Posts tagged brain

July 11, 2012

Two powerful brain chemical systems work together to paralyze skeletal muscles during rapid eye movement (REM) sleep, according to new research in the July 11 issue of The Journal of Neuroscience. The finding may help scientists better understand and treat sleep disorders, including narcolepsy, tooth grinding, and REM sleep behavior disorder.

During REM sleep — the deep sleep where most recalled dreams occur — your eyes continue to move but the rest of the body’s muscles are stopped, potentially to prevent injury. In a series of experiments, University of Toronto neuroscientists Patricia L. Brooks and John H. Peever, PhD, found that the neurotransmitters gamma-aminobutyric acid (GABA) and glycine caused REM sleep paralysis in rats by “switching off” the specialized cells in the brain that allow muscles to be active. This finding reversed earlier beliefs that glycine was a lone inhibitor of these motor neurons.

"The study’s findings are relevant to anyone who has ever watched a sleeping pet twitch, gotten kicked by a bed partner, or has known someone with the sleep disorder narcolepsy," said Dennis J. McGinty, PhD, a behavioral neuroscientist and sleep researcher at the University of California, Los Angeles, who was not involved in the study. "By identifying the neurotransmitters and receptors involved in sleep-related paralysis, this study points us to possible molecular targets for developing treatments for sleep-related motor disorders, which can often be debilitating," he said

The researchers measured electrical activity in the facial muscles responsible for chewing of sleeping rats. Brain cells called trigeminal motor neurons communicate the brain’s message to move to these muscles. Previous research suggested neurotransmitter receptors called ionotropic GABAA/glycine receptors in the motor neurons caused REM sleep paralysis. However, when the researchers blocked these receptors, REM sleep paralysis still occurred.

The researchers found that to prevent REM sleep paralysis, they had to block both the ionotropic receptors and metabotropic GABAB receptors, a different receptor system. In other words, when the motor cells were cut off from all sources of GABA and glycine, the paralysis did not occur, allowing the rats to exhibit high levels of muscle activity when their muscles should have been inactive. The data suggest the two neurotransmitters must both be present together to maintain motor control during sleep, rather than working separately.

The finding could be especially helpful for those with REM sleep disorder, a disease that causes people to act out their dreams. This can cause serious injuries to patients and others around them. It is also often an early indicator of neurodegenerative diseases, such as Parkinson’s.

"Understanding the precise mechanism behind these chemicals’ role in REM sleep disorder is particularly important because about 80 percent of people who have it eventually develop a neurodegenerative disease, such as Parkinson’s disease," study author Peever added. "REM sleep behavior disorder could be an early marker of these diseases, and curing it may help prevent or even stop their development,” he said.

Provided by University of Toronto

Source: medicalxpress.com

July 11, 2012

A new study shows that taking part in a stress management program may help people with multiple sclerosis (MS) prevent new disease activity. The study is published in the July 11, 2012, online issue of Neurology, the medical journal of the American Academy of Neurology.

A weekly stress management program for patients with multiple sclerosis (M.S.) prevented the development of new brain lesions, a marker of the disease’s activity in the brain, according to new Northwestern Medicine research. Brain lesions in M.S. often precede flare-ups of symptoms such as loss of vision or use of limbs or pain.

"This is the first time counseling or psychotherapy has been shown to affect the development of new brain lesions," said David Mohr, principal investigator of the study and professor of preventive medicine at Northwestern University Feinberg School of Medicine. "In M.S., the prevention of new brain lesions is an important marker used to judge how effective medications are."

"The new finding is an important step and the strongest evidence we have to date that stress is involved in M.S.," Mohr added.

The results indicate that stress management therapy may be a useful adjunct treatment with drug therapy for M.S., but a larger clinical trial is needed to confirm this, Mohr said.

The study is published in the July 11, 2012 issue of Neurology, the medical journal of the American Academy of Neurology.

Mohr’s previous research showed a connection between psychological distress and the development of new brain lesions. Stress is one of many factors, he said, that influence whether the underlying M.S. disease processes escalate to the point of a new lesion or a relapse. Mohr has spent more than a decade studying the link between emotional distress, including a study on depression, and M.S.

For an event to be stressful, a person has to feel it is a threat to something important, and that he or she doesn’t have any control over it.

"We taught patients strategies to evaluate how much of a threat something truly is," Mohr said. "When people overestimate the threat of an event or underestimate their ability to manage it, we teach them how to evaluate their own thinking about the stress and how to challenge and change that thinking to a more realistic and helpful appraisal of the actual threat. That often leads to improved ability to manage stressful events."

Patients also were taught how to calm their physical reactions to stress through relaxation and meditation to cope with stressful events that couldn’t be avoided.

In the national clinical trial, 121 patients were randomized to receive stress management therapy for M.S. or be in a control group. Those in the therapy group received 16 sessions over a 24-week period during which they were taught coping skills to enhance their ability to prevent stressful events from occurring and to improve their capacity to manage their responses to stressful events that did arise. They also received a 24-week post-treatment follow-up. Two-thirds of the patients were women, who have a higher incidence of M.S.

MRI neuroimaging showed the stress management therapy reduced two types of new brain lesions common in multiple sclerosis.

The first type, gadolinium-enhancing brain lesions, indicates a breakdown of the blood-brain barrier, allowing the immune system access to attack and damage brain cells. Gadolinium is injected into an M.S. patient during the MRI and can be observed passing through the blood-brain barrier, if these types of lesions are present. These lesions may disappear over time or may leave more permanent damage in the brain.

The second type, a T2 brain lesion, is a more global marker of the effect of M.S. on the brain and is a more permanent lesion. These markers are commonly used in evaluating M.S. medications in Phase II trials. If the lesions are decreased, the implication is the drug is working.

Among patients who received stress management therapy, 55 percent had a new gadolinium-enhancing brain lesion during the treatment period, compared to 77 percent of those in the control group. Similarly, 43 percent receiving stress management therapy had a new T2 brain lesion during the treatment period, compared to 70 percent in the control group. The stress reduction prevented new lesions whether or not the patients were taking M.S. disease-modifying medications (e.g., beta-interferons or glatiramer acetate).

But the improvement in brain lesions didn’t last after the stress management program ended.

"This suggests that we will need to develop treatments that are more sustainable over longer periods of time," Mohr said. "It’s difficult for people to come in for treatment once a week over long periods of time, due both to cost and time constraints. We are looking at telemedicine programs that can be delivered via a computer or a smartphone to people in their environment at much lower costs than traditional therapy."

The study did not show a statistical difference in the rate of clinical M.S. symptoms, but Mohr said he didn’t expect one in such a small number of participants. The outcome goal of this trial was only to see if the stress reduction affected the brain lesions.

While the results are positive, Mohr said, it’s premature to make recommendations for patients regarding use of stress management therapy. “I don’t want to see patients decide not to take their medication and use this instead,” he emphasized.

Provided by American Academy of Neurology

Source: medicalxpress.com

July 11, 2012

Communication between the brain and muscle must be strong for us to eat, breathe or walk. Now scientists have found that a protein known to be on the surface of muscle cells must be present in both tissues to ensure the conversation is robust.

Communication between the brain and muscle must be strong for us to eat, breathe or walk. Now scientists have found that a protein known to be on the surface of muscle cells must be present in both tissues to ensure the conversation is robust. Credit: Phil Jones

Scientists at the Medical College of Georgia at Georgia Health Sciences University have shown that without LRP4 in muscle cells and neurons, communication between the two cells types is inefficient and short-lived.

Problems with the protein appear to contribute to disabling disorders such as myasthenia gravis and other forms of muscular dystrophy. The MCG scientists reported finding antibodies to LRP4 in the blood of about 2 percent of patients with muscle-degenerating myasthenia gravis in Archives of Neurology earlier this year.

Scientists know that LRP4 plays an important role in the muscle cell, where it receives cues from the brain cell that it’s time to form the receptors that will be enable ongoing communication between the two, said Dr. Lin Mei, Director of the GHSU Institute of Molecular Medicine and Genetics and corresponding author of the study in the journal Neuron.

However when Dr. Haitao Wu deleted LRP4 just from muscle cells, a connection – albeit a weak one – still formed between muscle and brain cells. The mice survived several days during which they experienced some of the same muscle weakness as patients with myasthenia gravis. “That’s against the dogma,” Mei said. “If LRP4 is essential only in the muscle cells, how could the mice survive?” When they totally eliminated LRP4, neuromuscular junctions never formed and the mice didn’t survive.

Additional evidence suggests that LRP4 in the neurons is vital, said Wu, postdoctoral fellow and the study’s first author. “When we knocked out the LRP4 gene in the muscles, there was some redundant function coming from the motor neuron, like a rescue attempt,” he said. They documented the neuron reaching out to share LRP4 with the muscle cell. Unfortunately, the gesture was not sufficient.

"The nerve does not get the stop signal," Mei said, referencing images of too-long neurons that never got the message from the muscle that they have gone far enough. When they cut the elongated nerves, they found they didn’t contain enough vesicles, little packages of chemical messengers that are the hallmark of brain cell communication. On the receiving end, muscle cells developed receptors that were too small and too few – hence, the tenuous communication network. "When LRP4 in the muscle is taken out, not surprisingly, the muscle has some kind of a problem," Mei said. "What was very surprising was that the motor neurons also have problems.”

"The talk between motor neurons and muscle cells is very critical to the synapse formation and the very precise action between the two," Wu said. Mei’s lab earlier established that the conversation goes both ways.

The scientists believe about 60 percent of the LRP4 comes from muscle cells, about 20 percent from brain cells – which helps explain why the brain’s effort to share is insufficient – and the remainder from cells in spaces between the two. In addition to better explaining nerve-muscle communication, the scientists hope their findings will eventually enable gene therapy that delivers LRP4 to bolster insufficient levels in patients.

Other early and key players in establishing nerve-muscle conversation include agrin, a protein that motor neurons release to direct construction of the synapse, a sort of telephone line between the nerve and muscle. MuSK on the muscle cell surface initiates critical internal cell talk so synapses can form and receptors that enable specific commands will cluster at just the right spot.

Mei’s lab reported in Neuron in 2008 that agrin starts talking with LRP4 on the muscle cell surface, then recruits the enzyme MuSK to join the conversation. LRP4 and MuSK become major components of the receptor needed for the muscle cell to receive the message agrin is sending.

The agrin-MuSK signaling pathway has been implicated in muscular dystrophy, a group of genetic diseases that lead to loss of muscle control because of problems with neurons, muscle cells and/or their communication. Some reports have implicated a mutant MuSK as a cause of muscular dystrophy and autoantibodies (antibodies the body makes against itself) to MuSK have been found in the blood of some patients.

Provided by Georgia Health Sciences University

Source: medicalxpress.com

July 11, 2012

An inflated sense of memory function in people with dementia may influence their likelihood of seeking help, new Flinders University research shows.

As part of her PhD, Flinders research associate Dr. Chris Materne studied the disparity between memory perception and performance in people with dementia.

In the first stage of the project, Dr. Materne analysed data from the Australian Longitudinal Study of Aging which showed that most survey participants believed their memory had remained stable over the 11-year assessment, despite tests showing a decline in memory performance.

She then conducted an intervention with 13 individuals, from a larger group of 23 people with dementia, using spaced retrieval memory training to help them achieve a specific task or activity, such as remembering to lock the front door or keep their glasses in the same spot.

“Spaced retrieval works by helping people remember specific information or tasks by getting them to respond to a prompt question over progressively increasing intervals of time,” Dr. Materne said.

“In one case we helped a man remember to put his glasses in the same place because he was always losing them which made both him and his wife quite distressed,” she said.

“We think the training taps into procedural memory so it becomes habitual rather than explicit memory, such as memory for facts, which tends to decline before procedural memory when you have dementia.”

The technique was conducted once a week for six weeks, with seven out of the 13 participants still able to perform their nominated activity or task after six months.

The 23 participants were also asked to rate their performance based on a specific question, such as how many people they could name in a photo with 10 faces.

While most respondents were initially over-confident in their abilities, with some claiming to be able to name all 10 faces, their perceptions did change over time to more accurately reflect their cognitive function.

About one third of family carers, however, initially considered their loved ones memory to be better than what the person with dementia actually reported.

“In the longitudinal sample people didn’t feel their memory had changed over time because the questions were more general but when we asked specific, detailed questions about memory in the smaller study, the respondents came to recognise their declining performance.”

Dr. Materne said the research highlighted the need for more comprehensive assessments when diagnosing dementia to increase the accuracy of peoples’ perceptions, and therefore their likelihood of seeking help.

Provided by Flinders University

Source: medicalxpress.com

ScienceDaily (July 11, 2012) — Stanford University School of Medicine scientists have laid bare a novel molecular mechanism responsible for the most important symptom of major depression: anhedonia, the loss of the ability to experience pleasure. While their study was conducted in mice, the brain circuit involved in this newly elucidated pathway is largely identical between rodents and humans, upping the odds that the findings point toward new therapies for depression and other disorders.

Additionally, opinion leaders hailed the study’s inventive methodology, saying it may offer a much sounder approach to testing new antidepressants than the methods now routinely used by drug developers.

While as many as one in six Americans is likely to suffer a major depression in their lifetimes, current medications either are inadequate or eventually stop working in as many as 50 percent of those for whom they’re prescribed.

"This may be because all current medications for depression work via the same mechanisms," said Robert Malenka, MD, PhD, the Nancy Friend Pritzker Professor in Psychiatry and Behavioral Sciences. "They increase levels of one or another of two small molecules that some nerve cells in the brain use to signal one another. To get better treatments, there’s a great need to understand in greater detail the brain biology that underlies depression’s symptoms." The study’s first author is Byung Kook Lim, PhD, a postdoctoral scholar in Malenka’s laboratory.

Malenka is senior author of the new study, published July 12 in Nature, which reveals a novel drug target by showing how a hormone known to affect appetite turns off the brain’s ability to experience pleasure when an animal is stressed. This hormone, melanocortin, signals to an ancient and almost universal apparatus deep in the brain called the reward circuit, which has evolved to guide animals toward resources, behaviors and environments — such as food, sex and warmth — that enhance their prospects for survival.

"This is the first study to suggest that we should look at the role of melanocortin in depression-related syndromes," said Eric Nestler, MD, PhD, professor and chair of neuroscience and director of the Friedman Brain Institute at Mount Sinai School of Medicine in New York. Nestler was not involved in the study but is familiar with its contents.

Read more …

ScienceDaily (July 11, 2012) — In the current online issue of PLoS ONE, researchers at the University of California, San Diego School of Medicine say they have identified a set of laboratory-based biomarkers that can be useful for understanding brain-based abnormalities in schizophrenia. The measurements, known as endophenotypes, could ultimately be a boon to clinicians who sometimes struggle to recognize and treat the complex and confounding mental disorder.

"A major problem in psychiatry is that there are currently no laboratory tests that aid in diagnosis, guide treatment decisions or help predict treatment response or outcomes," said Gregory A. Light, PhD, associate professor of psychiatry and the study’s first author. "Diagnoses are currently based on a clinician’s ability to make inferences about patients’ inner experiences."

Diagnosing and treating schizophrenia is a particularly troubling challenge. The disorder, which affects about 1 percent of the U.S. population or roughly 3 million people, is characterized by a breakdown of normal thought processes and erratic, sometimes dangerous or harmful, behaviors.

"Schizophrenia is among the most severe and disabling conditions across all categories of medicine," said Light, who also directs the Mental Illness, Research, Education and Clinical Center at the San Diego VA Healthcare System.

The precise cause or causes of schizophrenia are not known, though there is a clear genetic component, with the disorder more common in some families.

Clinicians typically diagnose schizophrenia based upon inferences drawn from the patient’s inner experiences. That is, their ability to describe what’s happening inside their minds.

"But even the best clinicians struggle with diagnostic complexities based on sometimes fuzzy clinical phenomenology," said Light. The clinical challenge is compounded by the fact that "many schizophrenia patients have cognitive and functional impairments," said Light. They may not be able to reasonably explain how or what they think.

Light and colleagues investigated whether a select battery of neurophysiological and neurocognitive biomarkers could provide clinicians with reliable, accurate, long-term indicators of brain dysfunction, even when overt symptoms of the disorder were not apparent. These markers ranged from tests of attention and memory to physiological assessments of basic perceptual processes using scalp sensors to measure brain responses to simple sounds.

The researchers measured the biomarkers in 550 schizophrenia patients, and then re-tested 200 of the patients one year later. They found that most of the markers were significantly abnormal in schizophrenia patients, were relatively stable between the assessments and were not affected by modest fluctuations in clinical status of the patient.

Light said further research is required, including whether the endophenotypes can differentiate other psychiatric disorders, be used to anticipate patient response to different kinds of drugs or non-pharmacological interventions or even be used to predict which subjects are at high risk of developing a psychotic illness.

"We believe this paper is an important step towards validating laboratory-based biomarkers for use in future genomic and clinical treatment studies of schizophrenia," Light said.

Source: Science Daily

July 11, 2012

(Medical Xpress) — Johns Hopkins researchers say they have discovered that the central nervous system’s oligodendroglia cells, long believed to simply insulate nerves as they “fire” signals, are unexpectedly also vital to the survival of neurons. Damage to these insulators appears to contribute to brain injury in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease for the Yankee baseball great who died from the disease.

The discovery, described online in the journal Nature, suggests that a previously unknown — and unexpected — function of these cells is to supply nutrition to the principal brain cells, neurons. This new pathway may prove to be an important and novel therapeutic target for ALS, the researchers say, and potentially other diseases that attack the body’s nerve fibers, such as multiple sclerosis.

"More than 100 years after their discovery, we have now found a fundamentally new property in the way oligodendroglia work in the brain, laying the foundation for a new approach to try to treat debilitating neurodegenerative diseases,” says Jeffrey D. Rothstein, M.D., Ph.D., a professor of neurology and neuroscience at the Johns Hopkins University School of Medicine, and the study’s leader. “We’ve added a whole new category to what they do in the brain.”

The cells responsible for the transfer of information and electrical impulses around the body, neurons work by transferring electrical charges from neuron to neuron. Axons, the wire-like extensions of the neurons, help move the messages, in some cases over many feet, from cell to cell. Oligodendroglia insulate axons, like rubber coating around an electrical wire, to speed up the conduction of information. Axonal death is a hallmark of ALS and most other neurodegenerative disorders, Rothstein says.

Rothstein and his colleagues say the other principal brain cells, the astroglia, were believed to be primarily responsible for providing energy to neurons in the form of glucose, but their experiments show that oligodendroglia are surprisingly crucial in feeding neurons — in the form of less energy-rich lactate, without which neurons and their axons die. Lactate has long been seen as a minor player in this process, but the Johns Hopkins team says it appears to be far more important to nerve cell survival. Moreover, they found that the protein MCT1, the dominant transporter of lactate in the brain, is only found in oligodendroglia.

Rothstein says their discovery was rooted in experiments during which scientists, using mice, knocked out the gene that makes the MCT1 protein and saw axons begin to die, even though they were still getting plenty of glucose.

As part of these experiments, the researchers engineered mice whose cells would light up if they were expressing MCT1. The scientists then determined that only oligodendroglia cells lit up, showing that MCTI is located on this type of cell alone. They also knocked out the MCT1 in cell cultures and found that neurons would begin to die, but would recover when fed lactate, proving the importance of MCT1 in providing this nutritional compound. They conducted the same experiments in mice and got similar results.

Finally, the researchers turned their attention to ALS, a disease where they had recently uncovered abnormalities related to oligodendroglia. In ALS mice, they found that MCT1 was missing in brain cells well before the disease developed, and they found similar results in ALS patients. Rothstein says the findings suggest that oligodendroglia injury — specifically injury to the mechanism that produces MCT1 — may be an important event in the onset and progression of ALS.

Rothstein, who is director of the Johns Hopkins University School of Medicine’s Brain Science Institute, says he hopes further research can establish that the activation of MCT1 in people will protect axons in those with ALS and other degenerative diseases.

Provided by Johns Hopkins University School of Medicine

Source: medicalxpress.com

July 11, 2012

In a paper published in the July 11 online issue of Science Translational Medicine, researchers at the University of California, San Diego School of Medicine have identified two key regulatory proteins critical to clearing away misfolded proteins that accumulate and cause the progressive, deadly neurodegeneration of Huntington’s disease (HD).

This is a human neuron. UC San Diego scientists have identified a pair of proteins that help clear away other misfolded proteins responsible for the progressive degeneration of brain cells in Huntington’s disease. Credit: UC San Diego School of Medicine

The findings explain a fundamental aspect of how HD wreaks havoc within cells and provides “clear, therapeutic opportunities,” said principal investigator Albert R. La Spada, MD, PhD, professor of cellular and molecular medicine, chief of the Division of Genetics in the Department of Pediatrics and associate director of the Institute for Genomic Medicine at UC San Diego.

"We think the implications are significant," said La Spada. "It’s a lead we can vigorously pursue, not just for Huntington’s disease, but also for similar neurodegenerative conditions like Parkinson’s disease and maybe even Alzheimer’s disease.”

In HD, an inherited mutation in the huntingtin (htt) gene results in misfolded htt proteins accumulating in certain central nervous system cells, leading to progressive deterioration of involuntary movement control, cognitive decline and psychological problems. More than 30,000 Americans have HD. There are no effective treatments currently to either cure the disease or slow its progression.

La Spada and colleagues focused on a protein called PGC-1alpha, which helps regulate the creation and operation of mitochondria, the tiny organelles that generate the fuel required for every cell to function.

"It’s all about energy," La Spada said. "Neurons have a constant, high demand for it. They’re always on the edge for maintaining adequate levels of energy production. PGC-1alpha regulates the function of transcription factors that promote the creation of mitochondria and allow them to run at full capacity.”

Previous studies by La Spada and others discovered that the mutant form of the htt gene interfered with normal levels and functioning of PGC-1alpha. “This study confirms that,” La Spada said. More surprising was the discovery that elevated levels of PGC-1alpha in a mouse model of HD virtually eliminated the problematic misfolded proteins.

Specifically, PGC-1alpha influenced expression of another protein vital to autophagy – the process in which healthy cells degrade and recycle old, unneeded or dangerous parts and products, including oxidative, damaging molecules generated by metabolism. For neurons, which must last a lifetime, the self-renewal is essential to survival.

"Mitochondria get beat up and need to be recycled," La Spada said. "PGC-1alpha drives this pathway through another protein called transcription factor EB or TFEB. We were unaware of this connection before, because TFEB is a relatively new player, though clearly emerging as a leading actor. We discovered that even without PGC-1alpha induction, TFEB can prevent htt aggregation and neurotoxicity."

In their experiments, HD mice crossbred with mice that produced greater levels of PGC-1alpha showed dramatic improvement. Production of misfolded proteins was essentially eliminated and the mice behaved normally. “Degeneration of brain cells is prevented. Neurons don’t die,” said La Spada.

PGC-1alpha and TFEB provide two new therapeutic targets for Huntington’s disease, according to La Spada. “If you can induce the bioenergetics and protein quality control pathways of nervous system cells to function properly, by activating the PGC-1alpha pathway and promoting greater TFEB function, you stand a good chance of maintaining neural function for an extended period of time. If we could achieve the level of increased function necessary to eliminate misfolded proteins, we might nip the disease process in the bud. That would go a long way toward treating this devastating condition.”

Provided by University of California - San Diego

Source: medicalxpress.com

July 11, 2012

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.

PET images using florbetapir dye to highlight beta-amyloid plaques show (A), a cognitively normal subject; (B) an amyloid-positive patient with Alzheimer’s disease; (C) a patient with mild cognitive impairment; and (D) a patient with mild cognitive impairment who progressed to dementia during the study. Credit: Slide courtesy of the journal Neurology.

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.

Provided by Duke University Medical Center

Source: medicalxpress.com