Alzheimer Related News Items
News as of 11/08/05
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Top Items
Diagnosing AD: Eyes Wide Open - The eyes have it. Scientists may have found a way to diagnose AD: check the eyes. As people age, they become more prone to age-related diseases. “AD is very difficult to diagnose at any stage, but in order for us to treat this disorder, we must be able to diagnose it early and intervene early,” said Dr. Lee Goldstein, an associate director of the Center for Ophthalmic Research at Brigham and Women’s Hospital in Boston. Researchers recently discovered the same protein, called beta amyloid, that builds up in the brains of AD patients also accumulates in the lens of the eye. As a result, they have developed a way to use a harmless laser to spot the protein buildup. “It’s a very simple noninvasive technique that relies on directing light into lens of the eye and then detecting that light on the outside after it interacts with the lens,” Goldstein explained. Goldstein then uses specially-designed eye drops that light up when they bind to amyloid proteins. This confirms their location at the edge of the lens, where the amyloid accumulates. “First and foremost, this will help us diagnose and treat patients who are suffering. Secondly, it’ll help us develop drugs,” Goldstein said. Goldstein said it’s hard to predict how soon his test will be able to help patients, but he hopes it will be available to doctors within the next two years. nbci.com Dallas/Ft. Worth 10/25/05
Drugs
Treating Dementia Patients With Antipsychotics - New research reveals antipsychotic drugs may lead to a small increased risk of death when used by people with dementia. According to research, antipsychotic medications are commonly used when aggression, delusions and other psychiatric symptoms are present in patients with dementia. A majority of elderly people with dementia develop symptoms like these during the course of their disease. Investogators from the University of Southern California, in Los Angeles, conducted a meta-analysis of 15 studies. Four different atypical antipsychotics were evaluated and compared with placebo. The four drugs studied were second-generation drugs called atypical antipsychotics. They include aripiprazole (Abilify), olanzapine (Zyprexa), quetiapine (Seroquel) and risperidone (Risperdal). There were 3,353 patients in the trials taking one of the drugs while 1,757 people received a placebo. Results of the study show more patients taking an atypical antipsychotic died than did those taking a placebo. There were 118 deaths in the group taking the drugs and 40 deaths in those on a placebo. Even though there were about 1,500 more people in the receiving the drugs, researchers say the difference between those two groups was statistically significant. The risk of death was 1.54-times higher for people taking an atypical antipsychotic than those not taking one. Most deaths were due to either heart-related effects or infections such as pneumonia. Lon Schneider, M.D., from USC, cautions psychosis is a serious problem in people with dementia. He says: “Aggression, hallucinations and delusions in dementia patients can also shorten a patient’s life, and result in poor care and rapid deterioration. It’s a difficult problem with no easy answers.” Dr. Schneider mentions there are caveats regarding the results. Most of the studies were short and the risk could be either higher or lower if patients were studied longer. He says the risk of death may also not be linked solely to the antipsychotics. He says: “These are mostly nursing home patients who are frail and medically ill. If the same sorts of analyses were done with other drugs -- antidepressants, anxiolytics, mood stabilizers, even cardiovascular or antihypertensive drugs -- we might see something similar as well. Drugs have side effects, and even as they help, they harm.” Dr. Schneider suggests, “Clinicians and families use this information to better and more cautiously judge the need for antipsychotics in dementia patients. It would be good for us all to be a little more cautious, and to stop using the medications if there doesn’t seem to be a clinical effect.” Ivanhoe Newswire 10/24/05 The Journal of the American Medical Association, 2005;294:1934-1943
Genes & Genetic Issues
New Jersey Announces Change to Aid Stem Cell Research - New Jersey announced 10/18/05
the creation of the nation’s first statewide public bank for umbilical and placental blood to be used both by stem cell researchers and patients in need of transplants. Blood from the placenta and umbilical cord contains stem cells, and researchers hope such cells can eventually play a role in curing diabetes, AIDS, multiple sclerosis and Parkinson’s and AD, as well as in helping patients with strokes or spinal cord injuries. Currently, less than 1 percent of placental and umbilical blood is donated for research, one expert estimated, and the rest is discarded as medical waste. New Jersey’s bank differs from banks in other states because it will provide free blood samples to researchers providing that the amount is not large enough for transplantation. By Tina Kelley NY Times 10/18/05
FDA Approves First Brain Stem Cell Transplant - Federal regulators on 10/21/05 approved what would be the first transplant of fetal stem cells into human brains, a procedure that if successful could open the door to treating a host of neural disorders. The transplant recipients will be children who suffer from a rare, fatal genetic disorder. The Food and Drug Administra-tion said that doctors at Stanford University Medical Center can begin the testing on six children afflicted with Batten disease, a degenerative malady that renders its young victims blind, speech-less and paralyzed before it kills them. The stem cells to be transplanted in the brain aren’t human embryonic stem cells, which are derived from days-old embryos. Instead, the cells are immature neural cells that are destined to turn into the mature cells that makeup a fully formed brain. Parkinson’s disease patients and stroke victims have received transplants of fully formed brain cells before, but the malleable brain cells involved here have never before been implanted. Batten disease is caused by a defective gene that fails to create an enzyme needed in the brain to help dispose of brain cellular waste. The waste piles up and kills healthy cells until the patient dies. Most victims die before they reach their teens. The idea is to inject the sick kids with healthy, immature neural stem cells that will “engraft” in a brain that will direct them to turn into cells able to produce the missing enzyme. Such an experiment showed promise in Batten-afflicted mice. AP 10/21/05
Caregivers
The Pablo Picasso AD Therapy - There is a growing effort to use art as a therapeutic tool for those in the grip of AD. Art therapy, both appreciating art and making it, has been used for decades as a nonmedical way to help a wide variety of people - abused children, prisoners and cancer and AD patients. But much of this work has taken place in nursing homes and hospitals. Now museums like the Modern and the Museum of Fine Arts, Boston, are trying to bring it into their galleries, using their collections as powerful ways to engage minds damaged by dementia. It seems to be working, though no one knows exactly how. While extensive research has been conducted on the effects of music and performing arts on brain function there has been comparatively little work done in the visual arts. What exists mostly is a stockpile of anecdotal evidence, encouraging but murky. Why did Willem de Kooning become more productive, almost maniacally so, as he descended into AD? Why does frontotemporal dementia, a relatively rare form of non-AD brain disease, cause some people who had no previous interest or aptitude for art to develop remarkable artistic talent and drive? “Certainly it’s not just a visual experience - it’s an emotional one,” said Oliver Sacks, the neurologist and writer. “In an informal way I have often seen quite demented patients recognize and respond vividly to paintings and delight in painting at a time when they are scarcely responsive to words and disoriented and out of it. I think that recognition of visual art can be very deep.” With no cure on the horizon, caregivers are increasingly exploring art as a way to help manage the disease, and they take encouragement from the results with music. Dr. Sacks noted that exposure to music can even result in lowered dosages for patients being medicated for cognitive and emotional disorders. One avenue of thinking about both music and art, he said, is that it engages parts of the brain that remain intact long after the onset of dementia and that have to do with procedural memory - the kind that governs routine activities like walking, eating, shaving. One musician whom Dr. Sacks has observed has almost entirely lost his memory, but his musical memory is intact. “Nietzsche used to say that we listened to music with our muscles,” he said. The question is whether a similar mechanism is at work in making and looking at art. The National Institute on Aging held a conference in Alexandria, Va., last year to allow researchers to compare notes on AD and artistic activity. One speaker, Bruce L. Miller, clinical director of the Memory and Aging Center at the University of California, San Francisco, said he believed that even sitting and looking at art is much more active than most people assume, and such activity could have positive effects on damaged brains. “There’s a lot of general excitement in this area, but not much known about it,” he said later in an interview. “I think there is, tucked in there, a research question that really hasn’t been answered yet, which is: by looking at or making art, is there a way to improve the brains of those with AD?” By Randy Kennedy NY Times 10/30/05
Research That Hits Home - In 2001, Ellen Proxmire faced a tough decision regarding her husband -- William Proxmire, the former Democratic senator. Diagnosed seven years earlier with AD, he frequently wandered from home. He even managed to escape from a locked hospital unit. Then she heard about Copper Ridge. Located 54 miles north of Washington in Sykesville, Md., “They saved our lives,” Ellen Proxmire said. She is fortunate, she knows, to be in a position to pay for premium care. Copper Ridge costs as much as $95,000 a year for assisted living (from $173 to $262 per day, depending on the level of care), up to $109,000 a year for nursing home care ($301 a day). Although the facility’s nursing home unit accepts people on Medicaid, the assisted living component is strictly private pay. In the nation’s 30 largest metropolitan areas, dementia care in assisted living averages $53,484 a year (about $148 a day), according to the Annapolis-based National Investment Center’s Market Area Profiles (NIC-MAP). Besides price, what distinguishes Copper Ridge is this: It is one of the world’s few residential facilities with a dual mission -- conducting academic research on dementia and applying that research to resident care. AD, the most common form of dementia, is an irreversible, progressive, terminal disease that disrupts brain function. The disease can run from three to 20 years, with an average term of eight years. Unlike many assisted living facilities for those with dementia, Copper Ridge cares for people until death. (The average resident stays there for two to three years before succumbing to the disease.) The facility’s research arm, the Copper Ridge Institute, is affiliated with Johns Hopkins University School of Medicine and Hopkins’s AD Research Center, one of 32 such centers funded by the National Institute on Aging.“Here, there’s so much freedom -- and safe freedom,” Ellen Proxmire said of Copper Ridge. The facility, which opened in 1994, was one of the first to incorporate a homier design. Each household of 20 residents boasts a family-size kitchen and dining room and a living room with a fireplace. Most residents have a private bedroom and half-bath. Window seats overlook courtyards. In good weather, residents can walk on paths through enclosed secure gardens or sit on benches, listening to rustling leaves and bubbling fountains. By Beth Baker Washington Post 11/1/05
Testing
Predicting AD Is More Wish Than Reality - A wide variety of detection methods are being studied, including the EEG (electroencephalograph), sophisticated brain-scanning techniques, paper-and-pencil neuropsychological tests, genetic tests and even scratch-and-sniff tests. But some experts worry that expectations for the tests run far ahead of the science. “People have a sense that they can go in at 55 and be assured they’re not going to get AD,” said Bill Thies of the Alzheimer’s Association. But the accuracy of the tests so far, he noted, is low. And, he said, he worries that if people who take the tests are told that they are at high risk, they may become unnecessarily anxious or start taking unproven drugs to try to avoid AD. “It’s dangerous to claim these tests are predictive,” said Dr. Steven DeKosky, director of the AD Research Center at the University of Pittsburgh. “Could you look at a scan of anybody and predict whether they’re not going to develop AD in say three or four years? No,” he said. “The differences are subtle; there isn’t anything that’s dramatically different in the brains of people who don’t yet have the disease.” Still, the tests offer the hope of more accurate prediction techniques in the future. “Five to 10 years ago, we wouldn’t have been talking about this whole issue of predicting AD in normal individuals,” said Dr. Ronald C. Peterson, director of AD research at the Mayo Clinic in Rochester, Minn. “That wasn’t even on the radar screen.” Dr. David Bennett, director of the AD center at Rush University Medical Center in Chicago, said that what was driving the push for early diagnosis was not so much the tests “but the realization that once the disease is full blown, the possibility of bringing someone back is small.” By Laurie Tarkan NY Times 10/25/05
10 Warning Signs Of AD
Do you suspect that you or someone you know has AD? This list of warning signs from the Alzheimer’s Association includes common symptoms of AD (some also apply to other dementias). If you have several of these symptoms, you should see a physician for a complete examination.
1. Memory loss that affects job skills. It’s normal to occasionally forget an assignment, deadline, or colleague’s name, but frequent forgetfulness or unexplainable confusion at home or in the workplace may signal that something’s wrong.
2. Difficulty performing familiar tasks. Busy people get distracted from time to time. For example, you might leave something on the stove too long or not remember to serve part of a meal. People with AD might prepare a meal and not only forget to serve it, but also forget that they made it.
3. Problems with language. Everyone has trouble finding the right word sometimes, but a person with Alzheimer’s disease may forget simple words or substitute inappropriate words, making his or her sentences difficult to understand.
4. Disorientation to time and place. It’s normal to momentarily forget the day of the week or what you need from the store. But people with AD can become lost on their own street, not knowing where they are, how they got there, or how to get back home.
5. Poor or decreased judgment. Choosing not to bring a sweater or coat along on a chilly night is a common mistake. A person with AD, however, may dress inappropriately in more noticeable ways, wearing a bathrobe to the store or several blouses on a hot day.
6. Problems with abstract thinking. Balancing a checkbook can be challenging for many people, but for someone withAD, recognizing numbers or performing basic calculation may be impossible.
7. Misplacing things. Everyone temporarily misplaces a wallet or keys from time to time. A person with AD may put these and other items in inappropriate places -- such as an iron in the freezer or a wristwatch in the sugar bowl -- and then not recall how they got there.
8. Changes in mood or behavior. Everyone experiences a broad range of emotions -- it’s part of being human. People with AD tend to exhibit more rapid mood swings for no apparent reason.
9. Changes in personality. People’s personalities may change somewhat as they age. But a person with AD can change dramatically, either suddenly or over a period of time. Someone who is generally easygoing may become angry, suspicious or fearful.
10. Loss of initiative. It’s normal to tire of housework, business activities or social obligations, but most people retain or eventually regain their interest. The person with AD may remain uninterested and uninvolved in many or all of his usual pursuits.
Prevention
Compound in Wine Reduces Levels of AD-causing Peptides - A study published 11/11/05 shows that resveratrol, a compound found in grapes and red wine, lowers the levels of the amyloid-beta peptides which cause the telltale senile plaques of AD. “Resveratrol is a natural polyphenol occurring in the in abundance in several plants, including grapes, berries and peanuts,” explains study author Philippe Marambaud. “The polyphenol is found in high concentrations in red wines. The highest concentration of resveratrol has been reported in wines prepared from Pinot Noir grapes. Generally, white wines contain 1% to 5% of the resveratrol content present in most red wines.” One of the characteristic features of AD is the deposition of amyloid-beta peptides in the brain. Philippe Marambaud and his colleagues at the Litwin-Zucker Research Center for the Study of AD and Memory Disorders in Manhasset, New York, administered resveratrol to cells which produce human amyloid-beta and tested the compound’s effectiveness by monitoring amyloid-beta levels inside and outside the cells. They found that levels of amyloid-beta in the treated cells were much lower than those in untreated cells. The researchers believe the compound acts by stimulating the degradation of amyloid-beta peptides by the proteasome, a barrel-shaped multi-protein complex that can specifically digest proteins into short polypeptides and amino acids. However, eating grapes may not be a cure for AD. “It is difficult to know whether the anti-amyloidogenic effect of resveratrol observed in cell culture systems can support the beneficial effect of specific diets such as eating grapes,” cautions Marambaud. “Resveratrol in grapes may never reach the concentrations required to obtain the effect observed in our studies. Grapes and wine however contain more than 600 different components, including well-characterized antioxidant molecules. Therefore, we cannot exclude the possibility that several compounds work in synergy with small amounts of resveratrol to slow down the progression of the neurodegenerative process in humans.” Innovations Report 11/7/05 Journal of Biological Chemistry 280 (45):37377-37382 11/11/05
A High Fat, Low Carbohydrate Diet Improves AD in Mice - Mice with the mouse model of AD show improvements in their condition (i.e. less AD) when treated with a high-fat, low-carbohydrate diet. Researchers found the brain protein, amyloid-beta, which is an indicator of AD, is reduced in mice on the so-called ketogenic diet. The report, by Samuel Henderson, from Accera, Inc, Colorado and colleagues from Belgium runs counter to previous studies suggesting a negative effect of fat on AD. “This work supports the premise that key aspects of AD can be altered by changes in metabolism. It also highlights the interaction of dietary components and how such components influence the metabolic state,” write the authors. The authors believe that insulin and the related hormone, insulin-related growth factor-1 (IGF-1), are the key players. “Insulin is often considered a storage hormone, since it promotes deposition of fat but insulin may also work to encourage amyloid-beta production.” Richard Feinman, editor of the journal, explains the relation between nutrients: “You might say that fat is the bomb, and insulin (from carbohydrate) is the fuse. Most studies of the deleterious effects of fat have been done in the presence of high carbohydrate. If carbs are high, dietary fat is not oxidized and is instead stored as body fat.” When carbohydrates are very low and fat is high, compounds called ketone bodies are generated (ketosis) and these compounds may play a role in the observed reduction in amyloid-beta. In association with a group from University of Washington led by Dr. Suzanne Craft, Henderson has previously shown cognitive improvement in patients with mild AD who were given a diet that raises ketone bodies. PR 10/16/05 Nutrition and Metabolism 2005, 2:28
Other Items
Nitric Oxide Inhibition Slows AD in Mice - A toxic gas appears to speed neurological decline in mice bred to mimic AD, and inhibiting the production of this gas -- called nitric oxide -- led to dramatic slowdowns in the rodents’ disease-related brain damage, according to a new study by researchers at the Weill Medical College of Cornell University. “The findings are preliminary, but drug companies have already developed agents that may safely inhibit the disease-associated form of the enzyme responsible for producing nitric oxide in the human brain. Our hope is that the results seen in this mouse study might someday be replicated in humans,” said lead researcher Dr. Carl Nathan, Professor of Microbiology and Chairman of the Department of Microbiology and Immunology at Weill Cornell Medical College. The Weill Cornell team focused their efforts on nitric oxide, which scientists only recently discovered plays a role in the biology of most living organisms. “This gas is produced by three enzymes. Where the brain is concerned, the culprit we looked at is an enzyme called iNOS,” said study senior author Dr. Flint Beal. The “i” in iNOS (so named by Dr. Nathan after its discovery in 1992) stands for “inducible.” “It’s an enzyme that is induced into action to produce nitric oxide during infection, inflammation, or an immune response,” Dr. Nathan said. As such, iNOS has no place in the healthy brain, but scientists have long noticed high levels of the enzyme in the brains of AD patients. “It shouldn’t be there -- it seems to be causing trouble without providing any benefit,” Dr. Beal said. He and Dr. Nathan suspected that an abnormal form of a protein called amyloid-beta -- a hallmark of AD-- may serve as an irritant, “fooling” the body into thinking that an infection-like process is underway, and spurring iNOS to begin producing nitric oxide. They also suspected that rising concentrations of nitric oxide in the brain accelerate AD progression. Medical News Today 11/8/05 November 7 issue of The Journal of Experimental Medicine 202(9):1163-1169 11/7/05
Alcoholism Research Reveals Promising New Approach to Treating AD - Saint Louis University research shows a new class of drugs may hold promise in treating brain chemical problems such as AD, says the principal investigator of research published in an early on-line version of Peptides. “We found that we can develop antisense – which is a molecular compound – to cross the blood brain barrier enough to alter brain function. This can have a profound effect on treating diseases that occur because there is too much or too little of a certain kind of protein in the brain,” says William A. Banks, M.D., professor of geriatrics and pharmacological and physiological sciences at Saint Louis University and principal investigator. “The blood brain barrier is the Holy Grail – it’s the most difficult tissue to pass through.” Antisense molecules are very specific compounds that scientists can create to plug into genetic pathways and block certain genes from producing harmful proteins. Many scientists believe that overproduction of the amyloid beta protein in the brain causes AD. Previous Saint Louis University research has found that scientists can develop antisense to cross the blood brain barrier and lower levels of amyloid beta protein in mice. Banks tested whether the antisense theory could be generalized to reduce other brain chemicals in a mouse study involving a different protein – the brain chemical methionine enkephalin (Met-Enk). Low brain levels of Met-Enk trigger alcohol consumption. High levels of Met-Enk cause animals to drink less. His study team created three different antisense compounds, which lowered brain levels of Met-Enk and caused mice to drink more alcohol. “The antisense inhibited the brain’s production of Met-Enk and, as predicted, the animals drank more,” says Banks, who also is a staff physician at Veterans Affairs Medical Center in St. Louis. But the findings are even more significant because they suggest that scientists can develop compounds that cross the blood brain barrier and turn off messenger genes that instruct cells to make or break down proteins in the brain that cause certain diseases, such as AD, Banks says. “We think our findings are going to be applicable in a general sense. This may stimulate the development of a new class of drug,” Banks says. “We’ve had success making antisense that can get into the brain. The alcohol results are fascinating, but the big story is drug development.” PR 10/25/05 Peptides available online doi:1016/peptides.2005.09.001
Snail Memory Boost Seen Promising for AD - A cancer drug may stimulate the production of proteins needed for long-term memory, supporting interest in the compound as a possible treatment for AD, researchers said on 10/24/05. Scientists at the Blanchette Rockefeller Neurosciences Institute and the Marine Biological Laboratory report that introducing bryostatin into a marine snail, days before a learning activity, caused a marked improvement in long-term memory. “This could be a real breakthrough for AD patients,” said Dr. Daniel Alkon, institute scientific director and lead author of the study. An early symptom of AD is losing the ability to store new memories for the long term and bryostatin appears to enhance this long-term storage. In the snail experiment, researchers put bryostatin in sea water, days in advance of any learning or training, causing certain proteins to be made by the neurons of the snails. When the snails were trained days later, instead of remembering something for a minute or two, they would remember it for weeks, researchers said. Last year, experiments in mice suggested bryostatin also helps prevent the protein buildup seen in the brains of AD victims. The institute has a patent (U.S. 6,825,229) for use of bryostatin to treat AD and is in discussion with the private sector on a partnership to shepherd the drug through clinical trials and any subsequent marketing efforts. “We believe we are on the right path toward providing AD patients and their families with a treatment that goes to the underlying cause of the disease,” institute president Dr. Robert D’Alessandri said in a statement. Reuters 10/22/05 Proceedings of the National Academy of Science published online 10.1073/pnas.0508001102
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