Vitamin D supplementation: Possible gain in life years combined with cost savings

February 10, 2021

Science Daily/German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ)

In recent years, three meta-analyses of clinical studies have come to the conclusion that vitamin D supplementation was associated with a reduction in the mortality rate from cancer of around 13 percent. Scientists at the German Cancer Research Center (DKFZ) have now transferred these results to the situation in Germany and calculated: If all Germans over the age of 50 were to take vitamin D supplements, up to 30,000 cancer deaths per year could possibly be avoided and more than 300,000 years of life could be gained -- in addition, health care costs could be saved.

For several years now, scientists have been investigating the influence of an adequate supply of vitamin D on the prognosis of numerous diseases. The focus is particularly on inflammatory diseases, diabetes, respiratory diseases and cancer.

Three meta-analyses of large clinical studies have been published in recent years on the question of how vitamin D supply affects cancer mortality rates. The studies* came to the same conclusion: cancer mortality is reduced by around 13 percent with vitamin D supplementation -- across all cancers. Only methodologically high-quality randomized trials from all parts of the world were included in the meta-analyses. Exactly what biological mechanisms might underlie this is not yet clear.

"In many countries around the world, the age-adjusted rate of cancer mortality has fortunately declined over the past decade," says Hermann Brenner, an epidemiologist at the German Cancer Research Center (DKFZ). "However, given the often considerable costs of many new cancer drugs, this success has often come at a high price. Vitamin D, on the other hand, is comparatively inexpensive in the usual daily doses."

Vitamin D deficiency is common in the elderly population and especially among cancer patients. Brenner and colleagues now calculated what costs would be incurred by vitamin D supplementation of the entire population of Germany from the age of 50. They contrasted this sum with the potential savings for cancer therapies, which are often associated with costs in the range of several 10,000 euros, particularly in the case of advanced cancers during the last months of patients' lives.

The scientists based this calculation on a daily administration of 1,000 international units of vitamin D at a cost of 25 euros per person per year. In 2016, approximately 36 million people over the age of 50 lived in Germany, resulting in annual supplementation costs of 900 million euros.

The researchers took the cost of cancer treatment from the scientific literature, assuming mean additional treatment costs of €40,000 for the last year of life. A 13 percent reduction in cancer mortality in Germany corresponded to approximately 30,000 fewer cancer-related deaths per year, the treatment costs of which amounted to €1.154 billion in the model calculation. Compared with the costs of vitamin supplementation, this model calculates an annual saving of €254 million.

The researchers determined the number of years of life lost at the time of cancer death using data from the German Federal Statistical Office. Brenner considers the costs and effort of a routine determination of the individual vitamin D level to be dispensable, since an overdose is not to be feared with a supplementation of 1000 international units. Such a prior testing had not been made in the clinical trials either.

"In view of the potentially significant positive effects on cancer mortality -- additionally combined with a possible cost saving -- we should look for new ways to reduce the widespread vitamin D deficiency in the elderly population in Germany. In some countries, foods have even been enriched with vitamin D for many years -- for example, in Finland, where cancer mortality rates are about 20 percent lower than in Germany. Not to mention that there is mounting evidence of other positive health effects of adequate vitamin D supply, such as in lung disease mortality rates," says Brenner, adding, "Finally, we consider vitamin D supplementation so safe that we even recommend it for newborn babies to develop healthy bones."

To improve one's vitamin D levels at absolutely no cost, DKFZ's Cancer Information Service recommends spending time outdoors in the sunshine, two to three times a week for about twelve minutes. Face, hands and parts of arms and legs should be uncovered and without sunscreen for this period of time.

https://www.sciencedaily.com/releases/2021/02/210210133333.htm

Coffee lovers, rejoice! Drinking more coffee associated with decreased heart failure risk

Circulation: Heart Failure Journal Report

February 9, 2021

Science Daily/American Heart Association

Dietary information from three large, well-known heart disease studies suggests drinking one or more cups of caffeinated coffee may reduce heart failure risk, according to research published today in Circulation: Heart Failure, an American Heart Association journal.

Coronary artery disease, heart failure and stroke are among the top causes of death from heart disease in the U.S. "While smoking, age and high blood pressure are among the most well-known heart disease risk factors, unidentified risk factors for heart disease remain," according to David P. Kao, M.D., senior author of the study, assistant professor of cardiology and medical director at the Colorado Center for Personalized Medicine at the University of Colorado School of Medicine in Aurora, Colorado.

"The risks and benefits of drinking coffee have been topics of ongoing scientific interest due to the popularity and frequency of consumption worldwide," said Linda Van Horn, Ph.D., R.D., professor and Chief of the Department of Preventive Medicine's Nutrition Division at the Northwestern University Feinberg School of Medicine in Chicago, and member of the American Heart Association's Nutrition Committee. "Studies reporting associations with outcomes remain relatively limited due to inconsistencies in diet assessment and analytical methodologies, as well as inherent problems with self-reported dietary intake."

Kao and colleagues used machine learning through the American Heart Association's Precision Medicine Platform to examine data from the original cohort of the Framingham Heart Study and referenced it against data from both the Atherosclerosis Risk in Communities Study and the Cardiovascular Health Study to help confirm their findings. Each study included at least 10 years of follow-up, and, collectively, the studies provided information on more than 21,000 U.S. adult participants.

To analyze the outcomes of drinking caffeinated coffee, researchers categorized consumption as 0 cups per day, 1 cup per day, 2 cups per day and ?3 cups per day. Across the three studies, coffee consumption was self-reported, and no standard unit of measure were available.

The analysis revealed:

• In all three studies, people who reported drinking one or more cups of caffeinated coffee had an associated decreased long-term heart failure risk.

• In the Framingham Heart and the Cardiovascular Health studies, the risk of heart failure over the course of decades decreased by 5-to-12% per cup per day of coffee, compared with no coffee consumption.

• In the Atherosclerosis Risk in Communities Study, the risk of heart failure did not change between 0 to 1 cup per day of coffee; however, it was about 30% lower in people who drank at least 2 cups a day.

• Drinking decaffeinated coffee appeared to have an opposite effect on heart failure risk -- significantly increasing the risk of heart failure in the Framingham Heart Study. In the Cardiovascular Health Study however; there was no increase or decrease in risk of heart failure associated with drinking decaffeinated coffee. When the researchers examined this further, they found caffeine consumption from any source appeared to be associated with decreased heart failure risk, and caffeine was at least part of the reason for the apparent benefit from drinking more coffee.

"The association between caffeine and heart failure risk reduction was surprising. Coffee and caffeine are often considered by the general population to be 'bad' for the heart because people associate them with palpitations, high blood pressure, etc. The consistent relationship between increasing caffeine consumption and decreasing heart failure risk turns that assumption on its head," Kao said. "However, there is not yet enough clear evidence to recommend increasing coffee consumption to decrease risk of heart disease with the same strength and certainty as stopping smoking, losing weight or exercising."

According to the federal dietary guidelines, three to five 8-ounce cups of coffee per day can be part of a healthy diet, but that only refers to plain black coffee. The American Heart Association warns that popular coffee-based drinks such as lattes and macchiatos are often high in calories, added sugar and fat. In addition, despite its benefits, research has shown that caffeine also can be dangerous if consumed in excess. Additionally, children should avoid caffeine. The American Academy of Pediatrics recommends that, in general, kids avoid beverages with caffeine.

"While unable to prove causality, it is intriguing that these three studies suggest that drinking coffee is associated with a decreased risk of heart failure and that coffee can be part of a healthy dietary pattern if consumed plain, without added sugar and high fat dairy products such as cream," said Penny M. Kris-Etherton, Ph.D., R.D.N., immediate past chairperson of the American Heart Association's Lifestyle and Cardiometabolic Health Council Leadership Committee, Evan Pugh University Professor of Nutritional Sciences and distinguished professor of nutrition at The Pennsylvania State University, College of Health and Human Development in University Park. "The bottom line: enjoy coffee in moderation as part of an overall heart-healthy dietary pattern that meets recommendations for fruits and vegetables, whole grains, low-fat/non-fat dairy products, and that also is low in sodium, saturated fat and added sugars. Also, it is important to be mindful that caffeine is a stimulant and consuming too much may be problematic -- causing jitteriness and sleep problems."

Study limitations that may have impacted the results of the analysis included differences in the way coffee drinking was recorded and the type of coffee consumed. For example, drip, percolated, French press or espresso coffee types; origin of the coffee beans; and filtered or unfiltered coffee were details not specified. There also may have been variability regarding the unit measurement for 1 cup of coffee (i.e., how many ounces per cup). These factors could result in different caffeine levels. In addition, researchers caution that the original studies detailed only caffeinated or decaffeinated coffee, therefore these findings may not apply to energy drinks, caffeinated teas, soda and other food items with caffeine including chocolate.

https://www.sciencedaily.com/releases/2021/02/210209083513.htm

Fungi in the gut prime immunity against infection

February 5, 2021

Science Daily/Weill Cornell Medicine

Common fungi, often present in the gut, teach the immune system how to respond to their more dangerous relatives, according to new research from scientists at Weill Cornell Medicine. Breakdowns in this process can leave people susceptible to deadly fungal infections.

The study, published Feb. 5 in Cell, reveals a new twist in the complex relationship between humans and their associated microbes, and points the way toward novel therapies that could help combat a rising tide of drug-resistant pathogens.

The new discovery stemmed from work on inflammatory bowel disease, which often causes patients to carry larger than normal populations of fungi in their guts. These patients often develop strong antibody responses against mannan, a molecule common to a wide range of fungal species. However, Dr. Iliyan Iliev, associate professor of immunology in medicine in the Division of Gastroenterology and Hepatology at Weill Cornell Medicine, noticed that healthy controls in these studies also had some level of anti-fungal antibodies. "There was no actual evidence for fungal infections in the healthy individuals that we examined, so we started thinking about the possible function of those antibodies," said Dr. Iliev, who is senior author on the study and a member of the Jill Roberts Institute for Research in Inflammatory Bowel Disease.

The team developed a platform that allowed them to determine which gut fungi are targeted by antibodies in the blood of individual patients. They detected a strong response against the yeast Candida albicans. Turning to experiments in mice, Dr. Iliev and Itai Doron, a Weill Cornell Medicine Graduate School of Medical Sciences doctoral candidate in the lab and lead author on the study, found that colonizing the animals' guts with Candida albicans caused them to develop antibodies against the fungus in their bloodstreams, even though they didn't develop blood-borne fungal infections. Instead, the animals' immune cells appeared to transport fungal antigens to the spleen, stimulating the production of circulating antibodies in the bloodstream. "Those fungi just educate that immune response," Dr. Iliev said.

Iliev and his colleagues mimicked this process by treating mice with immunosuppressive drugs. When a Candida species colonizes the gut of these mice, the fungus moves into the bloodstream, causing a fatal infection. Treating the mice with purified anti-fungal antibodies from donor animals protected the immunosuppressed mice from these infections. The same strategy worked against infection with either Candida albicans or the emerging pathogenic yeast Candida auris, which has become a major cause of fungal disease in immunosuppressed patients and the elderly in recent years.

Collaborating with researchers at INSERM in Paris, France, the Weill Cornell Medicine team also looked at serum from patients with mutations in a gene called CARD9. This mutation affects a critical adapter protein in the immune system, leaving the affected individuals susceptible to severe fungal infections. Dr. Iliev's team found that the serum of these patients lacked the anti-fungal antibodies normally seen in serum of patients without this mutation. Experiments in mice confirmed an essential and specific role for CARD9 in priming the production of anti-fungal antibodies.

Graphic depicting relationship between fungi in gut, antibody levels and CARD gene Relationship between gut fungi, anti-fungal antibodies, CARD9 gene, and fungal immunity. Image courtesy of the Iliev lab.

The results suggest that normal intestinal fungi such as Candida albicans may function as a kind of intestinal vaccine against fungal infection in healthy people, by inducing the production of bloodborne antibodies that can target multiple species of potentially pathogenic fungi. When those fungi do enter the bloodstream, the antibodies bind them and target them for destruction by cells of the immune system. In patients with suppressed immunity, the anti-fungal antibodies may decline, leaving them vulnerable to fungal infection. New therapies that involve either stimulating the production of anti-fungal antibodies, or injecting such purified antibodies directly into patients' bloodstreams, could potentially help combat these increasingly common infections.

If that approach works, it would be a welcome development. "Many fungal infections in immunosuppressed patients and elderly patients are happening by translocation of pathogenic Candida species from the gastrointestinal tract, and the survival rates upon systemic spreading are alarmingly low," said Dr. Iliev.

https://www.sciencedaily.com/releases/2021/02/210205155813.htm

How air pollution may increase the risk of cardiovascular disease

Fine particulate air pollution stimulates production of inflammatory cells, leading to inflammation of the arteries

February 4, 2021

Science Daily/Massachusetts General Hospital

Tiny particles of air pollution -- called fine particulate matter -- can have a range of effects on health, and exposure to high levels is a known risk factor for cardiovascular disease. New research led by investigators at Massachusetts General Hospital (MGH) reveals that fine particulate matter has a detrimental impact on cardiovascular health by activating the production of inflammatory cells in the bone marrow, ultimately leading to inflammation of the arteries. The findings are published in the European Heart Journal.

The retrospective study included 503 patients without cardiovascular disease or cancer who had undergone imaging tests at MGH for various medical reasons. The scientists estimated participants' annual average fine particulate matter levels using data obtained from the U.S. Environment Protection Agency's air quality monitors located closest to each participant's residential address.

Over a median follow-up of 4.1 years, 40 individuals experienced major cardiovascular events, such as heart attacks and strokes, with the highest risk seen in participants with higher levels of fine particulate matter at their home address. Their risk was elevated even after accounting for cardiovascular risk factors, socioeconomic factors, and other key confounders. Imaging tests assessing the state of internal organs and tissues showed that these participants also had higher bone marrow activity, indicating a heightened production of inflammatory cells (a process called leukopoiesis), and elevated inflammation of the arteries. Additional analyses revealed that leukopoiesis in response to air pollution exposure is a trigger that causes arterial inflammation.

"The pathway linking air pollution exposure to cardiovascular events through higher bone marrow activity and arterial inflammation accounted for 29% of the relationship between air pollution and cardiovascular disease events," says co-first author Shady Abohashem, MD, a cardiovascular imaging fellow at MGH. "These findings implicate air pollution exposure as an underrecognized risk factor for cardiovascular disease and suggest therapeutic targets beyond pollution mitigation to lessen the cardiovascular impact of air pollution exposure."

Co-first author Michael Osborne, MD, a cardiologist at MGH, explains that therapies targeting increased inflammation following exposure to fine particulate matter may benefit patients who cannot avoid air pollution. "Importantly, most of the population studied had air pollution exposures well below the unhealthy thresholds established by the World Health Organization, suggesting that no level of air pollution can truly be considered safe," he says.

https://www.sciencedaily.com/releases/2021/02/210204135742.htm

Alcohol consumption linked to portion of cancer incidence and mortality

Findings call for implementation of policies and cancer control efforts to reduce alcohol consumption

January 19, 2021

Science Daily/American Cancer Society

A new study finds that alcohol consumption accounts for a considerable portion of cancer incidence and mortality in all 50 states and the District of Columbia. The article, which appears in Cancer Epidemiology, states that the proportion of cancer cases attributable to alcohol consumption ranged from a high of 6.7% in Delaware to a low of 2.9% in Utah. Similarly, Delaware had the highest proportion of alcohol-related cancer deaths (4.5%) and Utah had the lowest (1.9%).

This study conducted by Farhad Islami, MD, PhD, and colleagues at the American Cancer Society is the first to estimate contemporary proportions and counts of alcohol-attributable cancer cases and deaths for all states. Data shows the proportions were generally higher in New England and Western states and lower in Midwestern and Southern states.

"This information is important for prioritizing state-level cancer prevention and control efforts to reduce alcohol consumption and the burden of alcohol-related cancers," said Dr. Islami.

The proportion of alcohol-related cancers was far greater for some individual cancer types. For oral cavity/pharyngeal cancer cases, for example, it ranged from 36% in Utah to 62.5% in Delaware and was 45% or more in 45 states and the District of Columbia. By sex, alcohol-related cancer cases and deaths for most evaluated cancer types were higher among men, in part reflecting higher levels of alcohol consumption among men.

In the U.S. on average, alcohol consumption accounted for 4.8% of cancer cases and 3.2% of cancer deaths, or about 75,200 cancer cases and 18,950 cancer deaths annually, during 2013 to 2016.

In addition, the authors say, "healthcare providers and public health practitioners can educate the community to expand the currently limited awareness of the cancer-related risks of alcohol consumption." The American Cancer Society's guideline for Diet and Physical Activity for Cancer Prevention states that it is best not to consume alcohol; for those who do drink, consumption should be limited to no more than 1 drink per day for women and 2 drinks per day for men.

https://www.sciencedaily.com/releases/2021/01/210119114255.htm

One small alcoholic drink a day is linked to an increased risk of atrial fibrillation

January 17, 2021

Science Daily/European Society of Cardiology

A study of nearly 108,000 people has found that people who regularly drink a modest amount of alcohol are at increased risk of atrial fibrillation, a condition where the heart beats in an abnormal rhythm.

The study, published today (Wednesday) in the European Heart Journal [1], found that, compared to drinking no alcohol at all, just one alcoholic drink a day was linked to a 16% increased risk of atrial fibrillation over an average (median) follow-up time of nearly 14 years. This means that while four teetotallers in 100 might develop atrial fibrillation over the period of the study, five per 100 might develop the condition if they consumed alcohol starting with slightly more than an alcoholic drink a week and more than 75% of them consumed up to one drink a day [2]. The researchers categorised one alcoholic drink as containing 12 g of ethanol, which is the equivalent of a small (120 ml) glass of wine, a small beer (330 ml) or 40 ml of spirits.

It is well known that people who drink a lot of alcohol regularly are at increased risk of developing heart failure, and heart failure can increase the incidence of atrial fibrillation. Several studies have shown a slightly higher risk of heart problems for people who never drink alcohol; they often show that this risk reduces for people who drink a modest amount, and then rises sharply the more alcohol is consumed, creating a 'J' shape on graphs. Until now, it has not been clear whether this was also the case for atrial fibrillation.

However, in the current study led by Professor Renate Schnabel, a consultant cardiologist at the University Heart and Vascular Center, Hamburg-Eppendorf (Germany), researchers found that although low doses of alcohol were associated with a reduced risk of heart failure compared to teetotallers, a similar 'J' shape reduction in risk was not seen for atrial fibrillation. This suggests that the increased risk of atrial fibrillation among people drinking small amounts of alcohol was not triggered by heart failure.

Prof. Schnabel said: "To our knowledge, this is the largest study on alcohol consumption and long-term incidence of atrial fibrillation in the community. Previous studies have not had enough power to examine this question, although they have been able to show a relationship between alcohol intake and other heart and blood vessel problems, such as heart attack and heart failure. In our study, we can now demonstrate that even very low regular alcohol consumption may increase the risk of atrial fibrillation.

"These findings are important as the regular consumption of alcohol, the 'one glass of wine a day' to protect the heart, as is often recommended for instance in the lay press, should probably no longer be suggested without balancing risks and possible benefits for all heart and blood vessel diseases, including atrial fibrillation."

The researchers analysed information on 107,845 people taking part in five community-based studies in Sweden, Norway, Finland, Denmark and Italy. The participants underwent medical examinations at the time they joined the studies between 1982 and 2010 and provided information on their medical histories, lifestyles (including alcohol and tobacco consumption), employment and education levels. A total of 100,092 participants did not have atrial fibrillation when they enrolled and their median age was nearly 48 years (range 24-97 years).

During the median follow-up period of nearly 14 years, 5,854 people developed atrial fibrillation. The associations between alcohol consumption and the risk of atrial fibrillation were similar for all types of alcoholic drinks and for men and women.

In addition to the 16% increased risk of atrial fibrillation compared to teetotallers seen in people who consumed only one alcoholic drink a day, the researchers found that the risk increased with increasing alcohol intake; up to two drinks a day was associated with a 28% increased risk and this went up to 47% for those who consumed more than four.

The exact mechanisms by which modest amounts of alcohol could trigger atrial fibrillation are not known. Studies have shown that heavy drinking over a short period of time can trigger 'holiday heart syndrome' in some people, and in some atrial fibrillation patients, small amounts of alcohol can trigger arrhythmia episodes.

Limitations of the study include the fact that study participants reported the type and quantity of alcohol they drank and this could lead to under-reporting; the information available did not enable the researchers to look at the effects of binge drinking; some episodes of atrial fibrillation can be asymptomatic and so may not have been reported; only adults across Europe were included in the analyses and so it may not be possible for the results to be generalised to other populations; as the study was observational, it can show only an association between alcohol intake and atrial fibrillation and not that alcohol causes atrial fibrillation.

In an accompanying editorial [3], Jorge A. Wong and David Conen from the Population Health Research Institute at McMaster University, Hamilton, Canada, write that the research "makes an important contribution to our understanding of the relationship between alcohol intake and incident AF, in particular at the lower spectrum of alcohol consumption. A significant relationship between alcohol and AF was identified, and even small quantities of alcohol were associated with an increased, albeit small, risk of incident AF.

"Together with a recent randomized trial showing that a reduction in alcohol intake led to a reduction in AF recurrence, these data suggest that lowering alcohol consumption may be important for both prevention and management of AF. Importantly, any reduction in low-to-moderate alcohol consumption to potentially prevent AF needs to be balanced with the potentially beneficial association low amounts of alcohol may have with respect to other cardiovascular outcomes . . . The net clinical benefit of consuming low amounts of alcohol requires further study, ideally in adequately powered randomized trials. Until then, each individual has to make its own best educated decision as to whether consuming up to one alcoholic drink per day is worthwhile and safe."

https://www.sciencedaily.com/releases/2021/01/210117132231.htm

Poor gut health connected to severe COVID-19

January 12, 2021

Science Daily/American Society for Microbiology

People infected with COVID-19 experience a wide range of symptoms and severities, the most commonly reported including high fevers and respiratory problems. However, autopsy and other studies have also revealed that the infection can affect the liver, kidney, heart, spleen -- and even the gastrointestinal tract. A sizeable fraction of patients hospitalized with breathing problems also have diarrhea, nausea and vomiting, suggesting that when the virus does get involved in the GI tract it increases the severity of the disease.

In a review published this week in mBio, microbiologist Heenam Stanley Kim, Ph.D, from Korea University's Laboratory for Human-Microbial Interactions, in Seoul, examined emerging evidence suggesting that poor gut health adversely affects COVID-19 prognosis. Based on his analysis, Kim proposed that gut dysfunction -- and its associated leaky gut -- may exacerbate the severity of infection by enabling the virus to access the surface of the digestive tract and internal organs. These organs are vulnerable to infection because they have widespread ACE2 -- a protein target of SARS-CoV-2 -- on the surface.

"There seems to be a clear connection between the altered gut microbiome and severe COVID-19," Kim said.

Studies have demonstrated that people with underlying medical conditions including high blood pressure, diabetes and obesity face a higher risk of severe COVID-19. Risk also increases with age, with older adults most vulnerable to the most serious complications and likelihood of hospitalization. But both of these factors -- advanced age and chronic conditions -- have a well-known association with an altered gut microbiota. This imbalance can affect gut barrier integrity, Kim noted, which can allow pathogens and pathobionts easier access to cells in the intestinal lining.

So far, the link between gut health and COVID-19 prognosis hasn't been empirically demonstrated, Kim noted. Some researchers have argued, he said, that unhealthy gut microbiomes may be an underlying reason for why some people have such severe infections.

What studies have been done hint at a complicated relationship. A study on symptomatic COVID-19 patients in Singapore, for example, found that about half had a detectable level of the coronavirus in fecal tests -- but only about half of those experienced GI symptoms. That study suggests that even if SARS-CoV-2 reaches the GI tract, it may not cause problems. Kim also noted that a person's gut health at the time of infection may be critical for symptom development.

Many recent studies have found reduced bacterial diversity in gut samples collected from COVID-19 patients, compared to samples from healthy people. The disease has also been linked to a depletion of beneficial bacterial species -- and the enrichment of pathogenic ones. A similar imbalance has been associated with influenza A infection, though the 2 viruses differ in how they change the overall microbial composition.

The depleted bacterial species associated with COVID-19 infection include some families that are responsible for producing butyrate, a short-chain fatty acid, which plays a pivotal role in gut health by reinforcing gut-barrier function.

Kim said he started analyzing the studies after realizing that wealthy countries with a good medical infrastructure -- including the United States and nations in Western Europe -- were among the hardest hit by the virus. The "western diet" that's common in these countries is low in fiber, and "a fiber-deficient diet is one of the main causes of altered gut microbiomes," he said, "and such gut microbiome dysbiosis leads to chronic diseases."

The pathogenesis of COVID-19 is still not fully understood. If future studies do show that gut health affects COVID-19 prognosis, Kim argued, then clinicians and researchers should exploit that connection for better strategies aimed at preventing and managing the disease. Eating more fiber, he said, may lower a person's risk of serious disease. And fecal microbiota transplantation might be a treatment worth considering for patients with the worst cases of COVID-19.

The problem with gut health goes beyond COVID-19, though, he said. Once the pandemic passes, the world will still have to reckon with chronic diseases and other problems associated with poor gut health.

"The whole world is suffering from this COVID-19 pandemic," Kim said, "but what people do not realize is that the pandemic of damaged gut microbiomes is far more serious now."

https://www.sciencedaily.com/releases/2021/01/210112085347.htm

Higher coffee intake may be linked to lower prostate cancer risk

Each additional daily cup associated with reduction in risk of nearly 1%

January 11, 2021

Science Daily/BMJ

Drinking several cups of coffee every day may be linked to a lower risk of developing prostate cancer, suggests a pooled data analysis of the available evidence, published in the online journal BMJ Open.

Each additional daily cup of the brew was associated with a reduction in relative risk of nearly 1%, the findings indicate.

Prostate cancer is the second most common cancer, and the sixth leading cause of cancer death in men. Nearly three out of four cases occur in the developed world, and since the 1970s, new cases of the disease have risen sharply in Asian countries, including Japan, Singapore, and China.

Coffee consumption has been linked to a lower relative risk of liver, bowel, and breast cancers, but as yet, there is no conclusive evidence for its potential role in prostate cancer risk reduction.

In a bid to advance understanding of the issue, the researchers trawled research databases for relevant cohort studies published up to September 2020.

They pooled the data from 16: 15 reported on the risk of prostate cancer associated with the highest, compared with the lowest, coffee consumption; 13 reported on the risk associated with an additional daily cup. The highest level of consumption ranged from 2 to 9 or more cups a day; the lowest level ranged from none to fewer than 2 cups a day.

The included studies were carried out in North America (7), Europe (7) and Japan (2). They included more than 1 million men (1,081, 586) of whom 57,732 developed prostate cancer.

Compared with the lowest category of coffee consumption, the highest category was associated with a reduction in prostate cancer risk of 9%. And each additional daily cup was associated with a reduction in risk of 1%.

Further refining the analysis to localised and advanced prostate cancer, showed that compared with the lowest intake, the highest intake was associated with a 7% lower risk of localised prostate cancer, and a 12%-16% lower risk for advanced and fatal prostate cancer, respectively.

The researchers acknowledge that because of the observational design of the included cohort studies, unmeasured or uncontrolled factors in the original studies may have skewed the pooled risk estimate.

The amount of coffee drunk may also have been misclassified as it depended on recall. And the type of coffee and brewing methods varied among the studies. The design and methods of the included studies also varied, so caution in interpreting the findings is warranted, they say.

Nevertheless, there are plausible biological explanations for their findings, they highlight.

Coffee improves glucose metabolism, has anti-inflammatory and antioxidant effects, and affects sex hormone levels, all of which may influence the initiation, development and progression of prostate cancer, they point out.

And they conclude: "This study suggests that increased coffee consumption may be associated with a reduced risk of prostate cancer. Further research is still warranted to explore the underlying mechanisms and active compounds in coffee.

"If the association is further proved to be a causal effect, men might be encouraged to increase their coffee consumption to potentially decrease the risk of prostate cancer."

https://www.sciencedaily.com/releases/2021/01/210111190137.htm

Make-up of gut microbiome may influence COVID-19 severity and immune response

Imbalances in type and volume of bacteria may also be implicated in 'long COVID'

January 11, 2021

Science Daily/BMJ

The variety and volume of bacteria in the gut, known as the microbiome, may influence the severity of COVID-19 as well as the magnitude of the immune system response to the infection, suggests research published online in the journal Gut.

Imbalances in the make-up of the microbiome may also be implicated in persisting inflammatory symptoms, dubbed 'long COVID', the findings suggest.

COVID-19 is primarily a respiratory illness, but the evidence suggests that the gut may also have a role.

As the gut is the largest immunological organ in the body and its resident microbes are known to influence immune responses, the researchers wanted to find out if the gut microbiome might also affect the immune system response to COVID-19 infection.

They therefore obtained blood and stool samples and medical records from 100 hospital inpatients with laboratory-confirmed COVID-19 infection between February and May 2020 and from 78 people without COVID-19 who were taking part in a microbiome study before the pandemic.

The severity of COVID-19 was classified as mild in the absence of x-ray evidence of pneumonia; moderate if pneumonia with fever and respiratory tract symptoms were detected; severe if patients found it very difficult to breathe normally; and critical if they needed mechanical ventilation or experienced organ failure requiring intensive care.

To characterise the gut microbiome, 41 of the COVID patients provided multiple stool samples while in hospital, 27 of whom provided serial stool samples up to 30 days after clearance of SARS-CoV-2, the virus responsible for COVID-19.

Analysis of all 274 stool samples showed that the make-up of the gut microbiome differed significantly between patients with and without COVID-19, irrespective of whether they had been treated with drugs, including antibiotics.

COVID patients had higher numbers of Ruminococcus gnavus, Ruminococcus torques and Bacteroides dorei species than people without the infection.

And they had far fewer of the species that can influence immune system response, such as Bifidobacterium adolescentis, Faecalibacterium prausnitzii and Eubacterium rectale.

Lower numbers of F. prausnitzii and Bifidobacterium bifidum were particularly associated with infection severity after taking account of antibiotic use and patient age.

And the numbers of these bacteria remained low in the samples collected up to 30 days after infected patients had cleared the virus from their bodies.

COVID-19 infection prompts the immune system to produce inflammatory cytokines in response. In some cases, this response can be excessive ('cytokine storm'), causing widespread tissue damage, septic shock, and multiorgan failure.

Analysis of the blood samples showed that the microbial imbalance found in the COVID patients was also associated with raised levels of inflammatory cytokines and blood markers of tissue damage, such as C-reactive protein and certain enzymes.

This suggests that the gut microbiome might influence the immune system response to COVID-19 infection and potentially affect disease severity and outcome, say the researchers.

"In light of reports that a subset of recovered patients with COVID-19 experience persistent symptoms, such as fatigue, dyspnoea [breathlessness] and joint pains, some over 80 days after initial onset of symptoms, we posit that the dysbiotic gut microbiome could contribute to immune-related health problems post-COVID-19," they write.

This is an observational study, and as such, can't establish cause, added to which the gut microbiome varies widely among different populations, so the changes observed in this study may not be applicable to other COVID patients elsewhere, caution the researchers.

But they point to mounting evidence showing that gut microbes are linked to inflammatory diseases within and beyond the gut.

And they conclude: "Bolstering of beneficial gut species depleted in COVID-19 could serve as a novel avenue to mitigate severe disease, underscoring the importance of managing patients' gut microbiota during and after COVID-19."

https://www.sciencedaily.com/releases/2021/01/210111190135.htm

Link between gut microbes, diet and illnesses

January 11, 2021

Science Daily/King's College London

Diets rich in healthy and plant-based foods encourages the presence of gut microbes that are linked to a lower risk of common illnesses including heart disease, research has found.

A large-scale international study using metagenomics and blood chemical profiling has uncovered a panel of 15 gut microbes associated with lower risks of common conditions such as obesity and type 2 diabetes. The study has been published today in Nature Medicine from researchers at King's College London, Massachusetts General Hospital (MGH), Harvard T.H. Chan School of Public Health, the University of Trento, Italy, and health start-up company ZOE.

The PREDICT 1 (Personalized Responses to Dietary Composition Trial 1) analyzed detailed data on the composition of participants' gut microbiomes, their dietary habits, and cardiometabolic blood biomarkers. It uncovered strong links between a person's diet, the microbes in their gut (microbiome) and their health.

Researchers identified microbes that positively or negatively correlate 'good' and 'bad' with an individual's risk of certain serious conditions such as diabetes, heart disease and obesity. Surprisingly, the microbiome has a greater association to these markers than other factors, such as genetics. Some of the identified microbes are so novel that they have not yet been named.

The researchers defined a "healthy" diet as one that contained a mix of foods associated with a lower risk of chronic disease. They found that trial subjects who ate such a diet, or one rich in plants, were more likely to have high levels of specific 'good' gut microbes which are associated with a low risk of common illnesses. The researchers also found microbiome-based biomarkers of obesity as well as markers for cardiovascular disease and impaired glucose tolerance, which are key risk factors for COVID. These findings can be used to help create personalized eating plans designed specifically to improve one's health.

Dr. Sarah Berry, Reader in Nutrition Sciences at King's College London said, "As a nutritional scientist, finding novel microbes that are linked to specific foods, as well as metabolic health, is exciting. Given the highly personalised composition of each individuals' microbiome, our research suggests that we may be able to modify our gut microbiome to optimize our health by choosing the best foods for our unique biology."

For example, the findings reveal that having a microbiome rich in Prevotella copri and Blastocystis species was associated with maintaining a favorable blood sugar level after a meal. Other species were linked to lower post-meal levels of blood fats and markers of inflammation.

Professor Tim Spector, Epidemiologist from King's College London, who started the PREDICT study program and is scientific founder of ZO, said: "When you eat, you're not just nourishing your body, you're feeding the trillions of microbes that live inside your gut."

Nicola Segata, PhD, professor and principal investigator of the Computational Metagenomics Lab at the University of Trento, Italy and leader of the microbiome analysis in the study, said: "We were surprised to see such large, clear groups of what we informally call 'good' and 'bad' microbes emerging from our analysis. It is also exciting to see that microbiologists know so little about many of these microbes that they are not even named yet. This is now a big area of focus for us, as we believe they may open new insights in the future into how we could use the gut microbiome as a modifiable target to improve human metabolism and health."

https://www.sciencedaily.com/releases/2021/01/210111112208.htm

Bosses need appreciation, too

Study shows supervisors who feel appreciated have better outlook at work

December 10, 2020

Science Daily/University of Central Florida

'Tis the season to be grateful, even for your boss, according to a recent University of Central Florida study that suggests when supervisors feel appreciated, it gives them a boost of energy and optimism. In the end, that's good for employees and the organization's bottom line.

"Based on theory, we knew feeling appreciated by another person sends a strong signal that you are positively regarded, and feelings of positive regard evoke a sense of vigor -- or high energy," said Maureen Ambrose, the Gordon J. Barnett Professor of Business Ethics and a UCF Pegasus Professor. "This is important because research indicates when people possess higher levels of resources, in this case, energy, they are better able to maintain a positive outlook and engage in positive behaviors at work. We know when supervisors have feelings of depletion -- or low energy -- negative things happen. For example, when bosses have low energy, they engage in more abusive supervision, creating worse workplaces for their employees,"

Ambrose teamed up with Clemson professor and UCF alumna Susan Sheridan to examine feelings of appreciation and emotional expressions in the workplace. Typically, research in this area has focused solely on the downward influence of supervisors on their employees.

"Our study also found that feeling appreciated by employees was positively related, via energy, to supervisors' psychological well-being. Psychological well-being can buffer individuals from the negative effects of job stress," Ambrose said.

Lessening job stress on employees can have a significant impact on a business's bottom line. The American Institute of Stress estimates that job stress cos U.S. industry more than $300 billion a year in absenteeism, turnover, diminished productivity, and medical, legal and insurance costs.

The study asked supervisors to respond to surveys twice a day for 10 consecutive workdays. Each day participants recorded how much they felt appreciated by their subordinates, how energetic they felt and how it affected them personally (sense of optimism and life satisfaction) and professionally (job satisfaction).

"On days supervisors felt more appreciated, they had more energy, and this translated into higher levels of optimism, life satisfaction, job satisfaction and helping," says Sheridan, who earned her doctorate at UCF and is now an assistant professor of leadership at Clemson. "This was interesting because our field hasn't connected feeling appreciated to higher energy, and we typically look at how supervisors can boost the resources of subordinates -- not the other way around."

The study found that the external validation from feeling appreciated is especially powerful for those supervisors who lack a strong sense of validation from within.

Ambrose and Sheridan say they hope this research sparks a deeper examination into the role of gratitude and appreciation in the workplace and how employees influence supervisors.

"Anyone who has managed people knows how influential the relationships with subordinates can be," Ambrose said. "Taking this upwards perspective may help us better understand supervisors' lived experiences at work and why they do the things they do."

https://www.sciencedaily.com/releases/2020/12/201210145714.htm

Hypnotic suggestions can make a complex task easy by helping vision fill in the blanks

January 27, 2021

Science Daily/Association for Psychological Science

Popular folklore and anecdotal evidence suggest that people in a hypnotic or suggestible state can experience sensory hallucinations, such as perceiving sounds and sights that are not actually there. Reliable scientific evidence of these experiences, however, has been notoriously challenging to obtain because of their subjective nature.

New research published in the journal Psychological Science provides compelling evidence that hypnotic suggestions can help highly susceptible people "see" imaginary objects, equipping them with the missing details needed to solve an otherwise challenging visual puzzle.

"Hypnosis holds intriguing effects on human behavior," said Amir Raz, a researcher at McGill University and coauthor on the paper. "The careful, systematic study of hypnotic phenomena can answer important questions about mind-body interactions and advance novel therapies in medicine, psychology, and dentistry."

For their research, Raz and his colleagues divided 32 participants into two groups: those who were found to be highly hypnotizable and those who were less suggestible. The participants viewed an array of disconnected lines moving around on a display screen. The lines, if lengthened and connected, would have formed various geometric shapes, such as diamonds or triangles.

Participants had to determine whether the rotation of the incomplete geometric figures was clockwise or counterclockwise. This task was inherently difficult because the disconnected lines lacked the visual cues necessary to easily assess the direction of rotation. The participants' success rate was approximately 50-50, or no better than chance.

The participants were then given the hypnotic suggestion to imagine that something was blocking out part of each shape being observed. Afterward, they repeated the same task of determining the direction of rotation.

The results revealed that participants who were highly susceptible to hypnotic suggestion successfully "hallucinated" visual occluders on top of moving objects. This added imaginary element enabled the participants to better visualize the full geometric shapes and more accurately determine their direction of rotation. On average, their success rate improved to approximately 70%, a statistically significant change.

The participants in the less hypnotizable group, however, were no more likely to complete the observational task following hypnotic suggestion. "Although these results are consistent with our hypothesis, the data surprised us by revealing the decisive and robust nature of the effect," said Raz.

Previous work on hypnosis has often highlighted its capacity to suppress or remove certain perceptual experiences. The new research shows compelling evidence that a hypnotic suggestion can also enhance or introduce perceptual experiences.

"Our findings support the idea that, at least in some people, suggestions can add perceptual information to sensory input," said Raz. "This observation adds meaningful weight to theoretical, clinical, and applied aspects of the brain and psychological sciences."

https://www.sciencedaily.com/releases/2021/01/210127171840.htm

Mindfulness can improve mental health and wellbeing -- but unlikely to work for everyone

January 11, 2021

Science Daily/University of Cambridge

Mindfulness courses can reduce anxiety, depression and stress and increase mental wellbeing within most but not all non-clinical settings, say a team of researchers at the University of Cambridge. They also found that mindfulness may be no better than other practices aimed at improving mental health and wellbeing.

Mindfulness is typically defined as 'the awareness that emerges through paying attention on purpose, in the present moment, and nonjudgmentally to the unfolding of experience moment by moment'. It has become increasingly popular in recent years as a way of increasing wellbeing and reducing stress levels.

In the UK, the National Health Service offers therapies based on mindfulness to help treat mental health issues such as depression and suicidal thoughts. However, the majority of people who practice mindfulness learn their skills in community settings such as universities, workplaces, or private courses. Mindfulness-based programmes are frequently promoted as the go-to universal tool to reduce stress and increase wellbeing, accessible to anyone, anywhere.

Many randomised controlled trials (RCTs) have been conducted around the world to assess whether in-person mindfulness training can improve mental health and wellbeing, but the results are often varied. In a report published today in PLOS Medicine, a team of researchers from the Department of Psychiatry at the University of Cambridge led a systematic review and meta-analysis to examine the published data from the RCTs. This approach allows them to bring together existing -- and often contradictory or under-powered -- studies to provide more robust conclusions.

The team identified 136 RCTs on mindfulness training for mental health promotion in community settings. These trials included 11,605 participants aged 18 to 73 years from 29 countries, more than three-quarters (77%) of whom were women.

The researchers found that in most community settings, compared with doing nothing, mindfulness reduces anxiety, depression and stress, and increases wellbeing. However, the data suggested that in more than one in 20 trials settings, mindfulness-based programmes may not improve anxiety and depression.

Dr Julieta Galante from the Department of Psychiatry at the University of Cambridge, the report's first author, said: "For the average person and setting, practising mindfulness appears to be better than doing nothing for improving our mental health, particularly when it comes to depression, anxiety and psychological distress -- but we shouldn't assume that it works for everyone, everywhere.

"Mindfulness training in the community needs to be implemented with care. Community mindfulness courses should be just one option among others, and the range of effects should be researched as courses are implemented in new settings. The courses that work best may be those aimed at people who are most stressed or in stressful situations, for example health workers, as they appear to see the biggest benefit."

The researchers caution that RCTs in this field tended to be of poor quality, so the combined results may not represent the true effects. For example, many participants stopped attending mindfulness courses and were not asked why, so they are not represented in the results. When the researchers repeated the analyses including only the higher quality studies, mindfulness only showed effects on stress, not on wellbeing, depression or anxiety.

When compared against other 'feel good' practices such as exercise, mindfulness fared neither better nor worse. Professor Peter Jones, also from Cambridge's Department of Psychiatry, and senior author, said: "While mindfulness is often better than taking no action, we found that there may be other effective ways of improving our mental health and wellbeing, such as exercise. In many cases, these may prove to be more suitable alternatives if they are more effective, culturally more acceptable or are more feasible or cost effective to implement. The good news is that there are now more options."

The researchers say that the variability in the success of different mindfulness-based programmes identified among the RCTs may be down to a number of reasons, including how, where and by whom they are implemented as well as at whom they are targeted. The techniques and frameworks taught in mindfulness have rich and diverse backgrounds, from early Buddhist psychology and meditation through to cognitive neuroscience and participatory medicine -- the interplay between all of these different factors can be expected to influence how effective a programme is.

The number of online mindfulness courses has increased rapidly, accelerated further by the COVID-19 pandemic. Although this review has not looked at online courses, studies suggest that these may be as effective as their offline counterparts, despite most lacking interactions with teacher and peers.

Dr Galante added: "If the effects of online mindfulness courses vary as widely according to the setting as their offline counterparts, then the lack of human support they offer could cause potential problems. We need more research before we can be confident about their effectiveness and safety."

 https://www.sciencedaily.com/releases/2021/01/210111143422.htm

Rotten egg gas could guard against Alzheimer's disease

January 12, 2021

Science Daily/Johns Hopkins Medicine

Typically characterized as poisonous, corrosive and smelling of rotten eggs, hydrogen sulfide's reputation may soon get a face-lift thanks to Johns Hopkins Medicine researchers. In experiments in mice, researchers have shown the foul-smelling gas may help protect aging brain cells against Alzheimer's disease. The discovery of the biochemical reactions that make this possible opens doors to the development of new drugs to combat neurodegenerative disease.

The findings from the study are reported in the Jan. 11 issue of the Proceedings of the National Academies of Science.

"Our new data firmly link aging, neurodegeneration and cell signaling using hydrogen sulfide and other gaseous molecules within the cell," says Bindu Paul, M.Sc., Ph.D., faculty research instructor in neuroscience in the Solomon H. Snyder Department of Neuroscience at the Johns Hopkins University School of Medicine and lead corresponding author on the study.

The human body naturally creates small amounts of hydrogen sulfide to help regulate functions throughout the body, from cell metabolism to blood vessel dilation. The rapidly burgeoning field of gasotransmission shows that gases are major cellular messenger molecules, with particular importance in the brain. However, unlike conventional neurotransmitters, gases can't be stored in vesicles. Thus, gases act through very different mechanisms to rapidly facilitate cellular messaging. In the case of hydrogen sulfide, this entails the modification of target proteins by a process called chemical sulfhydration, which modulates their activity, says Solomon Snyder, D.Phil., D.Sc., M.D., professor of neuroscience at the Johns Hopkins University School of Medicine and co-corresponding author on the study.

Studies using a new method have shown that sulfhydration levels in the brain decrease with age, a trend that is amplified in patients with Alzheimer's disease. "Here, using the same method, we now confirm a decrease in sulfhydration in the AD brain," says collaborator Milos Filipovic, Ph.D., principal investigator, Leibniz-Institut für Analytische Wissenschaften -- ISAS.

For the current research, the Johns Hopkins Medicine scientists studied mice genetically engineered to mimic human Alzheimer's disease. They injected the mice with a hydrogen sulfide-carrying compound called NaGYY, developed by their collaborators at the University of Exeter in the United Kingdom, which slowly releases the passenger hydrogen sulfide molecules while traveling throughout the body. The researchers then tested the mice for changes in memory and motor function over a 12-week period.

Behavioral tests on the mice showed that hydrogen sulfide improved cognitive and motor function by 50% compared with mice that did not receive the injections of NaGYY. Treated mice were able to better remember the locations of platform exits and appeared more physically active than their untreated counterparts with simulated Alzheimer's disease.

The results showed that the behavioral outcomes of Alzheimer's disease could be reversed by introducing hydrogen sulfide, but the researchers wanted to investigate how the brain chemically reacted to the gaseous molecule.

A series of biochemical experiments revealed a change to a common enzyme called glycogen synthase β (GSK3β). In the presence of healthy levels of hydrogen sulfide, GSK3β typically acts as a signaling molecule, adding chemical markers to other proteins and altering their function. However, the researchers observed that in the absence of hydrogen sulfide, GSK3β is overattracted to another protein in the brain called Tau.

When GSK3β interacts with Tau, Tau changes into a form that tangles and clumps inside nerve cells. As Tau clumps grow, the tangled proteins block communication between nerves, eventually causing them to die. This leads to the deterioration and eventual loss of cognition, memory and motor function that is characteristic of Alzheimer's disease.

"Understanding the cascade of events is important to designing therapies that can block this interaction like hydrogen sulfide is able to do," says Daniel Giovinazzo, M.D./Ph.D. student, the first author of the study.

Until recently, researchers lacked the pharmacological tools to mimic how the body slowly makes tiny quantities of hydrogen sulfide inside cells. "The compound used in this study does just that and shows by correcting brain levels of hydrogen sulfide, we could successfully reverse some aspects of Alzheimer's disease," says collaborator on the study Matt Whiteman, Ph.D., professor of experimental therapeutics at the University of Exeter Medical School.

The Johns Hopkins Medicine team and their international collaborators plan to continue studying how sulfur groups interact with GSK3β and other proteins involved in the pathogenesis of Alzheimer's disease in other cell and organ systems. The team also plans to test novel hydrogen sulfide delivery molecules as part of their ongoing venture.

https://www.sciencedaily.com/releases/2021/01/210112110103.htm

Better heart health scores in midlife linked to lower risk of late-life dementia

Findings support views that maintaining lifelong heart health behaviors could reduce dementia risk

December 15, 2020

Science Daily/PLOS

A long-term study of 1,449 people in Finland found that those who had better scores on standard metrics of cardiovascular health in midlife, especially for behavioral factors such as smoking, had a lower risk of dementia later in life. Yajun Liang of Karolinska Institutet in Stockholm, Sweden, and colleagues present these findings in the open-access journal PLOS Medicine.

Previous research suggests that efforts to address modifiable risk factors, such as behaviors that impact heart health, could reduce the global number of people with dementia by up to one third. However, there is a lack of evidence on potential links between risk of late-life dementia and scores on standard heart health metrics in midlife and late life.

To gain further clarity on late-life risk of dementia, Liang and colleagues analyzed data on 1,449 participants in the Finnish Cardiovascular Risk Factors, Aging and Dementia study, enrolled 1972¬-1987 and assessed in 1998, and 744 dementia-free survivors were followed further into late life (2005¬-2008). Participants' heart health was evaluated from midlife to late life according to six factors classified as three behavioral (smoking status, physical activity, and body mass index) and three biological factors (fasting plasma glucose, total cholesterol, and blood pressure). Dementia was diagnosed in 61 persons in the first follow up, and additional 47 persons in the second.

The researchers found that participants with intermediate or ideal cardiovascular health scores from midlife onwards, especially for behavioral factors, had a lower risk of dementia later in life than participants with poor scores.

The researchers found no significant overall association between heart health scores measured in late life and risk of dementia. However, when looking specifically at biological factors, ideal scores in late life were actually associated with greater risk of dementia. The authors note that this could be because some biological hallmarks of dementia might overlap with "ideal" scores on these factors, such as lower blood pressure and lower cholesterol. They also note that the major limitations of this study include the lack of data on diet and midlife plasma glucose, and high rate of attrition.

These findings suggest that maintaining lifelong cardiovascular health, particularly in the areas of smoking, exercise, and body mass index, could reduce dementia risk later in life.

https://www.sciencedaily.com/releases/2020/12/201215140840.htm

Apathy could predict onset of dementia years before other symptoms

December 14, 2020

Science Daily/University of Cambridge

Apathy -- a lack of interest or motivation -- could predict the onset of some forms of dementia many years before symptoms start, offering a 'window of opportunity' to treat the disease at an early stage, according to new research from a team of scientists led by Professor James Rowe at the University of Cambridge.

Frontotemporal dementia is a significant cause of dementia among younger people. It is often diagnosed between the ages of 45 and 65. It changes behaviour, language and personality, leading to impulsivity, socially inappropriate behaviour, and repetitive or compulsive behaviours.

A common feature of frontotemporal dementia is apathy, with a loss of motivation, initiative and interest in things. It is not depression, or laziness, but it can be mistaken for them. Brain scanning studies have shown that in people with frontotemporal dementia it is caused by shrinkage in special parts at the front of the brain -- and the more severe the shrinkage, the worse the apathy. But, apathy can begin decades before other symptoms, and be a sign of problems to come.

"Apathy is one of the most common symptoms in patients with frontotemporal dementia. It is linked to functional decline, decreased quality of life, loss of independence and poorer survival," said Maura Malpetti, a cognitive scientist at the Department of Clinical Neurosciences, University of Cambridge.

"The more we discover about the earliest effects of frontotemporal dementia, when people still feel well in themselves, the better we can treat symptoms and delay or even prevent the dementia."

Frontotemporal dementia can be genetic. About a third of patients have a family history of the condition. The new discovery about the importance of early apathy comes from the Genetic Frontotemporal dementia Initiative (GENFI), a collaboration between scientists across Europe and Canada. Over 1,000 people are taking part in GENFI, from families where there is a genetic cause of Frontotemporal dementia.

Now, in a study published today in Alzheimer's & Dementia: The Journal of the Alzheimer's Association, Professor Rowe and colleagues have shown how apathy predicts cognitive decline even before the dementia symptoms emerge.

The new study involved 304 healthy people who carry a faulty gene that causes frontotemporal dementia, and 296 of their relatives who have normal genes. The participants were followed over several years. None had dementia, and most people in the study did not know whether they carry a faulty gene or not. The researchers looked for changes in apathy, memory tests and MRI scans of the brain.

"By studying people over time, rather than just taking a snapshot, we revealed how even subtle changes in apathy predicted a change in cognition, but not the other way around," explained Malpetti, the study's first author. "We also saw local brain shrinkage in areas that support motivation and initiative, many years before the expected onset of symptoms."

People with the genetic mutations had more apathy than other members of their family, which over two years increased much more than in people with normal genetics. The apathy predicted cognitive decline, and this accelerated as they approached the estimated age of onset of symptoms.

Professor Rogier Kievit from the Donders Institute, Radboud University Medical Center at Nijmegen and MRC Cognition and Brain Sciences Unit at Cambridge, said: "Apathy progresses much faster for those individuals who we know are at greater risk of developing frontotemporal dementia, and this is linked to greater atrophy in the brain. At the start, even though the participants with a genetic mutation felt well and had no symptoms, they were showing greater levels of apathy. The amount of apathy predicted cognitive problems in the years ahead."

"From other research, we know that in patients with frontotemporal dementia, apathy is a bad sign in terms of independent living and survival. Here we show its importance in the decades before symptoms begin," said Professor James Rowe from the Department of Clinical Neurosciences, joint senior author.

Professor Rowe said the study highlights the importance of investigating why someone has apathy. "There are many reasons why someone feels apathetic. It may well be an easy to treat medical condition, such as low levels of thyroid hormone, or a psychiatric illness such as depression. But doctors need to keep in mind the possibility of apathy heralding a dementia, and increasing the chance of dementia if left unaddressed, particularly if someone has a family history of dementia.

"Treating dementia is a challenge, but the sooner we can diagnose the disease, the greater our window of opportunity to try and intervene and slow or stop its progress."

https://www.sciencedaily.com/releases/2020/12/201214192356.htm

High blood pressure at any age, no matter how long you have it, may speed cognitive decline

December 14, 2020

Science Daily/American Heart Association

High blood pressure appears to accelerate a decline in cognitive performance in middle-aged and older adults, according to new research published today in Hypertension, an American Heart Association journal.

Nearly half of American adults have high blood pressure or hypertension. Having high blood pressure is a risk factor for cognitive decline, which includes such things as memory, verbal fluency, attention and concentration. Blood pressure of 120 mmHg -- 129 mmHg systolic (the top number in a reading) or higher is considered elevated. Systolic pressure above 130 mmHg, or diastolic pressure (the bottom number) of 80 mmHg or higher is considered hypertension.

"We initially anticipated that the negative effects of hypertension on cognitive function would be more critical when hypertension started at a younger age, however, our results show similar accelerated cognitive performance decline whether hypertension started in middle age or at older ages," said study author Sandhi M. Barreto, M.D., M.Sc., Ph.D., professor of medicine at the Universidade Federal de Minas Gerais in Belo Horizonte, Brazil. "We also found that effectively treating high blood pressure at any age in adulthood could reduce or prevent this acceleration. Collectively, the findings suggest hypertension needs to be prevented, diagnosed and effectively treated in adults of any age to preserve cognitive function."

Barreto and colleagues analyzed findings from an existing study that included blood pressure and cognitive health information for more than 7,000 adults in Brazil, whose average age was about 59 years old at the study's start. The study participants were followed for an average of nearly 4 years; testing included analysis of memory, verbal fluency and executive function, which includes attention, concentration and other factors associated with thinking and reasoning.

Their analysis found:

• Systolic blood pressure between 121 and 139 mmHg or diastolic blood pressure between 81 and 89 mmHg with no antihypertensive medication use was associated with accelerated cognitive performance decline among middle-aged and older individuals.

• The speed of decline in cognition happened regardless of hypertension duration, meaning high blood pressure for any length of time, even a short duration, might impact a person's speed of cognitive decline.

• Adults with uncontrolled hypertension tended to experience notably faster declines in memory and global cognitive function than adults who had controlled hypertension.

"In addition to other proven benefits of blood pressure control, our results highlight the importance of diagnosing and controlling hypertension in patients of any age to prevent or slow down cognitive decline," Barreto said. "Our results also reinforce the need to maintain lower blood pressure levels throughout life, since even prehypertension levels were associated with cognitive decline."

According to Barreto, some of the study's limitations are the relatively short follow-up period and that the participants self-reported the hypertension diagnosis at baseline.

"Although the participants of our study are adults from Brazil, we believe that our findings are applicable to other regions. Previous studies have shown that similar unhealthy behaviors and risk factors, including hypertension, are common in the development of cardiovascular diseases in different populations across the globe," Barreto said.

https://www.sciencedaily.com/releases/2020/12/201214090133.htm

Diet modifications -- including more wine and cheese -- may help reduce cognitive decline

December 10, 2020

Science Daily/Iowa State University

The foods we eat may have a direct impact on our cognitive acuity in our later years. This is the key finding of an Iowa State University research study spotlighted in an article published in the November 2020 issue of the Journal of Alzheimer's Disease.

The study was spearheaded by principal investigator, Auriel Willette, an assistant professor in Food Science and Human Nutrition, and Brandon Klinedinst, a Neuroscience PhD candidate working in the Food Science and Human Nutrition department at Iowa State. The study is a first-of-its-kind large scale analysis that connects specific foods to later-in-life cognitive acuity.

Willette, Klinedinst and their team analyzed data collected from 1,787 aging adults (from 46 to 77 years of age, at the completion of the study) in the United Kingdom through the UK Biobank, a large-scale biomedical database and research resource containing in-depth genetic and health information from half-a-million UK participants. The database is globally accessible to approved researchers undertaking vital research into the world's most common and life-threatening diseases.

Participants completed a Fluid Intelligence Test (FIT) as part of touchscreen questionnaire at baseline (compiled between 2006 and 2010) and then in two follow-up assessments (conducted from 2012 through 2013 and again between 2015 and 2016). The FIT analysis provides an in-time snapshot of an individual's ability to "think on the fly."

Participants also answered questions about their food and alcohol consumption at baseline and through two follow-up assessments. The Food Frequency Questionnaire asked participants about their intake of fresh fruit, dried fruit, raw vegetables and salad, cooked vegetables, oily fish, lean fish, processed meat, poultry, beef, lamb, pork, cheese, bread, cereal, tea and coffee, beer and cider, red wine, white wine and champaign and liquor.

Here are four of the most significant findings from the study:

1. Cheese, by far, was shown to be the most protective food against age-related cognitive problems, even late into life;

2. The daily consumption of alchohol, particularly red wine, was related to improvements in cognitive function;

3. Weekly consumption of lamb, but not other red meats, was shown to improve long-term cognitive prowess; and

4. Excessive consumption of salt is bad, but only individuals already at risk for Alzheimer's Disease may need to watch their intake to avoid cognitive problems over time.

"I was pleasantly surprised that our results suggest that responsibly eating cheese and drinking red wine daily are not just good for helping us cope with our current COVID-19 pandemic, but perhaps also dealing with an increasingly complex world that never seems to slow down," Willette said. "While we took into account whether this was just due to what well-off people eat and drink, randomized clinical trials are needed to determine if making easy changes in our diet could help our brains in significant ways."

Klinedinst added, "Depending on the genetic factors you carry, some individuals seem to be more protected from the effects of Alzheimers, while other seem to be at greater risk. That said, I believe the right food choices can prevent the disease and cognitive decline altogether. Perhaps the silver bullet we're looking for is upgrading how we eat. Knowing what that entails contributes to a better understanding of Alzheimer's and putting this disease in a reverse trajectory."

Willette and Klinedinst acknowledge the valuable contributions of the other members of the research team: Scott Le, Colleen Pappas, Nathan Hoth, Amy Pollpeter and Qian Wang in the Iowa State department of Food Science and Human Nutrition; Brittany Larsen, Neuroscience graduate program at Iowa State; Yueying Wang and Li Wang, department of Statistics at Iowa State; Shan Yu, department of Statistics, University of Virginia; Karin Allenspach, department of Veterinary Clinical Sciences at Iowa State; Jonathan Mochel, department of Biomedical Sciences at Iowa State; and David Bennett, Rush Alzheimer's Disease Center, Rush Medical Center, Rush University.

https://www.sciencedaily.com/releases/2020/12/201210145850.htm

Blood test for Alzheimer's disease predicts future cognitive decline in healthy people

December 9, 2020

Science Daily/Brigham and Women's Hospital

Today, a clinician can order a blood test to check a patient's cholesterol or hemoglobin A1c levels -- biomarkers that help predict an individual's risk of cardiovascular disease or diabetes, respectively. But despite decades of advances in the understanding of Alzheimer's disease (AD), a blood test for predicting its risk remains elusive. Imaging scans of the brain and lumbar punctures that collect cerebrospinal fluid can offer diagnoses, but such tests are expensive and cumbersome for patients. Two years ago, investigators at Brigham and Women's Hospital reported the development of a blood test for a fragment of the protein tau, a hallmark of AD. Now, that test for levels of N-terminal fragment of tau (NT1) has been evaluated in participants in the Harvard Aging Brain Study (HABS), a cohort of cognitively normal, older adults who are followed closely over time. In Nature Communications, the authors report that baseline NT1 levels in the blood were highly predictive of the risk of cognitive decline and AD dementia.

"Our findings indicate that measuring a tau fragment in plasma can help predict which elderly people are likely to decline and how quickly they are likely to decline," said corresponding author Dennis Selkoe, MD, co-director of the Ann Romney Center for Neurologic Diseases. "We're excited because there are currently no commercially available blood tests to predict risk of AD in still-healthy individuals. Having such a blood test allows us to better screen people for enrollment in AD prevention trials and represents progress toward diagnostic tests for AD in medical care."

Selkoe cautions that a commercial test for routine clinical care likely remains several years away. But for clinical trials that seek to evaluate preventive treatments for AD, such as the large-scale clinical trials led by co-author Reisa Sperling, MD, MMSc, director of the Center for Alzheimer Research and Treatment at the Brigham NT1 levels could be measured before a participant enrolls in a the trial, and potentially also as a longitudinal measure to assess treatment response. The test ultimately represents a far less costly and less invasive alternative to imaging and lumbar punctures.

The current study, led by first author Jasmeer Chhatwal, MD, PhD, now an attending physician and scientist in the Massachusetts General Hospital Department of Neurology, evaluated the predictive value of NT1 among 236 cognitively normal participants in HABS. Participants were on average 74 years old when they entered HABS and were followed for an average of five years. Blood samples were collected in the first year.

The research team found that higher levels of NT1 in blood samples taken at the beginning of the trial were strongly associated with future clinical progression. The team divided participants into those with high, medium and low NT1 levels, finding that for the group with the highest levels, the risk of advancing to mild cognitive impairment (MC I) or AD dementia was 2.4-fold. NT1 levels predicted decline across multiple areas of memory, including episodic memory -- remembering specific events or experiences such as a person's birthday or a family visit -- and also predicted how fast the participant's cognition would decline. Imaging data showed that higher baseline NT1 blood levels were associated with elevated brain levels of ?-amyloid plaques and the accumulation of tangles of tau -- both classical signs of AD.

The authors note that relatively few participants in HABS progressed to AD, an important limitation of this cohort. They found that another brain protein -- known as NfL -- which has been studied by other groups, may also be associated with cognitive decline, especially among people who already show signs of cognitive deficits. NfL was a less strong predictor than NT1 in the study.

"The NT1 tau fragment may be a reflection of damage to neurons and synapses, allowing us to use blood samples to detect what is happening in a patient's brain years before they begin experiencing symptoms," said Selkoe. "This could give us an invaluable window of time in which to evaluate interventions for preventing cognitive decline and AD dementia."

https://www.sciencedaily.com/releases/2020/12/201209115147.htm

Drug reverses age-related mental decline within days

Rapid rejuvenation of mental faculties in aged mice implicates reversible physiological 'blockage' behind age-related cognitive losses

December 1, 2020

Science Daily/University of California - San Francisco

Just a few doses of an experimental drug can reverse age-related declines in memory and mental flexibility in mice, according to a new study by UC San Francisco scientists. The drug, called ISRIB, has already been shown in laboratory studies to restore memory function months after traumatic brain injury (TBI), reverse cognitive impairments in Down Syndrome, prevent noise-related hearing loss, fight certain types of prostate cancer, and even enhance cognition in healthy animals.

In the new study, published December 1, 2020 in the open-access journal eLife, researchers showed rapid restoration of youthful cognitive abilities in aged mice, accompanied by a rejuvenation of brain and immune cells that could help explain improvements in brain function.

"ISRIB's extremely rapid effects show for the first time that a significant component of age-related cognitive losses may be caused by a kind of reversible physiological 'blockage' rather than more permanent degradation," said Susanna Rosi, PhD, Lewis and Ruth Cozen Chair II and professor in the departments of Neurological Surgery and of Physical Therapy and Rehabilitation Science.

"The data suggest that the aged brain has not permanently lost essential cognitive capacities, as was commonly assumed, but rather that these cognitive resources are still there but have been somehow blocked, trapped by a vicious cycle of cellular stress," added Peter Walter, PhD, a professor in the UCSF Department of Biochemistry and Biophysics and a Howard Hughes Medical Institute investigator. "Our work with ISRIB demonstrates a way to break that cycle and restore cognitive abilities that had become walled off over time."

Could Rebooting Cellular Protein Production Hold the Key to Aging and Other Diseases?

Walter has won numerous scientific awards, including the Breakthrough, Lasker and Shaw prizes, for his decades-long studies of cellular stress responses. ISRIB, discovered in 2013 in Walter's lab, works by rebooting cells' protein production machinery after it gets throttled by one of these stress responses -- a cellular quality control mechanism called the integrated stress response (ISR; ISRIB stands for ISR InhiBitor).

The ISR normally detects problems with protein production in a cell -- a potential sign of viral infection or cancer-promoting gene mutations -- and responds by putting the brakes on cell's protein-synthesis machinery. This safety mechanism is critical for weeding out misbehaving cells, but if stuck in the on position in a tissue like the brain, it can lead to serious problems, as cells lose the ability to perform their normal activities, Walter and colleagues have found.

In particular, recent animal studies by Walter and Rosi, made possible by early philanthropic support from The Rogers Family Foundation, have implicated chronic ISR activation in the persistent cognitive and behavioral deficits seen in patients after TBI, by showing that, in mice, brief ISRIB treatment can reboot the ISR and restore normal brain function almost overnight.

The cognitive deficits in TBI patients are often likened to premature aging, which led Rosi and Walter to wonder if the ISR could also underlie purely age-related cognitive decline. Aging is well known to compromise cellular protein production across the body, as life's many insults pile up and stressors like chronic inflammation wear away at cells, potentially leading to widespread activation of the ISR.

"We've seen how ISRIB restores cognition in animals with traumatic brain injury, which in many ways is like a sped-up version of age-related cognitive decline," said Rosi, who is director of neurocognitive research in the UCSF Brain and Spinal Injury Center and a member of the UCSF Weill Institute for Neurosciences. "It may seem like a crazy idea, but asking whether the drug could reverse symptoms of aging itself was just a logical next step."

ISRIB Improves Cognition, Boosts Neuron and Immune Cell Function

In the new study, researchers led by Rosi lab postdoc Karen Krukowski, PhD, trained aged animals to escape from a watery maze by finding a hidden platform, a task that is typically hard for older animals to learn. But animals who received small daily doses of ISRIB during the three-day training process were able to accomplish the task as well as youthful mice, much better than animals of the same age who didn't receive the drug.

The researchers then tested how long this cognitive rejuvenation lasted and whether it could generalize to other cognitive skills. Several weeks after the initial ISRIB treatment, they trained the same mice to find their way out of a maze whose exit changed daily -- a test of mental flexibility for aged mice who, like humans, tend to get increasingly stuck in their ways. The mice who had received brief ISRIB treatment three weeks before still performed at youthful levels, while untreated mice continued to struggle.

To understand how ISRIB might be improving brain function, the researchers studied the activity and anatomy of cells in the hippocampus, a brain region with a key role in learning and memory, just one day after giving animals a single dose of ISRIB. They found that common signatures of neuronal aging disappeared literally overnight: neurons' electrical activity became more sprightly and responsive to stimulation, and cells showed more robust connectivity with cells around them while also showing an ability to form stable connections with one another usually only seen in younger mice.

The researchers are continuing to study exactly how the ISR disrupts cognition in aging and other conditions and to understand how long ISRIB's cognitive benefits may last. Among other puzzles raised by the new findings is the discovery that ISRIB also alters the function of the immune system's T cells, which also are prone to age-related dysfunction. The findings suggest another path by which the drug could be improving cognition in aged animals, and could have implications for diseases from Alzheimer's to diabetes that have been linked to heightened inflammation caused by an aging immune system.

"This was very exciting to me because we know that aging has a profound and persistent effect on T cells and that these changes can affect brain function in the hippocampus," said Rosi. "At the moment, this is just an interesting observation, but it gives us a very exciting set of biological puzzles to solve.

ISRIB May Have Wide-Ranging Implications for Neurological Disease

It turns out that chronic ISR activation and resulting blockage of cellular protein production may play a role in a surprisingly wide array of neurological conditions. Below is a partial list of these conditions, based on a recent review by Walter and colleague Mauro Costa-Mattioli of Baylor College of Medicine, which could potentially be treated with an ISR-resetting agent like ISRIB:

• Frontotemporal Dementia

• Alzheimer's Disease

• Amyotrophic Lateral Sclerosis (ALS)

• Age-related Cognitive Decline

• Multiple Sclerosis

• Traumatic Brain Injury

• Parkinson's Disease

• Down Syndrome

• Vanishing White Matter Disorder

• Prion Disease

ISRIB has been licensed by Calico, a South San Francisco, Calif. company exploring the biology of aging, and the idea of targeting the ISR to treat disease has been picked up by other pharmaceutical companies, Walter says.

One might think that interfering with the ISR, a critical cellular safety mechanism, would be sure to have serious side effects, but so far in all their studies, the researchers have observed none. This is likely due to two factors, Walter says. First, it takes just a few doses of ISRIB to reset unhealthy, chronic ISR activation back to a healthier state, after which it can still respond normally to problems in individual cells. Second, ISRIB has virtually no effect when applied to cells actively employing the ISR in its most powerful form -- against an aggressive viral infection, for example.

Naturally, both of these factors make the molecule much less likely to have negative side effects -- and more attractive as a potential therapeutic. According to Walter: "It almost seems too good to be true, but with ISRIB we seem to have hit a sweet spot for manipulating the ISR with an ideal therapeutic window.

https://www.sciencedaily.com/releases/2020/12/201201124144.htm