Exercise alters brain chemistry to protect aging synapses

Enhanced nerve transmission seen in older adults who remained active

January 7, 2022

Science Daily/University of California - San Francisco

When elderly people stay active, their brains have more of a class of proteins that enhances the connections between neurons to maintain healthy cognition, a UC San Francisco study has found.

This protective impact was found even in people whose brains at autopsy were riddled with toxic proteins associated with Alzheimer's and other neurodegenerative diseases.

"Our work is the first that uses human data to show that synaptic protein regulation is related to physical activity and may drive the beneficial cognitive outcomes we see," said Kaitlin Casaletto, PhD, an assistant professor of neurology and lead author on the study, which appears in the January 7 issue of Alzheimer's & Dementia: The Journal of the Alzheimer's Association.

The beneficial effects of physical activity on cognition have been shown in mice but have been much harder to demonstrate in people.

Casaletto, a neuropsychologist and member of the Weill Institute for Neurosciences, worked with William Honer, MD, a professor of psychiatry at the University of British Columbia and senior author of the study, to leverage data from the Memory and Aging Project at Rush University in Chicago. That project tracked the late-life physical activity of elderly participants, who also agreed to donate their brains when they died.

"Maintaining the integrity of these connections between neurons may be vital to fending off dementia, since the synapse is really the site where cognition happens," Casaletto said. "Physical activity -- a readily available tool -- may help boost this synaptic functioning."

More Proteins Mean Better Nerve Signals

Honer and Casaletto found that elderly people who remained active had higher levels of proteins that facilitate the exchange of information between neurons. This result dovetailed with Honer's earlier finding that people who had more of these proteins in their brains when they died were better able to maintain their cognition late in life.

To their surprise, Honer said, the researchers found that the effects ranged beyond the hippocampus, the brain's seat of memory, to encompass other brain regions associated with cognitive function.

"It may be that physical activity exerts a global sustaining effect, supporting and stimulating healthy function of proteins that facilitate synaptic transmission throughout the brain," Honer said.

Synapses Safeguard Brains Showing Signs of Dementia

The brains of most older adults accumulate amyloid and tau, toxic proteins that are the hallmarks of Alzheimer's disease pathology. Many scientists believe amyloid accumulates first, then tau, causing synapses and neurons to fall apart.

Casaletto previously found that synaptic integrity, whether measured in the spinal fluid of living adults or the brain tissue of autopsied adults, appeared to dampen the relationship between amyloid and tau, and between tau and neurodegeneration.

"In older adults with higher levels of the proteins associated with synaptic integrity, this cascade of neurotoxicity that leads to Alzheimer's disease appears to be attenuated," she said. "Taken together, these two studies show the potential importance of maintaining synaptic health to support the brain against Alzheimer's disease."

https://www.sciencedaily.com/releases/2022/01/220107100955.htm

Brain function boosted by daily physical activity in middle-aged, older adults

January 31, 2022

Science Daily/University of California - San Diego

A new study by researchers at University of California San Diego School of Medicine adds to the canon of research associating physical activity with cognitive performance, this time using 90 middle-aged and older subjects who wore accelerometers while physically active and completed mobile cognitive testing from home.

"The future of lifestyle interventions really needs to be remote-based," said Raeanne Moore, PhD, associate professor in the Department of Psychiatry at UC San Diego School of Medicine and principal investigator of the study. "The pandemic has made this especially clear."

On the days their physical activity increased, the study found, the 50- to 74-year-old participants performed more effectively on an executive function task, and on the days when their physical activity decreased, so too did their cognitive performance.

The findings published Jan. 31, 2022 in the journal JMIR mHealth and uHealth.

"It was a very linear relationship," Moore said. "We hypothesized that we would find this, but we couldn't be sure because we weren't telling people to increase their physical activity. They just did what they do every day."

First author Zvinka Zlatar, PhD, a clinical psychologist at UC San Diego School of Medicine, added: "Future interventions, in which we ask people to increase their physical activity, will help us determine if daily changes in physical activity lead to daily gains in cognition measured remotely or vice versa."

The correlation between physical activity and cognition remained when adjustments were made for various co-morbidities, such as HIV status, age, sex, education and race/ethnicity. But it held only for persons who function dependently -- who rely on others to perform the tasks of daily living, such as managing household activities or paying the bills.

"For them, physical activity may have a greater benefit on daily, real-world cognitive performance," Moore said, a finding consistent with research into Alzheimer's disease and related dementias.

Though it didn't fall within the purview of this study, Moore speculated that, because functionally independent adults likely perform more cognitively stimulating and social activities, which are known to have positive impacts on brain health, physical activity may have less of an impact on cognition.

Moore and Zlatar said their work has implications for the development of novel digital health interventions to preserve brain health in aging.

"We don't know yet if there's a cumulative, long-term effect to these small daily fluctuations in cognition," Zlatar said. "That's something we plan to study next -- to see if performing physical activity at different intensities over time, in unsupervised settings, can produce long-term improvements in brain health and sustained behavior change."

https://www.sciencedaily.com/releases/2022/01/220131164208.htm

Change of heart? It may affect thinking and memory skills in middle age

January 26, 2022

Science Daily/American Academy of Neurology

Subtle changes in the structure and the diastolic function of a person's heart between early adulthood and middle age may be associated with a decline in thinking and memory skills. The research is published in the January 26, 2022, online issue of Neurology®, the medical journal of the American Academy of Neurology. The diastolic function of the heart is when it rests between beats and the chambers fill with blood.

"Cardiovascular risk factors such as high blood pressure, high cholesterol and diabetes have been associated with an increased risk for cognitive impairment, but much less is known about heart structure and function and the risks for cognition," said study author Laure Rouch, PharmD, PhD, of the University of California, San Francisco. "We followed young adults for 25 years into middle age and found declines in thinking and memory skills independent of these other risk factors. Our findings are of critical importance in the context of identifying potential early markers in the heart of increased risk for later-life cognitive decline. Such abnormalities are common and often underdiagnosed as they do not produce any obvious symptoms."

The study looked at 2,653 people with an average age of 30. Participants had echocardiograms, ultrasound images of the heart, at the start of the study and again 20 and 25 years later. Echocardiograms are non-invasive and widely available.

Researchers used the images to measure the following: the weight of the left ventricle, one of four chambers of the heart; the volume of the blood that filled the left ventricle when pumping; and how well the left ventricle pumped blood to the body, specifically the percentage of blood pumped out of the heart.

Researchers found over 25 years, there was an average increase in the weight of the left ventricle of 0.27 grams per square meter per year (g/m2), with average weight of 81 g/m2 in the first year and 86 g/m2 in the last year. There was also an average increase in left atrial volume of 0.42 milliliters of blood per square meter (mL/m2) with average volume of 16 mL/m2 in the first year and 26 mL/m2 in the last year.

In the last year of the study, participants were given six cognitive tests to measure thinking and memory skills including global cognition, processing speed, executive function, delayed verbal memory and verbal fluency. Tests included tasks like recalling words from a list 10 minutes after looking at the list, as well as substituting symbols for numbers using a key at the top of the page.

After adjusting for factors like age, sex and education, researchers found that a greater than average increase from early to middle adulthood in the weight of a person's left ventricle was associated with lower midlife cognition on most tests.

Tests included a common dementia test that asks participants to do tasks like draw lines connecting alternating letters and numbers, and repeat five words, complete other tasks, and then repeat the same five words. Scores range from zero to 30 with 26 and higher representing normal cognition. Participants with a greater than average midlife increase in left ventricle weight had an average score of 22.7 while those without a greater than average increase in weight had an average score of 24.

Researchers also found a greater than average increase from early to middle adulthood in left atrial volume was associated with lower midlife global cognition.

However, a greater than average decrease in the percentage of blood pumped out of the left ventricle was not associated with cognition.

"What is interesting is that our results were similar after adjusting for cardiovascular risk factors such as high blood pressure, diabetes, smoking and obesity," Rouch said. "As early as young adulthood, even before the occurrence of cardiovascular disease, there may be heart abnormalities that could be risk markers for lower thinking and memory skills in middle age. In the future, a single echocardiogram may help identify people at higher risk of cognitive impairment."

Rouch said that future research should determine whether interventions to improve the structure and function of the heart could benefit brain health. She said, "The question of whether altered cardiac structure and function could be a risk factor for cognitive impairment has major public health implications and could reveal another important heart-brain connection."

A limitation of the study is echocardiograms were performed up to 25 years apart using slightly different procedures and equipment, which may make the data hard to compare.

https://www.sciencedaily.com/releases/2022/01/220126165518.htm

Study now links non-mutated Apolipoprotein E to dementia in the aging brain

January 26, 2022

Science Daily/Elsevier

Researchers exploring dementia-related proteins in the brain identified Apolipoprotein E (ApoE) as a key misfolded protein. About 25% of individuals, and 50% of individuals with Alzheimer disease, have a genetic mutation, the APOE ε4 allele -- a known risk factor for the disease. The researchers were surprised to find that even in the brains of patients without the disease-driving APOE ε4 allele, ApoE proteins were strongly enriched in dementia. Their findings appear in The American Journal of Pathology, published by Elsevier.

"Dementia is very complex, but you can simplify it: the disease is caused by 'gloppy proteins' in the brain," explained lead investigator Peter T. Nelson, MD, PhD, Sanders-Brown Center on Aging and Department of Pathology, University of Kentucky, Lexington, KY, USA. "I'm not making light of it -- these 'sticky' misfolded proteins often end up destroying the brain, the mind, the memories and everything else for millions of people who suffer from dementia. We want to understand specifically which proteins are the problem."

The investigators used mass spectrometry to characterize the complete set of proteins, or proteome, from the amygdalae of 40 participants from the University of Kentucky Alzheimer's Disease Center autopsy cohort. The amygdala is vulnerable to mis-aggregated proteins associated with dementia and is often affected even at the earliest stages of disease. The subjects ranged from cognitively normal to severe amnestic dementia. Although previous studies have examined the human amygdala proteome, none have reported on a sample of this size with dementia subjects and control subjects for comparison.

As anticipated, portions of proteins previously associated with neurodegenerative diseases were found in the brains of patients with dementia, including proteins called Tau (associated with neurofibrillary tangles), Aβ (associated with amyloid plaques), and α-Synuclein (associated with Lewy Body disease). Aβ and α-Synuclein correlated strongly with clinical diagnosis of dementia. Tau and Aβ proteins, but not α-Synuclein, were occasionally detectible in cognitively normal subjects and those with mild cognitive impairment. Overall, Dr. Nelson observes, the findings for these proteins were in line with expectations.

The data also revealed a close correlation between dementia diagnosis and the detection of ApoE peptides in the brain. The correlation with dementia for ApoE was even stronger than that seen for Tau, Aβ, or α-Synuclein. Moreover, the ApoE peptides were significantly enriched even in dementia patients who lack the APOE ε4allele. The results emphasize the relevance of the ApoE protein as an aberrantly aggregated protein in its own right, rather than just an "upstream" genetic risk factor.

"Our study adds to an evolving appreciation of multiple misfolded proteins in the human brain and moves the field forward by emphasizing that ApoE may be a stong contributor to the dementia prototype, even in individuals who do not have the disease-driving version of the APOE gene," said Dr. Nelson. "Even in persons lacking the APOE ε4 allele, ApoE may indeed be among the most impactful 'gloppy proteins' in aging brains."

https://www.sciencedaily.com/releases/2022/01/220126122408.htm

Seeing the same GP improves treatment for people with dementia

January 24, 2022

Science Daily/University of Exeter

People with dementia who see the same GP each time have lower rates of health complications and fewer emergency hospital admissions, according to a new study.

The research, led by the University of Exeter and published in the British Journal of General Practice (BJGP) analysed more than 9,000patient records of people diagnosed with dementia in the Clinical Practice Research Datalink. The team found that people with dementia who were consistently seen by the same GP over the course of one year were given fewer medicines and were less likely to be given medicines that can cause problems like incontinence, drowsiness and falls. Those seeing the same GP over time were 35 per cent less likely to develop delirium, a state of confusion commonly experienced in dementia. Those who consistently saw the same GP were also 58 per cent less likely to experience incontinence, and almost ten per cent less likely to have an emergency hospitalisation, compared to those who had the most variation in GPs treating them.

The research was conducted in anonymised patient records of people with dementia aged 65 and over in 2016, who were followed-up for one year. This study includes people who visited a GP at least three times in the previous year.

Lead author Dr João Delgado, of the University of Exeter, said: "The number of people with dementia has been rising steadily and it is now one of the leading causes of death in the UK. In the absence of a cure, long-term care is particularly important. Treating people with dementia can be complex, because it often occurs together with other common diseases. Our research shows that seeing the same general practitioner consistently over time is associated with improved safe prescribing and improved health outcomes. This could have important healthcare impacts, including reduced treatment costs and care needs."

Delirium (an episode of more severe confusion) is common in dementia, and patients who develop delirium are more likely to die. Delirium and incontinence are very distressing for individuals, and require additional NHS resource. Extra hospital admissions are a high cost for the NHS.

Sir Denis Pereira Gray, co-author and GP researcher at the St Leonard's Practice, said: "These new findings show that GP continuity is associated with important benefits for patients. Whilst national policy makers have for years discouraged continuity, general practices can still provide good GP continuity through their internal practice organisation, for example, by using personal lists."

Dr Richard Oakley, Associate Director of Research at Alzheimer's Society said: "For the 900,000 people living with dementia in the UK, it's likely dementia isn't the only condition they're getting treatment for.

"It's clear from this study that consistently seeing the same GP has real benefits for people living with dementia -- better management and treatment of conditions, and lower risk of complications like delirium and incontinence, leading to improved quality of life.

"The pandemic has put GP services under immense pressure, so while we might not be able to get consistent GP care for everyone with dementia tomorrow, policymakers should absolutely be working with the NHS to build this into their plans as we emerge from the pandemic."

https://www.sciencedaily.com/releases/2022/01/220124194931.htm

Dementia: How to prevent cognitive decline

January 20, 2022

Science Daily/University of Montreal

Physical activity, nutrition and cognitively stimulating activities are all known to be good ways to prevent Alzheimer's disease and dementia. And older adults at risk can access a variety of lifestyle services to that end, including diet regimes and exercises for their body and mind.

Now an international team of researchers led by Université de Montréal psychology professor Sylvie Belleville has determined how many of those intervention sessions are needed prevent cognitive decline in people at risk: only about a dozen.

Published in Alzheimer's & Dementia : The Journal of the Alzheimer's Association, the study by Dr. Belleville and colleagues at the universities of Toulouse and Helsinki show that 12 to 14 sessions are all that's were needed to observe an improvement in cognition. Until now, the number of sessions or "doses" needed for optimal effect has been unknown.

"In pharmacological studies, every effort is made to define an optimal treatment dose needed to observe the expected effects, " said Belleville, a neuropsychologist and researcher at the research centere of the UdeM-affiliated Institut universitaire de gériatrie de Montréal. "This is rarely done in non-pharmacological studies, especially those on the prevention of cognitive decline, where little information is available to identify this dose.

"Defining an optimal number of treatment sessions is therefore crucial.," she continued. "Indeed, proposing too few sessions will produce no noticeable improvement effects, but too many sessions is also undesirable as these interventions are costly. They are costly both for the individual who follows the treatments, in terms of time and involvement, and for the organization offering these treatments."

The study is based on a secondary analysis of data from the three-year Multidomain Alzheimer Preventive Trial (MAPT) and looked at 749 participants who received a range of interventions aimed at preventing cognitive decline. These included dietary advice, physical activity and cognitive stimulation to improve or maintain physical and cognitive abilities.

People's individuality important

In their research, Belleville's team noted that people's individuality should be considered when determining the optimal treatment dose.

In their study, the researchers evaluated the effects of the sessions in terms of each participant's age, gender, education level, and cognitive and physical condition. The relationship between the "dose" each received and their cognitive improvement was then analyzed.

The main results show an increase with dose followed by a plateau effect after 12 to 14 sessions. In other words, you need enough dose to see an effect but offering more than 12 to 14 sessions of treatment does not mean better results. That said, participants with lower levels of education or more risk factors for frailty did benefit from more sessions.

The conclusion? It's important to identify and target an optimal dose and to customize the treatment for each individual, the researchers say. Not only is "dosage" an important component of behavioural interventions, it can also provide valuable information when time and money are limited, helping public-health agencies develop effective prevention programs and offer guidance to older adults and clinicians.

https://www.sciencedaily.com/releases/2022/01/220120091141.htm

Study may help clinicians use sleep brain wave patterns to diagnose dementia and other forms of cognitive impairment

Researchers define parameters for automated detection methods.

January 12, 2022

Science Daily/Massachusetts General Hospital

Certain brain wave patterns that occur while an individual sleeps may be assessed by clinicians to help them diagnose dementia and other conditions related to memory, language, and thinking. A new study published in Sleep that was led by investigators at Massachusetts General Hospital (MGH) and Beth Israel Deaconess Medical Center (BIDMC) could help improve automated methods for detecting these brain wave patterns, or sleep spindles, and for correlating them with cognitive function.

Sleep spindles are bursts of brain activity that occur during non-REM sleep and can be assessed through electroencephalograms (EECs) involving non-invasive electrodes placed on the scalp. Spindles are considered a "fingerprint" that vary among individuals, are highly heritable, and tend to be consistent from night to night.

"With the rising burden of neurodegenerative disease, there is a pressing need for a sensitive biomarker of cognition. This has led to a surge of research examining sleep spindles, an oscillatory pattern of brain activity observed during sleep, and their role in various neuropsychiatric conditions and cognitive performance," says lead author Noor Adra, a clinical research coordinator at MGH.

Although sleep spindles and other brain features represent promising potential electrophysiologic markers of neurodegenerative and psychiatric diseases, detecting and assessing sleep spindles is not straightforward. "People have already known that these transient high frequency events during sleep in the brain are closely linked to cognition, especially to learning and memory. But when you try to detect spindles among more than 100 sleep recordings, things become less clear -- such as what is the best threshold, what is the best minimum duration, etc.," says co-author Haoqi Sun, PhD, an investigator in the department of Neurology at MGH.

Sleep spindles are typically analyzed through visual inspection of EEGs, but automated methods can offer more consistent results. No consensus exists for parameters for such automated methods, however.

To address these issues, the investigators designed sleep-related experiments involving 167 adults to characterize how spindle detection parameter settings influence the association between spindle features and cognition and identified parameters that best correlate with cognitive performance.

The team also found that sleep spindles were most strongly linked with what's known as fluid intelligence, which relies on abstract thinking and problem-solving skills and declines during early stages of dementia. "Therefore, our findings support sleep spindles as a sleep-based biomarker of fluid cognition," says Adra. "By optimizing the detection of this proposed sleep-based biomarker of cognition, we hope to guide future studies that examine the sensitivity of this biomarker in neurodegenerative populations."

"Sleep spindles are one among many important measurable features of brain activity during sleep that provide a window into the brain's current state of health and individuals' risk for developing brain disease or cognitive decline. Now that we better understand how to measure sleep spindles, we can add these into a growing arsenal of brain health indicators that can be measured during sleep," adds co-senior author M. Brandon Westover, MD, PhD, an investigator in the department of Neurology at MGH and director of Data Science at the MGH McCance Center for Brain Health. "These indicators will be essential tools in our quest to develop treatments that can preserve and enhance brain heath."

https://www.sciencedaily.com/releases/2022/01/220112105627.htm

Remembering faces and names can be improved during sleep

Research finds memory reactivation — combined with quality sleep — is key

January 12, 2022

Science Daily/Northwestern University

For those who rarely forget a face, but struggle with names, the remedy for boosting learning may as near as your pillow.

New research by Northwestern University is the first to document the effect reactivating memory during sleep has on face-name learning.

The researchers found that people's name recall improved significantly when memories of newly learned face-name associations were reactivated while they were napping. Key to this improvement was uninterrupted deep sleep.

"It's a new and exciting finding about sleep, because it tells us that the way information is reactivated during sleep to improve memory storage is linked with high-quality sleep," said lead author Nathan Whitmore, a Ph.D. candidate in the Interdepartmental Neuroscience Program at Northwestern.

The paper, "Targeted memory reactivation of face-name learning depends on ample and undisturbed slow-wave sleep," will publish Jan. 12 in the Nature partner journal NPJ: Science of Learning.

The paper's senior author is Ken Paller, professor of psychology and director of the Cognitive Neuroscience Program at Weinberg College of Arts and Sciences at Northwestern. The paper was also co-authored by Adrianna Bassard, Ph.D. candidate in psychology at Northwestern.

The research team found that for study participants with EEG measures (a recording of electrical activity of the brain picked up by electrodes on the scalp) that indicated disrupted sleep, the memory reactivation didn't help and may even be detrimental. But in those with uninterrupted sleep during the specific times of sound presentations, the reactivation led to a relative improvement averaging just over 1.5 more names recalled.

The study was conducted on 24 participants, aged 18-31 years old, who were asked to memorize the faces and names of 40 pupils from a hypothetical Latin American history class and another 40 from a Japanese history class. When each face was shown again, they were asked to produce the name that went with it. After the learning exercise, participants took a nap while the researchers carefully monitored brain activity using EEG measurements. When participants reached the N3 "deep sleep" state, some of the names were softly played on a speaker with music that was associated with one of the classes.

When participants woke up, they were retested on recognizing the faces and recalling the name that went with each face.

The researchers say the finding on the relationship between sleep disruption and memory accuracy is noteworthy for several reasons.

"We already know that some sleep disorders like apnea can impair memory," said Whitmore. "Our research suggests a potential explanation for this -- frequent sleep interruptions at night might be degrading memory."

The lab is in the midst of a follow-up study to reactivate memories and deliberately disrupt sleep in order to learn more about the relevant brain mechanisms.

"This new line of research will let us address many interesting questions -- like whether sleep disruption is always harmful or whether it could be used to weaken unwanted memories," said Paller, who also holds the James Padilla Chair in Arts & Sciences at Northwestern. "At any rate, we are increasingly finding good reasons to value high-quality sleep."

https://www.sciencedaily.com/releases/2022/01/220112094000.htm

Keeping active through varied activities can reduce risk of developing dementia

December 17, 2021

Science Daily/Simon Fraser University

Older adults who participate in a variety of different activities are able to reduce their risk of developing dementia, according to a new study from researchers at Simon Fraser University.

The team found that engaging in a combination of hobbies, such as light exercise and connecting with loved ones, can reduce memory decline in adults between the ages of 65 and 89 more than any individual activity.

Their findings, published in the journal Aging show that the effects of engaging in a combination of activities increased with age and was more impactful than historical factors such as education level or baseline memory.

The study examined data from the National Institute on Aging's Health and Retirement Study and included 3,210 participants aged 65 to 89. Study participants were asked how often they engaged in 33 activities from 'never' to 'at least once a month' to 'several times a month' up to 'daily'.

Researchers created a machine learning model to analyze the activities' impact on memory. The activities ranged from hobbies such as baking or cooking, reading, playing cards and games to walking for 20 minutes, or socializing with family and friends through letters, email, phone calls or in-person visits.

"Our study results show that the risk of developing dementia can be reduced through a combination of active, daily activities -- things like using a computer and playing word games," says study co-author Sylvain Moreno, an associate professor at SFU's School of Interactive Arts and Technology (SIAT) and CEO/scientific director of the Digital Health Circle, based at SFU.

"Scientists believed that genetics were the main factor influencing cognitive health but our findings show the reverse. With age, your choice of daily activities is more important than your genetics or your current cognitive skills," Moreno adds.

The researchers suggest their study results could have a significant impact on aging health policies, including promoting new social prescribing programs to help older adults keep mentally active into their senior years.

Social prescribing involves connecting older adults to a range of activities in the community such as gardening, art classes or volunteering.

Older adults are more at risk of developing dementia and other neurodegenerative disorders for which there is no cure, which is why prevention is so important.

"Today, around 55 million people have dementia and this number will almost triple by 2050 with an aging population," says Moreno. "Care for patients with dementia is challenging, labour-intensive, and chronic, which generates high costs for health systems."

Their research demonstrates that strategies for prevention are effective and a social prescribing approach to healthcare can help people maintain healthy cognitive function as they age.

https://www.sciencedaily.com/releases/2021/12/211217102857.htm

Cataract surgery linked with lessened dementia risk

December 6, 2021

Science Daily/University of Washington School of Medicine/UW Medicine

Cataracts affect most older adults at risk for dementia, and now researchers are finding strong evidence that cataract surgery is associated with a lower risk of developing dementia.

The Adult Changes in Thought (ACT) study is a long-standing, Seattle-based observational study at Kaiser Permanente Washington of more than 5,000 participants older than 65. Based on the longitudinal data of over 3,000 ACT study participants, researchers have now found that subjects who underwent cataract surgery had nearly 30% lower risk of developing dementia from any cause compared with those who did not. This lowered risk persisted for at least a decade after surgery. Cataract surgery was also associated with lower risk of Alzheimer disease dementia specifically. The results were reported Dec. 6 in JAMA Internal Medicine.

Lead researcher Dr. Cecilia S Lee, associate professor and Klorfine Family Endowed Chair in ophthalmology at the University of Washington School of Medicine, said the observational study adjusted for a number of potential confounders, yet still yielded a strong association.

"This kind of evidence is as good as it gets in epidemiology," Lee said. "This is really exciting because no other medical intervention has shown such a strong association with lessening dementia risk in older individuals."

The mechanisms by which cataract surgery and lessened dementia risk are associated was not determined in this study. Researchers hypothesize that people may be getting higher quality sensory input after cataract surgery, which might have a beneficial effect in reducing the risk of dementia.

"These results are consistent with the notion that sensory input to the brain is important to brain health," said co-author Dr. Eric B. Larson, a principal investigator of the ACT study, and senior investigator at Kaiser Permanente Washington Health Research Institute.

Lee said another hypothesis is that after cataract surgery, people are getting more blue light.

"Some special cells in the retina are associated with cognition and regulate sleep cycles, and these cells respond well to blue light," she said, "Cataracts specifically block blue light, and cataract surgery could reactivate those cells."

The study results highlight a strong case for further research on the eye-brain connection in dementia. Previous studies by Lee's group at the UW have shown a strong link between other retinal diseases, such as age-related macular degeneration, and the development of Alzheimer disease and dementia. Subjects with macular degeneration or other retinal degenerative diseases are more likely to develop dementia, In the current study, subjects undergoing vision-improving cataract surgery had lower risk of developing dementia. Further understanding the connection between the aging eye and brain may offer insights and potential therapies to slow or prevent age-related dementia.

The study: Researchers tracked participants diagnosed with a cataract or glaucoma but who did not have dementia at the time they volunteered for the study. Participants also did not have cataract surgery at the time of enrollment. Participants are evaluated every two years for cognitive abilities based on the Cognitive Abilities Screening Instrument, which scores in a range from 0-100. Participants with scores less than 85 undergo further neurological tests.

During follow-up of 3,038 participants (an average of 7.8 years per person), 853 subjects developed dementia, with 709 cases of Alzheimer disease. Approximately half of the participants (1,382 individuals or 45%) had cataract surgery. Analysis for risk of developing dementia showed that subjects who had undergone cataract surgery in either eye were about 30% less likely to develop any form of dementia for at least 10 years after their surgery.

Analysis was adjusted for an extensive list of factors including health-related confounders. Cataract surgery could appear to have a protective effect due to a healthy patient bias, where participants who underwent cataract surgery might have been healthier and at lower dementia risk. Researchers performed analyses to account for several types of potential bias, but still found strong associations when these factors were accounted for.

Researchers excluded eye surgeries in the two years prior to dementia diagnosis to rule out the possibility that people with cognitive decline prior to dementia diagnosis may have been less conscious of vision issues, and thus less likely to have undergone cataract surgery. Even with this group excluded, the researchers found lower risks of dementia associated with cataract surgery.

As another control, participants were also evaluated for a possible link between another type of eye surgery (glaucoma surgery) and dementia. In this case, no association was found.

Strengths of study: This was a community-based, prospective cohort study with more than 23,000 person-years of follow up. More than 98% of the ACT cohort were seen at least once by eye care clinicians, with an average of 27 encounters. Dementia diagnoses were made by a panel of experts using research criteria. The possibility of healthy patient bias and potential confounders were thoroughly investigated.

Limitations of study: Results could be explained by unmeasured or residual confounding factors, like any observational study. There could be coding errors for cataract diagnosis. Only the participant's first cataract surgery was evaluated so researchers don't know whether subsequent surgeries impacted dementia risk. The majority of the study population was White, and it is unclear if the effect would be observed in all populations.

"Innovative research like Dr. Lee's is helping to uncover how age-related changes in our senses contribute to dementia," said Dr. Howard Fillit, founding executive director and chief science officer of the Alzheimer's Drug Discovery Foundation (ADDF), a nonprofit dedicated solely to accelerate the discovery and development of drugs to treat and prevent Alzheimer's disease and related dementias.

https://www.sciencedaily.com/releases/2021/12/211206113004.htm

Elevated heart rate linked to increased risk of dementia

December 3, 2021

Science Daily/Karolinska Institutet

Having an elevated resting heart rate in old age may be an independent risk factor of dementia, according to a study at Karolinska Institutet in Sweden published in the journal Alzheimer's & Dementia: The Journal of the Alzheimer's Association. Since resting heart rate is easy to measure and can be lowered through exercise or medical treatment, the researchers believe that it may help to identify people with higher dementia risk for early intervention.

The number of people living with dementia is expected to increase to 139 million globally by 2050, from 55 million in 2020, according to the organisation Alzheimer's Disease International. Currently, there is no cure for dementia, but growing evidence suggests that maintaining a healthy lifestyle and cardiovascular health could help delay the onset of dementia and ease symptoms.

In this study, the researchers examined if resting heart rate in 2,147 individuals 60 years old or older and living in Stockholm could be linked to dementia and cognitive decline independent of other known risk factors, such as cardiovascular disease.

The study, which followed the participants for up to 12 years, showed that individuals with a resting heart rate of 80 beats per minute or higher on average had 55 percent higher risk of dementia than those with a heart rate of 60-69 beats per minute. The association remained significant after adjusting for potential confounders such as various cardiovascular diseases. Still, the researchers caution that the result may have been affected by undetected cardiovascular events and the fact that more participants with cardiovascular disease died during the follow-up period and thus didn't have time to develop dementia.

The study cannot establish a causal relationship, but the researchers offer several plausible explanations for the association, including the effect of underlying cardiovascular diseases and cardiovascular risk factors, stiffened arteries, and imbalance between sympathetic and parasympathetic nerve activities.

"We believe it would be valuable to explore if resting heart rate could identify patients with high dementia risk," says the study's leading author Yume Imahori, a researcher at the Department of Neurobiology, Care Sciences and Society, Karolinska Institutet. "If we follow such patients' cognitive function carefully and intervene early, the onset of dementia might be delayed, which can have a substantial impact on their quality of life."

The study was led by senior lecturer Dr Chengxuan Qiu and the data was derived from the Swedish National study on Aging and Care in Kungsholmen (SNAC-K).

The research was funded by the Swedish Ministry of Health and Social Affairs, the Swedish Research Council, the Swedish Research Council for Health, Working Life and Welfare, the Swedish Foundation for International Cooperation in Research and Higher Education, Karolinska Institutet and the European Union.

https://www.sciencedaily.com/releases/2021/12/211203081519.htm

Potential new treatment for Alzheimer’s disease would be relatively cheap

November 30, 2021

Science Daily/RIKEN

Researchers at the RIKEN Center for Brain Science (CBS) in Japan have discovered that the protein α-endosulfine (ENSA) is involved in the development of Alzheimer's disease. Studies in mice showed that eliminating this protein entirely or using drugs to block its function reduced physical changes in the brain associated with the disease and improved memory. Drug therapy that aims to block ENSA activity could be a more effective treatment than what is currently available, as well as being cheaper. This study was published in the scientific journal Molecular Psychiatry.

The hallmark of Alzheimer's disease in the brain is the accumulation of amyloid β peptide (Aβ). For years, researchers have been trying to determine how and why this happens. Takaomi Saido and his team at RIKEN CBS have developed a mouse model of the disease that shows both Aβ accumulation and memory deficits similar to what is seen in humans. Using this model mouse, they have already discovered a series of events in the brain that lead to the formation of Aβ plaques. Key among them is reduced levels of the enzyme neprilysin, which itself is caused by reduced levels of the hormone somatostatin. Levels of both neprilysin and somatostatin go down as we age, which can explain why Alzheimer's disease usually strikes older people.

The new study focused on treating Alzheimer's disease in mice by figuring out how somatostatin controls neprilysin levels in the brain. According to first author Naoto Watamura, "the first step in this process was actually the most difficult because we had to develop an in vitro system that could screen for neprilsyin regulators in conditioned medium generated by hippocampal neurons." Once they accomplished this, they were able to identify ENSA as the regulator. Testing showed that ENSA reduced neprilysin activity and that it rose to abnormally high levels in the brains of mice that lacked somatostatin. This means that somatostatin normally keeps ENSA in check, which in turn keeps neprilsyin levels high, allowing Aβ to be destroyed before it accumulates.

Next the team focused on ENSA in living animals. Using CRISPR technology, they created ENSA knockout mice and then bred them with the Alzheimer's disease model mice. Aβ accumulation in these new mice was much lower than in the original model mice, indicating that abnormally high levels of ENSA could be an as yet unidentified symptom or biomarker of Alzheimer's disease. This was confirmed when the researchers detected high level of ENSA in the model mice and in the brains of people with Alzheimer's disease.

What exactly is ENSA doing in the brain? Tests showed that ENSA blocks a potassium channel in the hippocampus, a part of the brain needed for making and recalling memories. "Because we got the same results from blocking the KATP channel as we did from the ENSA knockout mice," says Watamura, "we reasoned that helping the channel stay open would combat the excess ENSA that we observed in Alzheimer's disease." To test this theory, the researchers fed the model mice with diazoxide -- a drug that activates the KATP channel -- and tested their memory. They found that while the untreated Alzheimer's disease model mice exhibited their characteristically poor memory, the treated model mice performed just as well as normal mice. A look at the brains of the treated mice showed that they lacked the hallmark Aβ plaques.

"Our findings point directly to a potential way of preventing and treating Alzheimer's disease," says Watamura. "On top of that, compared with Aβ-targeting immunotherapy, such as the drug aducanumab, which was recently approved by the FDA, synthetic agonists for the KATP channel are less expensive and would be more acceptable to aging societies around the world."

https://www.sciencedaily.com/releases/2021/11/211130101245.htm

Starting physical activity three days post-concussion is safe, has better outcomes

January 26, 2022

Science Daily/University of Ottawa

Resuming non-contact physical activity 72 hours after a concussion is safe, and may also reduce symptoms and the risk of delayed recovery, suggests the first and largest real-world, randomized clinical trial on the topic to be conducted with children and youth aged 10 to 18.

Led by researchers at the CHEO Research Institute, the multi-site study was published by the British Journal of Sports Medicine, the world’s leading journal in the field. Previous randomized clinical trials have been smaller in nature, conducted in the lab or only used a sport-related population.

“The findings of this study should give every health-care professional who manages kids with concussions the confidence to prescribe early and controlled return to physical activity, even if they have symptoms,” said Andrée-Anne Ledoux, the study’s corresponding author and a scientist at the CHEO Research Institute, a pediatric health-care and research centre in Ottawa, Canada.

“The study confirms that early return to physical activity is safe, can reduce concussion symptoms and reduces the rate of delayed recovery,” added Ledoux, who is also an assistant professor at the University of Ottawa. “Gone are the days of resting in a dark room.”

Called PedCARE, the clinical trial divided 456 participants into two groups. One group rested until symptom resolution after their concussion and the second group started to re-introduce physical activity 72 hours after the concussion, according to a set protocol. They regularly answered a standard survey about their symptoms and their activity levels were recorded using an accelerometer.

At two weeks, symptoms were comparable between both groups, which means that early physical activity was not harmful. When examining results of everyone who stayed within the prescribed level of activity, those who re-introduced physical activity early showed improved symptoms and a reduced rate of delayed recovery, when compared to those who rested until they were symptom free.

The study sets out guidelines for gradually introducing physical activity back into the daily routine of a child or youth. For example, at 72 hours after the injury, the youth should start walking for 15 minutes at a moderate level. If symptoms are tolerable the youth should increase their physical activity intensity the next day, for example, light jogging. If symptoms are not tolerable while doing physical activity or after physical activity, the next day the child or youth should return to the last well-tolerated physical activity intensity and re-attempt progression after 24 hours. They must be cleared by their primary care provider before returning to contact sports.

https://www.sciencedaily.com/releases/2022/01/220126165529.htm

Anxiety and PTSD linked to increased myelin in brain's gray matter

Resilience to stress and differential symptoms correlate with regional changes in the brain

January 7, 2022

Science Daily/University of California - Berkeley

A recent study links anxiety behavior in rats, as well as post traumatic stress disorder (PTSD) in military veterans, to increased myelin -- a substance that expedites communication between neurons -- in areas of the brain associated with emotions and memory.

The results, reported by scientists at the University of California, Berkeley, and UC San Francisco (UCSF), provide a possible explanation for why some people are resilient and others vulnerable to traumatic stress, and for the varied symptoms -- avoidance behavior, anxiety and fear, for example -- triggered by the memory of such stress.

If, as the researchers suspect, extreme trauma causes the increased myelination, the findings could lead to treatments -- drugs or behavioral interventions -- that prevent or reverse the myelin production and lessen the aftereffects of extreme trauma.

Myelin is a layer of fatty substances and proteins that wraps around the axons of neurons -- essentially, the insulation around the brain's wiring -- to facilitate long-distance transmission of signals and, thus, communication between distant areas of the brain. The inner regions of the brain look white -- in fact, they are referred to as "white matter" -- because of the myelin encasing the many large bundles of axons there.

But the new study finds increased myelination of axons in so-called "gray matter," where most of the cell bodies of neurons reside and most of the wiring is less insulated with myelin. The extra myelination was found primarily in areas associated with memory.

Researchers at the San Francisco Veterans Affairs Medical Center conducted brain MRI scans of 38 veterans -- half with PTSD, half without -- and found an increase in myelination in the gray matter of those with PTSD compared to that seen in the brains of those not suffering from PTSD.

Colleagues at UC Berkeley, meanwhile, discovered a similar increase in myelination in the gray matter of adult rats subjected to an acute stressful event. While not all rats showed long-term effects from the stress -- just as not all traumatized veterans develop PTSD -- those that did had increased myelination in specific areas of the brain associated with particular symptoms of stress that was identical to what UCSF physicians found in veterans with PTSD.

Both veterans with PTSD and stressed rats that exhibited avoidance behavior, for example, had increased myelination in the hippocampus, often thought of as the seat of memory. Those exhibiting a fear response had increased myelination in the amygdala, which plays a key role in our response to strong emotions, such as fear or pleasure. Those suffering from anxiety had increased myelination in the dentate gyrus, a region critical to learning and memory.

"The combination of these studies in rats with our population of veterans with post traumatic stress disorders is, to me, really exciting," said senior author Dr. Thomas Neylan, director of the Posttraumatic Stress Disorders (PTSD) Clinic and the Stress and Health Research Program at the San Francisco VA. "At least it's another mechanism to think about as we develop new treatments. If we see enduring ability to shape myelin content in an adult brain, maybe treatments will help reverse this. That's where we want to go next with this."

People -- and rats -- vary in their response to stress

The correlation between the symptoms and the region of myelination was discovered because UC Berkeley researchers subjected the rats to a battery of more than a dozen tests to assess their specific behavioral response to acute stress.

"We understand that there's a lot of individual variation in humans, but with rats, they're genetically identical, so you think when you expose them to stress you're going to get the same response," said senior author Daniela Kaufer, UC Berkeley professor of integrative biology. "But the response is extremely variable. They sort of fall into groups, such that some are really resilient, and some are vulnerable. And the ones that are vulnerable are vulnerable in different ways: Some show avoidance behavior, and some show fear learning problems, and some show startle responses that are exaggerated."

According to Neylan, similar individuality is seen in people with PTSD. The new study suggests that the specific symptoms are related to which areas of the brain are being newly myelinated.

"There's a lot of heterogeneity across different people with PTSD; it's not one size fits all. Every PTSD patient generally has a mix of different symptoms," said Neylan, professor-in-residence in psychiatry at the UC San Francisco Weill Institute for Neurosciences. "Some people are very avoidant. Some people are very hyperreactive. The idea is that if you can show that these different symptom clusters have different neural circuitry, it might actually lead us closer to subtyping people in a way that we could be more targeted in our treatment."

The researchers, who published their results in December 2021 in the journal Translational Psychiatry, show that stress produces more of the brain's glial cells, called oligodendrocytes, which wrap around the axons of neurons and make the myelin. The increased myelin produced by these new oligodendrocytes could affect the speed of connections between neurons, making some connections hyperresponsive.

"In the gray matter of your cortex, most of the dendrites and axons -- the projections that come out of the neurons that help establish communications with other neurons -- can form thousands of connections, and most of them are unmyelinated," Neylan said. "But if experience leads you to start to lay down myelin to strengthen certain connections, let's say your ability to respond quickly to a fearful stimulus, you can speed up that circuit, but you lose the kind of broader adaptive flexibility that you normally would have with mostly unmyelinated axons and dendrites. People with PTSD become almost like a one-note musician -- they really know how to respond to fear. But that enhanced, quick response to fear may diminish their adaptive flexibility for non-fear-type behavior."

Acute stress boosts oligodendrocytes

In 2014, Kaufer and her UC Berkeley colleagues discovered that rats subjected to acute stress produced more oligodendrocytes in the brain's gray matter -- specifically, in the hippocampus. She proposed that this led to increased myelination of axons, potentially interfering with the speed at which signals traveled between different areas of the gray matter of the brain, such as the hippocampus and the amygdala. The new study bolsters that theory.

Neylan was intrigued by the 2014 findings and contacted Kaufer, and they've been collaborating ever since. Neylan teamed up with Linda Chao, UCSF professor of radiology, who developed a way to image myelin in the gray matter of the brain, and several years ago scanned the brains of 38 veterans who had experienced severe trauma, some with and some without PTSD.

At the time, scientists looking for changes in myelination related to brain disorders were focused on the cortex's white matter, which is mostly myelinated. In multiple sclerosis, for example, an autoimmune attack destroys myelin in the white matter. Kaufer was perhaps the first to find evidence of increased myelination in the gray matter associated with disease.

Chao and Neylan did find increased myelination of neurons in the gray matter of veterans with PTSD, but not in those without PTSD. The worse the symptoms, the greater the myelination.

This led Kaufer and first author Kimberly Long, now a UCSF postdoctoral fellow, to see if they could also find increased myelin in gray matter after acute trauma in rats. After they focused on the specific symptoms of individual rats with PTSD, they found a correlation between symptoms and myelination in specific regions of the gray matter.

Chao subsequently reanalyzed the brain scans of her earlier group of 38 veterans and found the same correlation: Specific symptoms were associated with myelination in one region of gray matter, but not others.

Long and Kaufer then employed a type of viral gene therapy to rev up a transcription factor, called olig1, that increases the production of oligodendrocytes from stem cells in the gray matter. When Long injected the virus into the dentate gyrus of rats, the researchers found that this boosted the number of oligodendrocytes and generated symptoms of avoidance, even without any stress.

"The next question was, 'If I change oligodendrocyte genesis, am I going to change behavior?" Kaufer said. "The beginning of an answer is here in this paper -- it's yes. And now, there's a lot more to do to really understand that."

Neylan, Chao and Kaufer are collaborating on further studies, including looking for increased myelin in the brains of PTSD patients who have died, improving fMRI imaging of myelin in the brain, investigating the effects of chronic stress on the brain connections of rats, and using new high-resolution imaging to study the myelin deposition in gray matter.

https://www.sciencedaily.com/releases/2022/01/220107084437.htm

Feelings of fatigue predict early death in older adults

January 24, 2022

Science Daily/University of Pittsburgh

How fatigued certain activities make an older person feel can predict the likelihood death is less than three years away, according to research published today in the Journal of Gerontology: Medical Sciencesby University of Pittsburgh epidemiologists. It is the first study to establish perceived physical fatigability as an indicator of earlier mortality.

Older people who scored the highest in terms of how tired or exhausted they would feel after activities were more than twice as likely to die in the following 2.7 years compared to their counterparts who scored lower. Fatigability was assessed for a range of activities using the novel Pittsburgh Fatigability Scale.

"This is the time of year when people make -- and break -- New Year's resolutions to get more physical activity," said lead author Nancy W. Glynn, Ph.D., associate professor in the Department of Epidemiology at Pitt's Graduate School of Public Health. "I hope our findings provide some encouragement to stick with exercise goals. Previous research indicates that getting more physical activity can reduce a person's fatigability. Our study is the first to link more severe physical fatigability to an earlier death. Conversely, lower scores indicate greater energy and more longevity."

Glynn and her colleagues administered the Pittsburgh Fatigability Scale to 2,906 participants aged 60 or older in the Long Life Family Study, an international study that follows family members across two generations. Participants ranked from 0 to 5 how tired they thought or imagined that certain activities -- such as a leisurely 30-minute walk, light housework or heavy gardening -- would make them.

Follow-up for this work concluded at the end of 2019, to avoid any increased mortality impact from the COVID-19 pandemic, which gave the team an average of 2.7 years of data on each participant. After accounting for a variety of factors that influence mortality, such as depression, pre-existing or underlying terminal illness, age and gender, the team found that participants who scored 25 points or higher on the Pittsburgh Fatigability Scale were 2.3 times more likely to die in the 2.7 years after completing the scale, compared to their counterparts who scored below 25.

"There has been research showing that people who increase their physical activity can decrease their fatigability score," said Glynn, a physical activity epidemiologist. "And one of the best ways to increase physical activity -- which simply means moving more -- is by setting manageable goals and starting a routine, like a regular walk or scheduled exercise."

Beyond tying high fatigability to an earlier death, Glynn said the study demonstrates the value of the Pittsburgh Fatigability Scale, which she and colleagues created in 2014. It has since been translated into 11 languages.

"While the Pittsburgh Fatigability Scale has been widely adopted in research as a reliable, sensitive way to measure fatigability, it is underutilized in hospital settings and clinical trials," Glynn said. "My ultimate goal is to develop a physical activity intervention targeting a reduction in fatigability as a means to stem the downward spiral of impaired physical function common with the aging process. By reducing fatigability, one can change how they feel, potentially motivating them to do more."

Additional authors on this research are Theresa Gmelin, M.S.W., M.P.H., Yujia (Susanna) Qiao, Sc.M., Robert M. Boudreau, Ph.D., Kaare Christensen, M.D., and Anne B. Newman, M.D., all of Pitt; Sharon Renner, Ph.D., of Columbus State University; Mary F. Feitosa, Ph.D., of Washington University in St. Louis; Stephanie Cosentino, Ph.D., of Columbia University, and Stacy L. Andersen, Ph.D., of Boston University.

This research was supported by the National Institutes of Health's National Institute on Aging grants U01 AG023712, U01 AG023744, U01 AG023746, U01 AG023749, U01 AG023755, P01 AG08761, U19 AG063893, T32 AG000181 and K01 AG0057798.

https://www.sciencedaily.com/releases/2022/01/220124084616.htm

Green-med diet seems to slow age-related neurodegeneration

January 13, 2022

Science Daily/Ben-Gurion University of the Negev

A green Mediterranean diet, high in polyphenols and low in red and processed meat, seems to slow age-related brain atrophy, according to a new Ben-Gurion University of the Negev-led international study. The DIRECT PLUS 18-month long randomized control trial among approximately 300 participants is one of the longest and largest brain MRI trials in the world.

Their findings were published Tuesday in The American Journal of Clinical Nutrition.

The effect of diet on age-related brain atrophy is largely unproven. Participants were divided into three groups according to diet, and whole brain MRI measurements were taken before, and after the trial. Hippocampal-occupancy (HOC) and lateral-ventricle-volume (LVV) were measured as indicators of brain atrophy and predictors of future dementia. Brain MRI-derived data were quantified and segmented using NeuroQuant, an FDA (Food and Drug Administration) authorized fully automated tool.

Two hundred eighty-four men and women (88% men) aged 31-82 were randomly divided into three groups: A healthy dietary guidelines group, a Mediterranean diet group and a green Mediterranean diet. In the Mediterranean diet group, the participants were further provided walnuts rich in polyphenols. In the green- Mediterranean group the participants were further provided high polyphenol green components: 3-4 daily cups of green tea and a daily green shake of Mankai duckweed, as a substitute for dinner, with minimal consumption of red and processed meat. In addition, all three groups participated in physical activity programs based on aerobic exercise, including free gym memberships.

The trial was performed by Dr. Alon Kaplan and Prof. Iris Shai, professor at Ben-Gurion University, Israel, and adjunct professor at Harvard University, together with several international teams of brain experts. The researchers were surprised to identify dramatic changes in MRI-related brain atrophy within 18-24 months, whereas the rate of brain atrophy markers (i.e., hippocampal occupancy decline and lateral ventricle volume expansion) were significantly accelerated from the age of 50 years and up.

The researchers discovered a significant attenuation in brain atrophy over the 18 months in those who adhered to both Mediterranean diets; with greater magnitude in the green-MED group, specifically among participants over age 50. In addition, the researchers noticed that an improvement in insulin sensitivity was independently associated with attenuated brain atrophy.

Greater Mankai, green tea, and walnuts consumption and less red and processed meat consumption were significantly associated with lower hippocampal occupancy decline.

Participants were initially chosen based on abdominal girth size or dyslipidemia. They were all employees at a remote workplace in Israel (Nuclear Research Center in Dimona) where they did not leave the premises during the workday, and the lunch provided was monitored.

"The beneficial association between the green Mediterranean diet and age-related neurodegeneration might be partially explained by the abundance of polyphenols in plant-based food sources which have antioxidant and anti-inflammatory metabolites. Polyphenols can cross the blood-brain barrier (BBB), reduce neuroinflammation, and induce cell proliferation and adult-onset neurogenesis in the hippocampus," writes Prof. Shai, the lead author.

"Our findings might suggest a simple, safe, and promising avenue to slow age-related neurodegeneration by adhering to a green-Mediterranean diet," adds Dr. Alon Kaplan.

https://www.sciencedaily.com/releases/2022/01/220113111508.htm

Depression and anxiety spiked in pregnant women during COVID-19 pandemic

January 31, 2022

Science Daily/University of Essex

The COVID-19 pandemic caused a spike in depression and anxiety in expectant mums, a new study by the University of Essex has revealed.

The research found social support protected against anxiety symptoms associated with the pandemic but highlighted changes to maternity services forced by lockdown and other restrictions likely hit mental health.

It is speculated in the BMC Pregnancy and Childbirth-published paper that the removal of appointments and other changes to face-to-face contact may have affected well-being.

The senior author, Dr Silvia Rigato, said it was vital to "protect maternal wellbeing during pregnancy and beyond" and "to ensure that all children, and their new families, are given the best possible start in life."

The study found there was a spike in reported depression rates of 30 per cent from pre-pandemic levels, from 17 per cent to 47 per cent -- with anxiety rates also jumping up 37 per cent in expecting mothers to 60 per cent.

The peer-reviewed study of 150 women took place during the height of the Coronavirus crisis between April 2020 and January 2021 -- before the vaccination programme rolled out -- and was led by Dr Maria Laura Filippetti and Dr Rigato, researchers at the Essex Babylab in the University of Essex.

The paper showed that prenatal trauma, such as the one experienced during the COVID-19 pandemic, can significantly amplify vulnerability to mental health problems.

It also emerged from the study that pregnant women with higher depressive symptoms reported feeling less attached to their unborn babies.

Dr Rigato said: "While this result is in line with previous observations that women's mood during pregnancy influences the early relationship with her child, it reinforces the need for authorities to support women throughout their pregnancy and the postnatal period in order to protect their health and their infants' development."

Importantly, the research also revealed the positive effect that social support plays in protecting expecting mothers' mental health.

The authors found women who considered the impact of COVID-19 to be more negative showed higher levels of anxiety.

Crucially though, help from partners, family and friends, and the NHS acted as a protective factor and was associated with fewer negative symptoms.

Dr Filippetti said more must be done to help women during this vulnerable time in their lives.

She said: "The high rates of depression and anxiety during the pandemic highlighted by our study suggest that expectant women are facing a mental health crisis that can significantly interfere and impair mother-infant bonding during pregnancy, and can potentially impact on childbirth outcome, as well as later infant and child development."

It is now hoped the research will be used to help understand how the pandemic affected children's development, mum's mental health post-partum and how dads coped through pregnancy and beyond.?

https://www.sciencedaily.com/releases/2022/01/220131110457.htm

Microbiome of mother's vagina may affect infant mortality risk and baby's development

January 27, 2022

Science Daily/University of Maryland School of Medicine

A new study in mice from University of Maryland School of Medicine researchers showed that an unhealthy vaginal microbiome in pregnant mothers in combination with an unhealthy diet contributed to increased pup deaths and altered development in the surviving babies.

The researchers offset these deaths from the unhealthy vaginal microbiome by giving the mothers a healthier diet. The researchers say their findings could imply that simple interventions, such as access to a diet rich in fiber-containing fruits and vegetables, may help counteract some of the harmful effects on human babies that an unhealthy microbiome may impart -- particularly in vulnerable populations.

Their findings were published on November 1, 2021, in Nature Communications.

When babies pass through the birth canal, they are exposed to their mother's vaginal microbiome, where their skin is coated and they ingest their first microbes outside the sterile womb.

Women with certain chronic diseases, such as diabetes or high blood pressure, and those in low-resourced neighborhoods with limited access to healthcare and nutrition, are more at risk of having an unhealthy vaginal microbiome. These unhealthy vagina microbiomes have too many different kinds of bacteria, viruses, or yeast which, unlike diversity in the gut, is a bad thing in the vagina, increasing the likelihood for infections.

According to the U.S. Department of Health and Human Services, Black women in the U.S. have infant mortality rates 2.3 times higher than white women, and this is independent of education and income levels.

"We know what is healthy for mom is healthy for baby's brain development, and on the flip side stress contributes to disease risk," said Tracy Bale, PhD, Professor of Pharmacology at the University of Maryland School of Medicine and Director of the Center for Epigenetic Research in Child Health & Brain Development. "We wanted to identify biological factors that predict these negative health outcomes and determine how each one contributes to these inequities in our society."

A few years ago, the Bale laboratory showed that mouse pups delivered by C-section and given vaginal microbiomes from stressed mouse mothers had differences in how their brains developed and how they responded to later stress in their environment compared to those pups given microbiomes from unstressed moms.

Work on the human vaginal microbiome by Jacques Ravel, PhD, Professor of Microbiology and Immunology at the University of Maryland School of Medicine and Associate Director of the Institute for Genome Sciences, found that human vaginal microbiomes fall into five different groupings based on the resident microbes with four healthy variations, and one 'unhealthy' group.

Dr. Bale's research team wanted to know if this unhealthy vaginal microbiome might affect a baby's development and birth outcomes, similar to their previous mouse studies. They tested this idea by using vaginal microbiome samples from pregnant women in their C-section mouse model. First, they applied either the healthy or unhealthy bacterial samples into the mouse's vagina to recreate the gestational environment. Then, the pups born via C-section ingested the same vaginal microbiomes mimicking vaginal birth exposure. The researchers investigated which genes were turned on and off in the brains of the pups to see how the mothers' vaginal microbes affected their pups' development. They found these pups had early activation and development of their immune systems.

Next, to more accurately model a vulnerable and low-resourced population, the researchers repeated the study, but added the risk factor of prediabetes and obesity by swapping the pregnant mouse's normally healthy low-fat, high-fiber chow for an unhealthy high-fat, low-fiber diet. Sixty percent of the mouse pups exposed to the human unhealthy microbiomes and fed the unhealthy diet died within 48 hours of delivery. However, with the same microbiome exposure but on a healthy high-fiber diet, the death rate dropped by more than half.

Dr. Bale says that soluble fiber, like that found in fruits and vegetables, ferments in the gut, allowing the bacteria to produce short-chain fatty acids, which are needed for baby's brain development and are also effective anti-inflammatory agents for mom.

"The vaginal microbiome component led to dramatic changes in the brain through fetal immune system development, and it appears that this overactive immune system seems to up the risk for infant mortality," said Dr. Bale. "In humans we had observed these associations with unhealthy vaginal microbiomes, but now our work is allowing us to make these connections and to identify the mechanisms that ultimately affect pregnancy outcomes, perhaps as novel biomarkers that could be used in identifying women at risk."

Dean E. Albert Reece, MD, PhD, MBA, Executive Vice President for Medical Affairs, University of Maryland Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor at the University of Maryland School of Medicine, said, "These studies help to set the stage for what interventions may be tested to improve the health and wellness and reduce infant mortality rates, particularly in our most vulnerable populations."

https://www.sciencedaily.com/releases/2022/01/220127104217.htm

Women ages 35 and younger are 44% more likely to have an ischemic stroke than male peers

January 24, 2022

Science Daily/American Heart Association

Women ages 35 years and younger were 44% more likely to have an ischemic stroke (caused by blocked blood vessels in the brain) than their male counterparts, according to a new review of more than a dozen international studies on sex differences in stroke occurrence, published today in a Go Red for Women® 2022 spotlight issue of Stroke, a peer-reviewed journal of the American Stroke Association, a division of the American Heart Association.

"In this second annual Go Red Stroke issue, we have compiled some outstanding articles to inform our readers about multiple important clinical and translational science issues addressing gaps in our knowledge of stroke among women," said Stroke Editor-in-Chief Ralph L. Sacco, M.D., M.S., FAHA, chair of the department of neurology, and the Olemberg Family Chair in Neurological Disorders and executive director of the Evelyn F. McKnight Brain Institute at the University of Miami Leonard Miller School of Medicine, in Miami. "Stroke affects more women each year than men. We want all stroke professionals to know about the latest research on the recognition, prevention and treatment of strokes among women."

In the article, "Systematic Review of Sex Differences in Ischemic Strokes Among Young Adults- Are Young Women Disproportionately at Risk?" (Leppert et al.), researchers looked at the differences in stroke incidence among women and men in various young adult age groups. They reviewed studies from January 2008 to July 2021 published and indexed on PubMed, one of the largest online research databases in the world managed by the National Library of Medicine at National Institutes of Health. They included original studies that were population-based and focused on young adults 45 years of age and younger. The studies included data on any stroke type, including ischemic strokes; hemorrhagic strokes (a bleed that occurs when a weakened blood vessel ruptures); TIA, or transient Ischemic attack, also called a mini-stroke (caused by a serious, temporary clot); and cryptogenic strokes for which no known cause is identified. Most of the strokes in the review were ischemic strokes, which account for about 87% of all strokes.

The researchers identified 16 studies, including a combined total of 69,793 young adults with stroke (33,775 women and 36,018 men), from more than half a dozen countries, including the U.S., Canada, France and The Netherlands.

The authors' analysis identified the sex differences in the incidence of ischemic strokes was the greatest and most evident among adults younger than age 35 years, with an estimated 44% more women than men in this age group experiencing ischemic strokes. This sex difference narrowed among adults ages 35 to 45 years. Sex differences in older age groups were more difficult to determine due to wide variability in the way data was presented among the studies in this systemic review. The researchers were also not able to identify specific causes behind the higher prevalence of strokes in young women compared to young men.

Researchers noted the variables of their data set that posed limitations to their review included: study populations spanning different continents, including 15 different countries with varying levels of development, and the diversity of the study participants from numerous racial and ethnic groups; methodological differences among the studies; and possible publication bias because larger epidemiology studies may not have published results in the younger age groups due to the relatively small number of cases captured. According to the researchers, the incidence of ischemic stroke increases exponentially with age, and only 15% of all ischemic strokes occur in adults younger than age 50 years.

Based on their analysis, the researchers concluded, "Traditional atherosclerotic risk factors are a major contributor to ischemic strokes in both young men and women and become increasingly important with age. However, these risk factors are less prevalent in younger women and may not account for the observed higher incidence of ischemic strokes in women younger than age 35. Young women who are survivors of ischemic stroke also have worse outcomes, with 2 to 3 times higher risk of poorer functional outcomes compared to their male counterparts."

The researchers said more research is needed to better define the sex differences of ischemic stroke in young adults and the contributions that non-traditional risk factors, such as pregnancy, postpartum and hormonal contraceptives, may play in the overall burden of ischemic strokes in young women.

"Our finding suggests that strokes in young adults may be happening for different reasons than strokes in older adults. This emphasizes the importance of doing more studies of stroke in younger age groups so that we can better understand what puts young women at a higher risk of stroke," said study co-author Sharon N. Poisson, M.D., M.A.S., an associate professor of neurology at the University of Colorado, Denver. "Better understanding which young adults are at risk for stroke can help us to do a better job of preventing and treating strokes in young people."

https://www.sciencedaily.com/releases/2022/01/220124151037.htm

A spouse's education can positively impact their partner's overall health

January 24, 2022

Science Daily/Indiana University

Research has long shown that people with more schooling tend to experience better overall health. But can your spouse's education make you healthier?

According to a study by Indiana University researchers, the answer is yes.

The study, published in the Journal of Health and Social Behavior, found that spousal education is positively related to people's overall health, with an effect size that rivals the impact of a person's own education.

"Our results show that who you're married to, and how much education they have, matter for your health," said Andrew Halpern-Manners, an associate professor in the Department of Sociology at IU. "This provides further evidence that education, in addition to being valuable for individuals, is also a sharable resource."

The researchers used more than half a century's worth of data from the Wisconsin Longitudinal Study, a rich longitudinal study of individuals, their spouses, their siblings and their siblings' spouses that includes information about respondents' health, marriages, educational attainments and the educational attainments of their spouses. Due to the timing of the study, which began in 1957, it only refers to heterosexual couples.

Elaine M. Hernandez, co-author of the study and an assistant professor in the Department of Sociology at IU, said researchers have routinely observed a relationship between spousal education and health, but the nature of this relationship has been harder to establish. Because healthier people tend to have more schooling and to partner with those who also are highly educated, it can be difficult to isolate the unique effect of spousal education.

To address this, the team compared the self-rated health of siblings whose spouses had different levels of schooling. The idea, Halpern-Manners said was to find pairs of people who were as similar as possible across a variety of dimensions and then ask whether differences in their partners' education could explain differences in their health.

They found that the effect of spousal education on a person's self-assessed overall health is positive and relatively large, suggesting that people benefit from having more highly educated partners in the same way (and to roughly the same extent) that they benefit from being highly educated themselves.

This pattern was especially pronounced among women, whose health was more closely tied to spousal education than men's. This finding, Hernandez said, could reflect the time period (1960s-1970s) in which most of the respondents completed their education, married and entered the labor force.

"The fact that we observe significant cross-over effects means that education has health-enhancing benefits for the individual, but it also has tangible benefits for those around them -- especially intimate ties," Halpern-Manners said. "This underscores the importance of education -- as a public good worth investing in -- and suggests that its overall public health impact may be larger than we typically imagine."

https://www.sciencedaily.com/releases/2022/01/220124115051.htm