Exercise May Help You Survive a First Heart Attack

Henry Ford Hospital study links Fitness and Survival

Newswise, February 1, 2016– People who are fit are more likely to survive their first heart attack, according to a study of nearly 70,000 patients of Henry Ford Hospital in Detroit.

The results of the study by Henry Ford and the Johns Hopkins University School of Medicine will be published online February 1 in Mayo Clinic Proceedings.

“Our data suggests that doctors working with patients with cardiovascular risk factors should be saying, ‘Mr. Jones, you need to start an exercise program now to improve your fitness and chance of survival, should you experience a heart attack,’” says Clinton Brawner, PhD., Clinical Exercise Physiologist and Senior Bioscientific Clinical Staff Researcher at Henry Ford Health System.

“These findings suggest that higher aerobic fitness before a heart attack is associated with better short-term survival after the first heart attack.”

While several prior studies have reported a strong relationship between fitness and long-term risk of death in various patient populations, the study is the first to examine the association of early death following a first heart attack.

The analysis is part of the Henry Ford Exercise Testing Project, or FIT Project, a study of nearly 70,000 adults who completed a physician referred exercise stress test at Henry Ford Health System between 1991 and 2009.

In the current analysis of the Henry Ford data, the researchers focused on 2,061 patients who suffered their first heart attack after the stress test, during follow-up. Mean time between the exercise test and the first heart attack was six years.

Patients with a high level of fitness during their initial stress test at a Henry Ford Health System facility were 40% less likely to die within a year following their first heart attack compared to patients with lower fitness, according to the study.

“We knew that fitter people generally live longer, but we now have evidence linking fitness to survival after a first heart attack,” says Michael Blaha, M.D., M.P.H., director of clinical research at the Ciccarone Center for the Prevention of Heart Disease and assistant professor of medicine at the Johns Hopkins University School of Medicine.

“It makes sense, but we believe this is the first time there is documentation of that association.”

Those Henry Ford patients who were more active also reduced their likelihood of dying during the year following their first heart attack by 8 to 10% for each level of increased fitness they had reached during the stress test.

The results suggest that low fitness may represent a risk of death following a heart attack that is similar to traditional risk factors, such as smoking, high blood pressure, or diabetes, says Henry Ford’s Dr. Brawner.

The findings suggest doctors should include exercise when counseling patients about controlling their risk factors.

“While up to 50% of fitness may be based on genetics, physical activity is the only behavior we have that can improve fitness,” Dr. Brawner says.

Follow-up studies are needed to formally establish whether exercise training among individuals with low fitness and increased risk for a heart attack reduces the short-term mortality risk following a first heart attack, Dr. Brawner added.

Investigators also intend to look at whether patients with low fitness suffer more damage to their heart during their heart attack.

The primary investigator of the FIT project is Henry Ford cardiologist Mouaz Al-Mallah, M.D.

The lead author of the present analysis was Gabriel Shaya, M.S., of the University of Miami.

Additional investigators include Jonathan Ehrman, Ph.D., and Steven Keteyian, Ph.D., of Henry Ford Hospital; Blaha, Rupert Hung, B.A., Khurram Nasir, M.D., and Roger Blumenthal, M.D., of Johns Hopkins; and Waqas Qureshi, M.D., of Wake Forest University. 

Under the Weather? A Blood Test Can Tell If Antibiotics Are Needed

Newswise, February 1, 2016 -- Researchers at Duke Health are fine-tuning a test that can determine whether a respiratory illness is caused by infection from a virus or bacteria so that antibiotics can be more precisely prescribed.

The team of infectious disease and genomics experts at Duke has developed what they call gene signatures, patterns that reflect which of a patient’s genes are turned on or off, to indicate whether someone is fighting infection from a virus or bacteria. Results can be derived from a small sample of the patient’s blood.

The signatures were tested in an observational study described in the January 20 issue of Science Translational Medicine. They were found to be 87 percent accurate in classifying more than 300 patients with flu viruses, rhinovirus, several strep bacteria and other common infections, as well as showing when no infection was present.

With these findings, Duke researchers are a significant step closer to developing a rapid blood test that could be used in clinics to distinguish bacterial and viral infections and to guide appropriate treatment.

“A respiratory infection is one of the most common reasons people come to the doctor,” said lead author Ephraim L. Tsalik, M.D., Ph.D., assistant professor of medicine at Duke and emergency medicine provider at the Durham VA Medical Center.

“We use a lot of information to make a diagnosis, but there’s not an efficient or highly accurate way to determine whether the infection is bacterial or viral. About three-fourths of patients end up on antibiotics to treat a bacterial infection despite the fact that the majority have viral infections. There are risks to excess antibiotic use, both to the patient and to public health.”

Participants with respiratory problems were enrolled during visits to emergency departments at five hospitals, including Duke, the Durham VA Medical Center and UNC Hospital in Chapel Hill. The technique is more accurate than other tests that look for the presence of specific microbes, the authors report.

More precise ways of distinguishing infections could not only reduce unnecessary use of antibiotics, but also lead to more precise treatments of viruses, said senior author Geoffrey S. Ginsburg, M.D., Ph.D., director of Duke’s Center for Applied Genomics & Precision Medicine.

“Right now, we can give patients Tamiflu to help them recover from an influenza infection, but for most viral infections, the treatment is fluids and rest until it resolves,” Ginsburg said.

“In the next five to 10 years, we will likely see new antiviral medications for common bugs like respiratory syncytial virus (RSV) and even rhinovirus, (the predominant cause of the common cold), and guiding treatment choices will be even more important.”

Ginsburg and colleagues at Duke have been studying gene signatures in respiratory infections for nearly a decade, but only recently has technology allowed scientists to analyze a person’s genetic makeup, 25,000 genes at a time, he said.

The team had previously identified gene signatures associated with viral infections, but this is the first study to distinguish non-infectious illnesses and viral from bacterial infections at the patient’s molecular level.

Still, with current technology, measuring a person’s gene expression profile from blood could take as long as 10 hours. Study authors are currently working with developers to create a one-hour test that could be used in clinics.

“The ideal scenario, should this test ultimately be approved for broad use, is you would go to the doctor’s office and receive your results by the time you meet with your provider,” said senior author Christopher W. Woods, M.D., professor of medicine and associate director of Duke’s genomics center.

“We are working to develop a test that could be run in most clinical labs on existing equipment. We believe this could have a real impact on the appropriate use of antibiotics and guide the use of antiviral treatments in the future.”

In addition to Tsalik, Ginsburg and Woods, study authors include Ricardo Henao; Marshall Nichols; Thomas Burke; Emily R. Ko; Micah T. McClain; Lori L. Hudson; Anna Mazur; Debra H. Freeman; Tim Veldman; Raymond J. Langley; Eugenia B. Quackenbush; Seth W. Glickman; Charles B. Cairns; Anja K. Jaehne; Emanuel P. Rivers; Ronny M. Otero; Aimee K. Zaas; Stephen F. Kingsmore; Joseph Lucas; Vance G. Fowler; and Lawrence Carin.

This research was supported by the U.S. Defense Advanced Research Projects Agency (contracts N66001-07-C-2024; N66001-09-C-2082), by the National Institutes of Health (U01AI066569; P20RR016480; HHSN266200400064C; K24-AI093969), the Agency for Healthcare Research and Quality, the U.S. Department of Veterans Affairs Office of Research and Development (1IK2CX000530; 1IK2CX000611), and an in-kind contribution bioMérieux, Inc.

Growth Factor in Brain Tied to Slower Mental Decline

Newswise, January 29, 2016– Older people with higher amounts of a key protein in their brains also had slower decline in their memory and thinking abilities than people with lower amounts of protein from the gene called brain-derived neurotrophic factor, or BDNF, according to a study published in the January 27, 2016, online issue of Neurology®, the medical journal of the American Academy of Neurology.

“This relationship was strongest among the people with the most signs of Alzheimer’s disease pathology in their brains,” said study author Aron S. Buchman, MD, of Rush University Medical Center in Chicago and a member of the American Academy of Neurology.

“This suggests that a higher level of protein from BDNF gene expression may provide a buffer, or reserve, for the brain and protect it against the effects of the plaques and tangles that form in the brain as a part of Alzheimer’s disease.”

For the study, 535 people with an average age of 81 were followed until death, for an average of six years.

They took yearly tests of their thinking and memory skills, and after death, a neurologist reviewed their records and determined whether they had dementia, some memory and thinking problems called mild cognitive impairment or no thinking and memory problems.

Autopsies were conducted on their brains after death, and the amount of protein from BDNF gene expression in the brain was then measured. The participants were part of the Rush Memory and Aging Project and the Religious Orders Study.

The rate of cognitive decline was about 50 percent slower for those in the highest 10 percent of protein from BDNF gene expression compared to the lowest 10 percent.

The effect of plaques and tangles in the brain on cognitive decline was reduced for people with high levels of BDNF. In the people with the highest amount of Alzheimer’s disease hallmarks in their brains, cognitive decline was about 40 percent slower for people with the highest amount of protein from BDNF gene expression compared to those with the lowest amount.

On average, thinking and memory skills declined by about 0.10 units per year on the tests. Higher levels of protein from BDNF gene expression reduced the effect of plaques and tangles in the brain on cognitive decline by 0.02 units per year.

The researchers found that the plaques and tangles in the brain accounted for 27 percent of the variation in cognitive decline, demographics accounted for 3 percent and BDNF accounted for 2 percent.

Michal Schnaider Beeri, PhD, of the Icahn School of Medicine at Mount Sinai in New York, noted in an accompanying editorial that exercise has been shown to increase levels of BDNF in the blood, but that the relationship between BDNF protein levels in the blood and in the brain is not clear.

“More research is needed to confirm these findings, determine how this relationship between protein produced by BDNF gene expression and cognitive decline works and see if any strategies can be used to increase BDNF in the brain to protect or slow the rate of cognitive decline,” said Buchman.

Buchman noted that the study does not prove that BDNF is the cause of a slower rate of cognitive decline; further work is needed to determine if activities which increase brain BDNF gene expression levels protect or slow the rate of cognitive decline in old age.

The study was supported by the National Institutes of Health, Illinois Department of Public Health and the Robert C. Borwell Endowment Fund.

To learn more about Alzheimer’s disease, please visit www.aan.com/patients.

The American Academy of Neurology, an association of 30,000 neurologists and neuroscience professionals, is dedicated to promoting the highest quality patient-centered neurologic care. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as Alzheimer’s disease, stroke, migraine, multiple sclerosis, brain injury, Parkinson’s disease and epilepsy

UTEP Professor Shows That Hearing Aids Improve Memory, Speech

Newswise, January 29, 2016 — A recent study by Jamie Desjardins, Ph.D., an assistant professor in the speech-language pathology program at The University of Texas at El Paso, found that hearing aids improve brain function in persons with hearing loss.

Hearing loss, if left untreated, can lead to serious emotional and social consequences, reduced job performance and diminished quality of life. Untreated hearing loss also can interfere with cognitive abilities because so much effort is put toward understanding speech.

“If you have some hearing impairment and you’re not using hearing aids, maybe you can figure out what the person has said, but that comes with a cost,” Desjardins explained. “You may actually be using the majority of your cognitive resources – your brain power – in order to figure out that message.”

As people age, basic cognitive skills – working memory, the ability to pay attention to a speaker in a noisy environment, or the ability to process information quickly – begin to decline.

Desjardins studied a group of individuals in their 50s and 60s with bilateral sensorineural hearing loss who had previously never used hearing aids.

They took cognitive tests to measure their working memory, selective attention and processing speed abilities prior to and after using the hearing aids.

After two weeks of hearing aid use, tests revealed an increase in percent scores for recalling words in working memory and selective attention tests, and the processing speed at which participants selected the correct response was faster.

By the end of the study, participants had exhibited significant improvement in their cognitive function.

“Most people will experience hearing loss in their lifetime,” said Desjardins, who joined UTEP in 2013. “Think about somebody who is still working and they’re not wearing hearing aids and they are spending so much of their brainpower just trying to focus on listening.

“They may not be able to perform their job as well. Or if they can, they’re exhausted because they are working so much harder. They are more tired at the end of the day and it’s a lot more taxing. It affects their quality of life.”

Hearing loss affects more than 9 million Americans over the age of 65 and 10 million Americans ages 45 to 64, but only about 20 percent of people who actually need hearing aids wear them, Desjardins said.

Desjardins’ new study focuses on the use of hearing aids by Hispanics. Research shows that only five percent of Mexican-Americans wear hearing aids. She has developed a survey to investigate their attitudes toward hearing loss. The survey will be conducted at health fairs in the community, including the Mexican Consulate in El Paso, Texas.

Desjardins also will begin work on another study that will look at older bilingual people and their ability to understand speech.

Memory Capacity of Brain Is 10 Times More Than Previously Thought

Data from the Salk Institute shows brain’s memory capacity is in the petabyte range, as much as entire Web

Newswise, January 27, 2016—Salk researchers and collaborators have achieved critical insight into the size of neural connections, putting the memory capacity of the brain far higher than common estimates.

The new work also answers a longstanding question as to how the brain is so energy efficient and could help engineers build computers that are incredibly powerful but also conserve energy.

“This is a real bombshell in the field of neuroscience,” says Terry Sejnowski, Salk professor and co-senior author of the paper, which was published in eLife.

“We discovered the key to unlocking the design principle for how hippocampal neurons function with low energy but high computation power.

“Our new measurements of the brain’s memory capacity increase conservative estimates by a factor of 10 to at least a petabyte, in the same ballpark as the World Wide Web.”

Our memories and thoughts are the result of patterns of electrical and chemical activity in the brain.

 A key part of the activity happens when branches of neurons, much like electrical wire, interact at certain junctions, known as synapses. An output ‘wire’ (an axon) from one neuron connects to an input ‘wire’ (a dendrite) of a second neuron.

Signals travel across the synapse as chemicals called neurotransmitters to tell the receiving neuron whether to convey an electrical signal to other neurons. Each neuron can have thousands of these synapses with thousands of other neurons.

“When we first reconstructed every dendrite, axon, glial process, and synapse from a volume of hippocampus the size of a single red blood cell, we were somewhat bewildered by the complexity and diversity amongst the synapses,” says Kristen Harris, co-senior author of the work and professor of neuroscience at the University of Texas, Austin.

 “While I had hoped to learn fundamental principles about how the brain is organized from these detailed reconstructions, I have been truly amazed at the precision obtained in the analyses of this report.”

Synapses are still a mystery, though their dysfunction can cause a range of neurological diseases. Larger synapses—with more surface area and vesicles of neurotransmitters—are stronger, making them more likely to activate their surrounding neurons than medium or small synapses.

The Salk team, while building a 3D reconstruction of rat hippocampus tissue (the memory center of the brain), noticed something unusual.

In some cases, a single axon from one neuron formed two synapses reaching out to a single dendrite of a second neuron, signifying that the first neuron seemed to be sending a duplicate message to the receiving neuron.

At first, the researchers didn’t think much of this duplicity, which occurs about 10 percent of the time in the hippocampus.

But Tom Bartol, a Salk staff scientist, had an idea: if they could measure the difference between two very similar synapses such as these, they might glean insight into synaptic sizes, which so far had only been classified in the field as small, medium and large.

To do this, researchers used advanced microscopy and computational algorithms they had developed to image rat brains and reconstruct the connectivity, shapes, volumes and surface area of the brain tissue down to a nanomolecular level.

The scientists expected the synapses would be roughly similar in size, but were surprised to discover the synapses were nearly identical.

“We were amazed to find that the difference in the sizes of the pairs of synapses were very small, on average, only about eight percent different in size. No one thought it would be such a small difference. This was a curveball from nature,” says Bartol.

Because the memory capacity of neurons is dependent upon synapse size, this eight percent difference turned out to be a key number the team could then plug into their algorithmic models of the brain to measure how much information could potentially be stored in synaptic connections.

It was known before that the range in sizes between the smallest and largest synapses was a factor of 60 and that most are small.

But armed with the knowledge that synapses of all sizes could vary in increments as little as eight percent between sizes within a factor of 60, the team determined there could be about 26 categories of sizes of synapses, rather than just a few.

“Our data suggests there are 10 times more discrete sizes of synapses than previously thought,” says Bartol. In computer terms, 26 sizes of synapses correspond to about 4.7 “bits” of information.

Previously, it was thought that the brain was capable of just one to two bits for short and long memory storage in the hippocampus.

“This is roughly an order of magnitude of precision more than anyone has ever imagined,” says Sejnowski.

What makes this precision puzzling is that hippocampal synapses are notoriously unreliable. When a signal travels from one neuron to another, it typically activates that second neuron only 10 to 20 percent of the time.

“We had often wondered how the remarkable precision of the brain can come out of such unreliable synapses,” says Bartol.

One answer, it seems, is in the constant adjustment of synapses, averaging out their success and failure rates over time. The team used their new data and a statistical model to find out how many signals it would take a pair of synapses to get to that eight percent difference.

The researchers calculated that for the smallest synapses, about 1,500 events cause a change in their size/ability (20 minutes) and for the largest synapses, only a couple hundred signaling events (1 to 2 minutes) cause a change.

“This means that every 2 or 20 minutes, your synapses are going up or down to the next size. The synapses are adjusting themselves according to the signals they receive,” says Bartol.

“Our prior work had hinted at the possibility that spines and axons that synapse together would be similar in size, but the reality of the precision is truly remarkable and lays the foundation for whole new ways to think about brains and computers,” says Harris.

“The work resulting from this collaboration has opened a new chapter in the search for learning and memory mechanisms.” Harris adds that the findings suggest more questions to explore, for example, if similar rules apply for synapses in other regions of the brain and how those rules differ during development and as synapses change during the initial stages of learning.

“The implications of what we found are far-reaching,” adds Sejnowski. “Hidden under the apparent chaos and messiness of the brain is an underlying precision to the size and shapes of synapses that was hidden from us.”

The findings also offer a valuable explanation for the brain’s surprising efficiency. The waking adult brain generates only about 20 watts of continuous power—as much as a very dim light bulb.

The Salk discovery could help computer scientists build ultraprecise, but energy-efficient, computers, particularly ones that employ “deep learning” and artificial neural nets—techniques capable of sophisticated learning and analysis, such as speech, object recognition and translation.

“This trick of the brain absolutely points to a way to design better computers,” says Sejnowski. “Using probabilistic transmission turns out to be as accurate and require much less energy for both computers and brains.”

Other authors on the paper were Cailey Bromer of the Salk Institute; Justin Kinney of the McGovern Institute for Brain Research; and Michael A. Chirillo and Jennifer N. Bourne of the University of Texas, Austin.

The work was supported by the NIH and the Howard Hughes Medical Institute.

Researchers Find Brain Levels of Vitamin B12 Decrease with Age and Are Prematurely Low in People with Autism and Schizophrenia

International Collaborative Study Led by Nova Southeastern University Researcher

Newswise, January 27, 2016 – A new study published in the online journal, Public Library of Science One (PLOS One) found that Vitamin B12 levels in the brain are significantly decreased in the elderly and are much lower in individuals with autism or schizophrenia, as compared to their peers at similar ages.

For example, children with autism under the age of 10 were found to have three times lower brain B12 levels, which is similar to levels for generally healthy adults in their 50s, indicating a premature decrease.

The international research team led by Richard Deth, Ph.D., professor of pharmacology at Nova Southeastern University’s (NSU) College of Pharmacy, analyzed tissue from otherwise healthy deceased donors along with tissue from donors who had autism or schizophrenia to make the comparisons.

“These are particularly significant findings because the differences we found in brain B12 with aging, autism and schizophrenia are not seen in the blood, which is where B12 levels are usually measured.” said Dr. Deth.

“The large deficits of brain B12 from individuals with autism and schizophrenia could help explain why patients suffering from these disorders experience neurological and neuropsychiatric symptoms.”

The study also found healthy elderly people in the age range of 61-80 have about three times lower levels of total brain B12 than younger age groups, which is a result of normal aging. This normal decrease may help adjust brain metabolism to sustain its function across the lifespan.

An active form of B12 called methylcobalamin, or methyl B12, supports normal brain development by its control through a process known as epigenetic regulation of gene expression.

Remarkably, the brain level of methyl B12 was found to be more than 10 times lower in healthy elderly people than in healthy younger people. A lower than normal level of methyl B12 in the brain could adversely affect neurodevelopment in younger years and could disrupt learning and memory later in life.

Both autism and schizophrenia are associated with oxidative stress, which also plays an important role in aging, and oxidative stress may underlie the decreased brain B12 levels observed in this study.

The findings suggest the need for further research to determine if the use of supplemental methyl B12 and antioxidants like glutathione could help prevent oxidative stress and be useful in treating these conditions.

The research team consisted of Dr. Deth; Yiting Zhang (Northeastern University); Nathaniel Hodgson (Harvard University); Malav S. Trivedi (Nova Southeastern University); Hamid Abdolmaleky (Boston University); and Margot Fournier, Michel Cuenod and Kim Quang Do (Lausanne University, Switzerland).

Their findings are published in the peer-reviewed journal, PLOS1 in an article titled “Decreased brain levels of vitamin B12 in aging, autism and schizophrenia.” Read the full article at: http://dx.plos.org/10.1371/journal.pone.0146797

Research reported in this press release was supported by the Autism Research Institute.

1 in 7 Colorectal Cancer Patients Diagnosed Before Recommended Screening Age

Colorectal cancer in younger people linked to more advanced disease but better survival

Newswise, January 27, 2016 — Nearly 15 percent of patients diagnosed with colorectal cancer were younger than 50, the age at which screening recommendations begin.

The study by researchers at the University of Michigan Comprehensive Cancer Center also found that younger patients were more likely to have advanced disease. The authors suggest this is in part because they are diagnosed only after their cancers have grown large enough to cause symptoms.

“Colorectal cancer has traditionally been thought of as a disease of the elderly. This study is really a wake-up call to the medical community that a relatively large number of colorectal cancers are occurring in people under 50,” says study author Samantha Hendren, M.D., M.P.H., associate professor of surgery at the University of Michigan Medical School.

“To put this in context, breast cancer screening often begins at age 40, and less than 5 percent of invasive breast cancers occur in women under that age. Our study found that about 15 percent of colorectal cancers are diagnosed before the screening age of 50,” she adds.

The study identified 258,024 patients diagnosed with colon or rectal cancer from the Surveillance, Epidemiology and End Results database, a national database of cancer incidence. Results appear in the journal Cancer.

The authors found that younger patients were more likely to receive aggressive surgery and radiation therapy. In addition, this group had better survival rates, both overall and by stage.

Among patients whose cancer had spread to distant organs, 21 percent of younger patients survived beyond five years, compared to 14 percent of older patients.

The improved survival could be in part due to the more aggressive treatment, the authors suggest.

The findings suggest the need for more awareness of warning signs of colorectal cancer: anemia, a dramatic change in the size or frequency of bowel movements, and bleeding with bowel movements.

The authors also say that more people need to consider family history of colorectal cancer, which is a significant risk factor.

Should guidelines change to begin screening at an earlier age? Hendren says not so fast.

“This would be a big and costly change, and I don’t know whether it would help more people than it would hurt,” she says. “A lot of research would be required to understand this before any changes should be made.”

Meanwhile, the more aggressive treatment and longer survival for younger patients suggest the need to improve long-term survivorship resources.

“The cancer community needs to prepare for the increasing number of very young colorectal cancer survivors who will need long-term support to cope with the physical and psychological consequences of their disease and treatments,” Hendren says.