1. New cases of dementia in the UK fall by 20 percent over two decades

    April 25, 2016 by Ashley

    From the University of Cambridge media release:

    seniors_companionshipThe UK has seen a 20% fall in the incidence of dementia over the past two decades, according to new research from England, led by the University of Cambridge, leading to an estimated 40,000 fewer cases of dementia than previously predicted. However, the study, published today in Nature Communications, suggests that the dramatic change has been observed mainly in men.

    Reports in both the media and from governments have suggested that the world is facing a dementia ‘tsunami’ of ever-increasing numbers, particularly as populations age. However, several recent studies have begun to suggest that the picture is far more complex. Although changing diagnostic methods and criteria are identifying more people as having dementia, societal measures which improve health such as education, early- and mid-life health promotion including smoking reduction and attention to diet and exercise may be driving a reduction in risk in some countries. Prevalence (the proportion of people with dementia) has been reported to have dropped in some European countries but it is incidence (the proportion of people developing dementia in a given time period) that provides by far the most robust evidence of fundamental change in populations.

    As part of the Medical Research Council Cognitive Function and Ageing Study (CFAS), researchers at the University of Cambridge, Newcastle University, Nottingham University and the University of East Anglia interviewed a baseline of 7,500 people in three regions of the UK (Cambridgeshire, Newcastle and Nottingham) between 1991 and 1994 with repeat interviews at two years to estimate incidence. Then 20 years later a new sample of over 7,500 people from the same localities aged 65 and over was interviewed with a two year repeat interview again. This is the first time that a direct comparison of incidence across time in multiple areas, using identical methodological approaches, has been conducted in the world.

    The researchers found that dementia incidence across the two decades has dropped by 20% and that this fall is driven by a reduction in incidence among men at all ages. These findings suggest that in the UK there are just under 210,000 new cases per year: 74,000 men and 135,000 women — this is compared to an anticipated 250,000 new cases based on previous levels. Incidence rates are higher in more deprived areas.

    Even in the presence of an ageing population, this means that the number of people estimated to develop dementia in any year has remained relatively stable, providing evidence that dementia in whole populations can change. It is not clear why rates among men have declined faster than those among women, though it is possible that it is related to the drop in smoking and vascular health improving in men.

    Professor Carol Brayne, Director of the Cambridge Institute of Public Health, University of Cambridge, says: “Our findings suggest that brain health is improving significantly in the UK across generations, particularly among men, but that deprivation is still putting people at a disadvantage. The UK in earlier eras has seen major societal investments into improving population health and this appears to be helping protect older people from dementia. It is vital that policies take potential long term benefits into account. ”

    Professor Fiona Matthews from the Institute of Health and Society, Newcastle University and the MRC Biostatistics Unit, Cambridge adds: “Public health measures aimed at reducing people’s risk of developing dementia are vital and potentially more cost effective in the long run than relying on early detection and treating dementia once it is present. Our findings support a public health approach for long term dementia prevention, although clearly this does not reduce the need for alternative approaches for at-risk groups and for those who develop dementia.”

    The researchers argue that while influential reports continue to promote future scenarios of huge increases of people with dementia across the globe, their study shows that global attention and investment in reducing the risk of dementia can help prevent such increases.

    “While we’ve seen investment in Europe and many other countries, the lack of progress in access to education, malnutrition in childhood and persistent inequalities within and across other countries means that dementia will continue to have a major impact globally,” says Professor Brayne. “Our evidence shows that the so-called dementia ‘tsunami’ is not an inevitability: we can help turn the tide if we take action now.”

    Dr Rob Buckle, director of science programmes at the Medical Research Council, which funded the study, added: “It is promising news that dementia rates, especially amongst men, have dropped by such a significant amount over the last twenty years, and testament to the benefits of an increased awareness of a brain-healthy lifestyle. However, the burden of dementia will continue to have significant societal impact given the growing proportion of elderly people within the UK population and it is therefore as important as ever that we continue to search for new ways of preventing and treating the disease. This study does, however, reinforce the importance of long-term, quality studies that create a wealth of data of invaluable resource for researchers.”


  2. Remote Italian village could harbor secrets of healthy aging

    April 14, 2016 by Ashley

    From the University of California, San Diego Health Sciences media release:

    mediterranean diet fishThe average life expectancy in the United States is approximately 78 years old. Americans live longer, with better diets and improved health care, than ever before, but only 0.02 percent will hit the century mark.

    To understand how people can live longer throughout the world, researchers at University of California, San Diego School of Medicine have teamed up with colleagues at University of Rome La Sapienza to study a group of 300 citizens, all over 100 years old, living in a remote Italian village nestled between the ocean and mountains on the country’s coast.

    “We are the first group of researchers to be given permission to study this population in Acciaroli, Italy,” said Alan Maisel, MD, lead UC San Diego School of Medicine investigator and professor of medicine in the Division of Cardiovascular Medicine.

    The Acciaroli study group is known to have very low rates of heart disease and Alzheimer’s. It favors a Mediterranean diet markedly infused with the herb rosemary. Due to the location of the village, Maisel said locals also walk long distances and hike through the mountains as part of their daily activity.

    The goal of this long-term study is to find out why this group of 300 is living so long by conducting a full genetic analysis and examining lifestyle behaviors, like diet and exercise,” said Maisel. “The results from studying the longevity of this group could be applied to our practice at UC San Diego and to patients all over the world.”

    Maisel and his research team will work with their Italian counterparts to collect blood samples and distribute questionnaires to the group over the next six months.

    The study will also involve tests to look at metabolomics, biomes, cognitive dysfunction and protein biomarkers for risk of heart disease, Alzheimer’s, kidney disease and cancer.

    “This project will not only help to unlock some of the secrets of healthy aging, but will build closer ties with researchers across the globe, which will lead to more science and improved clinical care in our aging population,” said Salvatore DiSomma, MD, lead Italian investigator and professor of emergency medicine at University of Rome La Sapienza.

    Co-authors include Nicholas Schork, Robert Rissman, Chris Benner, Tatianna Kisseleva, William Kemen, Rob Knight, Dillip Jeste, Lori Daniels, and Mohit Jain, all with UC San Diego.

    The study is supported, in part, from European grants.


  3. Brain study reveals how long-term memories are erased

    March 31, 2016 by Ashley

    From the University of Edinburgh media release:

    mri scanVital clues about how the brain erases long term memories have been uncovered by researchers.

    The study in rats reveals how forgetting can be the result of an active deletion process rather than a failure to remember.

    It points towards new ways of tackling memory loss associated with conditions such as Alzheimer’s disease and other types of dementia.

    The findings could also help scientists to understand why some unwanted memories are so long-lasting — such as those of people suffering from post-traumatic stress disorders.

    Memories are maintained by chemical signalling between brain cells that relies on specialised receptors called AMPA receptors. The more AMPA receptors there are on the surface where brain cells connect, the stronger the memory.

    The team led by the University of Edinburgh found that the process of actively wiping memories happens when brain cells remove AMPA receptors from the connections between brain cells.

    Over time, if the memory is not recalled, the AMPA receptors may fall in number and the memory is gradually erased.

    The researchers also showed that actively forgetting information in this way helps the animals to adapt their behaviour according to their surroundings.

    Blocking the removal of AMPA receptors with a drug that keeps them at the surface of the cell stopped the natural forgetting of memories, the study found.

    Drugs that target AMPA receptor removal are already being investigated as potential therapies to prevent memory loss associated with diseases such as Alzheimer’s and dementia.

    However, researchers say that active forgetting could be an important facet of learning and memory. Further research is needed to understand what consequences blocking this process could have on the ability to take on new information and retrieve existing memories.

    Dr Oliver Hardt, of the Centre for Cognitive and Neural Systems at the University of Edinburgh, said: “Our study looks at the biological processes that happen in the brain when we forget something. The next step is to work out why some memories survive whilst others are erased. If we can understand how these memories are protected, it could one-day lead to new therapies that stop or slow pathological memory loss.”

    The study is published in The Journal of Neuroscience.


  4. Transmissibility of Alzheimer’s: No clinical symptoms

    by Ashley

    From the Medical University of Vienna media release:

    memory lossMedUni Vienna researchers have published the results of a clarifying research study on the potential transmissibility of Alzheimer’s disease. Although the protein associated with Alzheimer’s disease, amyloid-?, might be transmissible under very unusual circumstances, this does not go along with a transmission of the clinical manifestation of Alzheimer’s disease. The affected persons develop no clinical symptoms of the disease.

    Deposits of amyloid-? together with the tau protein in the brain constitute a distinctive biomarker of Alzheimer’s disease. In the last months, researchers from the UK and a research team from Switzerland and Austria attracted attention by stating that the amyloid-? protein might be transmitted to healthy persons in the context of medical procedures such as brain surgery. They examined the brain tissue of deceased persons who had received human growth hormone or dura mater transplants. This raised fears that the protein might be able to transmit the disease.

    The research group of Gabor G. Kovacs of the Institute of Neurology of MedUni Vienna could now for the first time microscopically examine and compare archived dura mater (the thick membrane covering of the brain) of donors. The results confirm that amyloid-? is transmissible from the dura mater to another brain. However, the microscopic appearance of the amyloid-? deposits differs from the usual appearance in Alzheimer’s disease.

    The amyloid-? protein remains in the vicinity of the operated tissue and does not spread considerably or affect other brain regions. There were also no clinical symptoms of Alzheimer’s disease and no characteristic deposits of the tau protein were seen.

    To determine if amyloid-? deposits can be found in the dura mater, the research group also examined the dura mater of elderly individuals. In this context, the researchers demonstrated for the first time that amyloid-? can also be stored by the dura mater. This was previously only known for cerebral tissue.

    “The study allows us to obtain a balanced opinion of the transmissibility of Alzheimer’s disease,” explained the principal investigator of the research study, Gabor G. Kovacs. “Despite the fact that it looks as if amyloid-?, the protein associated with Alzheimer’s, might be transmissible under very unusual circumstances, the clinical manifestation of Alzheimer’s disease is not transmitted. It is certainly not correct to talk of a transmissibility of the disease.”


  5. Link between gum disease and cognitive decline in Alzheimer’s

    March 22, 2016 by Ashley

    From the University of Southampton media release:

    senior researcher with tabletA new study jointly led by the University of Southampton and King’s College London has found a link between gum disease and greater rates of cognitive decline in people with early stages of Alzheimer’s Disease.

    Periodontitis or gum disease is common in older people and may become more common in Alzheimer’s disease because of a reduced ability to take care of oral hygiene as the disease progresses. Higher levels of antibodies to periodontal bacteria are associated with an increase in levels of inflammatory molecules elsewhere in the body, which in turn has been linked to greater rates of cognitive decline in Alzheimer’s disease in previous studies.

    The latest study, published in the journal PLOS ONE, set out to determine whether periodontitis or gum disease is associated with increased dementia severity and subsequent greater progression of cognitive decline in people with Alzheimer’s disease.

    In the observational study, 59 participants with mild to moderate Alzheimer’s Disease were cognitively assessed and a blood sample was taken to measure inflammatory markers in their blood. Participants’ dental health was assessed by a dental hygienist who was blind to cognitive outcomes. The majority of participants (52) were followed-up at six months when all assessments were repeated.

    The presence of gum disease at baseline was associated with a six-fold increase in the rate of cognitive decline in participants over the six-month follow-up period of the study. Periodontitis at baseline was also associated with a relative increase in the pro-inflammatory state over the six-month follow-up period. The authors conclude that gum disease is associated with an increase in cognitive decline in Alzheimer’s Disease, possibly via mechanisms linked to the body’s inflammatory response.

    Limitations of the study included the small number of participants; the authors advise that the study should be replicated ideally with a larger cohort. The precise mechanisms by which gum disease may be linked to cognitive decline are not fully clear and other factors might also play a part in the decline seen in participants’ cognition alongside their oral health.

    However, growing evidence from a number of studies links the body’s inflammatory response to increased rates of cognitive decline, suggesting that it would be worth exploring whether the treatment of gum disease might also benefit the treatment of dementia and Alzheimer’s Disease.

    Professor Clive Holmes, senior author from the University of Southampton, says: “These are very interesting results which build on previous work we have done that shows that chronic inflammatory conditions have a detrimental effect on disease progression in people with Alzheimer’s disease. Our study was small and lasted for six months so further trials need to be carried out to develop these results. However, if there is a direct relationship between periodontitis and cognitive decline, as this current study suggests, then treatment of gum disease might be a possible treatment option for Alzheimer’s.”

    Dr Mark Ide, first author from the Dental Institute at King’s College London says: “Gum disease is widespread in the UK and US, and in older age groups is thought to be a major cause of tooth loss. In the UK in 2009, around 80% of adults over 55 had evidence of gum disease, whilst 40% of adults aged over 65-74 (and 60% of those aged over 75) had less than 21 of their original 32 teeth, with half of them reporting gum disease before they lost teeth.

    “A number of studies have shown that having few teeth, possibly as a consequence of earlier gum disease, is associated with a greater risk of developing dementia. We also believe, based on various research findings, that the presence of teeth with active gum disease results in higher body-wide levels of the sorts of inflammatory molecules which have also been associated with an elevated risk of other outcomes such as cognitive decline or cardiovascular disease. Research has suggested that effective gum treatment can reduce the levels of these molecules closer to that seen in a healthy state.

    Previous studies have also shown that patients with Alzheimer’s Disease have poorer dental health than others of similar age and that the more severe the dementia the worse the dental health, most likely reflecting greater difficulties with taking care of oneself as dementia becomes more severe.”

     


  6. Blueberries, the well-known super fruit, could help fight Alzheimer’s

    March 17, 2016 by Ashley

    From the American Chemical Society media release:

    [ File # csp7675513, License # 1824922 ] Licensed through http://www.canstockphoto.com in accordance with the End User License Agreement (http://www.canstockphoto.com/legal.php) (c) Can Stock Photo Inc. / Fotosmurf

    The blueberry, already labeled a ‘super fruit’ for its power to potentially lower the risk of heart disease and cancer, also could be another weapon in the war against Alzheimer’s disease.

    New research being presented today further bolsters this idea, which is being tested by many teams. The fruit is loaded with healthful antioxidants, and these substances could help prevent the devastating effects of this increasingly common form of dementia, scientists report.

    The researchers present their work today at the 251st National Meeting & Exposition of the American Chemical Society (ACS).

    “Our new findings corroborate those of previous animal studies and preliminary human studies, adding further support to the notion that blueberries can have a real benefit in improving memory and cognitive function in some older adults,” says Robert Krikorian, Ph.D., leader of the research team. He adds that blueberries’ beneficial effects could be due to flavonoids called anthocyanins, which have been shown to improve animals’ cognition.

    Currently 5.3 million people suffer from Alzheimer’s disease. But that number is expected to increase, Krikorian notes, as the U.S. population ages. By 2025, the number of Americans with this degenerative disorder could rise 40 percent to more than 7 million, and it could almost triple by 2050, according to the Alzheimer’s Association.

    In an effort to find ways to slow down this alarming trend, Krikorian and colleagues at University of Cincinnati Academic Health Center conducted two human studies to follow up on earlier clinical trials.

    One study involved 47 adults aged 68 and older, who had mild cognitive impairment, a risk condition for Alzheimer’s disease. The researchers gave them either freeze-dried blueberry powder, which is equivalent to a cup of berries, or a placebo powder once a day for 16 weeks.

    “There was improvement in cognitive performance and brain function in those who had the blueberry powder compared with those who took the placebo,” Krikorian says. “The blueberry group demonstrated improved memory and improved access to words and concepts.” The team also conducted functional magnetic resonance imaging (fMRI), which showed increased brain activity in those who ingested the blueberry powder.

    The second study included 94 people aged 62 to 80, who were divided into four groups. The participants didn’t have objectively measured cognitive issues, but they subjectively felt their memories were declining. The groups received blueberry powder, fish oil, fish oil and powder or placebo.

    “The results were not as robust as with the first study,” Krikorian explained. “Cognition was somewhat better for those with powder or fish oil separately, but there was little improvement with memory.” Also, fMRI results also were not as striking for those receiving blueberry powder. He says that the effect may have been smaller in this case because these participants had less severe issues when they entered the study.

    Krikorian said the two studies indicate that blueberries may be more effective in treating patients with cognitive impairments, but may not show measurable benefit for those with minor memory issues or who have not yet developed cognitive problems.

    In the future, the team plans to conduct a blueberry study with a younger group of people, aged 50 to 65. The group would include people at risk of developing Alzheimer’s, such as those who are obese, have high blood pressure or high cholesterol. This work could help the researchers determine if blueberries could help prevent the onset of Alzheimer’s symptoms.

     


  7. Nutritional drink can help to conserve memory in case of prodromal Alzheimer’s disease

    March 15, 2016 by Ashley

    From the Saarland University media release:

    memory lossThis is the first time a randomized, double-blind, clinical trial has shown that a nutritional intervention can help to conserve the ability of prodromal AD patients to carry out everyday tasks, such as paying bills, or finding your way around, as measured by the Clinical Dementia Rating-Sum of Boxes (CDR-SB) — a combined measure for the ability to think and perform everyday tasks. This is important because those with prodromal AD currently have no approved, available pharmacological options.

    The study did not find a significant benefit in broad cognitive function (the study primary endpoint). Cognitive decline over the study period was less than originally expected when it was designed ten years ago, so differences found between the two groups were too small to be statistically significant. Project coordinator Professor Tobias Hartmann, Saarland University Germany, explained that this is the most likely reason the primary endpoint was not met.

    Professor Hilkka Soininen, Professor in Neurology MD, PhD from the University of Eastern Finland, who headed the clinical trial as part of the LipiDiDiet project, said: “Today’s results are extremely valuable as they bring us closer to understanding the impact of nutritional interventions on prodromal AD which we are now better at diagnosing but unable to treat due to a lack of approved pharmaceutical options.

    The LipiDiDiet study illustrates that this nutritional intervention can help to conserve brain tissue and also memory and patients’ ability to perform everyday tasks — possibly the most troubling aspects of the disease. We look forward to the results of subsequent analyses and the six year extension study which will provide further insights.”

    The clinical trial, headed by Professor Hilkka Soininen is part of a large EC project (LipiDiDiet) to explore the therapeutic and preventative impact of nutrition on neuronal and cognitive performance in ageing, AD and vascular dementia. LipiDiDiet is funded by the seventh Framework Programme (FP7) of the European Commission (EC) and coordinated by Professor Hartmann, Saarland University in Germany.

    Fortasyn Connect was selected by a consortium of leading researchers from 19 European institutes, for this 24-month, randomised, controlled, double-blind, multicentre study involving 311 patients — on the basis of its results in a previous EU project (LipiDiet).

    Nearly 47 million people have Alzheimer’s or a related dementia for which there is currently no cure.2 This number is expected to double every 20 years, reaching 74.7 million in 2030 and 131.5 million in 2050.2

    Study details

    The trial was the first to investigate the impact of Fortasyn Connect on patients with prodromal AD who were randomised to receive either Fortasyn Connect or an iso-caloric control drink once daily.

    The primary outcome parameter was selected to assess the effect on cognitive function (a broad measure of thinking) during 24 months intake of Fortasyn Connect compared with a control product. This was a cognitive composite score consisting of the CERAD 10-word immediate recall, delayed recall and recognition, category fluency and letter digit substitution test.

    Secondary outcome parameters were brain volumes (total hippocampal, whole-brain & ventricular volumes), the Clinical Dementia Rating Sum of Boxes (CDR-SB), Neuropsychological Test Battery composite scores: episodic memory, executive function/working memory composite and a complete composite score consisting of 16 subtests, progression to (AD) dementia, blood and CSF biomarkers, tolerance and safety.

    No significant difference was observed for the cognitive composite score. Predefined analyses showed significant differences between active and control study groups for hippocampal and whole-brain atrophy, and favourable effects for CDR Sum of Boxes and episodic memory (both were most pronounced in patients with high baseline cognition with regular intake). Analyses are ongoing for progression to (AD) dementia and blood and CSF biomarkers.

    Tobias Hartmann, the project’s coordinator, said “We have known for a while that diet can reduce the risk of developing dementia. Indeed, certain nutrients have been found to have a neuroprotective effect on the brain. However translating this into an effective intervention hasn’t been easy because single nutrients simply aren’t powerful enough to fight a disease like Alzheimer’s alone. Today’s clinical trial results have shown that the key is combining certain nutrients, in order to increase their effect.

    This is exciting because it shows that in the absence of effective drug options, we really have found something that can help slow down some of the most distressing symptoms in prodromal AD; especially in those who started the intervention early. Indeed those patients who have lost the least cognitive function, have the most to gain.”


  8. Scientists may have found the ‘trigger’ of Alzheimer’s disease

    March 14, 2016 by Ashley

    From the Lomonosov Moscow State University media release:

    brain scanA group of the Lomonosov Moscow State University scientists, together with their colleagues from the Institute of Molecular Biology, Russian Academy of Sciences and the King’s College London, succeeded in sorting out the mechanism of Alzheimer’s disease development and possibly distinguished its key trigger. Their article was published in Scientific Reports.

    ‘Alzheimer’s disease is a widespread degenerative damage of central nervous system leading to a loss of mental ability. Until now it was considered incurable,’ tells Vladimir Polshakov, the leading researcher, MSU Faculty of Fundamental Medicine. Though now scientists managed to distinguish the mechanism ‘running’ the disease development, so, a chance appeared to elaborate some new chemical compounds, that may work as an efficient cure.

    Several hypotheses are dedicated to the Alzheimer’s disease development. One of the most common is the so-called amyloid hypothesis.

    Amyloids (to be precise, beta-amyloid peptides) are molecular constructions of a protein type and in its normal healthy state they provide a protection to the brain cells. They live fast, and having fulfilled their function they fall prey to the work of proteases, the cleaning enzymes that cut all the used protein elements into harmless ‘slags’ that are further reclaimed or removed from a body. However, according to the amyloid hypothesis, at some point something goes wrong, and the cells’ protectors turn to be their killers.

    Moreover, those peptides start gathering, forming aggregations and hence getting out of the reach of proteases’ cutting blades. Within the amyloid hypothesis this mechanism is more or less precisely described on the later stages of the disease, when the toxic aggregations appeared already and further, when the brain is covered with amyloid plaques. However, the early stage of a beta-amyloid transformation into harmful organic products is highly unexplored.

    ‘We knew, for example, that a crucial role in initiation of such processes is played by ions of several transition metals, first of all — zinc,’ tells Vladimir Polshakov. ‘Zinc actually conducts a number of useful and healthy functions in a brain, though in this case it was reasonably suspected as a ‘pest’, and particularly as an initiator of a cascade of processes, leading to the Alzheimer’s disease. However, it remained unclear, what exactly happens during an interaction of zin? ions with peptide molecules, which amino acids bind zinc ions, and how such interaction stipulates a peptide aggregation. We set a goal to clarify at least some of those questions’.

    Scientists studied various pathogenic beta-amyloid peptides, their so-called metal binding domains — relatively short peptide regions, capable to bind metal ions. A number of experimental techniques were applied, including nuclear magnetic resonance (NMR) spectroscopy, used to determine the structure of the forming molecular complexes. Some spectra requiring higher sensitivity were additionally measured in London. According to Polshakov, the choice of the studied pathogens was ‘partly a luck’. One of the specimens was the product of so-called ‘English mutation’ — peptide, different from a common beta-amyloid peptide only with one amino acid substitution. Using the NMR spectroscopy scientists managed to sort out chemical processes and structural changes while a peptide molecules interact with zinc ion and undergo further aggregation.

    The second pathogen was an isomerized beta-amyloid peptide. It was not different from a normal one in its chemical composition, though one of its amino acid residues, aspartic acid, was in a form with a specific atomic positioning. Such isomerism happens spontaneously, without help of any enzymes, and is related to the ageing processes, another influential factor of the Alzheimer’s disease. Fellow biologists from the Moscow’s Institute of Molecular Biology showed recently, that administration of an isomerized peptide to transgenic mice led to an accelerated formation of amyloid plaques.

    With the presence of zinc ions, a metal binding domain of the isomerized peptide aggregated so fast that the forming structures were hard to detect. Though scientists managed to distinguish that despite all the differences in processes occurring to the ‘English mutant’ and isomerized peptide in presence of zinc ions, initial stages of these transformations were similar. The trigger happened to be the same — a role of a pathogenic aggregation’s seed was in both cases played by initially formed peptide dimers, i.e. two peptide molecules, connected to each other with help of zinc ion. Such dimers were also detected in normal human peptides, and the difference in all the studied forms could be explained by the speed of formation of corresponding dimer and its proneness to a further aggregation.

    Based on their findings, researches proposed the mechanism of zinc-controlled transformation of a peptide-protector into a peptide-killer. That mechanism, scientists notice, explains multiple experimental data, not only gathered by the group, but also collected by their colleagues in other laboratories preoccupied with the Alzheimer’s disease studies. Researchers also hope that thanks to a very certain targeting their discovery would help to produce new medicine capable to block beta-amyloid peptide aggregation stipulated by zinc ions.


  9. Blackouts in the brain: New complex systems perspective on Alzheimer’s Disease

    March 1, 2016 by Ashley

    From the Mayo Clinic media release:

    mind mazeAlzheimer’s disease relentlessly targets large-scale brain networks that support the formation of new memories.

    However, it remains a mystery as to why the disease selectively targets memory-related brain networks and how this relates to misfolded proteins seen by pathologists at autopsy. In an effort to bridge the divide between the targeted memory systems and the misfolded proteins and dying cells underneath, Mayo Clinic researchers have turned to the field of complex systems — an emerging field of science that studies how parts of systems give rise to collective behaviors and how the system interacts with its environment.

    In a study of 128 participants in the Alzheimer’s Disease Neuroimaging Initiative, which is published in the February issue of the journal Brain, the team of researchers led by Mayo Clinic neurologist David Jones, M.D., proposed a disease model as a pathologic interaction within a complex system composed of large-scale brain networks and small-scale molecules. They looked into the activity of the default mode network or DMN (a brain system known for being active when we perform tasks involving memory or when invoking mental constructs), and related this activity to measures of Alzheimer’s proteins. Building on their previous work on DMN activity, the team found that a failure that starts in this system cascades through the brain via increases in activity. These increases in activity traditionally have been understood as a compensatory process; however, this new study suggests that they also may be propagating the disease process throughout brain systems — just like rerouting of power surges can cause blackouts in a power grid.

    “We found that this load-shifting process itself may be a major culprit for the development of the Alzheimer’s disease,” says Dr. Jones, the study’s lead investigator and author. “It is not unlike a cascading failure of a power grid. When a hub goes down, other areas of the network are forced to compensate. If the burden shift is too high, it blows off the circuits, and the power is down. This type of failure in our large brain networks may be responsible for the development of the Alzheimer’s disease.”

    These findings, Dr. Jones believes, support a system model that would open up new avenues of preventive therapeutic interventions targeting large-scale brain activity in the years or even decades before symptoms. “This would be akin to cardiologists encouraging the lowering of blood pressure decades before plaques ever develop in the arteries in the heart,” Dr. Jones says.


  10. Drug prevents key age-related brain change in rats

    February 10, 2016 by Ashley

    From the Society for Neuroscience media release:

    brain scansAs brain cells age they lose the fibers that receive neural impulses, a change that may underlie cognitive decline. Researchers at the University of California, Irvine recently found a way to reverse this process in rats.

    The study was published Feb. 3, 2016 in The Journal of Neuroscience. Researchers caution that more studies are needed, but the findings shed light on the mechanisms of cognitive decline and identify potential strategies to stem it.

    “There’s a tendency to think that aging is an inexorable process, that it’s something in the genes and there’s nothing you can do about it,” said study co-author Gary Lynch. “This paper is saying that may not be true.”

    The researchers studied dendrites — the branch-like fibers that extend from neurons and receive signals from other neurons — in rats. Evidence from other studies in rodents, monkeys, and humans indicates that dendrites dwindle with age and that this process — called dendritic retraction — occurs as early as middle age.

    The team, led by Lynch, Julie Lauterborn, and Linda Palmer, wanted to know whether dendritic retraction was already underway in 13-month-old or “middle-aged” rats and, if it was, could they reverse it by giving rats a compound called an ampakine. Ampakines had previously been shown to improve age-related cognitive deficits in rats as well as increase production of a key growth factor, brain-derived neurotrophic factor (BDNF) in the brain.

    The researchers housed 10-month-old male rats in cages with enriched environments. Unlike standard cages, these enhanced cages provided ample space, a large running wheel, and several objects for the rats to explore. Eleven rats received an oral dose of the ampakine each day for the next three months while the other 12 rats received a placebo. During this three-month window the researchers conducted behavioral testing by monitoring the rats’ activity as they explored an unfamiliar environment. After three months the researchers examined an area of the rats’ brains associated with learning and memory, the hippocampus, and compared that with the hippocampi of two-and-a-half-month-old or “adolescent” rats.

    “Middle-aged” rats given the placebo had shorter dendrites and fewer dendritic branches than the younger rats. The brains of rats given the ampakine, however, were mostly indistinguishable from the young rats — dendrites in both were similar in length and in the amount of branching. What’s more, the researchers also found that treated rats had significantly more dendritic spines, the small projections on dendrites that receive signals from other neurons, than either the untreated rats or the young rats.

    The researchers found that anatomical differences between the rats also correlated with differences in a biological measure of learning and memory: the treated rats showed enhanced signaling between neurons — a phenomenon called long-term potentiation.

    Finally, differences between treated rats and untreated rats appeared in behavioral testing. Typically, rats placed in a new environment spend a lot of time randomly exploring. As they become more familiar, they settle into predicable patterns of activity. Rats receiving ampakine settled into predictable patterns in a foreign play arena by the second day of testing whereas the placebo group of rats continued randomly exploring.

    The treated rats had better memory of the arena and developed strategies to explore,” Lynch said, pointing out that they had in effect reversed the effects of aging in the brain.

    “The importance of optimizing cognitive function across the lifespan cannot be overstated,” said Carol Barnes, a neuroscientist at the University of Arizona who studies the effects of aging on the brain and was not involved in the study. This study “is particularly interesting because the drug effect was selective in the brain functions and behaviors that were changed. This is the kind of specificity that could make translation to the clinic possible,” she added.

    However, the researchers caution that much work remains to be done before the drug is tested in people.

    “The next step is to repeat the study,” Lynch said, noting there are a lot of implications associated with this research and they need to proceed with care. The researchers would also want to explore how many days of treatment are necessary to see the same results and whether the drug would also work in older rats and females as well as males.