Thursday, 19 July 2018

Test for Alzheimer’s disease directly measures synaptic loss



Yale researchers have tested a new method for directly measuring synaptic loss in individuals with Alzheimer’s disease. The method, which uses PET imaging technology to scan for a specific protein in the brain linked to synapses, has the potential to accelerate research for new Alzheimer’s treatments, the researchers said.
The study was published in JAMA Neurology.
Alzheimer’s disease affects 5.7 million Americans, and that number is expected to reach 14 million by the year 2050. To date, most of the research on the disease’s effects on the brain has been done post-mortem. To investigate new treatments, researchers have recently explored methods for measuring memory loss in living patients.
This was a collaborative study between researchers at the Yale PET Centre and the Yale Alzheimer’s Disease Research Unit (ADRU) to explore a new strategy for measuring synaptic loss — an established indicator of cognitive decline. A decrease in synapses, the junctions between nerve cells, correlates with cognitive impairment in Alzheimer’s disease patients, they said.
To quantify synaptic loss, the research team used a specific radioactive chemical, [11C]UCB-J, that binds with a protein, the SV2A, that is present in nearly all synapses. The researchers recruited 21 older adults with either early Alzheimer’s disease or normal cognitive ability. Each was injected with [11C]UCB-J and then scanned with high-resolution PET technology. The scans allowed the researchers to visualize synaptic “density” in different regions of the brain.
The researchers analysed the scans, as well as results from MRIs and cognitive evaluations for both groups. Compared to individuals with normal cognition, the participants with Alzheimer’s disease had a 41% reduction in the SV2A marker in an area of the brain associated with memory.
“We found that in early Alzheimer’s disease, there is loss of synaptic density in the region of the hippocampus,” said first author Ming-Kai Chen, M.D., associate professor of radiology and biomedical imaging, and co-medical director of the PET Centre.
The findings show that the non-invasive PET test can provide a direct measure of synaptic loss in adults with even mild cognitive impairment. “With this new biomarker, PET imaging for SV2A, we can measure synaptic density in the living human brain,” Chen noted.
The Yale team is currently recruiting more study participants to confirm their findings and potentially use the PET technique to assess Alzheimer’s disease drugs, they said.
This PET imaging tool is also being used in clinical research studies at Yale for other diseases of the brain where synapse loss is a critical component of the disease, said Richard Carson, co-author and director of Yale PET Centre. These diseases include Parkinson’s disease, epilepsy, drug abuse, depression, and schizophrenia.
“A critical barrier in Alzheimer’s research has been the inability to measure synaptic density in living individuals,” said ADRU Director Christopher Van Dyck, M.D. “Dr. Carson’s team has led a ground-breaking effort to provide us with this capability. For those of us in the Alzheimer’s field, in vivo assessment of synaptic density may transform our ability to track early Alzheimer’s pathogenesis and response to treatment.”
Other Yale authors are Adam P. Mecca, MD, Mika Naganawa, Sjoerd J. Finnema, Takuya Toyonaga, Shu-fei Lin, Soheila Najafzadeh, Jim Ropchan, Yihuan Lu, Julia W. McDonald, Hannah R. Michalak, Nabeel B. Nabulsi, Amy F. T. Arnsten, and Yiyun Huang. Carson is also a member of Yale Cancer Center.
The study was supported in part by The Dana Foundation David Mahoney Neuroimaging Grant, Yale Alzheimer’s Disease Research Center, and the National Institutes of Health. 
Source: Science Daily

Monday, 16 July 2018

Antioxidant benefits of sleep



Understanding sleep has become increasingly important in modern society, where chronic loss of sleep has become rampant and pervasive. As evidence mounts for a correlation between lack of sleep and negative health effects, the core function of sleep remains a mystery. But in a new study publishing 12 July in the open access journal PLOS Biology, Vanessa Hill, Mimi Shirasu-Hiza and colleagues at Columbia University, New York, found that short-sleeping fruit fly mutants shared the common defect of sensitivity to acute oxidative stress, and thus that sleep supports antioxidant processes. Understanding this ancient bi-directional relationship between sleep and oxidative stress in the humble fruit fly could provide much-needed insight into modern human diseases such as sleep disorders and neurodegenerative diseases.
Why do we sleep? During sleep, animals are vulnerable, immobile, and less responsive to their environments; they are unable to forage for food, mate, or run from predators. Despite the cost of sleep behavior, almost all animals sleep, suggesting that sleep fulfills an essential and evolutionary conserved function from humans to fruit flies.
The researchers reasoned that if sleep is required for a core function of health, animals that sleep significantly less than usual should all share a defect in that core function. For this study, they used a diverse group of short-sleeping Drosophila (fruit fly) mutants. They found that these short-sleeping mutants do indeed share a common defect: they are all sensitive to acute oxidative stress.
Oxidative stress results from excess free radicals that can damage cells and lead to organ dysfunction. Toxic free radicals, or reactive oxygen species, build up in cells from normal metabolism and environmental damage. If the function of sleep is to defend against oxidative stress, then increasing sleep should increase resistance to oxidative stress. Hill and co-workers used both pharmacological and genetic methods to show that this is true.
Finally, the authors proposed, if sleep has antioxidant effects, then surely oxidative stress might regulate sleep itself. Consistent with this hypothesis, they found that reducing oxidative stress in the brain by over expressing antioxidant genes also reduced the amount of sleep. Taken together, these results point to a bi-directional relationship between sleep and oxidative stress — that is, sleep functions to defend the body against oxidative stress and oxidative stress in turn helps to induce sleep.
This work is relevant to human health because sleep disorders are correlated with many diseases that are also associated with oxidative stress, such as Alzheimer’s, Parkinson’s, and Huntington’s diseases. Sleep loss could make individuals more sensitive to oxidative stress and subsequent disease; conversely, pathological disruption of the antioxidant response could also lead to loss of sleep and associated disease pathologies.
 Source: Science Daily

Thursday, 12 July 2018

Mindfulness May Ease Tinnitus Symptoms



New research has found that a mindfulness-based approach to tinnitus could transform treatment of the condition.
Led by Dr. Laurence McKenna from University College London Hospitals NHS Foundation Trust (UCLH) and Dr. Liz Marks from the Department of Psychology at the University of Bath, the new study found that mindfulness based cognitive therapy (MBCT) helps to significantly reduce the severity of tinnitus compared to relaxation-based treatments, an approach recommended by many tinnitus clinics.
Tinnitus, described as a sensation or awareness of sound that is not caused by an external sound source, affects approximately 6 million people in the UK — about 10 percent of the population. Approximately one in 100 people are very distressed or disabled by it and as many as one in 20 people are at least moderately distressed by it.
Tinnitus is associated with complaints of emotional stress, insomnia, auditory perceptual problems, and concentration problems, researchers report.
While there is no treatment to stop the tinnitus noise, the new research, funded by the British Tinnitus Association (BTA), shows that treatment can make it less severe, intrusive, and bothersome, the researchers say.
For the study, 75 patients took part in a trial at UCLH’s Royal National Throat, Nose and Ear Hospital, receiving either MBCT or relaxation therapy.
The study found that both treatments led to a reduction in tinnitus severity, psychological distress, anxiety, and depression for patients, according to the researchers.
“However, the MBCT treatment led to significantly greater reductions in tinnitus severity than the relaxation treatment, and this improvement lasted for longer,” Marks said. “In addition, 182 patients who completed MBCT routinely in our clinic showed a similar level of improvement.”
Relaxation therapy provides patients with specific skills to reduce stress arousal levels. In contrast, MBCT, taught by highly-trained clinical psychologists, teaches patients to pay purposeful, present-moment attention to experiences, rather than trying to suppress those experiences, the researchers explained.
Practicing mindfulness meditation can cultivate a more helpful way of responding to tinnitus, researchers add.
People learn how to “allow” and “accept” tinnitus, rather than having to “fight it” or “push it away,” the researchers noted.
“MBCT turns traditional tinnitus treatment on its head — so rather than trying to avoid or mask the noise, it teaches people to stop the battle with tinnitus,” Marks said.
“The mindfulness approach is radically different from what most tinnitus sufferers have tried before, and it may not be right for everyone,” she continued. “We are confident, however, that the growing research base has demonstrated how it can offer an exciting new treatment to people who may have found that traditional treatment has not been able to help them yet. We hope the results of our research will be one of the first steps to MBCT becoming more widely adopted.”
Source: Psych Central
 

Tuesday, 10 July 2018

Suppressing negative emotions during health scare may whip up spiral of fear



Trying to suppress worries during a health scare, like the recent Zika outbreak, may lead to an ever-intensifying cycle of emotional suppression and fear, according to a team of researchers.
In a study of pregnant women in areas of the United States vulnerable to the Zika virus, the researchers found that women who tried to suppress their fears reported higher levels of fear later, which, in turn, prompted more emotional suppression. Pregnant women were particularly concerned about Zika because media sources at the time reported that the virus, spread mainly by mosquitoes, could cause birth defects, including brain damage.
"It turns out that not only is suppression ineffective at handling fear, but it's counter-productive," said James Dillard, Distinguished Professor of Communication Arts and Sciences. "It creates a cycle of fear -- and it's a vicious cycle."
According to the researchers, suppression -- actively trying to tamp down fear -- is one strategy people use to manage their fears. Among other strategies, people may also try to avoid bad news, reappraise the situation, or contest the information with counter-arguments. While the researchers found that none of these strategies helped to manage fear during the Zika scare, suppression was the only strategy that they studied that actually increased the fear, said Dillard.
Ironically, the researchers -- who report their findings in the current issue of PLOS ONE -- suggested that, based on risk, the health problems associated with stress and anxiety caused by a health scare -- in this case, Zika -- may be as consequential as the actual disease. For example, while the pregnant women may have feared that Zika threatened the health of their unborn babies, previous studies of pregnant women during the 9/11 attacks showed that fear and stress reduced infant birth weights.
"When people become frightened there are some good things that can happen -- they search out information, they get politically engaged, they might engage in self-protective behavior -- but when people get really scared, it's harmful for them," said Dillard. "Stress hormones pour out and staying in that hyper-vigilant state -- fear -- is also resource intensive."
Dillard said that because people at risk will search on the web for information, public health officials should try to stay one step ahead of the outbreak and provide quality information about growing health crises.
He added that health officials may also want to inform the public about the stress and fear that may accompany disease outbreaks and other health concerns to help them manage their emotional response to the news.
"The other thing we can do that hasn't been done is we can warn people that they may become frightened to inoculate them against that emotional response," said Dillard, who also worked with Chun Yang and Ruobing Li, both former doctoral students in mass communications, Penn State. Yang and Li are currently assistant professors of communication at Louisiana State University.
While the study focused on fear of an epidemic, Dillard said the findings may also apply to other concerns, such as environmental and natural disasters.
The researchers recruited 1002 women between the ages of 18 and 35 who lived in Arizona, New Mexico, Texas, Louisiana, Mississippi, Alabama and Florida, all states that were thought to be in range of mosquitoes that could carry the disease, with 912 participants providing usable data. To calculate emotional responses and levels of fear over time, the researchers collected data in two waves. The first collection occurred between Feb. 10 and Feb. 20, 2016, nine days after the World Health Organization declared Zika an international health emergency. The second collection occurred between March 1 and March 15, 2016.
The researchers asked the participants to fill out a survey to assess their fear and their use of emotional regulation strategies, which included avoidance, reappraisal, contesting and suppression.
Future research could be aimed at identifying effective emotion regulation strategies to help people better cope with health scares and other concerns, according to the researchers.
Source : Science Daily

New type of depression identified


Scientists think depression occurs because of the mono-amine hypothesis, so named for the type of two chemicals that depressed people lack: serotonin and nor-epinephrine (NE). Ninety percent of antidepressant drugs are made based on this idea. They aim to re calibrate these two monoamines. For some of these patients, however, it may not be enough.
“Thirty percent of people on these drugs do not experience an effect,” Yumiko Saito and Yuki Kobayashi said. Both are neuroscientists in HU’s Graduate School of Integrated Arts and Sciences. “Obviously, we need a new drug! We need another explanation for what could cause depression.”
This study builds upon previous work in which her team found that RGS8 controls a hormone receptor called MCHR1. Parts of the brain involved with movement and mood regulation show signs of RGS8 expression. MCHR1, when active, helps regulate sleep, feeding, and mood responses. The researchers found that RGS8 inactivates MCHR1 in cultured cells.
Thus, the idea is that less RGS8 means increased depressed behavior. However, this effect had never been examined in a living being. Here Saito’s group studied depression in mice in two scopes: at the behavioral level, and at the immunohistological level.
First, the mice did a swim test, which is a common behavioral analysis method to assess depressive behaviors in animals. Researchers measure the time each mouse was active, then subtract it from the total test time, leaving researchers with an immobility time period.
Mice with more RGS8 in their nervous system recorded shorter immobility times than those with a normal amount of RGS8. When given an antidepressant drug that acts on monoamines, though, the RGS8 mice had even shorter immobility times. However, when the mice were given a drug that stops MCHR1 from working, immobility time did not change.
“These mice showed a new type of depression,” Saito remarked. “Monoamines appeared to not be involved in this depressive behavior. Instead, MCHR1 was.”
With that conclusion, the team looked at the mice’s brains under the microscope to determine the relationship between MCHR1 and RGS8. More specifically, they examined the size of cilia sprouting from cells in a region of the hippocampus called the CA1, where RGS8 concentration was highest. Cilia are TV antennae-like organelles involved in cellular communication.
The team found that RGS8 mice not only had less depressed behavior than those without extra RGS8, but they also had longer cilia. That is, mice that took the drug that stopped MCHR1 from working had longer cilia.
In the past ten years, scientists have been seeing that dysfunctional cilia are associated with disorders like obesity, kidney disease and retina disease. Not much is known about their relationship with mood disorders. These findings led Saito’s group to think that RGS8 is a promising candidate toward the development of new antidepressant drugs, which is a focus for future experiments.
Source: Science Daily

Monday, 9 July 2018

Agoraphobia


Agoraphobia refers to a fear of any place where escape may be difficult, including large open spaces or crowds, as well as various means of travel.
Symptoms
  • Fear or anxiety about:
    • being outside of the home alone
    • using public transportation
    • being in enclosed places (stores, movie theaters)
    • standing in line or being in a crowd
    • being in open spaces (markets, parking lots)
    • being in places where escape might be difficult
  • Active avoidance of all situations that provoke fear and anxiety
  • Becoming housebound for prolonged periods
  • Feelings of detachment or estrangement from others
  • Feelings of helplessness
  • Dependence upon others
  • Anxiety or panic attack (acute severe anxiety)
Causes
The etiology of most anxiety disorders, although not fully understood, has come into sharper focus in the last decade. In broad terms, the likelihood of developing anxiety involves a combination of life experiences, psychological traits, and/or genetic factors. Heritability for agoraphobia is reported to be 61 percent, making it the phobia most strongly linked to the genetic factor that represents predisposition to phobias. Some of the environmental factors that are known to be associated with the development of agoraphobia are experiencing stressful events (the death of a parent, being attacked or mugged) and being raised in a household characterized by little warmth and high levels of over protection.
Treatments
The goal of treatment is to help the agoraphobic person function effectively. The success of treatment usually depends upon the severity of the phobia. Systematic desensitization, also called “exposure therapy,” is a behavioral technique used to treat phobias. It is based on having the person relax, then imagine the components of the phobia, working from the least fearful to the most fearful. Graded real-life exposure has also been used with success to help people overcome their fears. This technique involves exposure to real aversive situations, progressing from less to more extreme situations. For example, a person might be in contact with a few people before they progressively spend time with large groups of people in order to overcome a fear of crowds. The individual will work with a therapist to develop coping strategies such as relaxation and breathing techniques. While “in-vivo” or real-life exposure is ideal, imagined exposure is an acceptable alternative in desensitization exercises. Treating agoraphobia with exposure therapy reduces anxiety and improves morale and quality of life within 75 percent of cases.
Other types of therapy, such as cognitive therapy, assertiveness training, biofeedback, hypnosis, meditation, relaxation, or couples therapy were found to be helpful for some patients. Cognitive behavioral therapy (CBT) is a combination of cognitive therapy, which can modify or eliminate thought patterns contributing to the patient’s symptoms, and behavioral therapy, which aims to help the patient change his or her behavior. 
Source : Psychology Today

Wednesday, 4 July 2018

Smoking and diabetes linked to brain Calcification

People who smoke or have diabetes may be at increased risk of calcification in a region of the brain crucial to memory, according to a new study published online in the journal Radiology.
Dementia is a major public health problem that affects tens of millions of people worldwide. One focus of dementia research has been the hippocampus, a brain structure important for both short- and long-term memory storage. Alzheimer's disease, the most common type of dementia, is associated with atrophy of the hippocampus.
Researchers have hypothesized that abnormal buildups of calcium, or calcifications, in the hippocampus may be related to vascular problems that could contribute to hippocampal atrophy and subsequent cognitive deterioration. However, published research on the association between hippocampal calcification and cognitive impairment is limited.
"We know that calcifications in the hippocampus are common, especially with increasing age," said the study's lead author, Esther J.M. de Brouwer, M.D., a geriatrician at the University Medical Center in Utrecht, the Netherlands. "However, we did not know if calcifications in the hippocampus related to cognitive function."
Advances in imaging have provided opportunities to explore the role of hippocampal calcifications in dementia. The development of multiplanar brain CT scans has enabled better distinction between hippocampal calcifications and calcifications in nearby brain structures like the choroid plexus.
"A multiplanar CT scan makes it possible to see the hippocampus in different anatomical planes; for example, from top to bottom, right to left and front to back," Dr. de Brouwer said. "Before multiplanar CT scans, hippocampal calcifications were often mistaken for choroid plexus calcifications. So with multiplanar CT scans, hippocampal calcifications are better distinguished from calcifications in other areas."
Dr. de Brouwer and colleagues studied the association between vascular risk factors like high blood pressure, diabetes and smoking, and hippocampal calcifications. They also assessed the effects of calcifications on cognitive function.
The study group included 1,991 patients, average age 78 years, who had visited a memory clinic at a Dutch hospital between 2009 and 2015. The patients had a standard diagnostic workup including cognitive tests and brain CT scans. The researchers analyzed the CT scans for the presence and severity of hippocampal calcifications.
Of the 1,991 patients, 380, or 19.1 percent, had hippocampal calcifications. Older age, diabetes and smoking were associated with an increased risk of hippocampal calcifications on CT scans.
While the study was not designed to conclusively determine if smoking and diabetes increase the risk of hippocampal calcifications, the results strongly suggest a link.
"We do think that smoking and diabetes are risk factors," Dr. de Brouwer said. "In a recent histopathology study, hippocampal calcifications were found to be a manifestation of vascular disease. It is well known that smoking and diabetes are risk factors for cardiovascular disease. It is, therefore, likely that smoking and diabetes are risk factors for hippocampal calcifications."
There was no link between the presence and severity of hippocampal calcifications and cognitive function; a surprising finding, according to Dr. de Brouwer, with several possible explanations.
"The hippocampus is made up of different layers, and it is possible that the calcifications did not damage the hippocampal structure that is important for memory storage," she said. "Another explanation could be the selection of our study participants, who all came from a memory clinic."
The researchers plan to carry out additional studies in different groups of people to better understand possible links between these calcification and cognitive problems.
Source: Science Daily