Memory9

Sleep deprivation accelerates Alzheimer's brain damage

January 24, 2019

Science Daily/Washington University School of Medicine

A study in mice and people shows that sleep deprivation causes tau levels to rise and tau tangles to spread through the brain. Tau tangles are associated with Alzheimer's disease and brain damage.

 

Poor sleep has long been linked with Alzheimer's disease, but researchers have understood little about how sleep disruptions drive the disease.

 

Now, studying mice and people, researchers at Washington University School of Medicine in St. Louis have found that sleep deprivation increases levels of the key Alzheimer's protein tau. And, in follow-up studies in the mice, the research team has shown that sleeplessness accelerates the spread through the brain of toxic clumps of tau - a harbinger of brain damage and decisive step along the path to dementia.

 

These findings, published online Jan. 24 in the journal Science, indicate that lack of sleep alone helps drive the disease, and suggests that good sleep habits may help preserve brain health.

 

"The interesting thing about this study is that it suggests that real-life factors such as sleep might affect how fast the disease spreads through the brain," said senior author David Holtzman, MD, the Andrew B. and Gretchen P. Jones Professor and head of the Department of Neurology. "We've known that sleep problems and Alzheimer's are associated in part via a different Alzheimer's protein -- amyloid beta -- but this study shows that sleep disruption causes the damaging protein tau to increase rapidly and to spread over time."

 

Tau is normally found in the brain -- even in healthy people -- but under certain conditions it can clump together into tangles that injure nearby tissue and presage cognitive decline. Recent research at the School of Medicine has shown that tau is high in older people who sleep poorly. But it wasn't clear whether lack of sleep was directly forcing tau levels upward, or if the two were associated in some other way. To find out, Holtzman and colleagues including first authors Jerrah Holth, PhD, a staff scientist, and Sarah Fritschi, PhD, a former postdoctoral scholar in Holtzman's lab, measured tau levels in mice and people with normal and disrupted sleep.

 

Mice are nocturnal creatures. The researchers found that tau levels in the fluid surrounding brain cells were about twice as high at night, when the animals were more awake and active, than during the day, when the mice dozed more frequently. Disturbing the mice's rest during the day caused daytime tau levels to double.

 

Much the same effect was seen in people. Brendan Lucey, MD, an assistant professor of neurology, obtained cerebrospinal fluid -- which bathes the brain and spinal cord -- from eight people after a normal night of sleep and again after they were kept awake all night. A sleepless night caused tau levels to rise by about 50 percent, the researchers discovered.

 

Staying up all night makes people stressed and cranky and likely to sleep in the next chance they get. While it's hard to judge the moods of mice, they, too, rebounded from a sleepless day by sleeping more later. To rule out the possibility that stress or behavioral changes accounted for the changes in tau levels, Fritschi created genetically modified mice that could be kept awake for hours at a time by injecting them with a harmless compound. When the compound wears off, the mice return to their normal sleep-wake cycle -- without any signs of stress or apparent desire for extra sleep.

 

Using these mice, the researchers found that staying awake for prolonged periods causes tau levels to rise. Altogether, the findings suggest that tau is routinely released during waking hours by the normal business of thinking and doing, and then this release is decreased during sleep allowing tau to be cleared away. Sleep deprivation interrupts this cycle, allowing tau to build up and making it more likely that the protein will start accumulating into harmful tangles.

 

In people with Alzheimer's disease, tau tangles tend to emerge in parts of the brain important for memory -- the hippocampus and entorhinal cortex -- and then spread to other brain regions. As tau tangles mushroom and more areas become affected, people increasingly struggle to think clearly.

 

To study whether the spread of tau tangles is affected by sleep, the researchers seeded the hippocampi of mice with tiny clumps of tau and then kept the animals awake for long periods each day. A separate group of mice also was injected with tau tangles but was allowed to sleep whenever they liked. After four weeks, tau tangles had spread further in the sleep-deprived mice than their rested counterparts. Notably, the new tangles appeared in the same areas of the brain affected in people with Alzheimer's.

 

"Getting a good night's sleep is something we should all try to do," Holtzman said. "Our brains need time to recover from the stresses of the day. We don't know yet whether getting adequate sleep as people age will protect against Alzheimer's disease. But it can't hurt, and this and other data suggest that it may even help delay and slow down the disease process if it has begun."

 

The researchers also found that disrupted sleep increased release of synuclein protein, a hallmark of Parkinson's disease. People with Parkinson's -- like those with Alzheimer's -- often have sleep problems.

https://www.sciencedaily.com/releases/2019/01/190124141536.htm

Exercise may lessen fall risk for older adults with Alzheimer's

Study indicates exercise may decrease risk of falling for older adults who have Alzheimer's disease and mental health challenges

October 29, 2018

Science Daily/American Geriatrics Society

A research team decided to explore whether exercise could reduce the risk of falling among community-dwelling people with Alzheimer's Disease who also had neuropsychiatric symptoms.

 

Alzheimer's disease (AD) is a brain disease that causes changes that kill brain cells. AD is a type of dementia, which causes memory loss and problems with thinking and making decisions. People with AD and other forms of dementia have difficulties performing the daily activities others might consider routine.

 

Dementia takes a toll on those who live with it -- and it also places a burden on caregivers. Along with problems connected to memory, language, and decision-making, dementia can cause neuropsychiatric symptoms, such as depression, anxiety, changes in mood, increased irritability, and changes in personality and behavior. People who have AD/dementia also have twice the risk for falls compared to people without dementia. About 60 percent of older adults with dementia fall each year.

 

Researchers suggest that having neuropsychiatric symptoms might predict whether an older person with AD/dementia is more likely to have a fall. We also know that exercise can reduce the number of falls in older adults with dementia. However, we don't know very much about how neuropsychiatric symptoms may increase the risk of falls, and we know even less about how exercise may reduce the risk of falls for people with dementia and neuropsychiatric symptoms. A research team decided to explore whether exercise could reduce the risk of falling among community-dwelling people with AD who also had neuropsychiatric symptoms.

 

To learn more, the researchers reviewed a study that investigated the effects of an exercise program for older adults with AD (the FINALEX trial). The study included a range of people living with different stages of AD/dementia and with neuropsychiatric symptoms. Their findings were published in the Journal of the American Geriatrics Society.

 

The original FINALEX study examined and compared older adults who had home- or group-based exercise training with people who didn't exercise but who received regular care. The researchers learned that the people who exercised had a lower risk for falls than those who didn't exercise. There was also a higher risk for falls among those who had lower scores on psychological tests and who didn't exercise.

 

This study revealed that people with AD/dementia and neuropsychiatric symptoms such as depression and anxiety have a higher risk for falls. Exercise can reduce the risk of falling for older adults with these symptoms. Further studies are needed to confirm these results.

https://www.sciencedaily.com/releases/2018/10/181029135235.htm

Stress can impair memory, reduce brain size in middle age

October 25, 2018

Science Daily/University of Texas Health Science Center at San Antonio

Stress may be causing impaired memory and brain shrinkage in middle-age adults, even before symptoms of Alzheimer's or other dementia begin, according to a new study.

 

Adults in their 40s and 50s with higher levels of cortisol -- a hormone linked to stress -- performed worse on memory and other cognitive tasks than peers of the same age with average cortisol levels, research found. Higher cortisol in the blood also was associated with smaller brain volumes, according to the study, published Oct. 24 in Neurology, the medical journal of the American Academy of Neurology.

 

"In our quest to understand cognitive aging, one of the factors attracting significant interest and concern is the increasing stress of modern life," said study senior author Sudha Seshadri, M.D., professor of neurology at UT Health San Antonio and founding director of the university's Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases. "One of the things we know in animals is that stress can lead to cognitive decline. In this study, higher morning cortisol levels in a large sample of people were associated with worse brain structure and cognition."

 

The cognitive data are from 2,231 participants in the Framingham Heart Study, for which Dr. Seshadri is a senior investigator; 2,018 participants also underwent magnetic resonance imaging (MRI) to measure brain volume. The team included Framingham collaborators at Harvard Medical School; the National Heart, Lung, and Blood Institute; Boston University School of Medicine; the University of California, Davis, at Sacramento; and UT Health San Antonio.

 

Blood serum cortisol, which varies in level throughout the day, was measured in early morning (between 7:30 and 9 a.m.) in each fasting participant. The study featured a relatively young sample of male and female participants (mean age 48.5).

 

"Cortisol affects many different functions, so it is important to fully investigate how high levels of the hormone may affect the brain," said study lead author Justin B. Echouffo-Tcheugui, M.D., Ph.D., of Harvard Medical School. "While other studies have examined cortisol and memory, we believe our large, community-based study is the first to explore, in middle-aged people, fasting blood cortisol levels and brain volume, as well as memory and thinking skills."

 

Memory loss and brain shrinkage were found in the study's middle-age participants before the onset of any symptoms, Dr. Echouffo-Tcheugui noted. He said it is important for physicians to counsel people with higher cortisol levels on ways to reduce stress, such as getting enough sleep and engaging in moderate exercise.

 

"The faster pace of life today probably means more stress, and when we are stressed, cortisol levels increase because that is our fight-or-flight response," Dr. Seshadri said. "When we are afraid, when we are threatened in any way, our cortisol levels go up. This study adds to the prevailing wisdom that it's never too early to be mindful of reducing stress."

 

Findings were adjusted for factors including age, sex, smoking and body mass index. The team asked whether having APOE4, a genetic risk factor for cardiovascular disease and Alzheimer's disease, might be associated with higher cortisol level. This did not prove to be the case.

https://www.sciencedaily.com/releases/2018/10/181025084043.htm

Memory 'brainwaves' look the same in sleep and wakefulness

October 9, 2018

Science Daily/University of Birmingham

Identical brain mechanisms are responsible for triggering memory in both sleep and wakefulness, new research has shown.

 

The study sheds new light on the processes used by the brain to 'reactivate' memories during sleep, consolidating them so they can be retrieved later.

 

Although the importance of sleep in stabilising memories is a well-established concept, the neural mechanisms underlying this are still poorly understood.

 

In this study, published in Cell Reports, scientists have been able to show for the first time in humans that distinctive neural patterns in the brain which are triggered when remembering specific memories while awake, reappear during subsequent sleep.

 

The findings provide further evidence of the beneficial effects of sleep on memory formation.

 

Gaining a more sophisticated understanding of these mechanisms also enhances our understanding of how memories are formed. This could ultimately help scientists unravel the foundations of memory disorders such as Alzheimer's and lead to the development of memory boosting interventions.

 

Working in partnership with researchers at the Donders Institute, in Holland, the team used a technique called Targeted Memory Reactivation, which is known to enhance memory. In the experiment, previously learned information -- in this case foreign vocabulary -- is played back to a person while asleep.

 

Using electroencephalography, the brain signals of the study participants were recorded while learning and remembering the foreign vocabulary before sleep.

 

Subsequently, the researchers recorded the distinct neural pathways activated as the sleeping volunteers' brains reacted to hearing the words they had learned.

 

Comparing neural signals fired by the brain in each state, the researchers were able to show clear similarities in brain activity.

 

Dr Thomas Schreiner, of the University of Birmingham's School of Psychology, who led the research, says: "Although sleep and wakefulness might seem to have little in common, this study shows that brain activity in each of these states might be more similar than we previously thought. The neural activity we recorded provides further evidence for how important sleep is to memory and, ultimately, for our well-being."

 

"If we can better understand how memory really works, this could lead to new approaches for the treatment of memory disorders, such as Alzheimer's disease."

 

Dr Tobias Staudigl, of the Donders Institute, is co-lead author of the study. He said: "Understanding how memories are reactivated in different states also provides insight into how these memories could be altered -- which might for example be interesting in therapeutic settings."

 

The team are planning a follow-on study, devising ways to investigate spontaneous memory activation during sleep. Using advanced machine learning techniques, the researchers can record and interpret neural patterns in the brain, identifying where memories are activated without the need for an external prompt.

https://www.sciencedaily.com/releases/2018/10/181009115003.htm

How sleep deprivation hinders memory

October 2, 2018

Science Daily/Michigan State University

Researchers have conducted the largest experimentally controlled study on sleep deprivation to date, revealing just how detrimental operating without sleep can be in everything from bakers adding too much salt to cookies to surgeons botching surgeries.

 

While sleep deprivation research isn't new, the level at which distractions hinder sleep-deprived persons' memories and challenge them from successfully completing tasks was not clear until MSU's team quantified the impact.

 

"If you look at mistakes and accidents in surgery, public transportation and even operating nuclear power plants, lack of sleep is one of the primary reasons for human error," said Kimberly Fenn, associate professor of psychology and director of the MSU Sleep and Learning Lab. "There are many people in critical professions who are sleep-deprived. Research has found that nearly one-quarter of the people with procedure-heavy jobs have fallen asleep on the job."

 

Published in the Journal of Experimental Psychology: General, Fenn's research is unlike previous studies because of its focus on sleep deprivation's impact on completing tasks. These tasks, Fenn explained, involve following directions and include multiple steps.

 

Some basic errors, such as adding salt twice to a recipe, might not be so serious. However, some of the world's greatest human-caused catastrophes -- like Chernobyl, the Exxon Valdez oil spill and the Challenger explosion -- along with daily train and car accidents have sleep deprivation at least partially to blame, she said.

 

Fenn hopes that her lab's findings will shed light on how critical sleep is to completing any task, be it large or small.

 

"Every day, approximately 11 sponges are left inside of patients who have undergone surgery. That's 4,000 potentially dire missteps each year and an example of a procedural task gone terribly wrong that can result from sleep deprivation," Fenn said. "Our research suggests that sleep-deprived people shouldn't perform tasks in which they are interrupted -- or, only perform them for short periods."

 

To test sleep deprivation's impact on how people follow steps in a task, Fenn's team brought 234 people into the sleep lab at 10 p.m. That night, all of the participants worked on a sequence-based procedure that involved following a series of tasks in order. Periodically, they were interrupted and had to remember where they were in the procedure before picking up again. At midnight, half of the participants went home to sleep while the other half stayed awake all night at the lab. The next morning, everyone completed the procedure once again.

 

What Fenn's team found was a stark jump in errors for those who were sleep-deprived.

 

"All participants met performance criteria in the evening, but roughly 15 percent of participants in the sleep-deprived group failed in the morning, compared to 1 percent of those who slept," Fenn said. "Furthermore, sleep-deprived participants not only showed more errors than those who slept but also showed a progressive increase in errors associated with memory as they performed the task -- an effect not observed in those who slept. This shows that the sleep-deprived group experienced a great deal of difficulty remembering where they were in the sequence during interruptions."

 

Memory maintenance, the research found, was the real culprit keeping the sleep-deprived from completing tasks successfully. With hindered memory maintenance, it's much more difficult to pick up a task where you left off without missteps, Fenn explained.

 

Fenn also explained that distractions we face every day -- whether receiving a text message or simply answering a question -- are unavoidable but especially harmful to sleep-deprived people.

 

"Operating with reduced cognitive capacity has wide-ranging effects," Fenn said. "Students may pull all-nighters and not retain information for their exams. More worrisome, individuals working critical jobs may put themselves and other members of society at risk because of sleep deprivation. It simply cannot be overlooked."

https://www.sciencedaily.com/releases/2018/10/181002114027.htm

Lowering blood pressure reduces risk of cognitive impairment

January 28, 2019

Science Daily/Wake Forest Baptist Medical Center

Intensive control of blood pressure in older people significantly reduced the risk of developing mild cognitive impairment (MCI), a precursor of early dementia, in a clinical trial led by scientists at Wake Forest School of Medicine, part of Wake Forest Baptist Health. However, the National Institutes of Health-supported Systolic Blood Pressure Intervention Trial (SPRINT) Memory and Cognition in Decreased Hypertension (SPRINT MIND) study did not prove that treating blood pressure to a goal of 120 mm Hg or less statistically reduced the risk of dementia. This result may have been due to too few new cases of dementia occurring in the study, the authors noted.

 

The results were reported in the Jan. 28 edition of the Journal of the American Medical Association.

 

MCI is defined as a decline in memory and thinking skills that is greater than expected with normal aging and is a risk factor for dementia. Dementia is defined as a group of symptoms associated with a decline in memory or other thinking skills severe enough to reduce a person's ability to perform everyday activities.

 

"As doctors treating older patients, we are encouraged to finally have a proven intervention to lower someone's risk for MCI," said the study's principal investigator, Jeff Williamson, M.D., professor of gerontology and geriatric medicine at Wake Forest School of Medicine. "In the study, we found that just three years of lowering blood pressure not only dramatically helped the heart but also helped the brain."

 

The objective of SPRINT MIND was to evaluate the effect of intensive blood pressure control on risk of dementia. Hypertension, which affects more than half of people over age 50 and more than 75 percent of those older than 65, has been identified as a potentially modifiable risk factor for MCI and dementia in previous observational studies.

 

The clinical trial, which enrolled 9361 volunteers, was conducted at 102 sites in the United States and Puerto Rico among adults 50 and older with hypertension but without diabetes or history of stroke. The participating group was 35.6 percent female, 30 percent black and 10.5 percent Hispanic and thus representative of the broader U.S. population.

 

Participants were randomly assigned to a systolic blood pressure goal of either less than 120 mm HG (intensive treatment) or less than 140 mm HG (standard treatment). They were then classified after five years as having no cognitive impairment, MCI or probable dementia.

 

"Although the study showed a 15 percent reduction in dementia in the intensively controlled group, we were disappointed that the results did not achieve statistical significance for this outcome," Williamson said. "Last week the Alzheimer's Association agreed to fund additional follow-up of SPRINT MIND participants in the hope that sufficient dementia cases will accrue, allowing for a more definitive statement on these outcomes."

 

SPRINT was stopped early due to the success of the trial in reducing cardiovascular disease. As a result, participants were on intensive blood pressure lowering treatment for a shorter period than originally planned. The authors concluded that the shorter time may have made it difficult to accurately determine the role of intensive blood pressure control on dementia cases.

 

Williamson said some caution should be exercised in interpreting the study result both because MCI was not the primary cognitive focus of the trial and because it is not clear what intensive blood pressure control may mean for the longer-term incidence of dementia. Although MCI considerably increases the risk of dementia, this progression is not inevitable and reversion to normal cognition is possible, he said.

https://www.sciencedaily.com/releases/2019/01/190128111703.htm

Brain wave device enhances memory function

October 22, 2018

Science Daily/University of California - Davis

The entrainment of theta brain waves with a commercially available device not only enhances theta wave activity, but also boosts memory performance, according to new research.

 

Electrical activity in the brain causes different types of brain waves that can be measured on the outside of the head. Theta waves occur at about five to six cycles per second, often associated with a brain that is actively monitoring something -- such as the brain of a rat navigating a maze.

 

In an earlier study, Charan Ranganath, professor of psychology, and colleagues at the Center for Neuroscience found that high levels of theta wave activity immediately before a memory task predicted better performance.

 

"Entrainment" devices use a combination of sound and lights to stimulate brain wave activity. The idea is that oscillating patterns in sensory inputs will be reflected in brain activity. The devices are marketed to address a range of problems such as anxiety, sleep issues, "low mood" and learning. However, there is very little published scientific evidence to support these claims.

 

Brooke Roberts, a postdoctoral researcher in Ranganath's lab, obtained a theta wave entrainment device and decided to test it. She had 50 volunteers either use the device for 36 minutes, or listen to 36 minutes of white noise, then do a simple memory test.

 

Improved memory performance

 

The subjects who had used the device showed both improved memory performance and enhanced theta wave activity, she found.

 

Roberts showed her results to Ranganath, who was intrigued but cautious and suggested new controls. They repeated the experiment with another 40 volunteers, but this time the control group received beta wave stimulations. Beta waves are a different type of brain wave pattern, occurring at about 12 to 30 cycles per second, associated with normal waking consciousness.

 

Once again, theta wave entrainment enhanced theta wave activity and memory performance.

 

Ranganath's lab also conducted a separate study using electrical stimulation to enhance theta waves. However, this actually had the opposite effect, disrupting theta wave activity, and temporarily weakened memory function.

 

Ranganath said he's surprised the devices work as well as they appear to do.

 

"What's surprising is that the device had a lasting effect on theta activity and memory performance for over half an hour after it was switched off," he said.

 

There is debate among neuroscientists over the function and role of these brain waves. Some researchers argue that they are simply a product of normal brain function with no particular role. Ranganath, however, thinks that they may play a role in coordinating brain regions.

 

"The neurons are more excitable at the peak of the wave, so when the waves of two brain regions are in sync with each other, they can talk to each other," he said.

 

Other authors on the paper are Alex Clarke, now at the University of Cambridge and Anglia Ruskin University, U.K.; and Richard Addante, now at California State University San Bernardino. Roberts is now a research scientist at QUASAR Inc., San Diego. The work was supported by a Guggenheim Fellowship and a Vannevar Bush Fellowship from the Office of Naval Research.

https://www.sciencedaily.com/releases/2018/10/181022172959.htm

 

Day-time naps help us acquire information not consciously perceived

'I'll sleep on it' proves scientifically sound advice

October 4, 2018

Science Daily/University of Bristol

The age-old adage 'I'll sleep on it' has proven to be scientifically sound advice, according to a new study which measured changes in people's brain activity and responses before and after a nap. The findings support the advice which suggests that a period of sleep may help weighing up pros and cons or gain insight before making a challenging decision.

 

The Medical Research Council-funded study, led by University of Bristol researchers, aimed to understand whether a short period of sleep can help us process unconscious information and how this might affect behaviour and reaction time.

 

The findings further reveal the benefits of a short bout of sleep on cognitive brain function and found that even during short bouts of sleep we process information that we are not consciously aware of.

 

While previous evidence demonstrates that sleep helps problem solving, resulting in enhanced cognition upon awaking; it was not clear whether some form of conscious mental process was required before or during sleep to aid problem solving. In this study, researchers hid information by presenting it very briefly and "masking" it -- so it was never consciously perceived -- the masked prime task. The hidden information, however, was processed at a subliminal level within the brain and the extent to which it interferes with responses to consciously perceived information was measured.

 

Sixteen healthy participants across a range of ages were recruited to take part in an experiment. Participants carried out two tasks -- the masked prime task and a control task where participants simply responded when they saw a red or blue square on a screen. Participants practiced the tasks and then either stayed awake or took a 90-minute nap before doing the tasks again.

 

Using an EEG, which records the electrical activity naturally produced in the brain, researchers measured the change in brain activity and response pre-and-post nap.

 

Sleep (but not wake) improved processing speed in the masked prime task -- but not in the control task -- suggesting sleep-specific improvements in processing of subconsciously presented primes.

 

The findings suggest that even a short bout of sleep may help improve our responses and process information. Therefore, the results here suggest a potentially sleep-dependent, task-specific enhancement of brain processing that could optimise human goal-directed behaviour.

 

Importantly, while it is already known that the process of acquiring knowledge and information recall, memory, is strengthened during sleep. This study suggests that information acquired during wakefulness may potentially be processed in some deeper, qualitative way during sleep

 

Dr LizCoulthard, Consultant Senior Lecturer in Dementia Neurology at the University of Bristol Medical School: Translational Health Sciences, said: "The findings are remarkable in that they can occur in the absence of initial intentional, conscious awareness, by processing of implicitly presented cues beneath participants' conscious awareness.

 

"Further research in a larger sample size is needed to compare if and how the findings differ between ages, and investigation of underlying neural mechanisms."

https://www.sciencedaily.com/releases/2018/10/181004095929.htm

More daytime sleepiness, more Alzheimer's risk?

Excessive daytime sleepiness linked with brain protein involved in memory-robbing disease

September 6, 2018

Science Daily/Johns Hopkins University Bloomberg School of Public Health

Analysis of data captured during a long-term study of aging adults shows that those who report being very sleepy during the day were nearly three times more likely than those who didn't to have brain deposits of beta amyloid, a protein that's a hallmark for Alzheimer's disease, years later.

 

The finding, reported Sept. 5 in the journal SLEEP, adds to a growing body of evidence that poor quality sleep could encourage this form of dementia to develop, suggesting that getting adequate nighttime sleep could be a way to help prevent Alzheimer's disease.

 

"Factors like diet, exercise and cognitive activity have been widely recognized as important potential targets for Alzheimer's disease prevention, but sleep hasn't quite risen to that status -- although that may well be changing," says Adam P. Spira, PhD, associate professor in the Department of Mental Health at the Johns Hopkins Bloomberg School of Public Health. Spira led the study with collaborators from the National Institute on Aging (NIA), the Bloomberg School and Johns Hopkins Medicine.

 

"If disturbed sleep contributes to Alzheimer's disease," he adds, "we may be able to treat patients with sleep issues to avoid these negative outcomes."

 

The study used data from the Baltimore Longitudinal Study of Aging (BLSA), a long-term study started by the NIA in 1958 that followed the health of thousands of volunteers as they age. As part of the study's periodic exams, volunteers filled a questionnaire between 1991 and 2000 that asked a simple yes/no question: "Do you often become drowsy or fall asleep during the daytime when you wish to be awake?" They were also asked, "Do you nap?" with response options of "daily," "1-2 times/week," "3-5 times/week," and "rarely or never."

 

A subgroup of BLSA volunteers also began receiving neuroimaging assessments in 1994. Starting in 2005, some of these participants received positron emission tomography (PET) scans using Pittsburgh compound B (PiB), a radioactive compound that can help identify beta-amyloid plaques in neuronal tissue. These plaques are a hallmark of Alzheimer's disease.

 

The researchers identified 123 volunteers who both answered the earlier questions and had a PET scan with PiB an average of nearly 16 years later. They then analyzed this data to see if there was a correlation between participants who reported daytime sleepiness or napping and whether they scored positive for beta-amyloid deposition in their brains.

 

Before adjusting for demographic factors that could influence daytime sleepiness, such as age, sex, education, and body-mass index, their results showed that those who reported daytime sleepiness were about three times more likely to have beta-amyloid deposition than those who didn't report daytime fatigue. After adjusting for these factors, the risk was still 2.75 times higher in those with daytime sleepiness.

 

The unadjusted risk for amyloid-beta deposition was about twice as high in volunteers who reported napping, but this did not reach statistical significance.

 

It's currently unclear why daytime sleepiness would be correlated with the deposition of beta-amyloid protein, Spira says. One possibility is that daytime sleepiness itself might somehow cause this protein to form in the brain. Based on previous research, a more likely explanation is that disturbed sleep -- due to obstructive sleep apnea, for example -- or insufficient sleep due to other factors, causes beta-amyloid plaques to form through a currently unknown mechanism, and that these sleep disturbances also cause excessive daytime sleepiness.

 

"However, we cannot rule out that amyloid plaques that were present at the time of sleep assessment caused the sleepiness," he added.

 

Animal studies in Alzheimer's disease models have shown that restricting nighttime sleep can lead to more beta-amyloid protein in the brain and spinal fluid. A handful of human studies have linked poor sleep with greater measures of beta-amyloid in neuronal tissue.

 

Researchers have long known that sleep disturbances are common in patients diagnosed with Alzheimer's disease -- caregiver stress from being up with patients at night is a leading reason for Alzheimer's disease patients to be placed in long-term care, Spira explains. Growing beta-amyloid plaques and related brain changes are thought to negatively affect sleep.

 

But this new study adds to growing evidence that poor sleep might actually contribute to Alzheimer's disease development, Spira adds. This suggests that sleep quality could be a risk factor that's modifiable by targeting disorders that affect sleep, such as obstructive sleep apnea and insomnia, as well as social- and individual-level factors, such as sleep loss due to work or binge-watching TV shows.

 

"There is no cure yet for Alzheimer's disease, so we have to do our best to prevent it. Even if a cure is developed, prevention strategies should be emphasized," Spira says. "Prioritizing sleep may be one way to help prevent or perhaps slow this condition."

https://www.sciencedaily.com/releases/2018/09/180906141501.htm

Measure of belly fat in older adults is linked with cognitive impairment

August 1, 2018

Science Daily/Trinity College Dublin

Data from over 5,000 adults over the age of 60 indicates that as waist:hip ratio increases, so does cognitive impairment. The findings have significant implications as the global prevalence of dementia is predicted to increase from 24.3 million in 2001 to 81.1 million by 2040.

 

Previous studies have found that people who are overweight do not perform as well on tests of memory and visuospatial ability compared to those who are normal weight. However, it is not well known if this is true in older adults. This is of concern within Ireland, as over half of the over 50s population is classified as being centrally obese, with only 16% of men and 26% of women reported to have a BMI (body mass index) within the normal range.

 

The researchers used data from the Trinity Ulster Department of Agriculture (TUDA) ageing cohort study comprising, which is a cross-border collaborative research project gathering data from thousands of elderly adults in Northern Ireland and Ireland.

 

The researchers found that a higher waist:hip ratio was associated with reduced cognitive function. This could be explained by an increased secretion of inflammatory markers by belly fat, which has been previously associated with a higher risk of impaired cognition. On the contrary, body mass index (BMI) was found to protect cognitive function. BMI is a crude measure of body fat and cannot differentiate between fat and fat-free mass (muscle), thus it is proposed that the fat-free mass component is likely to be the protective factor.

 

To the best of the authors' knowledge, this is one of the largest studies of older adults to report these findings. Given the high prevalence of overweight and obesity in the older population and the economic and social burden of cognitive dysfunction, the results suggest that reducing obesity and exposure to obeso-genic risk factors could offer a cost-effective public health strategy for the prevention of cognitive decline.

 

Clinical Associate Professor in Medical Gerontology at Trinity, Conal Cunningham, is the senior author of the study. He said: "While we have known for some time that obesity is associated with negative health consequences our study adds to emerging evidence suggesting that obesity and where we deposit our excess weight could influence our brain health. This has significant public health implications."

https://www.sciencedaily.com/releases/2018/08/180801115257.htm

Overnight brain stimulation improves memory

Non-invasive technique enhances memory storage without disturbing sleep

July 23, 2018

Science Daily/Society for Neuroscience

New research in humans demonstrates the potential to improve memory with a non-invasive brain stimulation technique delivered during sleep. The results come from a project that aims to better understand the process of memory consolidation, which could translate into improved memory function in both healthy and patient populations.

 

The transfer of memories from the hippocampus to the neocortex for long-term storage is thought to be enabled by synchronization of these parts of the brain during sleep. Nicholas Ketz, Praveen Pilly, and colleagues at University of New Mexico sought to enhance this natural process of overnight reactivation or neural replay to improve memory with a closed-loop transcranial alternating current stimulation system matching the phase and frequency of ongoing slow-wave oscillations during sleep.

 

Participants were trained and tested on a realistic visual discrimination task in which they had to detect potentially threatening hidden objects and people such as explosive devices and enemy snipers. The researchers found that when participants received stimulation during overnight visits to their sleep laboratory, they showed improved performance in detecting targets in similar but novel situations the next day compared to when they did not receive the stimulation, suggesting an integration of recent experience into a more robust and general memory.

 

Overnight memory changes correlated with stimulation-induced neural changes, which could be used to optimize stimulation in future applications.

 

These findings provide a method for enhancing memory consolidation without disturbing sleep.

https://www.sciencedaily.com/releases/2018/07/180723142907.htm

Treating dementia with the healing waves of sound

Ultrasound applied to brain could help treat patients with dementia

July 20, 2018

Science Daily/Tohoku University

Ultrasound waves applied to the whole brain improve cognitive dysfunction in mice with conditions simulating vascular dementia and Alzheimer's disease. It is possible that this type of therapy may also benefit humans.

 

The team, led by cardiologist Hiroaki Shimokawa, found that applying low-intensity pulsed ultrasound (LIPUS) to the whole brain of the mice improved blood vessel formation and nerve cell regeneration without having obvious side effects.

 

"The LIPUS therapy is a non-invasive physiotherapy that could apply to high-risk elderly patients without the need for surgery or anaesthesia, and could be used repeatedly," says Shimokawa.

 

Dementia affects about 50 million people worldwide, with 10 million new cases occurring every year. But there are currently no curative treatments available for vascular dementia or Alzheimer's disease, the most common causes of dementia. Also, the cells lining the brain's blood vessels are tightly packed, forming a blood-brain barrier that prevents large molecules from crossing into the brain tissue. This limits the types of drugs and cell therapies that could be made available to treat dementia.

 

Shimokawa and his team had conducted previous studies showing that LIPUS improved blood vessel formation in pigs with myocardial ischemia, a condition where there is reduced blood flow to the heart. Other studies have reported that LIPUS increases the production of proteins involved in nerve cell survival and growth, in addition to a role in promoting nerve regeneration. Focusing LIPUS treatment on a region in the brain called the hippocampus, which is involved in memory, has also been found to improve dementia in mice, but the details of how it does this need to be more fully investigated.

 

The Tohoku University team wanted to find out if whole-brain rather than focused LIPUS is effective in treating mouse models of dementia, and if it was, what was happening at the molecular levels to achieve this.

 

They found that cognitive impairment markedly improved in mice with conditions similar to vascular dementia and Alzheimer's disease when LIPUS was applied to the whole brain three times a day for 20 minutes each time. The mice with vascular dementia received the treatment on the first, third and fifth days following a surgical procedure that limited the brain's blood supply. The mice with a condition simulating Alzheimer's disease in humans received 11 LIPUS treatments over a period of three months.

 

At the molecular level, genes related to the cells lining blood vessels were turned on. Also, there was increased expression of an enzyme involved in blood vessel formation and a protein involved in nerve cell survival and growth.

 

The researchers conclude that their study, recently published in the journal Brain Stimulation, provides the first experimental evidence that whole-brain LIPUS therapy markedly improves cognitive dysfunctions without serious side effects by enhancing specific cells related to dementia's pathology.

 

The first clinical trials to evaluate the effectiveness and safety of the LIPUS treatment are already underway.

https://www.sciencedaily.com/releases/2018/07/180720092507.htm

Sugar improves memory in over-60s, helping them work smarter

July 18, 2018

Science Daily/University of Warwick

Sugar improves memory in older adults -- and makes them more motivated to perform difficult tasks at full capacity -- according to new research.

 

Led by PhD student Konstantinos Mantantzis, Professor Elizabeth Maylor and Dr Friederike Schlaghecken in Warwick's Department of Psychology, the study found that increasing blood sugar levels not only improves memory and performance, but makes older adults feel happier during a task.

 

The researchers gave young (aged 18-27) and older (aged 65-82) participants a drink containing a small amount of glucose, and got them to perform various memory tasks. Other participants were given a placebo -- a drink containing artificial sweetener.

 

The researchers measured participants' levels of engagement with the task, their memory score, mood, and their own perception of effort.

 

They found that increasing energy through a glucose drink can help both young and older adults to try harder compared to those who had the artificial sweetener. For young adults, that's where it ended, though: glucose did not improve either their mood or their memory performance.

 

However, older adults who had a glucose drink showed significantly better memory and more positive mood compared to older adults who consumed the artificial sweetener.

 

Moreover, although objective measures of task engagement showed that older adults in the glucose group put more effort into the task than those who consumed the artificial sweetener, their own self-reports showed that they did not feel as if they had tried any harder.

 

The authors concluded that short-term energy availability in the form of raised blood sugar levels could be an important factor in older adults' motivation to perform a task at their highest capacity.

 

Heightened motivation, in turn, could explain the fact that increased blood sugar levels also increase older adults' sense of self-confidence, decrease self-perceptions of effort, and improve mood. However, more research is needed to disentangle these factors in order to fully understand how energy availability affects cognitive engagement, and to develop clear dietary guidelines for older adults.

 

Konstantinos Mantantzis, a PhD student from the University of Warwick's Department of Psychology, commented:

 

"Over the years, studies have shown that actively engaging with difficult cognitive tasks is a prerequisite for the maintenance of cognitive health in older age. Therefore, the implications of uncovering the mechanisms that determine older adults' levels of engagement cannot be understated."

 

Dr Friederike Schlaghecken, from the University of Warwick's Department of Psychology, commented:

 

"Our results bring us a step closer to understanding what motivates older adults to exert effort and finding ways of increasing their willingness to try hard even if a task seems impossible to perform."

https://www.sciencedaily.com/releases/2018/07/180718104747.htm

Majority of older adults with probable dementia are likely unaware they have it

Less education and unaccompanied medical visits linked to lack of formal diagnosis or awareness of diagnosis

July 17, 2018

Science Daily/Johns Hopkins Medicine

An analysis of information gathered for an ongoing and federally sponsored study of aging and disability adds to evidence that a substantial majority of older adults with probable dementia in the United States have never been professionally diagnosed or are unaware they have been.

 

A Johns Hopkins Medicine analysis of information gathered for an ongoing and federally sponsored study of aging and disability adds to evidence that a substantial majority of older adults with probable dementia in the United States have never been professionally diagnosed or are unaware they have been.

 

A report of the findings was published in the July issue of the Journal of General Internal Medicine. Most of the findings, the researchers say, confirm previous similar estimates, but unaccompanied visits to a doctor or clinic emerged as a newly strong risk factor for lack of formal diagnosis or awareness of diagnosis.

 

"There is a huge population out there living with dementia who don't know about it," says Halima Amjad, M.D., M.P.H., assistant professor of medicine at the Johns Hopkins University School of Medicine and the study's lead author. "The implications are potentially profound for health care planning and delivery, patient-physician communication and much more," she says.

 

Overall, Amjad says, "If dementia is less severe and people are better able to perform day-to-day tasks independently, symptoms of cognitive loss are more likely masked, especially for patients who visit the doctor without a family member or friend who may be more aware of the patient's symptoms."

 

An estimated 5.7 million people in the United States live with dementia, according to the Alzheimer's Association, but only half of those have a documented, official diagnosis by a physician. Timely diagnosis is important for maintaining or improving health and planning care, says Amjad, so it's important to identify which populations are less likely to be diagnosed or less likely to be aware of their diagnosis.

 

Building on previous research, which identified activities and living conditions linked to dementia diagnosis, Amjad sought this time to pinpoint at-risk populations nationwide.

 

To do so, Amjad and the research team drew on data from the National Health and Aging Trends Study, an ongoing study of Medicare recipients ages 65 and older across the United States, and selected those who met criteria for probable dementia in 2011 and had three years of continuous fee-for-service Medicare claims before 2011. The latter information helped the researchers determine whether participants' physicians had billed for dementia diagnosis and/or care.

 

The research team identified 585 such adults and examined demographic data such as highest level of education attained, race/ethnicity and income, as well as data on whether participants were able to perform activities such as laundry, shopping or cooking on their own.

 

Among those with probable dementia, 58.7 percent were determined to be either undiagnosed (39.5 percent) or unaware of their diagnosis (19.2 percent).

 

Participants who were Hispanic, had less than a high school education, attended medical visits alone or were deemed more able to perform daily tasks were more likely to be undiagnosed. Specifically, those with at least a high school education had a 46 percent lower chance of being undiagnosed compared with those who had less education; and those who attended medical visits alone were twice as likely to be undiagnosed than those who were accompanied.

 

Participants who were diagnosed but unaware of their diagnosis had less education, attended visits alone more often and had fewer functional impairments. Those with at least a high school education had a 58 percent lower chance of being unaware compared with those who had less education. Those who attended medical visits alone were about twice as likely to be unaware than those who were accompanied. Each activity impairment decreased the chance of being unaware of diagnosis by 28 percent.

 

While Amjad acknowledges that the study is limited by potentially inaccurate self-reporting of dementia diagnoses, possible discrepancies between medical record documentation and billing codes, and the use of older data, she says the findings will likely help physicians be more alert to people who may need more careful screening.

 

"There are subsets of people doctors can focus on when implementing cognitive screening, such as minorities, those with lower levels of education and those who come in by themselves," says Amjad.

 

Looking forward, Amjad plans to study whether documentation of a dementia diagnosis is meaningful if patients and family members don't understand what a diagnosis means.

https://www.sciencedaily.com/releases/2018/07/180717094726.htm

Every person has a unique brain anatomy

July 10, 2018

Science Daily/University of Zurich

Like with fingerprints, no two people have the same brain anatomy, a study has shown. This uniqueness is the result of a combination of genetic factors and individual life experiences.

 

The fingerprint is unique in every individual: As no two fingerprints are the same, they have become the go-to method of identity verification for police, immigration authorities and smartphone producers alike. But what about the central switchboard inside our heads? Is it possible to find out who a brain belongs to from certain anatomical features? This is the question posed by the group working with Lutz Jäncke, UZH professor of neuropsychology. In earlier studies, Jäncke had already been able to demonstrate that individual experiences and life circumstances influence the anatomy of the brain.

 

Experiences make their mark on the brain

 

Professional musicians, golfers or chess players, for example, have particular characteristics in the regions of the brain which they use the most for their skilled activity. However, events of shorter duration can also leave behind traces in the brain: If, for example, the right arm is kept still for two weeks, the thickness of the brain's cortex in the areas responsible for controlling the immobilized arm is reduced. "We suspected that those experiences having an effect on the brain interact with the genetic make-up so that over the course of years every person develops a completely individual brain anatomy," explains Jäncke.

 

Magnetic resonance imaging provides basis for calculations

 

To investigate their hypothesis, Jäncke and his research team examined the brains of nearly 200 healthy older people using magnetic resonance imaging three times over a period of two years. Over 450 brain anatomical features were assessed, including very general ones such as total volume of the brain, thickness of the cortex, and volumes of grey and white matter. For each of the 191 people, the researchers were able to identify an individual combination of specific brain anatomical characteristics, whereby the identification accuracy, even for the very general brain anatomical characteristics, was over 90 percent.

 

Combination of circumstances and genetics

 

"With our study we were able to confirm that the structure of people's brains is very individual," says Lutz Jäncke on the findings. "The combination of genetic and non-genetic influences clearly affects not only the functioning of the brain, but also its anatomy." The replacement of fingerprint sensors with MRI scans in the future is unlikely, however. MRIs are too expensive and time-consuming in comparison to the proven and simple method of taking fingerprints.

 

Progress in neuroscience

 

An important aspect of the study's findings for Jäncke is that they reflect the great developments made in the field in recent years: "Just 30 years ago we thought that the human brain had few or no individual characteristics. Personal identification through brain anatomical characteristics was unimaginable." In the meantime magnetic resonance imaging has got much better, as has the software used to evaluate digitalized brain scans -- Jäncke says it is thanks to this progress that we now know better.

https://www.sciencedaily.com/releases/2018/07/180710104631.htm

Sleep disorder linked with changes to brain structure typical of dementia

July 4, 2018

Science Daily/European Lung Foundation

Obstructive sleep apnea is associated with changes to the structure of the brain that are also seen in the early stages of dementia, according to a new study.

 

OSA, where the walls of the throat relax and narrow during sleep stopping breathing, is known to reduce levels of oxygen in the blood. The new study suggests that this drop in oxygen may be linked to a shrinking of the brain's temporal lobes and a corresponding decline in memory.

 

The researchers say the study provides evidence that screening older people for OSA and giving treatment where needed could help prevent dementia in this population.

 

The study was led by Professor Sharon Naismith from the University of Sydney, Australia. She said: "Between 30 and 50% of the risk for dementia is due to modifiable factors, such as depression, high blood pressure, obesity and smoking. In recent years, researchers have recognised that various sleep disturbances are also risk factors for dementia. We wanted to look specifically at obstructive sleep apnoea and its effects on the brain and cognitive abilities."

 

The researchers worked with a group of 83 people, aged between 51 and 88 years, who had visited their doctor with concerns over their memory or mood but had no OSA diagnosis. Each participant was assessed for their memory skills and symptoms of depression, and each was given an MRI scan to measure the dimensions of different areas of the brain.

 

Participants also attended a sleep clinic where they were monitored overnight for signs of OSA using polysomnography. This technique records brain activity, levels of oxygen in the blood, heart rate, breathing and movements.

 

The researchers found that patients who had low levels of oxygen in their blood while they were sleeping tended to have reduced thickness in the left and right temporal lobes of the brain. These are regions known to be important in memory and affected in dementia.

 

They also found that this alteration in the brain was linked with participant's poorer ability to learn new information. The researchers say this is the first time a direct link of this kind has been shown.

 

Conversely, patients with signs of OSA were also more likely to have increased thickness in other regions of the brain, which the researchers say could be signs of the brain reacting to lower levels of oxygen with swelling and inflammation.

 

OSA is more common in older people and has already been linked with heart disease, stroke and cancer, but it can be treated with a continuous positive airway pressure (CPAP) device, which prevents the airway closing during sleep.

 

Professor Naismith added: "We chose to study this group because they are older and considered at risk of dementia. Our results suggest that we should be screening for OSA in older people. We should also be asking older patients attending sleep clinics about their memory and thinking skills, and carrying out tests where necessary.

 

"There is no cure for dementia so early intervention is key. On the other hand, we do have an effective treatment for OSA. This research shows that diagnosing and treating OSA could be an opportunity to prevent cognitive decline before it's too late."

 

Professor Naismith and her team are now working on research to find out whether CPAP treatment can prevent further cognitive decline and improve brain connectivity in patients with mild cognitive impairment.

 

Andrea Aliverti, Professor of Bioengineering at Politecnico di Milano, Italy, is Head of the European Respiratory Society's Assembly on Clinical Physiology and Sleep and was not involved in the research. He said: "We already know that as well as disrupting sleep, OSA can increase the risk of high blood pressure, type 2 diabetes, heart attack and stroke. This research adds to evidence that OSA is also linked to dementia and suggests a likely mechanism for the link. However, we can treat OSA and measures such as stopping smoking and losing weight can reduce the risk of developing the condition."

https://www.sciencedaily.com/releases/2018/07/180704194350.htm

Brain study paves way for therapy for common cause of dementia

July 4, 2018

Science Daily/University of Edinburgh

Scientists have uncovered a potential approach to treat one of the commonest causes of dementia and stroke in older people. Studies with rats found the treatment can reverse changes in blood vessels in the brain associated with the condition, called cerebral small vessel disease. Treatment also prevents damage to brain cells caused by these blood vessel changes, raising hope that it could offer a therapy for dementia.

 

Studies with rats found the treatment can reverse changes in blood vessels in the brain associated with the condition, called cerebral small vessel disease.

 

Treatment also prevents damage to brain cells caused by these blood vessel changes, raising hope that it could offer a therapy for dementia.

 

Small vessel disease, or SVD, is a major cause of dementia and can also worsen the symptoms of Alzheimer's disease. It is responsible for almost half of all dementia cases in the UK and is a major cause of stroke, accounting for around one in five cases.

 

Patients with SVD are diagnosed from brain scans, which detect damage to white matter -- a key component of the brain's wiring.

 

Until now, it was not known how changes in small blood vessels in the brain associated with SVD can cause damage to brain cells.

 

A team led by the University of Edinburgh found that SVD occurs when cells that line the small blood vessels in the brain become dysfunctional. This causes them to secrete a molecule into the brain.

 

The molecule stops production of the protective layer that surrounds brain cells -- called myelin -- which leads to brain damage.

 

Treating rats with drugs that stop blood vessel cells from becoming dysfunctional reversed the symptoms of SVD and prevented brain damage, tests found.

 

Researchers say that further studies will need to test whether the treatment also works when the disease is firmly established. They will also need to check if the treatment can reverse the symptoms of dementia.

 

Dementia is one of the biggest problems facing society, as people live longer and the population ages. Estimates indicate there are almost 47 million people living with dementia worldwide and the numbers affected are expected to double every 20 years, rising to more than 115 million by 2050.

 

The research, published in Science Translational Medicine, was carried out at the Medical Research Council Centre for Regenerative Medicine and the UK Dementia Research Institute at the University of Edinburgh. It was funded by the MRC, Alzheimer's Research UK and Fondation Leducq.

 

Professor Anna Williams, Group Leader at the University of Edinburgh's MRC Centre for Regenerative Medicine, said: "This important research helps us understand why small vessel disease happens, providing a direct link between small blood vessels and changes in the brain that are linked to dementia. It also shows that these changes may be reversible, which paves the way for potential treatments."

 

Dr Sara Imarisio, Head of Research at Alzheimer's Research UK said: "Changes to the blood supply in the brain play an important role in Alzheimer's disease as well as being a direct cause of vascular dementia. This pioneering research highlights a molecular link between changes to small blood vessels in the brain and damage to the insulating 'white matter' that helps nerve cells to send signals around the brain.

 

"The findings highlight a promising direction for research into treatments that could limit the damaging effects of blood vessel changes and help keep nerve cells functioning for longer. There are currently no drugs that slow down or stop Alzheimer's disease and no treatments to help people living with vascular dementia. Alzheimer's Research UK is very pleased to have helped fund this innovative research, which is only possible thanks to the work of our dedicated supporters."

 

Dr Nathan Richardson, the MRC's Head of Molecular and Cellular Medicine, commented: "This study is a great example of how innovative discovery science into regenerative mechanisms can be applied to improve our understanding of how vascular changes contribute to dementia. This research in rats opens up new possibilities for developing therapies for cerebral small vessel disease."

https://www.sciencedaily.com/releases/2018/07/180704161504.htm

Fish's use of electricity might shed light on human illnesses

June 21, 2018

Science Daily/University of Texas at Austin

African weakly electric fish, commonly called baby whales, use incredibly brief electrical pulses to sense the world around them and communicate with other members of their species. Part of that electrical mechanism exists in humans -- and by studying these fish, scientists may unlock clues about conditions like epilepsy.

 

Deep in the night in muddy African rivers, a fish uses electrical charges to sense the world around it and communicate with other members of its species. Signaling in electrical spurts that last only a few tenths of a thousandth of a second allows the fish to navigate without letting predators know it is there. Now scientists have found that the evolutionary trick these fish use to make such brief discharges could provide new insights, with a bearing on treatments for diseases such as epilepsy.

 

In a new paper in the journal Current Biology, scientists led by a team at The University of Texas at Austin and Michigan State University outline how some fish, commonly referred to as baby whales, have developed a unique bioelectric security system that lets them produce incredibly fast and short pulses of electricity so they can communicate without jamming one another's signals, while also eluding the highly sensitive electric detection systems of predatory catfish."

 

In a specialized electric organ near the tail, weakly electric fish, like the baby whales, possess a protein that also exists in the hearts and muscles of humans. The electrical pulses generated through this protein, called the KCNA7 potassium ion channel, last just a few tenths of a thousandth of a second, and some electric fish have adapted to discriminate between timing differences in electrical discharges of less than 10 millionths of a second.

 

"Most fish cannot detect electric fields, but catfish sense them. The briefer electric fish can make their electric pulse, the more difficult it is for catfish to track them," said Harold Zakon, a professor in the departments of Integrative Biology and Neuroscience.

 

The team identified a negatively charged patch in the KCNA7 protein that allows the channel in the electric fish to open quickly and be more sensitive to voltage, allowing for the extremely brief discharges.

 

What scientists have learned about these fish, the electrical signals they use and how they evolved may help humans in the future by shedding light on how those same electrical pathways operate in conditions such as epilepsy, where electrical pulses in the brain and muscles cause seizures. The finding also may have implications for discoveries about migraines and some heart conditions.

 

"Mutations in potassium channels that make them too sensitive or not sensitive enough to electrical stimuli can lead to epilepsy or cardiac and muscle diseases," said Swapna Immani, first author of the paper and a research associate in neuroscience and integrative biology. "So understanding what controls the sensitivity of potassium channels to stimuli is important for health as well as a basic understanding of ion channels."

 

Previous understanding of the same protein was based on potassium channels in fruit flies, but researchers say this paper suggests that the particular region with the negative patch might function differently in vertebrates.

 

Looking at the evolution of the specialized electric organ also can provide important windows into how genes change and express themselves. By studying unique or extreme abilities in the animal kingdom, much can be learned about the genetic basis of adaptations, the paper says.

 

"The take-home message of our project is that strange animals like weakly electric fish can give very deep insights into nature, sometimes with important biomedical consequences," said Jason Gallant, assistant professor of integrative biology at Michigan State University and a researcher on the project. "We discovered something at first blush that would seem like an idiosyncrasy of the biology of electric fish, which is always exciting but lacks broad applicability. Because of the relaxed evolutionary constraints on this important potassium channel in electric fish, which don't have to follow the same rules normally imposed by nervous system or muscle, the tinkering of natural selection has revealed a physical 'rule' that we suspect governs potassium channels more broadly."

https://www.sciencedaily.com/releases/2018/06/180621141054.htm

Fundamental rule of brain plasticity

June 21, 2018

Science Daily/Picower Institute at MIT

A series of complex experiments in the visual cortex of mice has yielded a simple rule about plasticity: When a synapse strengthens, others immediately nearby weaken.

 

Our brains are famously flexible, or "plastic," because neurons can do new things by forging new or stronger connections with other neurons. But if some connections strengthen, neuroscientists have reasoned, neurons must compensate lest they become overwhelmed with input. In a new study in Science, researchers at the Picower Institute for Learning and Memory at MIT demonstrate for the first time how this balance is struck: when one connection, called a synapse, strengthens, immediately neighboring synapses weaken based on the action of a crucial protein called Arc.

 

Senior author Mriganka Sur said he was excited but not surprised that his team discovered a simple, fundamental rule at the core of such a complex system as the brain, where 100 billion neurons each have thousands of ever-changing synapses. He likens it to how a massive school of fish can suddenly change direction, en masse, so long as the lead fish turns and every other fish obeys the simple rule of following the fish right in front of it.

 

"Collective behaviors of complex systems always have simple rules," said Sur, Paul E. and Lilah Newton Professor of Neuroscience in the Picower Institute and the department of Brain and Cognitive Sciences at MIT. "When one synapse goes up, within 50 micrometers there is a decrease in the strength of other synapses using a well-defined molecular mechanism."

 

This finding, he said, provides an explanation of how synaptic strengthening and weakening combine in neurons to produce plasticity.

 

Multiple manipulations

 

Though the rule they found was simple, the experiments that revealed it were not. As they worked to activate plasticity in the visual cortex of mice and then track how synapses changed to make that happen, lead authors Sami El-Boustani and Jacque Pak Kan Ip, postdoctoral researchers in Sur's lab, accomplished several firsts.

 

In one key experiment, they invoked plasticity by changing a neuron's "receptive field," or the patch of the visual field it responds to. Neurons receive input through synapses on little spines of their branch-like dendrites. To change a neuron's receptive field, the scientists pinpointed the exact spine on the relevant dendrite of the neuron, and then closely monitored changes in its synapses as they showed the mouse a target in a particular place on a screen that differed from the neuron's original receptive field. Whenever the target was in the new receptive field position they wanted to induce, they reinforced the neuron's response by flashing a blue light inside the mouse's visual cortex, instigating extra activity just like another neuron might. The neuron had been genetically engineered to be activated by light flashes, a technique called "optogenetics."

 

The researchers did this over and over. Because the light stimulation correlated with each appearance of the target in the new position in the mouse's vision, this caused the neuron to strengthen a particular synapse on the spine, encoding the new receptive field.

 

"I think it's quite amazing that we are able to reprogram single neurons in the intact brain and witness in the living tissue the diversity of molecular mechanisms that allows these cells to integrate new functions through synaptic plasticity," El-Boustani said.

 

As the synapse for the new receptive field grew, the researchers could see under the two-photon microscope that nearby synapses also shrank. They did not observe these changes in experimental control neurons that lacked the optogenetic stimulation.

 

But then they went further to confirm their findings. Because synapses are so tiny, they are near the limit of the resolution of light microscopy. So after the experiments the team dissected the brain tissues containing the dendrites of manipulated and control neurons and shipped them to co-authors at the Ecole Polytechnique Federal de Lausanne in Switzerland. They performed a specialized, higher-resolution, 3D electron microscope imaging, confirming that the structural differences seen under the two-photon microscope were valid.

 

"This is the longest length of dendrite ever reconstructed after being imaged in vivo," said Sur, who also directs the Simons Center for the Social Brain at MIT.

 

Of course, reprogramming a mouse's genetically engineered neuron with flashes of light is an unnatural manipulation, so the team did another more classic "monocular deprivation" experiment in which they temporarily closed one eye of a mouse. When that happens synapses in neurons related to the closed eye weaken and synapses related to the still open eye strengthen. Then when they reopened the previously closed eye, the synapses rearrange again. They tracked that action, too, and saw that as synapses strengthen, their immediate neighbors would weaken to compensate.

 

Solving the mystery of the Arc

 

Having seen the new rule in effect, the researchers were still eager to understand how neurons obey it. They used a chemical tag to watch how key "AMPA" receptors changed in the synapses and saw that synaptic enlargement and strengthening correlated with more AMPA receptor expression while shrinking and weakening correlated with less AMPA receptor expression.

 

The protein Arc regulates AMPA receptor expression, so the team realized they had to track Arc to fully understand what was going on. The problem, Sur said, is that no one had ever done that before in the brain of a live, behaving animal. So the team reached out to co-authors at the Kyoto University Graduate School of Medicine and the University of Tokyo, who invented a chemical tag that could do so.

 

Using the tag, the team could see that the strengthening synapses were surrounded with weakened synapses that had enriched Arc expression. Synapses with reduced amount of Arc were able to express more AMPA receptors whereas increased Arc in neighboring spines caused those synapses to express less AMPA receptors.

 

"We think Arc maintains a balance of synaptic resources," Ip said. "If something goes up, something must go down. That's the major role of Arc."

 

Sur said the study therefore solves a mystery of Arc: No one before had understood why Arc seemed to be upregulated in dendrites undergoing synaptic plasticity, even though it acts to weaken synapses, but now the answer was clear. Strengthening synapses increase Arc to weaken their neighbors.

 

Sur added that the rule helps explain how learning and memory might work at the individual neuron level because it shows how a neuron adjusts to the repeated simulation of another.

https://www.sciencedaily.com/releases/2018/06/180621141027.htm

Dementia can be caused by hypertension

June 13, 2018

Science Daily/Oxford University Press USA

A new study indicates that patients with high blood pressure are at a higher risk of developing dementia. This research also shows (for the first time) that an MRI can be used to detect very early signatures of neurological damage in people with high blood pressure, before any symptoms of dementia occur.

 

High blood pressure is a chronic condition that causes progressive organ damage. It is well known that the vast majority of cases of Alzheimer's disease and related dementia are not due to genetic predisposition but rather to chronic exposure to vascular risk factors.

 

The clinical approach to treatment of dementia patients usually starts only after symptoms are clearly evident. However, it has becoming increasingly clear that when signs of brain damage are manifest, it may be too late to reverse the neurodegenerative process. Physicians still lack procedures for assessing progression markers that could reveal pre-symptomatic alterations and identify patients at risk of developing dementia.

 

Researchers screened subjects admitted at the Regional Excellence Hypertension Center of the Italian Society of Hypertension in the Department of Angiocardioneurology and Translational Medicine of the I.R.C.C.S, Neuromed, in Italy. Researchers recruited people aged 40 to 65, compliant to give written informed consent and with the possibility to perform a dedicated 3 Tesla MRI scan.

 

This work was conducted on patients with no sign of structural damage and no diagnosis of dementia. All patients underwent clinical examination to determine their hypertensive status and the related target organ damage. Additionally, patients were subjected to an MRI scan to identify microstructural damage.

 

To gain insights in the neurocognitive profile of patients a specific group of tests was administered. As primary outcome of the study the researchers aimed at finding any specific signature of brain changes in white matter microstructure of hypertensive patients, associated with an impairment of the related cognitive functions.

 

The result indicated that hypertensive patients showed significant alterations in three specific white matter fiber-tracts. Hypertensive patients also scored significantly worse in the cognitive domains ascribable to brain regions connected through those fiber-tracts, showing decreased performances in executive functions, processing speed, memory and related learning tasks.

 

Overall, white matter fiber-tracking on MRIs showed an early signature of damage in hypertensive patients when otherwise undetectable by conventional neuroimaging. As these changes can be detected before patients show symptoms, these patients could be targeted with medication earlier to prevent further deterioration in brain function. These findings are also widely applicable to other forms of neurovascular disease, where early intervention could be of marked therapeutic benefit.

 

"The problem is that neurological alterations related to hypertension are usually diagnosed only when the cognitive deficit becomes evident, or when traditional magnetic resonance shows clear signs of brain damage. In both cases, it is often too late to stop the pathological process" said Giuseppe Lembo, the coordinator of this study.

 

"We have been able to see that, in the hypertensive subjects, there was a deterioration of white matter fibers connecting brain areas typically involved in attention, emotions and memory, said Lorenzo Carnevale, IT engineer and first author of the study. "An important aspect to consider is that all the patients studied did not show clinical signs of dementia and, in conventional neuroimaging, they showed no signs of cerebral damage. Of course, further studies will be necessary, but we think that the use of tractography will lead to the early identification of people at risk of dementia, allowing timely therapeutic interventions."

https://www.sciencedaily.com/releases/2018/06/180613101925.htm

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