1. Review findings: Taking B vitamins will not prevent Alzheimer’s disease

    July 15, 2014 by Ashley

    From the University of Oxford media release:

    multivitaminsTaking B vitamins doesn’t slow mental decline as we age, nor is it likely to prevent Alzheimer’s disease, conclude Oxford University researchers who have assembled all the best clinical trial data involving 22,000 people to offer a final answer on this debate.

    High levels in the blood of a compound called homocysteine have been found in people with Alzheimer’s disease, and people with higher levels of homocysteine have been shown to be at increased risk of Alzheimer’s disease. Taking folic acid and vitamin B-12 are known to lower levels of homocysteine in the body, so this gave rise to the ‘homocysteine hypothesis’ that taking B vitamins could reduce the risk of Alzheimer’s disease.

    The new analysis was carried out by the B-Vitamin Treatment Trialists’ Collaboration, an international group of researchers led by the Clinical Trial Service Unit at the University of Oxford. The researchers brought together data from 11 randomised clinical trials involving 22,000 people which compared the effect of B vitamins on cognitive function in older people against placebo. Participants receiving B vitamins did see a reduction in the levels of homocysteine in their blood by around a quarter. However, this had no effect on their mental abilities.

    When looking at measures of global cognitive function — or scores for specific mental processes such as memory, speed or executive function — there was no difference between those on B vitamins and those receiving placebo to a high degree of accuracy.

    ‘It would have been very nice to have found something different,’ says Dr Robert Clarke of Oxford University, who led the work. ‘Our study draws a line under the debate: B vitamins don’t reduce cognitive decline as we age. Taking folic acid and vitamin B-12 is sadly not going to prevent Alzheimer’s disease.’

    The study was funded by the British Heart Foundation, the UK Medical Research Council (MRC), Cancer Research UK, the UK Food Standards Agency and the Department of Health. The findings are published in the American Journal of Clinical Nutrition.

    ‘Taking supplements like B vitamins doesn’t prevent heart disease, stroke or cognitive decline,’ says Professor Clarke. ‘About 25% of the adult population take multi-vitamins, often with the idea that they are also good for the heart or the brain, but the evidence just isn’t there. Much better is to eat more fruit and vegetables, avoid too much red meat and too many calories, and have a balanced diet.’

    Maternal folic acid intake before and during early pregnancy reduces a woman’s risk of having a neural tube defect birth defect and those thinking of having a baby are routinely advised to take folic acid supplements. Countries that have adopted mandatory population-wide folic acid fortification programmes have also demonstrated reductions in neural-tube defect associated pregnancies without any adverse effects [This is not correct — Ed].

    Dr Simon Ridley, Head of Research at Alzheimer’s Research UK, said:

    ‘Although one trial in 2010 showed that for people with high homocysteine, B vitamins had some beneficial effect on the rate of brain shrinkage, this comprehensive review of several trials shows that B vitamins have not been able to slow mental decline as we age, nor are they likely to prevent Alzheimer’s. While the outcome of this new and far reaching analysis is not what we hoped for, it does underline the need for larger studies to improve certainty around the effects of any treatment.

    ‘Alzheimer’s is feared by many and it’s natural that people want to take action to try to prevent the disease, but people should always speak to their GP before changing their diet to include vitamin supplements. Research to understand how to prevent Alzheimer’s must continue, and in the meantime evidence shows that a number of simple lifestyle changes can help reduce the risk of the disease. Eating a healthy, balanced diet, taking regular exercise and keeping blood pressure and weight in check can all help lower the risk of Alzheimer’s.

    Dr James Pickett, Head of Research at Alzheimer’s Society said:

    ‘Given that many previous studies have shown that vitamin B doesn’t slow the progression of dementia or reduce risk, it’s not a huge surprise that a review of all of the evidence finds much the same. While taking B vitamins may not help everyone, they may have some benefits in specific groups of people with dementia. However, this study suggests that we need much more work to establish more evidence for this.

    One in three people over the age of 65 will develop dementia and yet research funding lags behind other conditions and we haven’t seen a new treatment made available in a decade. We need to see significantly more investment and recruit the next generation of leaders in research in order to deliver breakthroughs that could prove so vital to those affected by the condition.’

    Hugh Perry, chair of the MRC Neurosciences and Mental Health Board, said:

    ‘Science progresses through testing and re-testing previous research and sometimes overturning existing theories. Health advice always needs to be based on the best available data from the largest possible studies and this is even more important when the findings have implications for what we do or don’t eat and drink.’

    Clarke R, Bennet D, Parish S, Lewington S, Skeaff M, Eussen SJPM, Lewerin C, Stott DJ, Armitage J, Hankey GJ, Lonn E, Spence D, Galan P, de Groot LC, Halsey J, Dangour AD, Collins R, Grodstein F, on behalf of the B-Vitamin Treatment Trialists’ Collaboration. Effects of homocysteine lowering with B vitamins on cognitive aging: meta-analysis of 11 trials with cognitive data on 22,000 individuals. American Journal of Clinical Nutrition. 2014; 100:657-66. http://ajcn.nutrition.org/content/early/2014/06/25/ajcn.113.076349.abstract


  2. Study suggests brain’s “garbage truck” may hold key to treating Alzheimer’s and other disorders

    July 8, 2013 by Ashley

    From the University of Rochester Medical Center press release via ScienceDaily:

    senior alzheimerIn a perspective piece appearing today in the journal Science, researchers at University of Rochester Medical Center (URMC) point to a newly discovered system by which the brain removes waste as a potentially powerful new tool to treat neurological disorders like Alzheimer’s disease. In fact, scientists believe that some of these conditions may arise when the system is not doing its job properly.

    “Essentially all neurodegenerative diseases are associated with the accumulation of cellular waste products,” said Maiken Nedergaard, M.D., D.M.Sc., co-director of the URMC Center for Translational Neuromedicine and author of the article. “Understanding and ultimately discovering how to modulate the brain’s system for removing toxic waste could point to new ways to treat these diseases.”

    The body defends the brain like a fortress and rings it with a complex system of gateways that control which molecules can enter and exit. While this “blood-brain barrier” was first described in the late 1800s, scientists are only now just beginning to understand the dynamics of how these mechanisms function. In fact, the complex network of waste removal, which researchers have dubbed the glymphatic system, was only first disclosed by URMC scientists last August in the journal Science Translational Medicine.

    The removal of waste is an essential biological function and the lymphatic system — a circulatory network of organs and vessels — performs this task in most of the body. However, the lymphatic system does not extend to the brain and, consequently, researchers have never fully understood what the brain does its own waste. Some scientists have even speculated that these byproducts of cellular function where somehow being “recycled” by the brain’s cells.

    One of the reasons why the glymphatic system had long eluded comprehension is that it cannot be detected in samples of brain tissue. The key to discovering and understanding the system was the advent of a new imaging technology called two-photon microscopy which enables scientists to peer deep within the living brain. Using this technology on mice, whose brains are remarkably similar to humans, Nedergaard and her colleagues were able to observe and document what amounts to an extensive, and heretofore unknown, plumbing system responsible for flushing waste from throughout the brain.

    The brain is surrounded by a membrane called the arachnoid and bathed in cerebral spinal fluid (CSF). CSF flows into the interior of the brain through the same pathways as the arteries that carry blood. This parallel system is akin to a donut shaped pipe within a pipe, with the inner ring carrying blood and the outer ring carrying CSF. The CSF is draw into brain tissue via a system of conduits that are controlled by a type support cells in the brain known as glia, in this case astrocytes. The term glymphatic was coined by combining the words glia and lymphatic.

    The CSF is flushed through the brain tissue at a high speed sweeping excess proteins and other waste along with it. The fluid and waste are exchanged with a similar system that parallels veins which carries the waste out of the brain and down the spine where it is eventually transferred to the lymphatic system and from there to the liver, where it is ultimately broken down.

    While the discovery of the glymphatic system solved a mystery that had long baffled the scientific community, understanding how the brain removes waste — both effectively and what happens when this system breaks down — has significant implications for the treatment of neurological disorders.

    One of the hallmarks of Alzheimer’s disease is the accumulation in the brain of the protein beta amyloid. In fact, over time these proteins amass with such density that they can be observed as plaques on scans of the brain. Understanding what role the glymphatic system plays in the brain’s inability to break down and remove beta amyloid could point the way to new treatments. Specifically, whether certainly key ‘players’ in the glymphatic system, such as astrocytes, can be manipulated to ramp up the removal of waste.

    The idea that ‘dirty brain’ diseases like Alzheimer may result from a slowing down of the glymphatic system as we age is a completely new way to think about neurological disorders,” said Nedergaard. “It also presents us with a new set of targets to potentially increase the efficiency of glymphatic clearance and, ultimately, change the course of these conditions.”


  3. Study identifies protein that contributes to cognitive decline in Alzheimer’s

    July 2, 2013 by Ashley

    From the Columbia University Medical Center press release via EurekAlert!:

    confused seniorResearchers at Columbia University Medical Center (CUMC) have demonstrated that a protein called caspase-2 is a key regulator of a signaling pathway that leads to cognitive decline in Alzheimer’s disease.

    The findings, made in a mouse model of Alzheimer’s, suggest that inhibiting this protein could prevent the neuronal damage and subsequent cognitive decline associated with the disease. The study was published this month in the online journal Nature Communications.

    One of the earliest events in Alzheimer’s is disruption of the brain’s synapses (the small gaps across which nerve impulses are passed), which can lead to neuronal death. Although what drives this process has not been clear, studies have indicated that caspace-2 might be involved, according to senior author Michael Shelanski, MD, PhD, the Delafield Professor of Pathology & Cell Biology, chair of the Department of Pathology & Cell Biology, and co-director of the Taub Institute for Research on Alzheimer’s Disease and the Aging Brain at CUMC.

    Several years ago, in tissue culture studies of mouse neurons, Dr. Shelanski found that caspace-2 plays a critical role in the death of neurons in the presence of amyloid beta, the protein that accumulates in the neurons of people with Alzheimer’s. Other researchers have shown that caspase-2 also contributes to the maintenance of normal synaptic functions.

    Dr. Shelanski and his team hypothesized that aberrant activation of caspase-2 may cause synaptic changes in Alzheimer’s disease. To test this hypothesis, the researchers crossed J20 transgenic mice (a common mouse model of Alzheimer’s) with caspase-2 null mice (mice that lack caspase-2). They compared the animals’ ability to negotiate a radial-arm water maze, a standard test of cognitive ability, with that of regular J20 mice and of normal mice at 4, 9, and 14 months of age.

    The results for the three groups of mice were similar at the first two intervals. At 14 months, however, the J20/caspase-2 null mice did significantly better in the water maze test than the J20 mice and similarly to the normal mice. “We showed that removing caspase-2 from J20 mice prevented memory impairment — without significant changes in the level of soluble amyloid beta,” said co-lead author Roger Lefort, PhD, associate research scientist at CUMC.

    Analysis of the neurons showed that the J20/caspase-2 null mice had a higher density of dendritic spines than the J20 mice. The more spines a neuron has, the more impulses it can transmit.

    “The J20/caspase-2 null mice showed the same dendritic spine density and morphology as the normal mice—as opposed to the deficits in the J20 mice,” said co-lead author Julio Pozueta, PhD. “This strongly suggests that caspase-2 is a critical regulator in the memory decline associated with beta-amyloid in Alzheimer’s disease.”

    The researchers further validated the results in studies of rat neurons in tissue culture.

    Finally, the researchers found that caspase-2 interacts with RhoA, a critical regulator of the morphology (form and structure) of dendritic spines. “It appears that in normal neurons, caspase-2 and RhoA form an inactive complex outside the dendritic spines,” said Dr. Lefort. “When the complex is exposed to amyloid beta, it breaks apart, activating the two components.” Once activated, caspase-2 and RhoA enter the dendritic spines and contribute to their demise, possibly by interacting with a third molecule, the enzyme ROCK-II.

    This raises the possibility that if you can inhibit one or all of these molecules, especially early in the course of Alzheimer’s, you might be able to protect neurons and slow down the cognitive effects of the disease,” said Dr. Lefort.


  4. Study suggests memory improves for older adults using computerized brain-fitness program

    by Ashley

    From the UCLA press release via EurekAlert!:

    computer gaming seniorsUCLA researchers have found that older adults who regularly used a brain-fitness program on a computer demonstrated significantly improved memory and language skills.

    The UCLA team studied 69 dementia-free participants, with an average age of 82, who were recruited from retirement communities in Southern California. The participants played a computerized brain-fitness program called Dakim BrainFitness, which trains individuals through more than 400 exercises in the areas of short- and long-term memory, language, visual-spatial processing, reasoning and problem-solving, and calculation skills.

    The researchers found that of the 69 participants, the 52 individuals who over a six-month period completed at least 40 sessions (of 20 minutes each) on the program showed improvement in both immediate and delayed memory skills, as well as language skills.

    The findings suggest that older adults who participate in computerized brain training can improve their cognitive skills.

    The study’s findings add to a body of research exploring whether brain fitness tools may help improve language and memory and ultimately help protect individuals from the cognitive decline associated with aging and Alzheimer’s disease.

    Age-related memory decline affects approximately 40 percent of older adults. And while previous studies have shown that engaging in stimulating mental activities can help older adults improve their memory, little research had been done to determine whether the numerous computerized brain-fitness games and memory training programs on the market are effective in improving memory. This is one of the first studies to assess the cognitive effects of a computerized memory-training program.


  5. Study suggests storytelling program may help change medical students’ perspectives on dementia

    June 29, 2013 by Ashley

    From the Pennsylvania State University press release via EurekAlert!:

    doctor with patientTreating patients with dementia can be viewed as a difficult task for doctors, but Penn State College of Medicine researchers say that storytelling may be one way to improve medical students’ perceptions of people affected by the condition. Participation in a creative storytelling program called TimeSlips creates a substantial improvement in student attitudes.

    Daniel George, assistant professor of humanities, tested the effects of the TimeSlips program in an elective course he teaches at the college. Fourth-year medical students worked with patients at Country Meadows, a Hershey-based assisted living community. These patients are affected by advanced dementia and live in a memory-support unit requiring a locked environment.

    Medical students commonly perceive persons with dementia as being challenging to work with.

    “We currently lack effective drugs for dementia, and there’s a sense that these are cases where students can’t do much to benefit the patient,” George said. “The perception is that they’re hard to extract information from, you don’t know if that information is reliable, and there are often other complicated medical issues to deal with.”

    TimeSlips is a non-pharmacological approach to dementia care that uses creative storytelling in a group setting and encourages participants to use their imagination rather than focusing on their inability to remember chronologically. Pictures with a staged, surreal image –for example, an elephant sitting on a park bench — are shared with all participants, who are encouraged to share their impressions of what is happening in the picture. As part of George’s elective, medical students spent one month facilitating TimeSlips with groups of five to 10 residents and helping the residents build stories in poem form during their interactions.

    “All comments made during a session — even ones that do not necessarily make logical sense — are validated and put into the poem because it is an attempt to express meaning,” George said. “The sessions become energetic and lively as the residents are able to communicate imaginatively, in a less linear way. In the process, students come to see dementia differently. It is very humanizing, revealing personality and remaining strengths where our culture tends to just focus on disease, decline and loss.”

    Student attitudes were measured before and after the TimeSlips experience using a validated instrument called the Dementia Attitudes Scale. A significant improvement in overall attitude was observed over the course of the program, and students also demonstrated significant increases on sub-scales measuring comfort with people with dementia and knowledge about interacting with and treating these patients. Results were reported in the journal Academic Medicine.

    “In talking with my students, they consistently express their anxieties about medical school training them to see patients as a diagnosis rather than as a fully-fledged person,” George said. “An activity like TimeSlips, which emphasizes the creative spirit in people with fairly advanced dementia, helps give students a richer sense of who the person was and what made them tick.”

    At Penn State College of Medicine, which emphasizes the humanities in medical care and established the first Department of Humanities at a medical school in the nation, George hopes to expand TimeSlips volunteer opportunities to include all medical students and not exclusively fourth-year students. By reaching students earlier in their education and exposing them to a creative activity involving people with dementia, he hopes that TimeSlips could help nudge more trainees into geriatric medicine.

    As the incidence of dementia-related conditions is rising globally, the demand for high-quality, humanistic geriatric care is becoming more urgent,” George said.

    There has already been an effort to extend TimeSlips volunteer opportunities to nurses, faculty, staff and patients.

    “Several patients from our hospital, Penn State Milton S. Hershey Medical Center, have already begun taking part in the program,” he said. “Even though they are experiencing their own illnesses, they are able to find purpose in helping another vulnerable population through creative storytelling.”


  6. Study suggests blocking overactive receptor in Alzheimer’s recovers memory loss and more

    June 22, 2013 by Ashley

    From the Montreal Neurological Institute and Hospital press release via EurekAlert!:

    brain scanA new study shows that memory pathology in older mice with Alzheimer’s disease can be reversed with treatment.

    The study by researchers from the Montreal Neurological Institute and Hospital – The Neuro, at McGill University and at Université de Montréal found that blocking the activity of a specific receptor in the brain of mice with advanced Alzheimer’s disease (AD) recovers memory and cerebrovascular function. The results, published in the Journal of Neuroinflammation in May, also suggest an underlying mechanism of AD as a potential target for new therapies.

    “The exciting and important aspect of this study is that even animals with advanced pathology can be rescued with this molecule” says Dr. Edith Hamel, neuroscientist at The Neuro and lead investigator on the paper in collaboration with Dr Réjean Couture at the Department of Physiology at Université de Montréal. “We have rarely seen this type of reversal of AD symptoms before in our mouse model at this advanced age – when mice have been developing AD for one year.”

    The researchers found an increased level of a receptor known as bradykinin B1 receptor (B1R) in the brain of mice with AD, a receptor involved in inflammation.  “By administering a molecule that selectively blocks the action of this receptor, we observed important improvements in both cognitive and cerebrovascular function,” says Dr. Baptiste Lacoste, research fellow who conducted the study at The Neuro and now pursuing his training at Harvard Medical School in Boston.

    Alzheimer’s disease destroys nerve cells and also compromises the function of blood vessels in the brain. Not only were there improvements in learning and memory, but also marked recovery in blood flow and vascular reactivity, i.e. the ability of cerebral vessels to dilate or constrict when necessary.” Proper functioning of blood vessels in the brain is vital to providing nutrients and oxygen to nerve cells, and vascular diseases represent important risk factors for developing AD at an advanced age.x

    “Another interesting result that has not been seen before in our mouse model is a reduction by over 50% of toxic amyloid-beta peptide,” adds Dr. Hamel.  “In Alzheimer’s disease, protein fragments called amyloid-beta have a deleterious effect on the blood and nervous systems. Normally, these protein fragments are broken down and removed. In Alzheimer’s disease, the protein fragments clump together — a factor believed to contribute to neuronal and vascular dysfunction. We are not sure if these decreases contribute to the functional recovery, but we hope that our findings will aid in clarifying this issue and identifying new targets for therapeutic approaches.”

    The results show that an increase in B1R is associated with amyloid-beta plaques in Alzheimer’s disease mice with impaired memory, and that chronic blockade of B1R significantly improves learning, memory, cerebrovascular function, and several other pathological AD hallmarks in mice with a fully developed pathology. Together, these findings confirm a role of B1R in AD pathogenesis and the role of neuroinflammation as an underlying mechanism in AD. The next step would be to further investigate potential blockers of the bradykinin B1R as a potential treatment for AD in humans.

    This study was funded by the Canadian Institutes of Health Research and a postdoctoral fellowship award from the Alzheimer Society of Canada.

    Link to the study:  http://www.jneuroinflammation.com/content/10/1/57/abstract

     


  7. Study suggests stress hormone could trigger mechanism for the onset of Alzheimer’s

    by Ashley

    From the Temple University press release via HealthCanal:

    senior_medicationA chemical hormone released in the body as a reaction to stress could be a key trigger of the mechanism for the late onset of Alzheimer’s disease, according to a study by researchers at Temple University.

    Previous studies have shown that the chemical hormone corticosteroid, which is released into the body’s blood as a stress response, is found at levels two to three times higher in Alzheimer’s patients than non-Alzheimer’s patients.

    “Stress is an environmental factor that looks like it may play a very important role in the onset of Alzheimer’s disease,” said Domenico Praticò, professor of pharmacology and microbiology and immunology in Temple’s School of Medicine, who led the study. “When the levels of corticosteroid are too high for too long, they can damage or cause the death of neuronal cells, which are very important for learning and memory.”

    In their study, “Knockout of 5-lipoxygenase prevents dexamethasone-induced tau pathology in 3xTg mice,” published in the journal Aging Cell, the Temple researchers set up a series of experiments to examine the mechanisms by which stress can be responsible for the Alzheimer’s pathology in the brain.

    Using triple transgenic mice, which develop amyloid beta and the tau protein, two major brain lesion signatures for Alzheimer’s, the Temple researchers injected one group with high levels of corticosteroid each day for a week in order to mimic stress.

    While they found no significant difference in the mice’s memory ability at the end of the week, they did find that the tau protein was significantly increased in the group that received the corticosteroid. In addition, they found that the synapses, which allow neuronal cells to communicate and play a key role in learning and memory, were either damaged or destroyed.

    “This was surprising because we didn’t see any significant memory impairment, but the pathology for memory and learning impairment was definitely visible,” said Pratico. “So we believe we have identified the earliest type of damage that precedes memory deficit in Alzheimer’s patients.”

    Pratico said another surprising outcome was that a third group of mice that were genetically altered to be devoid of the brain enzyme 5-lipoxygenase appeared to be immune and showed no neuronal damage from the corticosteroid.

    In previous studies, Pratico and his team have shown that elevated levels of 5-lipoxygenase cause an increase in tau protein levels in regions of the brain controlling memory and cognition, disrupting neuronal communications and contributing to Alzheimer’s disease. It also increases the levels of amyloid beta, which is thought to be the cause for neuronal death and forms plaques in the brain.

    Pratico said the corticosteroid causes the 5-lipoxygenase to over-express and increase its levels, which in turn increases the levels of the tau protein and amyloid beta.

    “The question has always been what up-regulates or increases 5-lipoxygenase, and now we have evidence that it is the stress hormone,” he said. “We have identified a mechanism by which the risk factor — having high levels of corticosteroid — could put you at risk for the disease.

    “Corticosteroid uses the 5-lipoxygenase as a mechanism to damage the synapse, which results in memory and learning impairment, both key symptoms for Alzheimer’s,” said Pratico. “So that is strong support for the hypothesis that if you block 5-lipoxygenase, you can probably block the negative effects of corticosteroid in the brain.”

    The research was supported by National Institutes of Health and the Alzheimer Art Quilt Initiative.


  8. Study suggests Alzheimer’s and low blood sugar in diabetes may feed into each other

    June 12, 2013 by Ashley

    From the UCSF press release by Jeffrey Norris via HealthCanal:

    senior_medicationA new UC San Francisco-led study looks at the close link between diabetes and dementia, which can create a vicious cycle.

    Diabetes-associated episodes of low blood sugar may increase the risk of developing dementia, while having dementia or even milder forms of cognitive impairment may increase the risk of experiencing low blood sugar, according to the study published online Monday in JAMA Internal Medicine.

    Researchers analyzed data from 783 diabetic participants and found that hospitalization for severe hypoglycemia among the diabetic, elderly participants in the study was associated with a doubled risk of developing dementia later. Similarly, study participants with dementia were twice as likely to experience a severe hypoglycemic event.

    The study results suggest some patients risk entering a downward spiral in which hypoglycemia and cognitive impairment fuel one another, leading to worse health, said Kristine Yaffe, MD, senior author and principal investigator for the study, and a UCSF professor of psychiatry, neurology and epidemiology based at the San Francisco Veterans Affair Medical Center.

    “Older patients with diabetes may be especially vulnerable to a vicious cycle in which poor diabetes management may lead to cognitive decline and then to even worse diabetes management,” she said.

    Cognitive Function a Factor in Managing Diabetes

    The researchers analyzed hospital records of patients from Memphis and Pittsburgh, ages 70 to 79 at the time of enrollment, who participated in the federally funded Health, Aging and Body Composition (Health ABC) study, begun in 1997. The UCSF results are based on an average of 12 years of follow-up study. Participants in the Health ABC study periodically underwent tests to measure cognitive function.

    Nearly half of participants included in the newly published analysis were black, and the rest were white. None had dementia at the start of the study, and all either had diabetes at the beginning of the study or were diagnosed during the course of the study.

    “Individuals with dementia or even those with milder forms of cognitive impairment may be less able to effectively manage complex treatment regimens for diabetes and less able to recognize the symptoms of hypoglycemia and to respond appropriately, increasing their risk of severe hypoglycemia,” Yaffe said. “Physicians should take cognitive function into account in managing diabetes in elderly individuals.”

    Certain medications known to carry a higher risk for hypoglycemia — such as insulin secretagogues and certain sulfonylureas — may be inappropriate for older adults with dementia or who are at risk for cognitive impairment, according to Yaffe.

    Previous studies in which researchers investigated hypoglycemia and cognitive function have had inconsistent findings. A strength of the current study is that individuals were tracked from baseline over a relatively long time, and the older age of participants may also have been a factor in the highly statistically significant outcome, Yaffe said.

    Additional authors of the study were, Cherie Falvey, MPH, Ann Schwartz, PhD, MPH, and Nathan Hamilton from UCSF; Tamara Harris, MD, and Eleanor Simonsick, PhD, from the National Institute of Aging; Elsa Strotmeyer, PhD, MPH, and Andrea Metti, MPH, of the University of Pittsburgh; and Ronald Shorr, MD, of the University of Florida.

    The study was funded by the National Institutes of Health and by the American Health Assistance Foundation. Yaffe has served on data safety monitoring boards for Takeda Inc., Pfizer Inc., and Medivation Inc. and has served as a consultant for Novartis Inc.

     


  9. Researchers suggest new perspective needed for role of major Alzheimer’s gene

    May 31, 2013 by Ashley

    From the Washington University School of Medicine in St. Louis press release by Michael C. Purdy via HealthCanal:

    senior_medicationScientists’ picture of how a gene strongly linked to Alzheimer’s disease harms the brain may have to be revised, researchers at Washington University School of Medicine in St. Louis have found.

    People with harmful forms of the APOE gene have up to 12 times the risk of developing Alzheimer’s disease compared with those who have other variations of the gene.

    Many researchers believe that the memory loss and cognitive problems of Alzheimer’s result from the buildup over many years of brain amyloid plaques. The plaques are made mostly of a sticky substance called amyloid beta.

    For years, researchers have thought that the APOE gene increases Alzheimer’s risk by producing a protein that binds to amyloid beta. Scientists thought that this bond could make it easier for plaques to form.

    But in a new study now available online in the Proceedings of the National Academy of Sciences, Washington University researchers show that APOE and amyloid beta don’t bind together in cerebrospinal fluid and in fluids present outside cells grown in dishes. This means they are unlikely to bind together in the fluids circulating in the brain. The cerebrospinal fluid was taken from people who were cognitively normal but have forms of APOE that increase the risk of Alzheimer’s.

    “This is the first time we’ve looked at naturally produced APOE and amyloid beta to see if and how much they bind together, and we found that they have very little interaction in the fluids bathing the brain,” said David M. Holtzman, MD, the Andrew B. and Gretchen P. Jones Professor and head of neurology. “This suggests that we may need to rethink any therapeutic strategies that target APOE to slow amyloid plaque accumulation and Alzheimer’s.

    According to Holtzman, leading Alzheimer’s researchers recently agreed that targeting APOE is a promising approach both for gaining a better understanding of and improving treatments for Alzheimer’s. But to do that, scientists must first fully understand how the harmful forms of APOE increase risk of the disease.

    APOE is a major player in Alzheimer’s, there’s no question about that,” said Philip Verghese, PhD, a postdoctoral research associate. “We did some additional studies in mice and cell cultures that suggested the APOE protein may be blocking a pathway that normally helps degrade amyloid beta.”

    APOE is involved in the metabolism of fats, cholesterol and vitamins throughout the body. Scientists have identified three different forms of the gene that each make a slightly different version of the protein.

    One version, APOE 2, produces a protein that significantly reduces Alzheimer’s risk. Another, APOE 4, increases risk. Each person has two copies of the gene, and if both copies are APOE 4, the chance of developing Alzheimer’s rises dramatically.

    “About 60 percent of the patients we see in the Alzheimer’s clinics have at least one copy of APOE 4,” Holtzman said. “In contrast, only about 25 percent of cognitively normal 70-year-olds have a copy of APOE 4.”

    Verghese tested cerebrospinal fluid samples from people who had either two copies of APOE 4 or two copies of APOE 3, another form of the gene that is not associated with  increased Alzheimer’s risk.

    We also found that APOE 2, the protective form of the protein, doesn’t bind to amyloid beta in body fluids,” Verghese said.

    In follow-up studies, Verghese showed that APOE and amyloid beta “compete” to bind to a receptor on support cells in the brain known as astrocytes.

    “Studies by other researchers have shown that astrocytes can degrade amyloid beta,” Verghese said. “The receptor we identified may be important for getting amyloid beta into the astrocyte so it can be broken down. It’s possible that when the harmful forms of APOE bind to the receptor, this reduces the opportunities for amyloid to be degraded.”

    The researchers are planning follow-up studies of the effects of APOE-blocking treatments in mice.


  10. Study suggests cinnamon compounds may potentially help prevent Alzheimer’s

    May 29, 2013 by Ashley

    From the UC Santa Barbara press release via EurekAlert!:

    cinnamonCinnamon: Can the red-brown spice with the unmistakable fragrance and variety of uses offer an important benefit? The common baking spice might hold the key to delaying the onset of –– or warding off –– the effects of Alzheimer’s disease.

    That is, according to Roshni George and Donald Graves, scientists at UC Santa Barbara. The results of their study, “Interaction of Cinnamaldehyde and Epicatechin with Tau: Implications of Beneficial Effects in Modulating Alzheimer’s Disease Pathogenesis,” appears in the online early edition of the Journal of Alzheimer’s Disease, and in the upcoming Volume 36, issue 1 print edition.

    Alzheimer’s disease is the most common form of dementia, a neurodegenerative disease that progressively worsens over time as it kills brain cells. No cure has yet been found, nor has the major cause of Alzheimer’s been identified.

    However, two compounds found in cinnamon –– cinnamaldehyde and epicatechin –– are showing some promise in the effort to fight the disease. According to George and Graves, the compounds have been shown to prevent the development of the filamentous “tangles” found in the brain cells that characterize Alzheimer’s.

    Responsible for the assembly of microtubules in a cell, a protein called tau plays a large role in the structure of the neurons, as well as their function.

    “The problem with tau in Alzheimer’s is that it starts aggregating,” said George, a graduate student researcher. When the protein does not bind properly to the microtubules that form the cell’s structure, it has a tendency to clump together, she explained, forming insoluble fibers in the neuron. The older we get the more susceptible we are to these twists and tangles, Alzheimer’s patients develop them more often and in larger amounts.

    The use of cinnamaldehyde, the compound responsible for the bright, sweet smell of cinnamon, has proven effective in preventing the tau knots. By protecting tau from oxidative stress, the compound, an oil, could inhibit the protein’s aggregation. To do this, cinnamaldehyde binds to two residues of an amino acid called cysteine on the tau protein. The cysteine residues are vulnerable to modifications, a factor that contributes to the development of Alzheimer’s.

    “Take, for example, sunburn, a form of oxidative damage,” said Graves, adjunct professor in UCSB’s Department of Molecular, Cellular, and Developmental Biology. “If you wore a hat, you could protect your face and head from the oxidation. In a sense this cinnamaldehyde is like a cap.” While it can protect the tau protein by binding to its vulnerable cysteine residues, it can also come off, Graves added, which can ensure the proper functioning of the protein.

    Oxidative stress is a major factor to consider in the health of cells in general. Through normal cellular processes, free radical-generating substances like peroxides are formed, but antioxidants in the cell work to neutralize them and prevent oxidation. Under some conditions however, the scales are tipped, with increased production of peroxides and free radicals, and decreased amounts of antioxidants, leading to oxidative stress.

    Epicatechin, which is also present in other foods, such as blueberries, chocolate, and red wine, has proven to be a powerful antioxidant. Not only does it quench the burn of oxidation, it is actually activated by oxidation so the compound can interact with the cysteines on the tau protein in a way similar to the protective action of cinnamaldehyde.

    Cell membranes that are oxidized also produce reactive derivatives, such as Acrolein, that can damage the cysteines,” said George. “Epicatechin also sequesters those byproducts.”

    Studies indicate that there is a high correlation between Type 2 diabetes and the incidence of Alzheimer’s disease. The elevated glucose levels typical of diabetes lead to the overproduction of reactive oxygen species, resulting in oxidative stress, which is a common factor in both diabetes and Alzheimer’s disease. Other research has shown cinnamon’s beneficial effects in managing blood glucose and other problems associated with diabetes.

    Since tau is vulnerable to oxidative stress, this study then asks whether Alzheimer’s disease could benefit from cinnamon, especially looking at the potential of small compounds,” said George.

    Although this research shows promise, Graves said, they are “still a long way from knowing whether this will work in human beings.” The researchers caution against ingesting more than the typical amounts of cinnamon already used in cooking.

    If cinnamon and its compounds do live up to their promise, it could be a significant step in the ongoing battle against Alzheimer’s. A major risk factor for the disease –– age –– is uncontrollable. In the United States, Alzheimer’s presents a particular problem as the population lives longer and the Baby Boom generation turns gray, leading to a steep rise in the prevalance of the disease. It is a phenomenon that threatens to overwhelm the U.S. health care system. According to the Alzheimer’s Association, in 2013, Alzheimer’s disease will cost the nation $203 billion.

    Wouldn’t it be interesting if a small molecule from a spice could help?” commented Graves, “perhaps prevent it, or slow down the progression.”