Poor heart health predicts premature brain aging

August 22, 2022

Science Daily/University College London

By estimating people's brain age from MRI scans using machine learning, a team led by UCL researchers has identified multiple risk factors for a prematurely ageing brain.

They found that worse cardiovascular health at age 36 predicted a higher brain age later in life, while men also tended to have older brains than women of the same age, as they report in The Lancet Healthy Longevity.

A higher brain age was associated with slightly worse scores on cognitive tests, and also predicted increased brain shrinkage (atrophy) over the following two years, suggesting it could be an important clinical marker for people at risk of cognitive decline or other brain-related ill health.

Lead author Professor Jonathan Schott (UCL Dementia Research Centre, UCL Queen Square Institute of Neurology) said: "We found that despite people in this study all being of very similar real ages, there was a very wide variation in how old the computer model predicted their brains to be. We hope this technique could one day be a useful tool for identifying people at risk of accelerated ageing, so that they may be offered early, targeted prevention strategies to improve their brain health."

The researchers applied an established MRI based machine learning model to estimate the brain age of members of the Alzheimer's Research UK-funded Insight 46 study, led by Professor Schott. Insight 46 study members are drawn from the Medical Research Council National Survey of Health and Development (NSHD) 1946 British Birth Cohort. As the participants had been a part of the study throughout their lives, the researchers were able to compare their current brain ages to various factors from across the life course.

The participants were all between 69 and 72 years old, but their estimated brain ages ranged from 46 to 93.

The researchers were able to explain roughly one third of the variability in brain age by reviewing various factors from across the life course.

People with worse cardiovascular health at age 36 or 69 had worse brain health, as did those with increased cerebrovascular disease on MRI (relating to blood flow and blood vessels in the brain). This aligns with a previous study led by Professor Schott finding that high blood pressure at age 36 predicted poorer brain health late in life.

The study did not identify any associations between childhood cognitive function, education level or socioeconomic status, and a prematurely ageing brain.

The researchers also found that higher brain age was associated with higher concentration of neurofilament light protein (NfL) in the blood. NfL elevation is thought to arise due to nerve cell damage and is increasingly being recognised as a useful marker of neurodegeneration.

Dr Sara Imarisio, Head of Research at Alzheimer's Research UK, said: "The Insight 46 study is helping reveal more about the complex relationship between the different factors influencing people's brain health throughout their life. Using machine learning, researchers in this study have uncovered yet more evidence that poorer heart health in midlife is linked to greater brain shrinkage in later life. We're incredibly grateful to the dedicated group of individuals who have contributed to research their entire lives making this work possible."

https://www.sciencedaily.com/releases/2022/08/220822184219.htm

What older adults do while they sit affects dementia risk

August 22, 2022

Science Daily/University of Southern California

Adults aged 60 and older who sit for long periods watching TV or other such passive, sedentary behaviors may be at increased risk of developing dementia, according to a new study by USC and University of Arizona researchers.

Their study also showed that the risk is lower for those who are active while sitting, such as when they read or use computers.

The study was published today in the journal Proceedings of the National Academy of Sciences. It also revealed that the link between sedentary behavior and dementia risk persisted even among participants who were physically active.

"It isn't the time spent sitting, per se, but the type of sedentary activity performed during leisure time that impacts dementia risk," said study author David Raichlen, professor of biological sciences and anthropology at the USC Dornsife College of Letters, Arts and Sciences.

"We know from past studies that watching TV involves low levels of muscle activity and energy use compared with using a computer or reading," he said. "And while research has shown that uninterrupted sitting for long periods is linked with reduced blood flow in the brain, the relatively greater intellectual stimulation that occurs during computer use may counteract the negative effects of sitting."

Researchers used self-reported data from the U.K. Biobank, a large-scale biomedical database of more than 500,000 participants across the United Kingdom, to investigate possible correlations between sedentary leisure activity and dementia in older adults.

More than 145,000 participants aged 60 and older -- all of whom did not have a diagnosis of dementia at the start of the project -- used touchscreen questionnaires to self-report information about their levels of sedentary behavior during the 2006-2010 baseline examination period.

After an average of nearly 12 years of follow-up, the researchers used hospital inpatient records to determine dementia diagnosis. They found 3,507 positive cases.

Then, the team adjusted for certain demographics (e.g., age, sex, race/ethnicity, employment type) and lifestyle characteristics (e.g., exercise, smoking and alcohol use, time spent sleeping and engaging in social contact) that could affect brain health.

The impact of physical activity, mental activity on risk

The results remained the same even after the scientists accounted for levels of physical activity. Even in individuals who are highly physically active, time spent watching TV was associated with increased risk of dementia, and leisure-time spent using a computer was associated with a reduced risk of developing dementia.

"Although we know that physical activity is good for our brain health, many of us think that if we are just more physically active during the day, we can counter the negative effects of time spent sitting," said study author Gene Alexander, professor of Psychology and Evelyn F. McKnight Brain Institute at the University of Arizona.

"Our findings suggest that the brain impacts of sitting during our leisure activities are really separate from how physically active we are," said Alexander, "and that being more mentally active, like when using computers, may be a key way to help counter the increased risk of dementia related to more passive sedentary behaviors, like watching TV."

Knowing how sedentary activities impact human health could lead to some improvements.

"What we do while we're sitting matters, " Raichlen added. "This knowledge is critical when it comes to designing targeted public health interventions aimed at reducing the risk of neurodegenerative disease from sedentary activities through positive behavior change."

https://www.sciencedaily.com/releases/2022/08/220822174914.htm

Reprogramming the brain's cleaning crew to mop up Alzheimer's disease

August 11, 2022

Science Daily/University of California - San Francisco

The discovery of how to shift damaged brain cells from a diseased state into a healthy one presents a potential new path to treating Alzheimer's and other forms of dementia, according to a new study from researchers at UC San Francisco.

The research focuses on microglia, cells that stabilize the brain by clearing out damaged neurons and the protein plaques often associated with dementia and other brain diseases.

These cells are understudied, despite the fact that changes in them are known to play a significant role Alzheimer's and other brain diseases, said Martin Kampmann, PhD, senior author on the study, which appears Aug. 11 in Nature Neuroscience.

"Now, using a new CRISPR method we developed, we can uncover how to actually control these microglia, to get them to stop doing toxic things and go back to carrying out their vitally important cleaning jobs," he said. "This capability presents the opportunity for an entirely new type of therapeutic approach."

Leveraging the Brain's Immune System

Most of the genes known to increase the risk for Alzheimer's disease act through microglial cells. Thus, these cells have a significant impact on how such neurodegenerative diseases play out, said Kampmann.

Microglia act as the brain's immune system. Ordinary immune cells can't cross the blood-brain barrier, so it's the task of healthy microglia to clear out waste and toxins, keeping neurons functioning at their best. When microglia start losing their way, the result can be brain inflammation and damage to neurons and the networks they form.

Under some conditions, for example, microglia will start removing synapses between neurons. While this is a normal part of brain development in a person's childhood and adolescent years, it can have disastrous effects in the adult brain.

Over the past five years or so, many studies have observed and profiled these varying microglial states but haven't been able to characterize the genetics behind them.

Kampmann and his team wanted to identify exactly which genes are involved in specific states of microglial activity, and how each of those states are regulated. With that knowledge, they could then flip genes on and off, setting wayward cells back on the right track.

From Advanced Genomics to a Holy Grail

Accomplishing that task required surmount fundamental obstacles that have prevented researchers from controlling gene expression in these cells. For example, microglia are very resistant to the most common CRISPR technique, which involves getting the desired genetic material into the cell by using a virus to deliver it.

To overcome this, Kampmann's team coaxed stem cells donated by human volunteers to become microglia and confirmed that these cells function like their ordinary human counterparts. The team then developed a new platform that combines a form of CRISPR, which enables researchers to turn individual genes on and off -- and which Kampmann had a significant hand in developing -- with readouts of data that indicate functions and states of individual microglia cells.

Through this analysis, Kampmann and his team pinpointed genes that effect the cell's ability to survive and proliferate, how actively a cell produces inflammatory substances, and how aggressively a cell prunes synapses.

And because the scientists had determined which genes control those activities, they were able to reset the genes and flip the diseased cell to a healthy state.

Armed with this new technique, Kampmann plans to investigate how to control the relevant states of microglia, by targeting the cells with existing pharmaceutical molecules and testing them in preclinical models. He hopes to find specific molecules that act on the genes necessary to nudge diseased cells back to a healthy state.

Kampmann said that once the right genes are flipped, it's likely that the "repaired," microglia will resume their responsibilities, removing plaques associated with neurodegenerative disease and protecting synapses rather than taking them apart.

"Our study provides a blueprint for a new approach to treatment," he said. "It's a bit of a holy grail."

https://www.sciencedaily.com/releases/2022/08/220811135415.htm

Why thinking hard makes you tired

August 11, 2022

Science Daily/Cell Press

It's no surprise that hard physical labor wears you out, but what about hard mental labor? Sitting around thinking hard for hours makes one feel worn out, too. Now, researchers have new evidence to explain why this is, and, based on their findings, the reason you feel mentally exhausted (as opposed to drowsy) from intense thinking isn't all in your head.

Their studies, reported in Current Biology on August 11, show that when intense cognitive work is prolonged for several hours, it causes potentially toxic byproducts to build up in the part of the brain known as the prefrontal cortex. This in turn alters your control over decisions, so you shift toward low-cost actions requiring no effort or waiting as cognitive fatigue sets in, the researchers explain.

"Influential theories suggested that fatigue is a sort of illusion cooked up by the brain to make us stop whatever we are doing and turn to a more gratifying activity," says Mathias Pessiglione of Pitié-Salpêtrière University in Paris, France. "But our findings show that cognitive work results in a true functional alteration -- accumulation of noxious substances -- so fatigue would indeed be a signal that makes us stop working but for a different purpose: to preserve the integrity of brain functioning."

Pessiglione and colleagues including first author of the study Antonius Wiehler wanted to understand what mental fatigue really is. While machines can compute continuously, the brain can't. They wanted to find out why. They suspected the reason had to do with the need to recycle potentially toxic substances that arise from neural activity.

To look for evidence of this, they used magnetic resonance spectroscopy (MRS) to monitor brain chemistry over the course of a workday. They looked at two groups of people: those who needed to think hard and those who had relatively easier cognitive tasks.

They saw signs of fatigue, including reduced pupil dilation, only in the group doing hard work. Those in that group also showed in their choices a shift toward options proposing rewards at short delay with little effort. Critically, they also had higher levels of glutamate in synapses of the brain's prefrontal cortex. Together with earlier evidence, the authors say it supports the notion that glutamate accumulation makes further activation of the prefrontal cortex more costly, such that cognitive control is more difficult after a mentally tough workday.

So, is there some way around this limitation of our brain's ability to think hard?

"Not really, I'm afraid," Pessiglione said. "I would employ good old recipes: rest and sleep! There is good evidence that glutamate is eliminated from synapses during sleep."

There may be other practical implications. For example, the researchers say, monitoring of prefrontal metabolites could help to detect severe mental fatigue. Such an ability may help adjust work agendas to avoid burnout. He also advises people to avoid making important decisions when they're tired.

In future studies, they hope to learn why the prefrontal cortex seems especially susceptible to glutamate accumulation and fatigue. They're also curious to learn whether the same markers of fatigue in the brain may predict recovery from health conditions, such as depression or cancer.

https://www.sciencedaily.com/releases/2022/08/220811135344.htm

Non-invasive stimulation of the eye for depression and dementia

August 11, 2022

Science Daily/The University of Hong Kong

A joint research team from the LKS Faculty of Medicine, The University of Hong Kong (HKUMed) and City University of Hong Kong (CityU) has discovered that the electrical stimulation of the eye surface can alleviate depression-like symptoms and improve cognitive function in animal models. These significant findings were recently published in Brain Stimulation and the Annals of the New York Academy of Sciences.

Background

Major depression is the most common and severe psychiatric disorder across the world. Recently, the World Health Organization reported that the COVID-19 pandemic had triggered a massive increase in the number of people with anxiety and depression. About a quarter of patients do not respond adequately to the treatments available.

Dr Lim Lee Wei, Assistant Professor in the School of Biomedical Sciences, HKUMed and a former Lee Kuan Yew Research Fellow in Singapore, reported in 2015 that deep brain stimulation of the prefrontal cortex in the brains of animals could improve memory function and relieve depressive symptoms. These therapeutic effects were attributed to the growth of brain cells in the hippocampus, a region of the brain known to be involved in learning and memory function. However, this technique, also known as deep brain stimulation, is invasive and requires surgery to implant electrodes in the brain, which may cause side effects such as infections and other post-operative complications.

Research findings and significance

A team of Hong Kong researchers headed by Dr Lim Lee Wei; Dr Leanne Chan Lai-hang, Associate Professor in the Department of Electrical Engineering, CityU; Professor Chan Ying-shing, Dexter H C Man Family Professor in Medical Science, Professor of the School of Biomedical Sciences, Associate Dean (Development and Infrastructure), HKUMed, and Director of the Neuroscience Research Centre, HKU, have been looking for alternative ways to treat neuropsychiatric diseases. They discovered that the non-invasive stimulation of the corneal surface of the eye (known as transcorneal electrical stimulation, or TES) that activates brain pathways, resulted in remarkable antidepressant-like effects and reduced stress hormones in an animal model for depression. Furthermore, this technique induced the expression of genes involved in the development and growth of brain cells in the hippocampus.

In related experiments, Yu Wing-shan, PhD student, and other research members from the School of Biomedical Sciences, HKUMed, investigated whether this approach could be used to treat Alzheimer's disease, a common type of dementia with no definitive cure. They found that this non-invasive stimulation in mice drastically improved memory performance and reduced beta-amyloid deposits in the hippocampus, which is one of the hallmarks of Alzheimer's disease.

Dr Leanne Chan Lai-hang, an expert on the electrical stimulation of visual and non-visual brain targets, described this research, 'Transcorneal electrical stimulation is a non-invasive method initially developed to treat eye diseases, and it would be a major scientific breakthrough if it could be applied to treat neuropsychiatric diseases.'

'These research findings pave the way for new therapeutic opportunities to develop novel treatment for patients suffering from treatment-resistant depression and dementia. Nevertheless, clinical trials must be conducted to validate the efficacy and safety,' remarked Professor Chan Ying-shing.

https://www.sciencedaily.com/releases/2022/08/220811143013.htm

Which leisure activities are linked to lower risk of dementia?

August 10, 2022

Science Daily/American Academy of Neurology

Leisure activities, such as reading a book, doing yoga and spending time with family and friends, may help lower the risk of dementia, according to a new meta-analysis published in the August 10, 2022, online issue of Neurology®, the medical journal of the American Academy of Neurology. The meta-analysis reviewed available studies on the effects of cognitive activities, physical activities, and social activities and the risk of dementia.

"Previous studies have shown that leisure activities were associated with various health benefits, such as a lower cancer risk, a reduction of atrial fibrillation, and a person's perception of their own well-being," said study author Lin Lu, PhD, of Peking University Sixth Hospital in Beijing, China. "However, there is conflicting evidence of the role of leisure activities in the prevention of dementia. Our research found that leisure activities like making crafts, playing sports or volunteering were linked to a reduced risk of dementia."

The meta-analysis involved a review of 38 studies from around the world involving a total of more than 2 million people who did not have dementia. The participants were followed for at least three years.

Participants provided information on their leisure activities through questionnaires or interviews. Leisure activities were defined as those in which people engaged for enjoyment or well-being and were divided into mental, physical and social activities.

During the studies, 74,700 people developed dementia.

After adjusting for factors such as age, sex and education, researchers found that leisure activities overall were linked to a reduced risk of dementia. Those who engaged in leisure activities had a 17% lower risk of developing dementia than those who did not engage in leisure activities.

Mental activity mainly consisted of intellectual activities and included reading or writing for pleasure, watching television, listening to the radio, playing games or musical instruments, using a computer and making crafts. Researchers found that people who participated in these activities had a 23% lower risk of dementia.

Physical activities included walking, running, swimming, bicycling, using exercise machines, playing sports, yoga, and dancing. Researchers found that people who participated in these activities had a 17% lower risk of dementia.

Social activities mainly referred to activities that involved communication with others and included attending a class, joining a social club, volunteering, visiting with relatives or friends, or attending religious activities. Researchers found that people who participated in these activities had a 7% lower risk of dementia.

"This meta-analysis suggests that being active has benefits, and there are plenty of activities that are easy to incorporate into daily life that may be beneficial to the brain," Lu said. "Our research found that leisure activities may reduce the risk of dementia. Future studies should include larger sample sizes and longer follow-up time to reveal more links between leisure activities and dementia."

A limitation of the study was that people reported their own physical and mental activity, so they may not have remembered and reported the activities correctly.

https://www.sciencedaily.com/releases/2022/08/220810161200.htm

Low physical function after age 65 associated with future cardiovascular disease

August 31, 2022

Science Daily/American Heart Association

Among people older than age 65 who were assessed using a short physical function test, having lower physical function was independently associated with a greater risk of developing heart attack, heart failure and stroke, according to new research published today in the Journal of the American Heart Association, an open access, peer-reviewed journal of the American Heart Association.

The Short Physical Performance Battery (SPPB) used in this study is considered a measure of physical function, which includes walking speed, leg strength and balance. This study examined physical function, which is different from physical fitness.

"While traditional cardiovascular disease risk factors such as high blood pressure, high cholesterol, smoking or diabetes are closely linked to cardiovascular disease, particularly in middle-aged people, we also know these factors may not be as predictive in older adults, so we need to identify nontraditional predictors for older adults," said study senior author Kunihiro Matsushita, M.D., Ph.D., an associate professor in the department of epidemiology at the Johns Hopkins Bloomberg School of Public Health and the Division of Cardiology at the Johns Hopkins School of Medicine in Baltimore. "We found that physical function in older adults predicts future cardiovascular disease beyond traditional heart disease risk factors, regardless of whether an individual has a history of cardiovascular disease."

The Atherosclerosis Risk in Communities (ARIC) study, an ongoing community-based cohort enrolled 15,792 participants, ages 45-64 years from 1987-1989, to investigate the causes for atherosclerotic disease (plaque or fatty buildup in the arteries). Yearly and semi-yearly (beginning in 2012) check-ins included phone calls and in-person clinic exams.

The present study evaluated health data from ARIC visit 5 (2011-2013; all participants were older than age 65) as a baseline, when the SPPB physical function test was first collected. The SPPB measured physical function to produce a score according to walking speed, speed of rising from a chair without using your hands and standing balance.

Researchers analyzed health data for 5,570 adults (58% women; 78% white adults; 22% Black adults), average age of 75 from 2011 to 2019. Using SPPB scores, the physical function of the participants was categorized into three groups: low, intermediate and high, based on their test performance.

Researchers examined the association of SPPB scores with future heart attack, stroke and heart failure, as well as the composite of the three, adjusting for major cardiovascular disease risk factors, such as high blood pressure, smoking, high cholesterol, diabetes and history of cardiovascular disease.

The study found:

• Among all participants, 13% had low, 30% had intermediate and 57% had high physical function scores.

• During the 8 years of the study, there were 930 participants with one or more confirmed cardiovascular events: 386 diagnosed with heart attack, 251 who had a stroke and 529 heart failure cases.

• Compared to adults with high physical function scores, those with low physical function scores were 47% more likely to experience at least one cardiovascular disease event, and those with intermediate physical function scores had a 25% higher risk of having at least one cardiovascular disease event.

• The association between physical function and cardiovascular disease remained after controlling for traditional cardiovascular disease risk factors such as age, high blood pressure, high cholesterol and diabetes.

• The physical function score improved the risk prediction of cardiovascular disease outcomes beyond traditional cardiovascular risk factors regardless of whether individuals had a history of cardiovascular disease or were healthy.

"Our findings highlight the value of assessing the physical function level of older adults in clinical practice," said study lead author Xiao Hu, M.H.S., a research data coordinator in the department of epidemiology at the Johns Hopkins Bloomberg School of Public Health. "In addition to heart health, older adults are at higher risk for falls and disability. The assessment of physical function may also inform the risk of these concerning conditions in older adults."

Falls and fear of falling in older adults are major health issues, and they are associated with high injury rates, high medical care costs and significant impact on quality of life. A 2022 American Heart Association scientific statement, Preventing and managing falls in adults with cardiovascular disease, advises medication adjustments, reassessing treatment plans, considering non-drug treatment options and properly managing heart rhythm disorders to reduce fall risks among elderly adults.

"Our study adds additional evidence to past research, which has demonstrated the importance of maintaining physical function at an older age," Matsushita said. "The next questions are: what is the best way for older adults to maintain physical function, and whether interventions that improve physical function can reduce cardiovascular disease risk?"

The study had several limitations. The study population included only white and Black adults but did not include people from other racial or ethnic groups (ARIC began enrollment in 1985, when participation among people from diverse racial and ethnic backgrounds was more limited). The study also didn't account for individuals whose lack of mobility might prevent them from getting assessed at a research clinic. Additional research will be required to confirm the findings in people from more diverse racial and ethnic groups and people who have even less physical function.

https://www.sciencedaily.com/releases/2022/08/220831073837.htm

Many types of leisure time activities may lower risk of death for older adults

August 24, 2022

Science Daily/NIH/National Cancer Institute

Older adults who participate weekly in many different types of leisure time activities, such as walking for exercise, jogging, swimming laps, or playing tennis, may have a lower risk of death from any cause, as well as death from cardiovascular disease and cancer, according to a new study led by researchers at the National Cancer Institute, part of the National Institutes of Health.

The findings suggest that it's important for older adults to engage in leisure time activities that they enjoy and can sustain, because many types of these activities may lower the risk of death, the authors wrote.

The findings appear August 24 in JAMA Network Open.

Using data from 272,550 adults between the ages of 59 and 82 who had completed questionnaires about their leisure-time activities as part of the NIH-AARP Diet and Health Study, the researchers looked at whether participating in equivalent amounts of seven different exercise and recreational activities -- including running, cycling, swimming, other aerobic exercise, racquet sports, golf, and walking for exercise -- was associated with lowered risk of death.

The researchers found that achieving the recommended amount of physical activity per week through any combination of these activities was associated with a 13% lower risk of death from any cause compared with no participation in these activities. When they looked at the role of each activity individually, playing racquet sports was associated with a 16% reduction in risk and running with a 15% reduction. However, all the activities investigated were similarly associated with lower risks of death.

The second edition of the Physical Activity Guidelines for Americans recommends that adults engage in 2.5 to 5 hours of moderate-intensity aerobic physical activity, or 1.25 to 2.5 hours of vigorous-intensity aerobic physical activity, each week.

The levels of activity by the most active individuals (those who exceeded the recommended levels of physical activity) were associated with even greater reductions in the risk of death, but there were diminishing returns as activity levels increased. Even people who did some recreational activity, though less than the recommended amount, had a 5% reduction in risk of death than those who did not participate in any of the activities studied.

These activities were also associated with a lower risk of death from cardiovascular disease and cancer. Playing racquet sports was associated with the greatest reduction in risk of cardiovascular deaths (27% reduction), while running was associated with the greatest reduction in risk of cancer deaths (19% reduction).

https://www.sciencedaily.com/releases/2022/08/220824120834.htm

Musical tests can detect mental deterioration in old age

Integration of music with analysis of electrical brain activity

August 17, 2022

Science Daily/Tel-Aviv University

Researchers at Tel Aviv University have developed a method that employs musical tests and a portable instrument for measuring brain activity to detect cognitive decline in old age. According to the researchers, the method, which is based on the measurement of 15 minutes of electrical activity in the brain while performing simple musical tasks, can be easily implemented by any staff member in any clinic, without requiring special training.

The researchers: "Our method enables routine monitoring and early detection of cognitive decline in order to provide treatment and prevent rapid, severe deterioration. Prophylactic tests of this kind are commonly accepted for a variety of physiological problems such as diabetes, high blood pressure or breast cancer; however, to date no method has yet been developed to enable routine, accessible monitoring of the brain for cognitive issues." The researchers further note that tests of this kind are particularly important in light of increasing longevity and associated growth of the elderly population.

The study was led at Tel Aviv University by PhD student Neta Maimon from the School of Psychological Sciences and the Buchmann-Mehta School of Music, and Lior Molcho from Neurosteer Ltd, headed by Prof. Nathan Intrator from the Blavatnik School of Computer Science and the Sagol School of Neuroscience. Other participants included: Adi Sasson, Sarit Rabinowitz, and Noa Regev-Plotnick from the Dorot-Netanya Geriatric Medical Center. The article was published in the journal Frontiers in Aging Neuroscience.

As part of the study, the researchers developed a groundbreaking method combining a portable device for the measurement and innovative analysis of electroencephalography (EEG), developed by Neurosteer, and a short musical test of about 12-15 minutes, developed by Neta Maimon. During the test, the subject is connected to the portable EEG device by means of a adhesive band with only three electrodes attached to the forehead. The subject performs a series of musical-cognitive tasks according to audible instructions given automatically through earphones. The tasks include short melodies played by different instruments, with the subjects instructed to perform various tasks on them at varying levels of difficulty. For example, pressing a button each time any melody is played or pressing it only when the violin plays. In addition, the test includes several minutes of musically guided meditation designed to bring the brain to a resting state, as this state is known to indicate cerebral functioning in various situations.

Neta Maimon, who specializes in musical cognition, explains that music has great influence on different centers in the brain. On the one hand, music is known to be a quick mood stimulant, particularly of positive emotion. On the other hand, in different situations, music can be cognitively challenging, activating the frontal parts of the brain, especially if we try to concentrate on different aspects of the music, and at the same time perform a particular task.

According to Maimon, if we combine these two capabilities, we can create cognitive tests that are quite complex, yet also pleasant and easy to perform. Furthermore, music that is positive and reasonably rhythmic will enhance concentration and performance of the task. Thus, for example, the famous "Mozart effect," showing improved performance on intelligence tests after listening to Mozart's music, actually has nothing to do with Mozart's music, but rather the fact that music creates a positive mood and stimulates us to a state that is optimal for performing intelligence and creativity tests.

Accordingly, the researchers hypothesized that with musical tools, it would also be possible to challenge the subjects to an extent that would enable testing of the brain's frontal activity as well as raising their spirits, thus enhancing their performance on the test while the overall experience is pleasant.

The study included an experiment at the Dorot-Netanya Geriatric Medical Center. Neta Maimon: "Anyone hospitalized at Dorot, or any other geriatric rehabilitation institution, undergoes a standard test called "mini-mental," designed to evaluate their cognitive condition as a routine part of the intake process. The test is conducted by an occupational therapist specially trained for it, and includes a variety of tasks. For example, enumerating the days of the week or months of the year backwards. In this test, up to 30 points can be accrued. A high score indicates normal cognition.

The experiment included the testing of 50 elderly people hospitalized at Dorot who scored 18-30 on the mini-mental test, indicating various levels of cognitive functioning. The participants performed the musical-cognitive tasks, administered automatically. The EEG device registered the electrical activity in the brain during the activity, with the results analyzed using machine learning technology. This allowed mathematical indices to be identified that were precisely correlated with the mini-mental test scores; in other words, we obtained new neuro-markers (brain markers) that may stand alone as indices of the subject's cognitive status.

Maimon adds: "We have actually succeeded in illustrating that music is indeed an effective tool for measuring brain activity. The brain activity and response times to tasks correlated to the subjects' cerebral conditions (correlating to the mini-mental score assigned to them). More importantly, all those who underwent the experiment reported that, on the one hand, it challenged the brain, but on the other it was very pleasant to perform."

The researchers conclude: "Our method enables the monitoring of cognitive capability and detection of cognitive decline already in the early stages. all by simple and accessible means, with a quick and easy test that can be conducted in any clinic. This method is of special importance today due to the increase in longevity and accelerated population growth, particularly among the elderly. Today, millions of people around the world already suffer or are liable to suffer soon from cognitive decline and its dire consequences, and their number will only increase in the coming decades. Our method could pave the way towards efficient cognitive monitoring of the general population, and thus detect cognitive decline in its early stages, when treatment and prevention of severe decline are possible. It is therefore expected to improve the quality of life of millions around the world."

Keren Primor Cohen, CEO, Ramot at TAU: "We are pleased that a company based on a technology developed at TAU continues its collaboration on creative and multidisciplinary research. Ramot will continue to promote and invest in novel technologies, as well as help TAU researchers to maximize their research's potential."

https://www.sciencedaily.com/releases/2022/08/220817104010.htm

Hepatitis C drugs may reduce PTSD symptoms

August 22, 2022

Science Daily/Boston University School of Public Health

More than six percent of Americans will develop posttraumatic stress disorder (PTSD) in their lifetime. This potentially chronic condition disrupts lives, and can lead to or exacerbate existing health issues such as depression, anxiety, eating disorders, and suicidal thoughts.

Despite the high prevalence of PTSD, the US Food and Drug Administration has only approved two medications to treat this condition -- sertraline and paroxetine -- and both have shown only limited effectiveness in reducing PTSD symptoms.

PTSD is also common among military veterans; more than 10 percent of US Department of Veterans Affairs (VA) patients experience these symptoms. Two years ago, researchers at Boston University School of Public Health (BUSPH) and the White River Junction Veterans Affairs Medical Center in Vermont began to investigate whether existing medications may improve PTSD symptoms, with funding from the National Institute of Mental Health.

During an initial exploratory analysis among a national cohort of VA patients, the researchers unexpectedly found that several new direct acting antiviral (DAA) medications used to treat hepatitis C virus infection were associated with PTSD symptom improvement. The findings were published in the journal Biological Psychiatry.

Now, in a new, follow-up study, the researchers have conducted a more rigorous analysis to examine and compare the effectiveness of the previously identified DAAs in PTSD symptom improvement. Their new analysis suggests the most promising DAA for prospective study as a potential medication for PTSD in patients without hepatitis C virus infection.

Published online ahead of print in the American Journal of Epidemiology, the new study found that the medication combination glecaprevir and pibrentasvir had the strongest association with PTSD symptom improvement among the DAAs most prescribed in the VA.

"Many people have PTSD, but there few effective pharmacologic treatments and limited drug development for PTSD," says co-principal investigator and study senior author Jaimie Gradus, associate professor of epidemiology at BUSPH. "Existing effective treatments are mostly psychotherapy, and while they work well, there are also issues with them, including a lot of treatment drop-out and they're time-intensive, so adding to the suite of treatment options for people is a high priority."

The researchers examined the same national cohort of VA patients as the prior study, but narrowed the study group to include only patients diagnosed with hepatitis C.

"There really has been a lot of interest in finding new medications for PTSD in the field," says co-principal investigator Brian Shiner, a psychiatrist and acting associate chief of staff for research at the White River Junction VA Medical Center, as well as associate professor of psychiatry at Dartmouth University's Geisel School of Medicine. "The idea to look at VA data in this way grew out of a conversation in the scientific literature between the VA PTSD Psychopharmacology Working Group and the National Institutes of Mental Health. Paula Schnurr from the National Center for PTSD connected Jaimie and I, and we were really fortunate to obtain funding to bring a team together to do this work."

Using patient care data from VA medical records, Gradus, Shiner, and colleagues from the VA, BUSPH, Geisel, and Harvard Medical School studied 254 VA patients who were diagnosed with PTSD and hepatitis C between October 1999 and September 2019. The participants received one combination of FDA-approved hepatitis C medications, including glecaprevir and pibrentasvir (GLE/PIB); ledipasvir and sofosbuvir (LDV/SOF); or sofosbuvir and velpatasvir (SOF/VEL). The researchers monitored the patients' symptoms for both PTSD and HCV between two clinical visits over 8 to 12 weeks.

After adjusting for variables that could potentially influence results -- such as opioid prescription use, liver disease diagnoses, emergency department care for psychiatric crises -- the team found that the GLE/PIB medications were more strongly associated with PTSD symptom improvement that the LDV/SOF and SOF/VEL treatments, consistent with their previous results.

"At BUSPH, we have been working with our VA colleagues to look at PTSD symptom improvement in routine care using medical records for several years," Gradus says. "The level of improvement we see for GLE/PIB is impressive and over twice what we have seen for paroxetine and sertraline. I think we have done the best we can with medical records data, an important next step in this line of work will be a prospective placebo-controlled study in patients without hepatitis C virus infection."

"We recently received funding from the Department of Defense to study GLE/PIB as a potential treatment for PTSD in a prospective randomized placebo-controlled trial," Shiner says. He and Gradus will be involved with the project, and Vince Watts of the White River Junction VA Medical Center will serve as principal investigator. "It will be several years until we see the results, but this is a very exciting case where we used VA patient data to identify a potential treatment for PTSD, which is a very important problem for veterans' health. In this way, veterans have informed PTSD treatment development."

https://www.sciencedaily.com/releases/2022/08/220822145130.htm

Presence of certain bacteria in the saliva might indicate post-trauma in veteran soldiers

August 14, 2022

Science Daily/Tel-Aviv University

A scientific breakthrough from the Tel Aviv and Haifa Universities may facilitate speedy, objective and accurate diagnosis of people suffering from PTSD using saliva samples. As part of the study, the researchers characterized the psychological, social and medical conditions of about 200 participants, while at the same time collecting saliva samples from them.

The findings of this study show a typical microbial picture in the saliva of veteran soldiers who had experienced combat stress-related reactions (from the first Lebanon War) and are currently suffering from post-trauma.

According to the researchers, these results may help in the future to reach an accurate and objective diagnosis of people suffering from post-trauma, and to develop microbiotic-related medications (associated with the body's microbial ecology).

This study was published in Nature's Molecular Psychiatry journal.

The study was a joint effort by eminent scholars from various fields. It was led by Professor Illana Gozes and included Professor Noam Shomron, Dr. Shlomo Sragovich and Ph.D. student Guy Shapira, (all from TAU's Sackler Faculty of Medicine and Sagol School of Neuroscience) as well as Prof. Zahava Solomon from TAU's Gershon Gordon Faculty of Social Sciences, and Prof. Abraham Sagi-Schwartz and PhD student Ella Levert-Levitt from the Center for the Study of Child Development and the School of Psychological Sciences at Haifa University. The participants in the study came from a larger cohort of subjects from a comprehensive four-decade-long study of veterans by Prof. Solomon.

This study was also supported by IDF's Medical Corps Department of Health and Well-Being and Dr. Ariel Ben Yehuda, former chief of the above Department and currently, a Department Manager in the Mental Health Medical Center in Shalvata, Clallit Health Services. The study also involved collaboration with the Charité University Medicine in Berlin and its microbiology experts Dr. Markus M. Heimesaat and Professor Stefan Bereswill, as well as with the University of Hong Kong, which is studying the effects of air pollution, Professors Victor Li and Jacqueline Lam.

The researchers tested a unique group of about 200 Israeli veteran soldiers who had fought in the first Lebanon War in 1982. The test covered various psychological aspects, including sleep, appetite disorders, guilt, suicidal thoughts, social and spousal support, hostility, satisfaction with life, as well as issues of demographics, psychopathology, welfare, health and education.

Comparing the results of the subjects' microbial distribution to the psychological results and their responses to the welfare questionnaires, the researchers from the universities of Tel Aviv and Haifa found that people with PTSD and high psychopathological indications exhibit the same picture of bacteria in the saliva (a unique oral microbiotic signature). According to the researchers, this study is significant in that for the first time, we might be able to diagnose post-trauma by objective criteria and not just behavioral ones. It is interesting to note here that the saliva bacteria of those exposed to air pollution showed a correlation to the picture with PTSD, while the number of years of education showed a protective influence and a reverse picture of the microbial ecology in the saliva.

Prof. Illana Gozes: "To the best of our knowledge, this is the first depiction of a microbial signature in the saliva among veteran soldiers with PTSD. We were surprised to discover that about a third of the PTSD subjects had never been diagnosed with post-trauma, so they never received any recognition from the Ministry of Defense and the official authorities.

It must be stressed that until now, post-trauma diagnosis has been based solely on psychological and psychiatric measures. Thanks to this study, it may be possible, in the future, to use objective molecular and biological characteristics to distinguish PSTD sufferers, taking into account environmental influences. We hope that this new discovery and the microbial signatures described in this study might promote easier diagnosis of post-traumatic veteran soldiers so they can receive appropriate treatment."

https://www.sciencedaily.com/releases/2022/08/220810123612.htm

New insights on how some individuals with obesity can lose weight -- and keep it off

August 11, 2022

Science Daily/University of Ottawa

For decades, there's been a persistent one-size-fits-all approach to treating obesity: Embrace a diet that's low in calories. Yet evidence shows that this diet-focused approach simply doesn't work for a subset of adults with obesity who are adherent in a clinical weight management program.

Now, compelling new research published in the journal eBioMedicine challenges the deeply ingrained idea that diet alone should be adequate for everyone seeking to shed pounds.

The important conclusions could significantly improve public health by guiding the advent of personalized treatment plans that will help individuals with difficult-to-treat obesity lose weight -- and keep it off.

"It's exciting and important work. These findings have clinical implications and reveal molecular mechanisms that will drive research for many years to come," says Dr. Mary-Ellen Harper, an award-winning professor and research chair in mitochondrial bioenergetics at the uOttawa Faculty of Medicine who was the study's senior author.

Understanding distinct obesity phenotypes is key to teasing out insights into individual variations in weight loss. And for "diet-resistant" obesity -- patients in the bottom 20% for rate of weight loss following a low-calorie diet -- exercise training should be prioritized, as it decreases fat mass and boosts skeletal muscle metabolism.

The research team mined clinical data from over 5,000 records. Ultimately, 228 files were reviewed and a subset of 20 women with obesity were identified to undergo a closely supervised exercise program made up of 18 progressive sessions using treadmills and weights done three times per week for six weeks.

Using bioinformatics and machine learning approaches to analyze skeletal muscle, the results indicate that exercise preferentially improves skeletal muscle metabolism and enhances weight loss capacity for individuals with obesity who are deemed diet resistant.

These are the type of patients with difficult-to-treat obesity who have often been accused of non-adherence when they have not lost weight with diet restriction.

"For those individuals who have obesity and who've had enormous difficulty losing weight, the message for them is: You are in a group of individuals for whom exercise is particularly important. And that's really going to help you lose weight," says Dr. Ruth McPherson, a leader in cardiovascular genetics who is a professor at the uOttawa Faculty of Medicine and director of the Ruddy Canadian Cardiovascular Genetics Centre, Atherogenomics Laboratory and the Lipid Clinic at the Ottawa Heart Institute.

The stakes are high: The number of people who are overweight or obese has grown to epidemic proportions globally and obesity is a risk factor in a slew of chronic diseases. In Canada, two out of every three adults are overweight or obese, according to Statistics Canada.

Dr. Robert Dent, founder of the Ottawa Hospital's weight management clinic and an endocrinologist at uOttawa, described the findings as the "crowning glory" of the research work done alongside Drs. Harper and McPherson over two decades. The three partners have collaborated on numerous projects over the years, helping to unlock mysteries of mitochondrial energetics and the genetic predictors of weight loss.

"If you look at a large group of people who are overweight and trying to lose weight, they don't respond to exercise very much. But now we've found that people in this [diet-resistant] obesity phenotype really do," Dr. Dent says. "What the findings are telling us is that when we see individuals with obesity who don't respond to dietary restriction, they should be shunted over to physical activity."

The study has the potential to help reshape the science of weight-loss programs so they can be customized for individual patients. And since the study opens up various exciting research possibilities at the molecular level, the team is already recruiting for a study with a larger sample size.

https://www.sciencedaily.com/releases/2022/08/220811135349.htm

Babies born to older paternal cry differently, mouse pup study shows

August 23, 2022

Science Daily/Tohoku University

A baby's cry is a form of communication used to attract attention from adult caregivers, and every baby cries in a similar but distinct way. An international research team has studied the vocal behavior of baby mice, called pups, to determine how the age of the father affects the pups' vocal communication and body weight development. Their study will help them better understand vocal development in human babies.

The team published their findings in the journal iScience on August 10, 2022.

Research suggests that infant crying can serve as a marker of a baby's development. Altered crying in a baby may indicate a risk for autism spectrum disorder or other neurodevelopmental disorders. Researchers know that children with these disorders show particular crying patterns.

However, scientists do not fully understand what makes the crying patterns of these children different. Recent studies have shown that advanced paternal age is a risk factor for neurodevelopmental disorders and lower body weight in the offspring.

Wanting to better understand the connection between a father's age and vocal behavior in their offspring, a research team led by Professor Noriko Osumi, Tohoku University Graduate School of Medicine has conducted a study, using mice, to determine how paternal aging influences the vocal behavior of offspring.

One of the team's main findings was that the advanced paternal age causes alterations in early vocal behavior and increases the number of offspring with atypical developmental patterns. "This vocal feature of pups born to aged fathers is similar to that of pups from autism spectrum disorder model mice. Moreover, pups born to young fathers showed a rich repertoire, while those born to aged fathers exhibited a limited repertoire," said Professor Osumi.

In recent years, scientists have studied ultrasonic vocalizations in mice to learn more about the neurobiology of vocal communication. They know that when a pup is separated from its mother and littermates, it emits ultrasonic vocalizations consisting of various sound elements. When the mother hears these sounds, she responds by coming to retrieve the pup. This type of behavior in mice is similar to that of a human infant and mother.

The Tohoku University research team conducted a series of computational analyses of ultrasound vocalizations, comparing the pups of females who mated with young males and females who mated with older males. They separated the young pups from their mother and littermates, one by one, and recorded the ultrasonic vocalizations that occurred. Then the researchers analyzed the ultrasonic vocalization sonograms using machine learning tools.

The researchers examined the ultrasonic vocalization consisting of syllables. Their analyses showed that in pups with advanced age fathers, the syllables were reduced in number and duration. The syllable composition was also altered, with a more limited syllable repertoire in the pups with advanced age fathers. In addition, they measured the body weight of the pups after they completed each ultrasound vocalization recording. Comparing the weights, the team discovered that the pups with the advanced age fathers had consistently lower body weight gain than pups with young fathers.

In modern societies where humans are marrying and giving birth at older ages, advanced paternal age may represent a risk factor for neurodevelopmental disorders. This finding reiterates the clinical evidence that advanced paternal age is a risk factor for the atypical development observed in children with neurodevelopmental disorders and suggests that the effect of advanced paternal age could be detected in early infancy. As a next step, the team will be working to identify the neural basis governing ultrasound generation and the mechanisms by which advanced paternal age affects the offspring.

https://www.sciencedaily.com/releases/2022/08/220823162739.htm

Insufficient sleep in teenagers is associated with overweight and obesity

August 24, 2022

Science Daily/European Society of Cardiology

Adolescents who sleep less than eight hours a night are more likely to be overweight or obese compared to their peers with sufficient sleep,according to research presented at ESC Congress 2022. Shorter sleepers were also more likely to have a combination of other unhealthy characteristics including excess fat around the middle, elevated blood pressure, and abnormal blood lipid and glucose levels.

"Our study shows that most teenagers do not get enough sleep and this is connected with excess weight and characteristics that promote weight gain, potentially setting them up for future problems," said study author Mr. Jesús Martínez Gómez, a researcher in training at the Cardiovascular Health and Imaging Laboratory, Spanish National Centre for Cardiovascular Research (CNIC), Madrid, Spain. "We are currently investigating whether poor sleep habits are related to excessive screen time, which could explain why older adolescents get even less sleep than younger ones."

This study examined the association between sleep duration and health in 1,229 adolescents in the SI! Program for Secondary Schools trial in Spain. Participants had an average age of 12 years at baseline with equal numbers of boys and girls.

Sleep was measured for seven days with a wearable activity tracker three times in each participant at ages 12, 14 and 16 years. For optimal health, the American Academy of Sleep Medicine advises sleeping 9 to 12 hours a night for 6 to 12 year-olds and 8 to 10 hours for 13 to 18 year-olds. To simplify the analysis, the study used 8 hours or more as optimal. Participants were categorised as very short sleepers (less than 7 hours), short sleepers (7 to 8 hours), and optimal (8 hours or more).

Overweight and obesity were determined according to body mass index. The researchers calculated a continuous metabolic syndrome score ranging from negative (healthier) to positive (unhealthier) values that included waist circumference, blood pressure, and blood glucose and lipid levels.

At 12 years of age, only 34% of participants slept at least 8 hours a night, and this dropped to 23% and 19% at 14 and 16 years of age, respectively. Boys tended to get less sleep. Teenagers who got the most sleep also had better quality sleep, meaning they woke up less during the night and spent a higher proportion of the time in bed sleeping compared to those with shorter sleep. The prevalence of overweight/obesity was 27%, 24% and 21% at 12, 14 and 16 years of age, respectively.

Associations between sleep duration, overweight/obesity and metabolic syndrome score were analysed after adjusting for parental education, migrant status, moderate-to-vigorous physical activity, smoking status, energy intake, city (Madrid or Barcelona) and school.

Compared with optimal sleepers, overweight/obesity was 21% and 72% more likely in very short sleepers at 12 and 14 years, respectively. Short sleepers were 19% and 29% more likely to be overweight/obese compared with optimal sleepers at 12 and 14 years, respectively. Similarly, both very short and short sleepers had higher average metabolic syndrome scores at 12 and 14 years compared with optimal sleepers.

Mr. Martínez Gómez said: "The connections between insufficient sleep and adverse health were independent of energy intake and physical activity levels, indicating that sleep itself is important. Excess weight and metabolic syndrome are ultimately associated with cardiovascular diseases, suggesting that health promotion programmes in schools should teach good sleep habits. Parents can set a good example by having a consistent bedtime and limiting screen time in the evening. Public policies are also needed to tackle this global health problem."

https://www.sciencedaily.com/releases/2022/08/220824102909.htm

Preterm birth's link with educational attainment explored in U.K. primary and secondary schoolchildren

Preterm children experience higher rates of poor school attainment, but only kids born very preterm remain at risk by the end of secondary school

August 17, 2022

Science Daily/PLOS

All children born before full term are more likely to have poorer attainment during primary school compared with children born full term (39-41 weeks), but only children born very preterm -- before 32 weeks -- remain at risk of poor attainment at the end of secondary schooling, according to a new study published this week in the open-access journal PLOS ONE by Neora Alterman, Maria Quigley of Oxford Population Health, U.K., and colleagues.

Preterm birth, defined as birth before 37 complete weeks of gestation, accounts for approximately 11% of births globally. Previous studies have shown that children born preterm are at higher risk of poorer academic attainment in primary school compared with children born at full term. However, few studies have followed these children through secondary school, or examined the full spectrum of gestational ages at birth.

In the new study, the researchers used data on children born in England from 2000-2001 who were surveyed in the population-based UK Millennium Cohort Study. Of 11,695 children in that sample, the authors analyzed data on attainment in primary school (at age 11) for 6,950 pupils, and information on secondary school attainment (at age 16) for 7,131 pupils.

At the end of primary school, 17.7% of children had not achieved the expected level in both English and Mathematics. Compared to full term children, children born before 32 weeks or at 32-33 weeks were more than twice as likely not to meet these benchmarks (adjusted relative risk; aRR=2.06, 95% CI 1.46-2.92; aRR=2.13, 95% CI 1.44-3.13). Children born late preterm, at 34-36 weeks, or early term, at 37-38 weeks, were at smaller increased risk of not achieving expected attainment (aRR=1.18, 95% CI 0.94-1.49; aRR=1.21, 95% CI 1.05-1.38).

At the end of secondary school, 45.2% of pupils had not passed at least five General Certificate of Secondary Education (GCSE) examinations including English and Mathematics. Following adjustment, children born very preterm, before 32 weeks, had a 26% elevated risk of not passing five GCSEs (aRR=1.26, 95% CI 1.03-1.54), with 60% of students in this group not achieving five GCSEs. However, children born at any gestation between 32 and 38 weeks were not at elevated risk compared to children born at full term. Further studies are needed in order to confirm this result.

The authors conclude that children born very preterm may benefit from screening for cognitive and language difficulties prior to school entry to guide the provision of additional support during schooling.

The authors add: "Our study showed that birth at any gestational age earlier than full term was associated with poorer attainment at the end of primary school. However, at the end of compulsory education, these pupils had similar outcomes to their peers, except for pupils born at less than 32 weeks, who remained at risk of low attainment."

https://www.sciencedaily.com/releases/2022/08/220817144026.htm

Early-term births associated with higher rate of ADHD as reported by teachers

August 12, 2022

Science Daily/Rutgers University

Among children born at term (37-41 weeks), those born before 39 weeks are more likely to experience symptoms associated with attention-deficit/hyperactivity disorder (ADHD), according to a study by Rutgers Robert Wood Johnson Medical School.

ADHD, which affects more than 10 percent of U.S. school-age children, according to the Centers for Disease Control and Prevention, manifests early in childhood with symptoms of hyperactivity, impulsivity or inattention, and has known links to preterm birth (less than 37 weeks gestation). The study, published in the Journal of Pediatrics, is one of only a few to investigate the associations between gestational age at term (37-41 weeks) and a diagnosis or symptoms of ADHD. It is the first to include reports from teachers.

"Teachers' reports, in conjunction with maternal reports and physician evaluations, provide valuable input for the diagnosis of ADHD," said Nancy Reichman, author of the study and a professor of pediatrics at Rutgers Robert Wood Johnson Medical School. "Mother-reported symptoms generally reflect behaviors in the home or in small family or social groups, while teacher-reported symptoms reflect behaviors in a structured educational setting by professionals who work with a large number of children and observe the range of behaviors that students exhibit in classrooms."

Reichman and her team, which included Rutgers Robert Wood Johnson Medical School neonatology fellow Geethanjali Linguasubramanian, sought to estimate the associations between gestational age at term and 9-year-old children's symptoms of ADHD reported by their teachers.

They analyzed data on about 1,400 children in the Fragile Families and Child Wellbeing study, a U.S. birth cohort study that randomly sampled births in 75 hospitals in 20 large U.S. cities from 1998 to 2000 and re-interviewed mothers over nine years. During the nine-year follow-up, consent was obtained to contact the children's teachers, who were asked to evaluate their students using the Conners' Teacher Rating Scale-Revised Short Form, which includes symptoms of hyperactivity, ADHD, oppositional behavior and cognitive problems or inattention.

Overall, the Rutgers researchers found that children born early-term (37-38 weeks) had significantly higher scores on the teacher rating scales than children who were full-term (39-41 weeks) for hyperactivity, ADHD and cognitive problems or inattention, but that gestational age wasn't significantly associated with oppositional behavior.

Specifically, the researchers found that each week of gestational age at term was associated with 6 percent lower hyperactivity scores and 5 percent lower ADHD and cognitive problems or inattention scores, and that birth at 37 to 38 weeks was associated with 23 percent higher hyperactivity scores and 17 percent higher ADHD scores when compared with birth at 39 to 41 weeks.

"The findings add to growing evidence supporting current recommendations for delaying elective deliveries to at least 39 weeks and suggest that regular screenings for ADHD symptoms are important for children born at 37 to 38 weeks," Reichman said.

Preterm infants are at increased risk for ADHD because of immature brain development, she said. "Significant growth and development in various kinds of brain cells are observed between 34 and 40 weeks of gestation," said Reichman. "Infants born at full-term likely benefit from the additional one to two weeks of brain growth in utero compared with those born early-term."

https://www.sciencedaily.com/releases/2022/08/220812224142.htm

Water fluoridation: Effective prevention for tooth decay and a win for the environment

August 29, 2022

Science Daily/Trinity College Dublin

Trinity College Dublin researchers collaborating with University College London have demonstrated for the first time the low environmental footprint of water fluoridation compared to other preventive measures for tooth decay. The study is published in the British Dental Journal today [Monday 29th August 2022].

Water fluoridation is regarded as one of the most significant public health interventions of the twentieth century. But as the climate crisis worsens, the contribution of healthcare and the prevention of disease to the crisis must be considered. Action is urgent.

Influenced by this urgency, researchers quantified the environmental impact of water fluoridation for an individual five year-old child over a one-year period and compared this to the traditional use of fluoride varnish and toothbrushing programmes, which take place in selected schools across the UK, and internationally.

Today, over 35% of the world's population have access to water fluoridation, with studies showing significant reductions in dental caries. Whilst data on the clinical effectiveness and cost analysis of water fluoridation are available, there has been no data regarding its environmental impact up to now.

To quantify this impact, the research team performed a Life Cycle Assessment (LCA) by carefully measuring the combined travel, the weight and amounts of all products and the processes involved in all three preventive programmes (toothbrushing, fluoride varnish programmes and water fluoridation). Data was inputted into a specific environmental programme (OpenLCA) and the team used the Ecoinvent database, enabling them to calculate environmental outputs, including the carbon footprint, the amount of water used for each product and the amount of land use.

The results of the study, led by Brett Duane, Associate Professor in Dental Public Health at Trinity College, concluded that water fluoridation had the lowest environmental impact in all categories studied, and had the lowest disability-adjusted life years impact when compared to all other community-level caries prevention programmes. The study also found that water fluoridation gives the greatest return on investment.

Considering the balance between clinical effectiveness, cost effectiveness and environmental sustainability, researchers believe that water fluoridation should be the preventive intervention of choice.

This research strengthens the case internationally for water fluoridation programmes to reduce dental decay, especially in the most vulnerable populations.

Associate Professor Duane said: "As the climate crisis starts to worsen, we need to find ways of preventing disease to reduce the environmental impact of our health systems. This research clearly demonstrates the low carbon impact of water fluoridation as an effective prevention tool."

Professor Paul Ashley, Senior Clinical Lecturer (Honorary NHS Consultant), UCL Eastman Dental Institute added: "Renewed efforts should be made to increase access to this intervention."

https://www.sciencedaily.com/releases/2022/08/220829194742.htm

Sugar disrupts microbiome, eliminates protection against obesity and diabetes

August 29, 2022

Science Daily/Columbia University Irving Medical Cent

A study of mice found that dietary sugar alters the gut microbiome, setting off a chain of events that leads to metabolic disease, pre-diabetes, and weight gain.

The findings, published today in Cell, suggest that diet matters, but an optimal microbiome is equally important for the prevention of metabolic syndrome, diabetes, and obesity.

Diet alters microbiome

A Western-style high-fat, high-sugar diet can lead to obesity, metabolic syndrome, and diabetes, but how the diet kickstarts unhealthy changes in the body is unknown.

The gut microbiome is indispensable for an animal's nutrition, so Ivalyo Ivanov, PhD, associate professor of microbiology & immunology at Columbia University Vagelos College of Physicians and Surgeons, and his colleagues investigated the initial effects of the Western-style diet on the microbiome of mice.

After four weeks on the diet, the animals showed characteristics of metabolic syndrome, such as weight gain, insulin resistance, and glucose intolerance. And their microbiomes had changed dramatically, with the amount of segmented filamentous bacteria -- common in the gut microbiota of rodents, fish, and chickens -- falling sharply and other bacteria increasing in abundance.

Microbiome changes alter Th17 cells

The reduction in filamentous bacteria, the researchers found, was critical to the animals' health through its effect on Th17 immune cells. The drop in filamentous bacteria reduced the number of Th17 cells in the gut, and further experiments revealed that it's the Th17 cells that are necessary to prevent metabolic disease, diabetes, and weight gain.

"These immune cells produce molecules that slow down the absorption of 'bad' lipids from the intestines and they decrease intestinal inflammation," Ivanov says. "In other words, they keep the gut healthy and protect the body from absorbing pathogenic lipids."

Sugar vs. fat

What component of the high-fat, high-sugar diet led to these changes? Ivanov's team found that sugar was to blame.

"Sugar eliminates the filamentous bacteria, and the protective Th17 cells disappear as a consequence," says Ivanov. "When we fed mice a sugar-free, high-fat diet, they retain the intestinal Th17 cells and were completely protected from developing obesity and pre-diabetes, even though they ate the same number of calories."

But eliminating sugar did not help all mice. Among those lacking any filamentous bacteria to begin with, elimination of sugar did not have a beneficial effect, and the animals became obese and developed diabetes.

"This suggests that some popular dietary interventions, such as minimizing sugars, may only work in people who have certain bacterial populations within their microbiota," Ivanov says.

In those cases, certain probiotics might be helpful. In Ivanov's mice, supplements of filamentous bacteria led to the recovery of Th17 cells and protection against metabolic syndrome, despite the animals' consumption of a high-fat diet.

Though people do not have the same filamentous bacteria as mice, Ivanov thinks that other bacteria in people may have the same protective effects.

Providing Th17 cells to the mice also provided protection and may also be therapeutic for people. "Microbiota are important, but the real protection comes from the Th17 cells induced by the bacteria," Ivanov says.

"Our study emphasizes that a complex interaction between diet, microbiota, and the immune system plays a key role in the development of obesity, metabolic syndrome, type 2 diabetes, and other conditions," Ivanov says. "It suggests that for optimal health it is important not only to modify your diet but also improve your microbiome or intestinal immune system, for example, by increasing Th17 cell-inducing bacteria."

https://www.sciencedaily.com/releases/2022/08/220829194721.htm

Single dose of alcohol is enough to modify the brain

August 26, 2022

Science Daily/University of Cologne

A research team from the University of Cologne and the Universities of Mannheim and Heidelberg has found that even the single administration of alcohol permanently alters the morphology of neurons. In particular, the structure of the synapses as well as the dynamics of mitochondria -- the powerhouses of the cell -- are influenced by alcohol. Using the genetic model system of the fruit fly Drosophila melanogaster, Professor Dr Henrike Scholz and her team members Michèle Tegtmeier und Michael Berger showed that changes in the migration of mitochondria in the synapses reduce the rewarding effect of alcohol. These results suggest that even a single consumption event can lay the foundation for alcohol addiction.

The study "Single-dose ethanol intoxication causes acute and lasting neuronal changes in the brain" has appeared in PNAS (Proceedings of the National Academy of Sciences).

Which changes in the brain accompany the transition from sporadic drinking to chronic alcohol abuse? That is the question a joint research project with working groups at the University of Mannheim-Heidelberg and the University of Cologne explored. Most scientific research has examined the effects of chronic alcohol consumption on the hippocampus -- the control centre of our brain. Because of this, little is known about the acute neuronal interactions of critical risk factors, such as a first alcohol intoxication at an early age, explained Henrike Scholz: 'We set out to discover ethanol-dependent molecular changes. These, in turn, provide the basis for permanent cellular changes following a single acute ethanol intoxication. The effects of a single alcohol administration were examined at the molecular, cellular and behavioural levels.' The working hypothesis was that, similar to the formation of memory after a single lesson, a single administration of ethanol would form a positive association with alcohol.

The team tested its hypothesis using research in fruit flies and mouse models and found ethanol-induced changes in two areas: mitochondrial dynamics and the balance between synapses in neurons. Mitochondria supply cells and especially nerve cells with energy. In order to optimally deliver the energy to the cells, the mitochondria move. The movement of the mitochondria was disturbed in the cells treated with ethanol. The chemical balance between certain synapses was also disturbed. These changes remained permanent and were confirmed by behavioural changes in the animals: Mice and fruit flies showed increased alcohol consumption and alcohol relapse later in life.

The morphological remodelling of neurons is a well-known basis for learning and memory. These so-called cellular plasticity mechanisms, which are central to learning and memory, are also thought to be at the core of the formation of associative memories for drug-related rewards. Therefore, some of the observed morphological changes may influence ethanol-related memory formation. Together with the migration of mitochondria in neurons, which are also important for synaptic transmission and plasticity, the researchers speculate that these ethanol-dependent cellular changes are critical for the development of addictive behaviours.

'It is remarkable that the cellular processes contributing to such complex reward behaviour are conserved across species, suggesting a similar role in humans,' said Henrike Scholz. 'It could be a possible general cellular process essential for learning and memory.'

Both of the observed mechanisms could explain observations made in mice that a single intoxication experience can increase alcohol consumption and alcohol relapse later in life. 'These mechanisms may even be relevant to the observation in humans that the first alcohol intoxication at an early age is a critical risk factor for later alcohol intoxication and the development of alcohol addiction,' explained Professor Scholz. 'This means that identifying lasting ethanol-dependent changes is an important first step in understanding how acute drinking can turn into chronic alcohol abuse.'

https://www.sciencedaily.com/releases/2022/08/220826113320.htm

Good sleepers have lower risk of heart disease and stroke

August 26, 2022

Science Daily/European Society of Cardiology

Nine in ten people do not get a good night's sleep, according to research presented at ESC Congress 2022.1 The study found that suboptimal sleep was associated with a higher likelihood of heart disease and stroke. The authors estimated that seven in ten of these cardiovascular conditions could be prevented if everyone was a good sleeper.

"The low prevalence of good sleepers was expected given our busy, 24/7 lives," said study author Dr. Aboubakari Nambiema of INSERM (the French National Institute of Health and Medical Research), Paris, France. "The importance of sleep quality and quantity for heart health should be taught early in life when healthy behaviours become established. Minimising night-time noise and stress at work can both help improve sleep."

Previous studies on sleep and heart disease have generally focused on one sleep habit, such as sleep duration or sleep apnoea, where breathing stops and starts while sleeping. In addition, prior studies have often assessed sleep at baseline only. The current study used a healthy sleep score combining five sleep habits. The researchers investigated the association between the baseline sleep score, and changes over time in the sleep score, and incident cardiovascular disease.

This study included 7,200 participants of the Paris Prospective Study III (PPP3), an observational community-based prospective cohort. Men and women aged 50 to 75 years and free of cardiovascular disease were recruited in a preventive medical centre between 2008 and 2011. The average age was 59.7 years and 62% were men. Participants underwent a physical examination and completed questionnaires on lifestyle, personal and family medical history, and medical conditions.

Questionnaires were used to collect information on five sleep habits at baseline and two follow up visits. Each factor was given 1 point if optimal and 0 if not. A healthy sleep score ranging from 0 to 5 was calculated, with 0 or 1 considered poor and 5 considered optimal. Those with an optimal score reported sleeping 7 to 8 hours per night, never or rarely having insomnia, no frequent excessive daytime sleepiness, no sleep apnoea, and an early chronotype (being a morning person). The researchers checked for incident coronary heart disease and stroke every two years for a total of 10 years.

At baseline, 10% of participants had an optimal sleep score and 8% had a poor score. During a median follow up of eight years, 274 participants developed coronary heart disease or stroke. The researchers analysed the association between sleep scores and cardiovascular events after adjusting for age, sex, alcohol consumption, occupation, smoking, body mass index, physical activity, cholesterol level, diabetes, and family history of heart attack, stroke or sudden cardiac death. They found that the risk of coronary heart disease and stroke decreased by 22% for every 1 point rise in the sleep score at baseline. More specifically, compared to those with a score of 0 or 1, participants with a score of 5 had a 75% lower risk of heart disease or stroke.

The researchers estimated the proportion of cardiovascular events that could be prevented with healthier sleep. They found that if all participants had an optimal sleep score, 72% of new cases of coronary heart disease and stroke might be avoided each year.

Over two follow ups, almost half of participants (48%) changed their sleep score: in 25% it decreased whereas in 23% it improved. When the researchers examined the association between the change in score and cardiovascular events, they found that a 1 point increment over time was associated with a 7% reduction in the risk of coronary heart disease or stroke.

Dr. Nambiema said: "Our study illustrates the potential for sleeping well to preserve heart health and suggests that improving sleep is linked with lower risks of coronary heart disease and stroke. We also found that the vast majority of people have sleep difficulties. Given that cardiovascular disease is the top cause of death worldwide, greater awareness is needed on the importance of good sleep for maintaining a healthy heart."

https://www.sciencedaily.com/releases/2022/08/220826113357.htm