May 5, 2012 

In an effort to identify the underlying causes of neurological disorders that impair motor functions such as walking and breathing, UCLA researchers have developed a novel system to measure the communication between stem cell-derived motor neurons and muscle cells in a Petri dish.

The study provides an important proof of principle that functional motor circuits can be created outside of the body using stem cell-derived neurons and muscle cells, and that the level of communication, or synaptic activity, between the cells could be accurately measured by stimulating motor neurons with an electrode and then measuring the transfer of electrical activity into the muscle cells to which the motor neurons are connected.

When motor neurons are stimulated, they release neurotransmitters that depolarize the membranes of muscle cells, allowing the entry of calcium and other ions that cause them to contract. By measuring the strength of this activity, one can get a good estimation of the overall health of motor neurons. That estimation could shed light on a variety of neurodegenerative diseasessuch as spinal muscular atrophy and amyotrophic lateral sclerosis, or Lou Gehrig’s disease, in which the communication between motor neurons and muscle cells is thought to unravel, said study senior author Bennett G. Novitch, an assistant professor of neurobiology and a scientist with the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.

The findings of the study appear May 4, 2012 in PLoS ONE, a peer-reviewed journal of the Public Library of Science.

"Now that we have this method to measure the strength of the communications between motor neurons and muscle cells, we may be able to begin exploring what happens in the earliest stages of motor neuron disease, before neuronal death becomes prevalent," Novitch said. "This can help us to pinpoint where things begin to go wrong and provide us with new clues into therapeutic interventions that could improve synaptic communication and promote neuronal survival."

Novitch said the synaptic communication activity his team was able to create and measure using mouse embryonic stem cell-derived motor neurons and muscle cells looks very similar what is seen in a mouse, validating that their model is a realistic representation of what is happening in a living organism.

"That gives us a good starting point to try to model what happens in cells that harbor genetic mutations that are associated with neurodegenerative diseases,. To do that, we had to first define an activity profile of normal synaptic communication," he said. "Some research suggests that a breakdown in this communication can be an early indication of disease progression or possibly an initiating event. Neurons that cannot effectively transmit information to muscle cells will eventually withdraw their contacts, causing both the neurons and muscle cells to degenerate over time. Hopefully, we can now create disease models that will allow us to study what is happening."

In this study, Novitch and his team, led by Joy Umbach, an associate professor of molecular and medical pharmacology, used mouse embryonic stem cells to create the motor neurons and previously established lines of muscle precursors to produce muscle fibers. They put both cells together in a Petri dish, and the cells were cultured in such a way to encourage communication. Novitch said the team wanted to see if they would naturally form synaptic contacts and whether or not there was neural transmission between them.

In less than a week, the neurons had reached out to the muscle cells and assembled the protein networks needed for synaptic communication, Novitch said.

To measure the connections between the cells, the scientists used a technique called dual patch clamp recording. Pipettes containing stimulating and recording electrodes are inserted into the membranes of the motor neurons and muscle cells, being careful not to injure them. With this method, they were able send an electrical current into the motor neurons and measure responses in the muscle cells, as well as visualize the muscular contractions.

"The in vitro system developed here might accordingly be expanded to assess the underlying cellular and molecular mechanisms that contribute to this decline in synaptic input to motor neurons," the study states. "Thus, in addition to their utility for helping to answer fundamental biological questions, these co-cultures have clear applications in addressing problems of medical significance."

Going forward, Novitch and his team hope to recreate and confirm the work using human stem cell-derived motor neurons and muscle cells and measure the synaptic communications with newly developed optical recording methods, which are less invasive than the patch clamp techniques used in this study.

Provided by University of California, Los Angeles

Source: medicalxpress.com

ScienceDaily (May 3, 2012) — Malfunctioning single proteins can cause disruptions in neuronal junctions leading to autistic forms of behavior. A current study, published in the scientific journal Nature, comes to this conclusion after examining genetically altered mice.

The study, in which scientists from Charité — Universitätsmedizin Berlin and the NeuroCure Cluster of Excellence contributed, thus supports the hypothesis that disruptions in neuronal junctions, i.e. synapses, could be the cause of the development of neuropsychiatric illnesses like autism. The international research team, that included scientists from Ulm University and the Institut Pasteur in Paris, ascribes a key role to the excitatory synapses. This finding could become an important step stone for future autism therapies.

Nerve cells communicate with each other via signal transmission to synaptic junctions. These junctions are stabilized through structural proteins, including the so-called ProSAP1/Shank2 protein. In order to understand the role that this protein has on synapses and ultimately in the development of autism, the researchers genetically modified mice and disabled the relevant protein. The choice of this protein was not arbitrary: In preparation for the current study, a number of the scientists involved found evidence that the mutation of this protein can lead to autism in humans. Various neuronal developmental disorders manifested through distinctive social and communicative behavioral features, as well as stereotyped behaviors are combined under the term of “autism.”

The absence of this structural protein in the mouse model also had visible implications: Animals with the mutated gene are hyperactive and demonstrate compulsive repetitions of particular features — like grooming, for example. In behavioral experiments, peculiarities in social and communicative interaction also become distinct. In the brains of the mice, researchers found noticeable mutations of synaptic junctions — specifically in excitatory synapses. When glutamate transmitters bind to glutamate receptors located at these junctions, the nerve cells become excitatory. If the mouse is lacking this structural protein, the transmitters increasingly find a related structural protein on the excitatory synapses, the ProSAP2/Shank3. This protein has also been implicated in the development of autism. At the same time, the composition of glutamate receptors mutates.

But what happens when this related structural protein in the mice is switched off? This is also examined in the study presented. The conclusion is that, in this case as well, mutations of the excitatory synapses occur. Obviously, both structural molecules alternate in fulfilling regular functions. “The study illustrates the significant role glutamatergic systems play in autism and thus contributes to understanding better synaptic changes in autism,” reports Stephanie Wegener, one of the participating scientists at Charité Berlin. The study is therefore an important part of the essential scientific foundation needed to develop possible therapies for autism.

Source: Science Daily

ScienceDaily (May 3, 2012) — The problems of living with bipolar have been well documented, but a new study by Lancaster University has captured the views of those who also report highly-valued, positive experiences of living with the condition.

Researchers at Lancaster’s Spectrum Centre, which is dedicated to the study of bipolar disorder, interviewed and recorded their views of ten people with a bipolar diagnosis, aged between 24 and 57. Participants in the study reported a number of perceived benefits to the condition ranging from to sharper senses to increased productivity.

The research was designed to explore growing evidence that some people with bipolar value their experiences and in some cases would prefer not to be without the condition.

Participants described a wide range of experiences and internal states that they believed they felt to a far greater intensity than those without the condition. These included increased perceptual sensitivity, creativity, focus and clarity of thought.

Some held (or had previously held) high functioning professional jobs or had been studying for higher level qualifications. They described in detail how they experienced times when tasks that are usually quite difficult or time consuming, would feel incredibly easy and the ability to achieve at a high level during these times was clearly immensely rewarding.

Others expressed the view that they felt ‘lucky’ or even ‘blessed’ to have the condition.

Alan, (not his real name) one of the interviewees, said: “It’s almost as if it opens up something in the brain that isn’t otherwise there, and I see colour much more vividly than I used to……So I think that my access to music and art are something for which I’m grateful to bipolar for enhancing. It’s almost as if it’s a magnifying glass that sits between that and myself.”

Researchers even found some people with bipolar reaped positive experiences from their lows such as greater empathy with the suffering of others.

Dr Fiona Lobban, who led the study, said: “Bipolar Disorder is generally seen as a severe and enduring mental illness with serious negative consequences for the people with this diagnosis and their friends and family. For some people this is very much the case. Research shows that long term unemployment rates are high, relationships are marred by high levels of burden on family and friends and quality of life is often poor. High rates of drug and alcohol misuse are reported for people with this diagnosis and suicide rates are twenty times that of the general population.

"However, despite all these factors researchers and clinicians are aware that that some aspects of bipolar experiences are also highly valued by some people. We wanted to find out what these positive experiences were.

"People were very keen to take part in this study and express views which some felt had to be hidden from the medical profession.

"It is really important that we learn more about the positives of bipolar as focusing only on negative aspects paints a very biased picture that perpetuates the view of bipolar as a wholly negative experience. If we fail to explore the positives of bipolar we also fail to understand the ambivalence of some people towards treatment."

Rita Long from Stockport was not part of the study but can identify with its findings. She was 40 when she was diagnosed with the condition but from her school days she was aware that she experienced the world differently to her twin sister.

"We were making Christmas cakes at school and I was so interested and excited by it and my sister says she remembers watching me and thinking, ‘I really wish I could get that excited about making a Christmas cake’. I noticed things, experienced them with a different level of intensity, we’d be on a walk and I’d be saying look at the colour of this, and my sister would be saying, ‘It’s just a berry’. Socially too, people with bipolar can be quite quick witted, humorous. Until much later in life I just presumed those things were part of my personality.

"I don’t want to underestimate how difficult the bad times can be that some people go through with bipolar but at the same time I feel very passionate about the positives. If we are going to move on as a society — in academia, in business, in entertainment — we need people who will push boundaries. People with bipolar can do that."

Source: Science Daily

ScienceDaily (May 3, 2012) — A team led by scientists at The Scripps Research Institute has shown that an extra copy of a brain-development gene, which appeared in our ancestors’ genomes about 2.4 million years ago, allowed maturing neurons to migrate farther and develop more connections.

A team led by Scripps Research Institute scientists has found evidence that, as humans evolved, an extra copy of a brain-development gene allowed neurons to migrate farther and develop more connections. (Credit: Photo courtesy of The Scripps Research Institute)

What genetic changes account for the vast behavioral differences between humans and other primates? Researchers so far have catalogued only a few, but now it seems that they can add a big one to the list. A team led by scientists at The Scripps Research Institute has shown that an extra copy of a brain-development gene, which appeared in our ancestors’ genomes about 2.4 million years ago, allowed maturing neurons to migrate farther and develop more connections.

Surprisingly, the added copy doesn’t augment the function of the original gene, SRGAP2, which makes neurons sprout connections to neighboring cells. Instead it interferes with that original function, effectively giving neurons more time to wire themselves into a bigger brain.

"This appears to be a major example of a genomic innovation that contributed to human evolution," said Franck Polleux, a professor at The Scripps Research Institute. "The finding that a duplicated gene can interact with the original copy also suggests a new way to think about how evolution occurs and might give us clues to human-specific developmental disorders such as autism and schizophrenia."

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ScienceDaily (May 3, 2012) — UCSF scientists have identified patterns of brain activity in the rat brain that play a role in the formation and recall of memories and decision-making. The discovery, which builds on the team’s previous findings, offers a path for studying learning, decision-making and post-traumatic stress syndrome.

Brain patterns through which the rats see rapid replays of past experiences are fundamental to their ability to make decisions. Disturbing those particular brain patterns impaired the animals’ ability to learn rules based on memories of things that had happened in the past. (Credit: © Oleg Kozlov / Fotolia)

The researchers previously identified patterns of brain activity in the rat hippocampus, a brain region critical for memory storage. The patterns sometimes represented where an animal was in space, and, at other times, represented fast-motion replays of places the animal had been, but no one knew whether these patterns indicated the process of memory formation and recollection.

In the journal Science this week (online May 3, 2012), the UCSF researchers demonstrated that the brain activity is critical for memory formation and recall. Moreover, they showed that the brain patterns through which the rats see rapid replays of past experiences are fundamental to their ability to make decisions. Disturbing those particular brain patterns impaired the animals’ ability to learn rules based on memories of things that had happened in the past.

"We think these memory-replay events are central to understanding how the brain retrieves past experiences and uses them to make decisions," said neuroscientist Loren Frank, PhD, a associate professor of physiology and a member of the Keck Center for Integrative Neuroscience at UCSF, who led the research with Shantanu Jadhav, PhD, a post-doctoral fellow. "They offer insight into how a past experience can have such a profound effect on how we think and feel."

The finding gives scientists a new way to investigate fundamental processes like learning and decision-making in animals and in people. It also may help shed light on memory disorders like post-traumatic stress disorder (PTSD), which is characterized by strong, disturbing and uncontrolled memories.

Without Links to the Past, Rats Face Indecision

Seeking to understand how the recall of specific memories in the brain guides our thinking, Frank and his colleagues built a system for detecting the underlying patterns of neuronal activity in rats. They fitted the animals with electrodes and built a system that enabled them to detect a specific pattern, called a sharp-wave ripple, in the hippocampus. Whenever they detected a ripple, they would send a small amount of electricity into another set of electrodes that would immediately interrupt the ripple event, in effect turning off all memory replay activity without otherwise affecting the brain.

The UCSF researchers knew that these sharp-wave ripples would be activated when the animals had to make choices about which direction to turn as they wended their way toward their reward: a few drops of sweetened condensed milk. These signals seem to be flashes of memory recall, said Frank, a rat’s past knowledge flooding back to inform it on what had happened in the past and where it might go in the future. Squashing the sharp-wave ripples, the UCSF team found, disrupted the recall and subverted the rat’s ability to correctly navigate the maze.

This shows, said Frank, that the sharp-wave ripples are critical for this type of memory recall. Through these brain waves, the rat reprocesses and replays old experiences in a fleeting instant — lessons from the past essential for shaping their perception of the present.

"We think these memory replay events are a fundamental constituent of memory retrieval and play a key role in human perspective and decision-making as well," he said. "These same events have been seen in memory tasks in humans, and now we know they are critical for memory in rats. We think that these fast-forward replays make up the individual elements of our own memories, which jump rapidly from event to event."

Next, the team wants to tease out information about how the rats actually use these memory replay events to make decisions and how amplifying or blocking specific replay events will change the way an animal learns and remembers. They also think that these events could be important for understanding memory problems, as when stressful memories intrude into daily life.

Source: Science Daily

May 3, 2012

Under some conditions, the brains of embryonic chicks appear to be awake well before those chicks are ready to hatch out of their eggs. That’s according to an imaging study published online on May 3 in Current Biology, a Cell Press publication, in which researchers woke chick embryos inside their eggs by playing loud, meaningful sounds to them. Playing meaningless sounds to the embryos wasn’t enough to rouse their brains.

This image shows an X-ray computed-tomography image of the chicken embryo skeleton inside an egg, which shows the developmental stage, together with a positron emission tomography image showing nervous system activity in the brain. Balaban et al., publishing in Current Biology, report the activity in chicken embryo brains is inversely related to behavioral activity, with different sleep-like states emerging for the first time. Playing meaningful sounds selectively induced patterns of embryonic brain activity similar to awake, post-hatching animals. Image 3D rendering by Carmen García-Villalba. Credit: Balaban et al. Current Biology

The findings may have implications not only for developing chicks and other animals, but also for prematurely born infants, the researchers say. Pediatricians have worried about the effects of stimulating brains that are still under construction, especially as modern medicine continues to push back the gestational age at which preemies can reliably survive.

"This work showed that embryo brains can function in a waking-like manner earlier than previously thought—well before birth," said Evan Balaban of McGill University. "Like adult brains, embryo brains also have neural circuitry that monitors the environment to selectively wake the brain up during important events."

That waking-like brain activity appears in a latent but inducible state during the final 20 percent of embryonic life, the researchers found. At that point, sleep-like brain activity patterns also emerge.

Before that major dividing line in development—for the first 80 percent of embryonic life— “embryos are in a state that is neither like sleep nor waking,” Balaban said. He suggests it may be useful to compare that state to what happens when people are comatose or under the influence of anesthesia.

This entire line of work was made possible by a new generation of molecular brain imagers developed by Balaban’s coauthors Juan-José Vaquero and Manuel Desco at the Universidad Carlos III in Madrid. Those state-of-the art machines can detect very small amounts of tracer molecules and pinpoint them to a tiny region of the brain (about 0.7 mm, or less than 3/100ths of an inch).

The researchers say they were surprised to capture waking-like activity before birth. And there were other surprises, too. The embryo brains they observed showed considerable variation in activity, for one.

Before the emergence of sleep and waking patterns of brain activity, the chick embryos in their study exhibited lots of spontaneous movement, even as their higher-brain regions remained inactive. Once the chicks reached that 80 percent mark in development, higher-brain regions began crackling with activity. At the same time, those physical movements ceased as the embryos entered a sleep-like state.

"The last 30 percent of fetal brain development is a more interesting time than we previously thought, because it’s when complex whole-brain functions that depend on coordination of widely separated brain areas first emerge," Balaban said. "Embryos begin to cycle through a variety of brain states and are even capable of showing waking-like brain activity."

That might explain instances of complex fetal and early neonatal learning. “It also raises questions about the longer-term developmental consequences that such brain activity may have, if it is induced before intrinsic brain wiring is sufficiently completed,” Balaban said, “for example, in babies born very prematurely. We are excited by the possibility that the techniques developed here can now be used to provide answers to these questions.”

Provided by Cell Press

Source: medicalxpress.com

ScienceDaily (May 2, 2012) — Results of a new study reported recently by psychology researcher Lisa Scott and colleagues at the University of Massachusetts Amherst confirm that although infants are born with equal abilities to tell apart people within multiple races, by age 9 months they are better at recognizing faces and emotional expressions of people within groups they interact with most.

For part of the UMass Amherst study of infants and recognition of individuals of other races, a net of recording sensors was placed on the infant’s head to record brain activity while they viewed own-race and other-race emotion faces (happy, sad) that either matched or did not match a corresponding emotion sound (laughing, crying). This measure helps researchers understand how the brain develops in response to experience during the first year of life. Lisa Scott is pictured adjusting the head net on an infant subject. (Credit: UMass Amherst)

The researchers found that by 9 months, infants show a decline in their ability to tell apart two faces within another race and to accurately match emotional sounds with emotional expressions of different-race individuals. This is the first investigation of this effect in infancy and supports other studies suggesting that emotion recognition is less accurate for other-race faces than own-race faces. Scott’s paper was singled out for special mention as the “Editor’s Choice” article in the May issue of Developmental Science.

This research suggests that throughout the first year of life, babies are developing highly specialized perceptual abilities in response to important people in their environment, such as family members. This focus of attention to familiar groups of people compared to unfamiliar groups is hypothesized to be the root of later difficulties some adults have in identifying and recognizing faces of other races.

This is similar to how babies learn language. Early in infancy babies do not know yet which sounds are meaningful in their native language, so they treat all sounds similarly. But as they learn the language spoken around them, their ability to tell apart sounds within other languages declines and their ability to differentiate sounds within their native language improves.

Scott says, “In addition to providing information critical for understanding how infants learn about the surrounding environment, the results of this research may serve as a guide for early education and interventions designed to reduce later racial prejudice and stereotyping” Scott states. “These results suggest that biases in face recognition and perception begin in preverbal infants, well before concepts about race are formed. It is important for us to understand the nature of these biases in order to reduce or eliminate them.”

For this study, each infant came to the lab with a parent for a one-hour session that included showing infants pictures of faces and having them listen to sounds while their looking time and brain activity were recorded. Forty-eight Caucasian infants with little to no previous experience with African-American or black individuals participated in this study.

Infants completed two tasks. The first was designed to assess their ability to tell the difference between two faces within their own race and two faces within another, unfamiliar, race. For the second task, a net of recording sensors was placed on the infant’s head to record brain activity while they viewed own-race and other-race emotion faces (happy, sad) that either matched or did not match a corresponding emotion sound (laughing, crying).

Consistent with previous reports, 5-month-old infants were found to equally tell apart faces from both races, whereas 9-month-old infants were better at telling apart two faces within their own race, Scott and colleagues report.

Further, measures of brain activity revealed differential neural processing of own-race compared to other-race emotional faces at 9 months. However, 5-month olds exhibited similar processing for both own- and other-race faces. In addition, infants were found to shift their processing of face-related emotion information from neural regions in the front of the brain to neural regions in the back of the brain from 5 to 9 months of age. This shift in neural processing helps researchers understand how the brain develops in response to experience during the first year of life.

Source: Science Daily

ScienceDaily (May 2, 2012) — A highly toxic beta-amyloid — a protein that exists in the brains of Alzheimer’s disease victims — has been found to greatly increase the toxicity of other more common and less toxic beta-amyloids, serving as a possible “trigger” for the advent and development of Alzheimer’s, researchers at the University of Virginia and German biotech company Probiodrug have discovered.

Pyroglutanylated beta-amyloid (green) accumulates in the brains of mice genetically engineered to overproduce it. The red cells are astrocytes, which invade brain regions where the amyloid is deposited and neurons die. The blue structures are nuclei of neurons and astrocytes. (Credit: University of Virginia)

The finding, reported in the May 2 online edition of the journal Nature, could lead to more effective treatments for Alzheimer’s. Already, Probiodrug AG, based in Halle, Germany has completed phase 1 clinical trials in Europe with a small molecule that inhibits an enzyme, glutaminyl cyclase, that catalyzes the formation of this hypertoxic version of beta-amyloid.

"This form of beta-amyloid, called pyroglutamylated (or pyroglu) beta-amyloid, is a real bad guy in Alzheimer’s disease," said principal investigator George Bloom, a U.Va. professor of biology and cell biology in the College of Arts & Sciences and School of Medicine, who is collaborating on the study with scientists at Probiodrug. "We’ve confirmed that it converts more abundant beta-amyloids into a form that is up to 100 times more toxic, making this a very dangerous killer of brain cells and an attractive target for drug therapy."

Bloom said the process is similar to various prion diseases, such as mad cow disease or chronic wasting disease, where a toxic protein can “infect” normal proteins that spread through the brain and ultimately destroy it.

In the case of Alzheimer’s, severe dementia occurs over the course of years prior to death.

"You might think of this pyroglu beta-amyloid as a seed that can further contaminate something that’s already bad into something much worse — it’s the trigger," Bloom said. Just as importantly, the hypertoxic mixtures that are seeded by pyroglu beta-amyloid exist as small aggregates, called oligomers, rather than as much larger fibers found in the amyloid plaques that are a signature feature of the Alzheimer’s brain.

And the trigger fires a “bullet,” as Bloom puts it. The bullet is a protein called tau that is stimulated by beta-amyloid to form toxic “tangles” in the brain that play a major role in the onset and development of Alzheimer’s. Using mice bred to have no tau genes, the researchers found that without the interaction of toxic beta-amyloids with tau, the Alzheimer’s cascade cannot begin. The pathway by which pyroglu beta-amyloid induces the tau-dependent death of neurons is now the target of further investigation to understand this important step in the early development of Alzheimer’s disease

"There are two matters of practical importance in our discovery," Bloom said. "One, is the new insights we have as to how Alzheimer’s might actually progress — the mechanisms which are important to understand if we are to try to prevent it from happening; and second, it provides a lead into how to design drugs that might prevent this kind of beta-amyloid from building up in the first place."

Said study co-author Hans-Ulrich Demuth, a biochemist and chief scientific officer at Probiodrug, “This publication further adds significant evidence to our hypothesis about the critical role pyroglu beta-amyloid plays in the initiation of Alzheimer’s Disease. For the first time we have found a clear link in the relationship between pyroglu beta-amyloid, oligomer formation and tau protein in neuronal toxicity.”

Bloom and his collaborators are now looking for other proteins that are needed for pyroglu beta-amyloid to become toxic. Any such proteins they discover are potential targets for the early diagnosis and/or treatment of Alzheimer’s disease.

Source: Science Daily

ScienceDaily (May 2, 2012) — A drug prescribed for Alzheimer’s disease does not ease clinically significant agitation in patients, according to a new study conducted by researchers from the U.K., U.S. and Norway. This is the first randomized controlled trial designed to assess the effectiveness of the drug (generic name memantine) for significant agitation in Alzheimer’s patients.

Previous studies suggested memantine could help reduce agitation and improve cognitive functions such as memory. Led by the University of East Anglia in the U.K., the new research found that while memantine does improve cognitive functioning and neuropsychiatric symptoms such as delusion, mood and anxiety, it is no more effective in reducing significant agitation than a placebo.

"Memantine is quite commonly prescribed for Alzheimer’s disease in the U.S. Despite the negative findings regarding agitation, this trial opens a door of hope," said Regenstrief Institute investigator Malaz Boustani, M.D., MPH, associate professor of medicine at the Indiana University School of Medicine and associate director of the IU Center for Aging Research. "Memantine does appear to help with other behavioral and psychological symptoms of Alzheimer’s disease."

Dr. Boustani, a co-author of the study, is also the medical and research director of the Healthy Aging Brain Center at Wishard Health Services.

"Efficacy of memantine for agitation in Alzheimer’s dementia: a randomized double-blind placebo controlled trial"published in PLoS ONEon May 2. Authors of the study are from Indiana University; the University of East Anglia, University College London, University of Kent, Aston University, Oxleas National Health Service Foundation Trust and Kings College London, all in the U.K.; and the University of Stavanger in Norway.

An estimated 5.4 million Americans have Alzheimer’s disease according to the Alzheimer’s Association. Many are agitated. They may, for example, pace continually, become physically or verbally aggressive or scream persistently. In addition to harming quality of life for the patient, agitation places enormous strain on relationships with family members and care providers, and often results in institutionalization.

"People who have mild symptoms [of agitation] often respond to changes in the environment or psychological treatment, but these methods are impractical in severe agitation," said Chris Fox, M.D., of Norwich Medical School at University of East Anglia, who led the research. "Our findings regarding memantine are disappointing with respect to severe agitation — particularly as the alternative antipsychotic medications can have significant side effects such as increased rates of stroke and death. However, we hope our study will highlight the urgent need for investment in safe and effective new treatments for this growing disease."

The team of researchers studied 153 nursing home residents and hospital inpatients with severe Alzheimer’s from September 2007 to May 2010. All the study participants displayed significant agitation requiring clinical treatment. Half were given memantine, and half received a placebo. The researchers reported signficant improvement in cognitive function and for overall neuropsychiatric symptoms for the group given memantine, but no statistically significant difference in terms of the severe agitation that was the primary focus of the study.

Memantine is approved by the U.S. Food and Drug Administration for Alzheimer’s disease. The trial was sponsored by East Kent Hospitals University National Health Service Foundation Trust in the U.K. The study was funded by Lundbeck, a manufacturer of memantine.

"This research suggests that even though memantine can have real benefits for people in the later stages of Alzheimer’s, it may not have all the answers," said Anne Corbett, research manager at the Alzheimer’s Society of the U.K., which was not involved in the research. "However, prescribers should not see the only alternative as being to hand out antipsychotics. These overprescribed drugs double the risk of death and treble the risk of stroke and should always be a last resort for people with dementia."

Source: Science Daily

ScienceDaily (May 2, 2012) — A new study suggests that eating foods that contain omega-3 fatty acids, such as fish, chicken, salad dressing and nuts, may be associated with lower blood levels of a protein related to Alzheimer’s disease and memory problems. The research is published in the May 2, 2012, online issue of Neurology®, the medical journal of the American Academy of Neurology.

"While it’s not easy to measure the level of beta-amyloid deposits in the brain in this type of study, it is relatively easy to measure the levels of beta-amyloid in the blood, which, to a certain degree, relates to the level in the brain," said study author Nikolaos Scarmeas, MD, MS, with Columbia University Medical Center in New York and a member of the American Academy of Neurology.

For the study, 1,219 people older than age 65, free of dementia, provided information about their diet for an average of 1.2 years before their blood was tested for the beta-amyloid. Researchers looked specifically at 10 nutrients, including saturated fatty acids, omega-3 and omega-6 polyunsaturated fatty acids, mono-unsaturated fatty acid, vitamin E, vitamin C, beta-carotene, vitamin B12, folate and vitamin D.

The study found that the more omega-3 fatty acids a person took in, the lower their blood beta-amyloid levels. Consuming one gram of omega-3 per day (equal to approximately half a fillet of salmon per week) more than the average omega-3 consumed by people in the study is associated with 20 to 30 percent lower blood beta-amyloid levels.

Other nutrients were not associated with plasma beta-amyloid levels. The results stayed the same after adjusting for age, education, gender, ethnicity, amount of calories consumed and whether a participant had the APOE gene, a risk factor for Alzheimer’s disease.

"Determining through further research whether omega-3 fatty acids or other nutrients relate to spinal fluid or brain beta-amyloid levels or levels of other Alzheimer’s disease related proteins can strengthen our confidence on beneficial effects of parts of our diet in preventing dementia," said Scarmeas.

Source: Science Daily