Alzheimer Related News Items

News as of 12/08/03

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Top Items

NSAIDs May Help Brain Heal Itself - Two studies shed new light on the role of brain inflammation in diseases such as AD and other dementias. The results of both studies indicate that treatment with nonsteroidal anti-inflammatory drugs (NSAIDs), which include aspirin and other aspirin-like drugs, can restore brain cell (neuron) production and lower levels of beta-amyloid by reducing inflammation. In one study Dr. Steven Paul and researchers from the drug maker Eli Lilly and Co. report anti-inflammatory drugs can reduce the production of amyloid-beta, including amyloid-beta-42. The buildup of amyloid-beta-42 seems to be the most harmful form of amyloid-beta seen in the brains of AD patients. Paul’s team found that a G protein, “Rho,” increases amyloid-beta levels as it interacts with another molecule, called “Rock.” In experiments in mice, the researchers found NSAIDs blocked the Rho-Rock interaction, lowering brain levels of beta-amyloid. In the second report a team led by Theo Palmer, an assistant professor of neurosurgery at Stanford University, experimented with rats to see the effect reducing brain inflammation might have on neuron production. “The dogma for many decades has been that the brain doesn’t replace neurons, but that is not true. There are regions of the brain that continue to make neurons throughout life. These new neurons are made by stem cells called precursors,” Palmer says. These new neurons might be important for memory and learning, he adds. The team found that in rats in which brain inflammation was induced, the production of new neurons stopped. However, when they treated the rats with the anti-inflammatory drug indomethacin, the production of neurons was completely restored.

These results suggest memory and learning problems seen in conditions such as AD and other dementias, stroke and traumatic brain injury might benefit from a simple drug such as indomethacin, Palmer says. “However, we don’t know if that will turn out to be true,” Palmer notes. “We also don’t know whether making new neurons really plays a functional role in memory and learning.” By Steven Reinberg HealthDay Reporter 11/13/03 Science Nov. 14, 2003: 302: 1215-1217 (Steven Paul et al ) and Science Dec 5, 2003 1760-1765 (Theo Palmer et al)

Drugs

Mindset First to Receive Patent for AD Vaccine - An Israeli company called Mindset BioPharmaceuticals has become the first to obtain a patent for a vaccine for AD according to CEO Daniel Chain, who made the announcement at the Society of Neuroscience Meeting in New Orleans. “We believe this to be the first patent ever issued that specifically is directed to a peptide for use as a vaccine and immunizing composition against the AD toxin, beta-amyloid,” Chain told ISRAEL21c. Mindset`s vaccine, invented by scientists at New York University School of Medicine, and licensed to Mindset for development, elicits a response against the beta-amyloid protein known to be toxic to nerve cells and to form insoluble aggregates that accumulate in the brains of AD patients. This unique vaccine approach is based on soluble, synthetic homologues of the human amyloid toxin, which were found to be highly immunogenic when tested in animals. Also, in relevant animal models of AD, the Mindset vaccine was shown to inhibit the deposition of toxic amyloid fibrils and to improve cognition. The vaccine is still in the preclinical stage and is unlikely to enter clinical trials before 2006, according to Chain. By ISRAEL21c staff 11/30/03 The Patent Number was not given. However see the published patent application US 2002/0086847 for representative materials at http://www.uspto.gov/patft/index.html .

Synthetic Marijuana Eases AD Agitation - Dronabinol, a synthetic version of the active ingredient in marijuana, helps reduce agitation in people with AD. A Phase II, open label, randomized, parallel-group study of 54 patients by researchers at Monmouth Medical Center in Long Branch, N.J. concluded that the reduced agitation experienced by AD patients may offer some relief to family caregivers. “Our results show dronabinol [also known as Marinol] is an effective treatment for behavioral agitation in patients with AD and may ultimately help reduce the stress often experienced by caregivers,” lead investigator Dr. Joel S. Ross says in a prepared statement. “While difficult for the patient, the effects of agitation can greatly impact the emotional and physical health of family members and caregivers. By reducing patients’ agitation, caregivers are able to focus more time and energy on their patients’ overall well being,” Ross says. HealthDayNews 11/20/03

MorphoSys Presents Animal Data for Antibodies to Treat AD - MorphoSys AG presented successful in vivo results of their collaboration with Roche in AD at the 33rd Annual Meeting of the Society for Neuroscience in New Orleans. Within the scope of its collaboration, MorphoSys generated antibodies using its proprietary human HuCAL® antibody technology, which were highly specific to human amyloid plaques. In an animal study conducted by Roche, systemically administered antibodies showed highly specific binding to amyloid plaques in the brain of transgenic mice that are models for human AD. The antibodies were shown to cross the blood-brain-barrier and to bind to beta-amyloid plaques within the brain. The selected HuCAL® antibodies against A-beta represent unique tools for application in AD, both diagnostically and therapeutically. Press Release 12/3/03

Two AD Drugs Tested - The first drug study, sponsored by Merck, uses “HG secretagogue.”In mice, this compound has been shown to increase production of human growth hormone and thereby, prevent the formation of beta amyloid plaques in the brain and to help the body absorb the plaques. There are 22 sites for the trial. Participants may take part in the research regardless of the AD drugs or treatments they currently are undergoing. The second study sponsored by Elan Corp. and Wyeth-Ayerest Labs. involves giving AD patients antibodies to amyloid plaques, an approach similar to a vaccine tested last year that was suspended. The new antibody study will take a different tack by giving patients the antibody directly, thereby reducing the risk. Patients will receive one injection during the study, which will be watched closely by scientists and regulators for any adverse reactions the treatment might cause. There are five sites participating in that trial. Participants must be diagnosed with mild to moderate AD and may be taking other medications unless they are deemed unsafe with the vaccine. By Kerry Fehr-Snyder The Arizona Republic 12/5/03

Genes & Genetic Issues

New Study on AD Genes - Italian investigators have identified additional genes responsible for a type of inherited AD. AD is characterized by increasing memory loss and a decline in the ability to think and function. Research has linked the condition to the formation of plaque and protein build up in the brain. Studies have also shown the disease runs in some families, and researchers have been busy over the past decade looking for genetic mutations that put people at increased risk. Some of the mutations appear to involve a protein called presenilin, which is associated with the formation of plaque. The investigators collected DNA samples from 45 people with the inherited form of AD known as familial AD, or FAD. The samples were tested for presenilin mutations. Families were then assessed to see how particular mutations impacted their experience with the disease. Researchers found one mutation (a novel Ser130Leu in the PS2 gene) was associated with variable age at the time of diagnosis. Members of this family developed AD anywhere from age 35 to age 85. Two other novel mutations in the PS1 gene(Cys92Ser in exon 4 and Leu174Met in exon 6) were linked to an early age at diagnosis -- from about 49 to 54. The investigators believe these findings add to the growing body of knowledge about AD and how it is passed on through the genes in families. They write, “The identification of new mutations is important, particularly for developing diagnostic testing programs based on the frequency of mutations in specific populations and for further enlarging our understanding of the great variability of the FAD phenotype.” Ivanhoe Newswire 11/28/03 Archives of Neurology, 2003;60:1541-1544

Funding Limits Don’t Slow Cell Research - White House restrictions on federally funded embryonic stem cell research are not slowing studies in this new medical field, the head of the National Institutes of Health said 11/26/03. If the restrictions become a problem, he will ask President Bush to reopen the issue, Elias Zerhouni said in an interview with The Associated Press. Zerhouni said that research into the medical uses of embryonic stem cells is still at a very early stage and that approved cell lines are ample to meet current laboratory needs. “The policy as it stands today is appropriate for the stage of the science,” said Zerhouni. If it becomes scientifically clear that the White House policy is forming a roadblock to using stem cells to treat disease, he said, “I’ll be the first to go the president and say we have reached a point where we need a debate here.” By Paul Recer, AP Science Writer 11/26/03

EU to Fund Stem Cell Research Despite Ethics Split - The European Commission will fund controversial research using stem cells harvested from human embryos, despite the failure of EU ministers to agree ethical guidelines, a commissioner said on 12/3/03. The European Union remained split after the second meeting in a week between those states saying the research could lead to a cure for diseases such as AD, and predominantly Catholic countries which insist the research is unethical. By David Milliken Reuters Health 12/3/03

Caregivers

Finding an AD Facility - People with AD often end up living in an assisted care facility, especially during the disease’s advanced stages. But since many nursing homes lack the resources to handle AD patients, finding the right home for a family member can be difficult. The Miami Jewish Home and Hospital for the Aged suggests these tips. Make sure the facility has been licensed to handle the special needs of AD patients. Check that the staff is qualified and trained to work with people who have progressive memory disorders. See that the patient rooms are clean and spacious. And ask whether house rules allow rooms to be personalized with family photographs and mementoes from home. Make sure the premises is secure. This is vital for a place that cares for AD patients. Check that the programs offered will keep your relative alert, interested and entertained. Take a close look at the residents and how they’re being treated.

Choose a facility that allows as much access to your relative as you need. HealthDayNews 11/13/03

Dementia Caregivers Go From Distress to Relief - Family members who care for relatives with dementia experience a great deal of distress in the year before the patient dies, but tend to feel relief when the person passes away. In the study author Richard Schulz , a professor at the University of Pittsburgh, and his colleagues looked at 217 family caregivers to persons with dementia during the year preceding the patient’s death and for a period of time after the death. At the time of enrollment, the mean age of the caregivers was 65, of whom 84.3 percent were women. About half were spouses and half were non-spouses (usually children). The mean age of the patients was 81. Half of the caregivers reported spending at least 46 hours a week assisting patients with activities of daily living (such as bathing and eating) and instrumental activities of daily living (such as preparing meals and handling finances). More than half (59 percent) said they felt they were on duty 24 hours a day. Almost half of the caregivers who worked outside home said they had to reduce their work hours because of the demands of caregiving, while 18 percent of the total number of caregivers stopped working entirely. Almost three-quarters (72 percent) of the caregivers said the death of the patient was somewhat or very much a relief to them. “I had not seen this recovery phenomenon, this reduction in depression post-bereavement,” Schulz says. “Caregivers typically show an increase in depression pre- to post-death, which you don’t get here.” The message, Schulz continues, is that “if you want to understand bereavement, you really need to look at it in the context of where and how it’s taking place.”. By Amanda Gardner HealthDay Reporter 11/12/03 New England Journal of Medicine 11/13/03 349: no. 20 1936-1942

NIH Establishes Toll-Free AD Hotline - Federal health officials offer free help to those who notice changes in older family members. The National Institutes of Health recently established a toll-free telephone program for caregivers, friends and family members who worry that a loved one may be suffering from AD. Studies show that family members are often the first to notice early changes, but in many cases, aren’t sure if they are true symptoms of a memory problem. “We know that half of persons with AD go unrecognized. This is primarily because the early symptoms are subtle, are often dismissed by family and friends and often times unrecognized by medical practitioners,” said Dr. Mark Sager, who is with the Wisconsin Alzheimer’s Institute. The hotline, called the Alzheimer’s Early Recognition Telephone System (ALERTS), is anonymous and confidential. It offers a brief screening test that can tell someone who is worried about memory problems whether they need to get help. The toll-free number is (800) 289-4974. The Web page for ALERTS is http://www.medsch.wisc.edu/wai/alerts.html

Testing

Brain Changes May Point to Future AD - Shrinkage of an area of the brain, seen on successive MRI scans, predicts future mental decline in healthy elderly people, New York University researchers report. Precise measurement of regional brain loss, or atrophy, will be of value in identifying individuals at heightened risk for mental deterioration, Dr. Henry Rusinek told Reuters Health. “Until now, people were looking at whole brain atrophy, but ... we know that certain areas are more directly affected by declining memory function,” he explained. Rusinek and colleagues studied 45 high-functioning healthy adults age 60 or older. Two MRIs were performed approximately two years apart to measure the rate of atrophy of an area of the brain called the medial temporal lobe. The rate of temporal lobe atrophy was “striking” in the 13 subjects who exhibited cognitive decline, the radiologist said. Cognitive decline was associated with “more than twice the amount of shrinkage” observed in the stable individuals. The researchers calculate that an annual medial temporal lobe loss of 0.7 percent predicted the development of mental impairment with about 90 percent accuracy. Put another way, the findings indicate that each 0.1 percent loss of temporal lobe per year increases the odds for mental decline by 70 percent. These results should help in tracking the efficacy of treatments for AD, the researchers write. By Karla Gale Reuters Health 11/25/03 Radiology, December 2003;229:691-696

Brain’s ‘daydream’ network offers detection for AD diagnosis - Researchers have discovered surprising differences in the ability of younger and older adults to shut down a brain network normally active during periods of passive daydreaming. The differences, which are especially pronounced in people with dementia, may provide a clear and powerful new method for diagnosing individuals in the very early stages of AD. “In young adults, there are parts of the brain that are very active during a passive free-thinking state, but these areas appear to shut down dramatically or ‘turn off’ when the person is asked to do something,” said Cindy Lustig, researcher at Washington University in St. Louis. “Interestingly, older people, especially those with AD, don’t show this same kind of brain activity during free- thinking, resting conditions.” In a study Lustig and colleagues detail results of functional magnetic resonance imaging (fMRI) tests conducted on groups of young adults, older adults and adults experiencing early signs of AD-related dementia. They focused on what happens in regions that are active when the brain has no particular task at hand, regions that are focal points for a baseline, passive processing mode, one that seems to operate when the mind free to wander and daydream. “What we found in our study is that rather than turning these regions off when asked to concentrate, as young adults do, people with AD seem to turn them on,” Lustig said. “This might reflect a ‘broken brain’ in AD, making it hard for people to turn these brain regions on or off appropriately; more optimistically, it might be an attempt to compensate for the memory problems that come with AD.” Innovations Report 11/26/03 Proceeding of the National Academy of Science 11/25/03 100; no. 20 14504-14509

Visualizing AD - Using recently developed techniques for imaging individual cells in living animals, a team led by researchers at Washington University School of Medicine in St. Louis has watched as AD-like brain plaques damage mouse brain cells. The results were presented 11/12/03 at the 33rd Annual Meeting of the Society for Neuroscience in New Orleans. “This work is very exciting,” says principal investigator David M. Holtzman, M.D. “We’ve been able to visualize damaged nerve connections in living animals and follow them over time in the same animal. Our next step is to determine whether such damage is reversible.” In the 1990s, biologists discovered the protein that makes certain jellyfish luminescent also could be used to generate fluorescent cells in other species. By shining light on a living mouse engineered to contain these proteins, researchers can watch cellular activity over time using a multiphoton microscope, a sophisticated new microscope technique. Holtzman’s team used this technique to examine the brains of mice that develop plaques similar to those characteristic of AD. The mice also were engineered to have a subset of brain cells, or neurons, that express yellow fluorescent protein. Using this model, they observed neurons becoming increasingly disrupted by brain plaques over time. “We plan to use this system to further examine the process of nerve cell damage and degeneration,” Holtzman says. “This line of research should provide new insight into the underlying processes involved in the development of AD and help us determine whether the proteins that accumulate as brain plaques are a useful and feasible target for AD therapies.” Press Release 11/12/03

Prevention

Copper May Guard Against AD - Researchers say mice with more copper in their brain cells are less likely to develop the toxic protein fragments called amyloid-beta associated with AD. In one study, German scientists found mice with a genetic predisposition to the brain disease lived longer and had less amyloid-beta when they drank copper-laced water than did those that didn’t get the supplements. In a second study, scientist in Canada and the United States showed that mutant mice with high amounts of copper in their brain cells had about half the amyloid-beta buildup as mice without the mutation. The size of the effect was as great as that of experimental vaccines that target the harmful proteins, says study leader David Westaway, a brain researcher at the University of Toronto. “There has been the suggestion that elevations of copper can help drive AD, but we don’t get that,” Westaway says. “When we drove up levels of copper in the brain, some of the hallmarks of AD improved.” Thomas Bayer, a neuroscientist at Saarland University Medical Center, in Homburg/Saar, Germany, and leader of the other study, says, “If you give mice copper, either in water or by genetic manipulation, you reduce amyloid-beta” and prolong their life. By Adam Marcus HealthDay Reporter 11/10/03 Proceedings of the National Academy of Sciences 11/25/03 vol. 100, no. 24, 14187-14192 (Bayer et al) and 14193-14198 (Westaway et al)

Keeping Health in Mind: 10 Steps to Keep Your Memory Sharp - The following 10 steps are suggested by Paul Takahashi, M.D., a specialist in geriatrics at Mayo Clinic, Rochester, Minn., and an expert on cognitive decline. 1: Exercise your mind - just as physical activity keeps your body strong, mental activity keeps your mind sharp and agile. 2: Stay physically active - daily physical activity can help improve blood flow . Include three activities in your routine: aerobic activity, strength training and stretching. 3: Eat, drink and be healthy - eat a diet rich in fruits and vegetables which contain antioxidants - substances that protect and nourish brain cells and drink water which is essential to the human body. 4: Develop a system of reminders and cues. Write things down; establish a routine; and practice repetition to ingrain information in your mind. 5: Take time to remember things - forgetfulness may indicate nothing more than having too much on your mind. Slow down and pay full attention to the task at hand, whatever it may be. 6: Learn relaxation techniques - stress and anxiety can interfere with concentration, so it’s important to take time to relax - - really relax. 7: Keep a positive attitude happiness plays an enormous role in your outlook on life and optimists tend to live longer. 8: Talk to your doctor - if you or your family worry about your memory, get evaluated. Your doctor may be able to determine whether the cause is treatable. 9: Check your levels - know your blood pressure, cholesterol and blood sugar levels. Also make sure your thyroid gland is functioning normally. 10: Keep your perspective - everyone has difficulty remembering things at times. So don’t lose sight of how much you do remember. Wisdom is built from a lifetime of memories. Full article at http://www.mayoclinic.com/invoke.cfm?id=HA00001

Other Items

New Insights into AD - Scientists at the Buck Institute for Age Research in Novato CA have discovered that brains affected by AD might try to heal themselves by growing new nerve cells. The finding contradicts the common belief that the production of new nerve cells diminishes with the progression of AD. The new study raises the possibility that treatments might be developed to boost the natural process of nerve-cell birth, called neurogenesis, forestalling or repairing degenerative neurological damage. Dr. David Greenberg said that while new nerve cell growth is limited in adults, he and other scientists have already established that such cells continue to be born in adults who have suffered acute brain injury, including stroke. The cells migrate to the damaged area of the brain, but it is not yet known if those cells repair the brain. Greenberg said the next step will be to try to stimulate new nerve growth in mice or rats. If those experiments succeed, he believes the results might apply to other chronic neurological conditions, such as Parkinson’s and Huntington’s diseases. By Jane Futcher Marin Independent Journal reporter 12/02/03 Published online before print 12/5/03 Proceedings of the National Academy of Science 10.1073/pnas.2634794100

AD Shunt - Researchers across the country are testing a device called the COGNIShunt® (Eunoe, Inc., Pleasanton, CA) for patients with early-stage AD. The shunt is designed to increase circulation and drainage of cerebral spinal fluid. This fluid surrounds the brain and flows through spaces (ventricles) within the brain. Normally, the fluid is continually produced and drained. But as people age, the flow of cerebrospinal fluid begins to stagnate. Investigators theorize the abnormal protein fragments in the cerebrospinal fluid don’t drain efficiently. Improper drainage allows protein deposits to build in the brain, leading to the formation of the plaques and tangles that are characteristic of AD. The COGNIShunt is inserted through a tiny hole in the skull and placed inside a ventricle. The device works like a valve, enabling small amounts of cerebrospinal fluid to drain from the brain and into the stomach. The drainage will naturally be replaced with “fresh” cerebrospinal fluid. The COGNIShunt is the first multi-centered clinical trial to look at a surgical approach to AD. Participants are randomized into two groups – active shunt and inactive shunt (placebo) – and followed for nine months. Then, those who are assigned the inactive shunt will be given the option of having the shunt turned on. All participants will be followed another nine months for a total of 18 months of follow-up. Researchers say the COGNIShunt is still not a cure for AD. However, they hope to show the device, when used in combination with medication, may halt or significantly slow progression of the disease. The current phase III clinical trial will recruit about 250 patients. For information about the COGNIShunt® or referral to a site, call (888) 469-6463, or on the Web at: http://www.clinicaltrials.gov/ct/gui/show/NCT00056628?order+10 . The COGNIShunt trial is ongoing in the following U.S. cities: Scottsdale, AZ; Tucson, AZ; Little Rock, AK; La Jolla, CA; San Francisco, CA; Fort Myers, FL; St. Petersburg, FL; Tampa, FL; Atlanta, GA; Indianapolis, IN; Louisville, KY; Springfield, MA; St. Louis, MS; Brooklyn, NY; Johnson City, NY; New York, NY; Cleveland, OH; Columbus. OH; Portland, OR; Pittsburgh, PA; East Providence, RI; Madison, TN; San Antonio, TX; Alexandria, VA. By Laura Michels www.hoinews.com 11/25/03

AD Leaves Reagan Unable to Speak, Feed Himself - Ravaged by AD, former US president Ronald Reagan is no longer able to speak or feed himself and does not recognize his family. People magazine said in its December 5 edition that the United States’ 40th president, who is 92, spends his days confined to a hospital bed in a small room in his Los Angeles mansion with his wife, former first lady Nancy Reagan, almost constantly at his bedside. And the emotional and physical strain is taking a heavy toll on the increasingly-frail Nancy Reagan, 82, who fiercely protects her ailing husband’s dignity to the extent that even their closest friends are barred from seeing him, the magazine said. Reagan’s step-daughter Patti Davis wrote in the magazine that her father was unable to talk or walk and said it was only his robust physical constitution that was keeping him alive. “It makes me realize that my mother and I have been so protective of his condition since he became ill -- almost a decade now -- that it has allowed people to imagine he is still talking, still walking, still able to stumble into a moment of clarity,” she wrote. “But it would be a disservice to every family who has an AD victim in their embrace to say any of that is true, and I don’t believe my father would want us to lie.” AFP 12/5/03

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