Delirium is widespread among older people but often goes ignored and untreated, according to new research by US and UK researchers including the University of East Anglia.

Published in the September issue of the Journal of Hospital Medicine, the findings show that delirium - or acute confusion – is common among older adults in hospitals and nursing homes. It has a negative impact on cognition and independence, significantly increases the risk of developing dementia, and triples the likelihood of death. Yet this common, acute condition is frequently either undiagnosed or accepted as inevitable.

Led by the Regenstrief Institute and Indiana University, the research team reviewed 45 years of research encompassing 585 studies. They found that one in three cases of delirium were preventable and are calling for delirium to be identified and treated early to prevent poor long-term prognosis.

“As a geriatric psychiatrist I have seen that around 50 per cent or people with dementia in hospital develop delirium,” said co-author Dr Chris Fox, of Norwich Medical School at the University of East Anglia.

“This is because in addition to having dementia, they have multiple risk factors that can predispose and precipitate delirium – including serious illnesses and pre-existing cognitive impairment. In addition, hospital staff commonly label the signs as dementia related and do not pick up the delirium.”

“We need to develop better mechanisms for diagnosing delirium so that prompt treatment regimes can be initiated.”

In general patient groups, more than 60 per cent of delirium cases are not recognised or treated, and significant numbers of elderly patients leave hospital with ongoing delirium which has been missed.

The authors, led by Dr Babar Khan of the Regenstrief Institute and Indiana University School of Medicine, said that delirium could be prevented by eliminating restraints, treating depression, ensuring that patients have access to glasses and hearing aids, and prescribing classes of antipsychotics that do not negatively affect the aging brain. They also noted the need for a more sensitive screening tool for delirium, especially when administered by a non-expert.

“Delirium is extremely common among older adults in intensive care units and is not uncommon in other hospital units and in nursing homes, but too often it is ignored or accepted as inevitable,” said Dr Khan. “Delirium significantly increases risk of developing dementia and triples likelihood of death. It cannot be ignored.”

Co-author Dr Malaz Boustani, of the Regenstrief Institute, Indiana University School of Medicine and Wishard Healthy Aging Brain Center, said: “Having delirium prolongs the length of a hospital stay, increases the risk of post-hospitalization transfer to a nursing home, increases the risk of death and may lead to permanent brain damage.”

(Source: uea.ac.uk)

Contrary to the prevailing theories that music and language are cognitively separate or that music is a byproduct of language, theorists at Rice University’s Shepherd School of Music and the University of Maryland, College Park (UMCP) advocate that music underlies the ability to acquire language.

“Spoken language is a special type of music,” said Anthony Brandt, co-author of a theory paper published online this month in the journal Frontiers in Cognitive Auditory Neuroscience. “Language is typically viewed as fundamental to human intelligence, and music is often treated as being dependent on or derived from language. But from a developmental perspective, we argue that music comes first and language arises from music.”

Brandt, associate professor of composition and theory at the Shepherd School, co-authored the paper with Shepherd School graduate student Molly Gebrian and L. Robert Slevc, UMCP assistant professor of psychology and director of the Language and Music Cognition Lab.

“Infants listen first to sounds of language and only later to its meaning,” Brandt said. He noted that newborns’ extensive abilities in different aspects of speech perception depend on the discrimination of the sounds of language – “the most musical aspects of speech.”

The paper cites various studies that show what the newborn brain is capable of, such as the ability to distinguish the phonemes, or basic distinctive units of speech sound, and such attributes as pitch, rhythm and timbre.

The authors define music as “creative play with sound.” They said the term “music” implies an attention to the acoustic features of sound irrespective of any referential function. As adults, people focus primarily on the meaning of speech. But babies begin by hearing language as “an intentional and often repetitive vocal performance,” Brandt said. “They listen to it not only for its emotional content but also for its rhythmic and phonemic patterns and consistencies. The meaning of words comes later.”

Brandt and his co-authors challenge the prevailing view that music cognition matures more slowly than language cognition and is more difficult. “We show that music and language develop along similar time lines,” he said.

Infants initially don’t distinguish well between their native language and all the languages of the world, Brandt said. Throughout the first year of life, they gradually hone in on their native language. Similarly, infants initially don’t distinguish well between their native musical traditions and those of other cultures; they start to hone in on their own musical culture at the same time that they hone in on their native language, he said.

The paper explores many connections between listening to speech and music. For example, recognizing the sound of different consonants requires rapid processing in the temporal lobe of the brain. Similarly, recognizing the timbre of different instruments requires temporal processing at the same speed — a feature of musical hearing that has often been overlooked, Brandt said.

“You can’t distinguish between a piano and a trumpet if you can’t process what you’re hearing at the same speed that you listen for the difference between ‘ba’ and ‘da,’” he said. “In this and many other ways, listening to music and speech overlap.” The authors argue that from a musical perspective, speech is a concert of phonemes and syllables.

“While music and language may be cognitively and neurally distinct in adults, we suggest that language is simply a subset of music from a child’s view,” Brandt said. “We conclude that music merits a central place in our understanding of human development.”

Brandt said more research on this topic might lead to a better understanding of why music therapy is helpful for people with reading and speech disorders. People with dyslexia often have problems with the performance of musical rhythm. “A lot of people with language deficits also have musical deficits,” Brandt said.

More research could also shed light on rehabilitation for people who have suffered a stroke. “Music helps them reacquire language, because that may be how they acquired language in the first place,” Brandt said.

(Source: news.rice.edu)

Misfolded proteins can cause various neurodegenerative diseases such as spinocerebellar ataxias (SCAs) or Huntington’s disease, which are characterized by a progressive loss of neurons in the brain. Researchers of the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch, Germany, together with their colleagues of the Université Paris Diderot, Paris, France, have now identified 21 proteins that specifically bind to a protein called ataxin-1. Twelve of these proteins enhance the misfolding of ataxin-1 and thus promote the formation of harmful protein aggregate structures, whereas nine of them prevent the misfolding (PLoS Genetics).

Proteins only function properly when the chains of amino acids, from which they are built, fold correctly. Misfolded proteins can be toxic for the cells and assemble into insoluble aggregates together with other proteins. Ataxin-1, the protein that the researchers have now investigated, is very prone to misfolding due to inherited gene defects that cause neurodegenerative diseases. The reason for this is that the amino acid glutamine is repeated in the amino acid chain of ataxin-1 very often - the more glutamine, the more toxic the protein. Approximately 40 repeats of glutamine are considered to be toxic for the cells.

Now, Dr. Spyros Petrakis, Dr. Miguel Andrade, Professor Erich Wanker and colleagues have identified 21 proteins that mainly interact with ataxin-1 and influence its folding or misfolding. Twelve of these proteins enhance the toxicity of ataxin-1 for the nerve cells, whereas nine of the identified proteins reduce its toxicity.

Furthermore, the researchers detected a common feature in the structure of those proteins that enhances toxicity and aggregation. It is a special structure scientists call “coiled-coil-domain” because it resembles a double twisted spiral or helix. Apparently this structure promotes aggregation, because proteins that interact with ataxin-1 and have this domain enhance the toxic effect of mutated ataxin-1. As the researchers said, this structure could be a potential target for therapy: “A careful analysis of the molecular details could help to discover drugs that suppress toxic processes.”

(Source: mdc-berlin.de)

Scientists at Washington University School of Medicine in St. Louis have taken one of the first detailed looks into how Alzheimer’s disease disrupts coordination among several of the brain’s networks. The results, reported in The Journal of Neuroscience, include some of the earliest assessments of Alzheimer’s effects on networks that are active when the brain is at rest.

“Until now, most research into Alzheimer’s effects on brain networks has either focused on the networks that become active during a mental task, or the default mode network, the primary network that activates when a person is daydreaming or letting the mind wander,” says senior author Beau Ances, MD, assistant professor of neurology. “There are, however, a number of additional networks besides the default mode network that become active when the brain is idling and could tell us important things about Alzheimer’s effects.”

Ances and his colleagues analyzed brain scans of 559 subjects. Some of these subjects were cognitively normal, while others were in the early stages of very mild to mild Alzheimer’s disease. Scientists found that all of the networks they studied eventually became impaired during the initial stages of Alzheimer’s.

“Communications within and between networks are disrupted, but it doesn’t happen all at once,” Ances says. “There’s even one network that has a momentary surge of improved connections before it starts dropping again. That’s the salience network, which helps you determine what in your environment you need to pay attention to.”

Other networks studied by the researchers included:

• the dorsal attention network, which directs attention toward things in the environment that are salient;

• the control network, believed to be active in consciousness and decision-making; and

• the sensory-motor network, which integrates the brain’s control of body movements with sensory feedback (e.g., did the finger that just moved strike the right piano key?).

Scientists also examined Alzheimer’s effects on a brain networking property known as anti-correlations. Researchers identify networks by determining which brain areas frequently become active at the same time, but anti-correlated networks are noteworthy for the way their activities fluctuate: when one network is active, the other network is quiet. This ability to switch back-and-forth between networks is significantly diminished in participants with mild to moderate Alzheimer’s disease.

The default mode network, previously identified as one of the first networks to be impaired by Alzheimer’s, is a partner in two of the three pairs of anti-correlated networks scientist studied.

“While we can’t prove this yet, one hypothesis is that as things go wrong in the processing of information in the default mode network, that mishandled data is passed on to other networks, where it creates additional problems,” Ances says.

It’s not practical to use these network breakdowns to clinically diagnose Alzheimer’s disease, Ances notes, but they may help track the development of the disease and aid efforts to better understand its spread through the brain.

Ances plans to look at other markers for Alzheimer’s disease in the same subjects, such as levels in the cerebrospinal fluid of amyloid beta, a major component of Alzheimer’s plaques.

(Source: news.wustl.edu)

MRI brain scans no longer just show the various regions of brain activity; nowadays the networks in the brain can now be imaged with ever greater precision. This will make functional MRI (fMRI) increasingly powerful in the coming years, leading to tools that can be used in cognitive neuroscience. This is the claim made by Prof. David Norris in his inaugural lecture as Professor of Neuroimaging at the University of Twente on 13 September.

During the twenty years since the invention of fMRI (functional Magnetic Resonance Imaging) developments have come thick and fast, from initially identifying active brain regions to more complex analysis of the connections and hubs in the brain. In his inaugural lecture Norris describes how this has been achieved thanks to not only a growing understanding of the underlying biophysics but also rapid technological developments: scanners with larger magnetic fields, better image-processing techniques and algorithms. His aim is to go beyond merely localizing which parts of the brain are active. The challenge is to answer two questions: How are the various regions interconnected, structurally and functionally? What do the networks in our brains look like?

Faster and more powerful

Back in the 19^th century scientists observed increased blood flow in brain regions that are functionally active. fMRI enables the change in oxygen content to be seen. Haemoglobin, the substance that transports oxygen in the blood, can take the form of oxyhaemoglobin (when it is still combined with oxygen) and deoxyhaemoglobin (when the oxygen has been released), each of which has different magnetic properties. One of the complicating factors when interpreting the scans is that various physiological mechanisms are at work simultaneously, causing the deoxyhaemoglobin level to rise and fall. One of the remedies to increase accuracy, Norris explains, has been to increase the magnetic field strength: there are now MRI scanners operating at 7 Tesla. At the same time the speed at which laminae can be imaged has gone up by leaps and bounds: the entire brain can be scanned in three seconds with a precision of 1 millimetre.

Hubs

The functional connections between parts of the brain can be registered by means of blood flow, but MRI also enables the structural and anatomical connections to be seen. This involves measuring the movement of water molecules caused by the ‘white matter’ in nerve fibres. This technology is known as diffusion-weighted imaging (DWI). Combining these technologies provides a wealth of fresh information on the networks in the brain and the places where many connections come together, the ‘hubs’. Not only have ‘known networks’ thus been proven, so have networks that neuroscience posits as plausible but that have never been measured.

Image showing the distribution of connector hubs on the surface of a flattened brain. The top two figures show the medial views of each hemisphere, the bottom two show the external views.

CMI

The new Centre for Medical Imaging that is to come to the University of Twente campus will soon provide extensive facilities for collaborating in the field of fMRI, says Norris, who is also on the staff of the Donders Institute in Nijmegen.

(Source: utwente.nl)