Alzheimer Related News Items

News as of 5/08/04

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Top Items

Scientists Hope Improved AD Vaccine Will Hold Promise - Scientists told an AD conference on 4/15/04 that they’re hopeful a new and improved vaccine can attack brain plaques associated with the debilitating brain disease. But researchers cautioned the treatment is undergoing preliminary tests to determine whether it produces dangerous side effects that derailed an earlier version of the treatment. The pharmaceutical firm Elan Corp. is conducting clinical trials of the new vaccine in the United States on a small group of AD patients, said Dr. Dale Schenk, Elan’s chief scientific officer. He said it’s hoped the vaccine will attack the brain-damaging plaques, called beta amyloid. “I think the total data is very encouraging, but we still have clinical development to go,” Schenk told reporters at the conference. “I feel bullish about it ultimately working and I’m hopeful that it will.” Schenk said the new treatment works by injecting the antibodies directly into the patient, bypassing the immune system and possibly averting a harmful response. If the first phase is successful, Phase 2 trials would determine whether the vaccine has an effect on AD symptoms. Dr. Roger Nitsch of the University of Zurich said the new vaccine could be promising as long as rates of brain inflammation are reduced or eliminated. Canadian Press 4/15/04

Gene Therapy Surgery Helps AD - Study - Genetically engineered cells helped revive brain activity of AD patients when surgically implanted in their brains, U.S. researchers reported on 4/27/04. The experiment involved eight volunteers with early-stage AD and was meant to show only that the technique was safe. But their brains showed increased activity afterwards and the disease seemed to progress more slowly in some, the researchers told a meeting of the American Academy of Neurology. “These results are intriguing,” Dr. Mark Tuszynski said in a statement. “If these effects are borne out in larger, controlled trials, this could be a significant advance over existing therapies for AD.” For their experiment Tuszynski and colleagues at the University of California, San Diego first took skin samples from their patients. Then they genetically modified these skin cells to make them produce extra nerve growth factor, a protein that prevents cell death and stimulates cell function. They implanted these boosted cells into a brain region where cells degenerate in AD. They targeted the cholinergic system, which is important in memory and cognitive function. A similar experiment in old monkeys restored atrophied brain cells to near-normal size and number, and restored connections between the brain cells, Tuszynski said. A year after surgery, most of his human patients seem healthy with no adverse effects, Tuszynski told the meeting. Reuters 5/8/04  

Research Results Hold Promise for Stroke Survivors With Dementia - A well-known medication, Aricept, used to treat AD has shown continued benefits for at least 12 months for stroke survivors experiencing the deterioration of thinking abilities caused by stroke or multiple strokes, also called vascular dementia (VaD) according to one recent study. Researchers reported 5/504 at the American Psychiatric Association meeting the results of a study using the drug Aricept(R) (donepezil hydrochloride) with 453 patients diagnosed with VaD. The study was designed to determine if the drug was safe and effective long-term (one year) and could help maintain or improve the memory loss and cognitive function that can be caused by VaD. The results indicated that patients receiving Aricept® sustained their cognitive function, which was measured by their AD Assessment Scale cognitive scores. National Stroke Association (NSA) is optimistic about the findings and hopes further research will show the same promising results. “The finding of sustained memory benefit for stroke survivors at 12 months with the drug Aricept(R) strengthens the evidence that benefits of Aricept® may apply in an even more important manner in stroke survivors compared to AD patients,” said Dr. Dan Hanley, Chairman of the National Stroke Association Professional Advisory Committee and professor of neurology at Johns Hopkins Hospital. PR 5/5/04

New Study Results Show Benefit for AD Patients Taking Lipitor - Results of a Sun City, Arizona research study unveiled at a news conference on 4/14/04 in Montreal showed that Lipitor, a cholesterol-lowering medication, slows the progression and reduces the deterioration of AD. D. Larry Sparks, Ph.D., a senior scientist at the Sun Health Research Institute, made the announcement . He is the principal investigator for the 63-participant AD Cholesterol- Lowering Treatment Trial. A total of two-thirds of patients on active medication derived some clinical benefit. Half of the patients stabilized or actually improved. Participants in Dr. Sparks’ one-year treatment trial received either Lipitor or a placebo. Conducted as a double-blind study, mild to moderately affected patients were allowed to continue use of the FDA-approved AD medications (acetylcholine esterase inhibitors). “This is truly exciting news,” Dr. Sparks exclaims. “Results indicate not only a slowing in deterioration of function and memory but also an improvement in mood and behavior. No prior clinical trials have actually shown long-term improvement in patients with AD.” PR 4/14/04

Reminyl (Galantamine)

Galantamine Confers Benefits in Patients With Pure Vascular Dementia - Galantamine significantly improves cognition in patients with pure vascular dementia, researchers reported here on April 27th at the American Academy of Neurology 56th Annual Meeting. Alexander Auchus, MD, Clinical Director, University Memory and Aging Center, Case Western Reserve University, Cleveland, Ohio, presented results in 788 patients. All subjects had a diagnosis of vascular dementia. The researchers found that patients treated with galantamine 8 or 12 mg BID had a statistically significant improvement in cognitive function compared to placebo. By Jill Stein Doctor’s Guide 4/29/04

Reminyl (Galantamine) May Reduce Specific Behavioral Symptoms in Patients With AD - New data is the first to suggest that treatment with Reminyl® (galantamine hydrobromide) may reduce specific behavioral symptoms in patients with mild to moderate AD, which may contribute to a reduction in caregiver distress. The study had three key findings: patients who exhibited behavioral disturbances at the start of the study experienced robust reductions in symptoms; patients who did not have behavioral disturbances showed less emergence of symptoms; and, the reduction in behavioral-related caregiver distress was statistically significant. The findings from the 21-week study reported that patients treated with 16 or 24 mg/day of Reminyl who exhibited behavioral disturbances when they entered the study experienced meaningful reductions (29 percent to 48 percent) in aberrant motor behavior, agitation and anxiety versus placebo. Additionally, patients treated with up to 24 mg/day, who were without behavioral symptoms at baseline, revealed significantly less emergence of aberrant motor behavior, apathy and disinhibition than patients on placebo. “The study tracked caregiver distress as it related to the patient’s behavior. The reduction in behavior-related caregiver distress was modest but significant in the caregivers of patients receiving Reminyl 24 mg/day compared with those on placebo,” said Jeffrey Cummings, M.D., director, University of California at Los Angeles (UCLA) Alzheimer’s Center, the lead author on the study. “Reducing caregiver distress is important because of the integral role caregivers play in the overall management of patients with AD.” Doctor’s Guide 4/19/04 GET CITE March issue of the American Journal of Psychiatry Mar 2004;161:532-538

Namenda (Memantine)

Memantine Improves Functional Outcome Among AD Patients - Patients with moderate- to-severe disease who are given memantine, an antiglutamatergic agent, plus donepezil, a cholinesterase inhibitor, show better functional outcomes than do those given donepezil alone, say researchers. Pierre N. Tariot, MD, Professor of Psychiatry and Neurology at the University of Rochester Medical Center in Rochester, New York, United States, presented the findings of a double-blind, parallel arm, placebo-controlled trial investigating memantine’s efficacy in this patient group, on May 6th at the American Psychiatric Association (APA) 157th Annual Meeting. The study enrolled over 400 patients with a diagnosis of probable AD. At week 24, patients treated with memantine and donepezil showed significantly less decline in daily function on the AD Cooperative Study Activities of Daily Living Inventory scale. “Further analysis of this data show that the better outcomes in the memantine arm were due to a better ability to groom successfully, ability to watch and understand TV, to find their own belongings and to be left alone,” Dr. Tariot said. The study was funded by Forest Laboratories, Inc., the U.S. marketer of memantine. By Charlene Laino Doctor’s Guide May 7, 2004

Memantine + Stable Acetylcholinesterase Inhibitor Provides Benefits to AD Patients - Memantine treatment in conjunction with ongoing donepezil therapy is associated with less functional and behavioural deterioration in AD than donepezil therapy alone, researchers said on April 29th at the American Academy of Neurology 56th Annual Meeting. Memantine is a low-moderate affinity, uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist that is thought to allow normal physiological activation while blocking prolonged pathological activation of the NMDA receptor -- a factor implicated in the pathology of AD. Donepezil is an acetylcholinesterase inhibitor. Jeffrey Cummings, MD, University of California, Los Angeles, United States reported the results of a 24-week trial, in which 395 patients with moderate to severe AD who were on a stable donepezil regimen were randomised to memantine or placebo.

Memantine/donepezil treatment resulted in significantly greater functional ability compared to placebo/donepezil for grooming, watching television, being left alone, toileting, and finding belongings. The study was funded by Forest Laboratories, Inc., the U.S. marketer of Memantine. By Jill Stein Doctor’s Guide April 30, 2004

Namenda (Memantine) Appears to Produce Positive Effect on Brain Activity In Patients With Mild to Moderate AD - Forest Laboratories, Inc. announced 4/28/04 the results of a randomized, placebo- controlled, PET (positron emission tomography) imaging pilot study designed to measure the effect Namenda™ (memantine HCl) has on functional brain activity in patients with mild to moderate AD. The results in this pilot study suggest that, compared to placebo-treated patients, treatment with Namenda may positively affect cerebral glucose metabolism in the brains of patients with mild to moderate AD. “By using the PET brain- imaging technique, we observed increased metabolic activity of Namenda in areas of a patient’s brain associated with language and attention,” said Steven G. Potkin, M.D., Professor in the Department of Psychiatry and Human Behavior at the University of California, Irvine, and lead investigator of the PET study presented at the American Academy of Neurology (AAN) Annual Meeting 4/27/04. “While these data are from a small number of patients and need to be confirmed in larger scale studies, they indicate that Namenda may be able to reverse the cerebral metabolic decrease often associated with disease worsening in patients with mild to moderate AD who do not receive treatment.” Doctors Guide 4/28/04

Curry Found Useful Against AD - Italian and U.S. researchers have found evidence that curry can stave off AD, the Times of London reported 4/19/04. Scientists from Italy’s University of Catania and New York Medical College found that curry’s curcumin oil is a chemical trigger that enhances enzyme activity, protecting the brain against the progression of neuro-degenerative disease. A chemical compound extracted from tumeric, curcumin has been found to work wonders on many illnesses, be it as an antiseptic, a guard against liver damage or a medication to assist the treatment of cancer and Aids. Studies on rats found that curcumin induces an enzyme, hemeoxygenase, which operates as a defence mechanism against “free radicals,” rogue molecules that cause cells to function abnormally and die. The damage done by free radicals to intracellular targets such as DNA or proteins has been shown to be a major cause of diseases such as AD and are thought to be a major factor in the way people age. The new research showed that rat neurons exposed to higher concentrations of curcumin were less affected by cell damage due to increased levels of hemeoxygenase. United Press International via COMTEX 4/19/04

New Research Suggests Additional Role for Prana Technology Against AD - Prana Biotechnology Limited’s MPACs (metal protein attenuating compounds) have previously been shown to lower the levels of beta-amyloid in the brain -- the main component of amyloid plaques that are a feature of AD. The new research suggests that that these MPACs may also be effective in preventing beta-amyloid from attaching itself to and damaging COX-2, the key enzyme that mediates inflammation in the brain often associated with AD. Levels of beta amyloid/COX-2 complexes were found to be elevated significantly in the brains of patients with AD. Professor Ashley Bush of Harvard Medical School, Chief Scientific Consultant to Prana, and senior author on the paper, said “Our current findings explain how the interaction of beta-amyloid with brain copper corrupts the normal metabolism of COX-2 in AD. These findings further validate Prana’s MPAC drug approach, which targets the adverse metal interaction with amyloid. MPACs stop the beta-amyloid/metal complex from damaging COX-2. These findings also may explain why anti-inflammatory drugs would not be effective in AD.” PR 5/3/04 The Journal of Biological Chemistry 279(15):14673-14678

Genes & Genetic Issues

Cells from Adult Bone Marrow Can Be Converted into Brain Stem Cells for Transplant-ation - Hope for people with Parkinson’s disease, AD, stroke and other neurodegenerative diseases may ultimately come from their own bodies. Research that will be presented at the American Academy of Neurology 56th Annual Meeting 4/29/04, shows that cells taken from adult human bone marrow can be converted into brain stem cells that meet the criteria for transplantation into the brain. “It’s exciting to think that some day a person with AD could use their own bone marrow to create brain cells that could potentially restore their functioning and make up for cells that were lost,” said study author and neurologist Alexander Storch, MD, of the University of Ulm in Ulm, Germany. Use of the cells from adult human bone marrow, called stromal cells, eliminates the ethical and logistical issues that arise with the use of cells from fetal tissue, Storch said. And use of cells from bone marrow that would be converted and transplanted into the same person’s brain eliminates ethical issues and immune-system problems that can arise when the body rejects cells from an outside source. For the study, the researchers took the adult human bone marrow stromal cells and cultured them with growth factors. Other benefits of this process are that the cells can be converted quickly – within a few weeks – and a small amount of bone marrow can produce a large amount of converted cells, Storch said. More research is needed before the converted cells can be tested in humans. Animal studies are under way to explore the regenerative potential of the converted cells in animal models of acute and chronic neurodegenerative disorders, such as stroke and Parkinson’s disease. The researchers also need to determine the best way to administer the cells into the brain. PR 4/29/04

OHSU Researchers Uncover Genes Involved in Early Stages of AD - Researchers at Oregon Health & Science University (OHSU) have identified a set of genes that appear to be involved in the development of AD. They hope this information will help scientists create of methods for early detection of the disease and for the development of therapeutic strategies to delay or even stop its progression. “Through studying a mouse model of AD, the research team found that a series of genes related to mitochondrial metabolism in brain cells were more active than in normal mice,” P. Hemachandra Reddy, Ph.D., of the OHSU Neurological Sciences Institute said. “Mitochondria are structures located in the cytoplasm of cells that produce energy for the cell. Prior research has linked AD to mitochondrial function. However this is the first time genes that are responsible for early cellular change in AD pathogenesis have been identified.” Currently, there are no early detectable biomarkers for AD, and there is a lack of understanding of the functional changes caused by this disease, particularly at its early stages. To intervene before neurons become irreversibly damaged, an understanding of early cellular events in the progression of AD is critical. Studies of “pre-symptomatic” human subjects suggest that pathologic changes in the brain occur years before symptoms are evident, suggesting that the brain tissue from patients dying from AD exhibits physiologic features indicative of a very late stage in the degenerative process. By studying 11,283 mouse genes and using a gene chip technology called microarray, OHSU scientists were able to identify a much smaller set of distinct genes that functioned differently in the diseased mice from those in healthy mice. These genes are involved in mitochondrial energy metabolism and programmed cell death. “This work likely will sharpen the focus of research on the possible links between mitochondrial gene expression and damage that occurs within and to neurons as AD progresses. Understanding these links could lead to the development of novel and effective interventions for this disease,” said Stephen Snyder, Ph.D., of the National Institute on Aging’s (NIA) Neuroscience and Neuro-psychology of Aging Program. PR 4/27/04 paper, which will be published online on April 27, prior to its appearance in the journal Human Molecular Genetics Abstract at

http://hmg.oupjournals.org/cgi/content/abstract/ddh140v1

Low Vitamin B May Impair Memory in Some Seniors - A variant of a lipid gene called APOE4 is known to increase the chances of a person developing AD. A Swedish study has now shown that carriers of this gene are more vulnerable to the effects of low vitamin B12 levels on mental function in old age. Among healthy individuals over age 75, APOE4 carriers have more memory lapses when vitamin B12 falls below normal levels, according to the study conducted at the Karolinska Institute in Stockholm. Dr. David Bunce, of the University of London, and colleagues note that low levels of B vitamins have been associated with decreases in mental function. To further investigate, Bunce’s team determined the APOE4 status of 167 individuals age 75 and older and performed a range of cognitive tests. In the most demanding test, participants were presented with a list of 12 unrelated nouns, at a rate of one word every 2 seconds. They were immediately given 2 minutes to recall the words. In the APOE4-positive group, average scores for this test were 3.68 for those with low B12 and 6.48 for those with normal levels. Corresponding scores in the non-APOE4 group were 4.78 and 5.32. Analysis showed that recall performance was significantly lower in the low-B12, APOE4-positive group. The investigators also found that low folate levels had a similar effect, although it was not as strong. They conclude, “There is good reason to consider inclusion of vitamin B12 and folate supplements as part of preventive health regimens for older persons,” especially APOE4 carriers. Reuters Health 4/14/04 Neuropsychology, April 2004, 18(2):362-370

White House to Discuss Stem Cells With House - Members of Congress who have been lobbying the White House to loosen restrictions on research with human embryonic stem cells have been promised a meeting with a White House representative the week of May 9th. Several Hill-watchers said it would be the first face-to-face meeting between lawmakers and the White House on the issue in more than two years. The meeting comes as pressure is growing on several fronts to allow federal funding of research on embryos slated for disposal at fertility clinics. A letter similar to the House version is being circulated in the Senate. And Nancy Reagan is to appear at a California event the weekend of May 8-9, 2004, to support stem cell research. Some scientists believe the cells can form the basis of cures for AD, which has long afflicted former president Ronald Reagan, as well as a number of other ailments. “People on both sides of the aisle are realizing that the policy is not working,” Rep. Diana DeGette (D-Colo.) said. If the White House is not responsive, she added, she is confident that a “solid majority” of the House would legislate a change. The meeting should not be taken to suggest that the White House is reconsidering its stance, said spokesman Trent Duffy, who added that House members can expect to receive a response to their letter soon. By Rick Weiss Washington Post Staff Writer 5/9/04

Caregivers

Counseling Helps AD Caregivers - Spouses, who are usually the primary caregivers for those with AD, often experience stress, depression, and other mental health problems as a result of the continuing and demanding levels of care required. A study by New York researchers has found counseling and long-term support programs help ease depression of spouses caring for AD patients. The New York University School of Medicine study showed the support programs’ mental health benefits for the caregivers were long lasting. “The intensive intervention in this new study was very brief -- only six counseling sessions -- and yet that seems to have had a very long lasting effect,” said lead author Mary Mittelman. “I explain it as a snowball effect, whereby the benefits that started in the counseling sessions led to changes that many families made in the way they interacted afterwards.” UPI 5/3/04 American Journal of Psychiatry May 2004;161:850-856

Helping Kids Understand AD - When a loved one is diagnosed with AD, the entire family feels the impact. And understanding what is happening to that loved one can be difficult and confusing for children. However, there is help. Maria Shriver, First Lady of California and a former NBC News correspondent, has written a book for children and families dealing with AD. It’s titled, “What’s Happening to Grandpa?” and she speaks with special authority on the subject as her own father, Sargent Shriver, was diagnosed with AD last year. Shriver discussed the book on “Today” on 5/4/04. Her children’s book offers a touching and optimistic story about the disease, that encourages awareness, acceptance and dialogue among family and friends. An excerpt is at http://www.msnbc.msn.com/id/4893329/

Testing

Mayo Researchers Invent Targeted Imaging Probe to Aid Early AD Diagnosis - Mayo Clinic researchers have devised a way to produce enhanced MRI (magnetic resonance imaging) pictures of the destructive brain lesions that cause AD. This advance using laboratory mice lays the foundation for the first imaging-based diagnostic test for living AD patients. The new technique is currently used only with specially-bred laboratory animals, but is expected to move to human trials if these early results are sustained. “We are encouraged by these results because they suggest we are close to developing an AD diagnostic tool people have been waiting on for decades,” says Mayo Clinic neurology researcher and principal investigator, Joseph Poduslo, Ph.D. “A simple MRI evaluation for AD would ease the suffering of so many families, and hopefully, vastly improve patient-care options.” PR 4/30/04 The findings will appear in the May 25th issue of the journal Biochemistry, No. 20, vol. 43

Researchers Identify Novel Method of Distinguishing AD from Other Types of Dementia - Testing blood flow in a specific region of the brain may boost the degree of diagnostic certainty of AD in difficult cases from 90 percent to almost 100 percent, said Dr. Frederick Bonte, director of the Nuclear Medicine Center at the University of Texas Southwestern. They use single- photon emission computed tomography (SPECT) can be used to identify a characteristic sign of AD and distinguish it from a group of illnesses known as frontotemporal diseases, which comprise the second-leading cause of dementia in the elderly. SPECT is a radioisotope test that produces a three-dimensional picture of the amount of blood flowing in certain regions of the brain. People with AD have reduced blood flow in some areas of the brain, one of which is called the posterior cingulate cortex. This region helps process information from the parietal cortex and the hippocampus, which are responsible for storing vocabulary words and geographical infor-mation. “This is the first publication using the posterior cingulate to rule out frontotemporal disease,” said Dr. Bonte, the study’s lead author. “If the blood flow is significantly reduced to that structure, you have identified AD,and you have simultaneously excluded the frontotemporal dementias.” PR 05/05/04 Journal of Nuclear Medicine 2004 45:771-774

Finding May Help Identify AD - Scientists have found an area in the brains of monkeys and rats that loses a significant number of cells as the animals age, a finding they say could help doctors differentiate between normal age-related mental decline and AD in humans. Dr. Scott Small and his colleagues at Columbia University College of Physicians and Surgeons published data from AD patients last year showing that a sliver of tissue that surrounds the top of the hippocampus, called the entorhinal cortex, is damaged early on in the mind-robbing disease. The entorhinal cortex is a gateway into the hippocampus, shuttling information in and out of the region. But now, the New York researchers have found that aged rats have changes in another region of the hippocampus called the dentate gyrus. And because these older animals don’t get AD, the entorhinal cortex remains intact. These differences may make it possible to distinguish between a living AD brain and one that exhibits the memory loss caused by old age. “This is good news,” said Carol Barnes, a co-author with Small on the study. “If these systems work the same way in humans, it means that AD won’t be a problem for everyone.” Some scientists believe AD will occur in everyone — if they live long enough. By Jamie Talan Newsday 5/4/04 Proceedings of the National Academy of Sciences 101(18):7181-7186

OHSU Study: Rate of Brain Volume Loss Predicts Dementia - The rate of brain volume loss may help doctors predict whether a patient will develop dementia before they even start showing signs of the disease, Oregon Health & Science University researchers in the OHSU School of Medicine’s Department of Neurology discovered. They found that rates of total brain volume loss may help identify patients with mild cognitive impairment who are at high risk of developing dementia. The discovery could help doctors plan early treatment strategies and prevention studies. Joseph F. Quinn, M.D., study co-author and assistant professor of neurology, called the findings “very important.” The study was presented 4/27/04 at the 56th annual meeting of the American Academy of Neurology. None of the subjects were cognitively impaired at the start of the study. Tests were conducted to determine cognitive ratings for each individual and their placement in one of three categories: intact cognition, mild cognitive impairment that was stable, and mild cognitive impairment that progressed to AD. Researchers found the rate of total brain volume loss was “significantly” different between the three groups. Mildly cognitively impaired individuals who progressed to dementia had a greater rate of atrophy than the cognitively intact group, while the stable impairment group had an intermediate rate of total volume loss. Hippocampus volume predicted which mildly cognitively impaired individuals would stay stable and which would decline to AD with 70 percent accuracy, while the rate of brain volume loss was 62 percent accurate in predicting cognitive outcome. Combining both variables produced the strongest model: 75 percent accuracy. Scientists have known for several years that people with mild cognitive impairment have some brain atrophy, but until now they haven’t known the impact of the rate or total amount of this shrinkage, prior to symptoms, on determining whether, or when, a person develops dementia later in life. PR 4/28/04

Prevention

Do Antioxidants Contribute to Heart Disease? - Taking antioxidant vitamins, a practice done daily by millions of Americans in hopes of preventing heart disease, may actually contribute to it by boosting production of “bad” cholesterol. New research on rodents shows that high doses of the much ballyhooed antioxidant nutrients -- vitamins C, E, and beta-carotene -- stimulate their liver’s production of very low density lipoproteins (VLDL), which convert in the bloodstream to low-density lipoprotein (LDL), the so-called “bad” cholesterol that accumulates along artery walls and leads to atherosclerosis, or hardening of the arteries. This suggests that getting doses of antioxidants usually found in vitamin supplements -- but not what is found in food -- may be “potentially harmful” for the heart, says researcher Edward A. Fisher, MD, PhD, director of the Lipid Treatment and Research Center at New York University Medical Center. “If you’re concerned about heart disease, our study offers another reason not to take them,” he tells WebMD. “But it’s not as simple as whether you should take, or not take, vitamin E or other antioxidants. What our study shows is that in some situations, oxidative stress might be good and in others it is bad.” His research, published in the Journal of Clinical Investigation, is reportedly the first to link antioxidant vitamins with increased VLDL production. And that’s what it makes it important, says one expert. By Sid Kirchheimer WebMD Medical News 5/3/04 J. Clin. Invest. 113:1277-1287 (2004)

Other Items

Brain Memory Bank is ‘Key’ to AD - Scientists have identified a region of the brain, the anterior cingulate, as responsible for long-term memory, bringing closer the development of treatments for AD. The breakthrough opens up a new field of research into ways to treat diseases that affect the memory. It has long been known that the hippocampus processes recent memories and that it stores the information permanently. However, the storing and processing of more long-term recall has, until now, been a mystery. Alcino Silva, of the Brain Research Institute at the University of California Los Angeles, said the findings suggested dementia is caused by the anterior cingulate malfunctioning. “If the anterior cingulate malfunctions, a recalled memory may be too fragmented to make sense. This could be what happens during dementia. Now that we know where to look, we are one step closer to developing drugs to target genes or processes of the brain that may be related to memory disorders.” By Nic Fleming Telegraph (UK) 5/8/04 Science 304(5672): 881-883 7 May 2004

Possible New Treatment Strategy for AD - A new study published 4/16/04 in mice identifies one of the missing steps in how AD develops and suggests a possible new treatment strategy, according to researchers at Columbia University Medical Center and Weill Cornell Medical College and their colleagues. The researchers, led by Shi Du Yan, M.D. and Joyce W. Lustbader, Ph.D. at Columbia and Hao Wu, Ph.D., at Weill Cornell, created a crystal form of two molecular components of the disease. “The crystal complex is the first demonstration that beta-amyloid peptide binds to a protein called ABAD (β-amyloid-bindiing alcohol dehydrogenase) and accumulates inside the mitochondria in brain cells,” Lustbader said. Many researchers believe that AD occurs when beta-amyloid clusters in and ultimately kills brain cells by causing the production of destructive free radicals in the mitochondria. “Our findings suggest that one way to treat AD would be to develop a drug that prevents the beta-amyloid peptides from binding with ABAD, which might prevent the cascade of damage that AD typically leads to,” Yan said. PR 4/16/04 Science 304 (5669):448-452 16 April 2004

AD Cuts Life Expectancy in Half - Study - An AD diagnosis cuts a person’s remaining life expectancy in half, according to a report on 4/3/04 that gives a new estimate of how long patients will live with the disease. The study of 521 people with newly diagnosed AD found that the median survival period was 4.2 years for men and 5.7 years for women, about half what a person of the same age who did not have the disease would be expected to live. Previously there has been no firm estimate of life expectancy with AD. Dr. Eric Larson and colleagues at the University of Washington followed 521 men and women over 60 who had been recently diagnosed with AD. Those diagnosed in their 70s lived longer than those diagnosed at age 85 or older, said Larson, director of the Center for Health Studies at the Group Health Cooperative in Seattle and a former medical director of the University of Washington Medical Center. “This finding moves us toward a more precise vision of the course that AD may take in people with certain clinical characteristics,” Larson said in a statement. “For doctors, this provides very useful data for gauging the prognosis of an (AD) patient. For patients and their caregivers, as difficult as this may be to hear, it can help in making appropriate plans for the future.” The study, funded by the National Institute on Aging. Reuters Health 4/6/04 Annals of Internal Medicine 2004; 501-509

Holding on to Memories: Techniques for Seniors to Overcome Those ‘Senior Moments’ - Although cognitive and physical changes occur during the aging process, many of us have these moments well before we reach the golden years. According to Ruth Kandel, a physician at the Hebrew Rehabilitation Center for Aged, the most important thing is not to worry too much about forgetfulness. “‘Senior moments’ do not define dementia,” she said. For whatever reason, we blame these moments on the aging process when, in fact, a variety of other factors could influence mental capabilities. Seniors’ cognitive functions can be hampered by hearing and vision problems and emotional factors such as depression. But lifestyle factors such as alcohol, sleep, stress, and medications -- even relatively harmless antihistamines -- can affect memory and performance for people of every age. Kandel says that even small lifestyle changes can impact memory and cognitive function. But it is possible to give yourself a mental boost and fight aging. Adrienne Rosenberg, director for the Advanced Cognitive Training for Independent and Vital Elderly, ACTIVE, project, said, “As the old saying goes, ‘If you use it, you won’t lose it.’” ACTIVE, a National Institutes of Health-sponsored research program at the Hebrew Rehabilitation Center, tested exercises designed to improve cognitive performance. The researchers hoped to determine if cognitive exercises could keep minds in shape just as physical exercise keeps bodies in shape. Rosenberg and her colleagues taught strategies based on a fourstep approach known as MOVA -- meaningfulness, organization, visualization and association. MOVA states that people are more likely to remember things more easily if they have meaning. Items such as grocery lists can be better recalled when their components are grouped into categories -- for example, produce, dairy and household products. Visualization is a technique that can be helpful when trying to remember a name. By closing your eyes and visualizing a person’s face, you may recall it. And by associating a new piece of knowledge with something else you already know, you have a greater chance of remembering it down the road. “What’s great is that these principles can be used together,” said Rosenberg. ACTIVE researchers found that participants improved in specific memory tasks and believe that the training can carry over to daily activities. According to Rosenberg, the ultimate goal is fewer nursing home admissions, driving accidents and falls among the senior population. Kandel’s advice is to purchase a notebook, keep a list of things to remember, and form a habit of checking the list each day, which may not feel comfortable in the beginning. Kandel said that “senior moments” deserve more attention when the changes become more significant and impact everyday function. “If people are worried, they should speak with their doctors,” she said. By Michelle Apuzzio Boston Herald 5/5/04 Wednesday, May 5, 2004 The web page on the ACTIVE program is http://www.hebrewrehab.org/senior_care/cpc_activeseniors.cfm

AD - Recent Discoveries Pave the Way Toward New Treatments - Lennart Mucke, MD, director of the Gladstone Institute of Neurological Disease and Professor of Neuroscience at the University of California, San Francisco (UCSF), discussed on April 29 at the American Academy of Neurology (AAN) 56th Annual Meeting the latest therapeutic targets and describe molecular markers of cognitive decline that may facilitate the assessment of new treatments for AD. “Ongoing studies are beginning to unravel the pathways that lead from the accumulation of toxic proteins in the brain to the biochemical alterations and cognitive decline in patients with AD,” said Mucke. His talk, “Markers and Mediators of Neuronal Deficits in Dementia,” highlighted recent discoveries that shed light on the processes underlying the memory loss and other cognitive deficits associated with AD. “Recently, we identified a number of mechanist-ically informative changes in the brains of transgenic mouse models of AD, and we have begun to validate the clinical relevance of these findings in human cases,” explained Mucke. “For instance, deficits in spatial learning and memory in our mice correlated tightly with the depletion of calcium-dependent proteins in specific brain regions. Similar abnormalities were then found in brains from patients with AD, and the greatest depletions were seen in the most severely demented people.” Mucke’s talk focused on these and other key findings from studies of transgenic mice and human brain tissues carried out at the Gladstone Institute of Neurological Disease. One study, for example, showed that high levels of amyloid proteins disrupt complex brain circuits in which memories are formed and stored. Mucke’s work in this area is contributing to an important paradigm shift in the field. Previously, the most widely held view was that large clumps of amyloid proteins in the brain (referred to as “plaques”) cause the neurological decline in AD. But studies conducted at Gladstone, UCSF, and other centers suggest that much smaller aggregates of these proteins are the real culprits. These findings are helping to resolve the controversy surrounding the role of amyloid proteins in AD. Other studies discussed have identified molecular pathways through which amyloid proteins may impair brain functions and have demonstrated that amyloid proteins can enhance the accumulation and toxicity of other disease-causing proteins. The latter finding may help explain the frequent clinical and pathological overlap between AD and Parkinson’s disease. In addition, Mucke described findings that explain how apolipoprotein E4 -- the best established genetic risk factor for AD -- can promote the development of this illness and how its harmful effects might be prevented or reversed with new therapeutic approaches now under development at Gladstone. PR 4/26/04

The Art of Aging Gracefully - Creativity May Aid Brain Function, Even Among Those with Dementia - Dr. Bruce Miller, a behavioral neurologist at UC San Francisco, said “Even though our brains age, it doesn’t diminish our ability to create.” The big question, as arts projects become more common in retirement and nursing homes, is whether tapping elders’ creativity truly brings them physical health benefits as well as joy. And if so, what works best? The National Institute on Aging and Society for the Arts in Healthcare brought scientists and artists together in April 2004 to galvanize interest in research on creativity to find out. Mental decline once was thought inevitable with aging. Scientists now know that’s not true, and the brain continually rewires and adapts itself even in old age. Even dementia “doesn’t wipe out all aspects of creativity,” says Miller. Indeed, some forms release astounding abilities to draw by people who never before did so, providing important clues to where the brain houses creative abilities. Take Jack, a businessman who claimed he’d never even been in an art museum. About the time he noticed problems speaking, he also began compulsively painting canvases full of brightly colored lines. His painting improved he even won awards as the language center of his brain decayed. By the time he painted a stunningly vivid purple and yellow portrait of a parrot, “He no longer knew what a bird was,” recalls Miller. Jack had an illness often confused with AD called “frontotemporal dementia.” It initially spares the parietal lobes important for visual artistry even as it destroys other regions crucial for verbal skills, Miller explains. With AD, in contrast, early damage to visual-artistry areas leaves patients unable to copy simple geometric designs. By Lauran Neergaard AP Medical Writer 5/3/04

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