Posts tagged science

ScienceDaily (June 15, 2012) — Exposure to low doses of Bisphenol A (BPA) during gestation had immediate and long-lasting, trans-generational effects on the brain and social behaviors in mice, according to a recent study accepted for publication in the journal Endocrinology, a publication of The Endocrine Society.

BPA is a human-made chemical present in a variety of products including food containers, receipt paper and dental sealants and is now widely detected in human urine and blood. Public health concerns have been fueled by findings that BPA exposure can influence brain development. In mice, prenatal exposure to BPA is associated with increased anxiety, aggression and cognitive impairments.

"We have demonstrated for the first time to our knowledge that BPA has trans-generational actions on social behavior and neural expression," said Emilie Rissman, PhD, of the University of Virginia School of Medicine and lead author of the study. "Since exposure to BPA changes social interactions in mice at a dose within the reported human levels, it is possible that this compound has trans-generational actions on human behavior. If we banned BPA tomorrow, pulled all products with BPA in them, and cleaned up all landfills tomorrow it is possible, if the mice data generalize to humans, that we will still have effects of this compound for many generations."

In this study, female mice received chow with or without BPA before mating and throughout gestation. Plasma levels of BPA in supplemented female mice were in a range similar to those measured in humans. Juveniles in the first generation exposed to BPA in utero displayed fewer social interactions as compared with control mice. The changes in genes were most dramatic in the first generation (the offspring of the mice that were exposed to BPA in utero), but some of these gene changes persisted into the fourth generation.

"BPA is a ubiquitous chemical, it is in the air, water, our food, and our bodies," said Rissman. "It is a man-made chemical, and is not naturally occurring in any plant or animal. The fact that it can change gene expression in mice, and that these changes are heritable, is cause for us to be concerned about what this may mean for human health."

Source: Science Daily

June 15, 2012

The research led by Newcastle University’s Dr Mark Cunningham and Professor Miles Whittington and supported by the Dr Hadwen Trust for Humane Research, indicates a novel electrical bio-marker in humans.

The brain produces electrical rhythms and using EEG - electrodes on the scalp - researchers were able to monitor the brain patterns in patients with epilepsy. Both in patients and in brain tissue samples the team were able to witness an abnormal brain wave noticeable due to its rapidly increasing frequency over time.

Comparing these to a musical ‘glissando’, an upwards glide from one pitch to another, the team found that this brain rhythm is unique to humans and they believe it could be related to epilepsy.

Dr Cunningham, senior lecturer in Neuronal Dynamics at Newcastle University said: “We were able to examine EEG collected from patients with drug resistant epilepsy who were continually monitored over a two week period. During that time we noticed patterns of electrical activity with rapidly increasing frequency, just like glissandi, emerging in the lead-up to an epileptic seizure.”

"We are in the early days of the work and we want to investigate this in a larger group of patients but it may offer a promising insight into when a seizure is going to start."

Professor Whittington added: “Classical composers such as Gustav Mahler are famous for using notes of rapidly increasing pitch – called glissando - to convey intense expressions of anticipation. Similarly we identified glissando-like patterns of brain electrical activity generated in anticipation of seizures in patients with epilepsy.”

The team recorded electrical activity taken from patients in Newcastle and Glasgow with the help of collaborators Dr Roderick Duncan and Dr Aline Russell and worked in collaboration with the Epilepsy Surgery Group at Newcastle General Hospital part of the Newcastle Hospitals NHS Foundation Trust.

Having received permission from patients to use brain tissue removed during an operation to cure their seizures, the team were able to observe and study in great detail glissando discharges in slices of this human epileptic tissue maintained in the lab.

Publishing in Epilepsia online, the team discovered that glissandi are highly indicative of pathology associated with human epilepsy and, unlike other forms of epileptic activity studied previously, are extremely difficult to reproduce in normal, non-epileptic brain tissue. The team worked with Professor Roger Traub at the IBM Watson Research Centre in New York to provide predictions using highly detailed computational models. By manipulating the chemical conditions surrounding human epileptic brain tissue according to these predictions, they discovered that glissandi did not require any of the conventional chemical connections between nerve cells thought to underlie most brain functions. Instead, glissandi were generated by a combination of large changes in the pH of the tissue, specific electrical properties of certain types of nerve cell and, most importantly, direct electrical connections between these nerve cells.

"This work also suggests that given the lengths one has to go to reproduce this experimentally in rodents that the glissandi may be a unique feature of the human epileptic brain," explains Dr Cunningham.

Dr Kailah Eglington, Chief Executive of the Dr Hadwen Trust, said: “Of all human brain disorders, epilepsy research ranks as one that currently employs substantial numbers of laboratory animals worldwide.

"Dr Cunningham’s work at Newcastle University aims to address the shortcomings of existing animal-based research by removing animals from the equation and addressing the issue directly in humans."

Provided by Newcastle University

Source: medicalxpress.com

June 15, 2012

The first large non-commercial study to investigate whether the main active constituent of cannabis (tetrahydrocannabinol or THC) is effective in slowing the course of progressive multiple sclerosis (MS) shows that there is no evidence to suggest this; although benefits were noted for those at the lower end of the disability scale.

The CUPID (Cannabinoid Use in Progressive Inflammatory brain Disease) study was carried out by researchers from the Peninsula College of Medicine and Dentistry (PCMD), Plymouth University. The study was funded by the Medical Research Council (MRC) and managed by the National Institute for Health Research (NIHR) on behalf of the MRC-NIHR partnership, the Multiple Sclerosis Society and the Multiple Sclerosis Trust.

The preliminary results of CUPID are to be presented by lead researcher Professor John Zajicek at the Association of British Neurologists’ Annual Meeting in Brighton on Tuesday 29th May.

CUPID enrolled nearly 500 people with MS from 27 centres around the UK, and has taken eight years to complete. People with progressive MS were randomised to receive either THC capsules or identical placebo capsules for three years, and were carefully followed to see how their MS changed over this period. The two main outcomes of the trial were a disability scale administered by neurologists (the Expanded Disability Status Scale), and a patient report scale of the impact of MS on people with the condition (the Multiple Sclerosis Impact Scale 29).

Overall the study found no evidence to support an effect of THC on MS progression in either of the main outcomes. However, there was some evidence to suggest a beneficial effect in participants who were at the lower end of the disability scale at the time of enrolment but, as the benefit was only found in a small group of people rather than the whole population, further studies will be needed to assess the robustness of this finding. One of the other findings of the trial was that MS in the study population as a whole progressed slowly, more slowly than expected. This makes it more challenging to find a treatment effect when the aim of the treatment is that of slow progression.

As well as evaluating the potential neuroprotective effects and safety of THC over the long-term, one of the aims of the CUPID study was to improve the way that clinical trial research is done by exploring newer methods of measuring MS and using the latest statistical methods to make the most of every piece of information collected. This analysis will continue for several months. The CUPID study will therefore provide important information about conducting further large scale clinical trials in MS.

Professor John Zajicek, Professor of Clinical Neuroscience at PCMD, Plymouth University, said: “To put this study into context: current treatments for MS are limited, either being targeted at the immune system in the early stages of the disease or aimed at easing specific symptoms such as muscle spasms, fatigue or bladder problems. At present there is no treatment available to slow MS when it becomes progressive. Progression of MS is thought to be due to death of nerve cells, and researchers around the world are desperately searching for treatments that may be ‘neuroprotective’. Laboratory experiments have suggested that certain cannabis derivatives may be neuroprotective.”

He added: “Overall our research has not supported laboratory based findings and shown that, although there is a suggestion of benefit to those at the lower end of the disability scale when they joined CUPID, there is little evidence to suggest that THC has a long term impact on the slowing of progressive MS.”

Dr Doug Brown, Head of Biomedical Research at the MS Society, said: “There are currently no treatments for people with progressive MS to slow or stop the worsening of disability. The MS Society is committed to supporting research in this area and this was an important study for us to fund. While this study sadly suggests THC is ineffective at slowing the course of progressive MS, we will not stop our search for effective treatments. We are encouraged by the possibility shown by this study that THC may have potential benefits for some people with MS and we welcome further investigation in this area.”

Provided by The Peninsula College of Medicine and Dentistry

Source: medicalxpress.com

June 15, 2012 By Angela Herring

Object manip­u­la­tion or tool use is almost a uniquely human trait, said Dagmar Sternad, director of Northeastern’s Action Lab, a research group inter­ested in move­ment coor­di­na­tion. “Not only does it require cer­tain cog­ni­tive abil­i­ties but also dis­tinct motor abilities.”

Professor Dagmar Sternad and postdoctoral researcher C.J. Hasson show that we subconsciously adjust our “safety margin” when we move a dynamic object like a cup of coffee based on the amount of variability in the situation. Credit: John Guillemin

Simply moving one’s own body, for instance by directing a hand toward a coffee cup, requires the orga­ni­za­tion of var­ious phys­i­o­log­ical sys­tems including the cen­tral and periph­eral ner­vous sys­tems and the mus­cu­loskeletal system.

Once the hand grasps and picks up the cup, the ques­tions become even more com­pli­cated. What if the cup is filled with liquid? At this point, the com­plexity of the con­trol problem bal­loons — the pres­ence of the liquid intro­duces non­linear fluid dynamics with the risk of a spill because of the inherent vari­ability in one’s movement.

Sternad, a pro­fessor of , biology, elec­trical and com­puter engi­neering and physics and post­doc­toral researcher C.J. Hasson are inter­ested in how we adapt our move­ment strate­gies when inter­acting with dynamic objects in the environment.

In a recent paper pub­lished in the Journal of Neu­ro­phys­i­ology, Hasson and Sternad explored the ques­tion by looking at the everyday task of manip­u­lating a cup of coffee. They show that how we adapt our move­ment strate­gies is directly related to the amount of vari­ability and reli­a­bility in our sur­round­ings and ourselves.

“Because we’re humans and not machines, we’re noisy and vari­able,” said Hasson. “We can’t expect that a move­ment will unfold exactly as we planned it.”

For the study, 18 healthy par­tic­i­pants vis­ited the Action Lab to play a video game, wherein they attempted to move a vir­tual cup filled with vir­tual liquid across a large video screen. Instead of a normal video-game con­troller, sub­jects moved the vir­tual cup by grasping a manip­u­landum — a large robotic arm. Sim­ilar to the real-life sce­nario, the robot sim­u­lated the forces one would feel from the weight of the object and the sloshing of the liquid in the cup.

They asked par­tic­i­pants to move the cup across the screen within a com­fort­able time of two sec­onds, a task for which there is an infi­nite number of pos­si­bil­i­ties. You could move fast for one second and slow for one second, slow for a half second and then fast for one and a half sec­onds. The team hypoth­e­sized that par­tic­i­pants would nat­u­rally adapt a safe move­ment strategy with prac­tice — and they did.

But the most intriguing result, said Hasson, was that the size of each participant’s safety margin —or how close they let the liquid get to the edge of the cup — could be pre­dicted by how vari­able they were in their move­ments. Those with more vari­ability tended to adapt a “safer” strategy with a larger safety margin.

“If you have a large safety margin and I move with a small margin, the ques­tion is, ‘Why am I more risky than you?’” Hasson said. “Well, you may find that I am much more con­sis­tent in my move­ments, so I don’t need a big safety margin. If you’re more vari­able, you need a larger safety margin.”

The results have impli­ca­tions in assessing elderly patients and patients of motor dis­or­ders such as cere­bral palsy. “If vari­ability deter­mines the move­ments that you do, maybe that’s an inter­ven­tion point,” said Sternad.

Provided by Northeastern University

Source: medicalxpress.com

June 15, 2012

Researchers from the Peninsula College of Medicine and Dentistry, University of Exeter, in collaboration with colleagues from Rutgers University, Newark and University College London, have furthered understanding of the mechanism by which the cells that insulate the nerve cells in the peripheral nervous system, Schwann cells, protect and repair damage caused by trauma and disease.

The findings of the study, published on-line by the Journal of Neuroscience and supported by the Wellcome Trust, are exciting in that they point to future therapies for the repair and improvement of damage to the peripheral nervous system.

The peripheral nervous system is the part of the nervous system outside the brain and the spinal cord. It regulates almost every aspect of our bodily function, carrying sensory information that allows us to feel the sun on our face and motor information, that allows us to move. It also controls the functions of all the organs of the body.

Damage can occur through trauma: it can occur in diabetic neuropathy (suffered by almost half of those with diabetes) and patients with common inherited conditions such as Charcot-Marie-Tooth (CMT) disease. There can be a wide range of symptoms, from loss of sensation in the hands and feet to problems with digestion, blood pressure regulation, sexual function and bladder control.

Schwann cells provide the insulation, or myelin sheath, for the nerve cells that carry electrical impulses to and from the spinal cord. Schwann cells, because of their plasticity, are able to revert back to an immature ‘repair’ cell to repair damage to the peripheral nervous system. The level of repair is remarkably good but incomplete repair, perhaps after the severance of a nerve, may lead to long-term loss of function and pain.

The ability of Schwann cells to demyelinate can make them susceptible to the disease process seen in conditions such as CMT. CMT affects one in 2500people, so is a comparatively common inherited disease of the nervous system. Mutations in the many different genes in CMT can cause cycles of repair and re-insulation (re-myelination) which lead to long-term damage and the death of both Schwann and nerve cells. There is currently no therapy for CMT and patients experience increased sensory and motor problems which may lead to permanent disability.

The research team believes that its work to understand the ability of Schwann cells to revert back to an immature state and stimulate repair will lead to therapies to improve damage from severe trauma and break the cycle of damage caused by CMT. They also believe that there may also be potential to improve repair in cases of diabetic neuropathy.

They have identified a DNA binding protein, cJun, as a key player in the plasticity that allows a Schwann cell to revert back to the active repair state. cJun may be activated by a number of pathways that convey signals from the surface of the Schwann cell to the nucleus. One such pathway, the p38 Mitogen Activated Protein Kinase Pathway, appears to play a vital role: it is activated after PNS damage and may promote the process of repair; conversely it may be abnormally activated in demyelinating diseases such as CMT.

Professor David Parkinson, Associate Professor in Neuroscience, Peninsula College of Medicine and Dentistry, University of Exeter, said: “The findings of our research are exciting because we have pinpointed and are understanding the mechanism by which our bodies can repair damage to the peripheral nervous system. With further investigation, this could well lead to therapies to repair nerve damage from trauma and mitigate the damage which relates to common illnesses, such as CMT.”

Provided by The Peninsula College of Medicine and Dentistry

Source: medicalxpress.com

June 15, 2012

Whether or not a neuron transmits an electrical impulse is a function of many factors. European research is using a heady mixture of techniques – molecular, microscopy and electrophysiological – to identify the necessary input for nerve transmission in the cortex.

Credit: Thinkstock

In the central nervous system (CNS), a nerve cell or neuron has a ‘forest’ of elaborate dendritic trees arising from the cell body. These literally receive many thousands of synapses (junctions that allow transmission of a signal) at positions around the tree. These inputs then are able to generate an impulse, or ‘spike’, known as an action potential at the initial part of the axon.

Previous research has confirmed that an activated synapse will generate an electric signal as a result of neurotransmitters released from pre-synaptic axons. Electrical recordings from the neocortex have confirmed that, in line with the cable theory prediction, that modulation of potential at the dendrite is highly distance-dependent from the cell body or soma.

The ‘Information processing in distal dendrites of neocortical layer 5 pyramidal neurons’ (Channelrhodopsin) project aimed to shed more light on how more distal sites in the ‘tree’ influence the action potential of the post-synaptic neuron. Furthermore, they investigated exactly how dendritic spikes can be generated, another issue about which there is little information so far.

Recent research has highlighted the importance of activation of N-methyl-D-aspartate (NMDA) receptors to bring about the production of a signal that will proceed to the soma and then result in a spike. There is also indirect evidence that interneurons targeting dendrites can control level of dendrite excitability.

Channelrhodopsin scientists simultaneously recorded the pre- and post-synaptic electrical recordings of identified interneurons and a special type of neuron, pyramidal cells that are primary excitation units in the mammalian cortex.

The project team first characterised the different types of inhibitory neuron deep in the cortex in layer 5 at apical tuft dendrites. The researchers then showed that a special type of inhibitory interneuron in the outer layer of the neocortex can suppress dendritic spiking in layer 5.

Project results show that a superficial inhibitory neuron can impact information processing in a specific pyramidal neuron. The research will have massive implications for neuroscience and help to unravel the integrative operations of CNS neurons.

Provided by CORDIS

Source: medicalxpress.com

ScienceDaily (June 14, 2012) — Rockville, Md. — Scientists have found new evidence that people spot a face in the crowd more quickly when teeth are visible — whether smiling or grimacing — than a face with a particular facial expression. The new findings, published in the Journal of Vision, counters the long held “face-in -the-crowd” effect that suggests only angry looking faces are detected more readily in a crowd.

Examples of stimuli — closed mouth and open mouth with visible teeth — presented in the experiment. (Credit: ARVO)

"The research concerned with the face-in-the-crowd effect essentially deals with the question of how we detect social signals of friendly or unfriendly intent in the human face," said author Gernot Horstmann, PhD, of the Center for Interdisciplinary Research and Department of Psychology at Bielefeld University, Germany. "Our results indicate that, contrary to previous assertions, detection of smiles or frowns is relatively slow in crowds of neutral faces, whereas toothy grins and snarls are quite easily detected."

In two studies, the researchers asked subjects to search for a happy or an angry face within a crowd of neutral faces, and measured the search speed. While the search was relatively slow when emotion was signaled with a closed mouth face, the speed search doubled when emotion was signaled with an open mouth and visible teeth. This was the case for both happy and angry faces, and happy faces were found even somewhat faster than angry faces.

Horstmann and his colleagues conducted these experiments as a result of discrepancies in previous studies that investigated visual search for emotional faces. According to the research team, the inconsistent results with respect to which of the two expressions are found faster — the happy face or the angry face — suggested that the emotional expression category could not be the only important factor determining the face-in- the-crowd effect.

The scientists believe this new study may explain the discrepancies. “This will probably inspire researchers to clarify whether emotion and, in particular, threat plays an additional, unique role in face detection,” said Horstmann.

Source: Science Daily

ScienceDaily (June 14, 2012) — An international team of researchers’ study of the spatial patterns of the spread of obesity suggests America’s bulging waistlines may have more to do with collective behavior than genetics or individual choices. The team, led by City College of New York physicist Hernán Makse, found correlations between the epidemic’s geography and food marketing and distribution patterns.

Supermarket. Physicists found correlations between the obesity epidemic’s geography and food marketing and distribution patterns. (Credit: © flashpics / Fotolia)

"We found there is a relationship between the prevalence of obesity and the growth of the supermarket economy," Professor Makse said. "While we can’t claim causality because we don’t know whether obesity is driven by market forces or vice versa, the obesity epidemic can’t be solved by focus on individual behavior."

The teams findings, published online this week in Scientific Reports, come as a policymakers are starting to address the role of environmental factors in obesity. For example, in New York Mayor Michael Bloomberg wants to limit serving sizes of soda sweetened with sugar to 16 ounces as a way to combat obesity.

The World Health Organization considers obesity a global epidemic similar to cancer or diabetes. It is a non-communicable disease for which no prevention strategy has been able to contain the spread.

Because obesity is related to increased calorie intake and physical inactivity, prevention has focused on changing individuals’ behaviors. However, prevalence of non-communicable diseases shows spatial clustering, and the spread of obesity has shown “high susceptibility to social pressure and global economic drivers.”

Professor Makse and his colleagues hypothesized that these earlier findings suggest collective behavior plays a more significant role in the spread of the epidemic than individual factors such as genetics and lifestyle choices. To study collective behavior’s role, they implemented a statistical clustering analysis based on the physics on the critical phenomena.

Using county-level microdata provided by the U.S. Centers for Disease Control Behavior Risk Factor Surveillance Systems for 2004 through 2008, they investigated spatial correlations for specific years. Over that time span, the pattern of the spreading of the epidemic, which has Greene County, Ala., as its epicenter, has shown that two clusters spanning distances of 1,000 kilometers have emerged; one along the Appalachian Mountains, the second in the lower Mississippi River valley.

The spatial map of obesity prevalence in the United States shows that neighboring areas tend to have similar percentages of their populations considered obese, i.e. have a body mass index greater than or equal to 30. Such areas are considered obesity clusters, and their spread can be seen in the maps from 2004 to 2008.

To assess the properties of these spatial arrangements, the researchers calculated an equal-time, two-point correlation function that measured the influence of a set of characteristics in one county on another county at a given distance. The characteristics studied were population density, prevalence of adult obesity and diabetes, cancer mortality rates and economic activity.

The researchers said the form of the correlations in obesity were reminiscent of those in physical systems at a critical point of second-order phase transition. Such systems are uncorrelated and characterized by short-range vanishing fluctuations when they are not at a critical stage.

However, at critical points long-range correlations appear, and these may signal the emergence of strong critical fluctuations in the spreading of obesity and diabetes. Consequently, they concluded the clustering patterns found in obesity were the result of “collective behavior, which may not merely be the consequence of fluctuations in individual habits.”

Professor Makse and his colleagues believe the correlations of fluctuations in the prevalence of obesity may be linked to demographic and economic variables. To test this hypothesis, they compared the spatial characteristics of industries associated with food production and sales, e.g. supermarkets, food and beverage stores, restaurants and bars, to other sectors of the economy.

Their analysis of spatial fluctuations in food economic activity gave rise to the same anomalous values as obesity and diabetes. Areas with above-average concentrations of food-related businesses had high-than-normal prevalence of obesity and diabetes.

In future studies, Professor Makse plans to apply physics concepts to measure the spread of cancer and diabetes. “The basic idea is that if a non-communicable disease is spreading like a virus, then environmental factors have to be at work,” he said. “If only genetics determined obesity, we wouldn’t have seen the correlations.”

Source: Science Daily

ScienceDaily (June 14, 2012) — The first U.S. population prevalence study of mutations in the gene that causes fragile X syndrome, the most common inherited form of intellectual disability, suggests the mutation in the gene — and its associated health risks — may be more common than previously believed.

Writing this month (June 2012) in the American Journal of Medical Genetics, a team of Wisconsin researchers reports that the cascade of genetic amino acid repeats, which accumulate over generations and culminate in the mutation of a single gene causing fragile X, is occurring with more frequency among Americans than previously believed. The study also shows that as the genetic basis for the condition is passed from generation to generation and amplified, risks to neurological and reproductive health emerge in many carriers.

"The premutation of this condition is much more prevalent than we previously thought and there are some clinical risks associated with that," explains Marsha Mailick Seltzer, director of the University of Wisconsin-Madison Waisman Center, who led the new study.

Fragile X is caused by the unexplained runaway expansion of a set of amino acid repeats in a single X chromosome gene known as FMR1. When fully mutated, the gene fails to express and produce a protein that’s required for healthy brain development. The syndrome, which is more common in boys, results in a spectrum of intellectual disability.

However, before the gene fully mutates, carriers of the faulty gene exhibit a smaller number of elevated repeats, which expand as the gene is passed from generation to generation. Normal FMR1 genes exhibit anywhere from five to 40 repeats. Carriers with a premutation may have anywhere from 55 to 200. Those with between 45 and 54 repeats are characterized as falling into a “gray zone.” Carriers of gray zone expansions often pass the mutation on to their children who themselves are at greater risk of having the premutation, and in subsequent generations the risk of a full mutation causing fragile X syndrome is high.

The goal of the new study was to calculate the prevalence in a U.S. population of the premutation and the gray zone. The research was based on data from the Wisconsin Longitudinal Study (WLS), also known as the “Happy Days study,” which for more than 50 years has tracked the careers, family life, health and education of more than 10,000 graduates of Wisconsin’s high school class of 1957.

Using genetic samples from 6,747 WLS participants, the team led by Seltzer, an expert on developmental disability and family life, found that 1 in 151 females and 1 in 468 males carry the fragile X premutation while 1 in 35 females and 1 of every 42 males fall into the gray zone.

"The prevalence is high, the second highest reported in the world literature," says Seltzer, noting that the incidence of fragile X varies by population and is higher in some places such as Israel, and lower in others like Asia.

The expansion of the FMR1 gene is known to vary across ethnic groups. The sample in the WLS study is primarily white and of northern European descent.

People with the premutation are more likely to have a child with disability; to have neurological symptoms such as numbness, dizziness and faintness; and, for women, to experience early menopause. Although these symptoms have been recognized previously in clinical studies, the WLS data represent an unbiased sample and supports those observations.

"This study confirms that there are health risks associated with the premutation," says Seltzer. "People with the premutation have a higher probability of neurological and reproductive problems. There is a significant public health burden."

Source: Science Daily

ScienceDaily (June 14, 2012) — No effective treatments are currently available for the prevention or cure of Alzheimer’s disease (AD), the most frequent form of dementia in the elderly. The most recognized risk factors, advancing age and having the apolipoprotein E Ɛ4 gene, cannot be modified or treated. Increasingly, scientists are looking toward other risk factors to identify preventive and therapeutic strategies. Much attention recently has focused on the metabolic syndrome (MetS), with a strong and growing body of research suggesting that metabolic disorders and obesity may play a role in the development of dementia.

A new supplement to the Journal of Alzheimer’s Disease provides a state-of-the-art assessment of research into the link between metabolic syndrome and cognitive disorders. The supplement is guest edited by Vincenza Frisardi, of the Department of Neurological and Psychiatric Sciences, University of Bari, and the Geriatric Unit and Gerontology-Geriatrics Research Laboratory, IRCCS, Foggia, Italy, and Bruno P. Imbimbo, Research and Development Department, Chiesi Farmaceutici, Parma, Italy.

The prevalence of MetS and obesity has increased over the past several decades. MetS is a cluster of vascular and metabolic risk factors including obesity, hypertension, an abnormal cholesterol profile, and impaired blood glucose regulation. “Although molecular mechanisms underlying the relationship between MetS and neurological disorders are not fully understood, it is becoming increasingly clear that cellular and biochemical alterations observed in MetS may represent a pathological bridge between MetS and various neurological disorders,” explains Dr. Frisardi.

Type 2 diabetes (T2D) has been linked with cognitive impairment in a number of studies. The risk for developing both T2D and AD increases proportionately with age, and evidence shows that individuals with T2D have a nearly twofold higher risk of AD than nondiabetic individuals.

Paula I. Moreira, Faculty of Medicine and Center for Neuroscience and Cell Biology, University of Coimbra, Portugal, outlines some of the likely mechanisms. Both AD and T2D present similar abnormalities in the mitochondria, which play a pivotal role in cellular processes that impair their ability to regulate oxidation in the cell. Human amylin, a peptide that forms deposits in the pancreatic cells of T2D patients, shares several properties with amyloid-ß plaques in the Alzheimer’s brain. Insulin resistance is another feature shared by both disorders. Impairment of insulin signalling is directly involved in the development of tau tangles and amyloid ß (Aß) plaques. “Understanding the key mechanisms underlying this deleterious interaction may provide opportunities for the design of effective therapeutic strategies,” Dr. Moreira notes.

In another article, author, José A. Luchsinger of the Division of General Medicine, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, notes that while there seems to be little dispute that T2D can cause cerebrovascular disease and vascular cognitive impairment, whether T2D can cause late onset AD remains to be determined. “Although the idea is highly speculative, the association between T2D and cognitive impairment may not be causal. Several lines of evidence provide some support to the idea that late onset Alzheimer’s disease could cause T2D, or that both could share causal pathways,” he notes. He reviews epidemiological, imaging, and pathological studies and clinical trials to provide insight. “Given the epidemic of T2D in the world, it’s important to determine whether the association between T2D and cognitive impairment, particularly late onset AD, is causal and if so, what are the mechanisms underlying it.”

Dr. Frisardi notes that most efforts by the pharmaceutical industry have been directed against the production and accumulation of amyloid-ß. “Unfortunately, these efforts have not produced effective therapies yet, since the exact mechanisms of AD are largely unknown. Given that the onset of AD most likely results from the interaction of genetic and environmental factors, the research agenda should consider new platforms of study, going beyond the monolithic outlook of AD, by synthesizing epidemiological, experimental, and biological data under a unique pathophysiological model as a point of reference for further advances in the field.”

Source: Science Daily