the Institute for Clinical Evaluative Sciences (ICES) shows there's been a decade-long drop in new diagnoses of both stroke and dementia in the most at-risk group—those who are 80 or older.
"Some have said we're on the cusp of an epidemic of dementia as the population ages," said study author Joshua Cerasuolo, a PhD candidate in epidemiology and biostatistics at Western's Schulich School of Medicine and Dentistry. "What this data suggests is that by successfully fighting off the risks of stroke - with a healthy diet, exercise, a tobacco-free life and high blood-pressure medication where needed - we can also curtail the incidence of some dementias.
"The take-home message is that we can prevent some dementias by preventing stroke," Cerasuolo said.
Published in the journal Alzheimer's & Dementia: The Journal of the Alzheimer's Association, this is the first study that has looked at the demographics of both stroke and dementia across Ontario since the province pioneered Canada's first stroke prevention strategy in 2000. That strategy includes more health centres able to manage stroke, more community and physician supports, better use of hypertensive mediation and well-promoted lifestyle changes to reduce risks. Five provinces have stroke strategies and five do not.
"With lifestyle changes, we can reduce our risks of both stroke and some dementias. That's a pretty powerful one-two punch," said Dr. Vladimir Hachinski a clinical neuroscientist at Western's Schulich School of Medicine and Dentistry, a Lawson Health Research Institute scientist and neurologist at London Health Sciences Centre. He is a world pioneer in stroke research and a co-supervisor of the research paper.
Hachinski said more research needs to take place to understand the specific relationships between stroke and dementia but this work suggests there are policy implications where stroke and dementia work can intersect.
"We have systems in place for stroke prevention and our hypothesis is that any studies looking at stroke prevention should also investigate dementia prevention," Hachinski said. "It's a good-news story for Ontario and it could be a good-news story elsewhere."
Most strokes are caused by the restriction or constriction of blood flow to the brain. Vascular dementia also develops as blood supply to the brain is reduced.
Hachinski said someone who has had a stroke is twice as likely to develop dementia. Someone who has had a diagnosis of stroke has also likely had several prior "silent" strokes that may have affected a patient's cognitive abilities.
The data mining took place using information from ICES, based in Toronto.
Specifically, it shows that the incidence of new stroke diagnosis among highest-risk group, people aged 80-plus, dropped by 37.9 per cent in a span of a little more than a decade. During the same timeframe, the incidence of dementia diagnoses in that age group fell by 15.4 per cent.
"As clinicians and researchers, we are still trying to get a handle on how to reduce a person's chances of dementia late in life. Some we can't influence - yet - but here is a pretty clear indication that we can take specific definitive steps to reduce our chances of dementia related to vascular disease," Hachinski said.

More information: Joshua O. Cerasuolo et al, Population-based stroke and dementia incidence trends: Age and sex variations, Alzheimer's & Dementia (2017). DOI: 10.1016/j.jalz.2017.02.010


Provided by University of Western Ontario

Exercise and vitamin D better together for heart health

Johns Hopkins researchers report that an analysis of survey responses and health records of more than 10,000 American adults for nearly 20 years suggests a "synergistic" link between exercise and good vitamin D levels in reducing the risk of heart attacks and strokes.

01 may 2017--Both exercise and adequate vitamin D have long been implicated in reducing heart disease risks, but in a new study—one not designed to show cause and effect—the researchers investigated the relationship between these two health factors and their joint role in heart health. Their findings, which were published in the April 1 issue of the Journal of Clinical Endocrinology & Metabolism, identified a positive and direct relationship between exercise and vitamin D levels in the blood, which may provide evidence that exercise may boost vitamin D stores. They also found that the two factors working together seemed to somehow do more than either factor alone to protect the cardiovascular system. The researchers caution that their study is an observational one and that long-term, carefully controlled clinical trials would be needed to establish evidence for cause and effect. Nevertheless, the study does support the notion that exposure to the "sunshine" vitamin D and exercise are indicators of good health.
"In our study, both failure to meet the recommended physical activity levels and having vitamin D deficiency were very common" says Erin Michos, M.D., M.H.S., associate director of preventive cardiology and associate professor of medicine at the Ciccarone Center for the Prevention of Heart Disease at the Johns Hopkins University School of Medicine. "The bottom line is we need to encourage people to move more in the name of heart health." Michos adds that exposure to a few minutes a day of sunlight in non-winter seasons, eating a well-balanced meal that includes oily fish such as salmon, along with fortified foods like cereal and milk, may be enough to provide adequate levels of vitamin D for most adults.
For their data analysis, the Johns Hopkins researchers used previously gathered information from the federally funded Atherosclerosis Risk in Communities study beginning in 1987 and collected from 10,342 participants initially free of heart or vascular disease. Information about participants was updated and followed until 2013, and included adults from Forsyth County, North Carolina; Jackson, Mississippi; greater Minneapolis, Minnesota; and Washington County, Maryland. The participants were an average age of 54 at the start of the study and 57 percent were women. Twenty-one percent were African-American, with the remaining participants identifying as white.
In the first visit between 1987 and 1989, participants self-reported their exercise levels, which were compared to the American Heart Association recommendations of more than 150 minutes per week of moderate intensity exercise or 75 minutes per week or more of vigorous intensity. The researchers used the information to classify each participant's exercise level as adequate, intermediate or poor. People with adequate exercise levels met the AHA's recommendations, those with intermediate levels exercised vigorously for up to 74 minutes per week or exercised moderately for less than 149 minutes a week, and those classified as poor didn't exercise at all. About 60 percent of the participants had inadequate exercise in the poor or intermediate categories. The researchers converted the exercise to metabolic equivalent tasks (METs), an exercise intensity scale used by cardiologists and other clinicians to assess fitness. They then calculated physical activity levels by multiplying METs by minutes per week of exercise.
Reviewing data from the second study visit by each participant between 1990 and 1992, the researchers measured vitamin D levels in the blood by detecting the amount of 25-hydroxyvitamin D. Anyone with less than 20 nanograms per milliliter of 25-hydroxyvitamin D was considered deficient for vitamin D, and levels above 20 nanograms per milliliter were considered adequate. Thirty percent of participants had inadequate vitamin D levels.
In the first part of their study, the Johns Hopkins team showed that exercise levels positively corresponded to vitamin D levels in a direct relationship, meaning that the more one exercised, the higher their vitamin D levels seemed. For example, people with adequate exercise had an average 25-hydroxyvitamin D level of 26.6 nanograms per milliliter, those with intermediate exercise had 24.4 nanograms per milliliter, and those with poor exercise had 22.7 nanograms per milliliter. Those meeting recommended levels of exercise at visit 1 had a 31 percent lower risk of being vitamin D deficient at visit 2. Yet, the researchers only saw such a positive relationship between exercise and vitamin D in whites and not African-Americans.
In the next part of the study, they found that the most active participants with the highest vitamin D levels had the lowest risk for future cardiovascular disease. Over the 19 years of the study, 1800 adverse cardiac events occurred, including heart attack, stroke or death due to heart disease or stroke. After adjusting the data for age, sex, race, education, smoking, alcohol use, blood pressure, diabetes, high blood pressure medication, cholesterol levels, statin use and body mass index, the researchers found that those people who met both the recommended activity levels and had vitamin D levels above 20 nanograms per milliliter experienced about a 23 percent less chance of having an adverse cardiovascular event than those people with poor physical activity who were deficient for vitamin D. On the other hand, people who had adequate exercise but were vitamin D deficient didn't have a reduced risk of an adverse event. In other words, the combined benefit of having adequate vitamin D and exercise levels was better than either health factor alone.
But Michos says that sun exposure may not be the whole story of the direct relationship found between exercise and vitamin D levels, since vitamin D produced by the skin after exposure to sunlight tends to level off when the body makes enough, and the levels in these participants didn't show signs of doing so. She says this points to evidence that there may be something else going on in the body that causes vitamin D and exercise to positively influence levels of each other. For example, people who exercise may also have other healthy habits that influence vitamin D levels such as lower body fat and a healthier diet. Alternatively, people who exercise may take more vitamin supplements.
As for the racial disparity they saw, this could mean promoting physical activity may not be as effective for raising vitamin D levels in African-Americans as in whites. Michos notes that people with darker skin produce vitamin D less efficiently after sun exposure, possibly due to the greater amount of melanin pigment, which acts as a natural sunscreen. African-Americans also tend to have lower levels of 25-hydroxyvitamin D overall but they don't seem to experience the same consequences, such as bone fractures, that whites have with similarly low levels.
Michos cautions that people who meet the recommended daily amount of 600 to 800 International Units a day and who have adequate levels of vitamin D don't need to take additional vitamin supplements. "More isn't necessarily better once your blood levels are above 20 nanograms per milliliter," says Michos. "People at risk of bone diseases, have seasonal depression, or are obese should have their physicians measure vitamin D levels to ensure they're adequate, but for many, the best way to ensure adequate blood levels of the vitamin is from sun exposure, healthy diet, being active and maintaining a normal body weight." She adds, "Just 15 minutes of sunlight in the summer produces about 3000 international units of vitamin D depending on latitude and skin pigmentation, which is equivalent to 30 glasses of milk. Just be sure to use sunscreen if you plan to be outside longer than 15 minutes."
While the health boost from regular physical activity is undisputed, the benefits of vitamin D supplements haven't yet been proven for heart health. Michos notes that a recent randomized clinical trial published in JAMA Cardiology failed to show any cardiovascular benefit with high-doses of monthly vitamin D supplements among participants living in New Zealand. She says that larger studies including more diverse populations of patients and different dosing regimens are currently on-going and, when published, will provide further insight and guide recommendations for patients.

More information: Kathleen Chin et al, Physical Activity, Vitamin D, and Incident Atherosclerotic Cardiovascular Disease in Whites and Blacks: The ARIC Study, The Journal of Clinical Endocrinology & Metabolism (2017). DOI: 10.1210/jc.2016-3743


Provided by Johns Hopkins University School of Medicine

A quarter of nursing home residents are colonized with drug-resistant bacteria

The significant presence of multidrug-resistant gram-negative bacteria (MDR-GNB), such as E. coli, among nursing home residents demonstrates the need for heightened infection control prevention and control measures in nursing homes, according to a meta-analysis published in the May issue of the American Journal of Infection Control, the official journal of the Association for Professionals in Infection Control and Epidemiology (APIC).

30 april 2017--The systematic literature review and meta-analysis, conducted by Sainfer Aliyu, MPhil, MSEd, MHPM, BSN, RN, and others at the Columbia University School of Nursing, found the prevalence of MDR-GNB colonization among sampled nursing home residents ranged from 11.2 percent to 59.1 percent, with a pooled average of 27 percent. Researchers also found that nine of the 12 studies involved identi?ed speci?c factors that are associated with increased MDR-GNB colonization risk, including advanced age, gender, comorbid chronic diseases, history of recurrent hospitalization, increased interaction with healthcare workers, frequent antimicrobial exposure, delayed initiation of effective antibiotic therapy, presence of medical devices, decreased functional status, advanced dementia, nonambulatory status, fecal incontinence, severe sepsis present on admission, and residency in a long-term care facility.
The study is thought to be the first systematic review and meta-analysis of its kind, and should raise concerns among infection control professionals and nursing home facilities.
"This study underscores the importance of having strong infection prevention programs in all nursing homes and long-term care facilities," said 2017 APIC President Linda Greene, RN, MPS, CIC, FAPIC. "Understanding the dynamics and cause of MDR-GNB transmission is crucial to identifying effective infection control strategies speci?c to these settings."
Nursing home residents are especially vulnerable to infections due to multiple comorbidities, advanced age, and immune dysfunction. In addition, living in a nursing home is itself considered a risk factor, as frequent transfers from nursing homes to acute care contribute to the in?ux of pathogens into hospital settings. Prevention and management of MDR-GNB in nursing homes are complicated and require extensive infection control resources due to challenges common to this setting such as understaffing, fewer resources, insufficient training, and inadequate surveillance.
"Identifying which patients are most prone to an increased risk of MDR-GNB will enable infection preventionists to tailor efforts and stem future contaminations," wrote Aliyu, et al. "The results of our study suggest that there is much more to be done with regard to infection prevention within nursing homes, and that increased measures must be taken with elderly patients in regard to MDR-GNB colonization."
According to the Centers for Disease Control and Prevention, the percentage of gram-negative bacteria that are resistant to drugs is increasing. MDR-GNB cause serious infections in healthcare settings including pneumonia, bloodstream infections, wound or surgical site infections, and meningitis. They are particularly worrisome because they are becoming resistant to nearly all drugs that would be considered for treatment, with fewer novel antibacterial agents being developed.

More information: Sainfer Aliyu et al, Prevalence of multidrug-resistant gram-negative bacteria among nursing home residents: A systematic review and meta-analysis, American Journal of Infection Control (2017). DOI: 10.1016/j.ajic.2017.01.022


Provided by Elsevier

Study finds new genetic variants associated with extreme old age

The search for the genetic determinants of extreme longevity has been challenging, with the prevalence of centenarians (people older than 100) just one per 5,000 population in developed nations.

29 april 2017--But a recently published study by Boston University School of Public Health and School of Medicine researchers, which combines four studies of extreme longevity, has identified new rare variants in chromosomes 4 and 7 associated with extreme survival and with reduced risks for cardiovascular and Alzheimer's disease.
The results, published in the Journals of Gerontology: Biological Sciences, highlight the importance of studying "truly rare survival, to discover combinations of common and rare variants associated with extreme longevity and longer health span," the authors said.
The research group, led by Paola Sebastiani, professor of biostatistics the BU School of Public Health (BUSPH), created a consortium of four studies—the New England Centenarian Study, the Long Life Family Study, the Southern Italian Centenarian Study, and the Longevity Gene Project - to build a large sample of 2,070 people who survived to the oldest one percentile of survival for the 1900 birth year cohort. The researchers conducted various analyses to discover longevity-associated variants (LAVs), and to characterize those LAVs that differentiated survival to extreme age.
Their analysis identified new "extreme longevity-promoting variants" on chromosomes 4 and 7, while also confirming variants (SNPs, or single nucleotide polymorphisms) previously associated with longevity.
In addition, in two of the datasets where researchers had age-of-onset data for age-related diseases, they found that certain longevity alleles also were significantly associated with reduced risks for cardiovascular disease and hypertension.
"The data and survival analysis provide support for the hypothesis that the genetic makeup of extreme longevity is based on a combination of common and rare variants, with common variants that create the background to survive to relatively common old ages (e.g. into the 80s and 90s), and specific combinations of uncommon and rare variants that add an additional survival advantage to even older ages," the authors wrote.
They said, however, that while the "yield of discovery" in the study was more substantial than in prior genome-wide association studies (GWAS) of extreme longevity, it remained disappointing, in that the two most significant genotypes discovered "are carried by a very small proportion of the cases included in the analysis," meaning that much of the genetic variability around extreme lifespan remains unexplained.
"We expect that many more uncommon genetic variants remain to be discovered through sequencing of centenarian samples," they wrote. "Larger sample sizes are needed to detect association of rare variants... and therefore promising associations that miss the threshold for genome-wide significance are important to discuss."


Provided by Boston University Medical Center

Antidepressant may enhance drug delivery to the brain

Normally, P-glycoprotein prevents most medicines from entering the brain by pumping them back into the blood stream (left). The addition of amitriptyline temporarily turns off P-glycoprotein pumps, allowing drug molecules to cross the blood-brain barrier (right). 

28 april 2017--NIH rat study suggests amitriptyline temporarily inhibits the blood-brain barrier, allowing drugs to enter the brain.
New research from the National Institutes of Health found that pairing the antidepressant amitriptyline with drugs designed to treat central nervous system diseases, enhances drug delivery to the brain by inhibiting the blood-brain barrier in rats. The blood-brain barrier serves as a natural, protective boundary, preventing most drugs from entering the brain. The research, performed in rats, appeared online April 27 in the Journal of Cerebral Blood Flow and Metabolism.
Although researchers caution that more studies are needed to determine whether people will benefit from the discovery, the new finding has the potential to revolutionize treatment for a whole host of brain-centered conditions, including epilepsy, stroke, human amyotrophic lateral sclerosis (ALS), depression, and others. The results are so promising that a provisional patent application has been filed for methods of co-administration of amitriptyline with central nervous system drugs.
According to Ronald Cannon, Ph.D., staff scientist at NIH's National Institute of Environmental Health Sciences (NIEHS), the biggest obstacle to efficiently delivering drugs to the brain is a protein pump called P-glycoprotein. Located along the inner lining of brain blood vessels, P-glycoprotein directs toxins and pharmaceuticals back into the body's circulation before they pass into the brain.
To get an idea of how P-glycoprotein works, Cannon said to think of the protein as a hotel doorman, standing in front of a revolving door at a lobby entrance. A person who is not authorized to enter would get turned away, being ushered back around the revolving door and out into the street.
"For example, as good as vegetables are for us to eat, they have molecules that could be toxic if they slipped into the brain," Cannon said. "They don't get in, because of P-glycoprotein, but this same protector also keeps out helpful therapeutics."
Cannon and his NIEHS colleagues initially found that amitriptyline significantly reduced P-glycoprotein's pump activity in brain capillaries from wild-type rats. Later, they saw amitriptyline had the same effect in brain capillaries from genetically modified rats designed to mimic human ALS. In both rat models, amitriptyline turned off P-glycoprotein within 10-15 minutes. When amitriptyline was removed, P-glycoprotein pump activity returned to full-strength.
NIEHS postbaccalaureate fellow David Banks is lead author on the paper and described amitriptyline's action on P-glycoprotein as rapid and reversible. It's these advantages that make the therapy so appealing.
"Most inventions developed at the bench don't make it to the clinic, but I'm hopeful that our findings will translate into better treatment options for doctors and their patients," Banks said.
Cannon anticipates that administering amitriptyline along with a lower dose of an opioid could relieve pain and reduce the negative side effects, such as constipation and addiction, usually seen with higher doses of prescribed opioids.
"As our nation faces increases in Alzheimer's disease, autism, and opioid abuse, we're hopeful that this discovery will help address these serious health challenges," said NIEHS Director Linda Birnbaum, Ph.D.

More information: David B Banks et al, Lysophosphatidic acid and amitriptyline signal through LPA1R to reduce P-glycoprotein transport at the blood–brain barrier, Journal of Cerebral Blood Flow & Metabolism (2017). DOI: 10.1177/0271678X17705786


Provided by National Institutes of Health

Many patients with Alzheimer's disease discontinue AChEIs

Discontinuation of acetylcholinesterase inhibitors (AChEIs) for treatment of Alzheimer's disease is common, with adverse effects and cost cited as major factors, according to a study published recently in the Journal of the American Geriatrics Society.

27 april 2017--Noll L. Campbell, Pharm.D., from the Purdue University School of Pharmacy in West Lafayette, Ind., and colleagues randomized 196 older adults with a diagnosis of possible or probable Alzheimer's disease who were initiating treatment with an AChEI to one of three AChEIs (1:1:1) for 18 weeks.
In the intent to treat analysis, the researchers found that discontinuation rates at the end of 18 weeks were 38.8 percent for donepezil, 53.0 percent for galantamine, and 58.7 percent for rivastigmine (P = 0.063). Adverse events explained 73.1 percent of discontinuation, while cost explained 25.4 percent. More than 81 percent of participants reported adverse events, but rates were similar between groups.
"This pragmatic comparative trial showed high rates of adverse events and cost-related nonadherence with AChEIs," the authors write.

More information: Abstract
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Suicide and genetics: a complicated association

From Mayo Clinic News Network 

24 april 2017--Dear Mayo Clinic: Why does it seem that suicide tends to run in families? Does it have anything to do with genetics?

A: The association between genetics and suicide is complicated. Research has shown that there is a genetic component to suicide. But it is only one of many factors that may raise an individual's risk. And even if someone is at high risk for suicide, that doesn't predict whether or not an individual will actually act on suicidal thoughts.
Genetic research, including studies involving twins, has revealed that many psychiatric conditions, including having suicidal tendencies, are influenced by genetics. While studies demonstrate that specific genes, such as one called the BDNF Met allele, can increase risk for suicide, it's more likely that a range of genes affect connections and pathways within the brain, and impact suicide risk.
Complicating matters further, a process called epigenetics also comes into play when considering the effect of genes on suicide. This process controls when certain genes are turned on or off as a person grows and develops, and it can be influenced by what happens in a person's environment.
For example, if someone goes through a difficult event as a child, that experience could have an impact on how or when a gene is activated within that person's brain. Researchers speculate that negative experiences influencing epigenetics in a person who has a family history of suicide could further compound that person's suicide risk.
In addition, it is known that 90 percent of people who die by suicide have a psychiatric illness at the time of death. Mood disorders, psychotic disorders, certain personality disorders and substance use disorders can increase suicide risk substantially. Each of those disorders has a genetic component, too.
It's important to understand, however, that an increased risk of suicide does not predict who will commit suicide. For some people - even those whose genetics may seem to predispose them to a higher suicide risk - the thought of suicide doesn't enter their minds. For others, suicide quickly may become a focus of their thoughts.
For those whose thoughts do turn to suicide, the way they arrive at suicidal thoughts may be a well-imprinted and familiar pathway. Psychotherapeutic treatment can help examine the process they go through to get to that point and find ways to interrupt the process.
Genetics, family history and environment all matter when it comes to the risk of suicide. But knowing risk factors is not a substitute for a thorough assessment of an individual's situation and the process he or she takes to arrive at suicidal thoughts.
If you or a loved one are concerned about your risk for suicide, or if you've had suicidal thoughts, talk to a mental health professional. To help you find ways to break the cycle that leads to suicidal thoughts, he or she can work with you to treat any psychiatric illness that may be present and help you understand the process you're going through when you turn to the possibility of suicide.
If you are in a suicide crisis or emotional distress, the National Suicide Prevention Lifeline provides free, confidential emotional support 24/7 at 1-800-273-8255 (toll-free).

Study finds obesity as top cause of preventable life-years lost

A team of researchers from Cleveland Clinic and New York University School of Medicine have found that obesity resulted in as much as 47 percent more life-years lost than tobacco, and tobacco caused similar life-years lost as high blood pressure.

22 april 2017--Preliminary work presented by Cleveland Clinic today at the 2017 Society of General Internal Medicine Annual Meeting analyzed the contribution of modifiable behavioral risk factors to causes-of-death in the U.S. population, using 2014 data.
Based on this preliminary work, the team found the greatest number of preventable life-years lost were due to (in order from greatest to least) obesity, diabetes, tobacco use, high blood pressure and high cholesterol. However, researchers also noted that some individuals may have needs that are very different than those of the broader U.S. population. For an obese and alcoholic patient, for example, alcohol use may be more important to address than obesity, even though obesity has a greater impact on the population.
Results highlight the clinical and public health achievement of smoking cessation efforts because 15 years ago, tobacco would have topped the list.
"Modifiable behavioral risk factors pose a substantial mortality burden in the U.S.," said Glen Taksler, Ph.D., internal medicine researcher from Cleveland Clinic and lead author of the study. "These preliminary results continue to highlight the importance of weight loss, diabetes management and healthy eating in the U.S. population."
A key takeaway is that three (diabetes, hypertension and high cholesterol) of the top five causes of death can be treated, so helping patients understand treatment options and approaches can have a powerful impact on life-years. The results also highlight the importance of preventive care in clinical practice and why it should be a priority for physicians.
To estimate the number of life-years lost to each modifiable risk factor, researchers examined the change in mortality for a series of hypothetical U.S. populations that each eliminated a single risk factor. They compared the results with the change in life-years lost for an "optimal" population that eliminated all modifiable risk factors. Recognizing that some less common factors might place substantial burden on small population subgroups, they also estimated life expectancy gained in individuals with each modifiable risk factor.
"The reality is, while we may know the proximate cause of a patient's death, for example, breast cancer or heart attack, we don't always know the contributing factor(s), such as tobacco use, obesity, alcohol and family history. For each major cause of death, we identified a root cause to understand whether there was a way a person could have lived longer."
Dr. Taksler and colleagues are continuing to conduct research in this area, and analyze and refine results.

More information: Research was presented at The Society of General Internal Medicine 2017 Annual Meeting, "Resilience and Grit: Pursuing Organizational Change & Preventing Burnout in GIM" April 19-22, 2017 in Washington, DC at the Washington Hilton Hotel (1919 Connecticut Avenue, NW Washington, DC 20009).


Provided by Cleveland Clinic

Review finds no benefit to aspirin for preserving cognitive function

An analysis of published studies found no evidence that low- dose aspirin buffers against cognitive decline or dementia or improves cognitive test scores.

21 april 2017--The review and meta-analysis included eight studies with 36,196 participants who were an average of 65 years old and did not have cognitive impairment at baseline. Participants were followed for an average of six years.
"Additional studies are needed to test the possibility that low-dose aspirin has beneficial effects when taken over a longer period and at an earlier age," said Dr. Nicola Veronese, lead author of the Journal of the American Geriatrics Society study.

More information: Nicola Veronese et al, Low-Dose Aspirin Use and Cognitive Function in Older Age: A Systematic Review and Meta-analysis, Journal of the American Geriatrics Society (2017). DOI: 10.1111/jgs.14883

Telestroke guidelines from American Telemedicine Association in Telemedicine and e-Health

Credit: Mary Ann Liebert, Inc., publishers

New guidelines to help clinicians use the latest telemedicine communication technologies to provide remote care for patients with symptoms of acute stroke are published in Telemedicine and e-Health.
Bart Demaerschalk, MD, Mayo Clinic College of Medicine, Phoenix, AZ, and a team of authors contributed to the article entitled "American Telemedicine Association: Telestroke Guidelines."

19 aril 2017-- The guidelines describe the network of audio-visual communication technologies and computer systems available to link an expert stroke team with a stroke physician at a distant site and the clinicians caring for a remote stroke patient, and to deliver telestroke clinical services.
Rapid diagnosis and treatment with a clot-disrupting drug in appropriate patients following ischemic stroke can improve outcomes. The timing of treatment delivery is a critical factor in ischemic stroke.
The coauthors of the new Telestroke Guidelines are from Mayo Clinic College of Medicine (Phoenix), Ascension Health and Columbia College of Nursing (Milwaukee, WI), Medical College of Georgia at Georgia Health Sciences University (Augusta), Yale School of Medicine (New Haven, CT), University of Cincinnati (OH), Massachusetts General Hospital (Boston, MA), University of Pittsburgh (PA), and InTouch Health (Santa Barbara, CA).
"The authors are to be commended for this outstanding work. These guidelines will be of great value to clinicians and the patients they treat," says Charles R. Doarn, MBA, Co-Editor-in-Chief of the Journal and Research Professor of Family and Community Medicine, University of Cincinnati, Ohio.

More information: Bart M. Demaerschalk et al, American Telemedicine Association: Telestroke Guidelines, Telemedicine and e-Health (2017). DOI: 10.1089/tmj.2017.0006


Provided by Mary Ann Liebert, Inc

Major bleeding risk from drugs similar in elderly

The risk of major bleeding is similar for older patients with atrial fibrillation taking either antiplatelet or anticoagulant drugs, according to a review published online April 10 in the Journal of Thrombosis and Haemostasis

18 april 2017--Marc Melkonian, M.D., from the Hôpitaux Universitaires Pitie-Salpêtrière-Charles Foix in France, and colleagues conducted a systematic review and meta-analysis to evaluate major bleeding in randomized and non-randomized controlled trials (RCTs) and parallel cohorts comparing antiplatelet drugs and oral anticoagulants in patients 65 years or older.
Based on seven RCTs (4,550 patients) and four cohort studies (38,649 patients), the researchers found that the risk of major bleeding on aspirin or clopidogrel was equal to that on warfarin in RCTs (relative risk [RR], 1.01; 95 percent confidence interval [CI], 0.69 to 1.48; moderate-quality evidence), lower than on warfarin in non-randomized cohort studies (RR, 0.87; 95 percent CI, 0.77 to 0.99; low-quality evidence), and not different when all studies were combined (RR, 0.86; 95 percent CI, 0.73 to 1.01). Any severity of bleeding (RR, 0.70; 95 percent CI, 0.57 to 0.86) and intracranial bleeding (RR 0.46; 95 percent CI, 0.30 to 0.73) were less frequent on antiplatelet drugs than on warfarin. Major bleeding might be higher with warfarin than aspirin in patients over 80 years old, according to subgroup analysis.
"Elderly patients treated with aspirin or clopidogrel suffer less any-severity bleeding but have a risk of major bleeding similar to that of oral anticoagulants, with the exception of intracranial bleeding," the authors write.

More information: Abstract

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Common sedatives linked to increased risk of pneumonia in people with Alzheimer's disease

Commonly used sedatives called benzodiazepines are associated with an increased risk of pneumonia when used in people with Alzheimer disease, according to a study published in CMAJ (Canadian Medical Association Journal).

17 april 2017--"An increased risk of pneumonia is an important finding to consider in treatment of patients with Alzheimer disease," writes Dr. Heidi Taipale, Kuopio Research Centre of Geriatric Care, University of Eastern Finland, Kuopio, Finland, with coauthors. "Benzodiazepines and Z-drugs are frequently prescribed for this population, and long-term use is typical. Pneumonia often leads to admission to hospital, and patients with dementia are at increased risk of death related to pneumonia."
Dementia, of which 60%-70% of cases are Alzheimer disease, is a risk factor for pneumonia, and many people with dementia are prescribed benzodiazepines and non- benzodiazepines (called Z-drugs), both of which have sedative effects.
To determine if there is a link between these drugs and pneumonia, Finnish researchers looked at data from national registries on 49 484 adults living in the community diagnosed with Alzheimer disease between 2005 and 2011 in Finland. The mean age of participants was 80 years and almost two-thirds (62.7%) were women. They matched 5232 patients taking benzodiazepines and 3269 patients taking Z-drugs with the remainder not taking either drug.
They found that benzodiazepines were linked to a 30% increased risk of pneumonia in patients with Alzheimer disease, and the risk was highest at the start of treatment (during the first 30 days).
Although the association with Z-drug use and pneumonia was not statistically significant, the authors did not conclude these drugs were safer as the study did not directly compare Z-drugs and benzodiazepines.
The authors suggest that the sedative nature of benzodiazepines may increase the risk of pneumonia by increasing the aspiration of saliva or food into the lungs.
The results are consistent with studies that have found an increased risk of pneumonia in patients of all ages taking benzodiazepines.
"Benefits and risks of the use of benzodiazepines should be carefully considered for patients with Alzheimer disease and include risk of pneumonia," the authors conclude.
In a related commentary, Dr. Paula Rochon from Women's College Hospital and the University of Toronto, with coauthors, writes this study "is a good reminder to clinicians to 'first do no harm' when prescribing these drugs for frail older women and men with dementia. Nonpharmacologic approaches should be the starting point when managing neuropsychiatric symptoms in this patient population, which should help to limit inappropriate use of these drugs."


Provided by Canadian Medical Association Journal

Occupational therapy ups functioning in frail seniors

For physically frail older adults, occupational therapy is associated with improved functioning, according to a review published online April 3 in the Journal of the American Geriatrics Society.

16 april 2017--Leen De Coninck, from the KU Leuven in Belgium, and colleagues conducted a systematic review and meta-analysis to examine the effectiveness of occupational therapy for improving performance in daily living activities among community-dwelling physically frail older people. Data were included from nine studies that met the inclusion criteria.
The researchers found that the studies were of reasonable quality with low risk of bias. Significant increases were seen in all primary outcome measures: mobility, functioning in daily living activities, and social participation. The pooled result was a standardized mean difference of −0.30 for functioning in daily living activities, −0.44 for social participation, and −0.45 for mobility. Positive trends were seen for all secondary outcome measures, with a significant correlation for fear of falling. There were no adverse effects for occupational therapy.
"There is strong evidence that occupational therapy improves functioning in community-dwelling physically frail older people," the authors write.

More information: Abstract

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Italian Emma Morano, last known survivor of 19th century, dies at 117

Emma Morano, then 16, is seen in Verbania, North Italy, on May 14, 2016

Emma Morano, an Italian woman believed to have been the oldest person alive and the last survivor of the 19th century, died Saturday at the age of 117, Italian media reported.
Morano, born on November 29 1899, died at her home in Verbania, in northern Italy, the reports said.
"She had an extraordinary life, and we will always remember her strength to move forward in life," the mayor of Verbania was quoted as saying.

16 april 2017--According to the US-based Gerontology Research Group (GRG), Morano ceded the crown of the world's oldest human being to Jamaican Violet Brown, who was born on March 10, 1900.
Morano's death means there is no one living known to have been born before 1900.
Her first love died in World War I, but she married later and left her violent husband just before the Second World War and shortly after the death in infancy of her only son.
She had clung to her independence, only taking on a full-time carer a couple of years ago, though she had not left her small two-room apartment for 20 years.
She had been bed-bound during her latter years.
In an interview with AFP last year, she put her longevity down to her diet.
"I eat two eggs a day, and that's it. And cookies. But I do not eat much because I have no teeth," she said in her home at the time, where the Guinness World Records certificate declaring her to be the oldest person alive held pride of place on a marble-topped chest of drawers.
Her dietary regime has intrigued the medical and scientific worlds.
The eldest of eight children, Morano outlived all of her younger siblings.

Married LGBT older adults are healthier, happier than singles, study finds

Same-sex marriage has been the law of the land for nearly two years—and in some states for even longer—but researchers can already detect positive health outcomes among couples who have tied the knot, a University of Washington study finds.

14 april 2017--For years, studies have linked marriage with happiness among heterosexual couples. But a study from the UW School of Social Work is among the first to explore the potential benefits of marriage among LGBT couples. It is part of a national, groundbreaking longitudinal study with a representative sample of LGBT older adults, known as "Aging with Pride: National Health, Aging, Sexuality/Gender Study," which focuses on how historical, environmental, psychological, behavioral, social and biological factors are associated with health, aging and quality of life.
UW researchers found that LGBT study participants who were married reported better physical and mental health, more social support and greater financial resources than those who were single. The findings were published in a February special supplement of The Gerontologist.
"In the nearly 50 years since Stonewall, same-sex marriage went from being a pipe dream to a legal quagmire to reality—and it may be one of the most profound changes to social policy in recent history," said lead author Jayn Goldsen, research study supervisor in the UW School of Social Work.
Some 2.7 million adults ages 50 and older identify as lesbian, gay, bisexual or transgender—a number that is expected to nearly double by 2060.
Among LGBT people, marriage increased noticeably after a 2015 U.S. Supreme Court ruling legalized same-sex marriage nationwide. A 2016 Gallup Poll found that 49 percent of cohabiting gay couples were married, up from 38 percent before the ruling.
For the UW study, more than 1,800 LGBT people, ages 50 and older, were surveyed in 2014 in locations where gay marriage was already legal (32 states and Washington, D.C.). About one-fourth were married, another fourth were in a committed relationship, and half were single. Married respondents had spent an average of 23 years together, while those in a committed, unmarried relationship had spent an average of 16 years.
Among the study participants, more women were married than men, and of the respondents who were married, most identified as non-Hispanic white.
Researchers found that, in general, participants in a relationship, whether married or in a long-term partnership, showed better health outcomes than those who were single. But those who were married fared even better, both socially and financially, than couples in unmarried, long-term partnerships.
Single LGBT adults were more likely to have a disability; to report lower physical, psychological, social and environmental quality of life; and to have experienced the death of a partner, especially among men.
The legalization of gay marriage at the federal level opens up access to many benefits, such as tax exemptions and Social Security survivor benefits that married, straight couples have long enjoyed. But that does not mean every LGBT couple was immediately ready to take that step.
According to Goldsen, marriage, for many older LGBT people, can be something of a conundrum—even a non-starter. LGBT seniors came of age at a time when laws and social exclusion kept many in the closet. Today's unmarried couples may have made their own legal arrangements and feel that they don't need the extra step of marriage—or they don't want to participate in a traditionally heterosexual institution.
Goldsen also pointed to trends in heterosexual marriage: Fewer people are getting married, and those who do, do so later.
"More older people are living together and thinking outside the box. This was already happening within the LGBT community—couples were living together, but civil marriage wasn't part of the story," she said.
The different attitudes among older LGBT people toward marriage is something service providers, whether doctors, attorneys or tax professionals, should be aware of, Goldsen said. Telling a couple they should get married now simply because they can misses the individual nature of the choice.
"Service providers need to understand the historical context of this population," she said. "Marriage isn't for everyone. It is up to each person, and there are legal, financial and potentially societal ramifications." For example, among the women in the study, those who were married were more likely to report experiencing bias in the larger community.
At the same time, Goldsen said, single LGBT older adults do not benefit from the marriage ruling, and other safeguards, such as anti-discrimination laws in employment, housing and public accommodations, are still lacking at the federal level.
Over time, Goldsen and colleagues will continue to examine the influence of same-sex marriage policy on partnership status and health.

More information: Jayn Goldsen et al, Who Says I Do: The Changing Context of Marriage and Health and Quality of Life for LGBT Older Adults, The Gerontologist (2017). DOI: 10.1093/geront/gnw174


Provided by University of Washington

Weak grip a strong predictor of metabolic disease and disability in adults

A simple test to determine a person's grip strength may be a predictor of developing metabolic disorders in middle or older age, a new cross-continental study has found. 

A simple test to determine a person's grip strength may be a predictor of developing metabolic disorders in middle or older age, a new cross-continental study has found.
The test locations, demographics and methodology all were selected for a reason.

13 april 2017--"Prevalence of chronic disease is highest in the U.S. and China," says Mark Peterson, Ph.D., M.S., FACSM, assistant professor of physical medicine and rehabilitation at Michigan Medicine and a member of the U-M Global Research, Education and Collaboration in Health and Institute for Healthcare Policy and Innovation. "There's a dire need to identify midlife predictors of disability and diabetes in both populations."
Peterson is the lead author on a new study, published in Journals of Gerontology Series A: Medical Sciences, that investigated if normalized grip strength—which is defined as a person's grip strength divided by their body mass—could serve as a biomarker for both cardiometabolic disease and physical disability in American and Chinese adults.
He teamed up with colleagues from the U-M School of Public Health, Michigan Medicine's Global REACH, the Institute for Social Science Survey and the National School of Development at Peking University in Beijing, China.
One reason for the study's geographic focus: "China represents a unique population," Peterson says. "It's the world's largest population of diabetics, which imposes a huge health and economic burden on their entire country."
He adds, "In 2015, China and the U.S. had a combined $320 billion in diabetes-related health care costs, according to the International Diabetes Federation. The aging populations in both countries are growing because of improved medical care of older adults and longer life expectancy. While on one hand that's great, on the other, it represents two populations that have increasing prevalence estimates of diabetes, cardiovascular health issues and functional impairments. The longer people live with those health issues, the greater the burden is to society."

Analyzing data sets

The research team used data on middle-aged and older adults from the U.S. National Health and Nutrition Examination Survey from 2011 to 2012 and 2013 to 2014, and the 2011 portion of the China Health and Retirement Longitudinal Study. These surveys were selected because they included measures of muscle strength capacity and the necessary information pertaining to disability and cardiometabolic diseases.
"We wanted to examine grip strength in particular because it is highly associated with overall body strength," Peterson says. "To asses someone's grip strength using a handgrip dynamometer takes less than 10 seconds, which makes it extremely attractive to adopt in a clinical or community setting at the population level."
The research team analyzed normalized grip strength for 4,544 U.S. and 6,030 Chinese study participants 50 years of age and older. The study group also had blood samples taken for nonfasting glycated hemoglobin and answered a questionnaire about impairments of functional limitation related to mobility. A subsample of 2,225 adults had fasting measures for glucose, insulin and triglycerides.
Using weighted logistic regression models, the team assessed the association between normalized grip strength and diabetes, hyperglycemia, hypertriglyceridemia, low HDL cholesterol, hypertension and physical disability. They controlled for age, sex and numerous socio-demographic characteristics.

A strong connection

Perhaps the largest finding of the study was that low normalized grip strength was greatly associated with both cardiometabolic diseases and physical disabilities in middle-age to older adults, both men and women, and in both the U.S. and Chinese populations.
For every 0.05 decrement in normalized grip strength in U.S. and Chinese adults, respectively, there were:

• 49 percent and 17 percent increased odds for diabetes
• 46 percent and 11 percent increased odds of hyperglycemia
• 15 percent and 11 percent increased odds of hypertriglyceridemia
• 22 percent and 15 percent increased odds of low HDL cholesterol
• 19 percent and 10 percent increased odds of hypertension
• 36 percent and 11 percent increased odds for disability status

Other highlights from the research team included:

• Prevalence of physical disabilities was higher among older adults (65 years old and older) compared to middle-aged adults (50 years old to 64.9 years old) in both populations.
• In U.S. adults, physical disability status, obesity and abdominal obesity were more prevalent, and diabetes prevalence was higher with increasing age in U.S. men.
• In Chinese adults, diabetes prevalence was higher for women than men in both middle-aged and older adults.
• Diabetes was more prevalent in U.S. than Chinese men in both age categories, but more prevalent in Chinese women than U.S. women.
• Normalized grip strength was higher in Chinese men and women than U.S. men and women in both age categories.

Peterson would like to see these research results translated to the clinical setting.
"We hope these findings illustrate how important a simple grip strength test could be in the clinical setting," Peterson says. "It's an easy way to screen and identify people who are at early risk for these health issues."

More information: Journals of Gerontology Series A: Medical Sciences, DOI: 10.1093/gerona/glx031


Provided by University of Michigan

AGA releases best practice advice on long-term PPI use

When proton pump inhibitors (PPIs) are appropriately prescribed, their benefits are likely to outweigh their risks, according to an American Gastroenterological Association (AGA) Clinical Practice Update1 published in Gastroenterology, the official journal of AGA. Additionally, there is currently insufficient evidence to recommend specific strategies for mitigating PPI adverse effects.

12 april 2017--The long-term use of PPIs by patients for gastroesophageal reflux disease (GERD), Barrett's esophagus and non-steroidal anti-inflammatory drug (NSAID) bleeding prophylaxis doubled in the U.S. from 1999 to 2012. Studies have shown that the number of adverse events doubled during the same period. AGA provides best practice advice for the use of PPIs based on expert opinion and relevant publications:
1. Patients with GERD and acid-related complications should take a PPI for short-term healing, maintenance of healing and long-term symptom control.
2. Patients with uncomplicated GERD who respond to short-term PPIs should subsequently attempt to stop or reduce them. Patients who cannot reduce PPIs should consider ambulatory esophageal pH/impedance monitoring before committing to lifelong PPIs to help distinguish GERD from a functional syndrome.
3. Patients with Barrett's esophagus and symptomatic GERD should take a long-term PPI.
4. Asymptomatic patients with Barrett's esophagus should consider a long-term PPI.
5. Patients at high risk for ulcer-related bleeding from NSAIDs should take a PPI, if they continue to take NSAIDs.
6. The dose of long-term PPIs should be periodically reevaluated so that the lowest effective PPI dose can be prescribed to manage the condition.
7. Long-term PPI users should not routinely use probiotics to prevent infection.
8. Long-term PPI users should not routinely raise their intake of calcium, vitamin B12 or magnesium beyond the recommended dietary allowance.
9. Long-term PPI users should not routinely screen or monitor bone mineral density, serum creatinine, magnesium or vitamin B12.
10. Specific PPI formulations should not be selected based on potential risks.

How to Discuss with Patients

It is necessary for health-care professionals to talk with their patients to ensure high-quality patient care. To help patients understand the importance of using PPIs as directed, AGA has developed talking points for health-care professionals to use to help facilitate discussions about the need to correctly use PPIs for condition and symptom management. Learn more at http://www.gastro.org/patient-care/conditions-diseases/gerd/#Talking to Patients.

1 Freedberg DE, Kim LS, Yang YX, The Risks and Benefits of Long-term Use of Proton Pump Inhibitors: Expert Review and Best Practice Advice From the American Gastroenterological Association, Gastroenterology (2016), DOI: 10.1053/j.gastro.2017.01.031.

http://www.gastrojournal.org/article/S0016-5085(17)30091-4/fulltext


Provided by American Gastroenterological Association

Mechanism of aging recovery for progeria patients revealed

'Y-27632' drug inhibits the phosphorylation level of ROCK and increases the oxidative phosphorylation efficiency of mitochondria. 

DGIST's research team has identified a mechanism that can recover the aging of patients with Hutchinson-Gilford Progeria Syndrome (HGPS). DGIST announced that the Chair Professor Park SangChul of New Biology (Head of Well-Aging Research Center) and the research team led by Professor Lee YoungSam has discovered a drug that can improve the aging of HGPS patients and identified the mechanism of aging recovery by using the drug.

05 april 2017--HGPS represents one of premature aging syndromes. The patients with HGPS experience growth retardation as well as age-associated symptoms such as skin wrinkles, hair loss, visual impairment, and cardiovascular diseases. Their average life expectancy is 13 years as they age 10 times faster than others. When it comes to aging control, improvement of biological function and solutions for aging of HGPS patients have been big challenges in academia.
This study needs to be highlighted as the research team has identified the molecular causal relationship between ROCK protein activation and mitochondrial dysfunction in the progression of cell senescence for the first time in the world.
DGIST's research team noted that the level of reactive oxygen species increases when mitochondrial function diminishes during the progression fibroblasts of the HGPS patients. By performing high-throughput screening system, the team found 'Y-27632' as an effective agent to control reactive oxygen species and discovered that this drug is effective in improving mitochondrial function.
Mitochondria are intracellular organelles that play a key role in energy and metabolism in cells. It is known that mitochondrial dysfunction causes aging of cells as it increases level of active oxygen and decreases energy production efficiency.
The research team found that 'Y-27632' drug inhibits the phosphorylation level of ROCK and increases the oxidative phosphorylation efficiency of mitochondria. The study also confirms that the drug recovers mitochondrial function and induces the recovery of aging cells by reducing nuclear membrane degeneration and genetic damage that are characteristics of HGPS patient cells.
The Chair Professor Park SangChul stated "This study is significant as we have newly discovered the means to control aging. We have also identified the mechanism to recover the function of aging cell through inhibition and recovery of mitochondrial dysfunction due to aging." He added "We will continue to carry out studies that will extend the healthy lifespan of humans through the verification of the mechanism in aging animal models as well as progeny animal models."

More information: Hyun Tae Kang et al, Chemical screening identifies ROCK as a target for recovering mitochondrial function in Hutchinson-Gilford progeria syndrome, Aging Cell (2017). DOI: 10.1111/acel.12584


Provided by Daegu Gyeongbuk Institute of Science and Technology

Cow's milk interferes with absorption of thyroid supplement levothyroxine

Taking the common oral thyroid hormone medication levothyroxine with a glass of cow's milk significantly decreases the body's ability to absorb the drug, a preliminary study finds. Results will be presented Sunday at ENDO 2017, the Endocrine Society's 99th annual meeting in Orlando, Fla.

02 april 2017--"These findings support previous research showing that calcium supplements can interfere with levothyroxine absorption," said principal investigator Deborah Chon, M.D., an endocrinology fellow at the UCLA David Geffen School of Medicine and the VA (Veterans Affairs) Greater Los Angeles Healthcare System, Los Angeles, Calif. "Decreased absorption means that patients may not get the full dose of thyroid hormone that they are prescribed."
Although it makes sense that milk, which contains calcium, might interfere with levothyroxine absorption, no study has proved that it does until now, according to Chon.
Levothyroxine is prescribed for patients with an underactive thyroid, called hypothyroidism, to replace the natural thyroid hormone thyroxine (T4) that is too low, or for patients with thyroid cancer, to suppress their thyroid stimulating hormone levels. In 2014, levothyroxine was the most commonly prescribed medication in the U.S., a survey from the IMS Institute for Healthcare Informatics (now QuintilesIMS) found.
Chon and fellow investigators studied 10 adults (six men and four women), with an average age of 33.7 years, who had no known thyroid disease and had normal thyroid hormone function at the start of the study. No one was allergic to cow's milk or levothyroxine, and none of the women were pregnant or using birth control pills.
Participants fasted overnight before each of two study visits, spaced a month apart. At one visit, participants took 1,000 micrograms of oral levothyroxine alone and at the other visit, they took the same dose concurrently with 12 ounces of 2 percent milk. Before dosing and one, two, four and six hours after ingestion of levothyroxine, participants gave blood samples for measurement of their total T4 levels. Chon said they tested with generic levothyroxine, which most of their patients are taking.
The investigators measured the levothyroxine absorption as the concentration of total T4 in the blood plotted on a graphic curve against time after drug administration, called area under the curve. Over the six hours after the participants took levothyroxine, those who consumed milk at the same time as the medicine had significantly lower total T4 absorption than when they took the drug alone: average area under the curve of 67.3 versus 73.5.
The manufacturer of a brand of levothyroxine recommends that the medication be taken preferably on an empty stomach, 30 to 60 minutes before eating food or taking other medications or vitamins.
"The main message of this study is that patients managed with thyroid hormone replacement therapy should be advised to avoid taking levothyroxine simultaneously with cow's milk, given its interference," Chon said.


Provided by The Endocrine Society

Brain changes in older adults increase risk for scams

Older adults who have been scammed by friends, relatives or strangers seem to behave just like elders who have avoided rip-offs. They are able to balance their checkbooks. They can remember and evaluate information. Their personalities are normal, and their arithmetic is fine.
But their brains are different.

01 april 2017--For the first time, researchers have found a biological basis for financial exploitation in the elderly. The team is led by a Cornell scientist with collaborators at York University in Toronto.
The exploited older people in their study had more atrophy and less connectivity in two key areas of the brain. One region signals a person when something significant is happening around them, and the other tells them how to read social cues, like other people's intentions. The team published their work March 28 in the Journals of Gerontology.
Together, these age-related changes in the brain may make older adults more vulnerable to financial exploitation – especially when one considers that family members are the most common perpetrators of financial abuse, said the study's lead author, Nathan Spreng, assistant professor of human development and a Rebecca Q. and James C. Morgan Sesquicentennial Faculty Fellow.
"It's not their fault they've been abused. It's not because they made a bad decision. There are biological reasons why these abuses have occurred, and we're trying to get a handle on that," said Spreng, who directs Cornell's Laboratory of Brain and Cognition.
"Older adults are having a harder time navigating these tough social situations. We need to start treating this as a medical problem and not a societal one," he added.
Previous studies have shown that family members are the most common financial abusers. In the study, a grandson continued to steal from a study participant even after she confronted him. A daughter charged $2,000 to a study participant's account without permission. In another instance, a son's girlfriend borrowed $4,000 and never paid it back.
Nearly one in 20 older adults can expect to be financially exploited beyond age 60, an incidence rate that is higher than many age-related diseases like cardiovascular disease, cancer and arthritis.
But this area is not very well studied, Spreng said, because many older adults are unaware or unwilling to report exploitation, embarrassed to reveal they have been scammed or want to protect their privacy. "It's hard to get scientific traction," Spreng said.
He and his colleagues tested 26 older adults, half of whom had been robbed by family members or neighbors or scammed online or by phone. The other half had been exposed to a rip-off scheme but had recognized and avoided it.
The researchers did extensive behavioral tests on both groups to see if they behaved differently. Using 45 assessments, they measured the study participants' memory, ability to pay attention to information and evaluate it, inhibitory control, aspects of personality and financial reasoning.
The only difference in behavior between the two groups was exploited elders reported feeling more anger and hostility.
But more significant differences showed up in the brain images.
The exploited elders had atrophy in the anterior insula and fewer connections from it to a broader brain network. The anterior insula signals when something salient is happening in the environment. In general, this area isn't as responsive in older adults compared with the young, particularly in negative situations, Spreng said.
"If older adults are, say, gambling, they get the same excitement that they might win something as younger adults do, but they don't have the same feeling of dread or disappointment for the losses. So, they're not as sensitive to losing money," he said.
This region was particularly atrophied in the study's exploited group, suggesting that the brain wasn't signaling they were facing a risky situation.
The exploited elders also had more atrophy and fewer neural connections in the medial prefrontal cortex, which helps us appraise social situations, like inferring the thoughts or intentions of others.
Surprisingly, the networks of the anterior insula and the medial prefrontal cortex were more connected to each other. This suggests that poor sensitivity to financial risk combined with reduced detection of untrustworthiness may leave older adults vulnerable to scams.
More, larger studies are needed to validate the neural mechanism, but this study could be a first step in identifying a way to predict who might be vulnerable to financial exploitation, Spreng said.
The time is right, Spreng said, because the current generation of elders is the wealthiest ever.
"There's a huge amount of money locked up in our elders' assets," he said. "And people are actively pursuing them."

More information: R. Nathan Spreng et al. Financial Exploitation Is Associated With Structural and Functional Brain Differences in Healthy Older Adults, The Journals of Gerontology: Series A (2017). DOI: 10.1093/gerona/glx051


Provided by Cornell University