1. 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.”


  2. 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

     


  3. 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.


  4. 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.

     


  5. Study suggests healthy lifestyle choices mean fewer memory complaints

    June 6, 2013 by Ashley

    From the UCLA press release via ScienceDaily:

    senior computer userResearch has shown that healthy behaviors are associated with a lower risk of Alzheimer’s disease and dementia, but less is known about the potential link between positive lifestyle choices and milder memory complaints, especially those that occur earlier in life and could be the first indicators of later problems.

    To examine the impact of these lifestyle choices on memory throughout adult life, UCLA researchers and the Gallup organization collaborated on a nationwide poll of more than 18,500 individuals between the ages of 18 and 99. Respondents were surveyed about both their memory and their health behaviors, including whether they smoked, how much they exercised and how healthy their diet was.

    As the researchers expected, healthy eating, not smoking and exercising regularly were related to better self-perceived memory abilities for most adult groups. Reports of memory problems also increased with age. However, there were a few surprises.

    Older adults (age 60-99) were more likely to report engaging in healthy behaviors than middle-aged (40-59) and younger adults (18-39), a finding that runs counter to the stereotype that aging is a time of dependence and decline. In addition, a higher-than-expected percentage of younger adults complained about their memory.

    These findings reinforce the importance of educating young and middle-aged individuals to take greater responsibility for their health — including memory — by practicing positive lifestyle behaviors earlier in life,” said the study’s first author, Dr. Gary Small, director of the UCLA Longevity Center and a professor of psychiatry and biobehavioral sciences at the Semel Institute for Neuroscience and Human Behavior at UCLA who holds the Parlow-Solomon Chair on Aging.

    Published in the June issue of International Psychogeriatrics, the study may also provide a baseline for the future study of memory complaints in a wide range of adult age groups.

    For the survey, Gallup pollsters conducted land-line and cell phone interviews with 18,552 adults in the U.S. The inclusion of cell phone-only households and Spanish-language interviews helped capture a representative 90 percent of the U.S. population, the researchers said.

    “We found that the more healthy lifestyle behaviors were practiced, the less likely one was to complain about memory issues,” said senior author Fernando Torres-Gil, a professor at UCLA’s Luskin School of Public Affairs and associate director of the UCLA Longevity Center.

    In particular, the study found that respondents across all age groups who engaged in just one healthy behavior were 21 percent less likely to report memory problems than those who didn’t engage in any healthy behaviors. Those with two positive behaviors were 45 percent less likely to report problems, those with three were 75 percent less likely, and those with more than three were 111 percent less likely.

    Interestingly, the poll found that healthy behaviors were more common among older adults than the other two age groups. Seventy percent of older adults engaged in at least one healthy behavior, compared with 61 percent of middle-aged individuals and 58 percent of younger respondents.

    In addition, only 12 percent of older adults smoked, compared with 25 percent of young adults and 24 percent of middle-aged adults, and a higher percentage of older adults reported eating healthy the day before being interviewed (80 percent) and eating five or more daily servings of fruits and vegetables during the previous week (64 percent).

    According to the researchers, older adults may participate in more healthy behaviors because they feel the consequences of unhealthy living and take the advice of their doctors to adopt healthier lifestyles. Or there simply could be fewer older adults with bad habits, since they may not live as long.

    While 26 percent of older adults and 22 percent of middle-aged respondents reported memory issues, it was surprising to find that 14 percent of the younger group complained about their memory too, the researchers said.

    “Memory issues were to be expected in the middle-aged and older groups, but not in younger people,” Small said. “A better understanding and recognition of mild memory symptoms earlier in life may have the potential to help all ages.”

    Small said that, generally, memory issues in younger people may be different from those that plague older generations. Stress may play more of a role. He also noted that the ubiquity of technology — including the Internet, texting and wireless devices that can result in constant multi-tasking, especially with younger people — may impact attention span, making it harder to focus and remember.

    Small noted that further study and polling may help tease out such memory-complaint differences. Either way, he said, the survey reinforces the importance, for all ages, of adopting a healthy lifestyle to help limit and forestall age-related cognitive decline and neurodegeneration.

    The Gallup poll used in the study took place between December 2011 and January 2012 and was part of the Gallup-Healthways Well-Being Index, which includes health- and lifestyle-related polling questions. The five questions asked were:

    (1) Do you smoke?

    (2) Did you eat healthy all day yesterday?

    (3) In the last seven days, on how many days did you have five or more servings of vegetables and fruits?

    (4) In the last seven days, on how many days did you exercise for 30 minutes or more?

    (5) Do you have any problems with your memory?


  6. 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.


  7. 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.”

     


  8. Study suggests no link between anesthesia and dementia in elderly

    May 16, 2013 by Ashley

    From the Mayo Clinic press release via HealthCanal:

    hospital stayElderly patients who receive anesthesia are no more likely to develop long-term dementia or Alzheimer’s disease than other seniors, according to new Mayo Clinic research.

    The study analyzed thousands of patients using the Rochester Epidemiology Project — which allows researchers access to medical records of nearly all residents of Olmsted County, Minn. — and found that receiving general anesthesia for procedures after age 45 is not a risk factor for developing dementia. The findings were published Wednesday, May 1, online in Mayo Clinic Proceedings.

    Researchers know that some elderly patients have problems with cognitive function for weeks, sometimes months, following surgical procedures, says senior author David Warner, M.D., a pediatric anesthesiologist at the Mayo Clinic Children’s Center.

    There has been concern that exposure to anesthesia may be associated with long-term cognitive changes including dementia, he says. The concern stems in part from a series of studies in which animals were exposed to anesthesia and lesions similar to those observed in Alzheimer’s disease appeared in the brain — including accumulation of amyloid, a protein associated with Alzheimer’s disease.

    “It’s reassuring we’re adding to the body of knowledge that there is not an association of anesthesia and surgery with Alzheimer’s,” Dr. Warner says. “There are a lot of things to worry about when an elderly person has surgery, but it seems that developing Alzheimer’s isn’t one of them.

    Researchers studied about 900 patients older than 45 who had dementia and lived in Olmsted County from 1985 to 1994. They compared that group to people of similar ages in Olmsted County who did not develop dementia during that time. Researchers found that about 70 percent of the patients in both groups needed surgery requiring general anesthesia — meaning those who had dementia and underwent surgery that included general anesthesia did not get worse, and those who did not have dementia and had surgery did not develop dementia as a result.

    Mayo Clinic anesthesiologist Juraj Sprung, M.D., Ph.D., is the study’s first author. The study was funded by Mayo Clinic and the National Center for Advancing Translational Sciences.

     


  9. Study sheds new light on early stage Alzheimer’s

    April 29, 2013 by Ashley

    From the Karolinska Institutet press release via ScienceDaily:

    The brainThe disrupted metabolism of sugar, fat and calcium is part of the process that causes the death of neurons in Alzheimer’s disease.

    Researchers from Karolinska Institutet in Sweden have now shown, for the first time, how important parts of the nerve cell that are involved in the cell’s energy metabolism operate in the early stages of the disease. These somewhat surprising results shed new light on how neuronal metabolism relates to the development of the disease.

    In the Alzheimer’s disease brain, plaques consisting of so called amyloid-beta-peptide (A?) are accumulated. It is also a well-known fact that the nerve cells of patients with Alzheimer’s disease have problems metabolising for example glucose and calcium, and that these disorders are associated with cell death. The metabolism of these substances is the job of the cell mitochondria, which serve as the cell’s power plant and supply the cell with energy.

    However, for the mitochondria to do this, they need good contact with another part of the cell called the endoplasmic reticulum (ER). The specialised region of ER that is in contact with mitochondria is called the MAM region. Earlier studies on yeast and other types of cells have shown that the deactivation of certain proteins in the MAM region disrupt the contact points between the mitochondria and the ER, preventing the delivery of energy to the cell and causing cell death.

    Now for the first time, researchers at Karolinska Institutet have studied the MAM region in nerve cells, and examined the interaction between the mitochondria and the ER in early stage Alzheimer’s disease. Although at this point in the development of the disease A? has not formed large, lumpy plaques, symptoms still appear, implying that A? that has not yet formed plaque is toxic to neurons.

    The team’s results are slightly surprising. When nerve cells are exposed to low doses of A?, it leads to an increase in the number of contact points between the mitochondria and the ER, causing more calcium to be transferred from the ER to the mitochondria. The resulting over-accumulation of calcium is toxic to the mitochondria and affects their ability to supply energy to the nerve cell.

    It’s urgent that we find out what causes neuronal death if we’re to develop molecules that check the disease,” says Maria Ankarcrona, docent and researcher at the Department of Neurobiology, Care Sciences and Society, and the Alzheimer’s Disease Research Centre of Karolinska Institutet. “In the long run we might be able to produce a drug that can arrest the progress of the disease at a stage when the patient is still able to manage their daily lives. If we can extend that period by a number of years, we’d have made great gains. Today there are no drugs that affect the actual disease process.”

    The researchers conducted their studies on mice bred to develop symptoms of Alzheimer’s disease. They also studied nerve cells from deceased Alzheimer’s patients and neurons cultivated in the laboratory.

    The study was financed by grants from the Swedish Research Council, the Swedish Alzheimer Foundation, the Gamla Tjänarinnor foundation, the Stohne Foundation and the Lundbeck Foundation, and through a donation from the Peter Thelin Family.


  10. Researchers develop new hypothesis for how Alzheimer’s could occur

    April 16, 2013 by Ashley

    From the Ruhr-University Bochum press release via EurekAlert!:

    brain puzzleA new hypothesis has been developed by researchers in Bochum on how Alzheimer’s disease could occur. They analysed the interaction of the proteins FE65 and BLM that regulate cell division. In the cell culture model, they discovered spherical structures in the nucleus that contained FE65 and BLM.

    The interaction of the proteins triggered a wrong signal for cell division. This may explain the degeneration and death of nerve cells in Alzheimer’s patients.

    The team led by Dr. Thorsten Müller and Prof. Dr. Katrin Marcus from the Department of Functional Proteomics in cooperation with the RUB’s Medical Proteome Centre headed by Prof. Helmut E. Meyer reported on the results in the “Journal of Cell Science“.

    Components of spherical structures in the nucleus identified

    The so-called amyloid precursor protein APP is central to Alzheimer’s disease. It spans the cell membrane, and its cleavage products are linked to protein deposits that form in Alzheimer patients outside the nerve cells. APP anchors the protein FE65 to the membrane, which was the focus of the current study. FE65 can migrate into the nucleus, where it plays a role in DNA replication and repair.

    Based on cells grown in the laboratory, the team led by Dr. Müller established that FE65 can unite with other proteins in the cell nucleus to form spherical structures, so-called “nuclear spheres”. Video microscopy showed that these ring-like structures merge with each other and can thus grow. “By using a special cell culture model, we were able to identify additional components of these spheres”, says Andreas Schrötter, PhD student in the working group Morbus Alzheimer at the Institute for Functional Proteomics. Among other things, the scientists found the protein BLM, which is known from Bloom’s syndrome – an extremely rare hereditary disease, which is associated with dwarfism, immunodeficiency, and an increased risk of cancer. BLM is involved in DNA replication and repair in the nucleus.

    The amount of FE65 determines the amount of BLM in the cell nucleus

    Müller’s team took a closer look at the function of FE65. By means of genetic manipulation, the researchers generated cell cultures, in which the FE65-production was reduced. A smaller amount of FE65 thus generated a smaller amount of the protein BLM in the nucleus. Instead, BLM collected in another area of the cell, the endoplasmic reticulum.

    In addition, the researchers found a lower rate of DNA replication in the genetically modified cells. In this way, FE65 influences the replication of the genetic material via the BLM protein. When the researchers cranked up the FE65-production again, the amount of BLM in the nucleus also increased again.

    FE65 as a possible trigger for Alzheimer’s

    In patients with Alzheimer’s disease, the protein APP, an interaction partner of FE65, changes. The interaction of the two molecules is important for the transport of FE65 into the nucleus, where it regulates cell division in combination with BLM. Müller’s team assumes that the altered APP-FE65 interaction mistakenly sends the cells the signal to divide. Since nerve cells normally cannot divide, they degenerate instead and die. “This hypothesis, which we pursue in the working group Morbus Alzheimer, also delivers new starting points for potential therapies, which are urgently needed for Alzheimer’s disease,” says Dr. Mueller. In the future, the team will also investigate whether and how the amount of BLM is altered in Alzheimer’s patients compared to healthy subjects.