Natural compound in basil may protect against Alzheimer's disease pathology
University of South Florida, October 5, 2021
Fenchol, a natural compound abundant in some plants including basil, can help protect the brain against Alzheimer's disease pathology, a preclinical study led by University of South Florida Health (USF Health) researchers suggests.
The new study published Oct. 5 in the Frontiers in Aging Neuroscience, discovered a sensing mechanism associated with the gut microbiome that explains how fenchol reduces neurotoxicity in the Alzheimer's brain.
Emerging evidence indicates that short-chain fatty acids (SCFAs)– metabolites produced by beneficial gut bacteria and the primary source of nutrition for cells in your colon—contribute to brain health. The abundance of SCFAs is often reduced in older patients with mild cognitive impairment and Alzheimer's disease, the most common form of dementia. However, how this decline in SCFAs contributes to Alzheimer's disease progression remains largely unknown.
Gut-derived SCFAs that travel through the blood to the brain can bind to and activate free fatty acid receptor 2 (FFAR2), a cell signaling molecule expressed on brain cellscalled neurons.
"Our study is the first to discover that stimulation of the FFAR2 sensing mechanism by these microbial metabolites (SCFAs) can be beneficial in protecting brain cells against toxic accumulation of the amyloid-beta (Aβ) protein associated with Alzheimer's disease," said principal investigator Hariom Yadav, Ph.D., professor of neurosurgery and brain repair at the USF Health Morsani College of Medicine, where he directs the USF Center for Microbiome Research.
One of the two hallmark pathologies of Alzheimer's disease is hardened deposits of Aβ that clump together between nerve cells to form amyloid protein plaques in the brain. The other is neurofibrillary tangles of tau protein inside brain cells. These pathologies contribute to the neuron loss and death that ultimately cause the onset of Alzheimer's, a neurodegenerative disease characterized by loss of memory, thinking skills and other cognitive abilities.
Dr. Yadav and his collaborators delve into molecular mechanisms to explain how interactions between the gut microbiome and the brain might influence brain health and age-related cognitive decline. In this study, Dr. Yadav said, the research team set out to uncover the "previously unknown" function of FFAR2 in the brain.
The researchers first showed that inhibiting the FFAR2 receptor (thus blocking its ability to "sense" SCFAs in the environment outside the neuronal cell and transmit signaling inside the cell) contributes to the abnormal buildup of the Aβ protein causing neurotoxicity linked to Alzheimer's disease.
Then, they performed large-scale virtual screening of more than 144,000 natural compounds to find potential candidates that could mimic the same beneficial effect of microbiota produced SCFAs in activating FFAR2 signaling. Identifying a natural compound alternative to SCFAs to optimally target the FFAR2 receptor on neurons is important, because cells in the gut and other organs consume most of these microbial metabolites before they reach the brain through blood circulation, Dr. Yadav noted.
Dr. Yadav's team narrowed 15 leading compound candidates to the most potent one. Fenchol, a plant-derived compound that gives basil its aromatic scent, was best at binding to the FFAR's active site to stimulate its signaling.
Further experiments in human neuronal cell cultures, as well as Caenorhabditis (C.) elegans (worm) and mouse models of Alzheimer's disease demonstrated that fenchol significantly reduced excess Aβ accumulation and death of neurons by stimulating FFAR2 signaling, the microbiome sensing mechanism. When the researchers more closely examined how fenchol modulates Aβ-induced neurotoxicity, they found that the compound decreased senescent neuronal cells, also known as "zombie" cells, commonly found in brains with Alzheimer's disease pathology.
Zombie cells stop replicating and die a slow death. Meanwhile, Dr. Yadav said, they build up in diseased and aging organs, create a damaging inflammatory environment, and send stress or death signals to neighboring healthy cells, which eventually also change into harmful zombie cells or die.
"Fenchol actually affects the two related mechanisms of senescence and proteolysis," Dr. Yadav said of the intriguing preclinical study finding. "It reduces the formation of half-dead zombie neuronal cells and also increases the degradation of (nonfunctioning) Aβ, so that amyloid protein is cleared from the brain much faster."
Before you start throwing lots of extra basil in your spaghetti sauce or anything else you eat to help stave off dementia, more research is needed—including in humans.
In exploring fenchol as a possible approach for treating or preventing Alzheimer's pathology, the USF Health team will seek answers to several questions. A key one is whether fenchol consumed in basil itself would be more or less bioactive (effective) than isolating and administering the compound in a pill, Dr. Yadav said. "We also want to know whether a potent dose of either basil or fenchol would be a quicker way to get the compound into the brain."
Researchers find sense of purpose associated with better memory
Florida State University, October 6, 2021
Add an improved memory to the list of the many benefits that accompany having a sense of purpose in life.
A new study led by Florida State University researchers showed a link between an individual's sense of purpose and their ability to recall vivid details. The researchers found that while both a sense of purpose and cognitive function made memories easier to recall, only a sense of purpose bestowed the benefits of vividness and coherence.
The study, which focused on memories related to the COVID-19 pandemic, was published in the journal Memory.
"Personal memories serve really important functions in everyday life," said Angelina Sutin, a professor in the College of Medicine and the paper's lead author. "They help us to set goals, control emotions and build intimacy with others. We also know people with a greater sense of purpose perform better on objective memory tests, like remembering a list of words. We were interested in whether purpose was also associated with the quality of memories of important personal experiences because such qualities may be one reason why purpose is associated with better mental and physical health."
Nearly 800 study participants reported on their sense of purpose and completed tasks that measured their cognitive processing speed in January and February 2020, before the ongoing coronavirus pandemic took hold in the U.S. Researchers then measured participants' ability to retrieve and describe personal memories about the pandemic in July 2020, several months into the public health crisis.
Participants with a stronger sense of purpose in life reported that their memories were more accessible, coherent and vivid than participants with less purpose. Those with a higher sense of purpose also reported many sensory details, spoke about their memories more from a first-person perspective and reported more positive feeling and less negative feeling when asked to retrieve a memory.
The researchers also found that depressive symptoms had little effect on the ability to recall vivid details in memories, suggesting that the connection between life purpose and memory recall is not due to the fewer depressive symptoms among individuals higher in purpose.
Purpose in life has been consistently associated with better episodic memory, such as the number of words retrieved correctly on a memory task. This latest research expands on those connections to memory by showing a correlation between purpose and the richness of personal memory.
"We chose to measure the ability to recall memories associated with the COVID-19 pandemic because the pandemic is an event that touched everyone, but there has been a wide range of experiences and reactions to it that should be apparent in memories," said co-author Martina Luchetti, an assistant professor in the College of Medicine.
Along with the association with better memory, previous research has found other numerous benefits connected with having a sense of purpose, from a lower risk of death to better physical and mental health.
"Memories help people to sustain their well-being, social connections and cognitive health," said co-author Antonio Terracciano, a professor in the College of Medicine. "This research gives us more insight into the connections between a sense of purpose and the richness of personal memories. The vividness of those memories and how they fit into a coherent narrative may be one pathway through which purpose leads to these better outcomes.
Vitamin D protects against severe asthma attacks
Queen Mary University of London, October 3, 2021
Taking oral vitamin D supplements in addition to standard asthma medication could halve the risk of asthma attacks requiring hospital attendance, according to research led by Queen Mary University of London (QMUL).
Asthma affects more than 300 million people worldwide and is estimated to cause almost 400,000 deaths annually. Asthma deaths arise primarily during episodes of acute worsening of symptoms, known as attacks or 'exacerbations', which are commonly triggered by viral upper respiratory infections.
Vitamin D is thought to protect against such attacks by boosting immune responses to respiratory viruses and dampening down harmful airway inflammation.
The new study, funded by the National Institute for Health Research, and published in The Lancet Respiratory Medicine, collated and analysed the individual data from 955 participants in seven randomised controlled trials, which tested the use of vitamin D supplements.
Overall, the researchers found that vitamin D supplementation resulted in:
- a 30 per cent reduction in the rate of asthma attacks requiring treatment with steroid tablets or injections - from 0.43 events per person per year to 0.30.
- a 50 per cent reduction in the risk of experiencing at least one asthma attack requiring Accident and Emergency Department attendance and/or hospitalisation - from 6 per cent of people experiencing such an event to 3 per cent.
Vitamin D supplementation was found to be safe at the doses administered. No instances of excessively high calcium levels or renal stones were seen, and serious adverse events were evenly distributed between participants taking vitamin D and those on placebo.
Lead researcher Professor Adrian Martineau said: "These results add to the ever growing body of evidence that vitamin D can support immune function as well as bone health. On average, three people in the UK die from asthma attacks every day. Vitamin D is safe to take and relatively inexpensive so supplementation represents a potentially cost-effective strategy to reduce this problem."
The team's use of individual participant data also allowed them to query the extent to which different groups respond to vitamin D supplementation, in more detail than previous studies.
In particular, vitamin D supplementation was found to have a strong and statistically-significant protective effect in participants who had low vitamin D levels to start with. These participants saw a 55 per cent reduction in the rate of asthma exacerbations requiring treatment with steroid tablets or injections - from 0.42 events per person per year to 0.19.
However, due to relatively small numbers of patients within sub-groups, the researchers caution that they did not find definitive evidence to show that effects of vitamin D supplementation differ according to baseline vitamin D status.
Professor Hywel Williams, Director of the NIHR Health Technology Assessment Programme, said: "The results of this NIHR-funded study brings together evidence from several other studies from over the world and is an important contribution to reducing uncertainties on whether Vitamin D is helpful for asthma - a common condition that impacts on many thousands of people worldwide."
Dr David Jolliffe from QMUL, first author on the paper, added: "Our results are largely based on data from adults with mild to moderate asthma: children and adults with severe asthma were relatively under-represented in the dataset, so our findings cannot necessarily be generalised to these patient groups at this stage. Further clinical trials are on-going internationally, and we hope to include data from them in a future analysis to determine whether the promise of today's results is confirmed in an even larger and more diverse group of patients."
Study Shows Lifestyle Choices Have Significant Impact on Multiple Chronic Conditions, Significant Implications For Reducing Costs
Yale University, October 05, 2021
In a study published in the Journal of Preventive Medicine, Adams and colleagues showed a linear association between a number of modifiable risk factors and multiple chronic conditions, making those modifications a key to health care cost savings and to preventing a wide range of conditions.
The data analyzed for the study, https://authors.elsevier.com/a/1VpFeKt2pmc9H, were from the publicly available 2013 Behavioral Risk Factor Surveillance System and included 483,865 non-institutionalized US adults ages 18 years old or older. Chronic conditions included asthma, arthritis, heart disease, stroke, chronic obstructive pulmonary disease (COPD), cognitive impairment, cancer other than skin, and kidney disease. Risk factors included obesity, current smoking, sedentary lifestyle, inadequate fruit and vegetable consumption and sleeping other than seven to eight hours, while depression, hypertension, high cholesterol, and diabetes were considered in each category.
Previous research by Thorpe and colleagues had estimated that the care of adults with four or more chronic conditions (17.1% of all adults in the study) is responsible for 77.6% of all health care costs in the U.S. today.
The potential savings by reducing just two risk factors (diabetes and hypertension) and their related comorbidity was estimated previously by Ormond and colleagues at $9 billion annually over one to two years and closer to $25 billion a year after 5 years or more, factoring in possible complications.
True Health Initiative founder, at Yale University Director and study co-author David L. Katz, MD, MPH, FACLM, pointed out that in addition to costs, another implication of the study results is an individual's access to healthcare if they have one or more of the chronic conditions.
"Although insurers decide what qualifies as a pre-existing condition, all the chronic conditions used in this study except cognitive impairment are commonly included," he said. "Individuals with a pre-existing condition could be denied coverage or face higher premiums. While having a pre-existing condition might not affect coverage for adults eligible for Medicare, over half of all adults with multiple chronic conditions are ages 18 to 64 years."
American College of Lifestyle Medicine President George Guthrie, MD, MPH, FACLM, said the study confirms the necessity for addressing the root cause of chronic conditions.
"The evidence shows that the risks for chronic disease are rooted in lifestyle choices," he said. "More than ever, it is important to emphasize lifestyle medicine as the first treatment option for preventing, treating, and in some cases, reversing the cause of chronic conditions. If we can help people with chronic conditions, we can add years to their life and life to their years, as well as lower the ever-increasing costs of healthcare for everyone."
Physical athletes' visual skills prove sharper than action video game players
University of Waterloo (Canada), October 7, 2021
Athletes still have the edge over action video gamers when it comes to dynamic visual skills, a new study from the University of Waterloo shows.
"Athletes involved in sports with a high-level of movement—like soccer, football, or baseball—often score higher on dynamic visual acuity tests than non-athletes," said Dr. Kristine Dalton of Waterloo's School of Optometry & Vision Science. "Our research team wanted to investigate if action video gamers—who, like e-sport athletes, are regularly immersed in a dynamic, fast-paced 2D video environment for large periods of time—would also show superior levels of dynamic visual acuity on par with athletes competing in physical sport."
While visual acuity (clarity or sharpness of vision) is most often measured under static conditions during annual check-ups with an optometrist, research shows that testing dynamic visual acuity is a more effective measure of a person's ability to see moving objects clearly—a baseline skill necessary for success in physical and e-sports alike.
Using a dynamic visual acuity skills-test designed and validated at the University of Waterloo, researchers discovered that while physical athletes score highly on dynamic visual acuity tests as expected, action video game players tested closer to non-athletes.
"Ultimately, athletes showed a stronger ability to identify smaller moving targets, which suggests visual processing differences exist between them and our video game players," said Alan Yee, a Ph.D. candidate in vision science. All participants were matched based on their level of static visual acuity and refractive error, distinguishing dynamic visual acuity as the varying factor on their test performance.
"Our findings show there is still a benefit to training in a 3D environment," said Dalton. "For athletes looking to develop stronger visual skills, the broader visual field and depth perception that come with physical training may be crucial to improving their dynamic visual acuity—and ultimately, their sport performance."
The study, Athletes demonstrate superior visual dynamic visual acuity, authored by Waterloo's School of Optometry & Vision Science's Dalton, Yee, Dr. Elizabeth Irving and Dr. Ben Thompson, was recently published in the journal Optometry and Vision Science.
Probiotic Akkermansia muciniphila and environmental enrichment reverse cognitive impairment associated with high-fat high-cholesterol consumption
University of Oviedo (Spain), September 8, 2021
Nonalcoholic steatohepatitis (NASH) is one of the most prevalent diseases globally. A high-fat, high-cholesterol (HFHC) diet leads to an early NASH model. It has been suggested that gut microbiota mediates the effects of diet through the microbiota–gut–brain axis, modifying the host’s brain metabolism and disrupting cognition. Here, we target NASH-induced cognitive damage by testing the impact of environmental enrichment (EE) and the administration of either Lacticaseibacillus rhamnosus GG (LGG) or Akkermansia muciniphila CIP107961 (AKK). EE and AKK, but not LGG, reverse the HFHC-induced cognitive dysfunction, including impaired spatial working memory and novel object recognition; however, whereas AKK restores brain metabolism, EE results in an overall decrease. Moreover, AKK and LGG did not induce major rearrangements in the intestinal microbiota, with only slight changes in bacterial composition and diversity, whereas EE led to an increase in Firmicutes and Verrucomicrobia members. Our findings illustrate the interplay between gut microbiota, the host’s brain energy metabolism, and cognition. In addition, the findings suggest intervention strategies, such as the administration of AKK, for the management of the cognitive dysfunction related to NASH.
In this study, we described cognitive, brain metabolism, and microbiota alterations associated with high-fat and high-cholesterol consumption. In addition, we clearly showed that environmental enrichment and A. muciniphila CIP107961 restore cognitive dysfunction. Furthermore, we revealed that cognitive improvement is associated with differential effects of environmental enrichment and this strain of A. muciniphila on brain metabolism and gut microbiota. Finally, we discovered that restored cognitive function was associated with the administration of A. muciniphila CIP107961, but not L. rhamnosus GG, which may be clinically relevant when selecting probiotics for treating HFHC-derived pathologies.
In conclusion, the microbiota and cognition are intimately connected through the gut–brain axis, and in HFHC pathologies they can be influenced by environmental enrichment and A. muciniphila CIP107961 administration. Cognitive improvement was accompanied by changes in brain metabolic activity and gut microbial composition analysis, pointing to specific microbiota targets for intervention in diet-induced pathologies. However, some mechanisms other than major changes in microbiota composition and the combined effect of environmental enrichment and A. muciniphila administration, which we identified in this study, may also be biologically relevant and will need to be investigated in future studies due to their relative contributions to the selection of effective treatments for patients.