Truly smart homes could help dementia patients live independently

by Dorothy Monekosso, The Conversation

Credit: PixOfPop/Shutterstock

You might already have what's often called a "smart home," with your lights or music connected to voice-controlled technology such as Alexa or Siri. But when researchers talk about smart homes, we usually mean technologies that use artificial intelligence to learn your habits and automatically adjust your home in response to them. Perhaps the most obvious example of this are thermostats that learn when you are likely to be home and what temperature you prefer, and adjust themselves accordingly without you needing to change the settings.

26 sept 2019--My colleagues and I are interested in how this kind of true smart home technology could help people with dementia. We hope it could learn to recognize the different domestic activities a dementia sufferer carries out throughout the day and help them with each one. This could even lead up to the introduction of household robots to automatically assist with chores.

The growing number of people with dementia is encouraging care providers to look to technology as a way of supporting human carers and improving patients' quality of life. In particular, we want to use technology to help people with dementia live more independently for as long as possible.

Dementia affects people's cognitive abilities (things like perception, learning, memory and problem-solving skills). There are many ways that smart home technology can help with this. It can improve safety by automatically closing doors if they are left open or turning off cookers if they are left unattended. Bed and chair sensors or wearable devices can detect how well someone is sleeping or if they have been inactive for an unusual amount of time.

Lights, TVs and phones can be controlled by voice-activated technology or a pictorial interface for people with memory problems. Appliances such as kettles, fridges and washing machines can be controlled remotely.

People with dementia can also become disoriented, wander and get lost. Sophisticated monitoring systems using radiowaves inside and GPS outside can track people's movements and raise an alert if they travel outside a certain area.

All of the data from these devices could be fed in to complex artificial intelligence that would automatically learn the typical things people do in the house. This is the classic AI problem of pattern matching (looking for and learning patterns from lots of data). To start with, the computer would build a coarse model of the inhabitants' daily routines and would then be able to detect when something unusual is happening, such as not getting up or eating at the usual time.

A finer model could then represent the steps in a particular activity such as washing hands or making a cup of tea. Monitoring what the person is doing step by step means that, if they forget halfway through, the system can remind them and help them continue.

Future smart homes could include robot carers. Credit: Miriam Doerr Martin Frommherz/Shutterstock

The more general model of the daily routine could use innocuous sensors such as those in beds or doors. But for the software to have a more detailed understanding of what is happening in the house you would need cameras and video processing that would be able to detect specific actions such as someone falling over. The downside to these improved models is a loss of privacy.

The smart home of the future could also come equipped with a humanoid robot to help with chores. Research in this area is moving at a steady, albeit slow, pace, with Japan taking the lead with nurse robots.

The biggest challenge with robots in the home or care home is that of operating in an unstructured environment. Factory robots can operate with speed and precision because they perform specific, pre-programmed tasks in a purpose-designed space. But the average home is less structured and changes frequently as furniture, objects and people move around. This is a key problem which researchers are investigating using artificial intelligence techniques, such as capturing data from images (computer vision).

Robots don't just have the potential to help with physical labor either. While most smart home technologies focus on mobility, strength and other physical characteristics, emotional well-being is equally important. A good example is the PARO robot, which looks like a cute toy seal but is designed to provide therapeutic emotional support and comfort.

Understanding interaction

The real smartness in all this technology comes from automatically discovering how the person interacts with their environment in order to provide support at the right moment. If we just built technology to do everything for people then it would actually reduced their independence.

For example, emotion-recognition software could judge someone's feelings from their expression could adjust the house or suggest activities in response, for example by changing the lighting or encouraging the patient to take some exercise. As the inhabitant's physical and cognitive decline increases, the smart house would adapt to provide more appropriate support.

There are still many challenges to overcome, from improving the reliability and robustness of sensors, to preventing annoying or disturbing alarms, to making sure the technology is safe from cybercriminals. And for all the technology, there will always be a need for a human in the loop. The technology is intended to complement human carers and must be adapted to individual users. But the potential is there for genuine smart homes to help people with dementia live richer, fuller and hopefully longer lives.

Provided by The Conversation 

This article is republished from The Conversation under a Creative Commons license. Read the original article.

First systematic review and meta-analysis suggests AI may be as effective as health professionals at diagnosing disease

by Lancet

Credit: CC0 Public Domain

Artificial intelligence (AI) appears to detect diseases from medical imaging with similar levels of accuracy as health-care professionals, according to the first systematic review and meta-analysis, synthesising all the available evidence from the scientific literature published in The Lancet Digital Health journal.

26 sept 2019--Nevertheless, only a few studies were of sufficient quality to be included in the analysis, and the authors caution that the true diagnostic power of the AI technique known as deep learning—the use of algorithms, big data, and computing power to emulate human learning and intelligence—remains uncertain because of the lack of studies that directly compare the performance of humans and machines, or that validate AI's performance in real clinical environments.

"We reviewed over 20,500 articles, but less than 1% of these were sufficiently robust in their design and reporting that independent reviewers had high confidence in their claims. What's more, only 25 studies validated the AI models externally (using medical images from a different population), and just 14 studies actually compared the performance of AI and health professionals using the same test sample," explains Professor Alastair Denniston from University Hospitals Birmingham NHS Foundation Trust, UK, who led the research.

"Within those handful of high-quality studies, we found that deep learning could indeed detect diseases ranging from cancers to eye diseases as accurately as health professionals. But it's important to note that AI did not substantially out-perform human diagnosis."

With deep learning, computers can examine thousands of medical images to identify patterns of disease. This offers enormous potential for improving the accuracy and speed of diagnosis. Reports of deep learning models outperforming humans in diagnostic testing has generated much excitement and debate, and more than 30 AI algorithms for healthcare have already been approved by the US Food and Drug Administration.

Despite strong public interest and market forces driving the rapid development of these technologies, concerns have been raised about whether study designs are biased in favour of machine learning, and the degree to which the findings are applicable to real-world clinical practice.

To provide more evidence, researchers conducted a systematic review and meta-analysis of all studies comparing the performance of deep learning models and health professionals in detecting diseases from medical imaging published between January 2012 and June 2019. They also evaluated study design, reporting, and clinical value.

In total, 82 articles were included in the systematic review. Data were analysed for 69 articles which contained enough data to calculate test performance accurately. Pooled estimates from 25 articles that validated the results in an independent subset of images were included in the meta-analysis.

Analysis of data from 14 studies comparing the performance of deep learning with humans in the same sample found that at best, deep learning algorithms can correctly detect disease in 87% of cases, compared to 86% achieved by health-care professionals.

The ability to accurately exclude patients who don't have disease was also similar for deep learning algorithms (93% specificity) compared to health-care professionals (91%).

Importantly, the authors note several limitations in the methodology and reporting of AI-diagnostic studies included in the analysis. Deep learning was frequently assessed in isolation in a way that does not reflect clinical practice. For example, only four studies provided health professionals with additional clinical information that they would normally use to make a diagnosis in clinical practice. Additionally, few prospective studies were done in real clinical environments, and the authors say that to determine diagnostic accuracy requires high-quality comparisons in patients, not just datasets. Poor reporting was also common, with most studies not reporting missing data, which limits the conclusions that can be drawn.

"There is an inherent tension between the desire to use new, potentially life-saving diagnostics and the imperative to develop high-quality evidence in a way that can benefit patients and health systems in clinical practice," says Dr. Xiaoxuan Liu from the University of Birmingham, UK. "A key lesson from our work is that in AI—as with any other part of healthcare—good study design matters. Without it, you can easily introduce bias which skews your results. These biases can lead to exaggerated claims of good performance for AI tools which do not translate into the real world. Good design and reporting of these studies is a key part of ensuring that the AI interventions that come through to patients are safe and effective."

"Evidence on how AI algorithms will change patient outcomes needs to come from comparisons with alternative diagnostic tests in randomised controlled trials," adds Dr. Livia Faes from Moorfields Eye Hospital, London. "So far, there are hardly any such trials where diagnostic decisions made by an AI algorithm are acted upon to see what then happens to outcomes which really matter to patients, like timely treatment, time to discharge from hospital, or even survival rates."

Writing in a linked Comment, Dr. Tessa Cook from the University of Pennsylvania, USA, discusses whether AI can be effectively compared to the human physician working in the real world, where data are "messy, elusive, and imperfect". She writes: "Perhaps the better conclusion is that, the narrow public body of work comparing AI to human physicians, AI is no worse than humans, but the data are sparse and it may be too soon to tell."

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More information: The Lancet Digital Health, www.thelancet.com/journals/lan … (19)30123-2/fulltext

Provided by Lancet 

Cellular aging is linked to structural changes in the brain

by Bettina Hennebach, Max Planck Society

To determine the role of telomer length on brain structure scientists measured their length with the DNA of leukocytes from the blood using a polymerase chain reaction. Additionally, they calculated the thickness of the cerebral cortex with MRI scans of study participants. Credit: MPI CBS

Telomeres are the protective caps of our chromosomes and play a central role in the aging process. Shorter telomeres are associated with chronic diseases and high stress levels can contribute to their shortening. A new study now shows that if telomeres change in their length, that change is also reflected in our brain structure. This association was identified by a team of scientists including Lara Puhlmann and Pascal Vrtička from the Max Planck Institute for Cognitive Brain Sciences in Leipzig together with Elissa Epel from the University of California and Tania Singer from the Social Neuroscience Lab in Berlin as part of Singer's ReSource Project.

26 sept 2019--Telomeres are protective caps at the ends of chromosomes that become shorter with each cell division. If they become so short that the genes they protect could be damaged, the cell stops dividing and renewing. Consequently, the cell is increasingly unable to perform its functions. This mechanism is one of the ways in which we age.

Telomere length is therefore regarded as a marker for the biological age of a person—in contrast to their chronological age. For two people of the same chronological age, the person with shorter telomeres has an increased risk of developing age-related diseases such as Alzheimer's or cancer, and even a shorter life expectancy.

Telomere lengthening?

One key to staying younger longer therefore seems to be related to the question: How do we slow down, stop, or even reverse the shortening of telomeres? Genetics and unhealthy lifestyle are important contributors to telomere shortening, along with psychological stress. Based on this knowledge, researchers have examined how much lifestyle can influence telomere length. Recent studies suggest that telomeres can change faster than previously thought, possibly taking just one to six months of mental or physical training to elongate. The exciting premise is that telomere lengthening may represent a reversal of biological aging processes. However, it remains unclear if telomere elongation actually reflects any improvement in a person's overall health and aging trajectory.

"To explore whether a short-term change in telomere length, after only a few months, might actually be associated with changes in a person's biological age, we linked it to another biomarker of aging and health: brain structure," explains Lara Puhlmann, now a member of the Research Group "Social Stress and Family Health' led by Veronika Engert at the Leipzig Max Planck Institute. The project had been initiated by Tania Singer as part of the ReSource Project.

Participants of the researchers' study underwent four MRI examinations, each spaced three months apart, and provided blood samples on the same dates. Using the DNA of leukocytes from the blood, the scientists were able to determine telomere length using a polymerase chain reaction. The MRI scans were used to calculate the thickness of the cerebral cortex of each participant. This outer layer of gray matter becomes thinner with age. It is also known that some neurological and age-related diseases are associated with faster cortical thinning in certain brain regions.

Fast changes in biological aging

The result: "Across systems, our biological aging appears to change more quickly than we thought. Indices of aging can vary together significantly in just three months," says Puhlmann. If the telomeres changed in length, this was associated with structural changes in the brain. In a period when participants' telomeres lengthened during the study, it was also more likely that their cortex had thickened at the same time. On the other hand, telomere shortening was associated with reductions of gray matter. This association occurred specifically in a brain region called the precuneus, which is a central metabolic and connectional hub.

The above results suggest that even short-term changes in telomere length over just three months might reflect general fluctuations in the body's health- and aging status. Many other questions, however, remain open. "We do not know, for example, which biological mechanism underlies the short-term changes in telomere length," explains the scientist, "or whether the short-term changes really have a longer-term effect on health."

Mental training

At the same time, the team of researchers investigated whether telomere length could be altered by nine months of mindfulness- and empathy-based mental training, and whether such systematic change in telomere length would also be reflected in cortical thickening or thinning. Previous data from the ReSource Project, which was supported by the European Research Council (ERC), had already shown that certain regions of the cortex can be thickened by training, depending on the respective mental training contents of three distinct modules, each lasting for three months. The physiological stress response could also be reduced by mental training with social aspects.

In contrast to their earlier work and previous findings from other groups, the team did not find any training effects on telomeres. Future studies will need to continue to address the question of which measures or behaviors most effectively stop or even reverse telomere shortening, and the biological aging process.

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More information: Lara M. C. Puhlmann et al. Association of Short-term Change in Leukocyte Telomere Length With Cortical Thickness and Outcomes of Mental Training Among Healthy Adults, JAMA Network Open (2019). DOI: 10.1001/jamanetworkopen.2019.9687

Journal information: JAMA Network Open 

Provided by Max Planck Society 

The dangers of vaping

by Katherine Unger Baillie, University of Pennsylvania

Credit: CC0 Public Domain

It's an increasingly common sight around the nation: A person lifts a device to their mouth, and suddenly their head appears engulfed in a vapor cloud.

26 sept 2019--Electronic cigarettes, which give rise to those drifts of fleeting, smokeless vapors, have exploded in popularity, introduced to the market in the early 2000s. A 2017 survey by the United States Centers for Disease Control and Prevention (CDC) indicated that 7 million U.S. adults used e-cigarettes, but the practice is growing fastest among young people. A survey from 2018 found that 37% of 12th graders had reported using the products in the past year. This rise comes as rates of cigarette smoking among young people have fallen significantly in recent years.

Makers of electronic cigarettes have billed them as a safer alternative to cigarettes. But with eight deaths and more than 500 instances of lung injury now linked to their use, the products are under scrutiny from the public as well as the CDC and U.S. Food and Drug Administration (FDA).

"The public health community used to feel that tobacco equals death, and it followed that not-tobacco equals not-death," says Frank Leone, director of Penn's Comprehensive Smoking Treatment Program and a pulmonologist at the Perelman School of Medicine. "Now that calculus is changing. People are starting to recognize that, sure, cigarette smoking has its risk profile, but electronic cigarettes have their own risk profile."

Electronic cigarettes, or e-cigarettes, are hand-held, battery-powered devices. Unlike cigarettes, they do not burn tobacco but rather contain a heating element that aerosolizes a nicotine-containing solution into a vapor, which users then inhale.

At Penn, physicians and other health workers have been seeing the nationwide trends in e-cigarette use reflected in the student population. Leone points to a recent survey, conducted by the Student Health Service, that suggested that undergraduates who began using the devices on campus were well informed about the dangers of smoking.

"These are people who have gotten the message that cigarettes are gross," says Leone. "They don't want to smoke. But they don't think of this as smoking."

According to the survey and Leone's experience, students don't necessarily even consider their habit as vaping. "They think of it as "Juuling,"" he says, referring to the maker of sleek e-cigarettes that can be charged in USB ports and have commandeered roughly a third of the market.

Juul and similar companies claim their devices are intended to help adult cigarette users quit. Yet aspects of the products make them appealing to use, particularly for younger people. For one, they use a single type of nicotine salt, nicotine benzoate, which is tasteless and doesn't elicit a caustic sensation when it hits the back of the throat, as many other types of naturally occurring nicotine salts do. Nicotine benzoate is also able to quickly traverse the blood-brain barrier, making it "precisely the right product for a young person to get maximum impact with minimum aversive sensations," Leone says.

What's more, their cartridges come in a variety of appealing flavors.

"Out of one side of their mouth Juul is all about helping adults have a choice," says Leone, "and out the other side they're selling mango- and crème brûlée- and strawberry shortcake-flavored solutions."

This facet of products of Juul and other manufacturers has led the FDA to consider a ban on flavored nicotine products, which seem to target young—even underage—users.

Leone notes that the flavors may also enhance the irresistible pull of the products on a biological level.

"Nicotine hooks itself onto sensory inputs to create its addictive potential," Leone says. "So it turns out that adding specific flavors to nicotine products enhances the nicotine's reinforcing capacity."

Perhaps in part for these reasons, while some individuals say e-cigarettes helped them quit smoking, Leone says researchers have not been able to reproduce those successes. Some evidence even suggests that e-cigarette use can actually impede smoking-cessation efforts.

What's clear is that vaping can cause harm and that the people who have died or experienced serious lung injuries from using e-cigarettes don't fit into a single bucket, says Leone: They have used different products for different lengths of time in different ways. This makes it hard to point a finger at one chemical, or one product, to blame. Rather, it suggests that the act of vaping itself is the problem.

"There's this false calculus that e-cigarettes have to be less harmful than cigarettes," he says. "They are harmful, period. You just can't mess with the lungs in any old way you want to and expect to get away with it."

As a part of promoting the safety and health of the whole community, Penn's Tobacco-Free Campus designation extends to electronic cigarette use. For students, staff, and faculty who want to stop using e-cigarettes, a variety of wellness resources are available. These programs rely on an incentivizing approach to quitting, focused on positively reinforcing healthy behaviors instead of eliciting a sense of fear or shame around them.

Students can tap the Student Health Service for support. "They're keyed into this problem, they're aware of it, they're looking out for it, and they know how to help people," says Leone.

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More information: Teresa W. Wang et al. Tobacco Product Use Among Adults—United States, 2017, MMWR. Morbidity and Mortality Weekly Report (2018). DOI: 10.15585/mmwr.mm6744a2

Provided by University of Pennsylvania 

Surgery may benefit women with two types of urinary incontinence

by National Institutes of Health

Credit: CC0 Public Domain

Surgery for stress urinary incontinence (leaking that occurs with a cough or sneeze) improves symptoms of another form of incontinence, called urgency urinary incontinence, in women who have both types, according to a study supported by the National Institutes of Health. The findings challenge current treatment guidelines, which suggest that the surgery may worsen urgency urinary incontinence in women with both forms, also called mixed urinary incontinence. The study appears in the Journal of the American Medical Association. Funding was provided by NIH's Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and Office of Research on Women's Health.

20 sept 2019--"Women with mixed urinary incontinence may have more bothersome symptoms than women with either stress or urgency urinary incontinence alone," said Donna Mazloomdoost, M.D., study author and program director of the NICHD Pelvic Floor Disorders Network. "The findings show promise in treating a condition that can be hard to manage under existing practices."

Roughly one-third to one-half of all women with urinary incontinence have mixed urinary incontinence. Urgency urinary incontinence results from the spontaneous contraction of bladder muscles, leading to a strong and sudden need to urinate. Stress urinary incontinence occurs when urine leaks out after abdominal pressure increases following a sneeze, cough, laugh or movement, which squeezes the bladder.

Standard treatment guidelines for mixed urinary incontinence often involve treating the two forms of incontinence independently. Urgency urinary incontinence often is first treated with behavioral techniques, such as trying to delay urinating for a brief period after feeling the urge, reducing liquid consumption, exercises to strengthen muscles around the bladder (involving pelvic floor physical therapy) and with medication. Surgery is not usually recommended early on. Stress incontinence also can be treated with exercises, and many women experience symptom improvement. However, in women who do not improve or opt out of the exercises, surgery may be offered.

The Effects of Surgical Treatment Enhanced with Exercise for Mixed Urinary Incontinence (ESTEEM) study is a randomized clinical trial that recruited 480 women with mixed urinary incontinence at centers across the United States. All participants underwent mid-urethral sling surgery, a well-established method that places a thin strip of mesh under the urethra; this helps prevent urine from leaking out during an exertion, such as a sneeze or cough. Participants were randomized to surgery alone or surgery with behavioral and pelvic floor muscle therapy, which included six visits with a trained health professional. They were followed for one year.

The women responded to a questionnaire, the urogenital distress inventory (UDI), which inquired about urinary symptoms. Symptoms are ranked from 0-300 points, depending on severity. They also responded to surveys on quality of life and perceptions of surgical success.

The study team found that both groups had significant improvements in their incontinence symptoms after surgery. The average UDI score for the surgery alone group was 176.8 before surgery and 40.3 a year after surgery; for the surgery and therapy combined group, the UDI score dropped from 178.0 to 33.8. According to the researchers, because the post-treatment UDI scores between the two groups did not differ greatly, adding behavioral and pelvic floor muscle therapy to the treatment may not result in better clinical outcomes.

However, the study team did find differences in other self-reported outcomes. The combined surgery and physical therapy group had fewer instances of incontinence a year after surgery and were less likely to receive additional treatment for urinary tract symptoms, suggesting they had more quality of life improvement than the surgery alone group.

"Current practice guidelines may be unnecessarily delaying surgery for women with mixed urinary incontinence," said Vivian W. Sung, M.D., M.P.H., the study's lead author and a professor at the Warren Alpert Medical School of Brown University in Providence, Rhode Island. "We hope these findings will improve how patients are counseled and treated."

The researchers called for additional research to identify which patients with mixed urinary incontinence are at risk for continued symptoms after surgery and to identify effective treatments for them.

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Clinical review published in JAMA

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More information: Vivian W. Sung et al. Effect of Behavioral and Pelvic Floor Muscle Therapy Combined With Surgery vs Surgery Alone on Incontinence Symptoms Among Women With Mixed Urinary Incontinence, JAMA (2019). DOI: 10.1001/jama.2019.12467

Journal information: Journal of the American Medical Association 

Provided by National Institutes of Health 

AAN recommends people 65+ be screened yearly for memory problems

by American Academy of Neurology

Credit: Public Domain

People with mild cognitive impairment have thinking and memory problems but usually do not know it because such problems are not severe enough to affect their daily activities. Yet mild cognitive impairment can be an early sign of Alzheimer's disease or other forms of dementia. It can also be a symptom of sleep problems, medical illness, depression, or a side effect of medications.

20 sept 2019--To help physicians provide the highest quality patient-centered neurologic care, the American Academy of Neurology (AAN) is recommending physicians measure how frequently they complete annual assessments of people age 65 and older for thinking and memory problems. This metric for yearly cognitive screening tests is part of an AAN quality measurement set published in the September 18, 2019, online issue of Neurology, the medical journal of the American Academy of Neurology.

A quality measure is a mathematical tool to help physicians and practices understand how often health care services are consistent with current best practices and are based on existing AAN guideline recommendations. Quality measures are intended to drive quality improvement in practice. Physicians are encouraged to start small using one or two quality measures in practice that are meaningful for their patient population, and measure use is voluntary.

"Since thinking skills are the most sensitive indicator of brain function and they can be tested cost-effectively, this creates an enormous opportunity to improve neurologic care," said author Norman L. Foster, MD, of the University of Utah in Salt Lake City and a Fellow of the American Academy of Neurology. "The American Academy of Neurology is recommending the measurement of annual cognitive screenings for everyone age 65 and older because age itself is a significant risk factor for cognitive decline and mild cognitive impairment is increasingly prevalent with older age. The measure complements past American Academy of Neurology quality measures released for Parkinson's disease, multiple sclerosis and stroke, and allows for a doctor to meet the measure with a recommended periodic three-minute cognitive test."

According to the 2018 AAN guideline on mild cognitive impairment, nearly 7 percent of people in their early 60s worldwide have mild cognitive impairment, while 38 percent of people age 85 and older have it.

The new AAN quality measurement set recommends doctors measure how often they conduct annual screenings to improve the recognition of mild cognitive impairment and allow for earlier intervention.

"We cannot expect people to report their own memory and thinking problems because they may not recognize that they are having problems or they may not share them with their doctors," said Foster. "Annual assessments will not only help identify mild cognitive impairment early, it will also help physicians more closely monitor possible worsening of the condition."

The new measurement set states that documenting mild cognitive impairment in a person's medical record can be invaluable in alerting other physicians and medical staff so that the best care is provided to that patient.

Early diagnosis can help identify forms of mild cognitive impairment that may be reversible, including those caused by sleep problems, depression or medications, and lead to treatments that can improve a person's quality of life such as correcting hearing loss and avoiding social isolation.

When mild cognitive impairment is not reversible and could develop into more severe forms of dementia like Alzheimer's disease, the quality measurement set recommends measuring how frequently people are given information about their condition as early as possible, so they can take steps to avoid exploitation, plan for their care and monitor their condition.

It is also important not to forget about family and caregivers. The measurement set also asks doctors to identify care partners to help describe symptoms. Doctors should quantify involvement with family and caregivers and provide them with information so that they too receive support and get access to services to help them cope if person's illness progresses and to improve their well-being.

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Can computer use, crafts and games slow or prevent age-related memory loss?

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Journal information: Neurology 

Provided by American Academy of Neurology 

Alcohol-producing gut bacteria could cause liver damage even in people who don't drink

by Cell Press

This graphical abstract shows how high-alcohol-producing Klebsiella pneumoniae (HiAlc Kpn) occurs in a large percentage of individuals with nonalcoholic fatty liver disease (NAFLD). Credit: Yuan et al./Cell Metabolism

Non-alcoholic fatty liver disease (NAFLD) is the build-up of fat in the liver due to factors other than alcohol. It affects about a quarter of the adult population globally, but its cause remains unknown. Now, researchers have linked NAFLD to gut bacteria that produce a large amount of alcohol in the body, finding these bacteria in over 60% of non-alcoholic fatty liver patients. Their findings, publishing September 19 in the journal Cell Metabolism, could help develop a screening method for early diagnosis and treatment of non-alcoholic fatty liver.

20 sept 2019--"We were surprised that bacteria can produce so much alcohol," says lead author Jing Yuan at Capital Institute of Pediatrics. "When the body is overloaded and can't break down the alcohol produced by these bacteria, you can develop fatty liver disease even if you don't drink."

Yuan and her team discovered the link between gut bacteria and NAFLD when they encountered a patient with severe liver damage and a rare condition called auto-brewery syndrome (ABS). Patients with ABS would become drunk after eating alcohol-free and high-sugar food. The condition has been associated with yeast infection, which can produce alcohol in the gut and lead to intoxication.

"We initially thought it was because of the yeast, but the test result for this patient was negative," Yuan says. "Anti-yeast medicine also didn't work, so we suspected [his disease] might be caused by something else."

By analyzing the patient's feces, the team found he had several strains of the bacteria Klebsiella pneumonia in his gut that produced high levels of alcohol. K. pneumonia is a common type of commensal gut bacteria. Yet, the strains isolated from the patient's gut can generate about four to six times more alcohol than strains found in healthy people.

Moreover, the team sampled the gut microbiota from 43 NAFLD patients and 48 healthy people. They found about 60% of NAFLD patients had high- and medium-alcohol-producing K. pneumonia in their gut, while only 6% of healthy controls carry these strains.

To investigate if K. pneumonia would cause fatty liver, researchers fed germ-free mice with high-alcohol-producing K. pneumonia isolated from the ABS patient for 3 months. These mice started to develop fatty liver after the first month. By 2 months, their livers showed signs of scarring, which means long-term liver damage had been made. The progression of liver disease in these mice was comparable to that of mice fed with alcohol. When the team gave bacteria-fed mice with an antibiotic that killed K. pneumonia, their condition was reversed.

"NAFLD is a heterogenous disease and may have many causes," Yuan says. "Our study shows K. pneumonia is very likely to be one of them. These bacteria damage your liver just like alcohol, except you don't have a choice."

However, it remains unknown why some people have high-alcohol-producing K. pneumonia strain in their gut while others don't.

"It's likely that these particular bacteria enter people's body via some carriers from the environment, like food," says co-author Di Liu at the Chinese Academy of Sciences. "But I don't think the carriers are prevalent—otherwise we would expect much higher rate of NAFLD. Also, some people may have a gut environment that's more suitable for the growth and colonization of K. pneumonia than others because of their genetics. We don't understand what factors would make someone more susceptible to these particular K. pneumonia, and that's what we want to find out next."

This finding could also help diagnose and treat bacteria-related NAFLD, Yuan says. Because K. pneumonia produce alcohol using sugar, patients who carry these bacteria would have a detectable amount of alcohol in their blood after drinking a simple glucose solution. "In the early stages, fatty liver disease is reversible. If we can identify the cause sooner, we could treat and even prevent liver damage."

"Having these bacteria in your gut means your body is exposed to alcohol constantly," Liu says. "So does being a carrier mean you would have higher alcohol tolerance? I'm genuinely curious!"

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Study examines the effect of alcohol consumption on survival in non-alcoholic fatty liver

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More information: Cell Metabolism, Yuan et al.: "Fatty liver disease caused by high alcohol-producing Klebsiella pneumoniae" https://www.cell.com/cell-metabolism/fulltext/S1550-4131(19)30447-4, DOI: 10.1016/j.cmet.2019.08.018

Journal information: Cell Metabolism 

Provided by Cell Press 

New study reveals a strong link between vitamin D deficiency and increased mortality, especially diabetes-related deaths

by Diabetologia

Credit: CC0 Public Domain

New research presented at this year's Annual Meeting of the European Association for the Study of Diabetes (EASD) in Barcelona, Spain (16-20 Sept) reveals that vitamin D deficiency is strongly linked to increased mortality, especially in younger and middle-aged people, and is particularly associated with diabetes-related deaths.

20 sept 2019--The research was conducted by Dr. Rodrig Marculescu and colleagues at the Medical University of Vienna, Austria. It analysed the effects of low 25-hydroxyvitamin D (25D) (referred to as vitamin D) levels in the blood on overall and cause-specific mortality in a large study cohort covering all age groups, and taken from a population with minimal vitamin D supplementation in old age.

Vitamin D deficiency is a widely prevalent and easily correctable risk factor for early death, and evidence for its link to mortality comes from numerous studies and clinical trials. The majority of this research to date has however come from looking at older populations, and the authors believe that many of the largest scale studies may have been affected by increased rates of vitamin D supplementation in old age. They also note: "Cause-specific mortalities and the impact of age on the association of vitamin D with the risk of death have not yet been reported in detail."

The researchers took their data from the records of all 78,581 patients (mean age 51.0 years, 31.5% male) who had a vitamin D (25D) measurement taken at the Department of Laboratory Medicine, General Hospital of Vienna between 1991 and 2011, which was then matched with the Austrian national register of deaths. The first 3 years of mortality following the vitamin D measurement were excluded from the analysis, and patients were followed for up to 20 years where possible, with a median follow-up of 10.5 years.

The authors used a blood level of vitamin D 50 nmol/L, a commonly used cut-off value for vitamin D deficiency, as their reference value to which other levels would be compared, and set their low and high levels for which risk would be calculated at 10 nmol/L and 90 nmol/L respectively.

The study found that vitamin D levels of 10 nmol/L or less were associated with a 2-3 fold increase in risk of death, with the largest effect being observed in patients aged 45 to 60 years (2.9 times increased risk). Levels of 90 nmol/L or greater were associated with a reduction in all-cause mortality of 30-40%, again with the largest effect being found in the 45 to 60-years-old age group (a 40% reduction in risk). No statistically significant associations between vitamin D levels and mortality were observed in patients over the age of 75

With regard to cause-specific mortality, the authors were surprised to find the strongest associations of vitamin D were with causes of death other than cardiovascular disease and cancer. Differences between the age groups were even more pronounced for these causes of death and, again, the largest effect was found in patients aged 45 to 60 years. Further subdivision of these non-cardiovascular, non-cancer causes of death revealed the largest effect of vitamin for diabetes with a 4.4 times higher risk of death from the disease in the vitamin D deficient group (less than or equal to 50 nmol/L) than for study participants whose serum vitamin D was above 50 nmol/L.

Plotting the risk of death according to vitamin D level in the various subgroups did not support a risk resurgence at higher vitamin D levels above 100 nmol/L. The authors say this further diminishes concerns about a possible negative effect of vitamin D in the higher concentration range, as have been shown in some previous studies reporting "inverse J-shaped" risk association (meaning risk decreased to a certain level of vitamin D and then started increasing again at higher levels).

The team conclude: "Our survival data from a large cohort, covering all age groups, from a population with minimal vitamin D supplementation at old age, confirm a strong association of vitamin D deficiency (under 50 nmol/L) with increased mortality. This association is most pronounced in the younger and middle-aged groups and for causes of deaths other than cancer and cardiovascular disease, especially diabetes."

The researchers go on to suggest that: "Our findings strengthen the rationale for widespread vitamin D supplementation to prevent premature mortality, emphasize the need for it early in life and mitigate concerns about a possible negative effect at higher levels."

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Provided by Diabetologia 

For the first time walking patterns identify specific types of dementia

by Newcastle University

Credit: CC0 Public Domain

Walking may be a key clinical tool in helping medics accurately identify the specific type of dementia a patient has, pioneering research has revealed.

20 sept 2019--For the first time, scientists at Newcastle University have shown that people with Alzheimer's disease or Lewy body dementia have unique walking patterns that signal subtle differences between the two conditions.

The research, published today in Alzheimer's & Dementia: The Journal of the Alzheimer's Association, shows that people with Lewy body dementia change their walking steps more—varying step time and length—and are asymmetric when they move, in comparison to those with Alzheimer's disease.

It is a first significant step towards establishing gait as a clinical biomarker for various subtypes of the disease and could lead to improved treatment plans for patients.

Useful diagnostic tool

Dr. Ríona McArdle, Post-Doctoral Researcher at Newcastle University's Faculty of Medical Sciences, led the Alzheimer's Society-funded research.

She said: "The way we walk can reflect changes in thinking and memory that highlight problems in our brain, such as dementia.

"Correctly identifying what type of dementia someone has is important for clinicians and researchers as it allows patients to be given the most appropriate treatment for their needs as soon as possible.

"The results from this study are exciting as they suggest that walking could be a useful tool to add to the diagnostic toolbox for dementia.

"It is a key development as a more accurate diagnosis means that we know that people are getting the right treatment, care and management for the dementia they have."

Current diagnosis of the two types of dementia is made through identifying different symptoms and, when required, a brain scan.

For the study, researchers analysed the walk of 110 people, including 29 older adults whose cognition was intact, 36 with Alzheimer's disease and 45 with Lewy body dementia.

The participants took part in a simple walking test at the Gait Lab of the Clinical Ageing Research Unit, an NIHR-funded research initiative jointly run by Newcastle Hospitals NHS Foundation Trust and Newcastle University.

Participants moved along a walkway—a mat with thousands of sensors inside—which captured their footsteps as they walked across it at their normal speed and this revealed their walking patterns.

People with Lewy body dementia had a unique walking pattern in that they changed how long it took to take a step or the length of their steps more frequently than someone with Alzheimer's disease, whose walking patterns rarely changed.

When a person has Lewy body dementia, their steps are more irregular and this is associated with increased falls risk. Their walking is more asymmetric in step time and stride length, meaning their left and right footsteps look different to each other.

Scientists found that analysing both step length variability and step time asymmetry could accurately identify 60% of all dementia subtypes—which has never been shown before.

Further work will aim to identify how these characteristics enhance current diagnostic procedures, and assess their feasibility as a screening method. It is hoped that this tool will be available on the NHS within five years.

Pioneering study

Dr. James Pickett, Head of Research at Alzheimer's Society, said: "In this well conducted study we can see for the first time that the way we walk may provide clues which could help us distinguish between Alzheimer's disease and Lewy body dementia.

"This research—funded by the Alzheimer's Society—is pioneering for dementia. It shows promise in helping to establish a novel approach to accurately diagnose different types of dementia.

"We know that research will beat dementia, and provide invaluable support for the 850,000 people living with the condition in the UK today. It's now vital that we continue to support promising research of this kind.

"We look forward to seeing larger, longer studies to validate this approach and shed light on the relationship between a person's gait and dementia diagnosis."

Dementia describes different brain disorders that triggers loss of brain function and these conditions are usually progressive and eventually severe.

It is estimated by the Alzheimer's Society that people living with dementia in the UK will rise to more than one million by 2025.

Future research at Newcastle University will look at alternative methods to assess walking as part of the €50 MOBILISED-D digital monitoring project, which aims to develop a system of small sensors that can be worn on the body during daily routine to assess how well you walk—a sign of health and wellbeing.

Living with Lewy body dementia

Father-of-four and grandfather-of-two John Tinkler has lived with Lewy body dementia for the past three years.

The 70-year-old, of Langley Park, County Durham, was diagnosed after starting to experience difficulties walking when he began to shuffle his feet and would regularly trip over.

John, his wife, Jenny, 59, and the rest of their family, have learned to cope with the difficult diagnosis and have had to adapt their lifestyles accordingly.

Jenny, a physiotherapist, said: "Since John's diagnosis things have been difficult and, over the years, he has deteriorated to the point where he fatigues easily, which affects his mobility, balance and coordination, and he is now struggling to get out of an armchair. In addition to this, he has joint pain and muscle cramps.

"When we were asked if John would like to take part in the Newcastle University research we didn't hesitate to say 'yes' because it's important that people do their bit to help research.

"The findings of the study are exciting because it can help lead to a definitive diagnosis of the subtype of dementia, which will allow patients to be on the right management programme as early as possible.

"If patients and their families know the specific type of dementia they are dealing with, this enables there to be a greater understanding of the specific needs of the person living with the condition.

"We are extremely lucky to live in an area where research into ageing is among the best there is. It would be fantastic if a screening tool like this was available within the NHS for dementia patients."

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More information: Alzheimer's & Dementia: The Journal of the Alzheimer's Association, DOI: 10.1016/j.jalz.2019.06.4953

Provided by Newcastle University