Education may be protective for people with gene for familial early onset Alzheimer's

August 5, 2020

Science Daily/American Academy of Neurology

Even for people who carry the gene for early onset Alzheimer's disease, more years of education may slow the development of beta-amyloid plaques in the brain that are associated with the disease, according to a new study published in the August 5, 2020, online issue of Neurology®, the medical journal of the American Academy of Neurology.

About 1-6% of people with Alzheimer's disease have rare genes that cause the disease in everyone who has them. This is called familial Alzheimer's disease. It leads to an early onset of the disease, when people are in their 30s to 50s.

"Because we've assumed that the effects of these genes can't be changed, very little research has been done on whether we can modify the trajectory of the disease," said study author Sylvia Villeneuve, PhD, of the McGill University in Montreal, Canada. "It's exciting to see that education may play a role in delaying the start of this devastating disease, which affects people during the prime of life."

Most people diagnosed with Alzheimer's have the sporadic form of the disease, which is thought to be caused by a combination of both environmental and genetic factors, including a gene variant called APOE ?4, or apolipoprotein E ?4. Having this gene variant is known to increase the development of amyloid plaques in the brain, even though it does not guarantee that the person will develop symptoms of Alzheimer's disease.

The study involved two groups: one group of 106 people with an average age of 67 who had a parent diagnosed with the sporadic form of Alzheimer's disease, of whom 39% had the APOE ?4 gene variant; and another group of 117 people with an average age of 35 who had the gene mutations linked to familial early onset Alzheimer's disease, of whom 31% also had the APOE ?4 gene variant. Each group had an average 15 years of education. None of the participants showed symptoms of the disease at the start of the study.

Participants had brain scans to determine levels of amyloid plaques.

Researchers found that in the people with familial early onset Alzheimer's, increasing levels of education were associated with lower levels of amyloid plaques in the brain. The strength of the association between education and plaque levels was similar to the strength of this same association in people at risk of sporadic Alzheimer's disease.

In both groups, people with less than 10 years of education had about twice the amount of amyloid plaques when compared to people with more than 16 years of education.

"While it has been believed that people with familial Alzheimer's disease, with its strong genetic causes, may have few ways to slow development of the disease, our study shows that education may be somewhat protective, perhaps promoting brain resistance against these plaques, just as it has been shown to be in people with unknown causes of the disease," said Villeneuve.

A limitation of the study was that most participants were white, so results may not be the same for all people. Also, the quality of education may be affected by other factors like socioeconomic status, so future studies should look more closely at other factors in addition to years of education to determine whether other environmental factors may be at play to explain these study results.

https://www.sciencedaily.com/releases/2020/08/200805160829.htm

Can sleep protect us from forgetting old memories?

Computational models examine how sleep encodes new memories while preventing damage to old ones

August 4, 2020

Science Daily/University of California - San Diego

From lowering your risk of obesity and cardiovascular disease to improving your concentration and overall daily performance, sleep has been proven to play a critical role in our health. In a new study, researchers at University of California San Diego School of Medicine report that sleep may also help people to learn continuously through their lifetime.

Writing in the August 4, 2020 online issue of eLife, researchers used computational models capable of simulating different brain states, such as sleep and awake, to examine how sleep consolidates newly encoded memories and prevents damage to old memories.

"The brain is very busy when we sleep, repeating what we have learned during the day. Sleep helps reorganize memories and presents them in the most efficient way. Our findings suggest that memories are dynamic, not static. In other words, memories, even old memories, are not final. Sleep constantly updates them," said Maksim Bazhenov, PhD, lead author of the study and professor of medicine at UC San Diego. "We predict that during the sleep cycle, both old and new memories are spontaneously replayed, which prevents forgetting and increases recall performance."

Bazhenov said that memory replay during sleep plays a protective role against forgetting by allowing the same populations of neurons to store multiple interfering memories. "We learn many new things on a daily basis and those memories compete with old memories. To accommodate all memories, we need sleep."

For example, imagine learning how to navigate to a parking lot by going left at one stop sign and right at one traffic light. The next day, you have to learn how to get to a different parking lot using different directions. Bazhenov said sleep consolidates those memories to allow recollection of both.

"When you play tennis, you have a certain muscle memory. If you then learn how to play golf, you have to learn how to move the same muscles in a different way. Sleep makes sure that learning golf does not erase how to play tennis and makes it possible for different memories to coexist in the brain," said Bazhenov.

The authors suggest that the restorative value of sleep may be what is lacking in current state-of-the-art computer systems that power self-driving cars and recognize images with performances that far exceed humans. However, these artificial intelligence systems lack the ability to learn continuously and will forget old knowledge when new information is learned. "We may need to add a sleep-like state to computer and robotic systems to prevent forgetting after new learning and to make them able to learn continuously," said Bazhenov.

Bazhenov said the study results could lead to developing new stimulation techniques during sleep to improve memory and learning. This may be particularly important in older adults or persons suffering from learning disabilities.

"While sleep is certainly involved in many important brain and body functions, it may be critical for making possible what we call human intelligence -- the ability to learn continuously from experience, to create new knowledge and to adapt as the world changes around us," said Bazhenov.

https://www.sciencedaily.com/releases/2020/08/200804122233.htm

New study shows how infrared lasers destroy harmful protein aggregates in Alzheimer's

August 4, 2020

Science Daily/Tokyo University of Science

The agglomeration of proteins into structures called amyloid plaques is a common feature of many neurodegenerative diseases, including Alzheimer's. Now, scientists reveal, through experiments and simulations, how resonance with an infrared laser, when it is tuned to a specific frequency, causes amyloid fibrils to disintegrate from the inside out. Their findings open doors to novel therapeutic possibilities for amyloid plaque-related neurodegenerative diseases that have thus far been incurable.

A notable characteristic of several neurodegenerative diseases, such as Alzheimer's and Parkinson's, is the formation of harmful plaques that contain aggregates -- also known as fibrils -- of amyloid proteins. Unfortunately, even after decades of research, getting rid of these plaques has remained a herculean challenge. Thus, the treatment options available to patients with these disorders are limited and not very effective.

In recent years, instead of going down the chemical route using drugs, some scientists have turned to alternative approaches, such as ultrasound, to destroy amyloid fibrils and halt the progression of Alzheimer's disease. Now, a research team led by Dr Takayasu Kawasaki (IR-FEL Research Center, Tokyo University of Science, Japan) and Dr Phuong H. Nguyen (Centre National de la Recherche Scientifique, France), including other researchers from the Aichi Synchrotron Radiation Center and the Synchrotron Radiation Research Center, Nagoya University, Japan, has used novel methods to show how infrared-laser irradiation can destroy amyloid fibrils.

In their study, published in Journal of Physical Chemistry B, the scientists present the results of laser experiments and molecular dynamics simulations. This two-pronged attack on the problem was necessary because of the inherent limitations of each approach, as Dr Kawasaki explains, "While laser experiments coupled with various microscopy methods can provide information about the morphology and structural evolution of amyloid fibrils after laser irradiation, these experiments have limited spatial and temporal resolutions, thus preventing a full understanding of the underlying molecular mechanisms. On the other hand, though this information can be obtained from molecular simulations, the laser intensity and irradiation time used in simulations are very different from those used in actual experiments. It is therefore important to determine whether the process of laser-induced fibril dissociation obtained through experiments and simulations is similar."

The scientists used a portion of a yeast protein that is known to form amyloid fibrils on its own. In their laser experiments, they tuned the frequency of an infrared laser beam to that of the "amide I band" of the fibril, creating resonance. Scanning electron microscopy images confirmed that the amyloid fibrils disassembled upon laser irradiation at the resonance frequency, and a combination of spectroscopy techniques revealed details about the final structure after fibril dissociation.

For the simulations, the researchers employed a technique that a few members of the current team had previously developed, called "nonequilibrium molecular dynamics (NEMD) simulations." Its results corroborated those of the experiment and additionally clarified the entire amyloid dissociation process down to very specific details. Through the simulations, the scientists observed that the process begins at the core of the fibril where the resonance breaks intermolecular hydrogen bonds and thus separates the proteins in the aggregate. The disruption to this structure then spreads outward to the extremities of the fibril.

Together, the experiment and simulation make a good case for a novel treatment possibility for neurodegenerative disorders. Dr Kawasaki remarks, "In view of the inability of existing drugs to slow or reverse the cognitive impairment in Alzheimer's disease, developing non-pharmaceutical approaches is very desirable. The ability to use infrared lasers to dissociate amyloid fibrils opens up a promising approach."

The team's long-term goal is to establish a framework combining laser experiments with NEMD simulations to study the process of fibril dissociation in even more detail, and new works are already underway. All these efforts will hopefully light a beacon of hope for those dealing with Alzheimer's or other neurodegenerative diseases.

https://www.sciencedaily.com/releases/2020/08/200804111501.htm

Baby boomers show concerning decline in cognitive functioning

Trend reverses progress over several generations, study finds

August 3, 2020

Science Daily/Ohio State University

In a reversal of trends, American baby boomers scored lower on a test of cognitive functioning than did members of previous generations, according to a new nationwide study.

Findings showed that average cognition scores of adults aged 50 and older increased from generation to generation, beginning with the greatest generation (born 1890-1923) and peaking among war babies (born 1942-1947).

Scores began to decline in the early baby boomers (born 1948-1953) and decreased further in the mid baby boomers (born 1954-1959).

While the prevalence of dementia has declined recently in the United States, these results suggest those trends may reverse in the coming decades, according to study author Hui Zheng, professor of sociology at The Ohio State University.

"It is shocking to see this decline in cognitive functioning among baby boomers after generations of increases in test scores," Zheng said.

"But what was most surprising to me is that this decline is seen in all groups: men and women, across all races and ethnicities and across all education, income and wealth levels."

Results showed lower cognitive functioning in baby boomers was linked to less wealth, along with higher levels of loneliness, depression, inactivity and obesity, and less likelihood of being married.

The study was published online recently in the Journals of Gerontology: Social Sciences.

Zheng analyzed data on 30,191 Americans who participated in the 1996 to 2014 Health and Retirement Survey, conducted by the University of Michigan. People over 51 years old were surveyed every two years.

As part of the study, participants completed a cognitive test in which they had to recall words they had heard earlier, count down from 100 by 7s, name objects they were shown and perform other tasks.

Other research has shown that overall rates of mortality and illness have increased in baby boomers, but generally found that the highly educated and wealthiest were mostly spared.

"That's why it was so surprising to me to see cognitive declines in all groups in this study," Zheng said. "The declines were only slightly lower among the wealthiest and most highly educated."

Zheng also compared cognition scores within each age group across generations so that scores are not skewed by older people who tend to have poorer cognition. Even in this analysis, the baby boomers came out on bottom.

"Baby boomers already start having lower cognition scores than earlier generations at age 50 to 54," he said.

The question, then, is what has happened to baby boomers? Zheng looked for clues across the lifetimes of those in the study.

Increasing cognition scores in previous generations could be tied to beneficial childhood conditions -- conditions that were similar for baby boomers, Zheng said.

Baby boomers' childhood health was as good as or better than previous generations and they came from families that had higher socioeconomic status. They also had higher levels of education and better occupations.

"The decline in cognitive functioning that we're seeing does not come from poorer childhood conditions," Zheng said.

The biggest factors linked to lower cognition scores among baby boomers in the study were lower wealth, higher levels of self-reported loneliness and depression, lack of physical activity and obesity.

Living without a spouse, being married more than once in their lives, having psychiatric problems and cardiovascular risk factors including strokes, hypertension, heart disease and diabetes were also associated with lower cognitive functioning among people in this generation.

"If it weren't for their better childhood health, move favorable family background, more years of education and higher likelihood of having a white-collar occupation, baby boomers would have even worse cognitive functioning," Zheng said.

There were not enough late baby boomers (born in 1960 or later) to include in this study, but Zheng said he believes they will fare no better. The same might be true for following generations unless we find a solution for the problems found here, he said.

While many of the problems linked to lower cognitive functioning are symptoms of modern life, like less connection with friends and family and growing economic inequality, other problems found in this study are unique to the United States, Zheng said. One example would be the lack of universal access and high cost of health care.

"Part of the story here are the problems of modern life, but it is also about life in the U.S.," he said.

One of the biggest concerns is that cognitive functioning when people are in their 50s and 60s is related to their likelihood of having dementia when they are older.

"With the aging population in the United States, we were already likely to see an increase in the number of people with dementia," Zheng said.

"But this study suggests it may be worse than we expected for decades to come."

https://www.sciencedaily.com/releases/2020/08/200803092125.htm

Memory loss reversed or abated in those with cognitive decline

July 31, 2020

Science Daily/IOS Press

Researchers sought to determine whether a comprehensive and personalized program, designed to mitigate risk factors of Alzheimer's disease could improve cognitive and metabolic function in individuals experiencing cognitive decline. Findings provided evidence that this approach can improve risk factor scores and stabilize cognitive function.

Latest research from Affirmativ Health succeeds in treating cognitive decline using personalized, precision medicine.

Affirmativ Health sought to determine whether a comprehensive and personalized program, designed to mitigate risk factors of Alzheimer's disease could improve cognitive and metabolic function in individuals experiencing cognitive decline. Findings provided evidence that this approach can improve risk factor scores and stabilize cognitive function.

July 31, 2020/Sonoma, CA Cognitive decline is a major concern of the aging population. Already, Alzheimer's disease affects approximately 5.4 million Americans and 30 million people globally. Without effective prevention and treatment, the prospects for the future are bleak. By 2050, it is estimated that 160 million people globally will have the disease, including 13 million Americans, leading to potential bankruptcy of the Medicare system. Unlike several other chronic illnesses, Alzheimer's disease is on the rise -- recent estimates suggest that Alzheimer's disease has become the third leading cause of death in the United States behind cardiovascular disease and cancer. Since its first description over 100 years ago, Alzheimer's disease has been without effective treatment. While researchers continue to seek out a cure, it is becoming clear that there are effective treatment options. More and more research supports the conclusion that Alzheimer's disease is not a disease of only Beta Amyloid plaques and Tao tangles but a complex and systemic disease. In this study of patients with varying levels of cognitive decline, it is demonstrated how a precision and personalized approach results in either stabilization or improvement in memory.

Interventions to stop the progression of Alzheimer's disease have been marginally successful at best. This study uses a more comprehensive, personalized approach addressing each participant's unique risk factors. "The findings, published in the Journal of Alzheimer's Disease Reports (Journal of Alzheimer's Disease Reports 4(1)), are encouraging and indicate that a more extensive clinical study is warranted," said Brian Kennedy, PhD, Director of The Centre for Healthy Aging, National University Health System, Singapore and Chief Scientific Officer, Affirmativ Health.

The Affirmativ Health scientific team, after thorough review of published research, has developed a comprehensive approach to addressing scientifically supported risk factors that have been rigorously defined as interventions to promote prevention, increased resiliency, and stabilization of brain function in the realm of AD and dementia. Utilizing cutting edge technology in concert with in-person coaching and consultation, we are demonstrating that a multi-modal and personalized approach promotes an improved resiliency and restoration of optimal brain function. The personalized therapeutic program includes genetics, an extensive blood panel, medical history and lifestyle data to evaluate relevant metabolic risk factors and nutrient levels associated with cognitive health. "Target laboratory levels differ from standard laboratory ranges as the goal is to reach optimized levels for cognitive health," Ginger Schechter, MD, Chief Medical Officer, Affirmativ Health

The study approach considers more than 35 factors known to contribute to cognitive decline. Results demonstrate that certain of those factors are more affected than others again demonstrating the need for a more precise treatment plan. "This study supports the need for an approach that focuses on a one-size fits one, not a one-size fits all, approach that comprehensively assesses all involved risk factors affecting memory loss," Denise M Kalos, CEO Affirmativ Health

In conjunction with the publication of this vital study, and to expose alternative treatment options for Alzheimer's disease and cognitive decline, the team at Affirmativ Health has written a book, Outsmart your Brain -- an Insider's Guide to Life-Long Memory. "Memory is not something that should diminish with age; you are never too young to start developing healthy habits that can ultimately impact your cognition," Outsmart Your Brain. This book leverages the foundation of Affirmativ Health's research to deliver a tips and tools guide for the maintenance of good cognitive health. "Far too few people understand how critical lifestyle and dietary choices are for brain function. 'Outsmart Your Brain' is an important tool to get this information into the hands of those who should know it, everyone!, in easy-to-understand language," Ryan R. Fortna, MD, PhD, Chief Medical/Scientific Officer, ADx Healthcare.

https://www.sciencedaily.com/releases/2020/07/200731104124.htm

Forty percent of dementia cases could be prevented or delayed by targeting 12 risk factors throughout life

July 30, 2020

Science Daily/University of Southern California - Health Sciences

Modifying 12 risk factors over a lifetime could delay or prevent 40% of dementia cases, according to an updated report by the Lancet Commission on dementia prevention, intervention and care presented at the Alzheimer's Association International Conference (AAIC 2020).

Twenty-eight world-leading dementia experts added three new risk factors in the new report -- excessive alcohol intake and head injury in mid-life and air pollution in later life. These are in addition to nine factors previously identified by the commission in 2017: less education early in life; mid-life hearing loss, hypertension and obesity; and smoking, depression, social isolation, physical inactivity and diabetes later in life (65 and up).

"We are learning that tactics to avoid dementia begin early and continue throughout life, so it's never too early or too late to take action," says commission member and AAIC presenter Lon Schneider, MD, co-director of the USC Alzheimer Disease Research Center's clinical core and professor of psychiatry and the behavioral sciences and neurology at the Keck School of Medicine of USC.

Dementia affects some 50 million people globally, a number that is expected to more than triple by 2050, particularly in low- and middle-income countries where approximately two-thirds of people with dementia live, according to the report. Women are also more likely to develop dementia than men.

However, in certain countries, such as the United States, England and France, the proportion of older people with dementia has fallen, probably in part due to lifestyle changes, demonstrating the possibility of reducing dementia through preventative measures, Schneider says.

Schneider and commission members recommend that policymakers and individuals adopt the following interventions:

• Aim to maintain systolic blood pressure of 130 mm Hg or less from the age of 40.

• Encourage use of hearing aids for hearing loss and reduce hearing loss by protecting ears from high noise levels.

• Reduce exposure to air pollution and second-hand tobacco smoke.

• Prevent head injury (particularly by targeting high-risk occupations).

• Limit alcohol intake to no more than 21 units per week (one unit of alcohol equals 10 ml or 8 g pure alcohol).

• Stop smoking and support others to stop smoking.

• Provide all children with primary and secondary education.

• Lead an active life into mid-life and possibly later life.

• Reduce obesity and the linked condition of diabetes.

The report also advocates for holistic, individualized and evidenced-based care for patients with dementia, who typically have more hospitalizations for conditions that are potentially manageable at home and are at greater risk for COVID-19. In addition, it recommends providing interventions for family caregivers who are at risk for depression and anxiety.

The commission members conducted a thorough investigation of all the best evidence in the field, including systematic literature reviews, meta-analyses and individual studies, to reach their conclusions.

https://www.sciencedaily.com/releases/2020/07/200730123651.htm

New blood test shows great promise in the diagnosis of Alzheimer's disease

July 29, 2020

Science Daily/Lund University

A new blood test demonstrated remarkable promise in discriminating between persons with and without Alzheimer's disease and in persons at known genetic risk may be able to detect the disease as early as 20 years before the onset of cognitive impairment, according to a large international study published today in the Journal of the American Medical Association (JAMA) and simultaneously presented at the Alzheimer's Association International Conference.

For many years, the diagnosis of Alzheimer's has been based on the characterization of amyloid plaques and tau tangles in the brain, typically after a person dies. An inexpensive and widely available blood test for the presence of plaques and tangles would have a profound impact on Alzheimer's research and care. According to the new study, measurements of phospho-tau217 (p-tau217), one of the tau proteins found in tangles, could provide a relatively sensitive and accurate indicator of both plaques and tangles -- corresponding to the diagnosis of Alzheimer's -- in living people.

"The p-tau217 blood test has great promise in the diagnosis, early detection, and study of Alzheimer's," said Oskar Hansson, MD, PhD, Professor of Clinical Memory Research at Lund University, Sweden, who leads the Swedish BioFINDER Study and senior author on the study who spearheaded the international collaborative effort. "While more work is needed to optimize the assay and test it in other people before it becomes available in the clinic, the blood test might become especially useful to improve the recognition, diagnosis, and care of people in the primary care setting."

Researchers evaluated a new p-tau217 blood test in 1,402 cognitively impaired and unimpaired research participants from well-known studies in Arizona, Sweden, and Colombia. The study, which was coordinated from Lund University in Sweden, included 81 Arizona participants in Banner Sun Health Research Institute's Brain Donation program who had clinical assessments and provided blood samples in their last years of life and then had neuropathological assessments after they died; 699 participants in the Swedish BioFINDER Study who had clinical, brain imaging, cerebrospinal fluid (CSF), and blood-based biomarker assessments; and 522 Colombian autosomal dominant Alzheimer's disease (ADAD)-causing mutation carriers and non-carriers from the world's largest ADAD cohort.

• In the Arizona (Banner Sun Health Research Institute) Brain Donation Cohort, the plasma p-tau217 assay discriminated between Arizona Brain donors with and without the subsequent neuropathological diagnosis of "intermediate or high likelihood Alzheimer's" (i.e., characterized by plaques, as well as tangles that have at least spread to temporal lobe memory areas or beyond) with 89% accuracy; it distinguished between those with and without a diagnosis of "high likelihood Alzheimer's" with 98% accuracy; and higher ptau217 measurements were correlated with higher brain tangle counts only in those persons who also had amyloid plaques.

• In the Swedish BioFINDER Study, the assay discriminated between persons with the clinical diagnoses of Alzheimer's and other neurodegenerative diseases with 96% accuracy, similar to tau PET scans and CSF biomarkers and better than several other blood tests and MRI measurements; and it distinguished between those with and without an abnormal tau PET scan with 93% accuracy.

• In the Colombia Cohort, the assay began to distinguish between mutation carriers and non-carriers 20 years before their estimated age at the onset of mild cognitive impairment.

In each of these analyses, p-tau217 (a major component of Alzheimer's disease-related tau tangles) performed better than p-tau181 (another component of tau tangles and a blood test recently found to have promise in the diagnosis of Alzheimer's) and several other studied blood tests.

Other study leaders include Jeffrey Dage, PhD, from Eli Lilly and Company, who developed the p-tau217 assay, co-first authors Sebastian Palmqvist, MD, PhD, and Shorena Janelidz, PhD, from Lund University, and Eric Reiman, MD, Banner Alzheimer's Institute, who organized the analysis of Arizona and Colombian cohort data.

In the last two years, researchers have made great progress in the development of amyloid blood tests, providing valuable information about one of the two cardinal features of Alzheimer's. While more work is needed before the test is ready for use in the clinic, a p-tau217 blood test has the potential to provide information about both plaques and tangles, corresponding to the diagnosis of Alzheimer's. It has the potential to advance the disease's research and care in other important ways.

"Blood tests like p-tau217 have the potential to revolutionize Alzheimer's research, treatment and prevention trials, and clinical care," said Eric Reiman, MD, Executive Director of Banner Alzheimer's Institute in Phoenix and a senior author on the study.

"While there's more work to do, I anticipate that their impact in both the research and clinical setting will become readily apparent within the next two years."

Alzheimer's is a debilitating and incurable disease that affects an estimated 5.8 million Americans age 65 and older. Without the discovery of successful prevention therapies, the number of U.S. cases is projected to reach nearly 14 million by 2050.

https://www.sciencedaily.com/releases/2020/07/200729114404.htm

COVID-19 increased anxiety, depression for already stressed college students

Study shows unprecedented increase in mental health challenges among undergraduates

July 27, 2020

Science Daily/Dartmouth College

College students were more anxious and depressed during the initial outbreak of COVID-19 than they were during similar time frames in previous academic years, according to a Dartmouth study.

The research also found that sedentary behavior increased dramatically during the onset of the public health crisis in early March.

The study, published in the Journal of Medical Internet Research, used a mix of smartphone sensing and digital questionnaires from more than 200 students participating in a research program that is tracking mental health throughout their undergraduate years.

"COVID-19 had an immediate negative impact on the emotional well-being of the college students we studied," said Jeremy Huckins, a lecturer on psychological and brain sciences at Dartmouth. "We observed a large-scale shift in mental health and behavior compared to the observed baseline established for this group over previous years."

Self-reported symptoms of depression and anxiety within the student research group spiked noticeably at the onset of COVID-19. At the time, major policy changes related to COVID-19 were also being put in place, including the request that students leave campus and the switch to remote learning.

These changes coincided with the end of classes and final exams, already one of the most stressful times for students in any academic term.

According to the study, anxiety and depression decreased slightly after the final exam period as students settled into shelter-in-place locations. This suggested some resilience in the face of COVID-19, but levels remained consistently higher than similar periods during previous academic terms.

Unlike previous terms studied, sedentary time increased dramatically during this year's spring break period.

"This was an atypical time for these college students. While spring break is usually a period of decreased stress and increased physical activity, spring break 2020 was stressful and confining for the students participating in this study. We suspect that this was the case for a large number of college students across the country," said Huckins.

The study used StudentLife, a sensing app developed at Dartmouth, to collect information from student volunteers. StudentLife passively collects behavioral information from user's smartphones such as duration of phone usage, number of phone unlocks, sleep duration, and sedentary time.

Data on depression and anxiety were collected using weekly, self-reported assessments also administered through the StudentLife app.

"This is the first time we have used sensor data from phones to give us unique behavioral insights into the reaction of students to the onset of the pandemic on a college campus," said Andrew Campbell, the Albert Bradley 1915 Third Century Professor of computer science at Dartmouth and one of the lead researchers of the StudentLife study. "We plan to further analyze how these students adjusted both physically and mentally during remote learning that leads on from this study."

In the research, the team also reported a connection between anxiety and COVID-19 news coverage. The link between depression and news reporting was apparent, but not as strong. As news coverage intensified, there was an increase in sedentary behavior and a longer duration of phone usage.

According to the study, the decrease in the number of locations visited was consistent with the social distancing and shelter-in-place policies implemented by local governments.

The study's findings on the uptake of social distancing recommendations contrasts with other research of college students in which governmental social distancing policies were not followed. Findings in the current study are also contrary to media depictions of college-age students flouting social distancing recommendations during the spring break period.

"Many people wouldn't expect college students to listen to social distancing orders, but these students did. We found that when social distancing was recommended by local governments, students were more sedentary and visited fewer locations on any given day," said Huckins. "Clearly the impact of COVID-19 extends beyond the virus and its direct impacts. An unresolved question is if mental health and physical activity will continue to degrade over time, or if we will see a recovery, and how long that recovery will take."

The research is part of a multiyear study focusing on the mental health of undergraduate students as they progress through their undergraduate careers. The complete study combines smartphone mobile sensing with functional neuroimaging.

"When we set out two years ago to follow 200 students across their college experiences, we could never have anticipated the inflection point in our data as a result of such a catastrophic event as the pandemic," added Campbell.

Upon completion of the full study, researchers will be able to extend their findings on the disruption at the start of the COVID-19 pandemic to the long-term impact of remote learning and social isolation that the students are experiencing.

More information on the StudentLife research program can be found at: https://studentlife.cs.dartmouth.edu

https://www.sciencedaily.com/releases/2020/07/200727114731.htm

Flu, pneumonia vaccinations tied to lower risk of Alzheimer's dementia

July 27, 2020

Science Daily/Alzheimer's Association

Flu (influenza) and pneumonia vaccinations are associated with reduced risk of Alzheimer's disease, according to new research reported at the Alzheimer's Association International Conference® (AAIC®) 2020.

Three research studies reported at AAIC 2020 suggest:

At least one flu vaccination was associated with a 17% reduction in Alzheimer's incidence. More frequent flu vaccination was associated with another 13% reduction in Alzheimer's incidence.

Vaccination against pneumonia between ages 65 and 75 reduced Alzheimer's risk by up to 40% depending on individual genes.

Individuals with dementia have a higher risk of dying (6-fold) after infections than those without dementia (3-fold).

"With the COVID-19 pandemic, vaccines are at the forefront of public health discussions. It is important to explore their benefit in not only protecting against viral or bacterial infection but also improving long-term health outcomes," said Maria C. Carrillo, Ph.D., Alzheimer's Association chief science officer.

"It may turn out to be as simple as if you're taking care of your health in this way -- getting vaccinated -- you're also taking care of yourself in other ways, and these things add up to lower risk of Alzheimer's and other dementias," Carrillo said. "This research, while early, calls for further studies in large, diverse clinical trials to inform whether vaccinations as a public health strategy decrease our risk for developing dementia as we age."

Seasonal Flu Vaccine May Reduce Incidence of Alzheimer's Dementia 

Previous research has suggested vaccinations may have a protective factor against cognitive decline, but there have been no large, comprehensive studies focused on the influenza (flu) vaccine and Alzheimer's disease risk, specifically. To address this gap, Albert Amran, a medical student at McGovern Medical School at The University of Texas Health Science Center at Houston, and team, investigated a large American health record dataset (n=9,066).

Amran and team found having one flu vaccination was associated with a lower prevalence of Alzheimer's (odds ratio 0.83, p<0.0001), and among vaccinated patients receiving the flu vaccine more frequently was associated with an even lower prevalence of Alzheimer's (odds ratio 0.87, p=0.0342). Thus, people that consistently got their annual flu shot had a lower risk of Alzheimer's. This translated to an almost 6% reduced risk of Alzheimer's disease for patients between the ages of 75-84 for 16 years.

The researchers found the protective association between the flu vaccine and the risk of Alzheimer's was strongest for those who received their first vaccine at a younger age -- for example, the people who received their first documented flu shot at age 60 benefitted more than those who received their first flu shot at age 70.

"Our study suggests that regular use of a very accessible and relatively cheap intervention -- the flu shot -- may significantly reduce risk of Alzheimer's dementia," Amran said. "More research is needed to explore the biological mechanism for this effect -- why and how it works in the body -- which is important as we explore effective preventive therapies for Alzheimer's."

Pneumonia Vaccine May Reduce Alzheimer's Risk Later in Life

Repurposing of existing vaccines may be a promising approach to Alzheimer's disease prevention. Svetlana Ukraintseva, Ph.D., Associate Research Professor in the Biodemography of Aging Research Unit (BARU) at Duke University Social Science Research Institute, and team, investigated associations between pneumococcal vaccination, with and without an accompanying seasonal flu shot, and the risk of Alzheimer's disease among 5,146 participants age 65+ from the Cardiovascular Health Study. The team also took into account a known genetic risk factor for Alzheimer's -- the rs2075650 G allele in the TOMM40 gene.

The researchers found that pneumococcal vaccination between ages 65-75 reduced risk of developing Alzheimer's by 25-30% after adjusting for sex, race, birth cohort, education, smoking, and number of G alleles. The largest reduction in the risk of Alzheimer's (up to 40%) was observed among people vaccinated against pneumonia who were non-carriers of the risk gene. Total number of vaccinations against pneumonia and the flu between ages 65 and 75 was also associated with a lower risk of Alzheimer's; however, the effect was not evident for the flu shot alone.

"Vaccinations against pneumonia before age 75 may reduce Alzheimer's risk later in life, depending on individual genotype," Ukraintseva said. "These data suggest that pneumococcal vaccine may be a promising candidate for personalized Alzheimer's prevention, particularly in non-carriers of certain risk genes."

Infection Substantially Increases Mortality in People with Dementia 

People living with dementia commonly experience other health conditions including viral, bacterial, and other infections. There is a growing trend in research to investigate whether infections might be worsening, more life-threatening or possibly causing dementia.

Janet Janbek, a Ph.D. student at the Danish Dementia Research Centre, Rigshospitalet and the University of Copenhagen in Denmark, and team, used data from national health registries to investigate mortality in Danish residents over age 65 (n=1,496,436) who had visited the hospital with an infection. They found that people with both dementia and such hospital visits died at a 6.5 times higher rate compared with people who had neither. Study participants with either dementia alone or infection-related contacts alone had a threefold increased rate. The rate of mortality was highest within the first 30 days following the hospital visit.

The researchers also found that for people living with dementia the mortality rates remained elevated for 10 years after the initial infection-related hospital visit, and mortality rates from all infections (including major infections like sepsis to minor ear infections) were higher compared with people without dementia or without an infection-related hospital visit.

"Our study supports the need to investigate these relations even further; to find out why infections are linked to higher mortality in people with dementia, specifically which risk factors and biological mechanisms are involved. This will help advance our understanding of the role of infections in dementia," said Janbek.

"Our study suggests that the health care system -- as well as relatives of people with dementia -- should have increased awareness of people with dementia who get infections, so they get the medical care they need. People with dementia require more specialized treatment even when their hospital visits are not directly due to their dementia but to what might appear to be an unrelated infection," Janbek added.

https://www.sciencedaily.com/releases/2020/07/200727114726.htm

What happens around an Alzheimer plaque?

July 22, 2020

Science Daily/VIB (the Flanders Institute for Biotechnology)

The brains of people living with Alzheimer's are riddled with plaques: protein aggregates consisting mainly of amyloid beta. Despite decades of research, the real contribution of these plaques to the disease process is still not clear. A research team led by Bart De Strooper and Mark Fiers at the VIB-KU Leuven Center for Brain & Disease Research in Leuven, Belgium used pioneering technologies to study in detail what happens in brain cells in the direct vicinity of plaques. Their findings, published in the prestigious journal Cell, show how different cell types in the brain work together to mount a complex response to amyloid plaques which is likely protective at first, but later on damaging to the brain.

The role of amyloid plaques in Alzheimer's disease has puzzled scientists ever since Alois Alzheimer first described them in the brain of a woman with young onset dementia. Now, over a century later, we have learned a lot about the molecular processes that lead to neurodegeneration and subsequent memory loss, but the relationship between the plaques and the disease process in the brain is still ambiguous.

"Amyloid plaques might act as a trigger or as a driver of disease, and the accumulation of amyloid beta in the brain likely initiates a complex multicellular neurodegenerative process," says professor Bart De Strooper (VIB-KU Leuven). His team set out to map the molecular changes that take place in cells near amyloid plaques.

"We used the latest technologies to analyze genome-wide transcriptomic changes induced by amyloid plaques in hundreds of small tissue domains," explains Mark Fiers, co-lead on the study. "In this way, we could generate a large data set of transcriptional changes that occur in response to increasing amyloid pathology, both in mouse and human brains."

Two co-expression networks

"We focused on the transcriptomic changes in the immediate neighborhood of the amyloid plaques, with a 50 micrometer perimeter," explains Wei-Ting Chen, a postdoc in De Strooper's team. In a well-studied genetic mouse model showing amyloid pathology, the scientists identified two novel gene co-expression networks that appeared highly sensitive to amyloid beta deposition.

Chen: "With increasing amyloid beta deposition, a multicellular co-expressed gene response was established encompassing no less than 57 plaque-induced genes." These genes were mainly expressed in astroglia and microglia, two types of supportive brain cells, and were not co-expressed in the absence of amyloid plaques.

"We also found interesting alterations in a second network, expressed mainly by another type of cells, namely oligodendrocytes," adds Ashley Lu, PhD student in the team. "This gene network was activated under mild amyloid stress but depleted in microenvironments with high amyloid accumulation."

"Many of the genes in both networks show similar alterations in human brain samples, strengthening our observations," adds Fiers.

Targeting plaques

"Our data demonstrate that amyloid plaques are not innocent bystanders of the disease, as has been sometimes suggested, but in fact induce a strong and coordinated response of all surrounding cell types," says De Strooper.

"Further work is needed to understand whether, and when, removal of amyloid plaques -- for instance by antibody therapy currently in development to treat amyloid plaques -- is sufficient to reverse these ongoing cellular processes."

Whether antibody binding to amyloid plaques could also modulate these glial responses remains to be determined. "It would in any case complicate the interpretation of the outcome of clinical trials as these cellular effects might be different between different antibodies," adds De Strooper.

https://www.sciencedaily.com/releases/2020/07/200722134916.htm

Physical stress on the job linked with brain and memory decline in older age

July 22, 2020

Science Daily/Colorado State University

A new study out of Colorado State University has found that physical stress in one's job may be associated with faster brain aging and poorer memory.

Aga Burzynska, an assistant professor in the Department of Human Development and Family Studies, and her research team connected occupational survey responses with brain-imaging data from 99 cognitively normal older adults, age 60 to 79. They found that those who reported high levels of physical stress in their most recent job had smaller volumes in the hippocampus and performed poorer on memory tasks. The hippocampus is the part of the brain that is critical for memory and is affected in both normal aging and in dementia.

Their findings were published this summer in Frontiers in Human Neuroscience under the research topic "Work and Brain Health Across the Lifespan."

"We know that stress can accelerate physical aging and is the risk factor for many chronic illnesses," Burzynska said. "But this is the first evidence that occupational stress can accelerate brain and cognitive aging."

She added that it is important to understand how occupational exposures affect the aging of our brains.

"An average American worker spends more than eight hours at work per weekday, and most people remain in the workforce for over 40 years," Burzynska said. "By pure volume, occupational exposures outweigh the time we spend on leisure social, cognitive and physical activities, which protect our aging minds and brains."

PHYSICAL DEMANDS AT WORK

Burzynska explained that the association between "physical stress" and brain/memory were driven by physical demands at work. These included excessive reaching, or lifting boxes onto shelves, not necessarily aerobic activity. This is important because earlier work by Burzynska and her colleagues showed that leisure aerobic exercise is beneficial for brain health and cognition, from children to very old adults. Therefore, the researchers controlled for the effects of leisure physical activity and exercise.

As expected, leisure physical activity was associated with greater hippocampal volume, but the negative association with physical demands at work persisted.

"This finding suggests that physical demands at work may have parallel yet opposing associations with brain health," Burzynska explained. "Most interventions for postponing cognitive decline focus on leisure, not on your job. It's kind of unknown territory, but maybe future research can help us make some tweaks to our work environment for long-term cognitive health."

She added that the results could have important implications for society.

"Caring for people with cognitive impairment is so costly, on economic, emotional and societal levels," Burzynska said. "If we can support brain health earlier, in middle-aged workers, it could have an enormous impact."

The researchers considered and corrected for several other factors that could be related to work environment, memory and hippocampus, such as age, gender, brain size, educational level, job title, years in the occupation and general psychological stress.

ONE PIECE OF THE PUZZLE

"The research on this topic is so fragmented," Burzynska said. "One previous study linked mid-life managerial experience with greater hippocampus volume in older age. Another showed that taxi drivers had larger hippocampi than a city's bus drivers, presumably due to the need to navigate. In our study, job complexity and psychological stress at work were not related to hippocampal volume and cognition. Clearly, our study is just one piece of the puzzle, and further research is needed."

The magnetic resonance imaging (MRI) data used for the study was collected at the University of Illinois Urbana-Champaign between 2011 and 2014.

CSU researchers now can collect MRI data with the new 3T scanner at the University's Translational Medicine Institute.

With this new capability, Burzynska, along with Michael Thomas and Lorann Stallones of CSU's Department of Psychology, is launching a new project, "Impact of Occupational Exposures and Hazards on Brain and Cognitive Health Among Aging Agricultural Workers," which will involve collecting MRI brain scans and identifying risk and protective factors that could help the agricultural community age successfully. The project recently obtained funding as an Emerging Issues Short-Term Project from the High Plains Intermountain Center for Agricultural Health and Safety.

https://www.sciencedaily.com/releases/2020/07/200722093448.htm

Music on the brain

A neurological study of classical musicians trained in different styles

July 20, 2020

Science Daily/University of Tokyo

A new study looks at differences between the brains of Japanese classical musicians, Western classical musicians and nonmusicians. Researchers investigated specific kinds of neural behavior in participants as they were exposed to unfamiliar rhythms and nonrhythmic patterns. Trained musicians showed greater powers of rhythmic prediction compared to nonmusicians, with more subtle differences between those trained in Japanese or Western classical music. This research has implications for studies of cultural impact on learning and brain development.

"Music is ubiquitous and indispensable in our daily lives. Music can reward us, comfort us and satisfy us emotionally," said Project Assistant Professor Tatsuya Daikoku from the International Research Center for Neurointelligence at the University of Tokyo. "So it's no surprise the effect of music on the brain is well-researched. However, many studies focus on Western classical music, pop, jazz, etc., whereas ours is the first study that investigates neural mechanisms in practitioners of Japanese classical music, known as gagaku."

Many Japanese performance arts, such as in Noh or Kabuki theater, include music that does not necessarily follow a regular beat pattern as Western classical music typically does. That is, Japanese classical music sometimes expands or contracts beats without mathematical regularity. This time interval is often referred to as ma, which is an important notion throughout Japanese culture.

Daikoku and his research partner, Assistant Professor Masato Yumoto from the Graduate School of Medicine, explored how different groups of trained musicians and nonmusicians responded to different rhythm patterns. The idea was to see how musical training might influence statistical learning, the way our brains interpret and anticipate sequential information: in this case, rhythms.

The researchers recorded participants' brain activity directly using a technique called magnetoencephalography, which looks at magnetic signals in the brain. From the data, Daikoku and Yumoto were able to ascertain that statistical learning of the rhythms took place in the left hemisphere of participants' brains. And importantly, there was a greater level of activity in those with musical training, be it in Japanese or Western classical music.

"We expected that musicians would exhibit strong statistical learning of unfamiliar rhythm sequences compared to nonmusicians. This has been observed in previous studies which looked at responses to unfamiliar melodies. So this in itself was not such a surprise," said Daikoku. "What is really interesting, however, is that we were able to pick out differences in the neural responses between those trained in Japanese or Western classical music."

These differences between Japanese and Western classical musicians are far more subtle and become apparent in the higher-order neural processing of complexity in rhythm. Though it is not the case that one culture or another performed better or worse than the other, this finding does imply that different cultural upbringings and systems of education can have a tangible effect on brain development.

"This research forms part of a larger puzzle we wish to explore -- that of differences and similarities between the languages and music of cultures and how they affect learning and development," said Daikoku. "We also look into music as a way to treat developmental disorders such as language impairment. Personally, I hope to see a rejuvenation of interest in Japanese classical music; perhaps this study will inspire those unfamiliar with such music to hear and cherish this key part of Japanese cultural history."

https://www.sciencedaily.com/releases/2020/07/200720093255.htm

Biggest risk factors identified to try and prevent Alzheimer's disease

Clinicians should identify and target 10 risk factors in their attempt to prevent Alzheimer's disease, say researchers

July 20, 2020

Science Daily/BMJ

There are at least 10 risk factors that appear to have a significant impact on a person's likelihood of developing Alzheimer's disease that could be targeted with preventative steps, suggests research published in the Journal of Neurology, Neurosurgery & Psychiatry.

Focusing on these factors, which include cognitive activity, high body mass index in late life, depression, diabetes, and high blood pressure, could provide clinicians with an evidence based guideline for prevention of Alzheimer's disease, but a lot more research is needed to come up with other promising approaches to preventing the condition.

Currently, around 850,000 people in the UK are affected by dementia -- around two thirds of which are Alzheimer's disease -- and the condition is a leading cause of death, not helped by the fact that there have been no new drug treatments for dementia in almost 20 years.

Experts are predicting rising case numbers as the population ages but recent research has suggested that the number of cases appears to be reducing, possibly due to lifestyle changes, better education and risk reduction strategies to prevent or delay dementia.

Existing evidence on preventing Alzheimer's disease is challenging to interpret due to varying study designs with different endpoints and credibility.

So an international team of researchers led by Professor Jin-Tai Yu at Fudan University in China, set out to review and analyse current evidence in order to produce evidence-based suggestions on Alzheimer's disease prevention.

The researchers gathered 395 studies (243 observational prospective studies and 152 randomised controlled trials) that were suitable for their analysis.

From analysing these, they proposed 21 suggestions based on the consolidated evidence available that could be used in practice by clinicians to try to prevent Alzheimer's disease.

Within these, there were what they referred to as "Class I" suggestions to target 19 different factors.

Nearly two-thirds of these suggestions would involve targeting vascular risk factors (such as high blood pressure and cholesterol levels) and lifestyle, strengthening the importance of keeping healthy to prevent Alzheimer's disease.

Ten of the suggestions were backed by strong evidence and included receiving as much education as possible in early life, participating in mentally stimulating activities such as reading, avoiding diabetes, stress, depression, head trauma, and high blood pressure in midlife.

A further nine suggestions had slightly weaker evidence to support them and included regular physical exercise, getting sufficient good quality sleep, maintaining a healthy body weight and good heart health in later life, avoiding smoking, and including vitamin C in the diet.

In contrast, two interventions were not recommended -- oestrogen replacement therapy and use of acetylcholinesterase inhibitors (drugs that increase communication between nerve cells).

The authors point to some study limitations, such as the fact that observational studies cannot indicate a clear causal relationship and randomised controlled trials cannot be generalisable beyond the specific sample, intervention, dose and duration studied.

In addition, the values of their suggestions might be limited by geographic variability, definition of exposure and prevalence of risk factors at population level.

Nevertheless, the authors say this was the most comprehensive and large-scale systematic review and meta-analysis for Alzheimer's disease to date, and the evidence based suggestions were put together by integrating a large amount of evidence from different types of existing research.

They conclude: "This study provides an advanced and contemporary survey of the evidence, suggesting that more high-quality observational prospective studies and randomised controlled trials are urgently needed to strengthen the evidence base for uncovering more promising approaches to preventing Alzheimer's disease."

https://www.sciencedaily.com/releases/2020/07/200720190920.htm

'Love hormone' oxytocin could be used to treat cognitive disorders like Alzheimer's

July 20, 2020

Science Daily/Tokyo University of Science

Alzheimer's disease progressively degrades a person's memory and cognitive abilities, often resulting in dementia. Amid efforts to find novel treatments for this disease, a recent breakthrough study by scientists from Japan shows that oxytocin―the hormone that we commonly know to induce feelings of love and well-being―can also effectively reverse some of the damage caused by amyloid plaques in the learning and memory center of the brain in an animal model of Alzheimer's.

Alzheimer's disease is a progressive disorder in which the nerve cells (neurons) in a person's brain and the connections among them degenerate slowly, causing severe memory loss, intellectual deficiencies, and deterioration in motor skills and communication. One of the main causes of Alzheimer's is the accumulation of a protein called amyloid β (Aβ) in clusters around neurons in the brain, which hampers their activity and triggers their degeneration. Studies in animal models have found that increasing the aggregation of Aβ in the hippocampus―the brain's main learning and memory center―causes a decline in the signal transmission potential of the neurons therein. This degeneration affects a specific trait of the neurons, called "synaptic plasticity," which is the ability of synapses (the site of signal exchange between neurons) to adapt to an increase or decrease in signaling activity over time. Synaptic plasticity is crucial to the development of learning and cognitive functions in the hippocampus. Thus, Aβ and its role in causing cognitive memory and deficits have been the focus of most research aimed at finding treatments for Alzheimer's.

Now, advancing this research effort, a team of scientists from Japan, led by Professor Akiyoshi Saitoh from the Tokyo University of Science, has looked at oxytocin, a hormone conventionally known for its role in the female reproductive system and in inducing the feelings of love and well-being. "Oxytocin was recently found to be involved in regulating learning and memory performance, but so far, no previous study deals with the effect of oxytocin on Aβ-induced cognitive impairment," Prof Saitoh says. Realizing this, Prof Saitoh's group set out to connect the dots.

Prof Saitoh and team first perfused slices of the mouse hippocampus with Aβ to confirm that Aβ causes the signaling abilities of neurons in the slices to decline or―in other words―impairs their synaptic plasticity. Upon additional perfusion with oxytocin, however, the signaling abilities increased, suggesting that oxytocin can reverse the impairment of synaptic plasticity that Aβ causes.

To find out how oxytocin achieves this, they conducted a further series of experiments. In a normal brain, oxytocin acts by binding with special structures in the membranes of brain cells, called oxytocin receptors. The scientists artificially "blocked" these receptors in the mouse hippocampus slices to see if oxytocin could reverse Aβ―induced impairment of synaptic plasticity without binding to these receptors. Expectedly, when the receptors were blocked, oxytocin could not reverse the effect of Aβ, which shows that these receptors are essential for oxytocin to act.

Oxytocin is known to facilitate certain cellular chemical activities that are important in strengthening neuronal signaling potential and formation of memories, such as influx of calcium ions. Previous studies have suspected that Aβ suppresses some of these chemical activities. When the scientists artificially blocked these chemical activities, they found that addition of oxytocin addition to the hippocampal slices did not reverse the damage to synaptic plasticity caused by Aβ. Additionally, they found that oxytocin itself does not have any effect on synaptic plasticity in the hippocampus, but it is somehow able to reverse the ill―effects of Aβ.

Prof Saitoh remarks, "This is the first study in the world that has shown that oxytocin can reverse Aβ-induced impairments in the mouse hippocampus." This is only a first step and further research remains to be conducted in vivo in animal models and then humans before sufficient knowledge can be gathered to reposition oxytocin into a drug for Alzheimer's. But, Prof Saitoh remains hopeful. He concludes, "At present, there are no sufficiently satisfactory drugs to treat dementia, and new therapies with novel mechanisms of action are desired. Our study puts forth the interesting possibility that oxytocin could be a novel therapeutic modality for the treatment of memory loss associated with cognitive disorders such as Alzheimer's disease. We expect that our findings will open up a new pathway to the creation of new drugs for the treatment of dementia caused by Alzheimer's disease."

https://www.sciencedaily.com/releases/2020/07/200720093308.htm

Synapse-saving proteins discovered, opening possibilities in Alzheimer's, schizophrenia

July 17, 2020

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

Researchers at The University of Texas Health Science Center at San Antonio (UT Health San Antonio) have discovered a new class of proteins that protect synapses from being destroyed. Synapses are the structures where electrical impulses pass from one neuron to another.

The discovery, published July 13 in the journal Nature Neuroscience, has implications for Alzheimer's disease and schizophrenia. If proven, increasing the number of these protective proteins could be a novel therapy for the management of those diseases, researchers said.

In Alzheimer's disease, loss of synapses leads to memory problems and other clinical symptoms. In schizophrenia, synapse losses during development predispose an individual to the disorder.

"We are studying an immune system pathway in the brain that is responsible for eliminating excess synapses; this is called the complement system," said Gek-Ming Sia, PhD, assistant professor of pharmacology in UT Health San Antonio's Long School of Medicine and senior author of the research.

"Complement system proteins are deposited onto synapses," Dr. Sia explained. "They act as signals that invite immune cells called macrophages to come and eat excess synapses during development. We discovered proteins that inhibit this function and essentially act as 'don't eat me' signals to protect synapses from elimination."

The system sometimes goes awry

During development, synapses are overproduced. Humans have the most synapses at the ages of 12 to 16, and from then to about age 20, there is net synapse elimination that is a normal part of the brain's maturation. This process requires the complement system.

In adults, synapse numbers are stable, as synapse elimination and formation balance out. But in certain neurological diseases, the brain somehow is injured and begins to overproduce complement proteins, which leads to excessive synapse loss.

"This occurs most notably in Alzheimer's disease," Dr. Sia said.

In mouse models of Alzheimer's disease, researchers have found that the removal of complement proteins from the brain protects it from neurodegeneration, he said.

"We've known about the complement proteins, but there was no data to show that there were actually any complement inhibitors in the brain," Dr. Sia said. "We discovered for the first time that there are, that they affect complement activation in the brain, and that they protect synapses against complement activation."

Future directions

Dr. Sia and his colleagues will seek to answer interesting questions, including:

• Whether complement system biology can explain why some people are more resistant and more resilient against certain psychiatric disorders;

• How the number of complement inhibitors can be changed and whether that could have clinical ramifications;

• Whether different neurons produce different complement inhibitors, each protecting a certain subset of synapses.

Regarding the last question, Dr. Sia said:

"This could explain why, in certain diseases, there is preferential loss of certain synapses. It could also explain why some people are more susceptible to synapse loss because they have lower levels of certain complement inhibitors."

The researchers focused on a neuronal complement inhibitor called SRPX2. The studies are being conducted in mice that lack the SRPX2 gene, that demonstrate complement system overactivation and that exhibit excessive synapse loss.

https://www.sciencedaily.com/releases/2020/07/200717133234.htm

Further evidence World Trade Center responders are at risk for dementia

July 28, 2020

Science Daily/Stony Brook University

Two studies led by Stony Brook University researchers to be presented virtually at the Alzheimer's Association International Conference on July 28, 2020, indicate that World Trade Center (WTC) first responders are at risk for developing dementia. The studies included individuals with signs of cognitive impairment (CI) who show neuroradiological abnormalities and changes in their blood similar to that seen in Alzheimer's disease patients and those with related dementias.

One study in Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring (DADM) shows that many responders with CI have reduced gray matter thickness in the brain consistent with neurodegenerative conditions and evidence their brain "age" is about 10 years older on average than the normal population. This research is in collaboration with scientists at the Icahn School of Medicine at Mount Sinai.

The other study, to be published in Translational Psychiatry, reveals some responders with post-traumatic stress disorder (PTSD) and mild CI possess protein changes in their blood consistent with Alzheimer's.

"The environmental exposures and psychological pressures experienced by responders during 911 and its aftermath has had an insidious effect on their health and well-being," says Benjamin Luft, MD, Director of the Stony Brook WTC Health and Wellness Program. "Now nearly 20 years post-911, clinicians who care for these individuals are seeing more patients who are showing signs of cognitive disorders and possible dementia. Findings from our new studies provide data for the first time that support the idea that this population of patients who have cognitive impairment not only have psychological problems such as PTSD but may be at high-risk for neurodegenerative disorders, a possibility that needs immediate and continued investigation."

One study is the first to use MRI imaging to assess the brain matter of WTC responder patients with and without symptoms of CI. The goal of this study is to determine if WTC responders in their midlife have developed CI due to changes in their brain possibly caused by neurotoxins they were exposed to at Ground Zero. The age range of patients was 45 to 65 years, an age range where cortical atrophy is rare in the normal population.

Researchers measured the brain cortex, the area responsible for cognition. Cortical thickness is a consistent measure of brain atrophy commonly used in studies of patients with Alzheimer's and related dementias. Imaging revealed areas of the cortex are atrophied in many WTC patients with cognitive impairment, compared to control subjects.

"While there are many reasons for cognitive decline because of brain changes, the loss of gray matter in the brain is one of the most concerning and can be measured by cortical thickness," explains Sean Clouston, PhD, lead author and Associate Professor of Family, Population and Preventive Medicine and in the Program in Public Health. "We found a direct correlation between those suffering from cognitive impairment and cortical thickness, indicating a reduction in gray matter of the brain at levels consistent with neurodegenerative disease."

The overall amount of cortical atrophy in responders with CI was significantly more than responders who did not have CI symptoms, as well as to the general population based on normative data.

According to the authors, the MRI imaging revealed that cortical thickness was significantly reduced in 23 out of 34 cortical regions among those with CI. These included the frontal, temporal and occipital lobes. When compared to published data, both responders with CI and those without CI showed significant reductions in cortical thickness in seven regions in or near the temporal lobe potentially indicative of a population-level effect.

Dr. Clouston said that the level of reduction in the cortical thickness in many responders is similar to that in patients with dementia and is "a possible indicator of early stage dementia with possible early onset dementia likely to occur for a portion of these individuals at midlife."

However, he explains that these patients need to be studied longitudinally to determine whether these changes progress over time. Additional imaging and other related brain research is also necessary to determine the cause or causes of brain atrophy in WTC responders.

The second study describes an analysis of 276 proteins in the blood in 181 WTC male responders in midlife -- their average age 55 years.

Each of the identified proteins are instrumental to a range of processes indicative of neurological diseases, cellular regulation, immunology, cardiovascular, inflammatory, developmental and metabolism functions.

Given that PTSD and mild CI are common to 911 responders -- which affect their cognitive and memory processes -- individuals with these conditions were studied.

By using a sophisticated process that identifies dysregulation of proteins among the 276 identified for the study, the researchers found that WTC responders with mild CI also had proteinopathy, or problematic changes in the proteome, consistent with Alzheimer's and related diseases as well as other neuropsychiatric conditions.

"We believe that neuro-inflammation is a possible mechanism in which responders with PTSD appear to be at a higher risk of developing mild cognitive impairment," said Dr. Luft, senior author. "We hope our unique analysis of proteins associated with cognitive impairment-related diseases in this population is an additional way to identify their risk based on changes in their body likely due from their exposures."

https://www.sciencedaily.com/releases/2020/07/200728113554.htm

The most important task for a PTSD service dog for veterans is disrupting anxiety

July 22, 2020

Science Daily/Purdue University

Science has shown that service dogs can benefit some veterans with PTSD. But the exact role service dogs play in the day-to-day lives of veterans -- and the helpfulness of the tasks they perform -- is less known.

A recent study led by Purdue University's College of Veterinary Medicine shows what trained tasks service dogs perform the most often and which ones are the most helpful to veterans with post-traumatic stress disorder. The study found that the task of disrupting episodes of anxiety ranked among the most important and most often used.

"There has been some debate on what kind of training PTSD service dogs need to be effective and how their assistance may be different than what a pet dog can provide," said Kerri Rodriguez, a human-animal interaction graduate student and a lead author on the study. "This study suggests that veterans are, in fact, using and benefiting from the specific trained tasks, which sets these dogs apart from pet dogs or emotional support dogs."

Rodriguez led the work with Maggie O'Haire, associate professor of human-animal interaction. Their research was published in Frontiers in Psychology. The study was done in conjunction with K9s For Warriors, with support and funding from Merrick Pet Care, and is in preparation for an ongoing large-scale clinical trial that is studying veterans with and without service dogs over an extended period of time.

The study found that, on average, the dog's training to both alert the veteran to any increasing anxiety and providing physical contact during anxiety episodes were reported to be the most important and the most often used in a typical day. Veterans with a service dog also rated all of the service dog's trained tasks as being "moderately" to "quite a bit" important for their PTSD.

Some trained tasks include picking up on cues veterans display when experiencing distress or anxiety and consequently nudging, pawing or licking them to encourage the veteran to focus on the dog. The service dogs also are trained to notice when veterans are experiencing anxiety at night and will actively wake up the person from nightmares.

The dogs also are trained to perform tasks in public -- such as looking the opposite way in a crowded room or store to provide a sense of security for the veteran.

The study also found that trained service dog tasks were used on average 3.16 times per day, with individual tasks ranging from an average of 1.36 to 5.05 times per day.

Previous research led by Rodriguez showed that the bond between a service dog and the veteran was a significant factor in the importance of untrained behaviors. Although all trained tasks were reported to be important for veterans' PTSD, those with a service dog actually rated the importance of untrained behaviors higher than the importance of trained tasks. This suggests that there are some therapeutic aspects of the service dog's companionship that are helping just as much, if not more, than the dog's trained tasks, Rodriguez said. "These service dogs offer valuable companionship, provide joy and happiness, and add structure and routine to veterans' lives that are likely very important for veterans' PTSD."

The study surveyed 216 veterans from K9s For Warriors, including 134 with a service dog and 82 on the waitlist. The study complements a previous publication published last year that focused specifically on the service dogs' training, behavior and the human-animal bond.

While service dogs were reported to help a number of specific PTSD symptoms such as having nightmares, experiencing flashbacks, or being hyperaware in public, there were some symptoms that service dogs did not help, such as amnesia and risk-taking.

"Both this research, as well as other related studies on PTSD service dogs, suggest that service dogs are not a standalone cure for PTSD," O'Haire said. "Rather, there appear to be specific areas of veterans' lives that a PTSD service dog can help as a complementary intervention to other evidence-based treatments for PTSD."

Veterans on the waitlist to receive a service dog expected the service dog's trained tasks to be more important for their PTSD and used more frequently on a daily basis than what was reported by veterans who already had a service dog.

"Veterans on the waitlist may have higher expectations for a future PTSD service dog because of feelings of hope and excitement, which may not necessarily be a bad thing," Rodriguez said. "However, it is important for mental health professionals to encourage realistic expectations to veterans who are considering getting a PTSD service dog of their own."

https://www.sciencedaily.com/releases/2020/07/200722142116.htm

Front-line physicians stressed and anxious at work and home

New study reports moderate to severe stress levels in ER doctors during the frenetic early phase of COVID-19 pandemic

July 21, 2020

Science Daily/University of California - San Francisco

Amid the COVID-19 chaos in many hospitals, emergency medicine physicians in seven cities around the country experienced rising levels of anxiety and emotional exhaustion, regardless of the intensity of the local surge, according to a new analysis led by UC San Francisco.

In the first known study to assess stress levels of U.S. physicians during the coronavirus pandemic, doctors reported moderate to severe levels of anxiety at both work and home, including worry about exposing relatives and friends to the virus. Among the 426 emergency physicians surveyed, most reported changes in behavior toward family and friends, especially decreased signs of affection.

"Occupational exposure has changed the vast majority of physicians' behavior at both work and home," said lead author Robert M. Rodriguez, MD, a professor of Emergency Medicine at UCSF. "At home, doctors are worried about exposing family members or roommates, possibly needing to self-quarantine, and the effects of excess social isolation because of their work on the front line."

The results, which appear July 21, 2020, in Academic Emergency Medicine, found slight differences between men and women, with women reporting higher stress. Among male physicians, the median reported effect of the pandemic on both work and home stress levels was 5 on a scale of 1 to 7 (1=not at all, 4=somewhat, and 7=extremely). For women, the median was 6 in both areas. Both men and women also reported that levels of emotional exhaustion or burnout increased from a pre-pandemic median of 3 to a median of 4 after the pandemic started.

Lack of PPE was associated with the highest level of concern and was also the measure most often cited that would provide greatest relief. The doctors also voiced anxiety about inadequate rapid diagnostic testing, the risk of community spread by discharged patients, and the well-being of coworkers diagnosed with COVID-19.

But the survey also showed clear-cut ways of mitigating anxiety:

• Improve access to PPE;

• Increase availability of rapid turnaround testing;

• Clearly communicate COVID-19 protocol changes;

• Assure access to self-testing and personal leave for front line providers.

The responses came from faculty (55 percent), fellows (4.5 percent), and residents (about 39 percent), with a median age of 35. Most physicians lived with a partner (72 percent), while some lived alone (nearly 15 percent) or with roommates (11 percent). Nearly 39 percent had a child under age 18.

The study involved healthcare providers at seven academic emergency departments and affiliated institutions in California, Louisiana and New Jersey. Researchers noted that the majority of study sites were in California, which at the time of the survey had not yet experienced the large surges of patients seen in other areas of the country. But the study found that median levels of anxiety in the California sites were similar to those in the New Orleans and Camden sites, which were experiencing surges at the time.

"This suggests that the impact of COVID-19 on anxiety levels is pervasive and that measures to mitigate stress should be enacted universally," Rodriguez said. "Some of our findings may be intuitive, but this research provides a critical early template for the design and implementation of interventions that will address the mental health needs of emergency physicians in the COVID-19 pandemic era."

The study is longitudinal, with this first phase focused on the early "acceleration" phase of the pandemic. Subsequent studies will address stressors that have arisen throughout the course of the pandemic, including childcare and homeschooling demands, the economic impact of fewer patients overall in the ER, and possible development of long-term post-traumatic stress.

https://www.sciencedaily.com/releases/2020/07/200721084205.htm

High school athletes require longer recovery following concussions

Epidemiologic findings from a high school population

July 21, 2020

Science Daily/Henry Ford Health System

High school athletes sustaining a concussion require careful attention when determining return-to-sport (RTS) readiness. The purpose of this study was to determine epidemiological and RTS data of a large cohort of high school athletes who sustained one or more concussions. Young athletes are typically sidelined for at least one month after suffering a concussion, according to a Henry Ford Hospital study that provides new perspective on concussions and brain injuries.

The study's results were published ahead of the Michigan High School Athletic Association's recent announcement that the fall high school sports season will begin as traditionally scheduled, with football practices starting on Aug. 10.

The findings published by Orthopedics, a nationally recognized, peer-reviewed journal for orthopedic surgeons, are from a study conducted between September 2013 and December 2016. The study focused on 357 high school adolescents who sustained one or more concussions by analyzing historical data and then comparing it to more recent findings tied to an increase in reported concussions among young athletes.

The average age of the study's patients was 15-and-a-half years with nearly 62% being males, the most common sport participated in by these athletes was football, followed by hockey and then soccer. From the study's participants, 14 % reported suffering from amnesia and 33 % reported a history of concussions. Results of the study include:

• Athletes with only one concussion required just over 30 days of recovery prior to returning to sport (RTS) while others who reported a second or more concussions required more time.

• The most common sport of injury was football (27.7%). There was a high incidence of previous concussion (33.1%), and 32 athletes sustained a recurrent concussion.

• Visual motor speed and reaction time scores decreased with recurrent concussions.

• Male and female athletes with a previous history of concussion, and those with delayed diagnosis, required increased time to RTS.

The research team also found that athletes who have suffered concussions have a higher incidence of non-contact lower extremity injuries due to balance issues after concussions which may have implications on the performance, safety and well-being of athletes. These findings will be the focus of the next study also led by Toufic Jildeh, M.D., administrative chief resident in Orthopaedic Surgery at Henry Ford Hospital.

One of the earliest studies on concussion data came from the NFL's mild traumatic brain injury committee and was published in the journal Neurosurgery in January 2004. Based on data collected between 1996 and 2001, researchers found that NFL players were sidelined for six or fewer days after a concussion.

A related 2019 study also led by Dr. Jildeh and published in American Journal of Sports Medicine showed a similar trend with NFL players being sidelined much longer.

"Historically, the literature reported a concussion prevalence of 4-5%, however recent studies have found that nearly 20% of adolescents have suffered at least one concussion, there's a huge disparity in terms of reporting over time," says Dr. Jildeh. Previously, it was thought that young age was a protective factor against concussion and that the neuroplasticity offered fast recovery. However, this thinking has been disproven with more recent studies.

"Concussions have been a pressing issue. We want to limit the number of concussions and head injuries in a young athlete," says Vasilios (Bill) Moutzouros, M.D., chief of Sports Medicine at Henry Ford and a study co-author, adding that younger athletes who suffer a concussion early in life are much more likely to experience longer term effects if they get repeatedly concussed.

Kelechi Okoroha, M.D., a Henry Ford sports medicine surgeon and study co-author, points to the findings as a baseline for young athletes with a history of concussions, "Depending on the number of concussions, the 30-day mark gives us a baseline for how much time adolescent athletes required before returning to sport," he says.

The study offers a lot of information to reflect on and build on according to Jeffrey Kutcher, M.D., medical director and sports neurologist at the Henry Ford Concussion and Sports Neurology Clinic, and global director of the Kutcher Clinic.

"Concussion diagnosis and management requires an individualized and comprehensive neurological approach to ensure we are accurately diagnosing and managing return to play effectively," says Dr. Kutcher who also serves as advisor to the players' associations for the National Football League and National Hockey League.

The study concludes that team physicians must be particularly mindful when evaluating an adolescent athlete due to the short and long-term neurocognitive implications, particularly as it pertains to RTS, and that high school athletes sustaining a concussion require careful attention when determining RTS readiness.

https://www.sciencedaily.com/releases/2020/07/200721094433.htm

Traditional PTSD therapy doesn't trigger drug relapse

People with addiction aren't getting effective treatment for PTSD due to incorrect presumptions

July 20, 2020

Science Daily/Johns Hopkins Medicine

Researchers have now demonstrated that behavior therapy that exposes people to memories of their trauma doesn't cause relapses of opioid or other drug use, and that PTSD severity and emotional problems have decreased after the first therapy session.

About a quarter of people with drug or alcohol use disorders also suffer from post-traumatic stress disorder (PTSD), which is typically caused by a traumatic or stressful life event such as rape or combat, and which leaves the person with intense anxiety. However, patients and health care providers have been reluctant to pursue the gold-standard treatment for PTSD -- cognitive behavioral therapy -- because they anticipate that thinking and talking about traumatic events during therapy will cause relapse.

Johns Hopkins researchers have now demonstrated that behavior therapy that exposes people to memories of their trauma doesn't cause relapses of opioid or other drug use, and that PTSD severity and emotional problems have decreased after the first therapy session.

These findings were published June 29 in the Journal of Traumatic Stress.

This work originated from a larger project in which Jessica Peirce, Ph.D., associate professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine, and her colleagues tested how to get often reluctant patients in addiction treatment to participate in PTSD therapy. In a 2017 article in the Journal of Consulting and Clinical Psychology, her team showed that patients with opioid dependence attended on average nine exposure therapy sessions for treating PTSD when given money as an incentive, compared with only one session without the incentive.

Building on this earlier work, for the new study, her team examined week-to-week comparisons of cravings for opioids or other drugs before and after therapy sessions, self-reported days of drug use, and other distress. The researchers found there was no increase in use of opioids or other drugs, or in reported instances of stress after therapy sessions to treat PTSD. By the ninth therapy session, PTSD severity scores decreased, on average, by 54% compared to the first session.

"Now that we have evidence that treating PTSD won't impact recovery, patients can request therapy, and mental health providers have a duty to make it available to their patients," says Peirce. "There is a lot more resilience within this population than many health care providers give them credit for, and not offering the proper treatment is doing patients a disservice."

https://www.sciencedaily.com/releases/2020/07/200720092838.htm