Gut bacteria affect brain health

Findings suggest new approach to treating Alzheimer's, other neurodegenerative diseases

January 12, 2023

Science Daily/Washington University School of Medicine

A growing pile of evidence indicates that the tens of trillions of microbes that normally live in our intestines -- the so-called gut microbiome -- have far-reaching effects on how our bodies function. Members of this microbial community produce vitamins, help us digest food, prevent the overgrowth of harmful bacteria and regulate the immune system, among other benefits. Now, a new study suggests that the gut microbiome also plays a key role in the health of our brains, according to researchers from Washington University School of Medicine in St. Louis.

The study, in mice, found that gut bacteria -- partly by producing compounds such as short chain fatty acids -- affect the behavior of immune cells throughout the body, including ones in the brain that can damage brain tissue and exacerbate neurodegeneration in conditions such as Alzheimer's disease. The findings, published Jan. 13 in the journal Science, open up the possibility of reshaping the gut microbiome as a way to prevent or treat neurodegeneration.

"We gave young mice antibiotics for just a week, and we saw a permanent change in their gut microbiomes, their immune responses, and how much neurodegeneration related to a protein called tau they experienced with age," said senior author David M. Holtzman, MD, the Barbara Burton and Reuben M. Morriss III Distinguished Professor of Neurology. "What's exciting is that manipulating the gut microbiome could be a way to have an effect on the brain without putting anything directly into the brain."

Evidence is accumulating that the gut microbiomes in people with Alzheimer's disease can differ from those of healthy people. But it isn't clear whether these differences are the cause or the result of the disease -- or both -- and what effect altering the microbiome might have on the course of the disease.

To determine whether the gut microbiome may be playing a causal role, the researchers altered the gut microbiomes of mice predisposed to develop Alzheimer's-like brain damage and cognitive impairment. The mice were genetically modified to express a mutant form of the human brain protein tau, which builds up and causes damage to neurons and atrophy of their brains by 9 months of age. They also carried a variant of the human APOEgene, a major genetic risk factor for Alzheimer's. People with one copy of the APOE4 variant are three to four times more likely to develop the disease than people with the more common APOE3variant.

Along with Holtzman, the research team included gut microbiome expert and co-author Jeffrey I. Gordon, MD, the Dr. Robert J. Glaser Distinguished University Professor and director of the Edison Family Center for Genome Sciences & Systems Biology; first author Dong-Oh Seo, PhD, an instructor in neurology; and co-author Sangram S. Sisodia, PhD, a professor of neurobiology at the University of Chicago.

When such genetically modified mice were raised under sterile conditions from birth, they did not acquire gut microbiomes, and their brains showed much less damage at 40 weeks of age than the brains of mice harboring normal mouse microbiomes.

When such mice were raised under normal, nonsterile conditions, they developed normal microbiomes. A course of antibiotics at 2 weeks of age, however, permanently changed the composition of bacteria in their microbiomes. For male mice, it also reduced the amount of brain damage evident at 40 weeks of age. The protective effects of the microbiome shifts were more pronounced in male mice carrying the APOE3 variant than in those with the high-risk APOE4variant, possibly because the deleterious effects of APOE4canceled out some of the protection, the researchers said. Antibiotic treatment had no significant effect on neurodegeneration in female mice.

"We already know, from studies of brain tumors, normal brain development and related topics, that immune cells in male and female brains respond very differently to stimuli," Holtzman said. "So it's not terribly surprising that when we manipulated the microbiome we saw a sex difference in response, although it is hard to say what exactly this means for men and women living with Alzheimer's disease and related disorders."

Further experiments linked three specific short-chain fatty acids -- compounds produced by certain types of gut bacteria as products of their metabolism -- to neurodegeneration. All three of these fatty acids were scarce in mice with gut microbiomes altered by antibiotic treatment, and undetectable in mice without gut microbiomes.

These short-chain fatty acids appeared to trigger neurodegeneration by activating immune cells in the bloodstream, which in turn somehow activated immune cells in the brain to damage brain tissue. When middle-aged mice without microbiomes were fed the three short-chain fatty acids, their brain immune cells became more reactive, and their brains showed more signs of tau-linked damage.

"This study may offer important insights into how the microbiome influences tau-mediated neurodegeneration, and suggests therapies that alter gut microbes may affect the onset or progression of neurodegenerative disorders," said Linda McGavern, PhD, program director at the National Institute of Neurological Disorders and Stroke (NINDS), which provided some of the funding for the study.

The findings suggest a new approach to preventing and treating neurodegenerative diseases by modifying the gut microbiome with antibiotics, probiotics, specialized diets or other means.

"What I want to know is, if you took mice genetically destined to develop neurodegenerative disease, and you manipulated the microbiome just before the animals start showing signs of damage, could you slow or prevent neurodegeneration?" Holtzman asked. "That would be the equivalent of starting treatment in a person in late middle age who is still cognitively normal but on the verge of developing impairments. If we could start a treatment in these types of genetically sensitized adult animal models before neurodegeneration first becomes apparent, and show that it worked, that could be the kind of thing we could test in people."

https://www.sciencedaily.com/releases/2023/01/230112155812.htm

Social isolation is a risk factor for dementia in older adults, point to ways to reduce risk

January 12, 2023

Science Daily/Johns Hopkins Medicine

In two studies using nationally representative data from the National Health and Aging Trends Study gathered on thousands of Americans, researchers from the Johns Hopkins University School of Medicine and Bloomberg School of Public Health have significantly added to evidence that social isolation is a substantial risk factor for dementia in community-dwelling (noninstitutionalized) older adults, and identified technology as an effective way to intervene.

Collectively, the studies do not establish a direct cause and effect between dementia and social isolation, defined as lack of social contact and interactions with people on a regular basis. But, the researchers say, the studies strengthen observations that such isolation increases the risk of dementia, and suggest that relatively simple efforts to increase social support of older adults -- such as texting and use of email -- may reduce that risk. In the United States, an estimated 1 in 4 people over age 65 experience social isolation, according to the National Institute on Aging.

"Social connections matter for our cognitive health, and it is potentially easily modifiable for older adults without the use of medication," says Thomas Cudjoe, M.D., M.P.H., assistant professor of medicine at the Johns Hopkins University School of Medicine and senior author of both of the new studies.

The first study, described Jan. 11 in the Journal of the American Geriatrics Society, used data collected on a group of 5,022 Medicare beneficiaries for a long-term study known as the National Health and Aging Trends, which began in 2011. All participants were 65 or older, and were asked to complete an annual two-hour, in-person interview to assess cognitive function, health status and overall well-being.

At the initial interview, 23% of the 5,022 participants were socially isolated and showed no signs of dementia. However, by the end of this nine-year study, 21% of the total sample of participants had developed dementia. The researchers concluded that risk of developing dementia over nine years was 27% higher among socially isolated older adults compared with older adults who were not socially isolated.

"Socially isolated older adults have smaller social networks, live alone and have limited participation in social activities," says Alison Huang, Ph.D., M.P.H., senior research associate at the Johns Hopkins Bloomberg School of Public Health. "One possible explanation is that having fewer opportunities to socialize with others decreases cognitive engagement as well, potentially contributing to increased risk of dementia."

Interventions to reduce that risk are possible, according to results of the second study, published Dec. 15 in the Journal of the American Geriatrics Society. Specifically, researchers found the use of communications technology such as telephone and email lowered the risk for social isolation.

Researchers for the second study used data from participants in the same National Health and Aging Trends study, and found that more than 70% of people age 65 and up who were not socially isolated at their initial appointment had a working cellphone and/or computer, and regularly used email or texting to initiate and respond to others. Over the four-year research period for this second study, older adults who had access to such technology consistently showed a 31% lower risk for social isolation than the rest of the cohort.

"Basic communications technology is a great tool to combat social isolation," says Mfon Umoh, M.D., Ph.D., postdoctoral fellow in geriatric medicine at the Johns Hopkins University School of Medicine. "This study shows that access and use of simple technologies are important factors that protect older adults against social isolation, which is associated with significant health risks. This is encouraging because it means simple interventions may be meaningful."

Social isolation has gained significant attention in the past decade, especially due to restrictions implemented for the COVID-19 pandemic, but more work needs to be done to identify at-risk populations and create tools for providers and caregivers to minimize risk, the researchers say. Future research in this area should focus on increased risks based on biological sex, physical limitations, race and income level.

https://www.sciencedaily.com/releases/2023/01/230112113224.htm

Fall rate nearly 50% among older Americans with dementia

Targeting specific fall-risk factors could improve fall screening and prevention strategies

January 12, 2023

Science Daily/Drexel University

With falls causing millions of injuries in older adults each year, it is an increasingly important public health concern. Older adults living with dementia have twice the risk of falling and three times the risk of incurring serious fall-related injuries, like fractures, compared to those without dementia. For older adults with dementia, even minor fall-related injuries can lead to hospitalization and nursing home admission. A new study from researchers in Drexel University's College of Nursing and Health Professions, has shed light on the many and varied fall-risk factors facing older adults in community-living environments.

Recently published in Alzheimer's & Dementia: The Journal of the Alzheimer's Association, the research led by Safiyyah Okoye, PhD, an assistant professor at Drexel, and Jennifer L. Wolff, PhD, a professor at Johns Hopkins Bloomberg School of Public Health, examined a comprehensive set of potential fall-risk factors -- including environmental factors, in addition to health and function -- in older community-living adults in the United States, both with and without dementia.

"Examining the multiple factors, including environmental ones like a person's home or neighborhood, is necessary to inform fall-risk screening, caregiver education and support, and prevention strategies for this high-risk population of older adults," said Okoye.

Despite awareness of this elevated risk, there are very few studies that have examined fall-risk factors among people with dementia living in a community setting (not nursing homes or other residential facilities). The studies that do exist, overwhelmingly focus on health and function factors. According to the authors, this is the first nationally representative study to compare a comprehensive set of potential risk factors for falls for older Americans living with dementia to those without dementia.

The research team examined data from the 2015 and 2016 National Health and Aging Trends Study (NHATS), a population-based survey of health and disability trends and trajectories of adults 65 and older in the U.S. They were able to obtain potential sociodemographic, health and function predictors of falls, as well as potential social and physical environmental predictors.

Data from NHATS showed that nearly half (45.5%) of older adults with dementia had experienced one or more falls in 2016, compared to less than one third (30.9%) of older adults without dementia.

Among older adults living with dementia, three characteristics stood out as significantly associated with a greater likelihood of falls: a history of falling the previous year; impaired vision; and living with others (versus alone). For older adults without dementia, financial hardship, a history of falling, fear of falling, poor lower extremity performance, depressive symptoms and home disrepair were strongly associated with increased risk of falls.

While prior history of falling and vision impairment are well-known risk factors for falls among older adults in general; the researchers' findings indicate that these were strong risk factors for falls among people living with dementia. According to the team, this suggests that people living with dementia should be assessed for presence of these characteristics. If they're present, the individuals should receive further assessment and treatment, including examining their feet and footwear, assessing their environment and ability to carry out daily living activities, among other items.

The finding that older adults living with dementia who lived with a spouse or with non-spousal others had higher odds of experiencing a fall, compared to those who lived alone, highlights that caregiver support and education are understudied components of fall prevention programs for older adults with dementia who live with family caregivers, and deserve greater attention from clinicians, researchers and policy makers.

"Overall, our findings demonstrate the importance of understanding and addressing fall-risk among older adults living with dementia," said Okoye. "It confirms that fall-risk is multidimensional and influenced by environmental context in addition to health and function factors."

The results of the study indicate the need to further investigate and design fall-prevention interventions, specifically for people living with dementia.

https://www.sciencedaily.com/releases/2023/01/230112090936.htm

Six minutes of high-intensity exercise could delay the onset of Alzheimer's disease

January 12, 2023

Science Daily/The Physiological Society 

Six minutes of high-intensity exercise could extend the lifespan of a healthy brain and delay the onset of neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease. New research published in The Journal of Physiology shows that a short but intense bout of cycling increases the production of a specialised protein that is essential for brain formation, learning and memory, and could protect the brain from age-related cognitive decline. This insight on exercise is part of the drive to develop accessible, equitable and affordable non-pharmacological approaches that anyone can adopt to promote healthy ageing.  

The specialised protein named brain-derived neurotrophic factor (BDNF) promotes neuroplasticity (the ability of the brain to form new connections and pathways) and the survival of neurons. Animal studies have shown that increasing the availability of BDNF encourages the formation and storage of memories, enhances learning and overall boosts cognitive performance. These key roles and its apparent neuroprotective qualities have led to the interest in BDNF for ageing research.

Lead author Travis Gibbons from University of Otago, New Zealand said: “BDNF has shown great promise in animal models, but pharmaceutical interventions have thus far failed to safely harness the protective power of BDNF in humans. We saw the need to explore non-pharmacological approaches that can preserve the brain’s capacity which humans can use to naturally increase BDNF to help with healthy ageing.”

To tease apart the influence of fasting and exercise on BDNF production the researchers, from the University of Otago, New Zealand, compared the following factors to study the isolated and interactive effects:

• Fasting for 20 hours,

• Light exercise (90-minute low intensity cycling),

• High-intensity exercise (six-minute bout of vigorous cycling),

• Combined fasting and exercise.

They found that brief but vigorous exercise was the most efficient way to increase BDNF compared to one day of fasting with or without a lengthy session of light exercise. BDNF increased by four to five-fold (396 pg L-1 to 1170 pg L-1) more compared to fasting (no change in BDNF concentration) or prolonged activity (slight increase in BDNF concentration, 336 pg L-1 to 390 pg L-1).

The cause for these differences is not yet known and more research is needed to understand the mechanisms involved. One hypothesis is related to the cerebral substrate switch and glucose metabolism, the brain’s primary fuel source. The cerebral substrate switch is when the brain switches its favoured fuel source for another to ensure the body’s energy demands are met, for example metabolising lactate rather than glucose during exercise. The brain’s transition from consuming glucose to lactate initiates pathways that result in elevated levels of BDNF in the blood.

The observed increase in BDNF during exercise could be due to the increased number of platelets (the smallest blood cell) which store large amounts of BDNF. The concentration of platelets circulating in the blood is more heavily influenced by exercise than fasting and increases by 20%.

12 physically active participants (six males, six females aged between 18 and 56 years) took part in the study. The balanced ratio of male and female participants was to provide a better representation of the population rather than indicate sex differences.

Further research is underway to delve deeper into the effects of calorie restriction and exercise to distinguish the influence on BDNF and the cognitive benefits.

Travis Gibbons said: “We are now studying how fasting for longer durations, for example up to three days, influences BDNF. We are curious whether exercising hard at the start of a fast accelerates the beneficial effects of fasting. Fasting and exercise are rarely studied together. We think fasting and exercise can be used in conjunction to optimise BDNF production in the human brain.”

https://www.sciencedaily.com/releases/2023/01/230112090919.htm

Feeling loved, optimistic or happy as a teen may lead to better health in adulthood

January 11, 2023

Science Daily/American Heart Association

Teenagers who reported feeling optimism, happiness, self-esteem, belongingness, and feeling loved and wanted were more likely to reach their 20s and 30s in good cardiometabolic health compared to teens with fewer of these positive mental health assets, according to new research published today in the Journal of the American Heart Association, an open access, peer-reviewed journal of the American Heart Association.

Previous studies have found that psychological facets of mental well-being, such as optimism and happiness, may be important modifiable factors related to better cardiometabolic health over time. While most of this research was conducted among older adults, this study focused earlier in life and considered a broader measure of cardiometabolic health, which also included indicators of blood sugar levels and inflammation.

"We learned a lot in the last few decades about the impact of discrimination and other social risks youth of color face that may explain their elevated rates of cardiometabolic disease, however, much less attention is paid to the inherent strengths they possess and the ways those strengths may be leveraged to advance health equity," said lead study author Farah Qureshi, Sc.D., M.H.S., an assistant professor at the Johns Hopkins Bloomberg School of Public Health in Baltimore. "In this study, we wanted to shift the paradigm in public health beyond the traditional focus on deficits to one that concentrates on resource building."

Researchers examined data from the National Longitudinal Study of Adolescent Health, which enrolled nearly 3,500 U.S. high schoolers (average age 16 years) in 1994 and were followed for more than two decades. Nearly half were girls, 67% were white youth, 15% were Black teens, 11% were Latino teenagers and 6% reported their race as either Native American, Asian, or "other." Researchers periodically collected data on the participants' health and well-being, with the most recent wave of data collection occurring in 2018, when their average age was 38.

Using initial survey responses from when participants were teenagers, researchers identified five mental health assets related to better cardiometabolic health outcomes: optimism, happiness, self-esteem, a sense of belonging and feeling loved. This information was cross-referenced with health data recorded over 3 decades to assess whether teens who had more of these positive assets were more likely to maintain optimal cardiometabolic health in adulthood.

To examine cardiometabolic health in this study, researchers reviewed health measures for seven cardiovascular and metabolic disease risk factors collected during clinic visits when participants were in their late 20s and 30s. The factors included high-density lipoprotein (HDL), or "good" cholesterol; non-HDL cholesterol -- calculated as total cholesterol minus HDL cholesterol; systolic blood pressure (top number); diastolic blood pressure (bottom number); hemoglobin A1c, a measure of blood sugar; C-reactive protein, a measure of inflammation; and body mass index, or BMI, the ratio of height to weight to estimate body fat.

The analysis found:

• Overall, 55% of youth had zero to one positive mental health asset, while 29% had two to three assets and 16% had four to five assets.

• As young adults, only 12% of participants maintained cardiometabolic health over time, and white youth were more likely to maintain good health later in life compared to Black or Latino youth.

• Teens with four to five positive mental health assets were 69% more likely to maintain positive cardiometabolic health as young adults.

• There was also a cumulative effect, with each additional mental health asset conferring a 12% greater likelihood of positive cardiometabolic health.

• Although psychological assets were found to be protective across all racial and ethnic groups, the largest health benefits were noted among Black youth. Black teens also reported having more positive mental health assets than youth of any other racial or ethnic groups.

Despite Black teens having the most assets and deriving the most health benefits from them, racial disparities in cardiometabolic health were still apparent in adulthood. Black individuals were the least likely to maintain good cardiometabolic health over time.

"These somewhat counterintuitive findings were surprising," Qureshi said. "When we dug deeper, we found that the absence of psychological assets being was particularly health-damaging for Black youth." She further elaborated that the findings point to the role structural racism plays in shaping cardiometabolic health patterns in the first decades of life: "For Black youth -- who face numerous barriers to achieving and sustaining optimal cardiometabolic health in adulthood -- not having these additional mental health resources makes a big difference."

"This work suggests that early investments in youth mental health may be a critical new frontier in the advancement of cardiometabolic health equity," according to Qureshi.

"We need more large-scale studies to monitor these and other positive mental health factors starting in childhood to understand how these assets may influence health and disease over the life course. This information may help us identify new ways to improve health and reduce disparities," she said.

Limitations of the study include that there were relatively few participants who were Latino, Asian or Native American and there were variations in blood sample collection methods over time.

Health care professionals measure cardiovascular health with the American Heart Association's Life's Essential 8 tool, which measures 4 indicators related to cardiovascular and metabolic health status (blood pressure, cholesterol, blood sugar and body mass index); and 4 behavioral/lifestyle factors (smoking status, physical activity, sleep and diet). According to Life's Essential 8 data:

• only 45% of U.S. adolescents have five or more indicators of ideal cardiovascular health, and the percentage declines in adulthood; and

• there are persistent differences in cardiovascular health levels by self-reported race and ethnicity, and these disparities are larger at younger ages.

https://www.sciencedaily.com/releases/2023/01/230111075843.htm

An education doesn't just make you smarter -- it protects your gut, seriously

January 11, 2023

Science Daily/Edith Cowan University

We've long known education is important for many aspects of life, but now a new benefit has been discovered: it can look after your gut health.

Landmark Edith Cowan University (ECU) research has found a better education has a strong genetic correlation and a protective causal association with several gut disorders.

A previous study from ECU's Centre for Precision Health (CPH) discovered a genetic link between gut health and Alzheimer's Disease (AD) but couldn't conclude whether one caused the other.

This study breaks new ground by finding that a higher level of education protects against gut disorders.

CPH Director and study supervisor Professor Simon Laws said these findings build upon the centre's previous work to provide further evidence of the strong links between the brain and gut, known as the gut-brain axis.

"Gut disorders and Alzheimer's may not only share a common genetic predisposition but may be similarly influenced by genetic variations underpinning educational attainment," Professor Laws said.

This large-scale study examined the genetic information of more than 766,000 individuals, with an emphasis on AD, cognitive traits and gut disorders, including peptic ulcer disease (PUD), gastritis-duodenitis, gastroesophageal reflux disease (GERD), irritable bowel syndrome, diverticulosis and inflammatory bowel disease (IBD).

It found higher levels of education and cognitive functioning reduced the risk of gut disorders.

Lead researcher Dr Emmanuel Adewuyi said the findings have significant implications.

"The results support education as a possible avenue for reducing the risk of gut disorders

by, for example, encouraging higher educational attainment or a possible increase in the length of schooling," he said.

"Hence, policy efforts aimed at increasing educational attainment or cognitive training may contribute to a higher level of intelligence, which could lead to better health outcomes including a reduced risk of gut disorders."

It goes both ways

ECU's study further revealed the gut may also influence the brain.

GERD showed evidence of causing a decline in cognitive function across a number of cognitive traits assessed in the study, such as intelligence, cognitive performance, educational attainment and educational qualification.

Although this is the first study to report this finding, the results support recent research reporting an increased incidence of dementia and GERD, which Dr Adewuyi said could help with earlier diagnoses and potential treatments.

"GERD may be a risk factor for cognitive impairment, so it's important for health workers to look for signs or symptoms of cognitive dysfunction in patients presenting with the gut disorder," he said.

"This could lead to earlier detection of cognitive decline and therefore earlier interventions aimed at reducing the rate of cognitive decline.

"More studies are needed to investigate whether treatment for, cure or remission of GERD can contribute to a reduced risk of cognitive decline."

The curious case of IBD

Interestingly, higher levels of education and cognitive function protecting against gut disorders was true of all the disorders examined in the study -- but largely with the exception of inflammatory bowel disease.

Further analysis reveals different effects of IBD on cognitive traits and AD at different genomic locations, indicating its relationship depend on effects at specific locations across the genome.

This new understanding may explain the lack of significant genetic correlation of IBD with cognitive traits and AD, and the inconsistency reported in previous observational studies.

Dr Adewuyi said this finding was also important, as it brings a new insight into the relationship of IBD with cognitive traits (and AD), which may shape the direction of future studies.

"For example, some risk genes for AD may be protective against IBD, and vice versa," he said.

'Relationship of cognition and Alzheimer's disease with gastrointestinal tract disorders: a large-scale genetic overlap and Mendelian randomisation analysis' was published in the International Journal of Molecular Sciences.

https://www.sciencedaily.com/releases/2023/01/230111075855.htm

Obesity linked to macular degeneration

January 10, 2023

Science Daily/University of Montreal

A Canadian study published in the journal Scienceelucidates a new molecular mechanism that may cause age-related macular degeneration (AMD).

The research at Hôpital Maisonneuve-Rosement, in Montreal, shows how life stressors such as obesity reprogram immune system cells and make them destructive to the eye as it ages.

"We wanted to know why some people with a genetic predisposition develop AMD while others are spared," said Université de Montréal ophtalmology professor Przemyslaw (Mike) Sapieha, who led the study by his postdoctoral fellow Dr. Masayuki Hata.

"Although considerable effort has been invested in understanding the genes responsible for AMD, variations and mutations in susceptibility genes only increase the risk of developing the disease, but do not cause it," Sapieha explained.

"This observation suggests that we must gain a better understanding of how other factors such as environment and lifestyle contribute to disease development."

AMD is a major cause of irreversible blindness worldwide and affected approximately 196 million people in 2020. It comes in two forms:

• dry AMD, characterized by the accumulation of fatty deposits at the back of the eye and the death of nerve cells in the eye,

• and wet AMD, which is characterized by diseased blood vessels that develop in the most sensitive part of the sight-generating tissue, called the macula.

Contact with pathogens

It is already known that the immune system in the eye of a person with AMD becomes dysregulated and aggressive. Normally, immune cells keep the eye healthy, but contact with pathogens such as bacteria and viruses can make them go awry.

At the same time, immune cells are also activated when the body is exposed to stressors such as excess fat in obesity, making being overweight the number one non-genetic risk factor for developing AMD, after smoking.

In their study, Sapieha and Hata used obesity as a model to accelerate and exaggerate the stressors experienced by the body throughout life.

They found that transient obesity or a history of obesity leads to persistent changes in the DNA architecture within immune cells, making them more susceptible to producing inflammatory molecules.

"Our findings provide important information about the biology of the immune cells that cause AMD and will allow for the development of more tailored treatments in the future," said Hata, now an ophthalmology professor at Kyoto University, in Japan.

The researchers hope their discovery will lead other scientists to broaden their interest beyond obesity-related diseases to other diseases characterized by increased neuroinflammation, including Alzheimer's disease and multiple sclerosis.

https://www.sciencedaily.com/releases/2023/01/230110191415.htm

New study links hearing loss with dementia in older adults

Findings highlight potential benefit of hearing aid

January 10, 2023

Science Daily/Johns Hopkins Bloomberg School of Public Health

A new study led by researchers at the Johns Hopkins Bloomberg School of Public Health found that older adults with greater severity of hearing loss were more likely to have dementia, but the likelihood of dementia was lower among hearing aid users compared to non-users.

The findings, from a nationally representative sample of more than 2,400 older adults, are consistent with prior studies showing that hearing loss might be a contributing factor to dementia risk over time, and that treating hearing loss may lower dementia risk.

The findings are highlighted in a research letter published online January 10 in the Journal of the American Medical Association.

"This study refines what we've observed about the link between hearing loss and dementia, and builds support for public health action to improve hearing care access," says lead author Alison Huang, PhD, MPH, a senior research associate in the Bloomberg School's Department of Epidemiology and at the Cochlear Center for Hearing and Public Health, also at the Bloomberg School.

Hearing loss is a critical public health issue affecting two-thirds of Americans over 70. The growing understanding that hearing loss might be linked to the risk of dementia, which impacts millions, and other adverse outcomes has called attention to implementing possible strategies to treat hearing loss.

For the new study, Huang and colleagues analyzed a nationally representative dataset from the National Health and Aging Trends Study (NHATS). Funded by the National Institute on Aging, the NHATS has been ongoing since 2011, and uses a nationwide sample of Medicare beneficiaries over age 65, with a focus on the 90-and-over group as well as Black individuals.

The analysis covered 2,413 individuals, about half of whom were over 80 and showed a clear association between severity of hearing loss and dementia. Prevalence of dementia among the participants with moderate/severe hearing loss was 61 percent higher than prevalence among participants who had normal hearing. Hearing aid use was associated with a 32 percent lower prevalence of dementia in the 853 participants who had moderate/severe hearing loss.

The authors note that many past studies were limited in that they relied on in-clinic data collection, leaving out vulnerable populations that did not have the means or capacity to get to a clinic. For their study, the researchers collected data from participants through in-home testing and interviews.

How hearing loss is linked to dementia isn't yet clear, and studies point to several possible mechanisms. Huang's research adds to a body of work by the Cochlear Center for Hearing and Public Health examining the relationship between hearing loss and dementia.

The study authors expect to have a fuller picture of the effect of hearing loss treatment on cognition and dementia from their Aging and Cognitive Health Evaluation in Elders (ACHIEVE) Study. Results from the three-year randomized trial are expected this year.

https://www.sciencedaily.com/releases/2023/01/230110150943.htm

Feeling depressed? Performing acts of kindness may help

Study finds helping others reduces focus on your own symptoms

January 10, 2023

Science Daily/Ohio State University

People suffering from symptoms of depression or anxiety may help heal themselves by doing good deeds for others, new research shows.

The study found that performing acts of kindness led to improvements not seen in two other therapeutic techniques used to treat depression or anxiety.

Most importantly, the acts of kindness technique was the only intervention tested that helped people feel more connected to others, said study co-author David Cregg, who led the work as part of his PhD dissertation in psychology at The Ohio State University.

"Social connection is one of the ingredients of life most strongly associated with well-being. Performing acts of kindness seems to be one of the best ways to promote those connections," Cregg said.

Cregg conducted the research with Jennifer Cheavens, professor of psychology at Ohio State. Their study was published recently in The Journal of Positive Psychology.

The research also revealed why performing acts of kindness worked so well: It helped people take their minds off their own depression and anxiety symptoms.

This finding suggests that one intuition many people have about people with depression may be wrong, Cheavens said.

"We often think that people with depression have enough to deal with, so we don't want to burden them by asking them to help others. But these results run counter to that," she said.

"Doing nice things for people and focusing on the needs of others may actually help people with depression and anxiety feel better about themselves."

The study involved 122 people in central Ohio who had moderate to severe symptoms of depression, anxiety, and stress.

After an introductory session, the participants were split into three groups. Two of the groups were assigned to techniques often used in cognitive behavioral therapy (CBT) for depression: planning social activities or cognitive reappraisal.

The social activities group was instructed to plan social activities for two days a week. Another group was instructed in one of the staples of CBT: cognitive reappraisal. These participants kept records for at least two days each week that helped them identify negative thought patterns and revise their thoughts in a way that could reduce depression and anxiety.

Members of the third group were instructed to perform three acts of kindness a day for two days out of the week. Acts of kindness were defined as "big or small acts that benefit others or make others happy, typically at some cost to you in terms of time or resources."

Some of the acts of kindness that participants later said they did included baking cookies for friends, offering to give a friend a ride, and leaving sticky notes for roommates with words of encouragement.

Participants followed their instructions for five weeks, after which they were evaluated again. The researchers then checked with the participants after another five weeks to see if the interventions were still effective.

The findings showed that participants in all three groups showed an increase in life satisfaction and a reduction of depression and anxiety symptoms after the 10 weeks of the study.

"These results are encouraging because they suggest that all three study interventions are effective at reducing distress and improving satisfaction," Cregg said.

"But acts of kindness still showed an advantage over both social activities and cognitive reappraisal by making people feel more connected to other people, which is an important part of well-being," he said.

In addition, the acts of kindness group showed greater improvements than the cognitive reappraisal group for life satisfaction and symptoms of depression and anxiety, results showed.

Cheavens noted that just participating in social activities did not improve feelings of social connection in this study.

"There's something specific about performing acts of kindness that makes people feel connected to others. It's not enough to just be around other people, participating in social activities," she said.

Cregg said that while this study used techniques of CBT, it is not the same experience as going through CBT. Those who undergo the full treatment may have better results than those in this study.

But the findings also show that even the limited CBT exposure given in this study can be helpful, Cheavens said.

"Not everyone who could benefit from psychotherapy has the opportunity to get that treatment," she said. "But we found that a relatively simple, one-time training had real effects on reducing depression and anxiety symptoms."

And beyond traditional CBT, acts of kindness may have additional benefits in creating social connections, Cregg said.

"Something as simple as helping other people can go above and beyond other treatments in helping heal people with depression and anxiety," he said.

https://www.sciencedaily.com/releases/2023/01/230110103424.htm

Gardening may help reduce cancer risk, boost mental health

January 6, 2023

Science Daily/University of Colorado at Boulder

Get more exercise. Eat right. Make new friends.

As we compile our lists of resolutions aimed at improving physical and mental health in 2023, new CU Boulder research suggests one addition could have a powerful impact: Gardening.

Funded by the American Cancer Society, the first-ever, randomized, controlled trial of community gardening found that those who started gardening ate more fiber and got more physical activity -- two known ways to reduce risk of cancer and chronic diseases. They also saw their levels of stress and anxiety significantly decrease.

The findings were published Jan. 4 in the journal Lancet Planetary Health.

"These findings provide concrete evidence that community gardening could play an important role in preventing cancer, chronic diseases and mental health disorders," said senior author Jill Litt, a professor in the Department of Environmental Studies at CU Boulder.

Filling the research gap

Litt has spent much of her career seeking to identify affordable, scalable and sustainable ways to reduce disease risk, especially among low-income communities.

Gardening seemed an ideal place to start.

"No matter where you go, people say there's just something about gardening that makes them feel better," said Litt, who is also a researcher with the Barcelona Institute for Global Health.

But solid science on its benefits is hard to come by. Without evidence, it's hard to get support for new programs, she said.

Some small observational studies have found that people who garden tend to eat more fruits and vegetables and have a healthier weight. But it has been unclear whether healthier people just tend to garden, or gardening influences health.

Only three studies have applied the gold standard of scientific research, the randomized controlled trial, to the pastime. None have looked specifically at community gardening.

To fill the gap, Litt recruited 291 non-gardening adults, average age of 41, from the Denver area. More than a third were Hispanic and more than half came from low-income households.

After the last spring frost, half were assigned to the community gardening group and half to a control group that was asked to wait one year to start gardening.

The gardening group received a free community garden plot, some seeds and seedlings, and an introductory gardening course through the nonprofit Denver Urban Gardens program and a study partner.

Both groups took periodic surveys about their nutritional intake and mental health, underwent body measurements and wore activity monitors.

A fiber boost

By fall, those in the gardening group were eating, on average, 1.4 grams more fiber per day than the control group -- an increase of about 7%.

The authors note that fiber exerts a profound effect on inflammatory and immune responses, influencing everything from how we metabolize food to how healthy our gut microbiome is to how susceptible we are to diabetes and certain cancers.

While doctors recommend about 25 to 38 grams of fiber per day, the average adult consumes less than 16 grams.

"An increase of one gram of fiber can have large, positive effects on health," said co-author James Hebert, director of University of South Carolina's cancer prevention and control program.

The gardening group also increased their physical activity levels by about 42 minutes per week. Public health agencies recommend at least 150 minutes of physical activity per week, a recommendation only a quarter of the U.S. population meets. With just two to three visits to the community garden weekly, participants met 28% of that requirement.

Study participants also saw their stress and anxiety levels decrease, with those who came into the study most stressed and anxious seeing the greatest reduction in mental health issues.

The study also confirmed that even novice gardeners can reap measurable health benefits of the pastime in their first season. As they have more experience and enjoy greater yields, Litt suspects such benefits will increase.

Blooming relationships

The study results don't surprise Linda Appel Lipsius, executive director of Denver Urban Gardens (DUG), a 43-year-old nonprofit that helps about 18,000 people each year grow their own food in community garden plots.

"It's transformational, even life-saving, for so many people," Lipsius said.

Many DUG participants live in areas where access to affordable fresh fruits and vegetables is otherwise extremely limited. Some are low-income immigrants now living in apartments -- having a garden plot allows them to grow food from their home country and pass on traditional recipes to their family and neighbors.

The social connection is also huge.

"Even if you come to the garden looking to grow your food on your own in a quiet place, you start to look at your neighbor's plot and share techniques and recipes, and over time relationships bloom," said Litt, noting that while gardening alone is good for you, gardening in community may have additional benefits. "It's not just about the fruits and vegetables. It's also about being in a natural space outdoors together with others."

Litt said she hopes the findings will encourage health professionals, policymakers and land planners to look to community gardens, and other spaces that encourage people to come together in nature, as a vital part of the public health system. The evidence is clear, she said.

https://www.sciencedaily.com/releases/2023/01/230106144500.htm

Treatment for combat-related PTSD advances with method shown to be fast, effective

January 5, 2023

Science Daily/University of Texas Health Science Center at San Antonio

Study findings out today in JAMA Network Open show an important step forward in treating the psychological injuries of war.

Researchers report that treatment for combat-related post-traumatic stress disorder (PTSD), which affects hundreds of thousands of U.S. military personnel and veterans, can be both fast and effective for a majority of patients. Their study showed clinically significant reductions in PTSD symptoms in more than 60 percent of patients and long-term remission of the diagnosis in more than 50 percent after three weeks of outpatient Prolonged Exposure therapy. Study participants similarly showed significant improvements in related disability and daily functioning.

Results were comparable whether patients received traditional Prolonged Exposure, also called PE, condensed into three weeks of daily treatment or an intensive outpatient format including several enhancements to address specific challenges of PTSD in war fighters.

The research team, led by Alan Peterson, PhD, of The University of Texas Health Science Center at San Antonio (UT Health San Antonio), conducted the randomized clinical trial with 234 military personnel and veterans recruited from four locations in South and Central Texas. The effort was part of the work of the Consortium to Alleviate PTSD (CAP), a national network jointly funded by the U.S. Departments of Defense and Veterans Affairs.

Dr. Peterson, professor of psychiatry and behavioral sciences at UT Health San Antonio and director of the CAP and the STRONG STAR Consortium, said the findings advance the group's previous research and significantly improve upon earlier outcomes.

Improving outcomes for our war fighters

"We're excited to see a more than 10-point increase in PTSD remission rates compared to a previous PE study we conducted, when we initiated the first ever clinical trials evaluating PTSD treatments in active-duty military populations," said Dr. Peterson.

That first study tested the standard PE protocol, with 10 sessions of 90 minutes each over the course of eight weeks, as well as a massed format, with daily 90-minute sessions over two weeks. The two delivery formats proved equally effective in reducing symptoms and leading to a loss of diagnosis, with remission rates under 50 percent initially after treatment, and treatment gains maintained by about 40 percent of patients six months later. The massed format had much lower dropout rates.

"Those initial results were encouraging, indicating that PE is effective for combat-related PTSD," said Dr. Peterson. "But with much lower success rates than in civilians treated with this therapy, we wanted to make and test treatment adaptations potentially to address unique aspects of combat-related PTSD and improve outcomes," he said. That is what the current study did.

Design and rationale of the current study

Prolonged Exposure includes patients' repeated retelling of their trauma stories along with homework assignments to engage in activities patients otherwise avoid because they trigger traumatic memories or anxious feelings. The goal is to help patients process thoughts about their trauma, calm the anxiety the memories provoke, and regain control of their lives.

It was thought that, in the original study -- particularly with the massed format -- patients may not have had adequate time to complete homework assignments and may also have faced a number of distractions. So, for both arms of the current study, patients took leave from work or other daily responsibilities to devote themselves full-time to treatment and recovery.

Also with the current study, treatment time in both arms was expanded from two weeks to three, with the consideration that combat-related PTSD is more difficult to treat, and patients may need additional time to process traumatic memories.

The comparison arm, called Massed-PE, had these treatment delivery changes only. The other arm, called Intensive Outpatient or IOP-PE, had several additional enhancements that researchers hypothesized would improve treatment outcomes with combat-related PTSD.

Dr. Peterson explained one example. "Oftentimes, a civilian trauma involves a one-time traumatic event, such as an accident, or a repeated trauma of a certain type, such as abuse," he said. "In the course of one or more combat deployments, service members may experience hundreds of traumatic events involving different types of traumas. They also may have experienced other types of trauma outside the combat environment. And so we wanted to adapt the traditional PE protocol, in which a patient focuses only on one primary trauma during treatment, and allow patients in this study to work with therapists on their three top traumas."

He said the treatment involved starting with the least distressing of those three traumas to gain confidence in the therapy, then working up to the most distressing trauma. Some of the other modifications included team-based treatment, with more than one clinician supporting a patient's care; clinic-based completion of homework assignments to decrease avoidance; brief therapist feedback sessions during the day for added support and increased opportunities for processing; involvement of a family member or friend during educational sessions to help improve social support; and post-treatment booster sessions to help maintain treatment gains.

Findings, implications and next steps

Outcomes differed from researchers' expectations in that both arms showed similar levels of reductions in PTSD symptoms and related disability, as well as similar increases in PTSD remission rates and improved psychosocial functioning over time. With some measures, Massed-PE led to greater improvements initially that decreased by the six-month follow-up. IOP-PE patients were more likely to maintain their improvements six months after treatment.

Since long-term outcomes did not differ significantly, researchers say the additional investment of resources needed for the IOP-PE format may not be warranted, but the overall study findings are highly positive.

"With about two thirds of participants reporting clinically meaningful symptom improvement and more than half losing their PTSD diagnosis, this study provides important new evidence that combat-related PTSD can be effectively treated -- in as little as three weeks," said Dr. Peterson.

He and his colleagues stated that, while condensed treatments may not be feasible for everyone, "results show that compressed formats adapted to the military context resulted in significant, meaningful and lasting improvements in PTSD, disability and functional impairments for most participants."

They say this makes condensed treatments an important option for U.S. service members and veterans after two decades of military operations in Iraq and Afghanistan. These treatments also could gain attention now as the war in Ukraine has raised international concerns about the risk of PTSD in military personnel and civilians.

Moving forward, the study team notes that their findings show room for continued improvement in treating combat-related PTSD. They add that the compressed treatment formats evaluated in this study are well suited for the evaluation of new, alternative modes of therapy combining cognitive-behavioral treatments with medications and medical devices. "We have those types of studies already underway," said Dr. Peterson.

https://www.sciencedaily.com/releases/2023/01/230105151330.htm

Blood pressure drug holds promise for treating PTSD

January 5, 2023

Science Daily/Medical College of Georgia at Augusta University

There is new evidence that a 50-year-old blood pressure drug could find new purpose as a treatment to mitigate the often life-altering effects of increasingly prevalent PTSD, scientists say.

Clonidine is commonly used as a high blood pressure medication and for ADHD. It's also already been studied in PTSD because clonidine works on adrenergic receptors in the brain, likely best known for their role in "fight or flight," a heightened state of response that helps keep us safe. These receptors are thought to be activated in PTSD and to have a role in consolidating a traumatic memory. Clonidine's sister drug guanfacine, which also activates these receptors, also has been studied in PTSD. Conflicting results from the clinical trials have clonidine, which has shown promise in PTSD, put aside along with guanfacine, which has not.

Scientists at the Medical College of Georgia at Augusta University say it's time for another look at clonidine.

They have laboratory evidence that while the two drugs bind to the same receptors, they do different things there, says Qin Wang, MD, PhD, neuropharmacologist and founding director of the Program for Alzheimer's Therapeutics Discovery at MCG.

Their results published in the journal Molecular Psychiatry suggest that clonidine could provide immediate treatment to the significant number of people emerging from the current pandemic with PTSD, as well as from longer-established causes like wars and other violence.

Large-scale clinical trials of clonidine in PTSD are warranted, the scientists write. Their studies also indicate that other new therapies could be identified by looking at the impact on activation of a key protein called cofilin by existing drugs.

The new studies looked in genetically modified mice as well as neurons that came from human stem cells, which have the capacity to make many cell types.

In the hippocampus, the center of learning and memory, they found that a novel axis on an adrenergic receptor called ɑ2A is essential to maintaining fear memories in which you associate a place or situation, like the site of a horrific car accident or school shooting, with fear or other distressing emotions that are hallmarks of PTSD.

In this axis, they found the protein spinophilin interacts with cofilin, which is known to control protrusions on the synapses of neurons called dendritic spines, where memories are consolidated and stored.

A single neuron can have hundreds of these spines which change shape based on brain activity and whose changing impacts the strength of the synapse, the juncture between two neurons where they swap information.

"Normally whenever there is a stimulation, good or bad, in order to memorize it, you have to go through a process in which the spines store the information and get bigger," Wang says, morphing from a slender profile to a more mushroom-like shape.

"The mushroom spine is very important for your memory formation," says corresponding author Wang, Georgia Research Alliance Eminent Scholar in Neuropharmacology. For these mushroom shapes to happen, levels of cofilin must be significantly reduced in the synapse where the spines reside. That is where clonidine comes in.

The scientists found clonidine interferes with cofilin's exit by encouraging it to interact with the receptor which consequently interferes with the dendritic spine's ability to resume a mushroom shape and retain the memory. Guanfacine, on the other hand, had no effect on this key player cofilin.

The findings help clarify the disparate results in the clinical trials of these two similar drugs, Wang says. In fact, when mice got both drugs, the guanfacine appeared to lessen the impact of clonidine in the essential step of reconsolidating -- and so sustaining -- a traumatic memory, indicating their polar-opposite impact at least on this biological function, Wang says.

There was also living evidence. In their studies that mimicked how PTSD happens, mice were given a mild shock then treated with clonidine right after they were returned to the place where they received the shock and should be recalling what happened earlier. Clonidine-treated mice had a significantly reduced response, like freezing in their tracks, compared to untreated mice when brought back to the scene. In fact, their response was more like the mice who were never shocked. Guanfacine had no effect on freezing behavior.

Obviously, Wang says, they cannot know for certain how much the mice remember of what previously happened, but clearly those treated with clonidine did not have the same overt reaction as untreated mice or those receiving guanfacine.

"The interpretation is that they don't have as strong a memory," she says, noting that the goal is not to erase memories like those of wartime, rather diminish their disruption in a soldier's life.

When a memory is recalled, like when you return to an intersection where you were involved in a horrific car wreck, the synapses that hold the memory of what happened there become temporarily unstable, or labile, before the memory restabilizes, or reconsolidates. This natural dynamic provides an opportunity to intervene in reconsolidation and so at least diminish the strength of a bad memory, Wang says. Clonidine appears to be one way to do that.

Adrenergic drugs like clonidine bind to receptors in the central nervous system to reduce blood levels of the stress hormones you produce like epinephrine (adrenaline) and norepinephrine, which do things like increase blood pressure and heart rate.

Studies like one that came out 15 years ago, which only looked at guanfacine, indicated it was of no benefit in PTSD. But then in 2021, a retrospective look at a cohort of 79 veterans with PTSD treated with clonidine, for example, indicated 72% experienced improvement and 49% were much improved or very much improved with minimal side effects.

Previous basic science studies also have indicated that manipulating the adrenergic receptor can impact fear memory formation and memory, but how has remained unknown.

PTSD has emerged as a major neuropsychiatric component of the COVID-19 pandemic, affecting about 30% of survivors, a similar percentage of the health care workers who care for them and an estimated 20% of the total population, Wang says, which means the impact on human health and health care systems could be "profound."

Psychotherapy is generally considered the most effective treatment for PTSD, and some medications, like antidepressants, can also be used, but there are limited drug options, which include only two drugs which have Food and Drug Administration approval specifically for the condition, she says. The lack of approved drugs has led to off-label uses of drugs like clonidine.

Cofilin is a key element in helping muscle cells and other cell types contract as well as the flexibility of the cytoskeleton of the dendritic spine. A single neuron can have thousands of dendritic spines which change shape based on brain activity and whose changing shape impacts the strength of the synapse.

The U.S. Department of Veterans Affairs defines post-traumatic stress disorder as a mental health problem that some people develop after experiencing or witnessing a life-threatening or traumatic event. While problems like feeling on edge, trouble sleeping and/or nightmares may last a few weeks or more after the event, if symptoms like these as well as flashbacks and increasingly negative thoughts continue, it's likely PTSD. Sometimes symptoms don't surface until months after the initial event.

https://www.sciencedaily.com/releases/2023/01/230105083101.htm

People sleep the least from early 30s to early 50s

December 23, 2022

Science Daily/University College London

People sleep less in mid-adulthood than they do in early and late adulthood, finds a new study led by UCL, University of East Anglia and University of Lyon researchers.

Sleep duration declines in early adulthood until age 33, and then picks up again at age 53, according to the findings published in Nature Communications.

The study, involving 730,187 participants spread over 63 countries, revealed how sleep patterns change across the lifespan, and how they differ between countries.

Study participants were playing the Sea Hero Quest mobile game, a citizen science venture designed for neuroscience research, created by Deutsche Telekom in partnership with Alzheimer's Research UK, UCL, UEA and game developers Glitchers. Designed to aid Alzheimer's research by shedding light on differences in spatial navigational abilities, over four million people have played Sea Hero Quest, contributing to numerous studies across the project as a whole.

In addition to completing tasks testing navigational ability, anyone playing the game is asked to answer questions about demographic characteristics as well as other questions that can be useful to neuroscience research, such as on sleep patterns.

The researchers, led by Professor Hugo Spiers (UCL Psychology & Language Sciences) and Dr Antoine Coutrot (CNRS, University of Lyon) found that across the study sample, people sleep an average of 7.01 hours per night, with women sleeping 7.5 minutes longer than men on average. They found that the youngest participants in the sample (minimum age 19) slept the most, and sleep duration declined throughout people's 20s and early 30s before plateauing until their early 50s and increasing again. The pattern, including the newly-identified key time points of age 33 when declining sleep plateaus and 53 for sleep to increase again, was the same for men and women, and across countries and education levels.

The researchers say the decline in sleep during mid-life may be due to demands of childcare and working life.

Professor Spiers said: "Previous studies have found associations between age and sleep duration, but ours is the first large study to identify these three distinct phases across the life course. We found that across the globe, people sleep less during mid-adulthood, but average sleep duration varies between regions and between countries."

People who report sleeping the most are in Eastern European countries such as Albania, Slovakia, Romania and the Czech Republic, reporting 20-40 minutes extra sleep per night and the least in South East Asian countries including the Philippines, Malaysia and Indonesia. People in the United Kingdom reported sleeping slightly less than the average. People tended to sleep a bit less in countries closer to the equator.

The researchers found that navigational ability was unaffected by sleep duration for most of the sample, except for among older adults (aged 54-70) whose optimal sleep duration was seven hours, although they caution that the findings among older adults might be impacted by underlying health conditions.

https://www.sciencedaily.com/releases/2022/12/221223103424.htm

Scientists find key reason why loss of smell occurs in long COVID-19

The inflammatory mechanism could also help explain other long COVID-19 symptoms

December 21, 2022

Science Daily/Duke University Medical Center

The reason some people fail to recover their sense of smell after COVID-19 is linked to an ongoing immune assault on olfactory nerve cells and an associated decline in the number of those cells, a team of scientists led by Duke Health report.

The finding, publishing online Dec. 21 in the journal Science Translational Medicine, provides an important insight into a vexing problem that has plagued millions who have not fully recovered their sense of smell after COVID-19.

While focusing on the loss smell, the finding also sheds light on the possible underlying causes of other long COVID-19 symptoms -- including generalized fatigue, shortness of breath, and brain fog -- that might be triggered by similar biological mechanisms.

"One of the first symptoms that has typically been associated with COVID-19 infection is loss of smell," said senior author Bradley Goldstein, M.D., Ph.D., associate professor in Duke's Department of Head and Neck Surgery and Communication Sciences and the Department of Neurobiology.

"Fortunately, many people who have an altered sense of smell during the acute phase of viral infection will recover smell within the next one to two weeks, but some do not," Goldstein said. "We need to better understand why this subset of people will go on to have persistent smell loss for months to years after being infected with SARS-CoV2."

In the study, Goldstein and colleagues at Duke, Harvard and the University of California-San Diego analyzed olfactory epithelial samples collected from 24 biopsies, including nine patients suffering from long-term smell loss following COVID-19.

This biopsy-based approach -- using sophisticated single-cell analyses in collaboration with Sandeep Datta, M.D., Ph.D., at Harvard University -- revealed widespread infiltration of T-cells engaged in an inflammatory response in the olfactory epithelium, the tissue in the nose where smell nerve cells are located. This unique inflammation process persisted despite the absence of detectable SARS-CoV-2 levels.

Additionally, the number of olfactory sensory neurons were diminished, possibly due to damage of the delicate tissue from the ongoing inflammation.

"The findings are striking," Goldstein said. "It's almost resembling a sort of autoimmune-like process in the nose."

Goldstein said learning what sites are damaged and what cell types are involved is a key step toward beginning to design treatments. He said the researchers were encouraged that neurons appeared to maintain some ability to repair even after the long-term immune onslaught.

"We are hopeful that modulating the abnormal immune response or repair processes within the nose of these patients could help to at least partially restore a sense of smell," Goldstein said, noting this work is currently underway in his lab.

He said the findings from this study could also inform additional research into other long-COVID-19 symptoms that might be undergoing similar inflammatory processes.

https://www.sciencedaily.com/releases/2022/12/221221154434.htm

Smoking increases chances of mid-life memory loss, confusion

Study findings support quitting for brain benefits, researchers say

December 21, 2022

Science Daily/Ohio State University

Middle-aged smokers are far more likely to report having memory loss and confusion than nonsmokers, and the likelihood of cognitive decline is lower for those who have quit, even recently, a new study has found.

The research from The Ohio State University is the first to examine the relationship between smoking and cognitive decline using a one-question self-assessment asking people if they've experienced worsening or more frequent memory loss and/or confusion.

The findings build on previous research that established relationships between smoking and Alzheimer's Disease and other forms of dementia, and could point to an opportunity to identify signs of trouble earlier in life, said Jenna Rajczyk, lead author of the study, which appears in the Journal of Alzheimer's Disease.

It's also one more piece of evidence that quitting smoking is good not just for respiratory and cardiovascular reasons -- but to preserve neurological health, said Rajczyk, a PhD student in Ohio State's College of Public Health, and senior author Jeffrey Wing, assistant professor of epidemiology.

"The association we saw was most significant in the 45-59 age group, suggesting that quitting at that stage of life may have a benefit for cognitive health," Wing said. A similar difference wasn't found in the oldest group in the study, which could mean that quitting earlier affords people greater benefits, he said.

Data for the study came from the national 2019 Behavioral Risk Factor Surveillance System

Survey and allowed the research team to compare subjective cognitive decline (SCD) measures for current smokers, recent former smokers, and those who had quit years earlier. The analysis included 136,018 people 45 and older, and about 11% reported SCD.

The prevalence of SCD among smokers in the study was almost 1.9 times that of nonsmokers. The prevalence among those who had quit less than 10 years ago was 1.5 times that of nonsmokers. Those who quit more than a decade before the survey had an SCD prevalence just slightly above the nonsmoking group.

"These findings could imply that the time since smoking cessation does matter, and may be linked to cognitive outcomes," Rajczyk said.

The simplicity of SCD, a relatively new measure, could lend itself to wider applications, she said.

"This is a simple assessment that could be easily done routinely, and at younger ages than we typically start to see cognitive declines that rise to the level of a diagnosis of Alzheimer's Disease or dementia," Rajczyk said. "It's not an intensive battery of questions. It's more a personal reflection of your cognitive status to determine if you're feeling like you're not as sharp as you once were."

Many people don't have access to more in-depth screenings, or to specialists -- making the potential applications for measuring SCD even greater, she said.

Wing said it's important to note that these self-reported experiences don't amount to a diagnosis, nor do they confirm independently that a person is experiencing decline out of the normal aging process. But, he said, they could be a low-cost, simple tool to consider employing more broadly.

https://www.sciencedaily.com/releases/2022/12/221221121301.htm

Evening hot spring soaks lower cases of hypertension in older Japanese adults

December 21, 2022

Science Daily/Kyushu University

Nothing beats a good soak in a hot bath, and when it really hits the spot, you can almost feel your worries and ailments diffusing out into steam.

Perhaps there is nowhere better to treat what ails you than the hot springs at the historical city of Beppu, located on the north-east shores of Kyushu. Not only does the city boast the most onsen -- Japanese for hot springs -- in the country, it is also a research hotbed for investigating the health benefits of onsen and treatments based on them.

In a paper published in Scientific Reports, researchers from Kyushu University's Beppu Hospital report that onsen bathing in the evening hours is linked to lower prevalence of hypertension in Japanese adults over 65.

Humanity's history with hot springs can be found as far back as ancient Egypt over 5,000 years ago. Onsen themselves are even referenced in Japan's oldest books and creation myths, and people have touted the health benefits of soaking in hot springs well into the modern age.

In 1931, Kyushu University founded the 'Onsen Therapy Research Institute' in the historical city of Beppu to study the therapeutic benefits of onsen. Over the 90 years since, the institute has grown to cover a range of modern medical fields including internal and external medicine, rehabilitation, gynecology, and cardiology. Nonetheless, it still conducts research on the health benefits of onsen and continues to make a name for itself as a national hot spring treatment research center.

"In 2011, the institute partnered with the city and conducted a massive survey of Beppu residents over 65 about their health and onsen habits," explains Satoshi Yamasaki, a Lecturer of internal medicine at the Beppu Hospital and first author of the study. "This is something we can uniquely do here in Beppu because onsen are a part of everybody's daily lives, especially for the elderly. There are local onsen facilities everywhere, and you can even connect onsen to your home utilities."

The survey collected information regarding medical history, onsen habits, and even the type of onsen frequented from over 11,000 people -- nearly one-third of Beppu city residents over 65. Since then, researchers like Yamasaki have been going through the trove of data, analyzing the connection between health and onsen use.

"I wanted to find out if long-term onsen bathing had any preventative effects on hypertension. Past research has shown that traditional thermal therapy and hot spring bathing are effective against various diseases including hypertension," continues Yamasaki. "In Japan especially, it is the leading cause of hospital visits and long-term prescription medication use."

In their data set, the team was able to pull out 4,001 individuals who currently have, or a history of, hypertension. Their first analysis found that having hypertension also increased the likelihood for the individual to have a history of other pathologies.

"These were the usual suspects of pathologies correlated with hypertension such as gout, arrhythmia, renal disease, and diabetes," Yamasaki explains. "But it was when we looked at an individual's onsen habits that we found something interesting. We found that individuals who bathed in onsen after 19:00 were roughly 15% less likely to have hypertension."

The team hypothesizes two main reasons for these findings: lower stress and faster sleep onset. Previous research has shown that faster onset of sleep can improve sleep quality and improved hypertension control. Moreover, thermal therapies such as sauna bathing have been shown to alter levels of stress markers in the blood and lead to better mitigation of hypertension.

"Of course, we must acknowledge some limitations in our study. Selection bias is expected whenever a questionnaire is used. We also could not account for the respondent's daily lifestyle that could affect hypertension, or if they are being treated for hypertension medically or with onsen," concludes Yamasaki. "Nonetheless, we found that habitual nighttime onsen bathing was associated with a lower prevalence of hypertension. To understand these results further, we will need more data from patients."

https://www.sciencedaily.com/releases/2022/12/221221090621.htm

During sleep, brain regions synchronize to create motor memory

December 19, 2022

Science Daily/University of California - San Francisco

When the Golden State Warriors' Steph Curry makes a free throw, his brain draws on motor memory. Now researchers at UC San Francisco (UCSF) have shown how this type of memory is consolidated during sleep, when the brain processes the day's learning to make the physical act of doing something subconscious.

The study, published Dec. 14, 2022, in Nature, shows the brain does this by reviewing the trials and errors of a given action. In the analogy, that means sorting through all the free throws Curry has ever thrown, weeding out the memory of all the actions except those that hit the mark, or that the brain decided were "good enough." The result is the ability to make the free throw with a high degree of accuracy without having to think about the physical movements involved.

"Even elite athletes makes errors, and that's what makes the game interesting," said Karunesh Ganguly, MD, PhD, a professor of neurology and member of the UCSF Weill Institute for Neurosciences. "Motor memory isn't about perfect performance. It's about predictable errors and predictable successes. As long as the errors are stable from day to day, the brain says, 'Let's just lock this memory in.'"

Ganguly and his team found that the "locking in" process involves some surprisingly complex communication between different parts of the brain and takes place during the deep restorative slumber known as non-REM sleep.

Sleep is important because our conscious brains tend to focus on the failures, said Ganguly, who previously identified the sleep-associated brain waves that influence skill retention.

"During sleep, the brain is able to sift through all the instances it's taken in and bring forward the patterns that were successful," he said.

Earthbound Motor Skills Wouldn't Work on Avatar's Planet Pandora

It was once thought that learning motor skills only required the motor cortex. But in recent years a more complex picture has emerged.

To look into this process more closely, Ganguly set rats on a task to reach for pellets. Then, the team looked at their brain activity in three regions during NREM sleep: the hippocampus, which is the region responsible for memory and navigation, the motor cortex and the prefrontal cortex (PFC).

Over the course of 13 days, a pattern emerged.

First, in a process called "fast learning," the PFC coordinated with the hippocampus, likely enabling the animal to perceive its motion with respect to the space around it and its location in that space. In this phase, the brain seemed to be exploring and comparing all the actions and patterns created while practicing the task.

Second, in a process called slow learning, the PFC appeared to make value judgements, likely driven by reward centers that were activated when the task was successful. It engaged in crosstalk with the motor cortex and the hippocampus, turning down the signals related to failures and turning up the ones related to successes.

Finally, as the electrical activity of the regions became synchronized, the role of the hippocampus diminished and the instances the brain had noted as rewarding came to the fore, where they were stored in what we call "motor memory."

While the rats were initially learning the task, their brain signals were noisy and disorganized. As time went on, Ganguly could see the signals synchronizing, until the rats were succeeding about 70 percent of the time. After that point, the brain seemed to ignore mistakes and maintained the motor memory as long as the level of success was stable. In other words, the brain starts to expect a certain level of error and does not update the motor memory.

Just like NBA players, the rats mastered a skill based on a mental model of how the world works, which they created from their physical experience with gravity, space and other cues. But this kind of motor learning wouldn't easily transfer to a situation where the cues and physical environment were different.

"If all that changed, for example, if Steph Curry was in the world of Avatar, he might not look as skilled initially," Ganguly said.

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What if Curry hurt a finger and had to learn to shoot baskets a little differently? The study offered an answer.

"It's possible to unlearn a task, but to do that, you have to stress the situation to a point where you're making mistakes," Ganguly said.

When the researchers made a slight change to the rats' pellet procurement task, the rats would make more mistakes and the researchers saw more noise in the rats' brain activity.

The change was small enough that the rats didn't have to go all the way back to the beginning of their learning, only to the "breaking point," and relearn the task from there.

But because motor memory gets ingrained as a set of motions that follow each other in time, Ganguly said, changing motor memory in a complex motion like free throwing a basketball might require changing a motion that is used to initiate the whole sequence.

If Curry usually bounces a basketball twice before he throws, Ganguly said, "It might be best to retrain the brain by bouncing it only once, or three times. That way, you'd start with a clean slate."

https://www.sciencedaily.com/releases/2022/12/221219164831.htm

Casting light on, and through, your eyelids

Science Daily/Osaka Metropolitan University

Summary:

Scientists measured the light transmittance of the eyelids when the eyes are closed, and found that perceived closed-eye brightness is significantly stronger than previously reported. The influence of color was also observed, with red light perceived as brighter and blue light perceived as darker. Additionally, there were significant differences between experimental participants; for some, their perception of brightness barely differed between open- and closed-eye conditions.

Can't sleep when your partner is on his or her smartphone? This may not be oversensitivity on your part; your eyelids probably deserve some of the blame. A scientist from Osaka Metropolitan University shows that eyelids transmit much more light than previously thought. The findings were published in Color Research and Application.

Sleep deprivation and sleep disorders are detrimental to health and interfere with daily life. Studies have been conducted to elucidate the mechanisms underlying various factors that affect sleep. One major factor is the lighting environment. Changes in light exposure during the daytime and nighttime or during sleep have been reported to influence circadian rhythms and sleep quality.

Currently, indices to describe the lighting environment, such as illuminance and color temperature, are based on visual characteristics under well-lit conditions when the eyes are open. However, given that the eyes are closed while sleeping, understanding the light transmittance of the eyelids and perceived closed-eye brightness is essential to properly describe the lighting environment during sleep. Although several studies have been carried out to measure eyelid transmittance, experimental conditions differed significantly from lighting environments in daily life: evaluations were conducted under extremely low illuminance, for example, or with only one eye.

Professor Hideki Sakai, from the Graduate School of Human Life and Ecology at Osaka Metropolitan University, applied a new method to measure the light transmittance of the eyelids when the eyes are shut. His results indicate that closed-eye perception of brightness is remarkably stronger than previously reported.

Professor Sakai conducted experiments on a total of 33 participants under relatively bright conditions (illuminance of 100 lux) in which each participant's entire face was illuminated. A lighting device was used to increase or decrease facial illuminance, and closed-eye light transmittance was measured by having the participants make adjustments to match the levels of brightness they perceived with their eyes closed and with their eyes open. Monochromatic red, yellow, green, and blue LEDs and a white LED were used as light sources.

The experiment results show that eyelid transmittance values were up to 10 times higher than those (i.e., 0.3%-14.5%) reported in the past. The color of the light also made a difference, with red light perceived as brighter and blue light perceived as darker. Additionally, Professor Sakai noted significant differences between individual participants; for some, their perception of brightness remained almost unchanged between the open- and closed-eye conditions.

"By properly understanding and utilizing the lighting environment when the eyes are closed, I hope to advance research on appropriate lighting not only during normal sleep but also in various other situations, such as during naps or riding late-night transportation," stated Professor Sakai. "Since light colors with low transmittance are perceived as dark only when people close their eyes, I think that this finding could be useful for designing lighting in spaces with both awake and sleeping people, such as evacuation centers."

https://www.sciencedaily.com/releases/2022/12/221219094858.htm

New support for a serotonin deficit in depression

Since the 1960s, researchers have postulated that major depression stems from disruptions in the serotonin neurotransmitter system, but the evidence for that idea, though plentiful, was indirect. In fact, a recent comprehensive analysis of existing studies concluded that there was not strong evidence to support the "serotonin hypothesis." In its wake, some in the field have called for a reexamination of the hypothesis. Not so fast, says a new study that provides direct evidence of disrupted serotonin release in the brains of individuals with depression.

The study appears in Biological Psychiatry, published by Elsevier.

Depression is among the most common mental illnesses and causes of disability worldwide. Despite the lack of direct evidence for disrupted serotonin signaling in the depressed brain, medications used to treat depression overwhelmingly target the serotonin signaling system to increase extracellular serotonin, also known as 5-hydroxytryptamine (5-HT). Only about half of patients respond to antidepressants, and fewer than 30% experience total remission. A better understanding of 5-HT dynamics in depression could help guide more effective therapies.

"Our thinking about the role of serotonin in depression has evolved significantly over the past decade. We once thought that serotonin changes could account for the entirety of depression. When this simple hypothesis could no longer be supported, some were inclined to dismiss any role for serotonin in depression," said John Krystal, MD, editor-in-chief of Biological Psychiatry. "The current study provides important new support for further exploration of the role of serotonin in depression. This is particularly timely, as drugs targeting serotonin receptors, such as psychedelics, are being explored as potential new treatments for mood disorders."

The study, conducted by Invicro, a global, imaging contract research organization, in collaboration with researchers from Imperial College London, King's College London, Copenhagen University, and the University of Oxford, used a novel imaging technique to look directly at the magnitude of serotonin released from neurons in response to a pharmacological challenge. In previous work, these researchers pioneered the use of positron emission tomography (PET) with the radioligand [11C]Cimbi-36 to detect serotonin release. In the current study, the researchers applied this methodology to compare serotonin release in 17 patients with depression and 20 healthy individuals.

David Erritzoe, MRCPsych, PhD, lead author of the paper, said, "This study used a new and more direct method to measure serotonin in the living human brain, and the results suggest reduced serotonin (release) functioning in depression. This imaging method, in combination with similar methods for other brain systems, has the potential to help us to better understand the varying -- sometimes limited or even lacking -- treatment responses that people with depression have to antidepressant medication."

Participants with depression and healthy controls underwent PET scanning with [11C]Cimbi-36 to measure 5-HT2A receptor availability in the frontal cortex; the two groups did not differ significantly at baseline. Both groups then received a dose of d-amphetamine, a stimulant drug that works to increase 5-HT concentration outside of neurons, where it interacts with 5-HT2A receptors and reduces the binding of [11C]Cimbi-36. In a second scanning session three hours after drug administration, healthy control participants had significantly reduced 5-HT2A receptor availability, indicating an increase in serotonin levels. Participants with depression, however, did not show a significant decrease in binding potential, suggesting they had a blunted serotonin release capacity in key brain regions.

The study found no relationship between the severity of depression and the extent of serotonin release capacity deficits. Of note, all patients were free of antidepressant medication, and 11 out of the 17 had never received antidepressant treatment, indicating that low serotonin release capacity is a feature of depression rather than a result of antidepressant treatment.

This first direct evaluation of serotonin levels in the brain of individuals with depression is a major step forward in laying to rest the speculations questioning the involvement of serotonergic neurotransmission in the pathology of depression. Depression is a multifaceted disorder that may have multiple causes, and different subtypes may involve multiple neurotransmitter systems. Serotonergic dysfunction is unlikely to explain all the clinical features encountered in this disorder. Nevertheless, this study demonstrates that serotonergic deficits are present in unmedicated depressed individuals.

Eugenii Rabiner, MBBCh, FCPsych SA, at Invicro and senior author of the paper said, "It has taken our field over 20 years to develop a method that enables the measurement of serotonin release in the living human brain. I am very pleased that we managed to develop this method and apply it to clarify this important aspect of the pathophysiology of depression. I hope that we can use this technique in future to explore the different symptoms of depression, as well as serotonergic deficits found in other conditions, such as Parkinson's disease."

https://www.sciencedaily.com/releases/2022/12/221215120730.htm

Patterns of lifespan weight gain/loss may predict dementia risk

Monitoring risk indicators such as weight patterns offer opportunities for early intervention

December 15, 2022

Science Daily/Boston University School of Medicine

Dementia is a growing global public health concern currently affecting 50 million people and is expected to rise dramatically to more than 150 million cases worldwide by 2050. Obesity, commonly measured by body mass index (BMI), continues to be a global epidemic and earlier studies suggested that obesity at midlife may lead to increased risk for dementia. But the association between BMI and the risk of dementia remains unclear.

Now, researchers from Boston University Chobanian & Avedisian School of Medicine and Chinese Academy of Medical Sciences & Peking Union Medical College, have found that different patterns of BMI changes over one's life course may be an indicator of a person's risk for dementia.

"These findings are important because previous studies that looked at weight trajectories didn't consider how patterns of weight gain/stability/loss might help signal that dementia is potentially imminent," explained corresponding author Rhoda Au, PhD, professor of anatomy and neurobiology.

Through the Framingham Heart Study, a group of participants was followed for 39 years and their weight was measured approximately every 2-4 years. The researchers compared different weight patterns (stable, gain, loss) among those who did and did not become demented.

They found the overall trend of declining BMI was associated with a higher risk of developing dementia. However, after further exploration, they found a subgroup with a pattern of initial increasing BMI followed by declining BMI, both occurring within midlife, which appeared to be central to the declining BMI-dementia association.

Au points out that for individuals, family members, and primary care physicians, it is relatively easy to monitor weight. "If after a steady increase in weight that is common as one gets older, there is an unexpected shift to losing weight post midlife, it might be good to consult with one's healthcare provider and pinpoint why. There are some potential treatments emerging where early detection might be critical in the effectiveness of any of these treatments as they are approved and become available," she adds.

The researchers hope this study will illustrate that the seeds for dementia risk are being sowed across many years, likely even across the entire lifespan. "Dementia is not necessarily inevitable and monitoring risk indicators such as something as easy to notice as weight patterns, might offer opportunities for early intervention that can change the trajectory of disease onset and progression."

https://www.sciencedaily.com/releases/2022/12/221215104559.htm