Changes in Patterns of Brain Activity Predict Fear Memory Formation

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Science News-Mar. 1, 2013 — Psychologists at the University of Amsterdam (UvA) have discovered that changes in patterns of brain activity during fearful experiences predict whether a long-term fear memory is formed. The research results have recently been published in the scientific journal Nature Neuroscience.

Researchers Renee Visser MSc, Dr Steven Scholte, Tinka Beemsterboer MSc and Prof. Merel Kindt discovered that they can predict future fear memories by looking at patterns of brain activity during fearful experiences. Up until now, there was no way of predicting fear memory. It was also, above all, unclear whether the selection of information to be stored in the long-term memory occurred at the time of fear learning or after the event.

Picture predicts pain stimulus
During magnetic resonance brain imaging (MRI), participants saw neutral pictures of faces and houses, some of which were followed by a small electric shock. In this way, the participants formed fear memories. They showed fear responses when the pictures were shown that were paired with shocks. This fear response can be measured in the brain, but is also evident from increased pupil dilation when someone sees the picture. After a few weeks, the participants returned to the lab and were shown the same images. Brain activity and pupil diameter were once again measured. The extent to which the pupil dilated when seeing the images that were previously followed by a shock, was considered an expression of the previously formed fear memory.

Pattern Analysis
In order to analyse the fMRI data, (spatial) patterns of brain activity (Multi-Voxel Pattern Analysis, or MVPA) were analysed. By correlating patterns of various stimulus presentations with each other, it is possible to measure the extent to which the representation of two stimuli is the same. It appears that images that have nothing in common, such as houses and faces, lead to increasing neural pattern similarity when they predict danger. This does not occur when they do not predict danger. This leads to the formation of stronger fear responses. The extent to which this occurs is an indication of fear memory formation: the stronger the response during learning, the stronger the fear response will be in the long term.

These findings may lead to greater insights into the formation of emotional memory. As a result, it is possible to conduct experimental research into the mechanisms that strengthen, weaken or even erase fear memory in a more direct fashion, without having to wait until the fear memory is expressed.

The research is part of the Vici project of Prof. Merel Kindt, which is funded by the Netherlands Organisation for Scientific Research (NWO).

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Biological Aging, Seen in Women With Alzheimer’s Risk Factor, Blocked by Hormone Therapy

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Feb. 13, 2013 — Healthy menopausal women carrying a well-known genetic risk factor for Alzheimer’s disease showed measurable signs of accelerated biological aging, a new study has found.
However, in carriers who started hormone therapy at menopause  and remained on that therapy, this acceleration was absent, the researchers said. Hormone therapy for non-carriers of the risk factor, a gene variant called ApoE4, had no protective effect on their biological aging.

“This shows that ApoE4 is contributing to aging at the cellular level well before any outward symptoms of decline become apparent,” said Natalie Rasgon, MD, PhD, professor of psychiatry and behavioral sciences at the Stanford University School of Medicine and director of the Stanford Center for Neuroscience in Women’s Health. “Yet, estrogen appears to have a protective effect for middle-aged women who are carrying this genetic risk factor.”

All people carry two copies of a gene called ApoE. (One copy is inherited from each parent). Like genes for eye or hair color, ApoE comes in more than one version. Some 15 to 20 percent of Americans carry at least one copy of ApoE4, a version that puts them at substantially increased risk for late-onset Alzheimer’s disease in comparison with people who are not ApoE4 carriers.

Rasgon is the senior author of a study involving 70 relatively well-educated, high-functioning women. It was published online Feb. 13 in PLOS ONE. First author Emily Jacobs, PhD, is a postdoctoral fellow at Harvard Medical School. When the work took place, Jacobs was associated with the lab of another study co-author, Elissa Epel, PhD, associate professor of psychiatry at the University of California-San Francisco.

“We know from numerous studies that ApoE4 is a major genetic risk factor for cognitive decline, Alzheimer’s disease and early mortality,” Jacobs said. “We wanted to see whether an accelerated rate of biological aging explained this risk.”

Another co-author of the study is Elizabeth Blackburn, PhD, professor of biochemistry and biophysics at UCSF, who won the Nobel Prize in 2009 for her work elucidating the mechanism by which intracellular features called telomeres act as biological clocks.

Telomeres are repeated sequences of alternating chemical units of DNA that cap the ends of each chromosome in every cell of all living creatures from fungi to humans. Their function is analogous to that of the plastic caps ringing the ends of a shoelace: They stabilize chromosomes, keeping them from unraveling and preventing other damage, too. But telomeres themselves are not perfectly stable. The process of cell division, as well as bouts of oxidative stress or inflammation, cause them to shorten. If they reach a point at which chromosomal integrity is challenged, this could give rise to cancer or other malfunction in the cell housing the challenged chromosomes. Evolution has engineered protective mechanisms into such cells so that they die or, at least, lose their ability to divide further. But this evolutionary emergency brake has its downside: It contributes to the slow but steady deterioration that manifests visibly in our aging skin and, less visibly, in all the other bodily organs.

Using telomere shortening as an index of biological aging, the investigators drew blood samples from almost 70 healthy women, most of them between the ages of 45 and 65, who had been on hormone therapy since menopause. These women were randomly divided into two groups. One group remained on hormones, while the second group discontinued therapy.

Blood samples from the volunteers were taken when they first entered the study and again two years later. Jacobs, Rasgon and their colleagues separated white blood cells from each sample, extracted the cells’ DNA and measured the length of each woman’s telomeres at both time points. Then they calculated the change in telomere length that had taken place over the two-year period.

“Telomere length is relatively easy to measure in blood cells, and it’s an emerging marker of biological aging,” said Jacobs. “It predicts the incidence of age-related diseases and mortality.”

Among the many other assessments the researchers made on these women was their ApoE status. They found that ApoE4 carriers’ telomeres were six times as likely as those of non-carriers to undergo significant shortening within the two-year study window. On average, the telomeres of ApoE4 carriers had shortened by an amount equivalent to what might be expected to take a decade, based on other studies of healthy women.

However, hormone therapy effectively zeroed out ApoE4’s negative influence on telomere length over time. Carriers who remained on this regimen showed no evidence of telomere shortening.

“Our take-home findings from this study were, first, that ApoE4 carriers are at greater risk of biological aging, which is associated with negative health outcomes and, second, that if you were a postmenopausal ApoE4 carrier, being on estrogen therapy was a good thing for telomere length, an established measure of biological aging at the cellular level,” Rasgon said. “This brings us a step closer to being able to identify which women will benefit the most from estrogen replacement therapy.”

In 2002, one arm of a large-scale longitudinal trial of women examining hormone therapy was halted due to an unexpected increase in adverse cardiovascular events among women on the therapy. The ensuing publicity resulted in women abandoning the regimen in droves. But the trial subjects among whom these ill effects occurred were women who had begun estrogen treatment years after reaching menopause. Subsequent studies have demonstrated that women who start treatment at menopause or soon afterward may experience some benefit.

Rasgon noted that in addition to timing and ApoE status, the type of estrogen formulation used may prove to be an important determinant of hormone therapy’s health impact. She said she expects to publish other work soon concerning the differential effects of different formulations.

Rasgon’s graduate student Heather Kenna was another Stanford co-author of the study, which was funded by National Institutes of Health grants (AG22008, RR-00070) and the Robert Wood Johnson Foundation Health and Society Scholars Program.

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Parkinson’s Treatment Can Trigger Creativity: Patients Treated With Dopamine-Enhancing Drugs Are Developing Artistic Talents

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Jan. 14, 2013 — Parkinson’s experts across the world have been reporting a remarkable phenomenon — many patients treated with drugs to increase the activity of dopamine in the brain as a therapy for motor symptoms such as tremors and muscle rigidity are developing new creative talents, including painting, sculpting, writing, and more.

Prof. Rivka Inzelberg of Tel Aviv University’s Sackler Faculty of Medicine first noticed the trend in her own Sheba Medical Center clinic when the usual holiday presents from patients — typically chocolates or similar gifts — took a surprising turn. “Instead, patients starting bringing us art they had made themselves,” she says.

Inspired by the discovery, Prof. Inzelberg sought out evidence of this rise in creativity in current medical literature. Bringing together case studies from around the world, she examined the details of each patient to uncover a common underlying factor — all were being treated with either synthetic precursors of dopamine or dopamine receptor agonists, which increase the amount of dopamine activity in the brain by stimulating receptors. Her report will be published in the journal Behavioral Neuroscience.

Giving in to artistic impulse Dopamine is involved in several neurological systems, explains Prof. Inzelberg. Its main purpose is to aid in the transmission of motor commands, which is why a lack of dopamine in Parkinson’s patients is associated with tremors and a difficulty in coordinating their movements.

But it’s also involved in the brain’s “reward system” — the satisfaction or happiness we experience from an accomplishment. This is the system which Prof. Inzelberg predicts is associated with increasing creativity. Dopamine and artistry have long been connected, she points out, citing the example of the Vincent Van Gogh, who suffered from psychosis. It’s possible that his creativity was the result of this psychosis, thought to be caused by a spontaneous spiking of dopamine levels in the brain.

There are seemingly no limits to the types of artistic work for which patients develop talents, observes Prof. Inzelberg. Cases include an architect who began to draw and paint human figures after treatment, and a patient who, after treatment, became a prize-winning poet though he had never been involved in the arts before.

It’s possible that these patients are expressing latent talents they never had the courage to demonstrate before, she suggests. Dopamine-inducing therapies are also connected to a loss of impulse control, and sometimes result in behaviors like excessive gambling or obsessional hobbies. An increase in artistic drive could be linked to this lowering of inhibitions, allowing patients to embrace their creativity. Some patients have even reported a connection between their artistic sensibilities and medication dose, noting that they feel they can create more freely when the dose is higher.

Therapeutic value Prof. Inzelberg believes that such artistic expressions have promising therapeutic potential, both psychologically and physiologically. Her patients report being happier when they are busy with their art, and have noted that motor handicaps can lessen significantly. One such patient is usually wheelchair-bound or dependent on a walker, but creates intricate wooden sculptures that have been displayed in galleries. External stimuli can sometimes bypass motor issues and foster normal movement, she explains. Similar types of art therapy are already used for dementia and stroke patients to help mitigate the loss of verbal communication skills, for example.

The next step is to try to characterize those patients who become more creative through treatment through comparing them to patients who do not experience a growth in artistic output. “We want to screen patients under treatment for creativity and impulsivity to see if we can identify what is unique in those who do become more creative,” says Prof. Inzelberg. She also believes that such research could provide valuable insights into creativity in healthy populations, too.

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Better Stroke Care, Everywhere: Study Boosts Local Hospitals’ Clotbuster Use

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Dec. 20, 2012 — From the moment a stroke occurs, patients must race against the clock to get treatment that can prevent lasting damage. Now, a new study shows the promise — and the challenges — of getting them state-of-the-art treatment safely at their local hospital, saving precious minutes.

The results come from an effort that tested methods to improve delivery of a time-sensitive, clot-busting drug in stroke patients at 24 community hospitals across Michigan. To date, clot-busting treatment has been mostly used at larger hospitals.

The research effort was coordinated by members of the University of Michigan Health System’s Department of Emergency Medicine, Department of Neurology and Stroke Program, which offered half the hospitals education and round-the-clock treatment assistance by phone. The study was funded by the National Institute of Neurological Disorders and Stroke at the National Institutes of Health.

By the end of the study, the community hospitals across Michigan that had the U-M experts as the “sixth man” on their teams did better at delivering the drug called tPA to eligible patients than those that didn’t.

The findings of the randomized controlled trial are published in Lancet-Neurology. They show that community hospitals can indeed improve patients’ chances of getting tPA in the first few hours of a stroke, without increased risk of dangerous bleeding.

Data from 22 of the hospitals show that tPA use more than doubled in the 11 hospitals that were randomly chosen to get the extra help, versus a smaller increase in the 11 that didn’t. Some hospitals even surpassed national targets for tPA use that large stroke centers don’t always reach — a true game-changing performance.

Across the U.S., less than 2 percent of stroke patients receive tPA — when more than 11 percent could — largely because of the time limits on its use and delays in getting patients to a hospital. That’s why it’s important for community hospitals to offer it.

The investigation, called INSTINCT for INcreasing Stroke Treatment through INterventional Change Tactics, demonstrates that tPA can be used safely and appropriately in the community hospital setting — and that more work needs to be done to expand public access to the only treatment approved by the U.S. Food and Drug Administration to reverse the effects of stroke. While improvement at the target community hospitals that got the education was statistically significant, it was not as large as hoped for. But the findings suggest that relatively low-cost and low-tech interventions can improve local stroke care.

Lead author Phillip Scott, M.D., a U-M emergency physician and principal investigator of the trial, likens the results to the performance of teams from smaller athletic conferences that beat larger, more celebrated teams, to reach the final stages of the annual NCAA college basketball tournament.

“This study suggests that community hospitals can evaluate and treat enough emergency stroke patients to keep their teams’ treatment skills sharp, but are of a size that creates rapid lines of communication and stable physican and nurse teams. This may facilitate rapid, safe stroke diagnosis and care,” says Scott, an associate professor of emergency medicine at the U-M Medical School. “Four of the hospitals that received the educational intervention achieved tPA use rates of 5 to 8 percent of all stroke patients, compared to only one of the control hospitals. That’s a rate many large medical centers strive to reach.”

“This study, while finding only modest improvements, provides encouraging evidence that intensive professional education at community hospitals has the potential to improve the use of tPA in acute stroke care,” said Scott Janis, Ph.D., program director at the NINDS. “Importantly, it also lays the groundwork for future strategies that should be explored to develop evidence-based interventions that would improve patient access to this proven therapy following stroke.”

How it was done, and more about the results:

The study started by collecting baseline data on stroke treatment from 2005 and 2006 at all the hospitals. After the sites were randomized, the U-M team offered continuing medical education classes at the hospitals, workshops at U-M, and other support, including 24-hour phone consultation availability, to the hospitals chosen to receive the intervention.

All the hospitals were in the lower peninsula of Michigan, and were chosen at random from among hospitals with at least 100 stroke discharges per year. All hospitals that participated stayed in the trial until data collection ended in 2010. Hospitals could hold primary stroke center designation, as granted by the Joint Commission, but could not be tertiary academic comprehensive stroke centers.

In all, 188 tPA treatments occurred among 15,065 stroke patients during the baseline period, and 557 treatments occurred among 25,758 stroke patients from 2007 to 2010. The authors note that tPA use at hospitals nationwide rose somewhat during the study period, due to factors such as insurance reimbursement and new data on tPA’s effectiveness at preventing disability.

The INSTINCT study findings were complicated by the fact that one of the hospitals enrolled in the trial became an academic stroke center after starting the study. When it and its matched hospital are excluded from the analysis, the remaining hospitals showed enough of an impact from the educational effort to be statistically significant — a 105 percent increased use of tPA over baseline.

“We essentially saw a doubling of tPA usage, using standard technologies for education and support. Importantly, the increase was achieved safely,” Scott says. “This shows we can translate the knowledge of effective stroke treatment into a community setting.” The size of the study, with 557 stroke patients treated after intervention began, makes it one of the largest tPA studies in the world.

More about stroke treatment:

The use of tPA in ischemic stroke has grown around the world in the last decade, but many patients who could get the drug still do not. The “treatment window” for tPA has been seen as three hours from the onset of stroke symptoms, though recent studies suggest patients can see benefit even four and a half hours out. The importance of early treatment, however, cannot be overstated, as patients treated earlier have greater benefits and the drug is not currently FDA-approved for use beyond three hours.

Considering that most stroke sufferers wait more than an hour after symptoms start before they seek help, and that travel time to a tPA-providing hospital is around 30 minutes, that leaves hospitals about an hour to do medical imaging, make a firm diagnosis and initiate tPA treatment.

Patients must then be monitored to check for brain bleeding, and to assess the impact of their stroke. To reliably accomplish this, a system for the care of acute stroke patients must already be in place when a patient arrives at the emergency department.

Patients who don’t reach a location where they can received standard tPA treatment in time can still potentially be treated with advanced catheter-based clot removal treatment at a major referral hospital such as U-M. These advanced therapies have a longer time window for treatment, but have not been proven more effective than early standard treatment. The Stroke Program at U-M is participating in multiple trials to improve advanced stroke treatment.

Additional authors: William Meurer, M.D., Shirley Frederiksen, M.S., and Robert Silbergleit, M.D. of U-M Emergency Medicine; John Kalbfleisch, Ph.D., Zhenzhen Xu, Ph.D. and Mary Haan, DrPH of the U-M School of Public Health; and Lewis B Morgenstern, M.D., of U-M Neurology. Morgenstern directs, and Scott, Meurer, Frederiksen and Silbergleit are members of, the U-M Stroke Program.

Funding source: NINDS R01-NS-050372

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Alzheimer’s Plaques in PET Brain Scans Identify Future Cognitive Decline

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Among patients with mild or no cognitive impairment, brain scans using a new radioactive dye can detect early evidence of Alzheimer’s disease that may predict future decline, according to a multi-center study led by researchers at Duke University Medical Center.

The finding is published online July 11, 2012, in the journal Neurology, the medical journal of the American Academy of Neurology. It expands on smaller studies demonstrating that early detection of tell-tale plaques could be a predictive tool to help guide care and treatment decisions for patients with Alzheimer’s disease.

“Even at a short follow-up of 18 months we can see how the presence of amyloid plaques affects cognitive function,” said P. Murali Doraiswamy, M.D., professor of psychiatry at Duke who co-led the study with R. Edward Coleman, M.D., professor of radiology at Duke . “Most people who come to the doctor with mild impairment really want to know the short-term prognosis and potential long-term effect.”

Doraiswamy said such knowledge also has some pitfalls. There is no cure for Alzheimer’s disease, which afflicts 5.4 million people in the United States and is the sixth-leading cause of death among U.S. adults. But he said numerous drugs are being investigated, and identifying earlier disease would improve research into their potential benefits and speed new discoveries, while also enhancing care and treatment of current patients.

In the Neurology study, 151 people who had enrolled in a multi-center test of a new radioactive dye called florbetapir (Amyvid) were recruited to participate in a 36-month analysis. Of those participants, 69 had normal cognitive function at the start of the study, 51 had been diagnosed with mild impairment, and 31 had Alzheimer’s dementia.

All completed cognitive tests and underwent a brain scan using Positron Emission Tomography, or PET imaging. The technology uses radioactive tracers designed to highlight specific tissue to create a three-dimensional picture of an organ or a biological function.

The dye used in the study, florbetapir, was recently approved by the U.S. Food and Drug Administration for PET imaging of the brain to estimate beta-amyloid plaque density in patients who are being evaluated for cognitive impairment. It binds to the amyloid plaques that characterize Alzheimer’s disease, providing a window into the brain to see if the plaques have formed, and how extensively.

Patients in the study were reassessed with additional cognitive exams at 18 months and 36 months. At the 18-month point, patients with mild cognitive impairment who had PET evidence of plaque at the trial’s start worsened to a great degree on cognitive tests than patients who had no evidence of plaque at the trial’s start. Twenty-nine percent of the plaque-positive patients in this group developed Alzheimer’s dementia, compared to 10 percent who started with no plaque.

Cognitively normal patients with a plaque-positive PET scan at the start of the study also showed more mental decline at 18 months compared to those who were negative for plaque.

The study additionally found that people with negative scans reversed from minimally impaired to normal more often than people with positive PET scan, suggesting test anxiety or concentration problems could have affected their initial performance.

“For the most part we have been blind about who would progress and who wouldn’t, so this approach is a step toward having a biomarker that predicts risk of decline in people who are experiencing cognitive impairment,” Doraiswamy said.

He said the study’s results provide initial data that needs to be verified by additional research. Final, 36-month data from the study has been completed and will be presented at the Alzheimer’s Association International Conference this week in Vancouver, Canada. Doraiswamy also cautioned that florbetapir is currently not approved to predict the development of dementia or other neurologic conditions and stressed that it should not be used as a screening tool in otherwise normal or minimally impaired people. Likewise, a positive scan is not necessarily diagnostic for Alzheimer’s by itself.

In addition to Doraiswamy and Coleman (who died in June), study authors included; Reisa A. Sperling and Keith A. Johnson of Massachusetts General Hospital, Boston Medical School; Eric M. Reiman of Banner Alzheimer’s Institute; Mat D. Davis of the University of Pennsylvania; Michael Grundman of Global R&D Partners and the University of California, San Diego; Marwan N. Sabbagh of Banner-Sun Health Research Institute; Carl H. Sadowsky of Nova SE University; Adam S. Fleisher of Banner Alzheimer’s Institute and UCSD; and Alan Carpenter, Christopher M. Clark (deceased), Abhinay D. Joshi, Mark A. Mintun, Daniel M. Skovronsky, and Michael J. Pontecorvo of Avid Radiopharmaceuticals.

The study was funded by Eli Lilly/Avid Radiopharmaceuticals, which markets florbetapir and conducted by Avid and the AV45-A11 study group, a consortium of Alzheimer’s clinical research centers. Doraiswamy receives advisory and speaker fees from Lilly/Avid, as well as other companies, and owns shares in Sonexa and Clarimedix.

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CONCERNED ABOUT MEMORY PROBLEMS?

TAKE ACTION…GET FREE, CONFIDENTIAL MEMORY SCREENINGS

TUESDAY, NOVEMBER 13, 2012

A. Why is memory screening so important?

Ø As the body ages, so does the brain, especially the ability to remember declines. There are many reasons that cause memory loss; stress, depression, vitamin deficiency, thyroid problems, medical illnesses, Alzheimer’s disease, or just normal aging memory decline.

Ø Memory screenings are the first step toward finding out if the person has early stages of Alzheimer’s dementia vs another condition vs normal aging memory decline.

Ø It is very important to identify the disease or problem that is causing memory loss. Early detection leads to early treatment, which in turn, leads to improved quality of life

Ø Memory screenings can also let the person know that everything is ok. The screenings could turn out normal and put the mind at ease.

Ø Normal scores on a memory screenings provides a valuable opportunity to establish a baseline score for future comparison

Ø A memory screening is not used to diagnose any particular illness & does not replace consultation with a qualified physician or health care provider

B. What is the process of memory screenings?

Ø A screening consists of a series of questions and tasks that are designed to test memory and thinking ability. These tools are non-invasive, safe, and reliable instruments that are sensitive to even mild brain dysfunction

Ø Feedback will be provided immediately following screenings.

Ø While health plans do not typically cover screenings, if additional testing is recommended, most health plans will cover the cost based on individual medical benefits. If necessary, referrals will be provided to seek further examination.

FOR ADDITIONAL INFORMATION, PLEASE CONTACT OUR OFFICE 949-481-8414

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New Biomarker In The Blood May Help Predict Alzheimer’s Disease

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ScienceDaily (July 18, 2012) — Higher levels of a certain fat in the blood called ceramides may increase a person’s risk of developing Alzheimer’s disease, according to a study published in the July 18, 2012, online issue of Neurology®, the medical journal of the American Academy of Neurology.

“Our study identifies this biomarker as a potential new target for treating or preventing Alzheimer’s disease,” said study author Michelle M. Mielke, PhD, an epidemiologist with the Mayo Clinic in Rochester, Minn. Mielke was with Johns Hopkins University at the time of the research.

For the study, 99 women between the ages of 70 and 79 and free of dementia in the Women’s Health and Aging Study II had their blood tested for levels of serum ceramides, a fatty compound found throughout the body that is associated with inflammation and cell death. The participants were placed into three groups: high, middle and low levels of ceramides. They were then followed for up to nine years. Of the 99 participants, 27 developed dementia and 18 of those were diagnosed with probable Alzheimer’s disease.

The study found that women who had the highest levels of the biomarker were 10 times more likely to develop Alzheimer’s disease than women with the lowest levels. Those with middle levels of the biomarker were nearly eight times more likely to develop the disease than those with the lowest levels.
“These findings are important because identifying an accurate biomarker for early Alzheimer’s that requires little cost and inconvenience to a patient could help change our focus from treating the disease to preventing or delaying it,” said Valory Pavlik, PhD, with the Alzheimer’s Disease and Memory Disorders Center of Baylor College of Medicine in Houston and a member of the American Academy of Neurology, in an accompanying editorial.

According to Pavlik, “While a larger, more diverse study is needed to confirm these findings, projections that the global prevalence of Alzheimer’s disease will double every 20 years for the foreseeable future have certainly increased the sense of urgency among researchers and health care agencies to identify more effective screening, prevention and treatment strategies.”
The study was supported by the National Institute on Aging, the National Institute of Neurological Disorders and Stroke and the Johns Hopkins Older Americans Independence Center.

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Adaptable Decision Making In The Brain 

ScienceDaily (June 19, 2012) — Researchers at the University of Iowa, together with colleagues from the California Institute of Technology and New York University, have discovered how a part of the brain helps predict future events from past experiences. The work sheds light on the function of the front-most part of the frontal lobe, known as the frontopolar cortex, an area of the cortex uniquely well developed in humans in comparison with apes and other primates.

Making the best possible decisions in a changing and unpredictable environment is an enormous challenge. Not only does it require learning from past experience, but it also demands anticipating what might happen under previously unencountered circumstances. Past research from the UI Department of Neurology was among the first to show that damage to certain parts of the frontal lobe can cause severe deficits in decision making in rapidly changing environments. The new study from the same department on a rare group of patients with damage to the very frontal part of their brains reveals a critical aspect of how this area contributes to decision making. The findings were published June 19 in the Journal of Neuroscience.

“We gave the patients four slot machines from which to pick in order to win money. Unbeknownst to the patients, the probability of getting money from a particular slot machine gradually and unpredictably changed during the experiment. Finding the strategy that pays the most in the long run is a surprisingly difficult problem to solve, and one we hypothesized would require the frontopolar cortex,” explains Christopher Kovach, Ph.D., a UI post-doctoral fellow in neurosurgery and first author of the study.

Contrary to the authors’ initial expectation, the patients actually did quite well on the task, winning as much money, on average, as healthy control participants.

“But when we compared their behavior to that of subjects with intact frontal lobe, we found they used a different set of assumptions about how the payoffs changed over time,” Kovach says. “Both groups based their decisions on how much they had recently won from each slot machine, but healthy comparison subjects pursued a more elaborate strategy, which involved predicting the direction that payoffs were moving based on recent trends. This points towards a specific role for the frontopolar cortex in extrapolating recent trends.”

Kovach’s colleague and study author Ralph Adolphs, Ph.D., professor of neuroscience and psychology at the California Institute of Technology, adds that the study results “argue that the frontopolar cortex helps us to make short-term predictions about what will happen next, a strategy particularly useful in environments that change rapidly — such as the stock market or most social settings.”

Adolphs also hold an adjunct appointment in the UI Department of Neurology.

The study’s innovative approach to understanding the function of this part of the brain uses model-based analyses of behavior of patients with specific and precisely characterized areas of brain damage. These patients are members of the UI’s world-renowned Iowa Neurological Patient Registry, which was established in 1982 and has more than 500 active members with selective forms of damage, or lesions, to one or two defined regions in the brain.

“The University of Iowa is one of the few places in the world where you could carry out this kind of study, since it requires carefully assessed patients with damage to specific parts of their brain,” says study author Daniel Tranel, Ph.D., UI professor of neurology and psychology and director of the UI Division of Behavioral Neurology and Cognitive Neuroscience.

In a final twist to the finding, the strategy taken by lesion patients was actually slightly better than the one used by comparison subjects. It happened that the task was designed so that the trends in the payoffs were, in fact, random and uninformative.

“The healthy comparison subjects seemed to perceive trends in what was just random noise,” Kovach says.

This implies that the functions of the frontopolar cortex, which support more complex and detailed models of the environment, at times come with a downside: setting up mistaken assumptions.

“To the best of my knowledge this is the first study which links a normal tendency to see a nonexistent pattern in random noise, a type of cognitive bias, to a particular brain region,” Kovach notes.

The researchers next want to investigate other parts of the frontal cortex in the brain, and have also begun to record activity directly from the brains of neurosurgical patients to see how single cells respond while making decisions. The work is also important to understand difficulties in decision making seen in disorders such as addiction.

The study, “Anterior prefrontal cortex contributes to action selection through tracking of recent reward trends,” also included authors David Rudrauf from the University of Iowa, John O’Doherty from the California Institute of Technology, and Nathaniel Daw from New York University.

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Breaking Point: When Does Head Trauma in Sports Lead to Memory Loss?

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ScienceDaily (Apr. 18, 2012) — A new study suggests there may be a starting point at which blows to the head or other head trauma suffered in combat sports start to affect memory and thinking abilities and can lead to chronic traumatic encephalopathy, or CTE, in the brain.

The research was released April 18 and will be presented as part of the Emerging Science program at the American Academy of Neurology’s 64th Annual Meeting in New Orleans April 21 to April 28, 2012.

“While we already know that boxing and other combat sports are linked to brain damage, little is known about how this process develops and who may be on the path to developing CTE, which is a degenerative brain disease found in athletes and others with a history of multiple concussions and brain damage,” said study author Charles Bernick, MD, of the Cleveland Clinic in Cleveland and a member of the American Academy of Neurology. CTE is only diagnosed through autopsy after death, but symptoms include memory loss, aggression and difficulty thinking.

The study involved 35 boxers and 43 mixed martial arts athletes with an average age of 29 who were part of the ongoing Professional Fighters Brain Health Study. The fighters were given computer tests that measured memory and thinking skills and underwent MRI brain scans. Years of fighting and number of fights were recorded based on self-reporting and published records. The fighters were then split into two groups: those who fought for nine or fewer years and those with more than nine years of fighting history.

In both groups, those with more years of fighting and more fights per year were more likely to have lower brain volumes in three areas of the brain. In those with fewer than nine years of fighting, there was no relationship between the years of fighting or the number of fights per year and the results on memory and thinking tests. But for those who had fought for nine or more years, those with more fights per year performed worse on the thinking and memory tests than those with fewer fights per year.

“Our study shows there appears to be a threshold at which continued repetitive blows to the brain begin to cause measurable changes in memory and thinking, despite brain volume changes that can be found earlier,” said Bernick.

The study was supported by the Lincy Foundation.

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Physical Activity May Reduce Alzheimer’s Disease Risk at Any Age

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ScienceDaily (Apr. 18, 2012) — Daily physical activity may reduce the risk of Alzheimer’s disease and cognitive decline, even in people over the age of 80, according to a new study by neurological researchers from Rush University Medical Center that will be published in the online issue of Neurology, the medical journal of the American Academy of Neurology on April 18.

“The results of our study indicate that all physical activities including exercise as well as other activities such as cooking, washing the dishes, and cleaning are associated with a reduced risk of Alzheimer’s disease,” said Dr. Aron S. Buchman, lead author of the study and associate professor of neurological sciences at Rush. “These results provide support for efforts to encourage all types of physical activity even in very old adults who might not be able to participate in formal exercise, but can still benefit from a more active lifestyle.”

“This is the first study to use an objective measurement of physical activity in addition to self-reporting,” said Dr. Aron S. Buchman, lead author of the study and associate professor of neurological sciences at Rush. “This is important because people may not be able to remember the details correctly.”

To measure total daily exercise and non-exercise physical activity, researchers from Rush asked 716 older individuals without dementia with an average age of 82 to wear a device called an actigraph, which monitors activity, on their non-dominant wrist continuously for 10 days.

All exercise and non-exercise physical activity was recorded. Study participants also were given annual cognitive tests during this ongoing study to measure memory and thinking abilities. Participants also self-reported their physical and social activities. Study participants were individuals from the Rush Memory and Aging Project, an ongoing, longitudinal community study of common chronic conditions of old age.

Over a mean of 3.5 years of follow-up, 71 participants developed Alzheimer’s disease The research found that people in the bottom 10 percent of daily physical activity were more than twice as likely (2.3 times) to develop Alzheimer’s disease as people in the top 10 percent of daily activity.

The study also showed that those individuals in the bottom 10 percent of intensity of physical activity were almost three times (2.8 times) as likely to develop Alzheimer’s disease as people in the top percent of the intensity of physical activity.

“Since the actigraph was attached to the wrist, activities like cooking, washing the dishes, playing cards and even moving a wheelchair with a person’s arms were beneficial,” said Buchman. “These are low-cost, easily accessible and side-effect free activities people can do at any age, including very old age, to possibly prevent Alzheimer’s.”

The number of Americans older than 65 years of age will double to 80 million by 2030. “Our study shows that physical activity, which is an easily modifiable risk factor, is associated with cognitive decline and Alzheimer’s disease. This has important public health consequences,” said Buchman.

Co-authors of the study from Rush are Patricia Boyle, PhD; Li Yu, PhD; Dr. Raj C. Shah; Robert S. Wilson, PhD; and Dr. David A. Bennett.

The National Institutes of Health, National Institute on Aging, the Illinois Department of Public Health and the Robert C. Borwell Endowment Fund helped fund the study.

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