The secret to staying young: New research highlights power of life long exercise to keep muscles healthy

March 21, 2022

Science Daily/The Physiological Society

Lifelong physical activity could protect against age-related loss of muscle mass and function, according to research published in The Journal of Physiology. Individuals aged 68 and above who were physically active throughout their life have healthier ageing muscle that has superior function and is more resistant to fatigue compared to inactive individuals, both young and old.

This is the first study to investigate muscle, stem cell and nerve activity in humans. The researchers from University of Copenhagen, Denmark, found that elderly individuals who keep physically active throughout their adult life, whether by taking part in resistance exercise, ball games, racket sports, swimming, cycling, running and/or rowing had a greater number of muscle stem cells, otherwise known as satellite cells in their muscle. These cells are important for muscle regeneration and long-term growth and protect against nerve decay.

46 male participants took part in the study. They were divided into three groups: young sedentary (15), elderly lifelong exercise (16) and elderly sedentary (15). They performed a heavy resistance exercise, sitting in a mechanical chair performing a knee extension movement to evaluate muscle function. The amount of force produced was measured. Blood samples were taken, and muscle biopsies were analysed from both legs. The researchers found elderly lifelong exercisers outperformed both the elderly and young sedentary adults.

Lead author, Casper Soendenbroe, University of Copenhagen, Denmark said:

"This is the first study in humans to find that lifelong exercise at a recreational level could delay some detrimental effects of ageing. Using muscle tissue biopsies, we've found positive effects of exercise on the general ageing population. This has been missing from the literature as previous studies have mostly focused on master athletes, which is a minority group. Our study is more representative of the general population aged 60 and above, as the average person is more likely to take part in a mixture of activities at a moderate level. That's why we wanted to explore the relation between satellite cell content and muscle health in recreationally active individuals. We can now use this as a biomarker to further investigate the link between exercise, ageing and muscle health."

"The single most important message from this study, is that even a little exercise seems to go a long way, when it comes to protecting against the age-related decline in muscle function. This is an encouraging finding which can hopefully spur more people to engage in an activity that they enjoy. We still have much to learn about the mechanisms and interactions between nerves and muscles and how these change as we age. Our research takes us one step closer."

It is worth noting that the study was only carried out in males and the average age was 73. As the effects of ageing on muscle health become more pronounced at 80+ years, follow up studies are needed to see if the benefits of lifelong exercise are maintained later in life. Further, investigation on recreational activity and muscle health need to be carried out in females.

https://www.sciencedaily.com/releases/2022/03/220321103818.htm

Novel heart ultrasound measures can be used to predict risk of developing dementia

March 22, 2022

Science Daily/University of Minnesota Medical School

Published in JAMA, research from the University of Minnesota assessed if there is a link between heart health and dementia.

Using echocardiography -- visual ultrasound of the heart -- the research team was able to identify novel measures that are linked to a higher dementia risk.

"Atrial myopathy, a condition characterized by abnormal left atrial function and size, is an independent risk factor for dementia," said Dr. Lin Yee Chen, director of the cardiac electrophysiology section at the U of M Medical School and M Health Fairview, and principal investigator of the NIH grant that funded this study. "In this community-based cohort study, lower left atrial function was associated with higher risk of dementia."

The study observed a cohort of 4,096 participants with an average age of 35 years. Participants were 60% women, 22% Black and 78% white. Of the cohort, there were 531 participants who developed dementia over a six year period.

When comparing the lowest to the highest quintile of left atrial function measures (reservoir strain, conduit strain, and contractile strain), the lowest quintile was significantly associated with 1.5 to 2.0-fold higher risk of developing dementia. These associations were independent of cardiovascular disease and atrial fibrillation. The research team found that the more common measures of left atrial size were not significantly associated with dementia.

"Results of this epidemiological study improve our understanding of the link between cardiovascular disease and increased risk of dementia," said Jacqueline D. Wright, Dr.P.H., a program officer in the division of cardiovascular sciences at the National Heart, Lung, and Blood Institute, part of the National Institutes of Health. "This study suggests that atrial myopathy increases risk of dementia, independently of atrial fibrillation. Further research may confirm this finding, help us to better define and diagnose atrial myopathy, and ultimately lead to improved treatments that reduce the chance of developing dementia later in life."

Researchers recommend additional studies to confirm their findings and to establish a robust definition for atrial myopathy.

https://www.sciencedaily.com/releases/2022/03/220322122557.htm

Lithium may decrease risk of developing dementia

March 17, 2022

Science Daily/University of Cambridge

Researchers have identified a link suggesting that lithium could decrease the risk of developing dementia, which affects nearly one million people in the UK.

The researchers, from the University of Cambridge, conducted a retrospective analysis of the health records of nearly 30,000 patients from Cambridgeshire and Peterborough NHS Foundation Trust. The patients were all over the age of 50 and accessed NHS mental health services between 2005 and 2019.

The analysis suggested that patients who received lithium were less likely to develop dementia than those who did not, although the overall number of patients who received lithium was small.

Their findings, reported in the journal PLoS Medicine, support the possibility that lithium could be a preventative treatment for dementia, and could be progressed to large randomised controlled trials.

Dementia is the leading cause of death in elderly Western populations, but no preventative treatments are currently available: more than 55 million people worldwide have dementia, with Alzheimer's disease the most common form.

"The number of people with dementia continues to grow, which puts huge pressure on healthcare systems," said Dr Shanquan Chen from Cambridge's Department of Psychiatry, the paper's first author. "It's been estimated that delaying the onset of dementia by just five years could reduce its prevalence and economic impact by as much as 40 percent."

Previous studies have proposed lithium as a potential treatment for those who have already been diagnosed with dementia or early cognitive impairment, but it is unclear whether it can delay or even prevent the development of dementia altogether, as these studies have been limited in size.

Lithium is a mood stabiliser usually prescribed for conditions such as bipolar affective disorder and depression. "Bipolar disorder and depression are considered to put people at increased risk of dementia, so we had to make sure to account for this in our analysis," said Chen.

Chen and his colleagues analysed data from patients who accessed mental health services from Cambridgeshire and Peterborough NHS Foundation Trust between 2005 and 2019. Patients were all over 50 years of age, received at least a one-year follow-up appointment, and had not been previously diagnosed with either mild cognitive impairment or dementia.

Of the 29,618 patients in the study cohort, 548 patients had been treated with lithium and 29,070 had not. Their mean age was just under 74 years, and approximately 40% of patients were male.

For the group that had received lithium, 53, or 9.7%, were diagnosed with dementia. For the group that had not received lithium, 3,244, or 11.2%, were diagnosed with dementia.

After controlling for factors such as smoking, other medications, and other physical and mental illnesses, lithium use was associated with a lower risk of dementia, both for short and long-term users. However, since the overall number of patients receiving lithium was small and this was an observational study, larger clinical trials would be needed to establish lithium as a potential treatment for dementia.

Another limitation of the study was the number of patients who had been diagnosed with bipolar disorder, which is normally associated with an increased risk of dementia. "We expected to find that patients with bipolar disorder were more likely to develop dementia, since that is the most common reason to be prescribed lithium, but our analysis suggested the opposite," said Chen. "It's far too early to say for sure, but it's possible that lithium might reduce the risk of dementia in people with bipolar disorder."

This paper supports others which have suggested lithium might be helpful in dementia. Further experimental medicine and clinical studies are now needed to see if lithium really is helpful in these conditions.

https://www.sciencedaily.com/releases/2022/03/220317143710.htm

Extended napping in seniors may signal dementia

Daytime sleep duration triples after Alzheimer's diagnosis

March 17, 2022

Science Daily/University of California - San Francisco

Daytime napping among older people is a normal part of aging -- but it may also foreshadow Alzheimer's disease and other dementias. And once dementia or its usual precursor, mild cognitive impairment, are diagnosed, the frequency and/or duration of napping accelerates rapidly, according to a new study.

The study, led by UC San Francisco and Harvard Medical School together with Brigham and Women's Hospital, its teaching affiliate, departs from the theory that daytime napping in older people serves merely to compensate for poor nighttime sleep. Instead, it points to work by other UCSF researchers suggesting that dementia may affect the wake-promoting neurons in key areas of the brain, the researchers state in their paper publishing March 17, 2022, in Alzheimer's and Dementia: The Journal of the Alzheimer's Association.

"We found the association between excessive daytime napping and dementia remained after adjusting for nighttime quantity and quality of sleep," said co-senior author Yue Leng, MD, PhD, of the UCSF Department of Psychiatry and Behavioral Sciences.

"This suggested that the role of daytime napping is important itself and is independent of nighttime sleep," said Leng, who partnered with Kun Hu, PhD, of Harvard Medical School, in senior-authoring the paper.

Watch-Like Devices, Annual Evaluations Used to Measure Naps, Cognition

In the study, the researchers tracked data from 1,401 seniors, who had been followed for up to 14 years by the Rush Memory and Aging Project at the Rush Alzheimer's Disease Center in Chicago. The participants, whose average age was 81 and of whom approximately three-quarters were female, wore a watch-like device that tracked mobility. Each prolonged period of non-activity from 9 a.m. to 7 p.m. was interpreted as a nap.

The device was worn every year continuously for up to 14 days, and once a year each participant underwent a battery of neuropsychological tests to evaluate cognition. At the start of the study 75.7% of participants had no cognitive impairment, while 19.5% had mild cognitive impairment and 4.1% had Alzheimer's disease.

For participants who did not develop cognitive impairment, daily daytime napping increased by an average 11 minutes per year. The rate of increase doubled after a diagnosis of mild cognitive impairment to a total of 24 minutes and nearly tripled to a total of 68 minutes after a diagnosis of Alzheimer's disease.

When the researchers looked at the 24% of participants who had normal cognition at the start of the study but developed Alzheimer's six years later, and compared them with those whose cognition remained stable, they found differences in napping habits. Participants who napped more than an hour a day had a 40% higher risk of developing Alzheimer's than those who napped less than an hour a day; and participants who napped at least once a day had a 40% higher risk of developing Alzheimer's than those who napped less than once a day.

The research confirms the results of a 2019 study, of which Leng was the first author, that found older men who napped two hours a day had higher odds of developing cognitive impairment that those who napped less than 30 minutes a day. The current study builds on these findings by evaluating both daytime napping and cognition each year, hence addressing directionality, Leng notes.

Loss of Wake-Promoting Neurons May Account for Longer Naps 

According to the researchers, increase in napping may be explained by a further 2019 study, by other UCSF researchers, comparing the postmortem brains of people with Alzheimer's disease to those without cognitive impairment. Those with Alzheimer's disease were found to have fewer wake-promoting neurons in three brain regions. These neuronal changes appear to be linked to tau tangles -- a hallmark of Alzheimer's, characterized by increased activity of enzymes causing the protein to misfold and clump.

"It is plausible that our observed associations of excessive daytime napping at baseline, and increased risk for Alzheimer's disease during follow-up, may reflect the effect of Alzheimer's disease pathology at preclinical stages," the authors noted.

The study shows for the first time that napping and Alzheimer's disease "seem to be driving each other's changes in a bi-directional way," said Leng, who is also affiliated with the UCSF Weill Institute for Neurosciences. "I don't think we have enough evidence to draw conclusions about a causal relationship, that it's the napping itself that caused cognitive aging, but excessive daytime napping might be a signal of accelerated aging or cognitive aging process," she said.

"It would be very interesting for future studies to explore whether intervention of naps may help slow down age-related cognitive decline."

https://www.sciencedaily.com/releases/2022/03/220317111848.htm

Plasma biomarker screening could improve accuracy, health equity in Alzheimer’s disease diagnosis

March 17, 2022

Science Daily/Mayo Clinic

A new study focuses on RNA molecules in plasma as biomarkers for Alzheimer's disease in African Americans -- the population at greatest risk for developing Alzheimer's disease. This approach enabled researchers to pinpoint specific molecules in plasma that could serve as biomarkers to confirm a diagnosis of Alzheimer's disease in this population.

Mayo Clinic researchers have identified a new set of molecular markers in blood plasma. This discovery could lead to the development of improved diagnostic tests for Alzheimer's disease. Alzheimer's disease is the most common form of dementia, affecting 6.2 million people in the U.S.

The Mayo Clinic study, published in eBioMedicine, is the first study to focus on RNA molecules in plasma as biomarkers for Alzheimer's disease in African Americans -- the population at greatest risk for developing Alzheimer's disease. This approach enabled researchers to pinpoint specific molecules in plasma that could serve as biomarkers to confirm a diagnosis of Alzheimer's disease in this population.

The study builds on previous research that identified genetic risk factors for Alzheimer's disease and established that RNA molecules in blood plasma could potentially be used as biomarkers.

In the study, researchers examined blood plasma messenger RNA molecules in 151 African Americans diagnosed with Alzheimer's disease and 269 African Americans diagnosed as cognitively unimpaired with Clinical Dementia Rating scale scores of zero. The researchers found that when the plasma levels of six messenger RNA molecules -- encoded by genes CLU, APP, CD14, ABCA7, AKAP9 and APOE -- were accounted for in their statistical models, they improved their ability to accurately identify participants with an Alzheimer's diagnosis by 8%. Researchers explain this is an improvement, compared to statistical models that account for only the presence of known risk factors, such as age and sex, and whether the person is a carrier of the APOE-e4 allele -- a gene known to increase the risk of Alzheimer's disease.

The researchers predict this discovery could lead to more accurate Alzheimer's disease screening for everyone, particularly for the people and communities at greatest risk.

"Having a comprehensive panel of biomarkers for use in screening will help with early detection of Alzheimer's disease, and it will also contribute to intervention strategies that can delay and mitigate the onset of the disease," says Joseph Reddy, Ph.D., a Mayo Clinic quantitative health sciences researcher and first author. "This could be especially relevant for African Americans -- a population underrepresented in Alzheimer's disease research -- who were the focus of this study."

The researchers predict that this discovery could contribute to the development of more accessible, minimally invasive screening options, enabling improved disease management.

"Many screening tests for Alzheimer's disease may not be accessible to all patients due to cost or lack of availability at health care facilities in their area," says Minerva Carrasquillo, Ph.D., a Mayo Clinic neurogeneticist and senior author. "Some tests rely on complex imaging techniques, or on obtaining a sample of cerebrospinal fluid from the patient. Obtaining a plasma sample only requires a blood draw, which is a routine procedure in most clinical settings."

The researchers indicate that future research will focus on identifying additional genetic biomarkers in blood plasma that may improve the accuracy of Alzheimer's disease diagnostic tests.

https://www.sciencedaily.com/releases/2022/03/220317111843.htm

Alzheimer’s: Protective immune cells active decades before symptom onset

Boosting the brain’s defenses could help combat the disease

March 17, 2022

Science Daily/DZNE - German Center for Neurodegenerative Diseases

In individuals with a genetic predisposition to Alzheimer's disease, the immune cells of the brain -- the "microglia" -- start exerting a protective effect up to two decades before the first symptoms appear. A team from Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) and Ludwig-Maximilians-Universität (LMU) München draws this conclusion based on a study of more than 200 volunteers, which they report in the journal The Lancet Neurology. In light of their study data, the scientists consider modulating the activity of microglia to be a promising therapeutic approach. To this end, they aim to develop drugs that target a cellular receptor called TREM2.

About one percent of all people with Alzheimer's develop the disease as a result of gene mutations that can be passed on from generation to generation. As part of the international DIAN (Dominantly Inherited Alzheimer Network) observational study, DZNE and LMU München are participating in research into this genetic form of Alzheimer's disease. The DIAN study cohort includes adults who carry gene mutations that cause Alzheimer's as well as their close relatives without mutations.

Measurements Over Several Years

For the current research, the team led by molecular biologist Prof. Christian Haass and neurologist Dr. Estrella Morenas-Rodríguez analyzed how signatures of microglial activation were related to the development of certain biomarkers of Alzheimer's disease. To this end, cerebrospinal fluid and cognition were assessed over a period of several years in 248 participants of the DIAN study comprising the different stages of Alzheimer's disease. The volunteers were also examined by magnetic resonance imaging (MRI) and positron emission tomography (PET) to visualize brain shrinkage and amyloid pathology -- both are hallmarks of Alzheimer's disease.

The starting point for the research team was a protein called TREM2. "This is a receptor on the surface of microglia, but parts of it can detach and are then detectable in the cerebrospinal fluid. It is known from laboratory studies, particularly in mice but also from our earlier human studies, that levels of TREM2 in the cerebrospinal fluid are a good indicator of microglial activity. TREM2 is a kind of activity switch. As TREM2 levels increase, so do microglial protective activities," explains Christian Haass, research group leader at DZNE and professor of biochemistry at LMU München. "For a long time, it was assumed that microglia mainly cause damage in the course of Alzheimer's disease, as they can fuel chronic inflammatory processes. However, there is growing evidence from my laboratory and many others that microglia have a protective effect at least at the beginning of the disease. This hypothesis is supported by our current data."

Estrella Morenas-Rodríguez, postdoctoral researcher in the Haass team at the time of the investigation and now junior group leader at Hospital Universitario 12 de Octubre in Madrid, Spain adds: "One of the determinant points which allowed us to make our observations, and that was also a challenge, was to be able to study for the first time the increase of the TREM2 marker longitudinally. That is, we measured the marker in several samples taken from the same individuals every one or two years. With that we could better capture the development of the different processes occurring in Alzheimer´s disease than studying samples at just one time point."

Conspicuous Long in Advance

People with a genetic predisposition to Alzheimer's usually develop the disease at a similar age as their relatives with the same mutation who already experience symptoms of dementia. Based on this experience, the researchers were able to estimate the time until the onset of symptoms for all study participants individually. In doing so, they came across early signs of the disease. "We found that TREM2 levels in the cerebrospinal fluid rise as early as 21 years before the estimated onset of the disease," Haass says. "We also observed that the faster TREM2 increases over the years, the slower pathological events progress in the brain that are typical of Alzheimer's. We can infer this from biomarkers for so-called amyloid proteins and tau proteins."

The brain examinations using MRI and PET pointed in a similar direction: In study participants in whom TREM2 levels rose rapidly, deposits of amyloid proteins that are characteristic of Alzheimer's developed more slowly and brain volume declined more slowly. "Besides the relationship with a slower pathological process, one of our most important and promising findings was to see how strikingly the faster TREM2 increase correlated with a slower cognitive decline in an early stage of Alzheimer´s disease. This has important implications for treatment," Morenas-Rodríguez notes.

"We see our findings as evidence that TREM2-mediated microglial activity has a protective effect," Haass says. "In our view, microglia become active as soon as the first amyloid proteins are deposited in the brain, a process, which we call seeding. In other words, at a very early stage of Alzheimer's and that is what we and our colleagues at the DZNE-Tübingen also observe in animal models."

Approach for New Therapies

For some time now, Haass and his team have been researching drugs that specifically reinforce the protective effect of microglia. Their target is the TREM2 receptor anchored on the cell surface. "We are still in the laboratory phase. However, the current results in humans show that modulating TREM2 is a promising strategy to develop new options against Alzheimer's. Although in this particular case we studied the genetic form of the disease, we consider that our findings also apply to the so-called sporadic variant of the disease, which is far more common. Certainly, it is crucial that treatment starts as early as possible. Today's therapies all come far too late to be really effective," says Haass.

https://www.sciencedaily.com/releases/2022/03/220317094758.htm

Large study on traumatic brain injury highlights global inequality in causes and treatment

March 17, 2022

Science Daily/University of Cambridge

A large study examining the surgical management of traumatic brain injuries highlights regional inequalities in both major causes and treatment of such injuries.

Neurosurgery experts from Cambridge have led the largest ever study examining the surgical management of traumatic brain injuries, highlighting regional inequalities in both major causes and treatment of such injuries.

The Global Neurotrauma Outcomes Study, funded by the NIHR, is published in The Lancet Neurology and provides data to assist in decision making and improving outcome for patients with traumatic brain injury globally.

The paper focuses on types of cases, the way they are managed, and death rates, and was compiled using data submitted by 159 hospitals in 57 countries to a central database, which the researchers then analysed. The researchers stratified countries into four tiers (very high, high, medium, low) according to their Human Development Index (HDI), which takes account of factors like life expectancy, education, and income.

The prospective study determined that patients in the low HDI tier were often young and tended to suffer skull fractures due to assault but were classified as 'mild' traumatic brain injury (TBI).

In the medium and high HDI tiers, patients were also young, but most had moderate to severe TBI caused by a road traffic collision and extradural haematoma -- a bleed on the outside of the dura mater, the membrane covering of the brain.

In the very high tier, patients tended to be older and presented with a moderate or severe TBI associated with a fall and acute subdural haematoma -- a bleed on the inner surface of the dura mater.

Quality of care was generally less favourable in lower HDI settings, including delays to surgery and a lack of postoperative monitoring equipment and intensive care. The very high HDI tier had the highest proportion of operations in which the most senior surgeon present in the operating theatre was a fully qualified neurosurgeon, while the medium HDI tier had the lowest proportion. The study also found significant variations between hospitals in the outcome of patients.

Angelos Kolias, Consultant Neurosurgeon at Cambridge University Hospitals NHS Foundation Trust (CUH) and NIHR Global Neurotrauma Research Group associate director, said: "The results show that overall mortality is low, reflecting the life-saving nature of surgery for traumatic brain injuries. Many of these patients would have died without an operation. However, we also need to address deficits in pre-hospital management and long-term rehabilitation."

David Clark, a trainee neurosurgeon and University of Cambridge research fellow, said: "A particularly important finding is that outcome is influenced more by hospital characteristics than country of origin, which raises the possibility that changing the systems and processes of care in individual hospitals might be able to improve mortality. The paper sows the seeds for discussion and change."

The research was funded by the NIHR using UK government aid to support global health research.

Alexis Joannides, Consultant Neurosurgeon at CUH and NIHR Global Neurotrauma Research Group informatics lead, added: "The contribution of several clinicians and researchers from several hospitals across the world has been possible due to the infrastructure and collaborations supported by the NIHR.

"The database and data management process used in the study have now laid the foundation for a global registry of traumatic brain injuries that we have established to support ongoing quality improvement and research in the field of traumatic brain injury."

Peter Hutchinson, Professor of Neurosurgery at the University of Cambridge and Director of the NIHR Global Neurotrauma Research Group, said: "This is the largest study in the world looking at the surgical management of head injuries and will be of practical value to clinicians and others planning strategies for the future.

"The collaboration across such a vast number of hospitals and countries, together with the support of the World Federation of Neurosurgical Societies and continental neurosurgical societies, has been phenomenal."

https://www.sciencedaily.com/releases/2022/03/220317111915.htm

Alzheimer’s pathology, not cognitive decline, drives neuropsychiatric symptoms

Biomarkers of pathology associated with apathy, anxiety

March 16, 2022

Science Daily/Elsevier

Alzheimer's disease (AD) eventually leads to severe cognitive decline, but most affected individuals also develop distressing neuropsychiatric symptoms. These earlier effects may be more subtle and are not well understood; it remains unclear whether they arise directly from AD pathology or secondarily as psychological reactions due to the cognitive deficits. Now, a new study examines the connections between biomarkers of AD's hallmark neuropathology, cognition, and other neuropsychiatric symptoms. The study appears in Biological Psychiatry, published by Elsevier.

The researchers, led by Oskar Hansson, MD, at Lund University in Sweden, tested cerebrospinal fluid or blood plasma from 356 cognitively unimpaired older adults for levels of the proteins amyloid-beta (Ab) and tau, which are thought to contribute to AD neurotoxicity, as well as markers of neurodegeneration.

Strikingly, the presence of Ab was associated with increased anxiety and apathy. Higher levels of apathy were also related to a more rapid cognitive decline.

"Most importantly, this study signals that certain neuropsychiatric symptoms such as apathy and anxiety develop predominantly due to underlying AD-related pathology and not due to the concomitant cognitive impairment," said Maurits Johansson, MD, lead author of the study. "It seems reasonable that neuropsychiatric symptoms would arise from neuropathology just as cognitive deficits do, especially because AD ultimately affects large areas of the brain," he added.

The study did not exclude a role for cognitive impairment altogether. For example, in one of the statistical analyses, cognitive decline slightly but significantly mediated the effect of amyloid pathology on the development of apathy.

"Combined with earlier studies, our findings strengthen the proposed idea that cognitive deficits and neuropsychiatric symptoms can develop independently, yet in parallel to one another. They have a common underlying neuropathology, but to some extent they can also reinforce one another," said Professor Hansson.

"These findings could ultimately lead to more efficient study design of clinical trials for AD in that they point to neuropsychiatric symptoms as potential alternative outcome measures," concluded Professor Hansson.

John Krystal, MD, Editor of Biological Psychiatry, said of the new findings, "We are used to thinking about Alzheimer's disease from the perspective of memory impairments. This new study highlights that the earliest signs of amyloid-related pathology may be changes in mood and behavior, particularly apathy and anxiety."

https://www.sciencedaily.com/releases/2022/03/220316100426.htm

Mechanism linking type 2 diabetes to Alzheimer’s disease

March 15, 2022

Science Daily/Osaka City University

Osaka City University suggests a possible mechanism linking diabetes to Alzheimer's disease in new discovery that amyloid-β in the blood comes from periphery organs like the pancreas and liver, not only the brain, and aids in blood glucose clearance by inhibiting insulin secretion.

A research group has revealed that amyloid-β (Aβ) detected in blood is secreted from peripheral tissues (pancreas, adipose tissue, skeletal muscle, liver, etc.) that are sensitive to glucose and insulin. Also, that Aβ secreted from peripheral tissues acts as a regulator on pancreatic β-cells to suppress insulin secretion. The results of this study indicate that blood Aβ levels fluctuate significantly with diet, and special care should be taken when using blood samples as a diagnostic marker for Alzheimer's disease, such as taking blood samples during fasting.

Researchers have identified amyloid beta (Aβ) detected in blood to originate from peripheral tissues, and that the peptide acts on pancreaticβ-cells to suppress insulin secretion, thereby regulating blood glucose levels. The study, which urges us to be careful when using blood Aβ levels as a diagnostic marker for Alzheimer's disease (AD), was published in The Proceedings of the National Academy of Sciences (PNAS), the official journal of the National Academy of Sciences.

"This work was finally published after about 11 years," says Professor Takami Tomiyama of the Department of Translational Neuroscience, Osaka City University Graduate School of Medicine. "It is not only an academic discovery, but also has implications in how we diagnose AD."

Based on what is known, this study sought to explore some unknowns. First, as AD is caused by the accumulation of Aβ in the brain, it is thought that Aβ levels in the blood reflect the pathology in the brain and are currently used as a diagnostic marker. However, Aβ is generated from the amyloid precursor protein (APP) through the function of two enzymes, β- and γ-secretases, and this mechanism is expressed in many of the body's peripheral tissues, not only in the brain, causing the origin of blood Aβ to remain unknown. Second, epidemiological studies have shown type 2 diabetes to be a strong risk factor for the development of AD, yet the mechanism linking these two diseases has eluded researchers as well.

"In our previous studies on mice injected with glucose," Professor Tomiyama explains, "we showed a transient increase in glucose and insulin to peak at 15 minutes, but blood Aβ levels to peak some 30-120 minutes later." In addition, previous studies have shown the oral administration of glucose to increase blood Aβ levels in patients with AD. These findings led the professor and his research team to explore the hypothesis that blood Aβ is secreted from peripheral tissues (pancreas, adipose tissue, skeletal muscle, liver, etc.) and it may contribute to the metabolism of glucose and insulin.

First, they examined the effects of glucose and insulin on blood Aβ levels of mice fasted for 16 hours. Collected blood samples from the tail vein at 0, 15, 30, 45, 60, 120, and 180 min intervals after the injection showed a transient increase in glucose, insulin, and Aβ, confirming previous studies.

Next, they explored the effect of Aβ on blood insulin levels by administering Aβ and glucose to fasted mice that cannot produce Aβ, called APP knock out mice. Measuring insulin in blood samples over time found that Aβ suppressed the glucose-stimulated rise in insulin.

Given that blood Aβ levels changed immediately upon introduction of glucose and insulin, the team focused on the mice pancreas, adipose tissue, skeletal muscle, liver, and kidneys to determine the origin of blood Aβ. They added glucose and insulin to isolated live peripheral tissues and measured the secreted Aβ. Results showed that Aβ was secreted from the pancreas upon glucose stimulation and from adipose tissue, skeletal muscle, and liver upon insulin stimulation. The kidneys, which is not involved in glucose or insulin metabolism, did not secrete Aβ upon either stimulus. They also found that when glucose and Aβ were added to pancreas tissue, levels of secreted insulin were suppressed.

Now that the origin of blood Aβ had been clarified, the team wanted to localize Aβ in the periphery tissues studied. "This would elucidate the cells involved with Aβ," adds Professor Tomiyama. "In addition to providing further validation to our findings, this would give us a more detailed picture from which we could draw conclusions to possible mechanisms connecting type 2 diabetes and AD."

Using immunohistochemistry to exploit the fact that antibodies bind to certain proteins, the team started with the pancreas tissue, detecting Aβonly in insulin (β cells). The team also found the β cells of mice with glucose injections to have less immunoreactions to Aβand insulin, suggesting during periods of fast, Aβ and insulin are stored in β cells and then released into circulation when stimulated with glucose. Similarly, tissue sections of each insulin-targeted organ were prepared and immunostained for Aβ and the bioactive substances specific to each tissue, called organokines. Aβ was found with the organokines of all the organ tissues tested, with less immunoreactions when stimulated with insulin.

"Our findings suggest that Aβ and organokines are stored during periods of fast and released into circulation when stimulated with insulin," adds Prof. Tomiyama. "A comprehensive understanding of the organokine action of peripheral Aβ is something we hope to develop in future work."

In addition to an explanation for the origin of Aβ in the blood, the research findings suggest a mechanism by which type 2 diabetes is a strong risk factor for the development of AD. In diabetes, Aβ levels in the blood are constantly elevated due to high levels of glucose and insulin. This inhibits Aβ to leave the brain to the periphery (transport through the blood-brain barrier and by body fluid flow through the brain parenchyma called the glymphatic system), causing Aβ to accumulate in the brain and develop into AD.

"Other more practical suggestions can be gleaned from this study," concludes Prof. Tomiyama, "our data suggest that as blood Aβ levels fluctuate significantly with diet, special care should be taken when diagnosing AD with blood Aβ."

https://www.sciencedaily.com/releases/2022/03/220315095012.htm

Cognitive decline key factor in predicting life expectancy in Alzheimer’s disease

March 14, 2022

Science Daily/UT Southwestern Medical Center

Cognitive decline is the biggest factor in determining how long patients with Alzheimer's disease will live after being diagnosed, according to a new study from researchers at UT Southwestern. The findings, published in the Journal of Alzheimer's Disease, are a first step that could help health care providers provide reliable prediction and planning assistance for patients with Alzheimer's disease and their families.

Using a National Alzheimer's Coordinating Center dataset on 764 autopsy-confirmed cases, C. Munro Cullum, Ph.D., Professor of Psychiatry, Neurology, and Neurological Surgery, and first author Jeffrey Schaffert, Ph.D., a postdoctoral fellow in clinical neuropsychology at UT Southwestern, identified seven factors that helped predict life expectancy variances among participants. These factors are the most predictive of how many years of life remain after diagnosis.

"Life expectancy for patients with Alzheimer's disease typically ranges from three to 12 years but can be longer in some cases. Families are anxious to know what to expect and how to best plan for the time ahead in terms of finances, family caregiving, and how they want to live out their lives," said Dr. Cullum, a neuropsychologist Investigator in the Peter O'Donnell Jr. Brain Institute who specializes in cognitive assessment. "We're trying to get them better answers."

Of the many variables studied, performance deficiencies on a brief cognitive screening test that focuses on orientation was the most significant predictor, accounting for about 20% of the variance in life expectancy. This was followed by sex, age, race/ethnicity, neuropsychiatric symptoms, abnormal neurological exam results, and functional impairment ratings.

"We found that beyond global cognitive function, patients who were older, non-Hispanic, male, and who had more motor and psychiatric symptoms had a significantly shorter life expectancy," Dr. Schaffert said.

The data was drawn from clinical records and autopsy reports on patients who died with Alzheimer's disease between 2005 and 2015. Alzheimer's disease was confirmed by traditional abnormalities observed in brain autopsy specimens, including the presence of abnormal protein aggregation. Life expectancy in the study group ranged from one month to 131 months after diagnosis, and most were diagnosed on their first visit.

Dr. Schaffert explained that past studies have focused on only a few of the 21 predictors identified for life expectancy. In this case, researchers had a complete dataset for 14 variables in this group, the largest to date. Moreover, past studies have not been autopsy-based, thereby confounding results with data from other forms of dementia that mimic Alzheimer's disease.

The researchers caution that prediction of life expectancy is complex and influenced by many factors. While the cognitive test used in the study was a relatively strong predictor, they plan to follow up using more sensitive measures of memory and other specific cognitive abilities as predictors and probe how the rate of decline in cognition may track with life expectancy. They also hope to expand the population base.

"This dataset was largely derived from well-educated white patients who donated their brains to research. We would like to extend this work to better reflect our more diverse patient population," Dr. Cullum said.

https://www.sciencedaily.com/releases/2022/03/220314181451.htm

How sugar promotes inflammation

March 22, 2022

Science Daily/University of Würzburg

People who consume sugar and other carbohydrates in excess over a long period of time have an increased risk of developing an autoimmune disease. In affected patients, the immune system attacks the body's own tissue and the consequences are, for example, chronic inflammatory bowel diseases such as Crohn's disease and ulcerative colitis, type 1 diabetes and chronic inflammation of the thyroid gland.

New targets for therapy

The underlying molecular mechanisms that promote autoimmune diseases are multilayered and complex. Now, scientists at the Julius Maximilians University of Würzburg (JMU) have succeeded in deciphering new details of these processes. Their work support the notion that excessive consumption of glucose directly promotes the pathogenic functions of certain cells of the immune system and that, conversely, that a calorie-reduced diet can have a beneficial effect on immune diseases. Based on these findings, they also identified new targets for therapeutic interventions: A specific blockade of glucose-depended metabolic processes in these immune cells can suppress excessive immune reactions.

Dr. Martin Väth is responsible for the study, which has now been published in the journal Cell Metabolism. He is a junior research group leader at the Institute of Systems Immunology -- a Max Planck research group under the umbrella of JMU that focusses on the interplay of the immune system with the organism. Collaborators from Amsterdam, Berlin, Freiburg and Leuven were also involved in this study.

Glucose transporter with a side job

Martin Väth explains: "Immune cells need large amounts of sugar in the form of glucose to perform their tasks. With the help of specialized transporters at their cell membrane, they can take up glucose from the environment." Together with his team, Väth has showed that a specific glucose transporter -- scientifically named GLUT3 -- fulfills additional metabolic functions in T cells besides the generating energy from sugar.

In their study, the scientists focused on a group of cells of the immune system that have not been known for very long: T helper cells of type 17, also called Th17 lymphocytes, which play an important role in regulating (auto-) inflammatory processes.

"These Th17 cells express lots of GLUT3 protein on their cell surface," Väth explains. Once taken up, glucose is readily converted to citric acid in the mitochondria before it is metabolized into acetyl-coenzyme A (acetyl-CoA) in the cytoplasm. Acetyl-CoA is involved in numerous metabolic processes, including the biosynthesis of lipids.

Influence on proinflammatory genes

However, acetyl-CoA fulfills additional functions in inflammatory Th17 cells. Väth and his team showed that this metabolic intermediate can also regulate the activity of various gene segments. Thus, glucose consumption has a direct influence on the activity of proinflammatory genes.

According to the researchers, theses new findings pave the way for the development of targeted therapy of autoimmune diseases. For example, blocking GLUT3-dependent synthesis of acetyl-CoA by the dietary supplement hydroxycitrate, which is used to treat obesity, can mitigate the pathogenic functions of Th17 cells and reduce inflammatory-pathological processes. The so-called "metabolic reprogramming" of T cells opens new possibilities to treat autoimmune diseases without curtailing protective immune cell functions.

https://www.sciencedaily.com/releases/2022/03/220322122836.htm

People with diabetes who eat less processed food at night may live longer

Study finds eating carbs earlier in the day is linked to better heart health

March 15, 2022

Science Daily/The Endocrine Society

The time of day that people with diabetes eat certain foods may be just as important to their well-being as portion size and calories, according to a new study published in the Endocrine Society's Journal of Clinical Endocrinology and Metabolism.

Mealtimes should be in line with the biological clock -- a natural, internal process that regulates the sleep-wake cycle and repeats every 24 hours. Health outcomes for people with diabetes may be improved if certain foods are eaten at different times of the day.

"We observed that eating potatoes in the morning, whole grains in the afternoon, greens and milk in the evening and less processed meat in the evening was associated with better long-term survival in people with diabetes," said Qingrao Song, M.D., of Harbin Medical University in Harbin, China. "Nutritional guidelines and intervention strategies for diabetes should integrate the optimal consumption times for foods in the future."

The researchers analyzed data from 4,642 people with diabetes from the National Health and Nutrition Examination Survey to determine their risk of dying from heart disease. They found people with diabetes who ate potatoes or starchy vegetables in the morning, whole grains in the afternoon, and dark vegetables such as greens and broccoli and milk in the evening were less likely to die from heart disease. Those who ate a lot of processed meat in the evening were more likely to die from heart disease.

https://www.sciencedaily.com/releases/2022/03/220315095028.htm

Chef’s kiss: Research shows healthy home cooking equals a healthy mind

New research has found being confident in the kitchen is not only good for your taste buds: it’s also good for your mental health

March 21, 2022

Science Daily/Edith Cowan University

New research from Edith Cowan University (ECU) has found being confident in the kitchen is not only good for your taste buds: it's also good for your mental health.

The study follows ECU's successful partnership with The Good Foundation and Jamie's Ministry of Food initiative, with a mobile food kitchen providing cooking classes in the community as well as at the University's Perth and SW campuses, throughout 2016 to 2018.

In total, 657 participants undertook the seven-week healthy cooking course.

At the same time, ECU Institute for Nutrition Research academics measured the program's effect on participants' cooking confidence and self-perceived mental health, as well as their overall satisfaction around cooking and diet-related behaviours.

Researchers found those who participated in the program saw significant improvements in general health, mental health and subjective vitality immediately after the program which remained six months after completing the course, when compared to the study's control group.

Improvements in cooking confidence, the ability to easily change eating habits and overcome lifestyle barriers to healthy eating were also reported.

Lead researcher Dr Joanna Rees said the study showed the importance of diet for mental health.

"Improving people's diet quality can be a preventive strategy to halt or slow the rise in poor mental health, obesity and other metabolic health disorders," she said.

"Future health programs should continue to prioritise the barriers to healthy eating such as poor food environments and time restrictions, whilst placing greater emphasis on the value of healthy eating via quick and easy home cooked meals, rich in fruit and vegetables and avoiding ultra-processed convenience foods."

It's not just the food 

The Institute has previously found a link between eating more fruits and vegetables, and improved longer term mental health in a larger study collecting more sophisticated dietary data, implying the participants in the current study may have felt better due to improved diet.

However, the study showed participants' mental health improved despite their reported diet not being found to have changed after completing the program.

Also, the mental health benefits were equal among participants who were overweight or obese, and those in a healthy weight range.

"This suggests a link between cooking confidence and satisfaction around cooking, and mental health benefits," Dr Rees said.

Who benefits most? 

The study also revealed cooking remains a highly gendered task.

At the start of the program, 77 per cent of participants who identified as female claimed to be confident about cooking, compared to just 23 per cent of those who identified as male.

But at the end of the program, cooking confidence and cooking skills were equal across both counterparts.

"This change in confidence could see change to the household food environment by reducing the gender bias and leading to a gender balance in home cooking," Dr Rees said.

"This in turn may help to overcome some of the barriers presented by not knowing how to cook, such as easing the time constraints which can lead to readymade meals which are high in energy but low in nutritional value."

'How a 7-Week Food Literacy Program Affects Cooking Confidence and Mental Health: Findings of a Quasi-Experimental Controlled Intervention Trial' was published inFrontiers in Nutrition.

https://www.sciencedaily.com/releases/2022/03/220321091919.htm

Brain differences in children with binge eating disorder

March 15, 2022

Science Daily/Keck School of Medicine of USC

Brain scans of children ages 9-10 with a type of eating disorder that causes uncontrollable overeating showed differences in gray matter density compared to their unaffected peers, according to a USC-led study.

Binge eating disorder, which affects about 3-5% of the U.S. population, is characterized by frequent episodes of eating large amounts of food and a sense of having no control over the behavior. The study's findings suggest that abnormal development in the brain's centers for reward and inhibition may play a role.

The recently published study is available online in the journal Psychiatry Research.

"In children with binge eating disorder, we see abnormality in brain development in brain regions specifically linked to reward and impulsivity, or the ability to inhibit reward," said lead author Stuart Murray, Della Martin Associate Professor of Psychiatry and the Behavioral Sciences at the Keck School of Medicine of USC, where he serves as director of the Eating Disorders Program.

"These kids have a very, very heightened reward sensitivity, especially toward calorically dense, high-sugar foods. The findings underscore the fact that this is not a lack of discipline for these kids."

Pandemic saw increase in eating disorders among young people

Experts say eating disorders in young people soared during the pandemic, along with steep increases in hospitalizations. Social isolation, stress, disruption of routine and a social media-fueled quest for perfection all exacerbated disorders such as anorexia, muscle dysmorphia and binge eating.

Binge eating disorder puts people at risk for obesity, metabolic syndrome, abnormal cardiac function and suicidal thoughts. Treatment goals include reducing the frequency of binge eating episodes by removing "trigger" foods, as well as addressing underlying anxiety or depression. Treatment with medication and talk therapy is effective about only half the time, Murray said.

For this study, Murray and his colleagues analyzed brain scans and other data from 71 children with diagnosed binge eating disorder and 74 children without binge eating disorder, who are part of a large longitudinal study called the Adolescent Brain and Cognitive Development Study. That study includes data of 11,875 children ages 9-10 who were enrolled in 2016-2018 and recruited from 21 sites around the U.S.

In the children with binge eating disorder, they saw elevations in gray matter density in areas that are typically "pruned" during healthy brain development. Synaptic pruning, a development phase that occurs between ages 2 and 10, eliminates synapses that are no longer used, making the brain more efficient. Disturbed synaptic pruning is linked to a number of psychiatric disorders.

"This study suggests to me that binge eating disorder is wired in the brain, even from a very, very early age," Murray said. "The question that we don't know, which is something that we will address in time, is whether successful treatment of binge eating disorder in kids helps correct brain development. The prognosis of almost all psychiatric diseases is better if you can treat them in childhood."

https://www.sciencedaily.com/releases/2022/03/220315162813.htm

Higher exposure to bisphenol A in the womb associated with increased risk for asthma and wheezing in school-age girls

Study of over 3,000 children from six European countries examines possible effects of prenatal exposure to bisphenols on respiratory health in childhood

March 18, 2022

Science Daily/Barcelona Institute for Global Health (ISGlobal)

An analysis of data from more than 3,000 mother-child pairs from six European countries indicates that prenatal exposure to bisphenol A may have negative effects on respiratory health in school-age girls. The results of a study led by the Barcelona Institute for Global Health (ISGlobal), an entity supported by the "la Caixa" Foundation, have just been published in the journal Environment International.

Bisphenols are chemical substances used in the manufacture of plastics and resins found in many consumer products, such as food cans, reusable bottles and toys. The most well-known is bisphenol A (BPA), a known endocrine disruptor used widely in the manufacture of food containers and the interior coatings of such recipients. The European Chemicals Agency (ECHA) included BPA on its list of substances of "very high concern" in 2017. Since then, some countries have limited its use, leading some manufacturers to replace BPA with other bisphenols.

Since it is known that bisphenols are present in maternal milk and that they can cross the placental barrier, the aim of the authors of the study published today was to discover whether prenatal exposure to these chemical compounds is associated with respiratory health problems in later years. The authors studied urine samples taken during pregnancy from more than 3,000 women from six European countries (Spain, France, Greece, Norway, the Netherlands and the United Kingdom) collected between 1999 and 2010 and data on the respiratory health of their offspring collected years later through questionnaires and spirometry.

Analysis of the urine samples revealed a high prevalence of BPA, which was found in 90% of the samples. The other bisphenols studied were, however, less prevalent at the time these samples were collected: the Netherlands was the only country where a notable presence of other bisphenols was detected among the study participants (bisphenol F in 40% of the samples and bisphenol S in 70%). This finding was probably due to the early switch to replacements for bisphenol A in that country.

The results of this study revealed an association in girls between concentrations of bisphenol A in maternal urine during pregnancy and an increased risk of asthma and wheezing at school age (a twofold increase in the concentration of bisphenol A was linked to a 13% higher risk of respiratory symptoms). This association was not, however, observed in boys or in the case of the other two bisphenols studied. Neither were any associations observed between prenatal bisphenol A exposure and lung function at school age.

"Our results are in line with those of earlier studies, which have also reported that bisphenol A has a negative impact on respiratory health in childhood. We believe that the effect may be due the fact that bisphenols can cross the placental barrier and interfere with the child's respiratory and immune systems during the developmental phase," explains Alicia Abellán, ISGlobal researcher and first author of the study.

Talking about the differences observed between girls and boys, Maribel Casas, ISGlobal researcher and last author of the study, makes the point that "bisphenols are endocrine disruptors and can interfere with sex hormones. As our findings suggest, this may give rise to differences in the effects they have depending on the sex of the person exposed."

https://www.sciencedaily.com/releases/2022/03/220318080253.htm

Early English lessons have lasting effects

March 18, 2022

Science Daily/Ruhr-University Bochum

An international research team has examined how English lessons in primary school affect language proficiency in this subject in secondary school. Children who started learning English in the first grade of primary school performed significantly better in listening and reading comprehension in grade nine than children who started in grade three. The study was a continuation of an earlier paper that had only covered the period up to the seventh grade and couldn't find any such learning advantage.

The team headed by Professor Markus Ritter from Ruhr-Universität Bochum (RUB) and Dr. Nils Jäkel from the University of Oulu, Finland, in cooperation with Dr. Michael Schurig from the Technical University of Dortmund, describes their findings in the journal System. The study will be published in the June 2022 edition, but is already freely accessible online. The researchers are collaborating within the university consortium UNIC: European University of Post-Industrial Cities.

Data from North Rhine-Westphalia

The study included data from around 3,000 students who participated in a longitudinal study conducted in North Rhine-Westphalia, Germany, between 2010 and 2014. The same data had also been used in the previous study, the results of which the researchers had published in 2017. At that time, they had compared two cohorts, one of which had started English lessons in grade one, the other in grade three. In grades five and seven, they had compared both cohorts in terms of English reading and listening comprehension. The new analysis incorporated another set of data collected in 2016 to measure the English performance of the same children in grade nine.

The previous study had found: Children who had started English lessons earlier in primary school performed worse in reading and listening comprehension in grade seven than children who had not started English lessons until grade three. However, the new analysis showed: In grade nine, the early starters in English performed better than the late starters in English.

Additional background variables such as gender, language of origin or cognitive abilities could not account for the difference between the poorer performance in the seventh grade and the late learning gains in the ninth grade.

Transition between school types decisive

"We believe the most plausible explanation is that lessons following the transition period in secondary school have been increasingly adapted to the needs of children who start to take English lessons at an early stage," concludes Nils Jäkel, formerly at RUB, now at the University of Oulu. "This explanation is in line with research that considers the transition between school types to play a key role in the long-term success of English language education across school boundaries." With this in mind, it is crucial to optimise the didactic coordination and alignment of English classes at the intersection of school types. In addition, it may be that pupils benefit in the long run from more implicit language lessons in primary school.

"We see a high need for research to elaborate factors for successful language education, and we recommend well-coordinated, evidence-based measures in educational policy overall," say the researchers.

https://www.sciencedaily.com/releases/2022/03/220318104921.htm

100g of cranberries a day improves cardiovascular health

March 22, 2022

Science Daily/King's College London

A new clinical trial found daily consumption of cranberries for one month improved cardiovascular function in healthy men.

The new study, published today in Food & Function, included 45 healthy men who consumed whole cranberry powder equivalent to 100g of fresh cranberries per day (9 g powder) or a placebo for one month. Those consuming cranberry had a significant improvement in flow-mediated dilation (FMD), which signals improvement of heart and blood vessel function. FMD is considered a sensitive biomarker of cardiovascular disease risk and measures how blood vessels widen when blood flow increases.

Dr. Ana Rodriguez-Mateos, Senior Lecturer in Nutrition at the Department of Nutritional Sciences at King's College London and senior author of the study, said: "The increases in polyphenols and metabolites in the bloodstream and the related improvements in flow-mediated dilation after cranberry consumption emphasise the important role cranberries may play in cardiovascular disease prevention. The fact that these improvements in cardiovascular health were seen with an amount of cranberries that can be reasonably consumed daily makes cranberry an important fruit in the prevention of cardiovascular disease for the general public."

Low consumption of fruits and vegetables is one of the top modifiable risk factors associated with a higher incidence of cardiovascular disease worldwide. Growing evidence continues to link the polyphenols from berries with heart health benefits. Cranberries are rich in unique proanthocyanidins that have distinct properties compared to polyphenols found in other fruits.

This study explored whole cranberry freeze-dried powder, equivalent to 100g of fresh cranberries, and its impact on cardiovascular health. The results demonstrated that consumption of cranberries as part of a healthy diet can help reduce the risk of cardiovascular disease by improving blood vessel function.

An initial pilot study was completed with five healthy young men to confirm the biological activity of the whole cranberry freeze-dried powder. The pilot concluded that cranberry consumption increased FMD and confirmed dosing. The main study was a gold standard study design examining 45 healthy men each consuming two packets of whole cranberry freeze-dried powder equivalent to 100g of fresh cranberries, or a placebo, daily for one month. The study found significant improvements in FMD two hours after first consumption and after one month of daily consumption showing both immediate and chronic benefit. In addition, metabolites were also identified and predicted the positive effects seen in FMD. These results conclude that cranberries can play an important role in supporting cardiovascular health and good blood vessel function.

Dr. Christian Heiss, Professor of Cardiovascular Medicine at the University of Surrey and co-author of the study said: "Our findings provide solid evidence that cranberries can significantly affect vascular health even in people with low cardiovascular risk. This study further indicates that specific metabolites present in blood after cranberry consumption are related to the beneficial effects."

https://www.sciencedaily.com/releases/2022/03/220322111245.htm

How gut microbes work to tame intestinal inflammation

March 16, 2022

Science Daily/Harvard Medical School

Bile acids made by the liver have long been known for their critical role in helping to absorb the food we ingest.

But, according to a series of new studies from Harvard Medical School, these fat- and vitamin-dissolving substances are also important players in gut immunity and inflammation because they regulate the activity of key immune cells linked to a range of inflammatory bowel conditions, such as ulcerative colitis and Crohn's disease.

An initial report in 2020 mapped out the effects of bile acids on mouse gut immunity, but left some key questions unanswered: First, just how do bile acids get gut immune cells to perform their immune-regulatory work? Second, which bacteria and bacterial enzymes produce these bile acids? Third, do these bile acids play a role in human intestinal inflammation?

Now, two studies led by the same team of investigators -- one published March 16 in Nature and one published in Cell Host & Microbe in 2021 -- answer these questions and add further clarity to the initial observations. The research, conducted at the intersection of chemical biology, microbiology, and immunology, was co-led by Sloan Devlin, assistant professor of biological chemistry and molecular pharmacology, and Jun Huh, associate professor of immunology at HMS.

The studies identify three bile acid metabolites and corresponding bacterial genes that produce molecules that affect the activity of inflammation-regulating immune cells. The work also demonstrates that the presence and activity of these bacteria and the immune molecules they produce are notably reduced in patients with inflammatory bowel disease (IBD).

"We carry trillions of bacteria in and on our bodies, and a growing body of research indicates that gut bacteria can affect host immune responses," Huh said. "Our findings provide a novel mechanistic insight into how these bacteria work to mediate immune regulation in the gut."

The findings, based on experiments in mice and human stool samples, reveal the identity of three critical microbial players in this cascade and the bacterial genes that regulate bile acid modification. Furthermore, they show that intestinal samples from patients with conditions such as ulcerative colitis or Crohn's disease have markedly lower levels of both the anti-inflammatory molecules and the bacterial genes responsible for their production.

The findings bring scientists a step closer to developing small-molecule treatments and live bacterial therapeutics that regulate intestinal inflammation.

"All three molecules and the bacterial genes that we discovered that produce these molecules are reduced in patients with IBD," Devlin said. "Restoring the presence of either the compounds or the bacteria that make them offers a possible therapeutic avenue to treat a range of inflammatory diseases marked by these deficiencies and affecting millions of people worldwide."

https://www.sciencedaily.com/releases/2022/03/220316120813.htm

Excess sugar consumption costs Canada’s health-care system $5 billion each year

Researchers urge use of taxation, education and subsidies to encourage better eating habits

March 16, 2022

Science Daily/University of Alberta

Researchers peg the economic burden of excessive sugar consumption in Canada at $5 billion a year, thanks to the direct and indirect costs related to 16 chronic diseases. The researchers call on governments to use taxation, subsidies, education and other measures to encourage healthier eating habits, saying it is 'an area of urgent need for action' in the post-COVID-19 pandemic era.

Imagine if the real cost to society of the food you buy at the grocery store was built right into each product's price. Everything with added sugar would cost a whole lot more, according to University of Alberta researchers in a new study in The Canadian Journal of Public Health.

They peg the economic burden of excessive sugar consumption in Canada at $5 billion a year, thanks to the direct and indirect costs related to 16 chronic diseases. The researchers call on governments to use taxation, subsidies, education and other measures to encourage healthier eating habits, saying it is "an area of urgent need for action" in the post-COVID-19 pandemic era.

"This pandemic has brought us more unhealthy lifestyles -- on the nutrition side, on the physical activity side and on screen time for kids. If we do not act now, we should expect more chronic diseases such as Type 2 diabetes in the years ahead," said principal investigator Paul Veugelers, professor in the U of A's School of Public Health.

"Health care costs for chronic diseases are ballooning," Veugelers said. "We not only need to make our health-care system more efficient, we should also act on the demand side by investing in primary prevention to ensure we have fewer patients with chronic diseases. Addressing sugar consumption is one strategy to achieve that."

Both Canada's Food Guide and the World Health Organization recommend we consume less than 10 per cent of our daily energy intake as "free sugar" from foods made with added sugar and naturally sweet juices, honey and syrup. For additional health benefits, less than five per cent is recommended.

Using data reported in the 2015 Canadian Community Health Survey on nutrition, the researchers found that two out of three Canadians eat more sugar than recommended. They then established risk estimates for 16 diet-related chronic conditions, including diabetes, cardiovascular diseases, cancer, kidney disease and low back pain. They calculated avoidable direct health-care costs such as doctors, hospitals and drugs, along with indirect costs like productivity losses due to illness and disability.

They concluded that if Canadians had followed the 10 per cent recommendation in 2019, an estimated $2.5 billion could have been saved, and $5 billion in costs could have been avoided by following the stricter five per cent recommendation.

Treatment and management of chronic diseases accounts for 67 per cent of all health-care costs in Canada, they reported, with an annual price tag of up to $190 billion.

The researchers estimated that limiting free sugar consumption to less than 10 per cent of energy intake could reduce the prevalence of diabetes by 27 per cent, and that benefit could reach 44.8 per cent if Canadians limited their sugar consumption to less than five per cent.

"Diabetes is just a very expensive condition to manage and to treat. It can occur at an early age, and you can live with it for a long, long time. Kidney issues, dialysis, amputation, those are just a few gruesome examples of where that disease trajectory can go," said Veugelers. "Patients require lots of health-care interactions that drive the costs of chronic diseases."

Forty countries and cities around the world have already introduced a special tax on sugar-sweetened beverages such as pop as a disincentive to consumption, building on lessons from tobacco control measures. Newfoundland and Labrador recently introduced Canada's first such tax and similar policies have been suggested elsewhere, but in this study the researchers push for a broader approach, because they found that only 17 per cent of the costs related to sugar consumption could be traced back to sugary drinks.

Instead, they advocate for higher taxes on all sugar-added products, and to put the tax revenues towards subsidies for healthful foods, education programs, limits on advertising to children, and better product labeling.

https://www.sciencedaily.com/releases/2022/03/220316091722.htm

Study shows link between socioeconomic deprivation and premature cardiovascular mortality

Research also discovers potentially worsening disparities in the U.S.

March 15, 2022

Science Daily/University Hospitals Cleveland Medical Center

People living in socially-deprived areas of the United Statesare more likely to die prematurely from cardiovascular (CV) complications according to new research published recently in Mayo Clinic Proceedings.The study, completed by researchers at University Hospitals (UH) Harrington Heart & Vascular Institute, found social deprivation can explain a significant proportion of the geographic variation in premature cardiovascular mortality in the U.S.

Socioeconomic deprivation is defined by a number of social and economic factors including education, income, employment and neighborhood environment. A large gap exists in explaining premature CV deaths across the U.S. which cannot be totally attributed to traditional risk factors such as high cholesterol. Recent evidence suggests socioeconomic deprivation is a risk factor for this type of mortality.

"Socioeconomic status plays a big role in access to preventive care, risk factor control, and incidence of disease," said Sadeer Al-Kindi, MD, cardiologist and co-director of the Center for Integrated and Novel Approaches in Vascular-Metabolic Disease (CINEMA) with UH Harrington Heart & Vascular Institute and the study's senior author. "UH is committed to improving the health of all people by advancing science and human health. A large part of that is discovering the root cause of disease. With this study, we wanted to determine whether premature cardiovascular mortality is associated with socioeconomic deprivation and how premature cardiovascular mortality changed over time by social deprivation."

In "Socioeconomic Deprivation and Premature Cardiovascular Mortality in the United States" researchers completed a cross-sectional analysis of United States county-level death certificate data from 1999 to 2018 using files maintained by the U.S. National Center for Health and Statistics. They looked at people from the ages of 25 to 64 who died from cardiovascular conditions. They used linear regression analysis to document two integrated metrics of socioeconomic deprivation: Social Deprivation Index (SDI) and county Area Deprivation Index (ADI).

Results from this research showed that counties with high social deprivation had the highest rates of premature cardiovascular deaths. Additionally, from 1999 to 2018 premature cardiovascular mortality decreased to a lesser extent in socially deprived counties compared with affluent counties. In fact, indicators of social deprivation directly explained a significant proportion of the geographic differences in premature CV mortality in the U.S.

"Health and structural inequities in poor communities have been ignored for too long. We now know that where you live, inequities and other components embedded in the environment are powerful determinants of mortality, often from chronic non-communicable disease. Most importantly, shedding light on this pervasive issue compels us to act upon the information," said Sanjay Rajagopalan, MD, Chief of Cardiovascular Medicine and Chief Academic and Scientific Officer of UH Harrington Heart & Vascular Institute and co-author of the study, as well as the Herman K. Hellerstein, MD, Chair in Cardiovascular Research.

UH is taking action in a multitude of ways, including through its work in the community thanks to the ACHIEVE GreatER initiative. A "transformative" $18.2 million federal grant from the National Institutes of Health's P50 program will facilitate medical and cardiovascular care provided directly to people living in Cuyahoga Metropolitan Housing Authority, one of the nation's largest and oldest subsidized housing programs. Additional efforts by the study team are focused on understanding the integrated social and environmental underpinnings of premature cardiovascular disease in Northeast Ohio and nationally.

"Regardless of where they live or how much money they make, all people should have the opportunity to receive the necessary medical resources and support to have a healthier life," said Dr. Mehdi Shishehbor, DO, MPH, PhD, President of UH Harrington Heart & Vascular Institute, and the Angela and James Hambrick Chair in Innovation.

Prior studies have explored the relationship between race and premature CV mortality or individual socioeconomic factors (income, high school education) and CV mortality.

"To our knowledge, this is the first study to demonstrate a longitudinal association between multiple integrated metrics of socioeconomic deprivation and premature cardiovascular mortality adjusted for traditional cardiovascular risk factors, while also showing potentially worsening disparities," said Dr. Al-Kindi.

https://www.sciencedaily.com/releases/2022/03/220315141751.htm