How age and sex influence our body clocks

February 7, 2023

Science Daily/Ecole Polytechnique Fédérale de Lausanne

The human body runs on a finely tuned clock synchronized to the 24-hour cycle of Earth's rotation, known as the circadian clock, which controls various physiological processes such as the sleep-wake cycle, hormone production, and metabolism.

In a new study, researchers led by Felix Naef at EPFL were able to uncover the organization of tissue-specific gene expression rhythms in humans, and shed light on how our body clocks depend on sex and age.

In model organisms, analyzing molecular rhythms is usually done using time-stamped measurements -- but such data are not readily available in humans. To work around this, the researchers used existing measurements from a large cohort of post-mortem donors, combined with a novel computer algorithm that was designed to assign internal clock times to nearly one thousand donors.

"Interestingly, the data-science algorithm we developed turned out to resemble models from magnetic systems, which are well studied in statistical physics," says Felix Naef. Using this innovative approach, the researchers obtained the first comprehensive and accurate whole-organism view of 24-hour gene expression rhythms in 46 human tissues.

The study found that the core clock machinery properties are conserved across the body and do not change significantly with sex and age. On the other hand, the analysis revealed extensive programs of gene expression rhythms across major compartments of metabolism, stress response pathways and immune function, and these programs peaked twice a day.

In fact, the emerging whole-body organization of circadian timing shows that rhythmic gene expression occurs as morning and evening waves, with the timing in the adrenal gland peaking first, while brain regions displayed much lower rhythmicity compared to metabolic tissues.

Dividing the donors by sex and age revealed a previously unknown richness of sex- and age- specific gene expression rhythms spread across biological functions. Strikingly, gene expression rhythms were sex-dimorphic (different in males and females) and more sustained in females, while rhythmic programs were generally reduced with age across the body.

Sex-dimorphic rhythms -- referring to the differences between males and females -- were particularly noticeable in the liver's "xenobiotic detoxification," the process by which liver breaks down harmful substances. Additionally, the study found that as people grow older, the rhythm of gene expression decreases in the heart's arteries, which may explain why older people are more susceptible to heart disease. This information could be useful in the field of "chronopharmacology," which is the study of how a person's internal clock affects the effectiveness and side effects of medication.

This study provides new insights into the complex interplay between our body clock, sex, and age. By understanding these rhythms, we might find new ways of diagnosing and treating pathologies such as sleep disorders and metabolic diseases.

https://www.sciencedaily.com/releases/2023/02/230203105329.htm

Learning with all your senses: Multimodal enrichment as the optimal learning strategy of the future

February 1, 2023

Science Daily/Technische Universität Dresden

Many educational approaches assume that integrating complementary sensory and motor information into the learning experience can enhance learning, for example gestures help in learning new vocabulary in foreign language classes. In her recent publication, neuroscientist Katharina von Kriegstein from Technische Universität Dresden and Brian Mathias of the University of Aberdeen summarize these methods under the term "multimodal enrichment." This means enrichment with multiple senses and movement. Numerous current scientific studies prove that multimodal enrichment can enhance learning outcomes. Experiments in classrooms show similar results.

In the review article, the two researchers compare these findings with cognitive, neuroscience, and computational theories of multimodal enrichment. Recent neuroscience research has found that the positive effects of enriched learning are associated with response in brain regions that serve perception and motor function. For example, hearing a recently learned foreign language word, may elicit activity in motor brain regions if the word was associated with the performance of a congruent gesture during learning. These brain responses are causal to the benefits of multimodal enrichment for learning outcome. Computer algorithms confirm this hypothesis.

"The brain is optimized for learning with all the senses and with movement. Brain structures for perception and motor skills work together to promote this type of learning. We hope that our deeper understanding of the brain's learning mechanisms, will facilitate the development of optimal learning strategies in the future," explains Brian Mathias.

Katharina von Kriegstein adds, "The results of the literature we reviewed contribute to our understanding of why several long-used learning strategies, such as parts of the Montessori method, are effective. They also provide clear clues as to why some approaches are not as effective. Recently uncovered neuroscientific mechanisms may inspire the updating of cognitive and computational theories of learning, providing new hypotheses about learning. We anticipate that such an interdisciplinary and evidence-based approach will lead to the optimization of learning and teaching strategies in the future, for both humans and artificial systems."

https://www.sciencedaily.com/releases/2023/02/230201134225.htm

Tuning into brainwave rhythms speeds up learning in adults

January 31, 2023

Science Daily/University of Cambridge

Scientists have shown for the first time that briefly tuning into a person's individual brainwave cycle before they perform a learning task dramatically boosts the speed at which cognitive skills improve.

Calibrating rates of information delivery to match the natural tempo of our brains increases our capacity to absorb and adapt to new information, according to the team behind the study.

University of Cambridge researchers say that these techniques could help us retain "neuroplasticity" much later in life and advance lifelong learning.

"Each brain has its own natural rhythm, generated by the oscillation of neurons working together," said Prof Zoe Kourtzi, senior author of the study from Cambridge's Department of Psychology. "We simulated these fluctuations so the brain is in tune with itself -- and in the best state to flourish."

"Our brain's plasticity is the ability to restructure and learn new things, continually building on previous patterns of neuronal interactions. By harnessing brainwave rhythms, it may be possible to enhance flexible learning across the lifespan, from infancy to older adulthood," Kourtzi said.

The findings, published in the journal Cerebral Cortex, will be explored as part of the Centre for Lifelong Learning and Individualised Cognition: a research collaboration between Cambridge and Nanyang Technological University (NTU), Singapore.

The neuroscientists used electroencephalography -- or EEG -- sensors attached to the head to measure electrical activity in the brain of 80 study participants, and sample brainwave rhythms.

The team took alpha waves readings. The mid-range of the brainwave spectrum, this wave frequency tends to dominate when we are awake and relaxed.

Alpha waves oscillate between eight to twelve hertz: a full cycle every 85-125 milliseconds. However, every person has their own peak alpha frequency within that range.

Scientists used these readings to create an optical "pulse": a white square flickering on a dark background at the same tempo as each person's individual alpha wave.

Participants got a 1.5-second dose of personalised pulse to set their brain working at its natural rhythm -- a technique called "entrainment" -- before being presented with a tricky quick-fire cognitive task: trying to identify specific shapes within a barrage of visual clutter.

A brainwave cycle consists of a peak and trough. Some participants received pulses matching the peak of their waves, some the trough, while some got rhythms that were either random or at the wrong rate (a little faster or slower). Each participant repeated over 800 variations of the cognitive task, and the neuroscientists measured how quickly people improved.

The learning rate for those locked into the right rhythm was at least three times faster than for all the other groups. When participants returned the next day to complete another round of tasks, those who learned much faster under entrainment had maintained their higher performance level.

"It was exciting to uncover the specific conditions you need to get this impressive boost in learning," said first author Dr Elizabeth Michael, now at Cambridge's Cognition and Brain Sciences Unit.

"The intervention itself is very simple, just a brief flicker on a screen, but when we hit the right frequency plus the right phase alignment, it seems to have a strong and lasting effect."

Importantly, entrainment pulses need to chime with the trough of a brainwave. Scientists believe this is the point in a cycle when neurons are in a state of "high receptivity."

"We feel as if we constantly attend to the world, but in fact our brains take rapid snapshots and then our neurons communicate with each other to string the information together," said co-author Prof Victoria Leong, from NTU and Cambridge's Department of Paediatrics.

"Our hypothesis is that by matching information delivery to the optimal phase of a brainwave, we maximise information capture because this is when our neurons are at the height of excitability."

Previous work from Leong's Baby-LINC lab shows that brainwaves of mothers and babies will synchronise when they communicate. Leong believes the mechanism in this latest study is so effective because it mirrors the way we learn as infants.

"We are tapping into a mechanism that allows our brain to align to temporal stimuli in our environment, especially communicative cues like speech, gaze and gesture that are naturally exchanged during interactions between parents and babies," said Leong.

"When adults speak to young children they adopt child-directed speech -- a slow and exaggerated form of speaking. This study suggests that child-directed speech may be a spontaneous way of rate-matching and entraining the slower brainwaves of children to support learning."

The researchers say that, while the new study tested visual perception, these mechanisms are likely to be "domain general": applying to a wide range of tasks and situations, including auditory learning.

They argue that potential applications for brainwave entrainment may sound like the stuff of science fiction, but are increasingly achievable. "While our study used complex EEG machines, there are now simple headband systems that allow you to gauge brain frequencies quite easily," said Kourtzi.

"Children now do so much of their learning in front of screens. One can imagine using brainwave rhythms to enhance aspects of learning for children who struggle in regular classrooms, perhaps due to attentional deficits."

Other early applications of brainwave entrainment to boost learning could involve training in professions where fast learning and quick decision-making is vital, such as pilots or surgeons. "Virtual reality simulations are now an effective part of training in many professions," said Kourtzi.

"Implementing pulses that sync with brainwaves in these virtual environments could give new learners an edge, or help those retraining later in life."

https://www.sciencedaily.com/releases/2023/01/230131101912.htm

Do sleep medications increase your chances of dementia?

January 31, 2023

Science Daily/University of California - San Francisco

A new study shows that sleep medications increase the risk of dementia in whites. But the type and quantity of the medication may be factors in explaining the higher risk.

It follows previous work that shows Blacks have a higher likelihood than whites of developing Alzheimer's, the most common type of dementia, and that they have different risk factors and disease manifestation.

The final corrected draft of the study publishes in the Journal of Alzheimer's Disease on Jan. 31, 2023.

In the study, approximately 3,000 older adults without dementia, who lived outside of nursing homes, were enrolled in the Health, Aging and Body Composition study and followed over an average duration of nine years. Their average age was 74; 42% were Black and 58% were white.

During the study, 20% developed dementia. White participants who "often" or "almost always" took sleep medications had a 79% higher chance of developing dementia compared to those who "never" or "rarely" used them. Among Black participants -- whose consumption of sleep aids was markedly lower -- frequent users had a similar likelihood of developing dementia than those who abstained or rarely used the medications.

Higher-Income Blacks May Be Less Likely to Get Dementia

"Differences may be attributed to socio-economic status" said first author Yue Leng, PhD, of the UCSF Department of Psychiatry and Behavioral Sciences and Weill Institute for Neurosciences. "Black participants who have access to sleep medications might be a select group with high socio-economic status and, thus, greater cognitive reserve, making them less susceptible to dementia.

"It's also possible that some sleep medications were associated with a higher risk of dementia than others."

The researchers found that whites, at 7.7%, were three times as likely as Blacks, at 2.7%, to take sleep medications often, five to 15 times a month, or almost always, 16 times a month to daily. Whites were almost twice as likely to use benzodiazepines, like Halcion, Dalmane and Restoril, prescribed for chronic insomnia.

Whites were also 10 times as likely to take trazodone, an antidepressant known by the trade names of Desyrel and Oleptro, that may also be prescribed as a sleep aid. And they were more than seven times as likely to take "Z-drugs," such as Ambien, a so-called sedative-hypnotic.

While future study may offer clarity on the cognitive risks or rewards of sleep medications and the role that race may play, patients with poor sleep should hesitate before considering medications, according to Leng.

"The first step is to determine what kind of sleep issues patients are dealing with. A sleep test may be required if sleep apnea is a possibility," she said. "If insomnia is diagnosed, cognitive behavioral therapy for insomnia (CBT-i) is the first-line treatment. If medication is to be used, melatonin might be a safer option, but we need more evidence to understand its long-term impact on health."

https://www.sciencedaily.com/releases/2023/01/230131101833.htm

Three or more concussions linked with worse brain function in later life

Experiencing three or more concussions is linked with worsened brain function in later life, according to major new research

January 30, 2023

Science Daily/University of Exeter

Experiencing three or more concussions is linked with worsened brain function in later life, according to major new research.

The study -- the largest of its kind -- also found having just one moderate-to-severe concussion, or traumatic brain injury (TBI), can have a long-term impact on brain function, including memory.

Led by teams at the University of Oxford and the University of Exeter, the research included data from more than 15,000 participants of the online PROTECT study, who were aged between 50 and 90 and based in the UK. They reported the severity and frequency of concussions they had experienced throughout their lives, and completed annual, computerised tests for brain function.

Published in the Journal of Neurotrauma, the paper found that people who reported three or more concussions had significantly worse cognitive function, which got successively worse with each subsequent concussion after that. Attention and completion of complex tasks were particularly affected.

Researchers say people who have had concussions should be warned of the dangers of continuing high-risk sport or work.

Lead investigator Dr Vanessa Raymont, from the University of Oxford, said: "We know that head injuries are a major risk factor for dementia, and this large-scale study gives the greatest detail to date on a stark finding -- the more times you injure your brain in life, the worse your brain function could be as you age.

"Our research indicates that people who have experienced three or more even mild episodes of concussion should be counselled on whether to continue high-risk activities. We should also encourage organisations operating in areas where head impact is more likely to consider how they can protect their athletes or employees."

The team found that participants who reported three episodes of even mild concussion throughout their lives had significantly worse attention and ability to complete complex tasks. Those who had four or more mild concussion episodes also showed worsened processing speed and working memory. Each additional reported concussion was linked to progressively worse cognitive function.

Furthermore, the researchers found that reporting even one moderate-to-severe concussion was associated with worsened attention, completion of complex tasks and processing speed capacity.

In the online PROTECT study, participants share detailed lifestyle information, and complete a suite of cognitive tests every year, for up to 25 years. This rich mine of data helps researchers understand how the brain ages, and the factors involved in maintaining a healthier brain in later life.

Dr Helen Brooker, a study co-author from the University of Exeter, said: "As our population ages, we urgently need new ways to empower people to live healthier lives in later life. This paper highlights the importance of detailed long-term studies like PROTECT in better understating head injuries and the impact to long term cognitive function, particularly as concussion has also been linked to dementia. We're learning that life events that might seem insignificant, life experiencing a mild concussion, can have an impact on the brain. Our findings indicate that cognitive rehabilitation should focus on key functions such as attention and completion of complex tasks, which we found to be susceptible to long-term damage."

Dr Susan Kohlhaas, Director of Research at Alzheimer's Research UK, said: "Studies like this are so important in unravelling the long-term risks of traumatic brain injury, including their effect on dementia risk. These findings should send a clear message to policy makers and sporting bodies, who need to put robust guidelines in place that reduce risk of head injury as much as possible."

https://www.sciencedaily.com/releases/2023/01/230130213948.htm

Why a high fat diet could reduce the brain's ability to regulate food intake

January 26, 2023

Science Daily/The Physiological Society

Regularly eating a high fat/calorie diet could reduce the brain’s ability to regulate calorie intake. New research in rats published in The Journal of Physiologyfound that after short periods of being fed a high fat/high calorie diet, the brain adapts to react to what is being ingested and reduces the amount of food eaten to balance calorie intake. The researchers from Penn State College of Medicine, US, suggest that calorie intake is regulated in the short-term by cells called astrocytes (large star-shaped cells in the brain that regulate many different functions of neurons in the brain) that control the signalling pathway between the brain and the gut. Continuously eating a high fat/calorie diet seems to disrupt this signalling pathway.

Understanding the brain’s role and the complex mechanisms that lead to overeating, a behaviour that can lead to weight gain and obesity, could help develop therapies to treat it. Obesity is a global public-health concern because it is associated with increased risk of cardiovascular diseases and type 2 diabetes. In England, 63% of adults are considered above a healthy weight and around half of these are living with obesity. One in three children leaving primary school are overweight or obese1.

Dr Kirsteen Browning, Penn State College of Medicine, US, said,

“Calorie intake seems to be regulated in the short-term by astrocytes. We found that a brief exposure (three to five days) of high fat/calorie diet has the greatest effect on astrocytes, triggering the normal signalling pathway to control the stomach. Over time, astrocytes seem to desensitise to the high fat food. Around 10-14 days of eating high fat/calorie diet, astrocytes seem to fail to react and the brain’s ability to regulate calorie intake seems to be lost. This disrupts the signalling to the stomach and delays how it empties.”

Astrocytes initially react when high fat/calorie food is ingested. Their activation triggers the release of gliotransmitters, chemicals (including glutamate and ATP) that excite nerve cells and enable normal signalling pathways to stimulate neurons that control how the stomach works. This ensures the stomach contracts correctly to fill and empty in response to food passing through the digestive system. When astrocytes are inhibited, the cascade is disrupted. The decrease in signalling chemicals leads to a delay in digestion because the stomach doesn’t fill and empty appropriately.

The vigorous investigation used behavioural observation to monitor food intake in rats (N=205, 133 males, 72 females) which were fed a control or high fat/calorie diet for one, three, five or 14 days. This was combined with pharmacological and specialist genetic approaches (both in vivo and in vitro) to target distinct neural circuits. Enabling the researchers to specifically inhibit astrocytes in a particular region of the brainstem (the posterior part of the brain that connects the brain to the spinal cord), so they could assess how individual neurons behaved to studying rats' behaviour when awake.

Human studies will need to be carried out to confirm if the same mechanism occurs in humans. If this is the case, further testing will be required to assess if the mechanism could be safely targeted without disrupting other neural pathways.

The researchers have plans to further explore the mechanism. Dr Kirsteen Browning said,

“We have yet to find out whether the loss of astrocyte activity and the signalling mechanism is the cause of overeating or that it occurs in response to the overeating. We are eager to find out whether it is possible to reactivate the brain’s apparent lost ability to regulate calorie intake. If this is the case, it could lead to interventions to help restore calorie regulation in humans.”

https://www.sciencedaily.com/releases/2023/01/230126100217.htm

More steps, moderate physical activity cuts dementia, cognitive impairment risk

January 25, 2023

Science Daily/University of California - San Diego

Senior women were less likely to develop mild cognitive impairment or dementia if they did more daily walking and moderate-to-vigorous physical activity, according to a new study led by the Herbert Wertheim School of Public Health and Human Longevity Science at University of California San Diego.

In the Jan. 25, 2023 online edition of Alzheimer's & Dementia: The Journal of the Alzheimer's Association, the team reported that, among women aged 65 or older, each additional 31 minutes per day of moderate-to-vigorous physical activity was associated with a 21 percent lower risk of developing mild cognitive impairment or dementia. Risk was also 33 percent lower with each additional 1,865 daily steps.

"Given that the onset of dementia begins 20 years or more before symptoms show, the early intervention for delaying or preventing cognitive decline and dementia among older adults is essential," said senior author Andrea LaCroix, Ph.D., M.P.H., Distinguished Professor at the Herbert Wertheim School of Public Health and Human Longevity Science at UC San Diego.

While there are several types, dementias are a debilitating neurological condition that can cause loss of memory, the ability to think, problem solve or reason. Mild cognitive impairment is an early stage of memory loss or thinking problems that is not as severe as dementias.

According to the United States Department of Health and Human Services, dementia affects more than 5 million people in this country. That number is expected to double by 2050.

More women live with and are at higher risk of developing dementia than men.

"Physical activity has been identified as one of the three most promising ways to reduce risk of dementia and Alzheimer's disease. Prevention is important because once dementia is diagnosed, it is very difficult to slow or reverse. There is no cure," said LaCroix.

However, because few large studies have examined device measures of movement and sitting in relation to mild cognitive impairment and dementia, much of the published research on the associations of physical activity and sedentary behavior with cognitive decline and dementia is based on self-reported measures, said first author, Steven Nguyen, Ph.D., M.P.H., postdoctoral scholar at the Herbert Wertheim School of Public Health.

For this study, the researchers sampled data from 1,277 women as part of two Women's Health Initiative (WHI) ancillary studies -- the WHI Memory Study (WHIMS) and the Objective Physical Activity and Cardiovascular Health (OPACH) study. The women wore research-grade accelerometers and went about their daily activities for up to seven days to obtain accurate measures of physical activity and sitting.

The activity trackers showed the women averaged 3,216 steps, 276 minutes in light physical activities, 45.5 minutes of moderate-to-vigorous physical activity and 10.5 hours of sitting per day. Examples of light physical activity could include housework, gardening or walking. Moderate-to-vigorous physical activity could include brisk walking.

The study findings also showed that higher amounts of sitting and prolonged sitting were not associated with higher risk of mild cognitive impairment or dementia.

Together, this information has clinical and public health importance as there is little published information on the amount and intensity of physical activity needed for a lower dementia risk, said Nguyen.

"Older adults can be encouraged to increase movement of at least moderate intensity and take more steps each day for a lower risk of mild cognitive impairment and dementia," said Nguyen.

"The findings for steps per day are particularly noteworthy because steps are recorded by a variety of wearable devices increasingly worn by individuals and could be readily adopted."

The authors said further research is needed among large diverse populations that include men.

https://www.sciencedaily.com/releases/2023/01/230125085831.htm

Traffic pollution impairs brain function

First-in-the-world study suggests that even brief exposure to air pollution has rapid impacts on the brain

January 24, 2023

Science Daily/University of British Columbia

A new study by researchers at the University of British Columbia and the University of Victoria has shown that common levels of traffic pollution can impair human brain function in only a matter of hours.

The peer-reviewed findings, published in the journal Environmental Health, show that just two hours of exposure to diesel exhaust causes a decrease in the brain's functional connectivity -- a measure of how The study provides the first evidence in humans, from a controlled experiment, of altered brain network connectivity induced by air pollution.

"For many decades, scientists thought the brain may be protected from the harmful effects of air pollution," said senior study author Dr. Chris Carlsten, professor and head of respiratory medicine and the Canada Research Chair in occupational and environmental lung disease at UBC. "This study, which is the first of its kind in the world, provides fresh evidence supporting a connection between air pollution and cognition."

For the study, the researchers briefly exposed 25 healthy adults to diesel exhaust and filtered air at different times in a laboratory setting. Brain activity was measured before and after each exposure using functional magnetic resonance imaging (fMRI).

The researchers analyzed changes in the brain's default mode network (DMN), a set of inter-connected brain regions that play an important role in memory and internal thought. The fMRI revealed that participants had decreased functional connectivity in widespread regions of the DMN after exposure to diesel exhaust, compared to filtered air.

"We know that altered functional connectivity in the DMN has been associated with reduced cognitive performance and symptoms of depression, so it's concerning to see traffic pollution interrupting these same networks," said Dr. Jodie Gawryluk, a psychology professor at the University of Victoria and the study's first author. "While more research is needed to fully understand the functional impacts of these changes, it's possible that they may impair people's thinking or ability to work."

Taking steps to protect yourself

Notably, the changes in the brain were temporary and participants' connectivity returned to normal after the exposure. Dr. Carlsten speculated that the effects could be long lasting where exposure is continuous. He said that people should be mindful of the air they're breathing and take appropriate steps to minimize their exposure to potentially harmful air pollutants like car exhaust.

"People may want to think twice the next time they're stuck in traffic with the windows rolled down," said Dr. Carlsten. "It's important to ensure that your car's air filter is in good working order, and if you're walking or biking down a busy street, consider diverting to a less busy route."

While the current study only looked at the cognitive impacts of traffic-derived pollution, Dr. Carlsten said that other products of combustion are likely a concern.

"Air pollution is now recognized as the largest environmental threat to human health and we are increasingly seeing the impacts across all major organ systems," says Dr. Carlsten. "I expect we would see similar impacts on the brain from exposure to other air pollutants, like forest fire smoke. With the increasing incidence of neurocognitive disorders, it's an important consideration for public health officials and policymakers."

The study was conducted at UBC's Air Pollution Exposure Laboratory, located at Vancouver General Hospital, which is equipped with a state-of-the-art exposure booth that can mimic what it is like to breathe a variety of air pollutants. In this study, which was carefully designed and approved for safety, the researchers used freshly-generated exhaust that was diluted and aged to reflect real-world conditions.

https://www.sciencedaily.com/releases/2023/01/230124112731.htm

Head injury is associated with doubled mortality rate long-term

More severe head injuries increased mortality rates in the 30-year study period

January 24, 2023

Science Daily/University of Pennsylvania School of Medicine

Adults who suffered any head injury during a 30-year study period had two times the rate of mortality than those who did not have any head injury, and mortality rates among those with moderate or severe head injuries were nearly three times higher, according to new research from the Perelman School of Medicine at the University of Pennsylvania, published today in JAMA Neurology.

In the United States, over 23 million adults age 40 or older report a history of head injury with loss of consciousness. Head injury can be attributed to a number of causes, from motor vehicle crashes, unintentional falls, or sports injuries. What's more, head injury has been linked with a number of long-term health conditions, including disability, late-onset epilepsy, dementia, and stroke.

Studies have previously shown increased short-term mortality associated with head injuries primarily among hospitalized patients. This longitudinal study evaluated 30 years of data from over 13,000 community-dwelling participants (those not hospitalized or living in nursing home facilities) to determine if head injury has an impact on mortality rates in adults over the long term. Investigators found that 18.4 percent of the participants reported one or more head injuries during the study period, and of those who suffered a head injury, 12.4 percent were recorded as moderate or severe. The median period of time between a head injury and death was 4.7 years.

Death from all causes was recorded in 64.6 percent of those individuals who suffered a head injury, and in 54.6 percent of those without any head injury. Accounting for participant characteristics, investigators found that the mortality rate from all-causes among participants with a head injury was 2.21 times the mortality rate among those with no head injury. Further, the mortality rate among those with more severe head injuries was 2.87 times the mortality rate among those with no head injury.

"Our data reveals that head injury is associated with increased mortality rates even long-term. This is particularly the case for individuals with multiple or severe head injuries," explained the study's lead author, Holly Elser, MD, PhD, MPH a Neurology resident at Penn. "This highlights the importance of safety measures, like wearing helmets and seatbelts, to prevent head injuries."

Investigators also evaluated the data for specific causes of death among all participants. Overall, the most common causes of death were cancers, cardiovascular disease, and neurologic disorders (which include dementia, epilepsy, and stroke). Among individuals with head injuries, deaths caused by neurologic disorders and unintentional injury or trauma (like falls) occurred more frequently.

When investigators evaluated specific neurologic causes of death among participants with head injury, they found that nearly two-thirds of neurologic causes of death were attributed to neurodegenerative diseases, like Alzheimer's and Parkinson's disease. These diseases composed a greater proportion of overall deaths among individuals with head injury (14.2 percent) versus those without (6.6 percent).

"Study data doesn't explain why the cause of death in individuals with head injuries is more likely to be from neurodegenerative diseases, which underscores the need for further research into the relationship between these disorders, head injury, and death," said Andrea L.C. Schneider, MD, PhD, an assistant professor of Neurology at Penn.

https://www.sciencedaily.com/releases/2023/01/230124192620.htm

Childhood trauma linked to civic environmental engagement, green behavior

January 23, 2023

Science Daily/University of Colorado at Boulder

Experiencing childhood trauma may lead an individual to volunteer, donate money or contact their elected officials about environmental issues later in life, according to recent research published in Scientific Reports.

The CU Boulder and Loyola University study is one of the first in the U.S. to associate childhood trauma and public, civic environmental engagement in adulthood. It also found that, in addition to people who experienced childhood trauma, those who traveled and had experiences in nature as children were also more likely to report engaging in private "green behavior" as adults, such as recycling, driving or flying less, and taking shorter showers.

"We set out to explore reasons or motivations why someone would get environmentally engaged versus not and experiencing childhood trauma emerged as a really powerful motivator," said lead author Urooj Raja, who earned her doctorate in environmental studies at CU Boulder in 2021.

As part of Raja's doctoral work, the researchers conducted a survey in 2020 using a nationally representative sample of about 450 U.S. adults to examine two types of environmental engagement. Public, civic engagement was measured in hours per month devoted to an environmental protection cause, such as writing letters to elected officials or donating time and resources to an organization. Private, green behavior was defined as self-reported actions adopted by individuals or households to reduce their environmental impact.

Previous research has shown that people who experience natural disasters as children are more likely to get involved in environmental causes, but these new findings show that childhood trauma of any kind is associated with increased interest in both private and public environment engagement as an adult. This indicates there may be something about a formative, negative experience that drives individuals to engage on a public or policy level with environmental issues, instead of only practicing green behavior.

"It suggests that there could be another way of looking at trauma," said Raja, now an assistant professor in the School of Communication at Loyola University Chicago.

While the researchers can't say exactly why experiencing traumatic events earlier in life boosts the likelihood of getting publicly involved in environmental issues, they note that previous research has associated trauma with a strong sense of empathy, and empathy with green behavior.

It could also partly be a coping mechanism, to attempt to keep bad things from happening to other people or living things, said Raja.

Drivers of environmental engagement 

Research in this area has often examined disengagement -- the reasons why people don't act on pressing environmental issues. Raja's team wanted to know: What drives those who do engage?

First, Raja interviewed 33 people who are highly engaged in environmental issues. She discovered that many had experienced some kind of childhood trauma.

"It emerged as a very powerful piece of why people wanted to and became engaged with environmental work," said Raja.

Second, they gathered survey data from about 450 U.S. adults who self-reported that they spent five hours or more in the past month working on environmental issues. They answered a series of questions about themselves, including their current civic engagement and green behavior, formative childhood experiences (gardening, swimming in a lake or going on a hike in the woods for the first time), and traumatic experiences in childhood (living in poverty or experiencing hunger, not having a safe home environment, losing a parent or sibling, dealing with health issues, or enduring sexual harassment, assault or bullying).

The data revealed that childhood experiences in nature, travel and trauma were all predictors of private, green behavior later in life. However, only childhood trauma was also significantly associated with public, civic engagement. Trauma also had the largest impact on predicting green behavior, compared to other formative life experiences.

Studies in decades past -- including work by Louise Chawla, professor emerita in the Program in Environmental Design -- have found a strong link between childhood travel and experiences in nature and pro-environmental attitudes and behaviors later in life. The new survey confirms that these types of childhood experiences still predict green behavior for adults today.

"This is another data point that supports the value of creating opportunities for people to connect with nature, and the importance of those experiences for cultivating a society that protects the natural resources that we all depend on," said Amanda Carrico, co-author of the new study and associate professor in the Department of Environmental Studies at CU Boulder.

A need for more resources and support 

Carrico, who is trained as an environmental psychologist and teaches courses on climate change, has noticed that many students and professionals in the field struggle not only with the weight of their work, but also with the experiences that may have led them to it.

"It's emotionally intense and exhausting," said Carrico, noting that those who work on mitigating climate change are also often part of communities directly affected by its growing impacts. "You're talking about a community of people that seem to be carrying other kinds of emotionally complex burdens."

The authors say that the findings only further emphasize the need for people engaged in public-facing or civic environmental work to have access to resources and support.

"People, in their own words, have said that we need better resources," said Raja. "Making the link between adverse childhood experiences and the need for more resources for people that do this type of work is an important first step to making that happen."

https://www.sciencedaily.com/releases/2023/01/230123083446.htm

Loneliness associated with unhealthful diets and physical inactivity among US college students

January 20, 2023

Science Daily/George Mason University

Transitioning to a new environment, as many college freshman do, can increase feelings of loneliness, and feelings of loneliness in college students have dramatically increased in the last decade, according to the National College Health Assessment. Additionally, a 2021 survey reported that 44% of U.S. college students described their weight as more than normal, i.e. either in the overweight or obese category. Though loneliness has been linked to unhealthy weight and physical inactivity, there is a lack of research on dietary behaviors in college students and the role it can play in obesity in college students.

With data from the Mason: Health Starts Here cohort study, Master of Nutrition alum Li Jiang found that loneliness was related to altered diet quality and physical inactivity. The research was done as part of Jiang's master's thesis, and Mason Nutrition and Food Studies Department Chair Lawrence J. Cheskin, Associate Professor Lilian de Jonge, former faculty member Cara Frankenfeld, and former postdoctoral fellow Ziaul H. Rana also contributed to the project.

"Our study supports a potential need for further research in understanding unhealthful dietary behavior and physical activity which may be related to loneliness, an emotion that impacts many college students," says Jiang.

Sedentary (19.2%) and low active (53.8%) behaviors were more frequent in students reporting high loneliness (score ranges of 4-6 and 7-9) than those reporting low loneliness (score of 10-12). Students reporting more loneliness had higher fat diets than students reporting less loneliness.

"Interventions to reduce loneliness may have a positive effect on health promotion in this population. This data go along with other initial findings from the Health Starts Here study that college students are not meeting healthy dietary guidelines or getting enough physical activity," said Cheskin, who has an MD.

The study is a cross-sectional study that analyzed baseline data collected in the first wave of Mason: Health Start Here in 2019, and was funded by George Mason University's Institute for BioHealth Innovation.

"Loneliness is associated with unhealthful dietary behaviors and physical inactivity among US college students," was published in November 2022 in the Journal of American College Health.

Mason: Health Starts Here is a first-of-its-kind transdisciplinary student cohort study to understand and improve the health and well-being of university students. This research will follow a broad sample of young adults, specifically Mason students, over time to capture the diversity of their experiences in college and how it affects their health and well-being.

https://www.sciencedaily.com/releases/2023/01/230120131311.htm

New research quantifies the 'wow' factor of sunrise and sunset

January 19, 2023

Science Daily/University of Exeter

A new study has identified the impact that fleeting natural events, such as sunrises and sunsets, can have on people, and sought to quantify their effects for the first time.

Despite a large body of research examining the impacts of nature on our mental health, most studies have assessed these effects under calm, blue skies. Surprisingly few have considered how we respond to variations in weather and the daily rhythms of the sun, changes referred to as 'ephemeral phenomena'.

To help close this gap, researchers used the latest computer graphics to show carefully controlled images of both urban and natural environments to more than 2,500 participants. When these scenes featured elements such as sunrise and sunset, participants considered them to be substantially more beautiful than when seen under sunny conditions at any other time of day.

Unexpectedly, the paper revealed that sunrise and sunset could also trigger significant boosts in people's feelings of awe. A typically difficult emotion to elicit, research indicates that awe has the potential to improve mood, enhance positive social behaviour, and increase positive emotions -- all valuable factors in enhancing overall wellbeing.

Published in the Journal of Environmental Psychology, the paper also considered rarer events, such as rainbows, thunderstorms, and starry, moonlit skies in the experiment. Each of these phenomena altered the extent to which people experienced beauty and awe in different landscapes, when compared to sunny, blue skies.

Crucially, these changes were also behind variations in how the environments were valued -- assessed by asking participants how much they would be willing to pay to experience each scene in the real world.

Participants were prepared to pay a premium of almost 10 per cent to visit a natural setting at sunrise compared to under blue skies. The research team said this kind of added value is normally attributed to more permanent features, such as scenic lakes or historic buildings. They suggested that encouraging people to experience sunsets and sunrises could help boost wellbeing, and might be used as part of green prescribing, where nature plays a therapeutic role in mental health treatment.

Alex Smalley, PhD fellow at the University of Exeter and lead author of the research, said: "We're all familiar with the urge to take a photo of a brilliant sunset or unexpected rainbow. The term 'sunset' has over 300 million tags on Instagram and people told us they'd be willing to pay a premium to experience these phenomena, but of course we can all experience them for free. Our research indicates that getting up a bit earlier for sunrise or timing a walk to catch sunset could be well worth the effort -- the 'wow' factor associated with these encounters might unlock small but significant bumps in feelings of beauty and awe, which could in turn have positive impacts for mental wellbeing."

The authors also noted how the occurrence of the phenomena they tested could vary greatly based on where people live. Those on east-facing coastlines might find sunrise easier to see, whilst those in the west might more frequently experience sunset. Equally, thunderstorms may be more common in summer in the UK, yet rainbows appear more often in winter. Alex Smalley added: "Most of the phenomena we tested can be fleeting and unpredictable, and we think this novelty is partly behind the effects we're seeing. Given their potential to change people's experiences in both natural and urban landscapes, there could be real value in highlighting how and where these events might be experienced, particularly in towns and cities."

https://www.sciencedaily.com/releases/2023/01/230119112753.htm

Music education benefits youth wellbeing

January 18, 2023

Science Daily/University of Southern California

The latest USC research on the impact of music education shows that for adolescents, the benefits appear to extend beyond a surge in neural connections in their brains. It actually boosts their wellbeing.

The study published Wednesday by the journal Frontiers In Psychology comes just weeks after voters statewide approved Prop. 28 to increase funding for arts and music education in California public schools.

A USC Thornton School of Music researcher said the results are especially meaningful amid a nationwide mental health crisis.

"We know that the pandemic has taken a toll on student mental health. The many narratives of learning loss that have emerged since the start of the pandemic paint a grim picture of what some call a 'lost generation'," said Beatriz Ilari, an associate professor of music education at the USC Thornton School of Music and corresponding author of the study. "Music might be an activity to help students develop skills and competencies, work out their emotions, engage in identity work and strengthen connections to the school and community."

The work was supported by grants including one from the Fender Play Foundation, a nonprofit organization that places instruments in the hands of youth who aspire to play and reap the powerful benefits of music education.

Evidence of those benefits continues to mount, although many states and school districts have reduced the amount of class time, faculty and curriculum dedicated to the arts amid budget crunches and changes in curriculum standards.

Ilari contributed to prior studies, including a longitudinal one by the USC Brain and Creativity Institute, that demonstrated children who learn a musical instrument have enhanced cognitive function. Other research also has shown music education contributes to improved creativity and confidence, better mental health and emotional stability, and student performance, according to a paper published last year by the International Journal of Environmental Research and Public Health.

Greater hope for the future

For the study, researchers examined the impact of music on "positive youth development," a measure of the strengths of adolescents and their potential to contribute to society developed by scholars from Tufts University. Researchers also included measures for school connectedness and hopeful future expectations.

The researchers administered anonymous, online surveys to 120 students from 52 Los Angeles Unified School District middle schools. The survey questions covered the key domains of positive youth development including competence and confidence. Past research shows that adolescents who manifest these attributes are more likely to make positive contributions to society and less likely to engage in risky behaviors later in life.

Ilari and her fellow researchers, including USC Thornton alumna Eun Cho, found many positive effects. They found that students who started music education before age 8 were more hopeful about the future, and younger students receiving musical training scored higher in key measures of positive youth development.

The research team also found that younger students scored higher in key development measures than their older peers. Sixth-grade students, for example, scored higher for overall positive youth development than -- eighth-graders, and scored higher in the confidence domain than both seventh and eighth-graders. Seventh-grade students also scored higher in overall positive youth development than eighth-graders.

In completing the study's survey questions, students were invited to choose from multiple gender categories beyond the usual binary gender options, including "non-binary" and "prefer not to answer," to identify themselves. Non-binary students scored lower in overall positive youth development and connection than girls. They also scored lower in confidence and connection than boys.

"Given the high levels of depression and suicide ideation among LGBTQ+ and non-gender conforming students, it is crucial that research examining adolescent well-being move beyond the gender binary," Ilari said. "In addition to filling critical gaps in the existing literature, results from our study can be used to inform the development of programs and policy for all young people."

The study included students of diverse backgrounds. However, students participating in a virtual music education program primarily came from poor neighborhoods, indicating disparities in access to formal music education.

In addition, the study explored students' engagement in different music programs, including the Virtual Middle School Music Enrichment (VMSME), a tuition-free, extracurricular program that focuses on popular music education and virtual learning. The program is available through a school district partnership with the Fender Play Foundation. Researchers found that students participating in multiple forms of music education and for longer periods of time scored higher in measures for competence and hopeful future expectations. Some participants in these groups were also enrolled in private lessons and/or playing in small ensembles that offer more individual attention than large group classes. In contrast, students in the extracurricular VMSME program came from low-income neighborhoods and participated in fewer extracurricular activities.

"By expanding access to instruments and music classes for students from low socioeconomic areas -- a population that is often left out of school music programs -- VMSME contributed to the democratization of music education," Ilari said. "Throughout the pandemic, students in public schools, especially in urban areas, were disproportionately impacted by the lockdowns that deprived them of physical and social contact with peers. VMSME brought together students from different neighborhoods and at a time when forming peer groups is essential to social identity development."

More research is needed to better understand disparities in access to formal music education, Ilari said, but she said programs that give student agency in their learning and allow them to engage with peers from other schools, like VMSME, have the potential to promote learning and wellbeing.

https://www.sciencedaily.com/releases/2023/01/230118195730.htm

Good news for athletes who are slow to recover from concussion

Most need just one more month to return to play

January 18, 2023

Science Daily/American Academy of Neurology

A new study suggests that athletes who recover more slowly from concussion may be able to return to play with an additional month of recovery beyond the typical recovery time, according to a new study published in the January 18, 2023, online issue of Neurology®, the medical journal of the American Academy of Neurology. Slow recovery was defined as taking more than 14 days for symptoms to resolve or taking more than 24 days to return to play, both of which are considered the typical recovery times for about 80% of athletes with concussion.

"Although an athlete may experience a slow or delayed recovery, there is reason to believe recovery is achievable with additional time and injury management," said study author Thomas W. McAllister, MD, of the Indiana University School of Medicine in Indianapolis. "This is an encouraging message that may help to relieve some of the discouragement that athletes can feel when trying to return to their sport. While some athletes took longer than 24 days to return to play, we found that three-quarters of them were able to return to sports if given just one more month to recover."

The study looked at 1,751 college athletes who had been diagnosed with a concussion by a team physician. Of the athletes, 63% were male and 37% were female. Male athletes participated primarily in football, soccer and basketball. Female athletes participated primarily in soccer, volleyball and basketball.

Participants were evaluated five times: within six hours after their injury, one to two days later, once free of symptoms, once cleared to return to play and at six months.

Participants reported symptoms daily to medical staff, up to 14 days following injury and then weekly if they had not yet returned to play.

A total of 399 athletes, or 23%, had a slow recovery.

Researchers found that of the athletes who took longer than 24 days to return to play, more than three-fourths, or 78%, were able to return to play within 60 days of injury, and four-fifths, or 83%, were able to return to play within 90 days of injury. Only 11% had not returned to play six months after injury.

For the slow recovery group, the average time for returning to play was 35 days after injury, compared to 13 days in the overall group.

"The results of this study provide helpful information for athletes and medical teams to consider in evaluating expectations and making difficult decisions about medical disqualification and the value of continuing in their sport," McAllister said.

A limitation of the study is that participants were all collegiate varsity athletes and may not be representative of other age groups or levels of sport, and the results may not apply to other types of mild brain injuries.

https://www.sciencedaily.com/releases/2023/01/230118195719.htm

In the wake of a wildfire, embers of change in cognition and brain function linger

People exposed to the deadly Camp Fire in 2018 displayed altered cognitive function months later; it's new evidence of a growing phenomenon known as 'climate trauma'

January 18, 2023

Science Daily/University of California - San Diego

n November 2018, the Camp Fire burned a total of 239 square miles, destroyed 18,804 structures and killed 85 people, making it the deadliest and most destructive wildfire in California history.

Three years later, researchers at University of California San Diego, published a novel study that looked at the psychological consequences, finding that exposure to "climate trauma" for affected residents resulted in increased and chronic mental health problems, such as post-traumatic stress disorder and depression.

In a new study, published in the January 18, 2023 online issue of PLOS Climate, senior author Jyoti Mishra, PhD, associate professor in the Department of Psychiatry at UC San Diego School of Medicine, director of the Neural Engineering and Translation Labs at UC San Diego, and associate director of the UC Climate and Mental Health Initiative, delved deeper with her colleagues. The study team reported that in a subset of persons exposed to the Camp Fire, significant differences in cognitive functioning and underlying brain activity were revealed using electroencephalography (EEG).

Specifically, the researchers found that fire-exposed individuals displayed increased activity in the regions of the brain involved in cognitive control and interference processing -- the ability to mentally cope with unwanted and often disturbing thoughts.

"To function well day-to-day, our brains need to process information and manage memories in ways that help achieve goals while ignoring or dispensing with irrelevant or harmful distractions," said Mishra.

"Climate change is an emerging challenge. It is already well-documented that extreme climate events result in significant psychological impacts. Warming temperatures, for example, have even been linked to greater suicide rates. As planetary warming amplifies, more forest fires are expected in California and globally, with significant implications for mental health effects.

"In this study, we wanted to learn whether and how climate trauma affected and altered cognitive and brain functions in a group of people who had experienced it during the Camp Fire. We found that those who were impacted, directly or indirectly, displayed weaker interference processing. Such weakened cognitive performance may then impair daily functioning and reduce wellbeing."

The study sample included 27 persons directly exposed to the Camp Fire (for example, their homes were destroyed), 21 who were indirectly exposed (they witnessed the fire, but were not directly impacted) and 27 control individuals. All participants underwent cognitive testing with synchronized EEG brain recordings.

Sixty-seven percent of the individuals directly exposed to the fire reported having experienced recent psychological trauma, as did 14 percent of the indirectly exposed individuals. None of the control individuals reported recent trauma exposure.

The EEG recordings showed that the brains of those individuals reporting trauma worked harder at interference processing and cognitive control, suggesting a compensatory effort but at a cost: potentially heightened risk of neurological dysfunction elsewhere.

"The evidence of diminished interference processing, along with altered functional brain responses, is useful because it can help guide efforts to develop resiliency intervention strategies," said Mishra.

"As the planet warms, more and more individuals will face extreme climate exposures, like wildfires, and having therapeutic tools that can address underlying neuro-cognitive issues will be an important complement to other socio-behavioral therapies."

https://www.sciencedaily.com/releases/2023/01/230118195708.htm

Vitamin D benefits and metabolism may depend on body weight

People with higher body mass index had a blunted response to vitamin D supplementation, explaining observed differences in outcomes such as cancer, diabetes, and autoimmune disease

January 17, 2023

Science Daily/Brigham and Women's Hospital

Researchers from Brigham and Women's Hospital, a founding member of the Mass General Brigham healthcare system, have found new evidence that vitamin D may be metabolized differently in people with an elevated body mass index (BMI). The study, appearing in JAMA Network Open, is a new analysis of data from the VITAL trial, a large nationwide clinical trial led by Brigham researchers that investigated whether taking vitamin D or marine omega-3 supplements could reduce the risk of developing cancer, heart disease, or stroke.

"The analysis of the original VITAL data found that vitamin D supplementation correlated with positive effects on several health outcomes, but only among people with a BMI under 25," said first author Deirdre K. Tobias, ScD, an associate epidemiologist in Brigham's Division of Preventive Medicine. "There seems to be something different happening with vitamin D metabolism at higher body weights, and this study may help explain diminished outcomes of supplementation for individuals with an elevated BMI."

Vitamin D is an essential nutrient involved in many biological processes, most notably helping our body absorb minerals, such as calcium and magnesium. While some of the vitamin D we need is made in the body from sunlight, vitamin D deficiencies are often treated with supplementation. Evidence from laboratory studies, epidemiologic research and clinical research has also suggested that vitamin D may play a role in the incidence and progression of cancer and cardiovascular disease, and it was this evidence that prompted the original VITAL trial.

The VITAL trial was a randomized, double-blind, placebo-controlled trial in 25,871 U.S. participants, which included men over the age of 50 and women over the age of 55. All participants were free of cancer and cardiovascular disease at the time of enrollment. While the trial found little benefit of vitamin D supplementation for preventing cancer, heart attack, or stroke in the overall cohort, there was a statistical correlation between BMI and cancer incidence, cancer mortality, and autoimmune disease incidence. Other studies suggest similar results for type 2 diabetes.

The new study aimed to investigate this correlation. The researchers analyzed data from 16,515 participants from the original trial who provided blood samples at baseline (before randomization to vitamin D), as well as 2,742 with a follow-up blood sample taken after two years. The researchers measured the levels of total and free vitamin D, as well as many other novel biomarkers for vitamin D, such as its metabolites, calcium, and parathyroid hormone, which helps the body utilize vitamin D.

"Most studies like this focus on the total vitamin D blood level," said senior author JoAnn E. Manson, MD, DrPH, chief of the Division of Preventive Medicine at the Brigham and principal investigator of VITAL. "The fact that we were able to look at this expanded profile of vitamin D metabolites and novel biomarkers gave us unique insights into vitamin D availability and activity, and whether vitamin D metabolism might be disrupted in some people but not in others."

The researchers found that vitamin D supplementation increased most of the biomarkers associated with vitamin D metabolism in people, regardless of their weight. However, these increases were significantly smaller in people with elevated BMIs.

"We observed striking differences after two years, indicating a blunted response to vitamin D supplementation with higher BMI," Tobias said. "This may have implications clinically and potentially explain some of the observed differences in the effectiveness of vitamin D supplementation by obesity status."

"This study sheds light on why we're seeing 30-40 percent reductions in cancer deaths, autoimmune diseases, and other outcomes with vitamin D supplementation among those with lower BMIs but minimal benefit in those with higher BMIs, suggesting it may be possible to achieve benefits across the population with more personalized dosing of vitamin D," said Manson. "These nuances make it clear that there's more to the vitamin D story."

The authors conclude that the VITAL findings are a call to action for the research community to continue exploring the potential benefits of vitamin D supplementation for preventing cancer and other diseases and to take BMI into account when evaluating the supplement's health impacts.

https://www.sciencedaily.com/releases/2023/01/230117110511.htm

Study explores effects of dietary choline deficiency on neurologic and system-wide health

Reaching adequate dietary choline intake is critical to offset organ pathologies and may help protect the brain against Alzheimer's disease

January 17, 2023

Science Daily/Arizona State University

Choline, an essential nutrient produced in small amounts in the liver and found in foods including eggs, broccoli, beans, meat and poultry, is a vital ingredient for human health. A new study explores deficiency in dietary choline adversely affects the body and may be a missing piece in the puzzle of Alzheimer's disease.

It's estimated that more than 90% of Americans are not meeting the recommended daily intake of choline. The current research, conducted in mice, suggests that dietary choline deficiency can have profound negative effects on the heart, liver and other organs.

Lack of adequate choline is also linked with profound changes in the brain associated with Alzheimer's disease. These include pathologies implicated in the development of two classic hallmarks of the illness, amyloid plaques, which aggregate in the intercellular spaces between neurons, and tau tangles, which condense within the bodies of neurons.

The new research, led by scientists at Arizona State University, describes pathologies in normal mice deprived of dietary choline as well as choline deficient transgenic mice, which already exhibit symptoms associated with the disease. In both cases, dietary choline deficiency results in liver damage, enlargement of the heart and neurologic alterations in the AD mice typically accompanying Alzheimer's disease, including increased levels of plaque-forming amyloid-beta protein and disease-linked alterations in tau protein.

Further, the study illustrates that choline deficiency in mice causes significant weight gain, and alterations in glucose metabolism, (which are tied to conditions such as diabetes), and deficits in motor skills.

In the case of humans, "it's a twofold problem," according to Ramon Velazquez, senior author of the study and Assistant professor with the ASU-Banner Neurodegenerative Disease Research Center. "First, people don't reach the adequate daily intake of choline established by the Institute of Medicine in 1998. And secondly, there is vast literature showing that the recommended daily intake amounts are not optimal for brain-related functions."

Ramon Velazquez led the new study on the importance of dietary choline for the brain and other organs. He is a researcher in the ASU-Banner Neurodegereative Disease Research Center.

The research highlights a constellation of physical and neurological changes linked to choline deficiency. Sufficient choline in the diet reduces levels of the amino acid homocysteine, which has been recognized as a neurotoxin contributing to neurodegeneration and is important for mediating functions such as learning and memory, through the production of acetylcholine.

The growing awareness of choline's importance should encourage all adults to ensure proper choline intake. This is particularly true for those on plant-based diets, which may be low in naturally occurring choline, given that foods high in choline are eggs, meats, and poultry.

Plant-based, choline-rich foods, including soybeans, Brussel sprouts and toast can help boost choline in these cases. Further, inexpensive, over-the-counter choline supplements are encouraged to ensure system-wide health and guard the brain from the effects of neurodegeneration.

Brain-boosting nutrient

Choline is needed to produce acetylcholine, a neurotransmitter that plays an essential role in memory, muscle control and mood. Choline also builds cell membranes and helps regulate gene expression. The established recommendations set forth by the Institute of Medicine were based on evidence preventing fatty liver disease in men. New lines of evidence imply that the established recommended daily intake of dietary choline for adult women (425mg/day) and adult men (550mg/day) may not be optimal for proper brain health and cognition. Additionally, ~90% of Americans are not meeting the recommendation levels and may not even be aware that dietary choline is required on a daily basis.

Despite decades of research and billions of dollars invested since the discovery of the devastating ailment over a century ago, there remains no therapy capable of slowing the advance of the illness. Yet, new research findings suggest that environmental and lifestyle changes, including adequate choline, may help protect the brain from Alzheimer's disease as well as improving overall health.

Velazquez is joined on the study by co-lead authors Nikhil Dave and Jessica Judd. The work is highly interdisciplinary, including researchers from the ASU Biosciences Mass spectrometry facility, and the Translational Cardiovascular Research Center at the University of Arizona College of Medicine in Phoenix, AZ.

"This collaborative work, spanning multiple institutions and surveying the molecular processes of aging at the systems level, adds to the body of evidence produced around the importance of dietary choline in healthy aging," said Nikhil Dave.

"What I found particularly compelling about this project was that multiple organs, whose malfunction can have implications for brain health, were negatively impacted by a choline deficient diet," said Jessica Judd.

The research appears in the current issue of the journal Aging Cell.

A prolific and mysterious killer

Alzheimer's disease is the leading cause of dementia and the fifth leading cause of death among Americans aged 65 and older. Today, Alzheimer's affects 6.5 million in the U.S. alone and is projected to strike close to 14 million Americans by 2060. By this time, the costs of managing Alzheimer's are expected to exceed a $20 trillion, threatening the healthcare infrastructure while causing immense suffering.

The accumulation of sticky protein fragments outside neurons, (which form amyloid-beta plaques), and the buildup of an abnormal form of the protein tau within the bodies of neurons (tau tangles) have long been recognized signposts of Alzheimer's disease. These brain alterations are typically followed by neurodegeneration, involving the damage and destruction of neurons. Plaques are believed to damage cell-to-cell communications in the brain while tangles block the transport of vital nutrients essential for proper cell function and survival.

In addition to amyloid-beta plaques and neurofibrillary tangles, the disease causes cell death in the brain and increasing cognitive impairment. The current work also found dysregulation of proteins in the hippocampus, a key structure affected in Alzheimer's disease, tied to learning and memory. Both normal and AD mice showed dysregulated proteins in the hippocampus with a choline deficient diet, with the AD model showing severe effects.

Gathering storm

The recent, dramatic increase in Alzheimer's disease incidence is of grave concern. Although deaths from stroke, heart disease and HIV decreased between 2000 and 2019, deaths from Alzheimer's increased more than 145%. In addition to the toll on patients caused by the disease, Alzheimer's has placed an immense burden on those caring for the sick. In 2021 alone, 16 billion hours of care were provided by over 11 million family members and other unpaid caregivers.

The first outward symptoms of the disease are usually related to language, memory, and thinking problems, as brain regions associated with these tasks tend to be among the first affected. Yet researchers now know that by the time the disease causes observable symptoms, it has been quietly ravaging the brain for 20 years or more.

Many factors contribute to the development of Alzheimer's disease, from genetic predisposition to age, lifestyle and environmental influences. For reasons that remain murky, females face an increased risk of developing the disease.

Recent studies have identified diet as a significant factor associated with preventing cognitive decline. In earlier research, Velazquez and his colleagues demonstrated that when mice were fed a high choline diet, their offspring showed improvements in spatial memory, compared with a normal choline regimen in the womb. Intriguingly, the beneficial effects of choline supplementation are transgenerational, not only protecting mice receiving choline supplementation during gestation and lactation, but also the subsequent offspring of these mice, suggesting inherited modifications in their genes.

Subsequent studies in the Velazquez lab showed that choline administered to female mice throughout life yielded improvements in spatial memory, compared with those receiving a normal choline regimen.

Multifaceted effects

The new study examines mice at 3-12 months or early to late adulthood, (roughly equivalent to 20-60 years of age for humans). In the case of both normal and transgenic mice displaying symptoms of Alzheimer's, those exposed to a deficient choline diet exhibited weight gain and adverse effects to their metabolism. Damage to the liver was observed through tissue analysis, as well as enlargement of the heart. Elevated soluble, oligomeric and insoluble amyloid-beta protein were detected as well as modifications to tau protein characteristic of those leading to neurofibrillary tangles in the brain.

Further, choline deficient mice performed poorly in a test of motor skills, when compared with mice receiving adequate choline in their diet. These adverse effects were heightened in the transgenic mice. Translating these findings to humans, this implies that people who are predisposed to Alzheimer's disease or in the throes of the illness should ensure they are getting enough choline.

The study also involved a detailed exploration of proteins in the hippocampus, an area of the brain acutely affected by Alzheimer's disease, as well as proteins detected in blood. Dietary choline deficiency altered important hippocampal networks. These pathologies include disruption of pathways associated with microtubule function and postsynaptic membrane regulation -- both essential for proper brain function. In blood, proteins produced in the liver that play a role in metabolic function were particularly dysregulated with the choline deficient diet.

"Our work provides further support that dietary choline should be consumed on a daily basis given the need throughout the body," Velazquez says.

Ultimately, controlled human clinical trials will be essential for establishing the effectiveness and appropriate dosages of choline, before encouraging lifelong choline supplementation. Nevertheless, the powerful new findings offer hope that choline may be one tool in the arsenal needed to defend the brain from neurodegeneration and age-related cognitive decline.

https://www.sciencedaily.com/releases/2023/01/230117193006.htm

The link between mental health and ADHD is strong -- so why aren't we paying attention?

January 16, 2023

Science Daily/University of Bath

Adults with high levels of attention-deficit hyperactivity disorder (ADHD) symptoms are more likely to experience anxiety and depression than adults with high levels of autistic traits, according to new research led by psychologists at the University of Bath in the UK.

This study is the first to show that ADHD is more predictive of poor mental health outcomes in adults than other neurodevelopmental conditions, like autism.

Until now, there has been a dearth of information on the effects of ADHD on poor mental health, with far more research focusing on the impact of autism on depression, anxiety and quality of life. As a result, people with ADHD have often struggled to access the clinical care they need to cope with their symptoms.

The authors of the study hope their findings will trigger new research into ADHD and ultimately improve the mental health outcomes for people with the condition. ADHD is a neurodevelopmental condition characterised by inattention and/or hyperactivity and impulsivity. The condition is estimated to affect between 3% and 9% of the population.

Blue Monday

Speaking on Blue Monday (January 16) -- the third Monday of January, described by some as the gloomiest day of the year -- lead researcher, Luca Hargitai, said: "Scientists have long known that autism is linked to anxiety and depression, but ADHD has been somewhat neglected.

"Researchers have also struggled to statistically separate the importance of ADHD and autism for mental health outcomes because of how frequently they occur together."

Ms Hargitai, a PhD Researcher at Bath, added: "Our aim was to precisely measure how strongly ADHD personality traits were linked to poor mental health while statistically accounting for autistic traits."

The new research -- a collaborative effort between the Universities of Bath, Bristol and Cardiff, and King's College London -- is published this week in Scientific Reports. It comes in the same month that two British TV personalities -- Johnny Vegas and Sue Perkins -- have opened up about their recent diagnoses of ADHD.

"The condition affects many people -- both children and adults -- and the fact that more people are willing to talk about it is to be welcomed," said Ms Hargitai. "The hope is that with greater awareness will come more research in this area and better resources to support individuals in better managing their mental health."

Overly active, as though driven by a motor

The study used a large, nationally representative sample of adults from the UK population. All participants completed gold standard questionnaires -- one on autistic traits, the other on ADHD traits -- responding to statements such as "I frequently get strongly absorbed in one thing" and "How often do you feel overly active and compelled to do things, like you were driven by a motor?"

The researchers found that ADHD traits were highly predictive of the severity of anxiety and depression symptoms: the higher the levels of ADHD traits, the more likely a person is to experience severe mental health symptoms. Through innovative analytical techniques, the study authors further confirmed that having more of an ADHD personality was more strongly linked to anxiety and depression than autistic traits.

These results were replicated in computerised simulations with a 100% 'reproducibility rate'. This showed, with great confidence, that ADHD traits are almost certainly linked to more severe anxiety and depression symptoms in adults than autistic traits.

Shifting the focus of research and clinical practice

Ms Hargitai said: "Our findings suggest that research and clinical practice must shift some of the focus from autism to ADHD. This may help to identify those most at risk of anxiety and depression so that preventative measures -- such as supporting children and adults with the management of their ADHD symptoms -- can be put in place earlier to have a greater impact on improving people's wellbeing."

According to Dr Punit Shah, senior author and associate professor of Psychology at Bath, another important aspect of the new study is that it advances scientific understanding of neurodevelopmental conditions.

"By addressing the shortcomings of previous research, our work provides fresh information about the complex links between neurodiversity and mental health in adults -- an area that is often overlooked.

"Further research is now needed to delve deeper into understanding exactly why ADHD is linked to poor mental health, particularly in terms of the mental processes that might drive people with ADHD traits to engage in anxious and depressive thinking.

"At the moment, funding for ADHD research -- particularly psychological research -- is lacking. This is especially pronounced when you compare it to the relatively high level of funds directed at autism.

"As the evidence becomes clear that ADHD isn't just a childhood condition but persists throughout life, we must adjust our research agendas to better understand ADHD in adulthood."

Commenting on the new findings, Dr Tony Floyd, CEO of ADHD Foundation, The Neurodiversity Foundation, said: "This research demonstrates clear evidence of the increased risks of mental health comorbidities associated with adult ADHD. This is a step towards recognising the broader impact of unmanaged and untreated ADHD. We hope this research will lead to more research being commissioned in this area. We also hope it will result in changes to the design and delivery of health services.

"The cost implications to the NHS of leaving ADHD untreated, and the need to better train health practitioners in both primary and secondary care, are now more apparent. And of course there are other costs too that need to be considered -- to the health of UK citizens with ADHD and to their family life, employability and economic wellbeing. These costs are often hidden but they are considerable.

"This research from Bath University will add to the growing national debate and the business case for a national review of health services for ADHD across a person's lifespan."

https://www.sciencedaily.com/releases/2023/01/230116112600.htm

Managing emotions better could prevent pathological aging

January 13, 2023

Science Daily/Université de Genève

Negative emotions, anxiety and depression are thought to promote the onset of neurodegenerative diseases and dementia. But what is their impact on the brain and can their deleterious effects be limited? Neuroscientists at the University of Geneva (UNIGE) observed the activation of the brains of young and older adults when confronted with the psychological suffering of others. The neuronal connections of the older adults show significant emotional inertia: negative emotions modify them excessively and over a long period of time, particularly in the posterior cingulate cortex and the amygdala, two brain regions strongly involved in the management of emotions and autobiographical memory. These results, to be published in Nature Aging, indicate that a better management of these emotions -- through meditation for example -- could help limit neurodegeneration.

For the past 20 years, neuroscientists have been looking at how the brain reacts to emotions. ''We are beginning to understand what happens at the moment of perception of an emotional stimulus,'' explains Dr Olga Klimecki, a researcher at the UNIGE's Swiss Centre for Affective Sciences and at the Deutsches Zentrum für Neurodegenerative Erkrankungen, who is last author of this study carried out as part of a European research project co-directed by the UNIGE. ''However, what happens afterwards remains a mystery. How does the brain switch from one emotion to another? How does it return to its initial state? Does emotional variability change with age? What are the consequences for the brain of mismanagement of emotions?''

Previous studies in psychology have shown that an ability to change emotions quickly is beneficial for mental health. Conversely, people who are unable to regulate their emotions and remain in the same emotional state for a long time are at higher risks of depression. ''Our aim was to determine what cerebral trace remains after the viewing of emotional scenes, in order to evaluate the brain's reaction, and, above all, its recovery mechanisms. We focused on the older adults, in order to identify possible differences between normal and pathological ageing,'' says Patrik Vuilleumier, professor in the Department of Basic Neurosciences at the Faculty of Medicine and at the Swiss Centre for Affective Sciences at the UNIGE, who co-directed this work.

Not all brains are created equal

The scientists showed volunteers short television clips showing people in a state of emotional suffering -- during a natural disaster or distress situation for example -- as well as videos with neutral emotional content, in order to observe their brain activity using functional MRI. First, the team compared a group of 27 people over 65 years of age with a group of 29 people aged around 25 years. The same experiment was then repeated with 127 older adults.

''Older people generally show a different pattern of brain activity and connectivity from younger people,'' says Sebastian Baez Lugo, a researcher in Patrik Vuilleumier's laboratory and the first author of this work. ''This is particularly noticeable in the level of activation of the default mode network, a brain network that is highly activated in resting state. Its activity is frequently disrupted by depression or anxiety, suggesting that it is involved in the regulation of emotions. In the older adults, part of this network, the posterior cingulate cortex, which processes autobiographical memory, shows an increase in its connections with the amygdala, which processes important emotional stimuli. These connections are stronger in subjects with high anxiety scores, with rumination, or with negative thoughts.''

Empathy and ageing

However, older people tend to regulate their emotions better than younger people, and focus more easily on positive details, even during a negative event. But changes in connectivity between the posterior cingulate cortex and the amygdala could indicate a deviation from the normal ageing phenomenon, accentuated in people who show more anxiety, rumination and negative emotions. The posterior cingulate cortex is one of the regions most affected by dementia, suggesting that the presence of these symptoms could increase the risk of neurodegenerative disease.

''Is it poor emotional regulation and anxiety that increases the risk of dementia or the other way around? We still don't know,'' says Sebastian Baez Lugo. ''Our hypothesis is that more anxious people would have no or less capacity for emotional distancing. The mechanism of emotional inertia in the context of ageing would then be explained by the fact that the brain of these people remains 'frozen' in a negative state by relating the suffering of others to their own emotional memories."

Could meditation be a solution?

Could it be possible to prevent dementia by acting on the mechanism of emotional inertia? The research team is currently conducting an 18-month interventional study to evaluate the effects of foreign language learning on the one hand, and meditation practice on the other. ''In order to further refine our results, we will also compare the effects of two types of meditation: mindfulness, which consists of anchoring oneself in the present in order to concentrate on one's own feelings, and what is known as 'compassionate' meditation, which aims to actively increase positive emotions towards others,'' the authors add.

This research is part of a large European study, MEDIT-AGEING, which aims to evaluate the impact of non-pharmacological interventions for better ageing.

https://www.sciencedaily.com/releases/2023/01/230113112746.htm

Support from others in stressful times can ease impact of genetic depression risk

Study in first-year doctors and recently widowed older adults shows greatest impact of social support in those with highest polygenic risk scores for depression

January 13, 2023

Science Daily/Michigan Medicine - University of Michigan

Reaching out to support a person when they're under stress is always a good idea. But a new study suggests that support could be especially important for someone whose genetic makeup makes them more likely to develop depression.

The study shows the importance of social support in buffering the risk of developing depression symptoms in general, using data from two very different groups of people under stress: new doctors in the most intense year of training, and older adults whose spouses recently died.

But the largest effect was seen in those who had the most genetic variation that raised the risk of depression.

The paper uses a measure of genetic risk called a polygenic risk score, which is based on decades of research about what tiny variations in specific genes are linked to depression risk.

Compared to individuals in the study who had low depression polygenic risk scores, the doctors and widows with higher risk scores had higher rates of depression after they lost social support, but also had lower rates of depression when they gained social support during stressful times.

The study, published in the American Journal of Psychiatry by a University of Michigan team, suggests that more could be done to target social support to those who can most benefit.

Genes, stress and social connection

"Our data show wide variability in the level of social support individuals received during these stressful times, and how it changed over time," said first author Jennifer Cleary, M.S., a psychology doctoral student at U-M who is doing her research with senior author Srijan Sen, M.D., Ph.D., of the U-M Medical School. "We hope these findings, which incorporate genetic risk scores as well as measures of social support and depressive symptoms, illuminate the gene-environment interactions and specifically the importance of social connection in depression risk."

Sen, who is the director of the Eisenberg Family Depression Center and a professor of psychiatry and neuroscience, adds that even as genetic research reveals more of the DNA variation related to depression vulnerability, learning how that variation leads to depression is crucial.

"Further understanding the different genetic profiles associated with sensitivity to loss of social support, insufficient sleep, excessive work stress and other risk factors could help us develop personalized guidance for depression prevention," he said. "In the meantime, these findings reaffirm how important social connections, social support and individual sensitivity to the social environment are as factors in wellbeing and preventing depression."

Different populations, similar patterns

The new study used data from two long-term studies that both capture genetic, mood, environment and other data from populations of participating individuals.

One is the Intern Health Study, which enrolls first-year medical residents (also called interns) around the United States and beyond, and which Sen directs.

The other is the Health and Retirement Study, based at the U-M Institute for Social Research and funded by the National Institute on Aging.

The data for the new paper came from 1,011 interns training at hospitals across the country, nearly half of whom were female, and from 435 recently widowed individuals, 71% of them women, who had data available from surveys conducted before and after their spouses died.

In the interns, as Sen and his team have shown in previous work, depressive symptoms increased dramatically (126%) during the stressful year of training that includes long and irregular work hours -- often in environments far from friends and family.

In the widows and widowers, depressive symptoms increased 34% over their pre-widowhood scores. This correlates with past research showing loss of a spouse can be one of the biggest stressors in a person's life, Cleary said.

A crossover effect

Then, the researchers factored together the depression symptom findings with each person's polygenic risk score for depression, and their individual responses to questions about connections with friends, family and other social supporters.

Most of the interns lost social support from their pre-internship days -- which fits well with the common experience of leaving the place where they attended medical school and going to a new environment where they may not know anyone.

Interns who had the highest polygenic risk scores and also lost social support had the highest scores on measures of depression symptoms later in the stressful intern year.

Those with the same high level of genetic risk who gained social support, though, had much lower depressive symptoms. In fact, it was lower than even their peers with low genetic risk, no matter what happened to their social support. The researchers call this a "crossover effect."

Unlike the interns, some widowed individuals reported an increase in social support after the loss of their spouse, potentially as friends and family reached out to offer help or just a listening ear.

But the crossover effect was visible in them, too. Widows with high genetic risk for depression who gained social support showed a much smaller increase in depressive symptoms than their peers with similar genetic risk who lost social support after losing a spouse.

There were also some widows who lost social support or didn't experience a change in support, and whose depressive symptoms didn't change. Cleary notes that in future work, it will be important to look at this group's history in light of any caregiving they may have done for a spouse with a long-term illness.

The team also hopes that other researchers will study this same interaction of genetic risk, stress and social support in other populations.

In the meantime, Cleary and Sen say, the message for anyone going through stressful times, or watching a friend or relative go through stressful times, is to reach out and maintain or strengthen social connections.

Doing so can have benefits both for the person under stress, and the person reaching out to them, they note.

Reducing the level of ongoing stress that the person is facing, whether it's at work, school, after a personal loss or in family situations can be critical.

And even though the study did not examine the role of professional mental health help, individual and group therapy is an important option for those who have developed depression or other mental health concerns.

Note: The polygenic risk score used in the study is validated for use on people of mainly European ancestry, which limits the ability to generalize the findings to people of other backgrounds. Sen notes that additional work is being done using data from the Intern Health Study and Health & Retirement Study to develop polygenic risk scores based on depression-related genetic traits in other populations including people of East Asian and African descent.

https://www.sciencedaily.com/releases/2023/01/230113112733.htm