Mindfulness training shows promise for people with MS

Study shows benefits for emotions, processing speed

May 18, 2020

Science Daily/Ohio State University

New research suggests mindfulness training may help multiple sclerosis patients in two very different ways: regulating negative emotions and improving processing speed.

People with MS who underwent the four-week mindfulness training not only improved more compared to those who did nothing -- they also improved compared to those who tried another treatment, called adaptive cognitive training.

"This was a small pilot study, so we need to replicate the results, but these findings were very encouraging," said Ruchika Prakash, corresponding author of the research and associate professor of psychology at The Ohio State University.

"It is exciting to find a treatment that may be helpful in more than one way for people with multiple sclerosis."

The findings were published recently in two journal articles: primary results in Rehabilitation Psychology, and secondary analysis in Neuropsychology.

Multiple sclerosis is the most common neurological disease in young adults and is estimated to affect nearly 1 million people in the United States. It damages the central nervous system and can lead to a variety of physical, emotional and cognitive problems.

The study involved 61 people with MS who were placed in one of three groups: four-week mindfulness training, four-week adaptive cognitive training, or a waitlist control group that did nothing during the study period, but received treatment afterward.

Mindfulness-based training involves practicing paying attention to the present moment in a nonjudgmental and accepting manner, Prakash said. Among the practices in the sessions, participants learned how to focus on the breath and to do mental "body scans" to experience how their body was feeling.

In the primary analysis of the study, led by former doctoral student Brittney Schirda, the researchers wanted to find out if mindfulness training helped multiple sclerosis patients deal with a common component of the disease: problems regulating their emotions.

"Studies suggest that 30 to 50 percent of MS patients experience some form of psychiatric disorder," Prakash said. "Anything we can do to help them cope is important for their quality of life."

Study participants completed a measure of emotional regulation at the beginning and end of the study. They were asked how much they agreed with questions like "When I'm upset, I lose control over my behavior" and "I experience my emotions as overwhelming and out of control."

Results showed that people in the mindfulness training group reported they were more able to manage their emotions at the end of the study when compared to those in the other two groups.

This included the group that received adaptive cognitive training (ACT), which has shown promise for MS patients in other studies. This ACT program used computerized games to help MS patients overcome some of their cognitive deficits that make everyday functioning more difficult, such as problems with paying attention, switching focus, and planning and organizing.

"Our results provide promising evidence that mindfulness training can help MS patients deal with their emotions in a more constructive and positive way," Prakash said.

In a secondary analysis of the same study, led by doctoral student Heena Manglani, participants were assessed on their processing speed and working memory, two cognitive functions that often decline in MS patients. They also completed additional measures of cognitive functioning.

Processing speed is the time it takes a person to complete mental tasks and is related to how well they can understand and react to the information they receive.

Findings showed that after four weeks of mindfulness training, MS patients showed significantly improved processing speed based on the tests used in the study -- more so than those in the other two groups.

"This is an exciting finding because processing speed is a core cognitive domain impacted in multiple sclerosis," Prakash said.

"We were somewhat surprised that this training intervention that we thought would mostly impact emotion regulation also enhanced processing speed."

Gains in working memory were similar in all three groups and there were no mindfulness-specific changes in other measures of cognitive functioning.

One of the reasons that mindfulness training is so promising is because it is an easily accessible treatment for all patients.

"Anyone can use mindfulness -- even individuals with limited mobility, who often find other training techniques, like exercise training, to be more challenging," Prakash said.

https://www.sciencedaily.com/releases/2020/05/200518144912.htm

Mindfulness program may benefit patients with irritable bowel syndrome

April 8, 2020

Science Daily/Wiley

Adults with irritable bowel syndrome experienced fewer gastrointestinal symptoms after they participated in a mindfulness program meant to reduce stress. Results of the study are published in Neurogastroenterology & Motility.

In the study, 53 women and 15 men with irritable bowel syndrome participated in an 8-week mindfulness-based stress reduction class.

Most participants experienced significant improvements from pre-treatment to 3 months follow up regarding gastrointestinal symptoms, quality of life, and anxiety related to gastrointestinal symptoms. Although increases in 3 of the 5 measured facets of mindfulness were found, increases in the ability to stay in the present moment and act with awareness seemed especially important.

"This study shows that people with irritable bowel syndrome can have significant improvements in their symptoms and quality of life without medication or diet change, just by participating in a mindfulness based stress reduction class," said senior author Kirsten Tillisch, MD, of the University of California, Los Angeles. "Further, it implicates a specific aspect of mindfulness as particularly important: acting with awareness. It appears that by improving this moment to moment awareness in their daily actions, people with irritable bowel syndrome feel better, possibly because this mindful activity in the present moment keeps the brain from going back to old fears or worries."

https://www.sciencedaily.com/releases/2020/04/200408085521.htm

Music intervention and mindfulness reduces the effect of mental fatigue

March 6, 2020

Science Daily/University of Southern Denmark Faculty of Health Sciences

A new study demonstrates that just 12 minutes of binaural beats and 4 weeks of mindfulness training are effective recovery strategies to counteract the negative effects of mental fatigue on sustained attention.

Mental fatigue is a psychobiological state caused by prolonged periods of demanding cognitive activity which results in slower reaction times and attention deficits. It affects the ability to focus and impacts the capacity to make optimal decisions during a given task. Mental fatigue is often responsible for accidents in traffic or the workplace and can lead to poor study efficiency. We know that mindfulness has been shown to have a positive effect on stress-coping and cognitive performance. There is also cumulating evidence suggesting that listening to binaural beats may increase sustained attention. Binaural beats is an auditory illusion which has been framed as a class of cognitive and neural entrainment (Kirk et al., 2019). Even though there are different tones of different frequency (165Hz in the left and 179 Hz in the right) presented in each ear the participant will hear one tone, which is the amalgamated difference between the two tones (beta range of 14 Hz).

In a new study, Johanne L. Axelsen (SDU), Ulrich Kirk (SDU) and Walter Staiano (University of Valencia) tests the efficacy of binaural beats compared to mindfulness as a cognitive recovery strategy to counteract the negative effect of mental fatigue on sustained attention. The study also tests whether the mindfulness interventions will show an effect for the on-the-spot novice group or for the experienced mindfulness group, who have practiced mindfulness for 4 weeks in an online-based mindfulness program through the app Headspace.

There were five phases of the study, in the initial phase the participants' mood were assessed (BRUMS) and they completed a sustained attention task to measure their mind wandering (SART). The second phase consisted of the mental fatigue treatment for 90 minutes (AX-CPT). Immediately afterwards, the participants' mood was assessed again, and the two on-the-spot interventions followed: either listening to a guided mindfulness meditation track for 12 min. or an audio track (with binaural beats) for 12 min. The control group was asked to relax for 12 min. After this the effects of the interventions were tested using the sustained attention task.

The results showed that there was indeed an effect of on-the-spot binaural beats on sustained attention while in a state of experimentally induced mental fatigue. Interestingly, the experienced mindfulness group performed significantly better than the rest of the groups on the sustained attention task already before the mental fatigue was induced. Furthermore, the group's performance was better than that of the novice mindfulness group and the control group after the mental fatigue was induced.

The results, and results from previous work by Kirk et al. (2019), indicate that binaural beats may help suppress mind-wandering and sharpening of attentional focus, which in turn reduces the negative effect of mental fatigue. The individual might feel more relaxed and less affected by mental fatigue after listening to the music.

The same goes for the experienced mindfulness group, their mindfulness training already showed on the first task where they performed better than the rest of the groups. This could indicate that practicing mindfulness helps you focus on the task at hand and is effective in offering strategies to handling stressful situations and economizing of mental energy.

Therefore, the study demonstrates that just 12 minutes of binaural beats and 4 weeks of mindfulness training were effective recovery strategies to counteract the negative effects of mental fatigue on sustained attention.

The researchers are currently investigating whether listening to binaural beats for a longer period or practicing mindfulness will improve stressed individuals' heart rate variability (HRV) and if this has an effect on performance in specific cognitive tasks.

https://www.sciencedaily.com/releases/2020/03/200306122509.htm

Exercise can slow or prevent vision loss

July 1, 2020

Science Daily/University of Virginia Health System

Exercise can slow or prevent the development of macular degeneration and may benefit other common causes of vision loss, such as glaucoma and diabetic retinopathy, new research suggests.

The new study from the University of Virginia School of Medicine found that exercise reduced the harmful overgrowth of blood vessels in the eyes of lab mice by up to 45%. This tangle of blood vessels is a key contributor to macular degeneration and several other eye diseases.

The study represents the first experimental evidence showing that exercise can reduce the severity of macular degeneration, a leading cause of vision loss, the scientists report. Ten million Americans are estimated to have the condition.

"There has long been a question about whether maintaining a healthy lifestyle can delay or prevent the development of macular degeneration. The way that question has historically been answered has been by taking surveys of people, asking them what they are eating and how much exercise they are performing," said researcher Bradley Gelfand, PhD, of UVA's Center for Advanced Vision Science. "That is basically the most sophisticated study that has been done. The problem with that is that people are notoriously bad self-reporters ... and that can lead to conclusions that may or not be true. This [study] offers hard evidence from the lab for very first time."

The Benefits of Exercise

Enticingly, the research found that the bar for receiving the benefits from exercise was relatively low -- more exercise didn't mean more benefit. "Mice are kind of like people in that they will do a spectrum of exercise. As long as they had a wheel and ran on it, there was a benefit," Gelfand said. "The benefit that they obtained is saturated at low levels of exercise."

An initial test comparing mice that voluntarily exercised versus those that did not found that exercise reduced the blood vessel overgrowth by 45%. A second test, to confirm the findings, found a reduction of 32%.

The scientists aren't certain exactly how exercise is preventing the blood vessel overgrowth. There could be a variety of factors at play, they say, including increased blood flow to the eyes.

Gelfand, of UVA's Department of Ophthalmology and Department of Biomedical Engineering, noted that the onset of vision loss is often associated with a decrease in exercise. "It is fairly well known that as people's eyes and vision deteriorate, their tendency to engage in physical activity also goes down," he said. "It can be a challenging thing to study in older people. ... How much of that is one causing the other?"

The researchers already have submitted grant proposals in hopes of obtaining funding to pursue their findings further.

"The next step is to look at how and why this happens, and to see if we can develop a pill or method that will give you the benefits of exercise without having to exercise," Gelfand said. "We're talking about a fairly elderly population [of people with macular degeneration], many of whom may not be capable of conducting the type of exercise regimen that may be required to see some kind of benefit." (He urged people to consult their doctors before beginning any aggressive exercise program.)

Gelfand, a self-described couch potato, disclosed a secret motivation for the research: "One reason I wanted to do this study was sort of selfish. I was hoping to find some reason not to exercise," he joked. "It turned out exercise really is good for you."

https://www.sciencedaily.com/releases/2020/07/200701100025.htm

Study finds exercise increases benefits of breast milk for babies

Even moderate exercise increases compound that reduces risk of heart disease, diabetes and obesity

June 29, 2020

Science Daily/Ohio State University Wexner Medical Center

A new study led by researchers at The Ohio State University Wexner Medical Center and College of Medicine finds even moderate exercise during pregnancy increases a compound in breast milk that reduces a baby's lifelong risks of serious health issues such as diabetes, obesity and heart disease.

Findings from the study published online today in the journal Nature Metabolism.

"We've done studies in the past that have shown that maternal exercise improves the health of offspring, but in this study, we wanted to begin to answer the question of why," said Kristin Stanford, a researcher at The Ohio State Wexner Medical Center's Diabetes and Metabolism Research Center and lead author of the study. "Because there is evidence that breast milk plays a major role, we wanted to isolate the effects of breast milk on offspring health."

To do that, Stanford and her team -- including researchers at the University of California, San Diego, Arkansas Children's Nutrition Center, and the Joslin Diabetes Center -- studied mice born from sedentary mothers and fed them milk from mothers who were active throughout pregnancy. They found that the health benefits from fit moms transferred to the pups, proving that they were, in fact, passed through breast milk and not simply inherited genetic traits.

Researchers also followed about 150 pregnant and postpartum women using activity trackers and found that those who had more steps per day had an increased amount of a compound known as 3SL in their breast milk, which they believe is responsible for these health benefits.

"The increase in 3SL were not necessarily related to exercise intensity, so even moderate exercise like a daily walk is enough to reap the benefits," said Stanford, an associate professor of physiology and cell biology at Ohio State's Dorothy M. Davis Heart and Lung Research Institute. "Exercise is also great for your overall health during and after pregnancy, so anything you can do to get moving is going to benefit both you and your baby."

Because many women are unable to breastfeed or experience complications that require bed rest, researchers are examining if they can isolate this beneficial compound found in the breast milk of active moms and add it to infant formula.

"This human milk oligosaccharide had a significant impact on offspring healthy. Being able to add this into formula could provide benefits for babies when women aren't able to breastfeed," Stanford said.

https://www.sciencedaily.com/releases/2020/06/200629120220.htm

Lifting weights makes your nervous system stronger, too

The first few weeks of weightlifting strengthen the reticulospinal tract, not muscles

June 29, 2020

Science Daily/Society for Neuroscience

Gym-goers may get frustrated when they don't see results from weightlifting right away, but their efforts are not in vain: the first few weeks of training strengthen the nervous system, not muscles. New research published in JNeurosci reveals how.

The brain orchestrates movement via two major neural highways descending to the spinal cord: the corticospinal tract (CST) and reticulospinal tract (RST). The CST is thought to be the dominant pathway, with the RST controlling posture. However, the CST does not change during strength training, so increased strength must stem from the more primitive RST.

Glover and Baker trained monkeys to pull a weighted handle using one arm, with the weight gradually increasing over twelve weeks. Each day, the scientists stimulated the motor cortex and the two motor tracts, measuring the resulting electrical activity in the arm muscles. Over the course of the training regimen, the electrical response from stimulating the cortex and RST increased -- a sign of strengthened signaling. After three more months of strength training, stimulating the RST elicited a greater response in the side of the spinal cord connected to the trained arm. Outputs from the reticulospinal tract become more powerful during weight training and could be the driving force behind increases in strength.

https://www.sciencedaily.com/releases/2020/06/200629132104.htm

The death marker protein cleans up your muscles after exercise

May 28, 2020

Science Daily/Faculty of Science - University of Copenhagen

Researchers at the University of Copenhagen's Department of Nutrition, Exercise and Sports have demonstrated that physical activity prompts a clean-up of muscles as the protein Ubiquitin tags onto worn-out proteins, causing them to be degraded. This prevents the accumulation of damaged proteins and helps keep muscles healthy.

Physical activity benefits health in many ways, including the building and maintenance of healthy muscles, which are important for our ability to move about normally, as well as to fulfill the vital role of regulating metabolism. As most of the carbohydrate that we eat is stored in muscle, our muscles are extremely important for regulating metabolism.

An intense bike ride boosts Ubiquitin activity

Maintaining muscular function is essential. Part of our ability to do so depends upon proteins -- the building blocks of muscles -- being degraded when worn-out and eliminated in a kind of clean up process that allows them to be replaced by freshly synthesized proteins.

Now, Danish researchers -- in collaboration with research colleagues at the University of Sydney, Australia -- have demonstrated that a single, intense, roughly 10-minute bicycle ride results in a significant increase in the activity of Ubiquitin, the 'death marker protein' and a subsequent intensification of the targeting and removal of worn-out proteins in muscles. This paves the way for an eventual build-up of new proteins:

"Muscles eliminate worn-out proteins in several ways," explains Professor Erik Richter of the Section for Molecular Physiology at UCPH's Department of Nutrition, Exercise and Sports. He continues:

"One of these methods is when Ubiquitin, "the death-marker," tags a protein in question. Ubiquitin itself is a small protein. It attaches itself to the amino acid Lysine on worn-out proteins, after which the protein is transported to a Proteasome, which is a structure that gobbles up proteins and spits them out as amino acids. These amino acids can then be reused in the synthesis of new proteins. As such, Ubiquitin contributes to a very sustainable circulation of the body's proteins."

Why physical activity is healthy

While extensive knowledge has been accumulated about how muscles regulate the build-up of new proteins during physical training, much less is known about how muscle contractions and exercise serve to significantly clean-up worn-out proteins. According to Professor Bente Kiens, another project participant: "The important role of Ubiquitin for 'cleaning-up' worn-out proteins in connection with muscular activity was not fully appreciated. Now we know that physical activity increases Ubiquitin tagging on worn-out proteins."

Professor Jørgen Wojtaszewski, a third Danish project participant, explains that their findings serve to strengthen the entire foundation for the effect of physical activity: "Basically, it explains part of the reason why physical activity is healthy. The beauty is that muscle use, in and of itself , is what initiates the processes that keep muscles 'up to date', healthy and functional."

There remains a great amount of knowledge that would be interesting to delve deeper into, as very little is known about how different training regimens, gender, diet and genetic background impact the process and thus, the possibility of influencing optimal muscle function.

About the study:

Six healthy, untrained men ages 26-28 years-old completed an 8-11 minute training session on an exercise bike. Blood tests and muscle biopsies were taken prior to and upon the completion of their training session. Thereafter, the muscle biopsies were studied using mass spectrometry, which demonstrated how Ubiquitin was used on a large scale to clean up damaged proteins.

https://www.sciencedaily.com/releases/2020/05/200528082552.htm

Molecular effects of exercise detailed

May 28, 2020

Science Daily/Stanford Medicine

A simple blood test may be able to determine how physically fit you are, according to a new study conducted by scientists at the Stanford University School of Medicine.

The test could complement treadmill tests, a more traditional clinical evaluation of fitness, and provide individuals with far more nuanced information about their body's molecular response to exercise.

The blood test is an offshoot of a complex study conducted by a team of researchers that took hundreds of thousands of molecular measurements from a group of individuals before and after exercising.

"Everybody knows exercise is good for you, but we really don't know what drives that at a molecular level," said Michael Snyder, PhD, professor and chair of genetics. "Our goal at the outset was to conduct a highly comprehensive analysis of what's happening in the body just after exercising."

The team tracked molecular markers of a wide array of biological processes, such as metabolism, immunity, oxidative stress and cardiovascular function. Hundreds of thousands of measurements from 36 study participants provided a window into the sea of chemical fluctuations the body experiences during intense exercise. To the scientists' knowledge, such comprehensive measurements of post-exercise molecular fluctuations have never been performed. What's more, the team saw that the participants who were most physically fit shared similar molecular signatures in their resting blood samples captured before exercise.

"It gave us the idea that we could develop a test to predict someone's level of fitness," said Kévin Contrepois, PhD, director of metabolomics and lipidomics in the Department of Genetics. "Aerobic fitness is one of the best measures of longevity, so a simple blood test that can provide that information would be valuable to personal health monitoring."

With the preliminary data, the team has created a proof-of-principle test, for which they've filed a patent application. The test is not currently available to the public.

A paper describing the study will be published May 28 in Cell. Snyder, who holds the Stanford W. Ascherman, MD, FACS, Professorship in Genetics, and Francois Haddad, MD, clinical professor of medicine, are co-senior authors of the study. Contrepois shares lead authorship with postdoctoral scholars Si Wu, PhD, and Daniel Hornburg, PhD, and with clinical assistant professor Kegan Moneghetti, MD, PhD.

A flurry of change

Snyder's team set out to better understand the molecular shifts that underlie changes in physical fitness. The gold standard of medical fitness assessments is a peak VO2 test, which measures a person's peak oxygen consumption during intense exercise and uses the score as a proxy for aerobic fitness. But Snyder and his team wanted more detail -- specifically, about the ways in which exercise initiates change at the molecular level.

They performed VO2 testing for 36 individuals, including Snyder, on a treadmill. Participants, both male and female, had an average body mass index of 29 kilograms/meter squared, and their age range was from 40 to 75 years old. Before the treadmill test, the researchers drew a baseline blood sample. Participants then donned an oxygen-measuring mask and ran at a slight incline until they reached peak oxygen consumption, at which point they stopped and got off the treadmill. The researchers took blood samples from participants 2 minutes, 15 minutes, 30 minutes and 60 minutes after they had reached their peaks.

"All of these measurements allow us to describe a choreography of molecular events that occur after physical exercise," Snyder said. "We know that exercise causes an array of physiological responses, such as inflammation, metabolism and hormone fluctuation, but these measurements allowed us to characterize those changes in unprecedented detail."

It turns out that in the first two minutes post-exercise, the body experiences an intense flurry of molecular activity. In most participants, molecular markers of inflammation, tissue healing and oxidative stress, a natural byproduct of metabolism, spiked sharply shortly after hopping off the treadmill, as their bodies began to recover. Molecular markers of metabolism varied, Snyder said. At 2 minutes, blood samples revealed evidence that the body was metabolizing certain amino acids for energy, but it switched to metabolizing glucose, a type of sugar, around 15 minutes. "The body breaks down glycogen as part of its exercise recovery response, so that's why we see that spike a little later," Snyder said. Glycogen is a form of stored glucose.

As part of the study, Snyder also compared the molecular response in individuals who were insulin resistant, meaning they're unable to process glucose properly, with the response in individuals who could process glucose normally. "The main difference we see is that insulin resistant individuals have a dampened immune response post-exercise," he said.

Blood test for fitness

Although it wasn't the team's original intent, they noticed some consistencies in the baseline measurements of the participants who performed better on the peak VO2 test. In these individuals, the researchers saw a strong correlation between a set of molecules and an individual's level of aerobic fitness. They discovered a collection of thousands of molecules -- including markers of immunity, metabolism and muscle activity -- that correlate with a person's aerobic fitness. "At this point, we don't fully understand the connection between some of these markers and how they are related to better fitness," Snyder said. The researchers hope to unravel those connections in a future investigation.

Snyder said that because the molecular profiling done in the study was so thorough, it wouldn't be practical for doctors to use in their clinics; it would be expensive and provide more information than necessary. But his team is working on whittling down the biomarkers to those that are most representative of a person's fitness level in an effort to make the test practical for broader use. Already, the team is developing an algorithm to select a subset of these molecules that are highly correlative to peak VO2 results, Contrepois said. As the researchers continue to optimize the fitness test, they hope it can one day be a faster, cheaper and more convenient way for people to objectively measure aerobic fitness.

https://www.sciencedaily.com/releases/2020/05/200528115826.htm

Replacing time spent sitting with sleep or light activity may improve your mood

May 20, 2020

Science Daily/Iowa State University

Moving more and sitting less was a challenge for many of us, even before states started issuing stay-at-home orders. Despite disruptions to our daily work and exercise routines, there are some subtle changes we can make at home to help improve our mental health.

New research, published by the American Journal of Preventive Medicine, found that substituting prolonged sedentary time with sleep was associated with lower stress, better mood and lower body mass index (BMI), and substituting light physical activity was associated with improved mood and lower BMI across the next year. Jacob Meyer, lead author and assistant professor of kinesiology at Iowa State University, says light activity can include walking around your home office while talking on the phone or standing while preparing dinner.

"People may not even think about some of these activities as physical activity," Meyer said. "Light activity is much lower intensity than going to the gym or walking to work, but taking these steps to break up long periods of sitting may have an impact."

Meyer and colleagues used data collected as part of the Energy Balance Study at the University of South Carolina. For 10 days, study participants, ranging in age from 21 to 35, wore an armband that tracked their energy expenditure. Meyer, director of the Wellbeing and Exercise Lab at Iowa State, says the data allowed researchers to objectively measure sleep, physical activity and sedentary time, rather than relying on self-reports.

In addition to the benefits of sleep and light physical activity, the researchers found moderate to vigorous activity was associated with lower body fat and BMI. Given the negative health effects of prolonged sedentary time, Meyer says the findings may encourage people to make small changes that are sustainable.

"It may be easier for people to change their behavior if they feel it's doable and doesn't require a major change," Meyer said. "Replacing sedentary time with housework or other light activities is something they may be able to do more consistently than going for an hour-long run."

Getting more sleep is another relatively simple change to make. Instead of staying up late watching TV, going to bed earlier and getting up at a consistent time provides multiple benefits and allows your body to recover, Meyer said. Sleeping is also unique in that it is time you're not engaging in other potentially problematic behaviors, such as eating junk food while sitting in front of a screen.

Something we can control

Making these subtle changes was associated with better current mood, but light physical activity also provided benefits for up to a year, the study found. While the research was conducted prior to the COVID-19 pandemic, Meyer says the results are timely given the growing mental health concerns during this time of physical distancing.

"With everything happening right now, this is one thing we can control or manage and it has the potential to help our mental health," Meyer said.

As states start to ease stay-at-home restrictions, Meyer is looking at changes in physical activity and sitting time with potentially interesting results for those who regularly worked out prior to the pandemic. Preliminary data from a separate study show a 32% reduction in physical activity. The question he and colleagues hope to answer is how current changes in activity interact with mental health and how our behaviors will continue to change over time.

https://www.sciencedaily.com/releases/2020/05/200520124958.htm

Exercise improves memory, boosts blood flow to brain

Study: 1-year workout program shows benefits for older people at risk of dementia

May 20, 2020

Science Daily/UT Southwestern Medical Center

Scientists have collected plenty of evidence linking exercise to brain health, with some research suggesting fitness may even improve memory. But what happens during exercise to trigger these benefits? New UT Southwestern research that mapped brain changes after one year of aerobic workouts has uncovered a potentially critical process: Exercise boosts blood flow into two key regions of the brain associated with memory. Notably, the study showed this blood flow can help even older people with memory issues improve cognition, a finding that scientists say could guide future Alzheimer's disease research.

"Perhaps we can one day develop a drug or procedure that safely targets blood flow into these brain regions," says Binu Thomas, Ph.D., a UT Southwestern senior research scientist in neuroimaging. "But we're just getting started with exploring the right combination of strategies to help prevent or delay symptoms of Alzheimer's disease. There's much more to understand about the brain and aging."

Blood flow and memory

The study, published in the Journal of Alzheimer's Disease, documented changes in long-term memory and cerebral blood flow in 30 participants, each of them 60 or older with memory problems. Half of them underwent 12 months of aerobic exercise training; the rest did only stretching.

The exercise group showed 47 percent improvement in memory scores after one year compared with minimal change in the stretch participants. Brain imaging of the exercise group, taken while they were at rest at the beginning and end of the study, showed increased blood flow into the anterior cingulate cortex and the hippocampus -- neural regions that play important roles in memory function.

Other studies have documented benefits for cognitively normal adults on an exercise program, including previous research from Thomas that showed aging athletes have better blood flow into the cortex than sedentary older adults. But the new research is significant because it plots improvement over a longer period in adults at high risk to develop Alzheimer's disease.

"We've shown that even when your memory starts to fade, you can still do something about it by adding aerobic exercise to your lifestyle," Thomas says.

Mounting evidence

The search for dementia interventions is becoming increasingly pressing: More than 5 million Americans have Alzheimer's disease, and the number is expected to triple by 2050.

Recent research has helped scientists gain a greater understanding of the molecular genesis of the disease, including a 2018 discovery from UT Southwestern's Peter O'Donnell Jr. Brain Institute that is guiding efforts to detect the condition before symptoms arise. Yet the billions of dollars spent on researching how to prevent or slow dementia have yielded no proven treatments that would make an early diagnosis actionable for patients.

UT Southwestern scientists are among many teams across the world trying to determine if exercise may be the first such intervention. Evidence is mounting that it could at least play a small role in delaying or reducing the risk of Alzheimer's disease.

For example, a 2018 study showed that people with lower fitness levels experienced faster deterioration of vital nerve fibers in the brain called white matter. A study published last year showed exercise correlated with slower deterioration of the hippocampus.

Regarding the importance of blood flow, Thomas says it may someday be used in combination with other strategies to preserve brain function in people with mild cognitive impairment.

"Cerebral blood flow is a part of the puzzle, and we need to continue piecing it together," Thomas says. "But we've seen enough data to know that starting a fitness program can have lifelong benefits for our brains as well as our hearts."

https://www.sciencedaily.com/releases/2020/05/200520084123.htm

Aerobics may be a smart workout for your brain at any age

May 13, 2020

Science Daily/American Academy of Neurology

It's never too late to lace up some sneakers and work up a sweat for brain health, according to a study published in the May 13, 2020, online issue of Neurology®, the medical journal of the American Academy of Neurology. The study suggests older adults, even couch potatoes, may perform better on certain thinking and memory tests after just six months of aerobic exercise.

"As we all find out eventually, we lose a bit mentally and physically as we age. But even if you start an exercise program later in life, the benefit to your brain may be immense," said study author Marc J. Poulin, Ph.D., D.Phil., from the Cumming School of Medicine at the University of Calgary in Alberta, Canada. "Sure, aerobic exercise gets blood moving through your body. As our study found, it may also get blood moving to your brain, particularly in areas responsible for verbal fluency and executive functions. Our finding may be important, especially for older adults at risk for Alzheimer's and other dementias and brain disease."

The study involved 206 adults who prior to starting the six-month exercise intervention worked out no more than four days per week at a moderate intensity for 30 minutes or less, or no more than two days per week a high intensity for 20 minutes or less per day. They had an average age of 66 and no history of heart or memory problems. Participants were given thinking and memory tests at the start of the study, as well as an ultrasound to measure blood flow in the brain. Physical testing was repeated at three months, and thinking and physical testing repeated at the end of the six months.

Participants were enrolled in a supervised aerobic exercise program held three days a week. As they progressed through the program, they increased their workout from an average of 20 minutes a day to an average of at least 40 minutes. In addition, people were asked to work out on their own once a week.

Researchers found that after six months of exercise, participants improved by 5.7% on tests of executive function, which includes mental flexibility and self-correction. Verbal fluency, which tests how quickly you can retrieve information, increased by 2.4%.

"This change in verbal fluency is what you'd expect to see in someone five years younger," Poulin said.

Before and after six months of aerobic activity, the participants' average peak blood flow to the brain was measured using ultrasound. Blood flow rose from an average of 51.3 centimeters per second (cm/sec) to an average of 52.7 cm/sec, a 2.8% increase. The increase in blood flow with exercise was associated with a number of modest but significant improvements in aspects of thinking that usually decline as we age, Poulin said.

"Our study showed that six months' worth of vigorous exercise may pump blood to regions of the brain that specifically improve your verbal skills as well as memory and mental sharpness," said Poulin. "At a time when these results would be expected to be decreasing due to normal aging, to have these types of increases is exciting."

A limitation of the study was that the people doing the exercise were not compared to a similar group of people who were not exercising, so the results may have been due to other factors, although the researchers tried to control for this by testing participants twice over six months before the start of the program. In addition, some of the exercise was unsupervised, so the amount reported may be unreliable.

https://www.sciencedaily.com/releases/2020/05/200513171130.htm

Exercise boosts motor skill learning via changes in brain's transmitters

Researchers find switch in chemical messaging is key prelude to motor skill acquisition

May 4, 2020

Science Daily/University of California - San Diego

Comparing the brains of mice that exercised with those that did not, researchers found that specific neurotransmitters switched following sustained exercise, leading to improved learning for motor-skill acquisition. Underscoring the critical benefits of exercise, even in a time of a global pandemic, the researchers found that mice that exercised acquired several demanding motor skills such as staying on a rotating rod or crossing a balance beam more rapidly than a non-exercised group.

Doctors have relentlessly impressed upon us the many benefits of exercise. Energy, mood, sleep and motor skills all improve with a regular fitness regimen that includes activities such as running. This has become of particular interest in the time of the COVID-19 pandemic.

But what happens in the brain during these improved states of health? The underlying neurological changes that open the door to these benefits have been unclear.

Now, Assistant Project Scientist Hui-quan Li and Distinguished Professor Nick Spitzer of the University of California San Diego have identified key neurological modifications following sustained exercise. Comparing the brains of mice that exercised with those that did not, Li and Spitzer found that specific neurons switched their chemical signals, called neurotransmitters, following exercise, leading to improved learning for motor-skill acquisition.

"This study provides new insight into how we get good at things that require motor skills and provides information about how these skills are actually learned," said Spitzer, the Atkinson Family Chair in the Biological Sciences Section of Neurobiology and a director of the Kavli Institute for Brain and Mind.

The study's results are published May 4 in Nature Communications.

Spitzer's laboratory discovered neurotransmitter switching in the adult mammalian brain and has led groundbreaking research on the ability of neurons to change their transmitter identity in response to sustained stimuli, typically leading to changes in behavior. After carrying out research that described neurotransmitter switching in depression, Spitzer and his colleagues began to turn their attention to how such switching might be involved in healthy conditions.

Li says the results underscore the importance of exercise, even at home during the current pandemic quarantine situation.

"This study shows that it's good for the brain to add more plasticity," said Li. "For people who would like to enhance their motor skill learning, it may be useful to do some exercise to promote this form of plasticity to benefit the brain. For example, if you hope to learn and enjoy challenging sports such as surfing or rock climbing when we're no longer sheltering at home, it can be good to routinely run on a treadmill or maintain a yoga practice at home now."

During the new study, Li and Spitzer compared mice that completed a week's worth of exercise on running wheels with mice that had no access to running wheels. They found that the exercised group acquired several demanding motor skills such as staying on a rotating rod or crossing a balance beam more rapidly than the non-exercised group.

When the brains of the running mice were examined, a group of neurons in the brain region known as the caudal pedunculopontine nucleus (cPPN) that regulates motor coordination was discovered to have switched neurotransmitters from acetylcholine to GABA.

To confirm their findings, the researchers used molecular tools to block the newly identified transmitter switch resulting from exercise. They found that the enhancement of motor skill learning in these mice was prevented. Based on their findings, the researchers propose a new model in which conversion of cPPN excitatory cholinergic neurons to inhibitory GABAergic neurons provides feedback control regulating motor coordination and skill learning.

The researchers say the discovery could lead to further findings where neurotransmitter switching leads to key motor skill changes. The researchers say they'd like to test ideas such as whether neurotransmitters could be deliberately switched to benefit motor skills, even without exercise. They also plan to conduct research on whether exercise similarly triggers benefits of motor skill learning in those with neurological disorders.

"We suggest that neurotransmitter switching provides the basis by which sustained running benefits motor skill learning, presenting a target for clinical treatment of movement disorders," the authors conclude in the paper.

Says Spitzer: "With an understanding of this mechanism comes the opportunity to manipulate and to harness it for further beneficial purposes. In the injured or diseased individual, it could be a way of turning things around... to give the nervous system a further boost."

https://www.sciencedaily.com/releases/2020/05/200504074712.htm

'Make physical activity part of children's routine' during lockdown

April 29, 2020

Science Daily/University of Strathclyde

Parents and carers should ensure that physical activity is part of the routine for children and families during the COVID-19 lockdown, according to an international study involving the University of Strathclyde.

The study, detailed in a comment article published in The Lancet Child & Adolescent Health, covers 15 nations. It found that time spent in places such as parks, beaches and community gardens reduced by nearly a third between the week ending 23 February -- before the World Health Organization (WHO) declared a COVID-19 pandemic -- and the week ending 5 April.

Travel by public transport was down by more than half -- 59% -- over the same period.

While these and other restrictions are in keeping with the global effort to halt the spread of COVID-19, the researchers found that they were having the effect of reducing still further what were often already low levels of physical activity in children.

The researchers make a number of recommendations to families, health professionals, teachers and policy-makers on promoting healthy activity, including:

• taking the opportunity to go outdoors, while observing distancing regulations

• incorporating physical activity into children's daily routines -- supported by use of electronic media -- and breaking up extended sedentary periods every 30 to 60 minutes; families should also be encouraged to join in while observing distancing regulations

• keeping children's bedtime and rising time consistent, keeping screens out of the rooms where they sleep and avoiding screen use before bedtime

• health professionals recommending current guidelines to parents, family members and caregivers

• promotion by governments of healthy movement behaviours in children as part of response strategies and public messages

• regular media messages promoting physical activity

Children advocating for their right to a healthy, active life within the COVID-19 restrictions.

Professor John Reilly, of Strathclyde's School of Psychological Sciences & Health, is the sole UK participant in the study.

He said: "The measures against COVID-19 are in place for a very good reason but this reduction in physical activity could be seen as an unintended consequence. Even before the lockdown measures, it was a major problem; our previous research has found that, in Scotland alone, fewer than 20% of children were meeting physical activity guidelines.

"It's important that people make whatever use of their environment they can and take the opportunities they can to keep physical activity going. The vast majority of children have access to outdoor spaces they can still use.

"While we have been fortunate with the weather during lockdown, even screen time can also incorporate activity resources, such as online fitness sessions. Breaks in screen time are also important but one reason physical activity is most needed just now is that school is the place where children most often have it.

"We have found that they are much less active on the non-school days of weekends and holidays; our concern is that they are missing out not only in education but also in activity."

Along with the UK, countries participating in the study were: China; Australia; Chile; South Africa; Morocco; Brazil; Mexico; United States; Russia; Sweden; South Korea; Netherlands, India and Canada.

The study reflects Good Health and Wellbeing, which is among the United Nations' Sustainable Development Goals. The University of Strathclyde is a signatory to the Goals, which the UN has set to pursue justice, peace, good health, responsible use of resources and the eradication of poverty and hunger.

Professor Reilly was also a member of an expert panel which produced WHO guidelines, published in 2019, on childhood physical activity.

https://www.sciencedaily.com/releases/2020/04/200429191851.htm

After a heart attack, physical activity makes you feel better

April 24, 2020

Science Daily/European Society of Cardiology

Heart attack patients who take part in a lifestyle improvement programme feel better -- especially when they do additional physical activity. That's the finding of a large study presented today on ACVC Essentials 4 You, a scientific platform of the European Society of Cardiology (ESC).

"Exercise improves fitness, which has both physical and mental health benefits," said study author Dr. Ben Hurdus of the University of Leeds, UK. "If you're more able to participate in activities that bring you happiness, then you're more likely to have a better quality of life."

Heart attack patients are typically offered lifestyle classes -- called cardiac rehabilitation -- unless they have a particular reason why it's not suitable for them. Classes include exercise, smoking cessation, advice on diet and stress management, and the importance of taking medications.

This study investigated the impact of those classes on how heart attack patients feel about their physical and mental health (collectively termed 'health-related quality of life'). Heart attacks have a detrimental effect on quality of life, including problems with mobility, self-care, and daily activities which many people take for granted such as work and leisure.

Previous research has shown a link between cardiac rehabilitation and improved quality of life in heart attack patients. However, most of these studies were conducted prior to modern drugs and procedures such as statins to lower 'bad' cholesterol and stents to open clogged arteries.

The EMMACE-3 study recruited 4,570 patients who were admitted to 48 hospitals across England with suspected heart attack in 2011 to 2013. Patients completed a questionnaire while in hospital and then at 1, 6, and 12 months after discharge. Questions included whether they attended cardiac rehabilitation, their perceived quality of life, and their physical activity levels.

Patients who attended cardiac rehabilitation had a higher quality of life at all time points compared to those who did not. Patients who went to cardiac rehabilitation and exercised 150 minutes or more per week had even higher quality of life scores compared to those who did neither.

Dr. Hurdus said: "Cardiac rehabilitation involves not only exercise but also advice on lifestyle and medications which likely all contribute to making people feel better. There are also the added social benefits such as being around other people in a similar situation and having that shared sense of community. People who also do more than the recommended minimum of 150 minutes of activity per week report even higher quality of life."

Professor Chris Gale, senior author from the University of Leeds concluded: "All heart attack patients should be referred for cardiac rehabilitation unless their healthcare professional advises against it. If it isn't discussed, speak to your local healthcare professional to see if is suitable for you."

https://www.sciencedaily.com/releases/2020/04/200424093602.htm

Slow, steady increase in exercise intensity is best for heart health

February 26, 2020

Science Daily/American Heart Association

For most people, the benefits of aerobic exercise far outweigh the risks, however, extreme endurance exercise -- such as participation in marathons and triathlons for people who aren't accustomed to high-intensity exercise -- can raise the risk of sudden cardiac arrest, atrial fibrillation (a heart rhythm disorder) or heart attacks, according to a new Scientific Statement "Exercise-Related Acute Cardiovascular Events and Potential Deleterious Adaptations Following Long-Term Exercise Training: Placing the Risks Into Perspective-An Update from the American Heart Association," published today in the Association's premier journal Circulation.

Aerobic exercises are activities in which the large muscles move in a rhythmic manner for a sustained time. They can be done at low intensity or high intensity and include walking, brisk walking, running, bicycling, swimming and many others.

"Exercise is medicine, and there is no question that moderate to vigorous physical activity is beneficial to overall cardiovascular health. However, like medicine, it is possible to underdose and overdose on exercise -- more is not always better and can lead to cardiac events, particularly when performed by inactive, unfit, individuals with known or undiagnosed heart disease," said Barry A. Franklin, Ph.D., chair of the writing committee for the new Scientific Statement, director of preventive cardiology and cardiac rehabilitation at Beaumont Health in Royal Oak, Michigan, professor of internal medicine at Oakland University William Beaumont School of Medicine in Rochester, Michigan.

"More people are running marathons, participating in triathlons and doing high-intensity interval training. The purpose of this statement is to put the benefits and risks of these vigorous exercise programs in perspective," said Franklin.

After reviewing more than 300 scientific studies, the writing committee found that, for the vast majority of people, the benefits of exercise and improving physical fitness outweigh the risks. Physically active people, such as regular walkers, have up to a 50% lower risk of heart attack and sudden cardiac death. However, the committee also identified potential risks with intense exercise training.

The writing group also reviewed a small study that concluded the risk of sudden cardiac death or heart attack is low among people participating in high-intensity exercise such as marathons and triathlons. However, over time, the risk of heart attack or sudden cardiac death among male marathon participants has risen, suggesting that these events are attracting higher risk participants (those who may have an underlying or undiagnosed cardiovascular condition such as heart rhythm abnormalities or a prior heart attack). For women, who comprised only 15% of the study population, the occurrence of sudden cardiac death was 3.5-fold less than in men.

Among participants in triathlons almost 40% of cardiac events occurred in first-time participants, indicating that inadequate training or underlying heart problems may be involved. The writing group also found that:

• Half of cardiac events occur in the last mile of a marathon or half-marathon, so maintaining a steady pace rather than sprinting is advised;

• The risk of cardiac events is greater at high altitudes, but can be decreased by spending at least one day acclimating to the elevation prior to strenuous activity;; and

• Risk of atrial fibrillation (AFib), a common heart arrhythmia that raises the risk of stroke, is beneficially reduced with moderate exercise volumes but is highest in people who are sedentary and almost as high in people who are engaged in very high volumes of exercise training, that is, high-intensity training (such as running 60-80 miles a week).

For people who want to become more active, the Association suggests that most people can start a light program of exercise and build up slowly to a moderate to vigorous exercise regimen without seeing a physician first, unless they have physical symptoms such as chest pain, chest pressure or severe shortness of breath while exercising. "It is important to start exercising -- but go slow, even if you were an athlete in high school," said Franklin.

In addition, people with known heart disease (such as a previous heart attack, bypass surgery or angioplasty) should get their doctor's approval prior to starting an exercise program.

For currently inactive/sedentary people, the Association also suggests checking with your doctor before engaging in any strenuous activities such as shoveling snow or racquet sports, which create rapid increases in heart rate and blood pressure and greatly increase the strain on the heart.

To implement a healthy physical activity program:

• Warm up before exercise by doing the planned activity -- such as walking -- at a slower pace to let your heart rate rise gradually;

• Walk on a level surface for 6-8 weeks, progressing to walking up hills, jogging or taking part in more vigorous activities as long as no symptoms occur such as shortness of breath, lightheadedness, chest pain or chest pressure;

• Increase the amount of time spent on exercise incrementally from five to ten minutes at the beginning and build up slowly to the desired time;

• Lower the intensity of your exercise when environmental conditions place a greater strain on the heart, such as high humidity or high altitude to which you are not accustomed;

• Cool down after exercise by walking at a slow pace to let your heart rate return to normal; and

• Stop and seek medical evaluation if you experience any heart-related symptoms such as lightheadedness, shortness of breath, or chest pain or pressure.

https://www.sciencedaily.com/releases/2020/02/200226072108.htm

How green space can reduce violent crime

Researchers seek to enhance public safety by harnessing nature

February 27, 2020

Science Daily/University of Virginia Health System

Properly designed and maintained outdoor green space has the potential to reduce violent crime and gun violence, to make communities safer and keep residents healthier, a new study suggests. Conversely, green space that is poorly designed and inadequately maintained can help crime take root and spread.

The findings come from a team of scientists that has assembled a big-picture review of research on the complicated relationship between nature and crime in urban areas. They identified several patterns that can help inform public policy, guide urban design and promote neighborhoods that are safe and pleasant to live in.

The project came about because members of the research team had been touched by crime, either directly or indirectly. "All of us had some sort of experience, personally or through family members. And we thought maybe we can do something about it," said Hessam Sadatsafavi, PhD, of the School of Medicine. "How to control violent crime is a polarizing issue. We are interested to see, as designers whose work is to shape the physical environment, if it's possible for us to contribute to this conversation and to take some actions to see if we, personally, can contribute to reducing crime."

The Weed of Crime Bears Bitter Fruit

The research, initiated at Cornell University, sought to synthesize the findings of many previous studies that looked at the effects of various forms of green space on crime and criminal behavior. "We said, OK, we have to start by understanding what is out there in terms of theory, what other people have found," Sadatsafavi said. "Green space can be a source of or increase the risk of crime in a neighborhood through some mechanism, and it can also reduce the risk. So why is that happening? Is there any way to find a solution to make the risk reduction more effective?"

The initial review was challenging because the topic is vast and can be approached from many angles. "You might talk about community gardens, you might talk about people's lawns," Sadatsafavi explained. "People who do the studies might go out and count the number of trees on sidewalks, or examine satellite images. Or look at the number of vacant lots that were turned into green space."

That, combined with the wide variety of crime examined and how it was reported, made it difficult for the researchers to draw specific conclusions. "But," Sadatsafavi said, "there are definitely patterns."

For example, nine studies looked at the effect of green space on gun violence. Six found that such interventions reduced crime, while three were inconclusive. "There is evidence that greening interventions at the urban level reduces violent crime, specifically gun violence," said Sadatsafavi, of UVA's Department of Emergency Medicine.

"By looking at all these studies, we were able to propose possible pathways [to reduce crime and] put together an overall picture of why this is happening, both in terms of gun violence and in terms of overall crime rate."

Sadatsafavi hopes that the researchers' findings, outlined in a paper in the International Journal of Environmental Research and Public Health, will lead to community interventions that keep people safe, decrease crime and promote better quality of life.

"The dream scenario for me, personally, is to raise awareness about the effectiveness and the cost effectiveness of these strategies," he said. "Our next goal as a team is to develop design guidelines for, say, how a community garden or small community park should be designed, to improve the positive effects of the green space and provide practical, hands-on information for people who are in the field, whether landscape architects or people who are starting their own community garden."

https://www.sciencedaily.com/releases/2020/02/200227144253.htm

Scientists find link between genes and ability to exercise

February 26, 2020

Science Daily/King's College London

A team of researchers have discovered a genetic mutation that reduces a patient's ability to exercise efficiently.

In a study published in The New England Journal of Medicine, a team including researchers from King's College London have found a link between a genetic mutation that affects cellular oxygen sensing and a patient's limited exercise capacity.

The team identified a patient who had a reduced rate of growth, persistent low blood sugar, a limited exercise capacity and a very high number of red blood cells.

The team carried out genetic and protein analysis of the patient, examined their respiratory physiology in simulated high altitude, measured their exercise capacity, and performed a series of metabolic tests.

The von Hippel-Lindau (VHL) gene is fundamental for cells to survive when oxygen availability is reduced. Following genetic analysis, an alteration on the VHL gene was identified and associated with impaired functionality in the patient's mitochondria, the powerhouse of the cell that uses oxygen to fuel cellular life. This reduced mitochondrial function efficiency limits the patient's aerobic exercise capacity compared to people without the mutation.

Dr Federico Formenti, School of Basic & Medical Biosciences, one of the leading authors of the study, comments: "The discovery of this mutation and the associated phenotype is exciting because it enables a deeper understanding of human physiology, especially in terms of how the human body senses and responds to reduced oxygen availability."

A new syndrome has been discovered that can alter the regulation of human metabolism and skeletal muscle function. This research puts the basis for the study of new mutations that affect the oxygen sensing pathways and the way these mutations are associated with the integrative function of the human body as a whole. Improving our understanding of these mechanisms may also contribute to the treatment of hypoxic conditions.

https://www.sciencedaily.com/releases/2020/02/200226171112.htm

Alzheimer risk genes converge on microglia

March 18, 2020

Science Daily/VIB (the Flanders Institute for Biotechnology)

Our DNA determines a large part of our risk for Alzheimer's disease, but it remained unclear how many genetic risk factors contribute to disease. A team led by Prof. Bart De Strooper (VIB-KU Leuven) and Dr. Mark Fiers now show that many of risk factors affect brain maintenance cells called microglia, and more particularly their response to amyloid-beta, one of the proteins aggregating in the brains of Alzheimer patients. The individual effects of small genetic variations are likely small, but the combination of hundreds of such subtle alterations might tip the balance and cause disease.

Why do some people get Alzheimer's disease while others do not, even when growing very old? Despite decades of research, we still don't know the full answer to this question. Epidemiological studies show that about two-thirds of a person's risk for Alzheimer's disease is genetically determined. A few dozen risk genes have been identified, however, recent evidence shows that there could be hundreds of additional genetic variants that each contribute in a small but significant way to disease risk.

From risk gene to disease mechanism

Bart De Strooper (VIB-KU Leuven) has been studying the mechanisms of Alzheimer's disease for decades. His team tries to find out what this combined genetic risk can teach us about how the disease develops in our brain: "Two crucial questions arise from the myriad of genetic studies. First, what is the link between these Alzheimer risk genes and the amyloid-beta plaques or tau tangles we find in Alzheimer brains; and second, are they all involved in one central cellular or molecular pathway, or do they define many parallel pathways that all lead to Alzheimer's?"

The researchers set out to understand when these genes are expressed and in particular, whether they respond to tau or amyloid?beta pathology. "When it comes to risk, you always need to take the context into account," explain Mark Fiers, co-lead author of the study. "If you don't wear your seatbelt in the car, there is no problem as long as you don't have an accident."

With this in mind, the researchers aimed to understand under which circumstances genetic risk for Alzheimer's comes into play. Fiers: "Almost every person develops some degree of Alzheimer pathology in the brain, i.e. amyloid-beta plaques and tau tangles. However, some people remain cognitively healthy despite a high pathology load, while others develop Alzheimer symptoms quite rapidly."

"To gain more insight we checked gene expression in two different mouse models of Alzheimer's, one displaying amyloid-beta and the other tau pathology, at different ages," says Annerieke Sierksma, a postdoctoral researcher in De Strooper's lab. "We identified that many of the genes linked to Alzheimer's risk are particularly responsive to amyloid-beta but not to tau pathology."

Microglia activation

The team identified 11 new risk genes that are significantly upregulated when facing increased amyloid-beta levels. All these genes are expressed in microglia, cells that play a key role in brain maintenance.

Ashley Lu, a PhD student closely involved in the analysis: "We could confirm that microglia exposed to amyloid-beta drastically switch to an activated status, something that occurs to a much lesser extent in the tau mice. These new insights indicate that a large part of the genetic risk of Alzheimer's disease involves the microglial response to amyloid-beta."

Understanding genetic risk 

Should we rethink the classical gene?based view, where certain mutations or genetic variants lead to disease? De Strooper thinks so: "One single genetic variant within a functional network will not lead to disease. However, multiple variants within the same network may tip the balance to a disease?causing disturbance. Such a hypothesis could also explain the conundrum that some /individuals with a lot of amyloid-beta in their brain do not develop clinical symptoms."

"While amyloid-beta might be the trigger of the disease, it is the genetic make?up of the microglia, and possibly other cell types, which determines whether a pathological response is induced," adds Fiers. "Identifying which genetic variants are crucial to such network disturbances and how they lead to altered gene expression will be the next big challenge."

Why mice?

"Profiling of postmortem brain tissue only provides insights into the advanced stages of the disease and does not allow to delineate cause-consequence relationships," explains De Strooper. "Genetically modified mouse models on the other hand only partially recapitulate the disease, but they allow for detailed insights into the initial steps of disease, which is of high relevance for preventative therapeutic interventions."

https://www.sciencedaily.com/releases/2020/03/200318104501.htm

Marine training may take more mental than physical grit

June 26, 2020

Science Daily/University of Southern California - Health Sciences

The United States military has a constant need for service members who can serve in elite and specialized military units, such as the Marine Corps. However, because the training courses for these forces is so rigorous, the dropout rate is high.

To help determine predictors of success or failure in elite military training, Leslie Saxon, MD, executive director of the USC Center for Body Computing, and fellow Center for Body Computing researchers monitored the physical and psychological activity of three consecutive classes of Marines and sailors enrolled in a 25-day specialized training course.

The results were published in the Journal of Medical Internet Research mHealth and uHealth.

A total of 121 trainees participated. Only slightly more than half (64) successfully completed the course.

Researchers found there was no correlation between finishing and performance on physical training standards, such as hikes or aquatic training. Physical markers such as heart rate or sleep status also did not play a role.

Rather, the biggest determinant was mental. Trainees who identified themselves as extroverted and having a positive affect -- the ability to cultivate a joyful, confident attitude -- were most likely to complete the course.

"These findings are novel because they identify traits not typically associated with military performance, showing that psychological factors mattered more than physical performance outcomes," says Saxon, who is also a cardiologist with Keck Medicine of USC and a professor of medicine (clinical scholar) at the Keck School of Medicine of USC.

Researchers were also able to pinpoint psychological stressors that triggered dropping out of the course. Trainees typically quit before a stressful aquatic training exercise or after reporting an increase in emotional or physical pain and a decrease in confidence. This led researchers to be able to predict who would drop out of the course one to two days in advance.

While Saxon has been studying human performance in elite athletes for 15 years, this was her first study involving the military. She partnered with the USC Institute for Creative Technologies, which has established military research programs, to run the study with a training company in Camp Pendleton, Calif. that trains Marines in amphibious reconnaissance. Typically, only around half of the participants finish the training.

The study authors collected baseline personality assessments of the trainees before the recruits began the course, assessing personality type, emotional processing, outlook on life and mindfulness. Researchers next provided subjects with an iPhone and Apple Watch, and a specially designed mobile application to collect continuous daily measures of trainees' mental status, physical pain, heart rate, activity, sleep, hydration and nutrition during training.

The mobile application also prompted trainees to answer daily surveys on emotional and physical pain, well-being and confidence in course completion and instructor support.

"This study, the first to collect continuous data from individuals throughout a training, suggests that there may be interventions the military can take to reduce the number of dropouts," says Saxon. "This data could be helpful in designing future training courses for Marines and other military units to increase the number of elite service members, as well as provide insights on how to help athletes and other high performers handle challenges."

Saxon is already testing whether or not various psychological interventions or coaching might encourage more trainees to stay the course.

https://www.sciencedaily.com/releases/2020/06/200626092737.htm

Female Gulf War combat veterans have persistent symptoms more than 25 years later

May 26, 2020

Science Daily/Medical College of Georgia at Augusta University

More than a quarter century after the Gulf War, female veterans who saw combat have nearly a twofold risk of reporting more than 20 total medical symptoms, like cognition and respiratory troubles, than their fellow female veterans who were not deployed, investigators report.

A sizeable percentage of the female combat veterans still report neurological symptoms; about two-thirds report difficulty remembering new information and trouble concentrating, investigators report in the Journal of Women's Health.

An association with more headaches among the combat veterans also was reported and there were "strong associations" between deployment status and respiratory symptoms with 39% of combat veterans still reporting difficulty breathing or shortness of breath. More than half also report a low tolerance for heat and cold.

"It's been over 25 years since the war ended and these are very persistent health outcomes," says Dr. Steven S. Coughlin, interim chief of the Division of Epidemiology in the Medical College of Georgia Department of Population Health Sciences. "This tells us that the way the Gulf War illness manifests itself may be different in female than male veterans, so it's important to take gender into account," says Coughlin.

Twenty years ago, female Gulf War veterans were reporting similar problems, investigators say. The newly reported findings indicate the women are showing increased frequency of symptoms over time and above the rate that would be expected with normal aging, the investigators say. Their reported symptoms correspond with higher rates of diabetes, osteoporosis, thyroid problems, asthma and irritable bowel syndrome in this and similar groups.

Additional studies are needed to find biomarkers of Gulf War illness in these former soldiers and effective treatments, they write.

"We think this has a lot of importance for the health of these veterans and hopefully, when combined with information from other studies, it will lead to improved treatment," Coughlin says.

Three hundred-and-one female Gulf War veterans from all military branches participated in the study, including 203 who were deployed and 98 who were not sent directly into a war zone.

Other persistent problems war zone veterans report include about a third saying they frequently cough when they do not have a cold. Many of their reported symptoms fit the definition of Gulf War illness, which includes having at least three of six symptom categories that include fatigue, neurological/cognitive/mood problems, pain as well as respiratory, gastrointestinal and skin problems. Younger, non-white, female Army veterans were likely to report the most symptoms, they say.

Their significant symptom burden would likely impact the veterans' quality of life and require medical evaluation and treatment, Coughlin and his colleagues write.

"We are trying to fill in this gap in the published literature about Gulf War illness among women veterans because they have been greatly understudied," Coughlin says, referencing the first conflict in which the United States included a sizeable female contingent directly in warfare.

The gender differences they are finding are consistent with earlier studies as well as other current ones coming out of Florida-based Nova Southeastern University, for example, where they are conducting a clinical trial to try to reverse some of the ill effects, he says.

The findings also are more evidence that the female veterans of the Gulf War may have more chronic health issues and conditions than other groups of women generally or female veterans specifically.

Coughlin theorizes that females may be more susceptible to some of the wartime hazards because on average their body size is smaller and because of other differences in physiology. "We can only speculate," he adds.

When troops started to come home from the Middle East following the conflict that lasted from August 1990 through February 1991, they reported a constellation of symptoms, including headaches, gastrointestinal complaints, skin ailments, forgetfulness, fatigue, particularly after exertion, and musculoskeletal pain, says Coughlin, who served as a senior epidemiologist with the Department of Veterans Affairs Central Office in Washington, D.C. The leading theory early on was that it was a psychogenic illness, somewhat similar to the PTSD experienced by many Vietnam War veterans. Now the consensus is that much of it results from the neurological impact of neurotoxins soldiers on the frontline were exposed to, Coughlin says.

"They were inundated with pesticides, there are a lot of biting flies and pests in that part of the world so they had uniforms infused with pesticides, a lot of them even wore a dog's flea collar for extra protection," he says. Soldiers also were asked to take pyridostigmine bromide, a drug given to patients with myasthenia gravis to improve muscle strength, prophylactically to help protect them from nerve agents in field, but the drug itself is mildly toxic to nerves and there is some evidence that, in combination with some of the insecticides used, it becomes more potent.

"Every time the alarms went off, they would have to take these little white pills," Coughlin says. There were other environmental toxins as well, like blown up munitions factories and low dose exposure to sarin nerve gas and others. "It's similar to what you see among agricultural workers exposed to pesticides," he notes. The veterans also were exposed to hazards such as smoke from oil well fires and burn pits used to incinerate waste, the investigators write.

The new study looked at the frequency and patterns of health symptoms in the female veterans as well as military service and lifestyle. The investigators theorized that symptoms associated with Gulf War illness would be more prominent in the women who saw conflict.

They found the deployed veterans were significantly more likely to report seven symptoms consistent with Gulf War illness, including low tolerance for heat or cold, difficulty breathing or shortness of breath, frequent coughing without having a cold, difficulty concentrating and remembering recent information, feeling down or depressed and anxious, the investigators write. Those deployed were more than twice as likely to report more total symptoms and nonwhites -- including American Indians, Alaska natives as well as Asian Americans and Pacific Islands Americans -- were four times more likely to report symptoms than whites. Older women were less likely than younger women to report symptoms and those enlisted in the Air Force and Navy were significantly less likely to report more symptoms than those in the Army.

Participants in the study were a mean age of early 50s and other demographics, like race, ethnicity and education, were similar, but those who saw combat were more likely to have served in the Army or Navy and less likely to have served in the Air Force.

They were taken from a national cohort of 1,318 Gulf War veterans created from the Veterans Affairs Cooperative Studies Program 585 Gulf War Era Cohort and Biorepository pilot study. Outcomes of female veterans in the group have not been reported separately. Women comprised 7% of the 700,000 military personnel to serve in the Gulf War, the largest number of women to serve in a war zone in U.S. military history at that time. The influx of the some 50,000 female Gulf War veterans resulted in the establishment of specialty clinics for them at VA hospitals. Evidence indicates about 19% of women veterans still have delayed or unmet health care needs, possibly because of expanded military roles for women, including increased exposure to combat, the investigators write.

Female veterans who have been involved in conflicts since the Vietnam War report higher rates of poor sleep quality, fatigue, insomnia, chronic pain, including headache and musculoskeletal complaints, respiratory problems and skin problems, as well as cognitive and mood related complaints, Coughlin and his colleagues write.

https://www.sciencedaily.com/releases/2020/05/200526091406.htm