Healthy lifestyle may offset genetic risk of dementia

July 14, 2019

Science Daily/University of Exeter

Living a healthy lifestyle may help offset a person's genetic risk of dementia, according to new research.

The study was led by the University of Exeter -- simultaneously published today in JAMA and presented at the Alzheimer's Association International Conference 2019 in Los Angeles. The research found that the risk of dementia was 32 per cent lower in people with a high genetic risk if they had followed a healthy lifestyle, compared to those who had an unhealthy lifestyle.

Participants with high genetic risk and an unfavourable lifestyle were almost three times more likely to develop dementia compared to those with a low genetic risk and favourable lifestyle.

Joint lead author Dr El?bieta Ku?ma, at the University of Exeter Medical School, said: "This is the first study to analyse the extent to which you may offset your genetic risk of dementia by living a healthy lifestyle. Our findings are exciting as they show that we can take action to try to offset our genetic risk for dementia. Sticking to a healthy lifestyle was associated with a reduced risk of dementia, regardless of the genetic risk."

The study analysed data from 196,383 adults of European ancestry aged 60 and older from UK Biobank. The researchers identified 1,769 cases of dementia over a follow-up period of eight years. The team grouped the participants into those with high, intermediate and low genetic risk for dementia.

To assess genetic risk, the researchers looked at previously published data and identified all known genetic risk factors for Alzheimer's disease. Each genetic risk factor was weighted according to the strength of its association with Alzheimer's disease.

To assess lifestyle, researchers grouped participants into favourable, intermediate and unfavourable categories based on their self-reported diet, physical activity, smoking and alcohol consumption. The researchers considered no current smoking, regular physical activity, healthy diet and moderate alcohol consumption as healthy behaviours. The team found that living a healthy lifestyle was associated with a reduced dementia risk across all genetic risk groups.

Joint lead author Dr David Llewellyn, from the University of Exeter Medical School and the Alan Turing Institute, said: "This research delivers a really important message that undermines a fatalistic view of dementia. Some people believe it's inevitable they'll develop dementia because of their genetics. However it appears that you may be able to substantially reduce your dementia risk by living a healthy lifestyle."

https://www.sciencedaily.com/releases/2019/07/190714142509.htm

Impaired learning linked to family history of Alzheimer's

July 10, 2019

Science Daily/eLife

Adults with a first-degree relative with Alzheimer's disease perform more poorly on online paired-learning tasks than adults without such a family history, and this impairment appears to be exacerbated by having diabetes or a genetic variation in the apolipoprotein E (APOE) gene linked to the disease.

The findings, published on Tuesday in eLife, may help identify people who have increased risk for developing Alzheimer's disease and could uncover new ways to delay or prevent the disease.

"Identifying factors that reduce or eliminate the effect of a family history of Alzheimer's disease is particularly crucial since there is currently no cure or effective disease-slowing treatments," says lead author Joshua Talboom, PhD, a Postdoctoral Fellow at the Translational Genomics Research Institute in Arizona, US.

Having a family history of Alzheimer's disease is a well-known risk factor for developing the condition, but the effects on learning and memory throughout a person's life are less clear. Some studies have been conducted in this area, but most have been too small to draw significant conclusions.

To enable a larger study, Talboom and colleagues created an easy-to-use website, http://www.mindcrowd.org, that participants could log on to and complete a memory test. Participants were asked to learn 12-word pairs and were then tested on their ability to complete the missing half of the pair when presented with one of the words.

The 59,571 individuals who participated were also asked to answer questions about their sex, education, age, language, country and health, including a question about whether one of their parents or siblings had been diagnosed with Alzheimer's disease. Those with a family history of Alzheimer's were able to match about two and one-half fewer word pairs than individuals without a family history. Having diabetes appeared to compound the learning impairments seen in individuals with a family history.

A subset of 742 participants who had a close relative with Alzheimer's submitted a sample of dried blood or saliva that the researchers tested for a genetic variation in the APOE gene linked to the disease. "The APOE genotype is an important genetic factor that influences memory, and we found that those with the variation performed worse on the memory test than those without the variation," Talboom explains.

Some characteristics, however, appeared to protect against memory and learning impairments in people with a family history of Alzheimer's disease. Participants with higher levels of education experience less of a decline in scores on the learning and memory test than people with lower levels of education, even when they have a family history of the disease. Women also appear to fair better despite having Alzheimer's disease risk factors.

"Our study supports the importance of living a healthy lifestyle, properly treating diseases such as diabetes, and building learning and memory reserve through education to reduce the cognitive decline associated with Alzheimer's disease risk factors," concludes senior author Matthew Huentelman, Professor of Neurogenomics at the Translational Genomics Research Institute, Arizona.

https://www.sciencedaily.com/releases/2019/07/190710131936.htm

'Hunger hormone' enhances memory

July 9, 2019

Science Daily/Society for the Study of Ingestive Behavior

A team of neuroscience researchers at the University of Southern California have identified a surprising new role for the "hunger hormone" ghrelin. Ghrelin has previously been recognized for its unique role in sending hunger signals from the gut to the brain, but, as presented this week at the annual meeting of the Society for the Study of Ingestive Behavior, these new findings suggest that it may also be important for memory control.

Ghrelin is produced in the stomach and secreted in anticipation of eating, and is known for its role to increase hunger. "For example, ghrelin levels would be high if you were at a restaurant, looking forward to a delicious dinner that was going to be served shortly," said Dr. Elizabeth Davis, lead author on the study. Once it is secreted, ghrelin binds to specialized receptors on the vagus nerve -- a nerve that communicates a variety of signals from the gut to the brain. "We recently discovered that in addition to influencing the amount of food consumed during a meal, the vagus nerve also influences memory function," said Dr. Scott Kanoski, senior author of the study. The team hypothesized that ghrelin is a key molecule that helps the vagus nerve promote memory.

Using an approach called RNA interference to reduce the amount of ghrelin receptor, the researchers blocked ghrelin signaling in the vagus nerve of laboratory rats. When given a series of memory tasks, animals with reduced vagal ghrelin signaling were impaired in a test of episodic memory, a type of memory that involves remembering what, when, and where something occurred, such as recalling your first day of school. For the rats, this required remembering a specific object in a specific location.

The team also investigated whether vagal ghrelin signaling influences feeding behavior. They found that when the vagus nerve could not receive the ghrelin signal, the animals ate more frequently, yet consumed smaller amounts at each meal. Dr. Davis thinks these results may be related to the episodic memory problems. "Deciding to eat or not to eat is influenced by the memory of the previous meal," says Davis. "Ghrelin signaling to the vagus nerve may be a shared molecular link between remembering a past meal and the hunger signals that are generated in anticipation of the next meal."

These novel findings add to our understanding of how episodic memories are generated, as well as the relationship between memory and eating behavior. In the future, researchers may be able to develop strategies for improving memory capacity in humans by manipulating ghrelin signaling from the gut to the brain.

https://www.sciencedaily.com/releases/2019/07/190709171807.htm

Indications why older people are more susceptible to Alzheimer's disease

July 8, 2019

Science Daily/DZNE - German Center for Neurodegenerative Diseases

The risk of developing Alzheimer's disease increases with age. Susanne Wegmann of the German Center for Neurodegenerative Diseases (DZNE) in Berlin and colleagues have uncovered a possible cause for this connection: Certain molecules involved in the disease, termed tau-proteins, spread more easily in the aging brain. This has been determined in laboratory experiments. The current study was carried out in close collaboration with researchers in the US at Harvard Medical School and Massachusetts General Hospital. The results were recently published in the journal Science Advances.

Alzheimer's disease usually begins with memory decline and later affects other cognitive abilities. Two different kinds of protein deposits in the patient's brain are involved in the disease: "Amyloid beta plaques" and "tau neurofibrillary tangles." The emergence of tau neurofibrillary tangles reflects disease progression: they first manifest in the brain's memory centers and then appear in other areas in the course of the disease. Tau proteins or tau aggregates probably migrate along nerve fibers and thereby contribute to the spreading of the disease throughout the brain.

Tau spreads more rapidly in aging brains

What is the role of aging in tau propagation? If the protein spread more easily in older brains, this could explain the increased susceptibility of older people to Alzheimer's disease. Wegmann and her colleagues tested this hypothesis.

Using a "gene vector" -- a tailored virus particle -- the scientists channeled the blueprint of the human tau protein into the brains of mice. Individual cells then began to produce the protein. Twelve weeks later, the researchers examined how far the tau protein had travelled from the production site. "Human tau proteins spread about twice as fast in older mice as compared to younger animals," Wegmann summarized the results.

The experimental part of the study was carried out in the laboratory of Bradley Hyman at Harvard Medical School in Boston, USA, where Susanne Wegmann worked for several years. In 2018, she moved to the DZNE's Berlin site, where her research group addresses various questions on tau-related disease mechanisms. Here, the major part of data analysis and summarizing the results took place.

Healthy and pathological tau

The experimental setting also allowed the scientists to analyze tau propagation in more detail. The protein exists in a healthy, soluble form in every neuron of the brain. However, in Alzheimer's disease, it can change its shape and convert into a pathological form prone to aggregate into fibrils. "It has long been thought that it is primarily the pathological form of tau that passes from one cell to the next. However, our results show that the healthy version of the protein also propagates in the brain and that this process increases in old age. Cells could also be harmed by receiving and accumulating large amounts of healthy tau," said Wegmann.

The findings from the study raise a number of questions that Wegmann will now tackle with her research group at the DZNE: Which processes underlie the increased spreading of tau in the aging brain? Is too much tau protein produced or too little defective protein removed? Answering these questions may open up new therapeutic options in the long term.

https://www.sciencedaily.com/releases/2019/07/190708135940.htm

A short bout of exercise enhances brain function

Researchers discover a gene in mice that's activated by brief periods of exercise

July 2, 2019

Science Daily/Oregon Health & Science University

Neuroscientists, working with mice, have discovered that a short burst of exercise directly boosts the function of a gene that increases connections between neurons in the hippocampus, the region of the brain associated with learning and memory.

Most people know that regular exercise is good for your health. New research shows it may make you smarter, too.

Neuroscientists at OHSU in Portland, Oregon, working with mice, have discovered that a short burst of exercise directly boosts the function of a gene that increases connections between neurons in the hippocampus, the region of the brain associated with learning and memory.

The research is published online in the journal eLife.

"Exercise is cheap, and you don't necessarily need a fancy gym membership or have to run 10 miles a day," said co-senior author Gary Westbrook, M.D., senior scientist at the OHSU Vollum Institute and Dixon Professor of Neurology in the OHSU School of Medicine.

Previous research in animals and in people shows that regular exercise promotes general brain health. However, it's hard to untangle the overall benefits of exercise to the heart, liver and muscles from the specific effect on the brain. For example, a healthy heart oxygenates the whole body, including the brain.

"Previous studies of exercise almost all focus on sustained exercise," Westbrook said. "As neuroscientists, it's not that we don't care about the benefits on the heart and muscles but we wanted to know the brain-specific benefit of exercise."

So the scientists designed a study in mice that specifically measured the brain's response to single bouts of exercise in otherwise sedentary mice that were placed for short periods on running wheels. The mice ran a few kilometers in two hours.

The study found that short-term bursts of exercise -- the human equivalent of a weekly game of pickup basketball, or 4,000 steps -- promoted an increase in synapses in the hippocampus. Scientists made the key discovery by analyzing genes that were increased in single neurons activated during exercise.

One particular gene stood out: Mtss1L. This gene had been largely ignored in prior studies in the brain.

"That was the most exciting thing," said co-lead author Christina Chatzi, Ph.D.

The Mtss1L gene encodes a protein that causes bending of the cell membrane. Researchers discovered that when this gene is activated by short bursts of exercise, it promotes small growths on neurons known as dendritic spines -- the site at which synapses form.

In effect, the study showed that an acute burst of exercise is enough to prime the brain for learning.

In the next stage of research, scientists plan to pair acute bouts of exercise with learning tasks to better understand the impact on learning and memory.

https://www.sciencedaily.com/releases/2019/07/190702184555.htm

Pink noise boosts deep sleep in mild cognitive impairment patients

Sound stimulation in deep sleep improved recall for some in small pilot study

June 28, 2019

Science Daily/Northwestern University

Gentle sound stimulation played during deep sleep enhanced deep sleep for people with mild cognitive impairment, who are at risk for Alzheimer's disease, a new study found. Those whose brains responded the most robustly to the sound stimulation showed an improved memory response the following day. These results suggest improving sleep is a promising novel approach to stave off dementia. The technology can be adapted for home use.

Gentle sound stimulation played during specific times during deep sleep enhanced deep or slow-wave sleep for people with mild cognitive impairment, who are at risk for Alzheimer's disease.

The individuals whose brains responded the most robustly to the sound stimulation showed an improved memory response the following day.

"Our findings suggest slow-wave or deep sleep is a viable and potentially important therapeutic target in people with mild cognitive impairment," said Dr. Roneil Malkani, assistant professor of neurology at Northwestern University Feinberg School of Medicine and a Northwestern Medicine sleep medicine physician. "The results deepen our understanding of the importance of sleep in memory, even when there is memory loss."

Deep sleep is critical for memory consolidation. Several sleep disturbances have been observed in people with mild cognitive impairment. The most pronounced changes include reduced amount of time spent in the deepest stage of sleep.

"There is a great need to identify new targets for treatment of mild cognitive impairment and Alzheimer's disease," Malkani added. Northwestern scientists had previously shown that sound stimulation improved memory in older adults in a 2017 study.

Because the new study was small -- nine participants -- and some individuals responded more robustly than others, the improvement in memory was not considered statistically significant. However, there was a significant relationship between the enhancement of deep sleep by sound and memory: the greater the deep sleep enhancement, the better the memory response.

"These results suggest that improving sleep is a promising novel approach to stave off dementia," Malkani said.

The paper will be published June 28 in the Annals of Clinical and Translational Neurology.

For the study, Northwestern scientists conducted a trial of sound stimulation overnight in people with mild cognitive impairment. Participants spent one night in the sleep laboratory and another night there about one week later. Each participant received sounds on one of the nights and no sounds on the other. The order of which night had sounds or no sounds was randomly assigned. Participants did memory testing the night before and again in the morning. Scientists then compared the difference in slow-wave sleep with sound stimulation and without sounds, and the change in memory across both nights for each participant.

The participants were tested on their recall of 44 word pairs. The individuals who had 20% or more increase in their slow wave activity after the sound stimulation recalled about two more words in the memory test the next morning. One person with a 40% increase in slow wave activity remembered nine more words.

The sound stimulation consisted of short pulses of pink noise, similar to white noise but deeper, during the slow waves. The system monitored the participant's brain activity. When the person was asleep and slow brain waves were seen, the system delivered the sounds. If the patient woke up, the sounds stopped playing.

"As a potential treatment, this would be something people could do every night," Malkani said.

The next step, when funding is available, is to evaluate pink noise stimulation in a larger sample of people with mild cognitive impairment over multiple nights to confirm memory enhancement and see how long the effect lasts, Malkani said.

https://www.sciencedaily.com/releases/2019/06/190628120531.htm

Dementia study links gene with damage to brain connections

June 27, 2019

Science Daily/University of Edinburgh

Insights into how a gene that increases the risk of Alzheimer's disease disrupts brain cells have been revealed by scientists.

Brain tissue from people with Alzheimer's showed that a protein called clusterin builds up in vital parts of neurons that connect cells and may damage these links.

Scientists say the findings shed light on the causes of the disease and will help to accelerate the search for a treatment.

The study, led by Professor Tara Spires-Jones at the University of Edinburgh, focused on synapses -- connections between brain cells that allow the flow of chemical and electrical signals. These signals are vital for forming memories and are key to brain health, experts say.

Researchers showed that synapses in people who had died with Alzheimer's contained clumps of clusterin, which could contribute to dementia symptoms. These synapses also contained clumps of amyloid beta, the damaging protein that is found in the brains of people with Alzheimer's.

People with a common risk gene, called apolipoprotein E4, had more clusterin and amyloid beta clumps in their synapses than people with Alzheimer's without the risk gene.

Those without dementia symptoms had even less of the damaging proteins in their synapses.

The discovery was made using powerful technology that allowed the scientists to view detailed images of more than one million synapses. Individual synapses are around 5000 times smaller than the thickness of a sheet of paper.

Synapse loss in Alzheimer's disease was previously established, but the clumping of damaging proteins together in synapses was unknown until now because of difficulties in studying them due to their tiny size.

Alzheimer's disease is the most common form of dementia, affecting around 500,000 people in the UK. It can cause severe memory loss and there is no cure.

Professor Spires-Jones, Programme Lead at the UK Dementia Research Institute at the University of Edinburgh, said: "We have identified another player in the host of proteins that damage synapses in Alzheimer's disease. Synapses are essential for thinking and memory, and preventing damage to them is a promising target to help prevent or reverse dementia symptoms. This work gives us a new target to work towards in our goal to develop effective treatments."

https://www.sciencedaily.com/releases/2019/06/190627114025.htm

Disrupted sleep in one's 50s, 60s raises risk of Alzheimer's disease

Protein tangles in the aging brain throw sleep rhythms out of sync, likely leading to memory loss

June 27, 2019

Science Daily/University of California - Berkeley

PET brain scans of healthy older adults show that those reporting lower sleep quality through their 50s and 60s have higher levels of tau protein, a risk factor for Alzheimer's disease. Previous studies link poor sleep to beta-amyloid tangles also, suggesting that protein tangles in the brain may cause some of the memory problems of AD and dementia. In addition, out-of-sync brain waves during sleep are associated with tau, providing a possible biomarker of dementia.

People who report a declining quality of sleep as they age from their 50s to their 60s have more protein tangles in their brain, putting them at higher risk of developing Alzheimer's disease later in life, according to a new study by psychologists at the University of California, Berkeley.

The new finding highlights the importance of sleep at every age to maintain a healthy brain into old age.

"Insufficient sleep across the lifespan is significantly predictive of your development of Alzheimer's disease pathology in the brain," said the study's senior author, Matthew Walker, a sleep researcher and professor of psychology. "Unfortunately, there is no decade of life that we were able to measure during which you can get away with less sleep. There is no Goldilocks decade during which you can say, 'This is when I get my chance to short sleep.'"

Walker and his colleagues, including graduate student and first author Joseph Winer, found that adults reporting a decline in sleep quality in their 40s and 50s had more beta-amyloid protein in their brains later in life, as measured by positron emission tomography, or PET. Those reporting a sleep decline in their 50s and 60s had more tau protein tangles. Both beta-amyloid and tau clusters are associated with a higher risk of developing dementia, though not everyone with protein tangles goes on to develop symptoms of dementia.

Based on the findings, the authors recommend that doctors ask older patients about changes in sleep patterns and intervene when necessary to improve sleep to help delay symptoms of dementia. This could include treatment for apnea, which leads to snoring and frequent halts in breathing that interrupt sleep, and cognitive behavioral therapy for insomnia (CBT-I), a highly effective way to develop healthy sleep habits. It may even include simple sleep counseling to convince patients to set aside time for a full eight hours of sleep and simple sleep hygiene tricks to accomplish that.

"The idea that there are distinct sleep windows across the lifespan is really exciting. It means that there might be high-opportunity periods when we could intervene with a treatment to improve people's sleep, such as using a cognitive behavioral therapy for insomnia," Winer said. "Beyond the scientific advance, our hope is that this study draws attention to the importance of getting more sleep and points us to the decades in life when intervention might be most effective."

The 95 subjects in the study were part of the Berkeley Aging Cohort Study (BACS), a group of healthy older adults -- some as old as 100 years of age -- who have had their brains scanned with PET, the only technique capable of detecting both beta-amyloid tangles and, very recently, tau tangles, in the brain.

Winer, Walker and their colleagues reported their results online last week in the Journal of Neuroscience.

Brain waves out of sync

The team also made a second discovery. They found that people with high levels of tau protein in the brain were more likely to lack the synchronized brain waves that are associated with a good night's sleep. The synchronization of slow brain waves throughout the cortex of the sleeping brain, in lockstep with bursts of fast brain waves called sleep spindles, takes place during deep or non-rapid eye movement (NREM) sleep. The team reported that the more tau protein older adults had, the less synchronized these brain waves were. This impaired electrical sleep signature may therefore act as a novel biomarker of tau protein in the human brain.

"There is something special about that synchrony," given the consequences of this tau protein disruption of sleep, Walker said. "We believe that the synchronization of these NREM brain waves provides a file-transfer mechanism that shifts memories from a short-term vulnerable reservoir to a more permanent long-term storage site within the brain, protecting those memories and making them safe. But when you lose that synchrony, that file-transfer mechanism becomes corrupt. Those memory packets don't get transferred, as well, so you wake up the next morning with forgetting rather than remembering."

Indeed, last year, Walker and his team demonstrated that synchronization of these brain oscillations helps consolidate memory, that is, hits the "save" button on new memories.

Several years ago, Walker and his colleagues initially showed that a dip in the amplitude of slow wave activity during deep NREM sleep was associated with higher amounts of beta-amyloid in the brain and memory impairment. Combined with these new findings, the results help identify possible biomarkers for later risk of dementia.

"It is increasingly clear that sleep disruption is an underappreciated factor contributing to Alzheimer's disease risk and the decline in memory associated with Alzheimer's," Walker said. "Certainly, there are other contributing factors: genetics, inflammation, blood pressure. All of these appear to increase your risk for Alzheimer's disease. But we are now starting to see a new player in this space, and that new player is called insufficient sleep."

The brain rhythms were recorded over a single eight-hour night in Walker's UC Berkeley sleep lab, during which most of the 31 subjects wore a cap studded with 19 electrodes that recorded a continual electroencephalogram (EEG). All had previously had brain scans to assess their burdens of tau and beta-amyloid that were done using a PET scanner at the Lawrence Berkeley National Laboratory and operated by study co-author William Jagust, professor of public health and a member of Berkeley's Helen Wills Neuroscience Institute.

Is sleep a biomarker for dementia?

Doctors have been searching for early markers of dementia for years, in hopes of intervening to stop the deterioration of the brain. Beta-amyloid and tau proteins are predictive markers, but only recently have they become detectable with expensive PET scans that are not widely accessible.

Yet, while both proteins escalate in the brain in old age and perhaps to a greater extent in those with dementia, it is still unknown why some people with large burdens of amyloid and tau do not develop symptoms of dementia.

"The leading hypothesis, the amyloid cascade hypothesis, is that amyloid is what happens first on the path to Alzheimer's disease. Then, in the presence of amyloid, tau begins to spread throughout the cortex, and if you have too much of that spread of tau, that can lead to impairment and dementia," Winer said.

Walker added that, "A lack of sleep across the lifespan may be one of the first fingers that flicks the domino cascade and contributes to the acceleration of amyloid and tau protein in the brain."

The hypothesis is supported, in part, by Jagust's PET studies, which have shown that higher levels of beta-amyloid and tau protein tangles in the brain are correlated with memory decline, tau more so than amyloid. Tau occurs naturally inside the brain's neurons, helping to stabilize their internal skeleton. With age, tau proteins seem to accumulate inside cells of the medial temporal lobe, including the hippocampus, the seat of short-term memory. Only later do they spread more widely throughout the cortex.

While Jagust has run PET scans on the brains of many healthy people, as well as those with dementia, many more subjects are needed to confirm the relationship between protein tangles and dementias like Alzheimer's disease. Because PET scanners are currently expensive and rare, and because they require injection of radioactive tracers, other biomarkers are needed, Walker said.

The new study suggests that sleep changes detectable in a simple overnight sleep study may be less intrusive biomarkers than a PET scan.

"As wearable technology improves, this need not be something you have to come to a sleep laboratory for," said Walker. "Our hope is that, in the future, a small head device could be worn by people at home and provide all the necessary sleep information we'd need to assess these Alzheimer's disease proteins. We may even be able to track the effectiveness of new drugs aimed at combating these brain proteins by assessing sleep."

"I think the message is very clear," Walker added. "If you are starting to struggle with sleep, then you should go and see your doctor and find ways, such as CBT-I, that can help you improve your sleep. The goal here is to decrease your chances of Alzheimer's disease."

https://www.sciencedaily.com/releases/2019/06/190627114105.htm

Snails show that variety is the key to success if you want to remember more

June 26, 2019

Science Daily/University of Sussex

Neuroscientists have revealed the factors that impact on memory interference, showing that a change is as good as a rest when it comes to retaining more information. They also discovered that timing plays a key role, as old information can effectively be replaced by new information when learning takes place during a memory lapse.

A change is as good as a rest when it comes to remembering more, according to new research by neuroscientists at the University of Sussex.

Dr Michael Crossley, Senior Research Fellow in Neuroscience, used pond snails to study the factors impacting on memory interference.

He found that, when tasked with learning two similar things, snails were only able to store and recall the first memory.

Conversely, when faced with learning two totally unrelated tasks, the snails were able to retain all the information and successfully store both memories.

Dr Crossley said: "The brain of a snail is much simpler than ours but there are some key parallels which mean studying them can help us to understand more about our own abilities for learning and memory.

"We know that multiple learning events occurring in quick succession can lead to competition between memories. This is why, when introduced to multiple people in one go, we can't usually remember every name.

"Up until now though, we weren't sure which factors were causing a memory to be remembered or forgotten."

With colleagues from Sussex Neuroscience, Dr Crossley trained snails using food-reward and aversive conditioning .

Using brain recording, they realised that the same neuron was used when snails tried to learn two similar things. This prompted an overlapping mechanism, which caused only one memory (the first one) to survive, known as proactive interference.

In contrast, when two different tasks were learnt, two separate neurons were used, resulting in no competition, no overlap and the successful storing of both memories.

Dr Crossley explained: "We realised that there is an overlapping or non-overlapping mechanism which plays a key role in determining which memories survive.

"So if we want to learn multiple things quickly, we should try learning different rather than similar topics."

For students, this means that they should practice interweaving -- switching between multiple different subjects in one day -- to retain the most information.

However, in the study published in the Nature group journal Communications Biology, Dr Crossley and his colleagues also found that the timing of new learning can play a big role in the interference of memories.

When they introduced new learning to a snail during a memory lapse (the stage at which information is temporarily forgotten as it is transferred from short to longer term memory) researchers found that an older memory was always lost. This is known as retroactive interference.

Dr Ildiko Kemenes, senior author on the paper, said: "In effect, we think the brain is deciding to replace the older learning, which hasn't yet been committed to long-term memory, for a newer one which it thinks might be more relevant.

"Interestingly, it's only when trying to learn something new during a memory lapse that this interference happens.

"This suggests that the older memory was only vulnerable due to new memories being formed. This makes sense when we think about humans as we wouldn't want a system where our memories are vulnerable if someone bumps into us at the wrong time!"

Scientists believe that the findings of their research, funded by BBSRC, gives us useful information about how memory is stored and how best we can learn and retain information.

https://www.sciencedaily.com/releases/2019/06/190626125039.htm

Your nose knows when it comes to stronger memories

New research points to value of unpleasant smells in strengthening recall

June 19, 2019

Science Daily/New York University

Memories are stronger when the original experiences are accompanied by unpleasant odors, a team of researchers has found. The study broadens our understanding of what can drive Pavlovian responses and points to how negative experiences influence our ability to recall past events.

"These results demonstrate that bad smells are capable of producing memory enhancements in both adolescents and adults, pointing to new ways to study how we learn from and remember positive and negative experiences," explains Catherine Hartley, an assistant professor in New York University's Department of Psychology and the senior author of the paper, which appears in the journal Learning and Memory.

"Because our findings spanned different age groups, this study suggests that aversive odors might be used in the future to examine emotional learning and memory processes across development," adds Alexandra Cohen, an NYU postdoctoral fellow and the paper's lead author.

The impact of negative experiences on memory has long been shown -- and is familiar to us. For example, if you are bitten by a dog, you may develop a negative memory of the dog that bit you, and your negative association may also go on to generalize to all dogs. Moreover, because of the trauma surrounding the bite, you are likely to have a better recollection of it than you would other past experiences with dogs.

"The generalization and persistence in memory of learned negative associations are core features of anxiety disorders, which often emerge during adolescence," notes Hartley.

In order to better understand how learned negative associations influence memory during this stage of development, the researchers designed and administered a Pavlovian learning task to individuals aged 13 to 25. Mild electrical shocks are often used in this type of learning task. In this study, the researchers used bad smells because they can be ethically administered in studying children.

The task included the viewing of a series of images belonging to one of two conceptual categories: objects (e.g., a chair) and scenes (e.g., a snow-capped mountain). As the study's participants viewed the images, they wore a nasal mask connected to an olfactometer. While participants viewed images from one category, unpleasant smells were sometimes circulated through the device to the mask; while viewing images from the other category, unscented air was used. This allowed the researchers to examine memory for images associated with a bad smell as well as for generalization to related images. In other words, if the image of a chair was associated with a bad smell, would memory be enhanced only for the chair or for objects in general?

What constitutes a "bad" odor is somewhat subjective. In order to determine which odors the participants found unlikable, the researchers had the subjects -- prior to the start of the experiment -- breathe in a variety of odors and indicate which ones they thought were unpleasant. The odors were blends of chemical compounds provided by a local perfumer and included scents such as rotting fish and manure.

As the subjects viewed the images, the scientists measured perspiration from the palm of the subjects' hands as an index of arousal -- a common research technique used to confirm the creation of a negative association (in this case, of a bad smell). A day later, researchers tested participants' memory for the images.

Their findings showed that both adolescents and adults showed better memory specifically for images paired with the bad smell 24 hours after they saw these images. They also found that individuals with larger arousal responses at the point when they might experience either a bad smell or clean air while viewing the image, regardless of whether or not a smell was actually delivered, had better memory 24 hours later. This suggests that unpredictability or surprise associated with the outcome leads to better memory.

https://www.sciencedaily.com/releases/2019/06/190619085701.htm

Sleep history predicts late-life Alzheimer's pathology

Findings suggest novel, sleep-based diagnosis and treatment methods

June 18, 2019

Science Daily/Society for Neuroscience

Sleep patterns can predict the accumulation of Alzheimer's pathology proteins later in life, according to a new study of older men and women published in JNeurosci. These findings could lead to new sleep-based early diagnosis and prevention measures in the treatment of Alzheimer's disease.

Alzheimer's disease is associated with disrupted sleep and the accumulation of tau and proteins in the brain, which can emerge long before characteristic memory impairments appear. Two types of hippocampal sleep waves, slow oscillations and sleep spindles, are synced in young individuals, but have been shown to become uncoordinated in old age.

Matthew Walker, Joseph Winer, and colleagues at the University of California, Berkeley found a decrease in slow oscillations/sleep spindle synchronization was associated with higher tau, while reduced slow-wave-activity amplitude was associated with higher ?-amyloid levels.

The researchers also found that a decrease in sleep quantity throughout aging, from the 50s through 70s, was associated with higher levels of ?-amyloid and tau later in life. This means that changes in brain activity during sleep and sleep quantity during these time frames could serve as a warning sign for Alzheimer's disease, allowing for early preventive care.

https://www.sciencedaily.com/releases/2019/06/190618102725.htm

Reaching and grasping: Learning fine motor coordination changes the brain

June 12, 2019

Science Daily/University of Basel

When we train the reaching for and grasping of objects, we also train our brain. In other words, this action brings about changes in the connections of a certain neuronal population in the red nucleus, a region of the midbrain. Researchers at the University of Basel's Biozentrum have discovered this group of nerve cells in the red nucleus. They have also shown how fine motor tasks promote plastic reorganization of this brain region. The results of the study have been published recently in Nature Communications.

Simply grasping a coffee cup needs fine motor coordination with the highest precision. This required performance of the brain is an ability that can also be learned and trained. Prof. Kelly Tan's research group at the Biozentrum, University of Basel, has investigated the red nucleus, a region of the midbrain that controls fine motor movement, and identified a new population of nerve cells which changes when fine motor coordination is trained. The more that grasping is practiced, the more the connections between the neurons of this group of nerve cells are strengthened.

The red nucleus, a little investigated region of the brain

Grasping is a skill that can be trained and improved, even in adults. For muscles to perform a movement correctly, brain commands must be transmitted through the spinal cord. The red nucleus, which, over the years, has received little attention in brain research, plays an important role in fine motor coordination. Here the brain learns new fine motor skills for grasping and stores what it has learned.

Kelly Tan's team has now investigated the red nucleus in more detail in the mouse model and analyzed its structure and neuronal composition. "We have found that this brain region is very heterogeneous and consists of different neuron populations," says Giorgio Rizzi, first author of the study.

Improved fine motor skills through plastic changes in the brain

The research team has characterized one of these neuron populations and demonstrated that learning new grasping movements strengthens the connections between the individual neurons. "When learning new fine motor skills, the coordination of this specific movement is optimized and stored in the brain as a code," explains Tan. "Thus, we have been able to also demonstrate neuroplasticity in the red nucleus."

In a further step, the team now wants to investigate the stability of these strengthened nerve cell connections in the red nucleus and find out to what extent they regress when the learned fine motor movements are not practiced. The findings could also provide new insights into the understanding of Parkinson's disease, in which affected individuals suffer from motor disorders. The team hopes to find out whether the neuronal connections in the red nucleus have also changed in these patients and to what extent fine motor training can restrengthen the neuronal network.

https://www.sciencedaily.com/releases/2019/06/190612093907.htm

How the brain changes when mastering a new skill

Research reveals new neural activity patterns that emerge with long-term learning

June 10, 2019

Science Daily/University of Pittsburgh

Researchers have discovered what happens in the brain as people learn how to perform tasks, which could lead to improved lives for people with brain injuries. The study revealed that new neural activity patterns emerge with long-term learning and established a causal link between these patterns and new behavioral abilities.

Mastering a new skill -- whether a sport, an instrument, or a craft -- takes time and training. While it is understood that a healthy brain is capable of learning these new skills, how the brain changes in order to develop new behaviors is a relative mystery. More precise knowledge of this underlying neural circuitry may eventually improve the quality of life for individuals who have suffered brain injury by enabling them to more easily relearn everyday tasks.

Researchers from the University of Pittsburgh and Carnegie Mellon University recently published an article in PNAS that reveals what happens in the brain as learners progress from novice to expert. They discovered that new neural activity patterns emerge with long-term learning and established a causal link between these patterns and new behavioral abilities.

The research was performed as part of the Center for the Neural Basis of Cognition, a cross-institutional research and education program that leverages the strengths of Pitt in basic and clinical neuroscience and bioengineering, with those of CMU in cognitive and computational neuroscience.

The project was jointly mentored by Aaron Batista, associate professor of bioengineering at Pitt; Byron Yu, associate professor of electrical and computer engineering and biomedical engineering at CMU; and Steven Chase, associate professor of biomedical engineering and the Neuroscience Institute at CMU. The work was led by Pitt bioengineering postdoctoral associate Emily Oby.

"We used a brain-computer interface (BCI), which creates a direct connection between our subject's neural activity and the movement of a computer cursor," said Oby. "We recorded the activity of around 90 neural units in the arm region of the primary motor cortex of Rhesus monkeys as they performed a task that required them to move the cursor to align with targets on the monitor."

To determine whether the monkeys would form new neural patterns as they learned, the research group encouraged the animals to attempt a new BCI skill and then compared those recordings to the pre-existing neural patterns.

"We first presented the monkey with what we call an 'intuitive mapping' from their neural activity to the cursor that worked with how their neurons naturally fire and which didn't require any learning," said Oby. "We then induced learning by introducing a skill in the form of a novel mapping that required the subject to learn what neural patterns they need to produce in order to move the cursor."

Like learning most skills, the group's BCI task took several sessions of practice and a bit of coaching along the way.

"We discovered that after a week, our subject was able to learn how to control the cursor," said Batista. "This is striking because by construction, we knew from the outset that they did not have the neural activity patterns required to perform this skill. Sure enough, when we looked at the neural activity again after learning we saw that new patterns of neural activity had appeared, and these new patterns are what enabled the monkey to perform the task."

These findings suggest that the process for humans to master a new skill might also involve the generation of new neural activity patterns.

"Though we are looking at this one specific task in animal subjects, we believe that this is perhaps how the brain learns many new things," said Yu. "Consider learning the finger dexterity required to play a complex piece on the piano. Prior to practice, your brain might not yet be capable of generating the appropriate activity patterns to produce the desired finger movements."

"We think that extended practice builds new synaptic connectivity that leads directly to the development of new patterns of activity that enable new abilities," said Chase. "We think this work applies to anybody who wants to learn -- whether it be a paralyzed individual learning to use a brain-computer interface or a stroke survivor who wants to regain normal motor function. If we can look directly at the brain during motor learning, we believe we can design neurofeedback strategies that facilitate the process that leads to the formation of new neural activity patterns."

https://www.sciencedaily.com/releases/2019/06/190610151934.htm

Brush your teeth -- postpone Alzheimer's

June 3, 2019

Science Daily/The University of Bergen

Researchers in Norway have discovered a clear connection between oral health and Alzheimer's disease.

You don't only avoid holes in your teeth by keeping good oral hygiene, researchers at the University of Bergen have discovered a clear connection between gum disease and Alzheimer´s disease.

The researchers have determined that gum disease (gingivitis) plays a decisive role in whether a person developes Alzheimer´s or not.

"We discovered DNA-based proof that the bacteria causing gingivitis can move from the mouth to the brain," says researcher Piotr Mydel at Broegelmanns Research Laboratory, Department of Clinical Science, University of Bergen (UiB).

The bacteria produces a protein that destroys nerve cells in the brain, which in turn leads to loss of memory and ultimately, Alzheimer´s.

Brush your teeth for better memory

Mydel points out that the bacteria is not causing Alzheimer´s alone, but the presence of these bacteria raise the risk for developing the disease substantially and are also implicated in a more rapid progression of the disease. However, the good news is that this study shows that there are some things you can do yourself to slow down Alzheimer´s.

"Brush your teeth and use floss." Mydel adds that it is important, if you have established gingivitis and have Alzheimer´s in your family, to go to your dentist regularly and clean your teeth properly.

New medicine being developed

Researchers have previously discovered that the bacteria causing gingivitis can move from the mouth to the brain where the harmful enzymes they excrete can destroy the nerve cells in the brain. Now, for the first time, Mydel has DNA-evidence for this process from human brains. Mydel and his colleagues examined 53 persons with Alzheimer´s and discovered the enzyme in 96 per cent of the cases.According to Mydel, this knowledge gives researchers a possible new approach for attacking Alzheimer´s disease.

"We have managed to develop a drug that blocks the harmful enzymes from the bacteria, postponing the development of Alzheimer´s. We are planning to test this drug later this year, says Piotr Mydel.

https://www.sciencedaily.com/releases/2019/06/190603102549.htm

A small electrical zap to the brain could help you retrieve a forgotten memory

May 31, 2019

Science Daily/University of California - Los Angeles

A study by UCLA psychologists provides strong evidence that a certain region of the brain plays a critical role in memory recall. The research, published in the Journal of Cognitive Neuroscience, also shows for the first time that using an electrical current to stimulate that region, the left rostrolateral prefrontal cortex, improves people's ability to retrieve memories.

"We found dramatically improved memory performance when we increased the excitability of this region," said Jesse Rissman, a UCLA assistant professor of psychology, and of psychiatry and biobehavioral sciences, the study's senior author.

The left rostrolateral prefrontal cortex is important for high-level thought, including monitoring and integrating information processed in other areas of the brain, Rissman said. This area is located behind the left side of the forehead, between the eyebrow and the hairline.

"We think this brain area is particularly important in accessing knowledge that you formed in the past and in making decisions about it," said Rissman, who also is a member of the UCLA Brain Research Institute.

The psychologists conducted experiments with three groups of people whose average age was 20. Each group contained 13 women and 11 men.

Participants were shown a series of 80 words on a computer screen. For each word, participants were instructed to either imagine either themselves or another person interacting with the word, depending on whether the words "self" or "other" also appeared on the screen. (For example, the combination of "gold" and "other" might prompt them to imagine a friend with a gold necklace.)

The following day, the participants returned to the laboratory for three tests -- one of their memory, one of their reasoning ability and one of their visual perception. Each participant wore a device that sent a weak electrical current through an electrode on the scalp to decrease or increase the excitability of neurons in the left rostrolateral prefrontal cortex. Increasing their excitability makes neurons more likely to fire, which enhances the connections between neurons, Rissman said.

(The technique, called transcranial direct current stimulation, or tDCS, gives most people a warm, mild tingling sensation for the first few minutes, said the study's lead author, Andrew Westphal, who conducted the study as a UCLA doctoral student and is now a postdoctoral scholar in neurology at UC San Francisco.)

For the first half of the hour-long study, all participants received "sham" stimulation -- meaning that the device was turned on just briefly, to give the sensation that something was happening, but then turned off so that no electrical stimulation was applied. This allowed the researchers to measure how well each participant performed the tasks under normal conditions. For the next 30 minutes, one group of participants received an electrical current that increased their neurons' excitability, the second group received current that suppressed neuron activity and the third group received only the sham stimulation. The researchers analyzed which group had the best recall of the words they saw the previous day.

First, the scientists noted that there were no differences among the three groups during the first half of the study -- when no brain stimulation was used -- so any differences in the second half of the experiment could be attributed to the stimulation, Westphal said.

Memory scores for the group whose neurons received excitatory stimulation during the second half of the study were 15.4 percentage points higher than their scores when they received the sham stimulation.

Scores for those who received fake stimulation during both sessions increased by only 2.6 percentage points from the first to the second session -- a statistically insignificant change that was likely was due to their increased familiarity with the task, according to the paper. And scores for the group whose neuron activity was temporarily suppressed increased by just five percentage points, which the authors also wrote was not statistically significant.

"Our previous neuroimaging studies showed the left rostrolateral prefrontal cortex is highly engaged during memory retrieval," Rissman said. "Now the fact that people do better on this memory task when we excite this region with electrical stimulation provides causal evidence that it contributes to the act of memory retrieval.

"We didn't expect the application of weak electrical brain stimulation would magically make their memories perfect, but the fact that their performance increased as much as it did is surprising and it's an encouraging sign that this method could potentially be used to boost people's memories."

The study's reasoning task asked participants to decide in seven seconds whether certain pairs of words were analogies. Half of the trials featured word pairs that were true analogies, such as "'moat' is to 'castle' as 'firewall' is to 'computer.'" (In both pairs, the first word protects the second from invasion.) The other half had word pairs that were related but not actually analogous.

Researchers found no significant differences in performance among the three groups.

For the final task, focusing on perception, subjects were asked to select which of four words has the most straight lines in its printed form. (One example: Among the words "symbol," "museum," "painter" and "energy," the word "museum" has the most straight lines.) Again, the researchers found no significant differences among the three groups -- which Rissman said was expected.

"We expected to find improvement in memory, and we did," Rissman said. "We also predicted the reasoning task might improve with the increased excitability, and it did not. We didn't think this brain region would be important for the perception task."

Why do people forget names and other words? Sometimes it's because they don't pay attention when they first hear or see it, so no memory is even formed. In those cases, the electrical stimulation wouldn't help. But in cases where a memory does form but is difficult to retrieve, the stimulation could help access it.

"The stimulation is helping people to access memories that they might otherwise have reported as forgotten," Westphal said.

Although tDCS devices are commercially available, Rissman advises against anyone trying it outside of supervised research.

"The science is still in an early stage," he said. "If you do this at home, you could stimulate your brain in a way that is unsafe, with too much current or for too long."

Rissman said other areas of the brain also play important roles in retrieving memories. Their future research will aim to better understand the contributions of each region, as well as the effects of brain stimulation on other kinds of memory tasks.

https://www.sciencedaily.com/releases/2019/05/190531173508.htm

High LDL linked to early-onset Alzheimer's

May 28, 2019

Science Daily/Veterans Affairs Research Communications

Researchers with the Atlanta Veterans Affairs Medical Center and Emory University have found a link between high LDL cholesterol levels and early-onset Alzheimer's disease. The results could help doctors understand how the disease develops and what the possible causes are, including genetic variation.

According to Dr. Thomas Wingo, lead author of the study, the results show that LDL cholesterol levels may play a causal role in the development of Alzheimer's disease.

The results appear in the May 28, 2019, issue of JAMA Neurology.

 "The big question is whether there is a causal link between cholesterol levels in the blood and Alzheimer's disease risk," says Wingo. "The existing data have been murky on this point. One interpretation of our current data is that LDL cholesterol does play a causal role. If that is the case, we might need to revise targets for LDC cholesterol to help reduce Alzheimer's risk. Our work now is focused on testing whether there is a causal link."

Wingo is a neurologist and researcher with the Atlanta VA and Emory University.

Elevated cholesterol levels have been linked to increased risk of Alzheimer's later in life. This risk may be due to genetic factors tied to cholesterol. Past research has shown that a major risk factor for Alzheimer's disease is a specific mutation in a gene referred to as APOE. It is the largest known single genetic risk factor for Alzheimer's disease. This APOE variant, called APOE E4, is known to raise levels of circulating cholesterol, particularly low-density lipoprotein (LDL). This type of cholesterol is sometimes referred to as "bad cholesterol" because high LDL levels can lead to a build-up of cholesterol in the arteries.

While late-onset Alzheimer's -- the common form of the disease -- appears to be linked to cholesterol, little research has been done on a possible connection between cholesterol levels and early-onset Alzheimer's risk.

Early-onset Alzheimer's is a relatively rare form of the condition. The disease is considered "early-onset" when it appears before age 65. About 10% of all Alzheimer's cases are early-onset. Past research has shown that the condition is largely genetics-based, meaning it is likely to be inherited if a parent has it.

Three specific gene variants (dubbed APP, PSEN1, and PSEN2) are known to be related to early-onset Alzheimer's disease. APOE E4 is also a risk factor in this form of the disease, as well. These gene variants explain about 10% of early-onset Alzheimer's disease cases, meaning that 90% of cases are unexplained.

To test whether early-onset Alzheimer's disease is linked to cholesterol and identify the genetic variants that might underlie this possible association, the researchers sequenced specific genomic regions of 2,125 people, 654 of whom had early-onset Alzheimer's and 1,471 of whom were controls. They also tested blood samples of 267 participants to measure the amount of LDL cholesterol.

They found that APOE E4 explained about 10% of early-onset Alzheimer's, which is similar to estimates in late-onset Alzheimer's disease. The researchers also tested for APP, PSEN1, and PSEN2. About 3% of early-onset Alzheimer's cases had at least one of these known early-onset Alzheimer's risk factors.

After testing blood samples, the researchers found that participants with elevated LDL levels were more likely to have early-onset Alzheimer's disease, compared with patients with lower cholesterol levels. This was true even after the researchers controlled for cases with the APOE mutation, meaning cholesterol could be an independent risk factor for the disease, regardless of whether the problematic APOE gene variant is present.

The researchers did not find a link between HDL (high-density lipoprotein) cholesterol levels and early-onset Alzheimer's, and only a very slight association between the disease and triglyceride levels.

The researchers also found a new possible genetic risk factor for early-onset Alzheimer's disease. Early-onset Alzheimer's cases were higher in participants with a rare variant of a gene called APOB. This gene encodes a protein that is involved in the metabolism of lipids, or fats, including cholesterol. The finding suggests a direct link between the rare APOB mutation and Alzheimer's disease risk, according to the researchers. However, the link between LDL-C level and early-onset Alzheimer's was not fully explained by APOE or APOB, suggestion that other genes and mechanisms also increase disease risk.

While the study shines light on possible risk factors for early-onset Alzheimer's disease, the researchers say that more research is needed to fully explain the connection between the disease and cholesterol. The relative rarity of early-onset Alzheimer's disease presents a challenge in finding enough samples to perform large genetic studies on the condition, they say.

https://www.sciencedaily.com/releases/2019/05/190528120558.htm

Altered brain activity in antisocial teenagers

May 28, 2019

Science Daily/University of Zurich

Teenage girls with problematic social behavior display reduced brain activity and weaker connectivity between the brain regions implicated in emotion regulation. The findings of an international study carried out by researchers from the University of Zurich and others now offer a neurobiological explanation for the difficulties some girls have in controlling their emotions, and provide indications for possible therapy approaches.

Becoming a teenager means going through a variety of physical and behavioral changes in the context of heightened emotionality. For everyday social functioning, as well as for personal physical and mental well-being, it is important that teenagers are able to recognize, process and control these emotions. For young people who are diagnosed with conduct disorder, this process is difficult, and may lead to antisocial or aggressive reactions that clearly lie outside the age-appropriate norms, e.g. swearing, hitting, stealing and lying. An international team of researchers from Switzerland, Germany and England have been able to demonstrate using functional magnetic resonance imaging that these behavioral difficulties are reflected in the brain activity.

Neural explanation for social deficits

The study involved almost 60 female teenagers aged between 15 and 18 who were asked to try to actively regulate their emotions while the researchers measured their brain activity. Half of the group had previously been diagnosed with conduct disorder, while the other half showed typical social development for their age. In the girls with problematic social behavior, less activity was seen in the prefrontal and temporal cortex, where the brain regions responsible for cognitive control processes are located. In addition, these regions were less connected to other brain regions relevant for emotion processing and cognitive control.

"Our results offer the first neural explanation for deficits in emotion regulation in teenage girls," says first author Professor Nora Raschle of the University of Zurich. "The difference in the neural activities between the two test groups could indicate fundamental differences in emotion regulation. However, it could also be due to delayed brain development in participants with conduct disorders."

Indications for therapy

Treatment for young people diagnosed with conduct disorders may target several levels: Helping them to recognize, process and express their emotions, as well as learning emotion regulation skills. "Our findings indicate that an increased focus on emotion regulation skills may be beneficial," says Raschle. Future studies will also look at the efficacy of specific therapy programs: "We will investigate cognitive-behavioral intervention programs that aim to enhance emotion regulation in girls with conduct disorder and see whether brain function and behavior may change accordingly," explains last author Christina Stadler of the Child and Adolescent Psychiatric Center in Basel.

It has not yet been investigated whether male teenagers with conduct disorder show similar brain activity during emotion regulation. According to the authors, there are several indicators that the neural characteristics of conduct disorders may be gender-specific. "However, most studies -- unlike ours -- focus on young men, for which reason the neuro-biological understanding established up to now is mainly related to males," says Raschle.

https://www.sciencedaily.com/releases/2019/05/190528095235.htm

Music helps to build the brains of very premature babies

May 28, 2019

Science Daily/Université de Genève

To help the brains of very premature newborns develop as well as possible despite the stressful environment of intensive care, researchers propose an original solution: music written especially for them. And the first results are surprising: medical imaging reveals that the neural networks of premature infants who have listened to this music are developing much better.

In Switzerland, as in most industrialized countries, nearly 1% of children are born "very prematurely," i.e. before the 32nd week of pregnancy, which represents about 800 children yearly. While advances in neonatal medicine now give them a good chance of survival, these children are however at high risk of developing neuropsychological disorders. To help the brains of these fragile newborns develop as well as possible despite the stressful environment of intensive care, researchers at the University of Geneva (UNIGE) and the University Hospitals of Geneva (HUG), Switzerland, propose an original solution: music written especially for them. And the first results, published in the Proceedings of the National Academy of Sciences (PNAS) in the United States, are surprising: medical imaging reveals that the neural networks of premature infants who have listened to this music, and in particular a network involved in many sensory and cognitive functions, are developing much better.

The Neonatal Intensive Care Unit at the HUG welcomes each year 80 children born far too early -- between 24 and 32 weeks of pregnancy, i.e. almost four months ahead of schedule for some of them. The vast majority will survive, but half will later develop neurodevelopmental disorders, including learning difficulties, attentional or emotional disorders. "At birth, these babies' brains are still immature. Brain development must therefore continue in the intensive care unit, in an incubator, under very different conditions than if they were still in their mother's womb," explains Petra Hüppi, professor at the UNIGE Faculty of Medicine and Head of the HUG Development and Growth Division, who directed this work. "Brain immaturity, combined with a disturbing sensory environment, explains why neural networks do not develop normally."

A tailor-made music

The Geneva researchers started from a practical idea: since the neural deficits of premature babies are due, at least in part, to unexpected and stressful stimuli as well as to a lack of stimuli adapted to their condition, their environment should be enriched by introducing pleasant and structuring stimuli. As the hearing system is functional early on, music appeared to be a good candidate. But which music? "Luckily, we met the composer Andreas Vollenweider, who had already conducted musical projects with fragile populations and who showed great interest in creating music suitable for premature children," says Petra Hüppi.

Lara Lordier, PhD in neurosciences and researcher at the HUG and UNIGE, unfolds the musical creation process. "It was important that these musical stimuli were related to the baby's condition. We wanted to structure the day with pleasant stimuli at appropriate times: a music to accompany their awakening, a music to accompany their falling asleep, and a music to interact during the awakening phases." To choose instruments suitable for these very young patients, Andreas Vollenweider played many kinds of instruments to the babies, in the presence of a nurse specialized in developmental support care. "The instrument that generated the most reactions was the Indian snake charmers' flute (the punji)," recalls Lara Lordier. "Very agitated children calmed down almost instantly, their attention was drawn to the music!" The composer thus wrote three sound environments of eight minutes each, with punji, harp and bells pieces.

More efficient brain functional connections through music

The study was conducted in a double-blind study, with a group of premature infants who listened to the music, a control group of premature infants, and a control group of full-term newborns to assess whether the brain development of premature infants who had listened to the music would be more similar to that of full-term babies. Scientists used functional MRI at rest on all three groups of children. Without music, premature babies generally had poorer functional connectivity between brain areas than full-term babies, confirming the negative effect of prematurity. "The most affected network is the salience network which detects information and evaluates its relevance at a specific time, and then makes the link with the other brain networks that must act. This network is essential, both for learning and performing cognitive tasks as well as in social relationships or emotional management," says Lara Lordier.

In intensive care, children are overwhelmed by stimuli unrelated to their condition: doors open and close, alarms are triggered, etc. Unlike a full-term baby who, in utero, adjusts its rhythm to that of its mother, the premature baby in intensive care can hardly develop the link between the meaning of a stimulus in a specific context. On the other hand, the neural networks of children who heard Andreas Vollenweider's music were significantly improved: the functional connectivity between the salience network and auditory, sensorimotor, frontal, thalamus and precuneus networks, was indeed increased, resulting in brain networks organisation more similar to that of full-term infants.

When children grow up

The first children enrolled in the project are now 6 years old, at which age cognitive problems begin to be detectable. Scientists will now meet again their young patients to conduct a full cognitive and socio-emotional assessment and observe whether the positive outcomes measured in their first weeks of life have been sustained.

https://www.sciencedaily.com/releases/2019/05/190528095220.htm

Examining ethical issues surrounding wearable brain devices marketed to consumers

May 22, 2019

Science Daily/Cell Press

Wearable brain devices are now being marketed directly to consumers and often claim to confer benefits like boosting memory and modulating symptoms of depression. But despite the size of this market, little is known about the validity of these claims and, substantiated or not, the related ethical consequences or repercussions.

In a perspective being published in the journal Neuron on May 22, a team of neuroethicists looked at the range of products being sold online and questioned the claims made by companies about these products. They identified 41 devices for sale, including 22 recording devices and 19 stimulating devices. The goal of the project was to look at issues of transparency, rights, and responsibility in the way these products are marketed and sold.

"When it comes to biotechnology, and in particular brain technology, there is a heightened level of responsibility around ethical innovation," says senior author Judy Illes, a professor of Neurology and Canada Research Chair in Neuroethics at the University of British Columbia. "The great news is that it doesn't cost a lot of money to innovate ethically: it just takes some more thought, good messaging, and consideration of potential consequences. There are many experts who are poised to help this industry in a practical, solution-oriented way. It's worth it for companies to take the time to do it right."

The authors established four general categories for the claims about wearable brain devices:

 ·     Wellness: benefits like stress reduction, improved sleep, and weight loss

·     Enhancement: including improved cognition and productivity and greater physical performance

·     Practical applications: uses like research and enhanced worker safety

·     Health: improvement of conditions such as those affecting behavior and attention, as well as certain neurodegenerative diseases

Despite wide-ranging claims, there have been few studies evaluating the scientific validity of any of them. The authors didn't seek to evaluate the products' effectiveness in this review. Instead, they looked at how manufacturers could communicate the potential outcomes from using these devices -- both positive and negative -- in a more ethically responsible way.

The neuroscience wearables market has parallels to other direct-to-consumer medical products. This includes herbs and supplements, home genetic testing kits, so-called wellness CT scans, and "keepsake" 3D ultrasounds offered to pregnant women. By marketing them for wellness or recreation rather than health, companies that sell these products and services are able to avoid regulatory oversight from agencies such as the Food and Drug Administration.

"We have concerns, however, that people could turn to these devices rather than seeking medical help when they might actually need it," Illes notes. "They may also choose these devices over conventional medical treatments that they have been offered. There are a lot of potential effects that we don't know much about."

Symptoms and side effects that could result from use of these products include redness or other irritation where the devices contact the skin, headaches, pain, tingling, and nausea. Some of the products mention the possibility of side effects in their packaging, but there haven't been any studies looking at how common or serious the effects may be.

The researchers note that warning labels advising consumers about risk are largely lacking. "I would consider this an important, responsible message to consumers, but as far as I know, few of these products have it," Illes says.

Illes and her team believe that because some of these products are marketed for children, who may be particularly vulnerable to their effects on the brain, extra caution is needed. "Their bodies and brains are still developing," she says. "What are the claims for these products and how do we manage and appreciate them both for their potential benefits and possible risks?" Additional caution may also be needed for use of neuroscience wearables in the elderly, another population that may have a higher risk of potential harm.

There are also issues related to neuroscience wearable products that record brain activity. "How are these data used, and who has access to them?" Illes asks. "These are things we don't know. We should be asking these questions."

https://www.sciencedaily.com/releases/2019/05/190522141818.htm

Weight gain and loss may worsen dementia risk in older people

Study recommends continuous weight control and monitoring of weight changes to prevent dementia development

May 20, 2019

Science Daily/BMJ

Older people who experience significant weight gain or weight loss could be raising their risk of developing dementia, suggests a study from Korea.

Dementia is an important health problem especially with increasing life expectancy and an ageing population. In 2015, there were an estimated 46.8 million people diagnosed with dementia.

Meanwhile, the global prevalence of obesity, which is closely related to cardiometabolic diseases, has increased by more than 100% over the past four decades.

There is existing evidence of a possible association between cardiometabolic risk factors (such as high blood pressure, cholesterol and blood sugar levels) and dementia. However, the association between body mass index (BMI) in late-life and dementia risk remains unclear.

Therefore, a team of researchers from the Republic of Korea set out to investigate the association between BMI changes over a two-year period and dementia in an elderly Korean population.

They examined 67,219 participants aged 60-79 years who underwent BMI measurement in 2002-2003 and 2004-2005 as part of the National Health Insurance Service-Health Screening Cohort in the country.

At the start of the study period, characteristics were measured including BMI, socioeconomic status and cardiometabolic risk factors.

The difference between BMI at the start of the study period and at the next health screening (2004-2005) was used to calculate the change in BMI.

After two years, the incidence of dementia was monitored for an average 5.3 years from 2008 to 2013.

During the 5.3 years of follow-up time, the numbers of men and women with dementia totaled 4,887 and 6,685, respectively.

Results showed that there appeared to be a significant association between late-life BMI changes and dementia in both sexes.

Rapid weight change -- a 10% or higher increase or decrease in BMI -- over a two-year period was associated with a higher risk of dementia compared with a person with a stable BMI.

However, the BMI at the start of the period was not associated with dementia incidence in either sex, with the exception of low body weight in men.

After breaking down the figures based on BMI at the start of the study period, the researchers found a similar association between BMI change and dementia in the normal weight subgroup, but the pattern of this association varied in other BMI ranges.

Cardiometabolic risk factors including pre-existing hypertension, congestive heart failure, diabetes and high fasting blood sugar were significant risk factors for dementia.

In particular, patients with high fasting blood sugar had a 1.6-fold higher risk of developing dementia compared to individuals with normal or pre-high fasting blood sugar.

In addition, unhealthy lifestyle habits such as smoking, frequent drinking and less physical activity in late life were also associated with dementia.

This is an observational study, so can't establish cause, and the researchers point to some limitations, including uncertainty around the accuracy of the definition of dementia and reliance on people's self-reported lifestyle habits, which may not be accurate.

However, the study included a large amount of data and reported various modifiable risk factors of dementia in late life.

As such, the researchers conclude: "Both weight gain and weight loss may be significant risk factors associated with dementia. This study revealed that severe weight gain, uncontrolled diabetes, smoking and less physical activity in late-life had a detrimental effect on dementia development.

"Our results suggest that continuous weight control, disease management and the maintenance of a healthy lifestyle are beneficial in the prevention of dementia, even in later life."

https://www.sciencedaily.com/releases/2019/05/190520190053.htm