Alzheimer Related News Items

News as of 07 /04/04

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British Study Sees Scant Value in AD Aricept - The most widely prescribed drug for AD, Aricept, does not delay the onset of disability or the need for a nursing home, British researchers are reported 6/25/04 in The Lancet, the British medical journal. The researchers say that the drug has “disappointingly little overall benefit” and is not cost-effective, and that better treatments are needed. The report is based on a study of 565 patients with mild to moderate AD who were assigned at random to receive either Aricept or a placebo and were then followed for up to three years. Although the patients taking the drug did have slightly higher scores on mental tests, after three years they did not differ from the placebo group in their rates of being put in a nursing home or becoming disabled. There were also no significant differences between the groups in behavioral or psychological symptoms or in the emotional well-being of the people taking care of the patients. Richard Gray, the director of the study and a professor of medical statistics at the University of Birmingham, in England, said in a telephone interview that Aricept offered “poor value for the money,” with such small benefits that patients and families would probably not notice a difference if they discontinued the drug. Earlier studies sponsored by drug companies and used in advertising campaigns had suggested that Aricept could delay a move to a nursing home by several years. Professor Gray’s findings make those claims implausible, according to an editorial in The Lancet by Dr. Lon S. Schneider, director of the Alzheimer’s Research Center of California at the University of Southern California. But in a telephone interview, Dr. Schneider said he prescribed Aricept and similar drugs and kept patients on them as long as the patients seemed not to be worsening. But he said Professor Gray’s research might make it easier for doctors to take a patient off the drug if it did not seem to be helping, because the study also showed that patients could stop taking Aricept without suffering a sharp mental decline. The belief that patients who quit the drug would “crash” mentally was widespread, Dr. Schneider said, but he called the idea a marketing claim and said the study refuted it. Aricept is the most popular AD in a class of drugs called cholinesterase inhibitors, approved to treat mild to moderate stages of the disease; it is made by the Eisai Company and marketed in the United States by Pfizer and Eisai. In a joint statement, Pfizer and Eisai said the Lancet study appeared unreliable because it was too small, and the results were inconsistent with previous research. By Denise Grady NY Times 6/25/04 Lancet 2004;363:2105-15

Blood Pressure Drop Warns of Dementia - Study - Elderly people whose blood pressure drops suddenly may be about to develop AD or other forms of dementia, researchers in Sweden reported on 7/1/04. Patients whose systolic blood pressure -- the top number -- dropped 15 points or more in six years or less had triple the risk of AD or other dementia, the team at the Karolinska Institutet in Stockholm found. “Our findings imply that poor blood flow in the brain, resulting from an extensive decline in blood pressure, may promote the dementia process,” Dr. Chengxuan Qiu, who led the study, said in a statement. “These findings indicate a possible threshold level in systolic pressure, especially for people with vascular disease in whom further reduction of blood pressure under this level may precipitate dementia onset,” Qiu added.“Using antihypertensive medications is important for high blood pressure and related disorders, but our findings suggest that it is necessary to monitor these drugs in the very old to avoid a probable dangerous drop of blood pressure under a certain threshold.” “Our data show no substantial differences in blood pressure levels at enrollment between non-demented persons and those that were demented three to six years later,” said Dr. Bengt Winblad, a professor of geriatric medicine at Karolinska Institutet. “However, some elderly people who experience a significant decline in systolic blood pressure three to six years before diagnosis do have an increased risk of dementia and AD.” The researchers said it is possible that degeneration of cells in the parts of the brain that regulate blood pressure may cause the pressure to fall. That could mean the low blood pressure was a symptom of dementia that could accelerate an already ongoing process. Reuters 7/1/04To be published in Stroke

Novel Monoclonal Antibody Undergoing Phase 1 Tests - The drug, AAB-001, is the first of its kind to emerge for testing since trials of an anti-amyloid vaccine were suspended two years ago due to medical complications. AAB-001 is a novel monoclonal antibody, using synthetically engineered antibodies directed to seek out and reduce amyloid for the treatment of AD. The monoclonal antibody is intended to provide the patient’s immune system with the capability to respond to the amyloid, a key difference from an earlier vaccine strategy. In that study, the vaccine, AN-1792, stimulated the patient to mount their own immune response, that is, produce their own antibodies. The primary purpose of this study is to evaluate the safety of AAB-001 and how well increasing doses of AAB-001 (in successive groups of subjects) are tolerated. A secondary purpose of the study is to measure the amount of AAB-001 in the blood, and how long it remains in the blood over time. AAB-001 is a new investigational drug and is not currently approved for commercial use by the U.S. Food and Drug Administration. In this study, AAB-001 is being given to humans for the first time. The study is sponsored by Wyeth Research, and is an initiative of the Elan/Wyeth Alzheimer’s Immunotherapy Program. The AD Research Center (ADRC) at the University of Pittsburgh is one of the research sites chosen to participate in the first human clinical trials. PR 6/24/04

Axonyx Initiates Second Phase III AD Trial with Phenserine - Axonyx Inc. announced 6/16/04 the initiation of its second Phase III international clinical trial with its lead AD drug, Phenserine. Phenserine is an acetylcholinesterase and beta amyloid precursor protein (B-APP) inhibitor that is being developed by Axonyx for the treatment of mild to moderate AD patients. Phenserine is currently also undergoing clinical testing in a Phase IIB study designed to evaluate Phenserine’s ability to lower the levels of the beta-amyloid precursor protein and beta-amyloid in the plasma and cerebrospinal fluid of mild to moderate AD patients. The presence of toxic beta-amyloid in the brains of AD patients is considered by many experts to be a key pathological event in the causation as well as the progression of AD. PR 6/16/04

Genes & Genetic Issues

Gene Loss Linked to AD - Scientists at the Children’s Hospital in Boston found that genes which play a key role in keeping our minds sharp gradually begin to turn off as we age. They hope the discovery could lead to new ways to preserve brain function and ward off AD. Lead researcher Professor Bruce Yankner said: “We found that genes that play a role in learning and memory were among those most significantly reduced in the ageing human cortex. These include genes that are required for communication between neurons.” Gene activity was assessed by measuring the amount of proteins that they produce. Protein levels were reduced in older individuals - and changes seemed to start for some in their 40s. However, the rate of deterioration seemed to vary between individuals. The researchers believe brain genes are particularly vulnerable to toxins in the environment, and to charged oxygen molecules called free radicals which are released by chemical reactions in the body. In addition to a reduction in activity in genes important for thought processes, they found evidence of greater activity among genes associated with stress and repair mechanisms and genes linked to inflammation and immune responses. This suggests that the ageing brain has to try to cope with increasing levels of damage. Professor Yankner said: “The brain’s ability to cope with these toxic insults and repair these genes declines with age. It will now be important to learn how to prevent this damage, and to understand precisely how it impacts brain function in the elderly.” Dr Yankner said it had already proved possible to repair ageing genes in the laboratory - but he stressed much more work was required to achieving the same effect in a living human brain. BBC News 6/12/04 Nature 429,883–891 (24 June 2004)

Stem Cells

Bush Defends Limits on Stem Cell Research - President George W. Bush on 6/15/04 defended his policy of strictly limiting stem cell research, despite pressure to reconsider after former President Ronald Reagan died of complications from AD. Reagan’s death on June 5 has galvanized an effort to allow stem cells to be used to seek a cure for AD, a brain-wasting illness. His widow, Nancy, has become a powerful spokeswoman for the push to broaden the use of stem cells in medical research. Bush, speaking to an audience of core conservative Christian supporters, underscored his opposition to most embryonic stem cell research. “Life is a creation of God, not a commodity to be exploited by man,” Bush told the Southern Baptist Convention via satellite. Although Bush did not specifically mention stem cells in the speech, a spokesman later confirmed that the rejection of the use of life as a “commodity” was a reference to his stance on stem cells. “It goes to the principle on which his policy was based,” said White House spokesman Trent Duffy. By Caren Bohan Reuters 6/15/04

Stem Cells An Unlikely Therapy for AD - Human embryonic stem cells have the capacity to morph into virtually any kind of tissue, leading many scientists to believe they could serve as a “universal patch” for injured organs. Among the more promising targets of such “cellular therapies” are: Parkinson’s disease, which affects a small and specialized population of brain cells; type-1 diabetes, caused by the loss of discrete insulin-producing cells in the pancreas; and spinal cord injuries in which a few crucial nerve cells die, such as the injury that paralyzed actor Christopher Reeve. But in contrast to Parkinson’s, diabetes and spinal injuries, AD involves the loss of huge numbers and varieties of the brain’s 100 billion nerve cells -- and countless connections, or synapses, among them. “The complex architecture of the brain, the fact that it’s a diffuse disease with neuronal loss in numerous places and with synaptic loss, all this is a problem” for any strategy involving cell replacement, said Huntington Potter, a brain researcher at the University of South Florida in Tampa. “We don’t even know what are the best cells to replace initially,” added Lawrence S.B. Goldstein, who studies stem cells and AD at the University of California at San Diego. “It’s complicated.” Goldstein and others emphasized that future AD patients could benefit if stem cell research is allowed to blossom. Scientists suspect, for example, that stem cell studies could help identify the molecular errors that underlie AD, which in turn would help chemists design drugs to slow or even reverse the disease. But that line of work could face formidable political hurdles. That is because the most frequently cited approach would require not just stem cells from spare embryos donated by fertility clinics -- a currently untapped source of cells that many want Bush to make available to federally funded researchers. It would also require the creation of cloned human embryos made from cells taken from AD patients. From such embryos, stem cells bearing the still-unidentified defects underlying AD could be removed and coaxed to grow into brain cells in lab dishes, and their development could be compared to the development of normal brain cells. While that experiment could shed important light on the earliest -- and perhaps most treatable -- stages of AD, a majority in Congress have said that the creation of cloned human embryos is an ethical line they are unwilling to cross. By Rick Weiss Washington Post 6/10/04

Caregivers

AD Patients Retain Unexpected Skills -Study - AD patients may be capable of learning new ways to use their brains, scientists said on 6/9/04 in a study suggesting it may be possible to help loved ones and caregivers better cope with their disease. The study shows the brains of AD patients are more intact than had been thought, at least early on in the disease. They may retain what is known as implicit, or unconscious, memory. “We are not suggesting that this is any kind of cure for the problem,” said Cindy Lustig, a memory researcher at Washington University in St. Louis. “What we are saying is that this is preserved, at least in the early stages, so let’s work on this to try and help them out.” Lustig and Howard Hughes Medical Institute researcher Randy Buckner worked with AD patients at these very early stages. They asked 34 young adults, 33 older adults without any AD symptoms, and 24 older adults showing memory loss and other symptoms of early-stage AD to classify words on a computer screen. While they did this, the researchers used functional magnetic resonance imaging to look at how and where their brains were working. It was a simple task and one that people could be expected to get quicker at doing as they practiced. All three groups did get quicker, even the AD patients, Lustig and Buckner reported. This is a characteristic of implicit memory -- one type of which is developed by repetition or “priming.” Lustig said a good analogy is saying the memory is unconscious. “When you ask an AD patient to try to deliberately remember something and they have to deliberately retrieve it, it is difficult for them,” she said in a telephone interview. But implicit memory lets someone remember how to do something without having to think about it -- for instance, many of the actions involved in touch-typing. While the volunteers used this implicit memory, their brains lit up on the fMRI in a characteristic way. The brains of the AD patients and to a degree the healthy older people worked harder at the task than the brains of the young people. But as they practiced, the MRI scans indicated that the task was becoming easier. “The findings suggest that if we can help people use these brain systems optimally by providing the right kinds of cues or task instructions, we may be able to improve their function,” said Bruckner. By Maggie Fox, Health and Science Correspondent Reuters 6/9/04 Neuron 42,865-875 (10 June 2004)

Testing

Medicare Proposes To Cover PET Scans - Federal health officials said 6/16/04 that they had made a preliminary decision to have Medicare pay for brain scans to help diagnose AD in some patients who show symptoms of the ailment. The decision, announced by the Centers for Medicare and Medicaid Services, a part of the Department of Health and Human Services, was the result of “an exhaustive review of the evidence” undertaken after the agency received “a request to reconsider its previous non-coverage decision.” The decision also came during a week of great attention to AD after Ronald Reagan’s death from the illness. “This new Medicare coverage will improve care for Americans living with suspected AD.” HHS Secretary Tommy G. Thompson said. “It is one of the many ways we’re working to help our Medicare beneficiaries with cognitive impairment get the best possible care based on the best scientific evidence.” PET -- or positron emission tomography, a 30-year-old imaging technology that can highlight areas of metabolic abnormalities in the body -- cannot make a diagnosis of AD. Under the coverage plan, however, Medicare would pay for its use to aid in the diagnosis of suspected AD when diagnosis “remains uncertain despite a thorough clinical evaluation.” Officials provided no estimate of the percentage of patients suspected of having AD that might be covered, or the potential cost to the nation. Tests typically cost about $2,500. By Rick Weiss Washington Post 6/17/04

AD Symptoms Show Early as 50s - In a study by Dr. Richard Caselli, head of the department of neurology at Mayo Clinic in Scottsdale and colleagues more than a hundred men and women, ages 50 to 59, were tested for certain mental abilities over time. Some had the APOE e4 gene marker; some didn’t. All were healthy; most were related to someone who’d had the disease. At intervals over six years, various tests were given to assess mental skills. In one test, participants heard a list of 15 words and then were asked to recall them. In another, they looked at a complicated picture and later had to draw it. Ten minutes later they were asked to draw it again. “The importance of the tests was measuring changes,” Caselli said. Based on performance, it wasn’t clear who did or didn’t have the gene. It was the degree of change from one test to the next, he said. On tests, decline in memory was much more pronounced among people who had the APOE e4 gene. But the loss was not evident in everyday life. Researchers also saw a rise in depression and feelings of paranoia - characteristics of some AD patients - in those with the gene. Caselli concludes that neurological degeneration may start many years before the symptoms are noticed. By Kate Nolan The Arizona Republic 6/26/04 Neurology 2004;62:1990-1995

Prevention

Estrogen Replacement Doesn’t Ward off Dementia - Hormone replacement with estrogen alone does not decrease, and may significantly increase, the risk of dementia or mild mental impairment in older postmenopausal women, according to new findings from the Women’s Health Initiative Memory Study (WHIMS). The latest findings support initial data from WHIMS reported last spring, which showed that estrogen plus progestin increased the risk of dementia in women aged 65 and older, and did not prevent memory loss. “Use of hormone therapy to prevent dementia or cognitive decline in women 65 years of age or older is not recommended,” the WHIMS team writes in the Journal of the American Medical Association. Launched in 1995, WHIMS looked at the effects of estrogen alone or with progesterone on the incidence of probable dementia or mild cognitive impairment in more than 7000 women 65 to 79 years of age. Additional findings from WHIMS reported separately in the journal show that hormone therapy (estrogen alone or with progestin) does not protect and may have an adverse effect on global mental function in older women. Taken together, “we see a consistent pattern of increased risk of dementia associated with hormone therapy and no protection of global cognitive functioning,” Dr. Steven R. Rapp, from Wake Forest University School of Medicine in Winston-Salem, North Carolina, and a WHIMS co-principal investigator told Reuters Health. “This addresses speculations that combination hormone therapy would affect risk differently than estrogen alone,” he added. In an editorial, Dr. Lon S. Schneider, from the University of Southern California, Los Angeles, says many questions remain regarding estrogen’s effects on the brain. “Most important is whether short-term use of estrogen over several years in early postmenopause is effective in reducing dementia 2 or 3 decades later.” By Megan Rauscher Reuters Health 6/22/04 Journal of the American Medical Association 2004;291:2959-2968

Antioxidant Riches Found in Unexpected Foods - Blueberries may be the poster children for antioxidant abundance, but a new study suggests the humble bean may be a more deserving candidate. The largest and most advanced analysis of the antioxidant content of common foods to date shows that disease-fighting antioxidants may be found in unexpected fruits and vegetables, such as beans, artichokes, and even the much-maligned Russet potato. Researchers found that small red beans contain more disease-fighting antioxidants than both wild and cultivated blueberries, which have been heralded in recent years for their high antioxidant content. In fact, three of the top five antioxidant-rich foods studied were beans. The study also shows that nuts and spices, such as ground cloves, cinnamon, and oregano, are rich in antioxidants, although they are generally consumed in much smaller amounts than fruits and vegetables. Antioxidants are believed to help prevent and repair oxidative stress, a process that damages cells within the body and has been linked to the development of cancer, heart disease, AD, and Parkinson’s disease. A big factor in all of this is what happens in the digestion and absorption process. though they have a high antioxidant capacity, they may not be absorbed. Cranberries, blueberries, and blackberries were ranked highest among the fruits studied. Beans, artichokes, and Russet potatoes were tops among the vegetables. Pecans, walnuts, and hazelnuts were the winners in the nut category, and ground cloves, cinnamon, and oregano were the top three antioxidant-rich spices. Below is the list of the top 20 food sources of antioxidants, based on their total antioxidant capacity per serving size with four categories : Rank, Food item, Serving size, and Total antioxidant capacity per serving size. 1. Small Red Bean (dried) - Half cup- 13727; 2. Wild blueberry- 1 cup- 13427; 3. Red kidney bean (dried)- Half cup- 13259; 4. Pinto bean- Half cup- 11864; 5. Blueberry (cultivated)- 1 cup- 9019; 6. Cranberry (whole)- 1 cup- 8983; 7. Artichoke (cooked)- 1 cup- (hearts) 7904; 8. Blackberry- 1 cup- 7701; 9. Dried Prune- Half cup- 7291; 10. Raspberry- 1 cup- 6058; 11. Strawberry- 1 cup- 5938; 12. Red Delicious apple- One- 5900; 13. Granny Smith apple- One- 5381; 14. Pecan - 1 ounce- 5095; 15. Sweet cherry- 1 cup- 4873; 16. Black plum- One- 4844; 17. Russet potato (cooked)- One- 4649; 18. Black bean (dried)- Half cup- 4181; 19. Plum- One- 4118; and 20. Gala apple- One- 3903. Registered dietitian David Grotto says he was amazed to see that unexpected foods, such as beans, potatoes, and artichokes, were so highly ranked by the study. “The message here is diverse diet is still optimal,” Grotto tells WebMD. “You don’t want to be on the all-red-bean diet because it may have the unique set of antioxidants that are attributed to beans, but it may not have many of the antioxidants that you would find in a wild blueberry.” Nor does it mean that you should limit your diet to only the foods that made the study’s top 20 list or start popping antioxidant supplements. “What we’re discovering is that we only know about a thimbleful of all the antioxidants that are probably within foods,” says Grotto, who is also a spokesman for the American Dietetic Association. “What’s unique about eating foods vs. supplements is that there is always more bang for the buck in eating the foods, and you get a lot of those compounds that we really don’t fully understand the benefits of yet.” Grotto recommends the following tips to incorporate more antioxidant-rich foods into your diet: Make bean cubes. Process leftover beans with a little vegetable broth in a food processor until it forms a thin paste. Pour into ice cube trays, and then use the frozen cubes to thicken soups and sauces. Substitute beans for meats. Most recipes that call for ground or cubed meats, such as stews and casseroles, also work with beans like lentils, chickpeas, or black beans in the starring role. Be berry sneaky. Toss a handful of berries on your breakfast cereal or blend them into fruit smoothies for a healthy breakfast or snack. But don’t despair if your favorite food didn’t make the list. Antioxidants are only one piece of the healthy eating puzzle. Some of those foods that are low in antioxidants may have other positive benefits, such as fiber, minerals, and other nutrients that are important. By Jennifer Warner WebMD Medical News 6/17/04 Journal of Agricultural and Food Chemistry; 2004; 52 (12) pp 4026-4037

Other Items

Reagans’ Experience Alters Outlook for AD Patients - An AD diagnosis means something very different today than when former president Ronald Reagan announced 10 years ago that he had the illness: More than any other AD patient in history, Reagan -- with his fame and sunny personality -- dramatically reduced the stigma attached to the deadly degenerative disease, advocates say. "Reagan helped make the world aware of that -- that this was a disease," said Sam Gandy of the Alzheimer’s Association, a national nonprofit advocacy organization. "The stigma is not completely gone, but the Reagans have done more than anyone else to smash that." In 1995, the Reagans launched the Ronald and Nancy Reagan Research Institute at the association, which Gandy said has helped to raise and distribute about $15 million for research into the disease. Nancy Reagan is an honorary board member at the association, and President Reagan’s daughter Maureen was an active board member until her death in 2001. Ronald Reagan died from AD June 5, 2004. Sen. Barbara A. Mikulski (D-Md.) and Sen. Christopher S. Bond (R-Mo.) announced in mid June they would introduce legislation in Reagan’s honor that would double funding for AD research at the National Institutes of Health. By Shankar Vedantam Washington Post Staff Writer 6/14/04