Alzheimer Related News Items

News as of 4/09/06

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For more AD information, see Alzheimer Information athttp://www.connext.net/~seniors/infoad.htm

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Top Items

Seed of AD Spotted - Karen Ashe at the University of Minnesota, Minneapolis, and her team studied a strain of mice that, like people, develop mild memory problems in middle age before getting more severe AD symptoms. The mice were genetically engineered to make a version of a human protein called amyloid-beta. Researchers know that this protein clogs the brains of AD patients late in the disease. By extracting amyloid-beta from the animals’ brains, the team discovered a knot of 12 proteins that appears outside brain cells just as memory loss occurs. These clusters, called Abeta*56 (also written as Aβ*56), are different from the large plaques of amyloid-beta that form later in AD patients. The “56” appears from a more complete description as a 56-kDa soluble amyloid-β assembly. The more of these clusters mice have, the worse their memories are, the team reports. And injecting clusters into the brains of rats causes temporary amnesia. Ashe proposes that the clusters of amyloid-beta could interrupt memory by jamming communication between neurons. She suggests that they could be one cause of the mild memory loss widely associated with old age. They could also prefigure the death of neurons and severe cognitive problems. “This may be the seed that defines who gets AD,” she says. The idea needs testing with additional experiments, Ashe says. She is scrutinizing the preserved brains of people who displayed early signs of AD and then died from other causes, to see whether they contain Aβ*56. Another key test is whether drugs that stop the protein clusters forming can halt memory loss in mice. “That’s the gold-standard proof of this hypothesis,” Ashe says. Spotting clusters of Aβ*56 in the blood might help doctors to identify who is at risk of disease, helping them to target possible treatments. Drugs or vaccines that stop the clusters forming might block the brain’s decline. By Helen Pearson news@nature.com 3/15/06 published Nature online 3/15/06 doi:10.1038/nature04533

A One-Two Punch for AD - AD has two hallmarks: protein clumps, called plaques, that cluster outside of neurons, and twisted protein fibers, called tangles, that build up inside neurons. In the vast majority of AD cases, scientists don't know what triggers build-up of these proteins, and they have been arguing heatedly for years about whether plaques or tangles are the true culprit behind the devastating cognitive decline caused by the disease. Now scientists at Harvard have identified an enzyme, Pin1, that can block build-up of both plaques and tangles in cellular models -- a finding that could help link these two perplexing neurological problems and provide a new avenue for drug development. Both plaques and tangles are caused by the abnormal build-up of proteins. Tangles are made up of a protein called tau, while plaques are made up of fragments of a protein called amyloid precursor protein (APP). In AD patients, both those proteins undergo chemical changes that make them more likely to clump together. In previous research, Kun Ping Lu, a biologist at Beth Israel Deaconess Medical Center and Harvard Medical School, found that an enzyme called Pin1 reverts the tau protein back to its healthy conformation, thereby preventing the formation of tangles. In the current paper [1], published 3/23/06 in the journal Nature, Lu and colleagues showed that Pin1 could also restore the APP protein to its normal shape, preventing the build-up of the toxic fragment that accumulates in plaques. “Pin1 is like the oil in a car engine. You need oil to keep it running smoothly; without it, things begin to break down. If you don’t have Pin1, proteins become misshapen and aggregate into tangles or plaques,” says Lu. By Emily Singer Technology Review 3/23/06 http://www.technologyreview.com/BioTech/wtr_16621,304,p1.html

Latest Lu paper [1] is Nature 440, 528-534 (23 March 2006) with an abstract at http://www.nature.com/nature/journal/v440/n7083/abs/nature04543.html

Drugs

Study Aims To Halt AD By Blocking Enzyme - Oregon Health & Science University (OHSU) is one of six sites around the country taking part in a double-blind, placebo-controlled study of the agent known as LY450139, a gamma secretase inhibitor manufactured by Eli Lilly and Co. This drug may prevent AD by blocking an enzyme that produces plaques believed to trigger the disorder. Gamma secretase is an enzyme that produces beta-amyloid by snipping a fragment of the protein from a larger protein that extends across the plasma membrane of the cell. The beta-amyloid fragments clump together to form dense, insoluble plaques inside the hippocampus, a curved, elongated ridge deep in the brain that controls learning and memory, and the cerebral cortex, the surface layer of gray matter of the cerebrum where sensory and motor information is coordinated. The gamma secretase enzyme is made up of a complex of four proteins, and LY450139 is thought to de-activate it by binding within the complex, although the exact location is still being studied. “There is a theory that beta-amyloid produces AD, so if you stop the amyloid, you stop the disease,” said Joseph Quinn, M.D., associate professor of neurology, and cell and developmental biology, OHSU School of Medicine and the Portland Veterans Affairs Medical Center. The study is “focused on the presumed underlying cause of the disease instead of symptoms. This is the beginning of the ‘anti-amyloid’ era of AD treatment, attacking what are thought to be the roots of the disease,” Quinn said. The 29-week-long study, set for completion in September, is a Phase II trial involving 45 participants that will determine LY450139’s safety, whether it causes any side effects, how much of the drug should be given and how long it can be detected in the blood. Science Daily 3/14/06

Blood-Pressure Drugs May Lower AD Risk - Taking medications to lower blood pressure, particularly diuretics, may help reduce risks for AD, a new study suggests. Experts speculate that high blood pressure may increase the risk of the brain-wasting disease. That means drugs that ease hypertension -- another name for high blood pressure -- might also lower AD risk. In fact, “we found that among people taking anti-hypertensives, there was an overall 40 percent reduction in the risk of developing AD over a three- to four-year period,” said study co-author Peter P. Zandi, an assistant professor at Johns Hopkins University’s Bloomberg School of Public Health. Drugs that lower blood pressure include diuretics, beta blockers and calcium channel blockers. While diuretics appeared to offer the greatest benefit to study participants, “we also found some evidence that there was a reduced risk with the use of calcium channel blockers,” Zandi added. In their study, Zandi and his colleagues collected data from 1995 to 1998 on nearly 3,300 elderly people living in Cache County, Utah. Among the people in the study, more than 1,500 used blood pressure medications. By 1998, 104 people had developed AD. The researchers found that people who were taking blood pressure medications at the start of the study were significantly less likely to develop AD compared with those who were not. The biggest effect was seen with the use of potassium-sparing diuretics -- drugs that contain additional components to maintain blood levels of potassium. These drugs were associated with more than a 70 percent reduction in the risk of developing AD, Zandi’s team found. Calcium channel blockers reduced the risk by up to 50 percent, but other blood pressure drugs had little effect on the development of AD, Zandi said. It’s unclear why some anti-hypertensives seem to reduce AD risk and others do not, Zandi said. “There may be something special about calcium channel blockers and potassium blockers, other than their effect on blood pressure,” he said. Zandi stressed that the findings need to be viewed with caution. “We don’t want people to change their anti-hypertensive medications based on this one report,” he said. “The study raises a hypothesis that needs to be fleshed out and explored though other studies.” Health Day News 3/13/06 3/13/06 online edition of the Archives of Neurology 2006;63:(doi:10.1001/archneru.63.5.noc60013)

Study of AD Drug Aricept Revives Questions on Risk - An unusual number of deaths among patients in a large study of Aricept, the most popular drug to treat AD, is raising concern among federal drug officials and some disease experts. In the study, of 974 patients who suffered from dementia related to heart disease, 11 deaths occurred among the patients taking Aricept, while no deaths occurred among those taking dummy pills. The Food and Drug Adminis-tration is examining the results of the study, said Susan Bro, an agency spokeswoman. The agency undertook a quick review of earlier Aricept studies and found no cause for concern, Ms. Bro said. “The drug remains a safe option for patients who are receiving it,” she said. But experts in AD said that the new study should not be dismissed and that it might indicate that Aricept and similar drugs increased the risks of heart disease. Because Aricept’s benefits in fighting AD are at best mild, any increase in risk should cause concern, they said. “These drugs are well known to slow the heart and constrict the respiratory passage ways,” said Dr. Lon Schneider, a professor of psychiatry, neurology and gerontology at the University of Southern California. Dr. Schneider said some patients might conclude from the results of the latest study that Aricept and similar drugs like Reminyl, Exelon and Tacrine were too risky for them or for family members. In the study, the difference between the number of deaths in the group taking Aricept and the comparison group that took placebo pills was statistically significant, meaning the difference was unlikely to have occurred by chance. Aricept is sold by Pfizer and by Eisai, a Japanese pharmaceutical maker. Pfizer reported that the drug had $346 million in sales last year. A Pfizer spokeswoman referred callers to Eisai, which conducted the study. Judee Shuler, an Eisai spokeswoman, said the study results were a statistical fluke. Patients given placebos in the study were unusually healthy, she said, making a comparison with the group taking Aricept unfair. Aricept remains safe, Ms. Shuler said, and the company is not recommending any changes to the drug’s label. By Gardiner Harris NY Times 3/17/06

New Drug Phenchlobenpyrrone Developed for AD Treatment - Researchers from the Chinese Academy of Sciences (CAS) are excited about a new drug that might prove to be a breakthrough for the treatment of AD. The new drug, which goes by the Latin name of Phenchlobenpyrrone, was approved by the State Food and Drug Administration for phase I clinical trials. Hao Xiaojiang, a principal investigator at the CAS Kunming Institute of Botany, said 3/15/06 in a telephone interview with Xinhua that animal tests showed that Phenchlo-benpyrrone was at least eight times more effective than the AD drug, Aniracetam granules. Pharmacological research showed that the new drug is able to protect the brain from anoxia and nerve cell damage. Research suggests it might also improve memory, Hao said. Xinhuanet 3/15/06

Genes & Genetic Issues

First Bladders Grown in Lab Transplanted - Researchers said 4/3/06 that they have grown complete urinary bladders in a laboratory and transplanted them into patients, improving their health and achieving a Holy Grail of medicine: the first cultivation of working replacements for failing solid organs in people. The “neo-bladders,” each one grown in a small laboratory container from a pinch of a patient’s own cells, have been working in seven young patients for an average of almost four years, according to a report released 4/4/06 by the British journal The Lancet. The organs have remained free of the many complications that bedevil the conventional practice of surgically constructing bladders from other tissues. If ongoing studies continue apace, the researchers said, they hope someday to offer patients more than a dozen other home- grown organs, including blood-vessel complexes, partial kidneys and perhaps hearts. “It was really uncharted territory in terms of how you do these things,” said Anthony Atala of Wake Forest University School of Medicine in Winston-Salem, N.C., who led the work with Alan Retik at Children’s Hospital and Harvard Medical School in Boston. “Were very pleased with how well theyre functioning.” Experts applauded the work as a coming of age for the long-struggling field of tissue engineering and as a possible way to bypass some of the controversy over embryonic stem cells. By Rick Weiss Washington Post Staff Writer 4/4/06 The Lancet early online publication, 4/4/06 DOI:10.1016/S014-6736(06)68438-9

Embryonic Stem Cell Success - Scientists in Germany said 3/24/06 they had retrieved easily obtained cells from the testes of male mice and transformed them into what appear to be embryonic stem cells, the versatile and medically promising biological building blocks that can morph into all kinds of living tissues. If similar starter cells exist in the testes of men, as several scientists 3/24/06 said they now believe is likely, then it may not be difficult for scientists to cultivate them in laboratory dishes, grow them into new tissues and transplant those tissues into the ailing organs of men who donated the cells. The technique would have vast advantages over the current approach to growing “personalized” replacement parts -- an approach that has stirred intense political controversy because it requires the creation and destruction of cloned human embryos as stem cell sources. The new work suggests that every male may already have everything he needs to regenerate new tissues -- at least with a little help from his local cell biologist. By Rick Weiss Washington Post Staff Writer 3/25/06 Nature advanced online publication 3/24/06 doi:10.1038/nature04697

UK Scientists Launch Big Genetic Database Project - A major project to collect DNA samples and medical data from 500,000 people was launched on 3/15/06 to study how genes, lifestyle and environment affect the risk of disease. The UK Biobank, the world’s biggest genetic database, will hold millions of samples in a robotically controlled facility near Manchester, England. The wealth of data that will be collected from men and women volunteers aged 45-69 will help scientists determine the genetic basis of diseases and why some people develop cancer, heart disease, diabetes, asthma or AD and others don’t. “Nothing like this has been attempted before in such fine detail on such a vast scale,” said Professor Rory Collins, chief executive of the Biobank. “We will get very reliable information about the causes of disease,” he told a news conference. By Patricia Reaney Reuters Health 3/15/06

Caregivers

Stigma, Denial Delay AD Diagnosis: Survey - Concern over stigma and denial can delay the diagnosis of AD for years, which means that patients do not receive treatment that could slow the disease progress, according to a survey released on 3/21/06. When spouses or other relatives who care for patients are concerned about the stigma associated with the disease, delay of the diagnosis averages 6 years after symptoms first appear, the survey by the Alzheimer’s Foundation of America showed. “Any delay in diagnosis is a setback for people with AD and their caregivers -- and a delay of two years or more is a serious and unnecessary setback,” said Eric Hall, chief executive officer of the foundation. “Diagnosis and treatment are essential because there are treatments available...that have shown to potentially help maintain a person’s ability to think clearly and perform everyday tasks for a longer period of time than if left untreated,” said Dr. Beth Safirstein, co-president and medical director at the MD Clinical/MD Clinical Trials Foundation Inc. in Hallandale Beach, Florida. By Joanne Morrison Reuters Health 3/21/06

Communicating Effectively with a Person Who Has AD - Because AD slowly erodes communication skills, an affected person’s words and behavior may make little or no sense to you. Your loved one may have just as much trouble deciphering your words. The resulting misunderstandings can fray the tempers of everyone involved, making communication even more difficult. It’s incredibly frustrating - for both of you. AD damage to pathways in the brain may make it more difficult to recall and to understand words. The frustration of having a precise word “on the tip of your tongue” becomes increasingly common for people with AD. Sometimes, one word is incorrectly substituted for another. Or your loved one may just invent an entirely new word to describe a familiar object. He or she may get stuck in a groove, like a skipping record, and repeat the same word or question over and over. People with AD may also (1) lose their train of thought, (2) struggle to organize words logically, (3) need more time to understand what you’re saying and (4) curse or use offensive language. To help: (1) Make allowances. Try to remember that your loved one is not acting this way on purpose. Try not to take it personally. It’s the disease talking, not your loved one. (2) Show interest. Maintain eye contact and stay near your loved one, so he or she will know you’re listening and trying to understand. (3) Avoid distractions and noise. Communication is difficult, if not impossible, against a background of competing sights and sounds. (4) Keep things simple. Use short sentences and plain words. Avoid complicated questions or directions. (5) Don’t interrupt. It may take several minutes for your loved one to respond. Avoid criticizing, hurrying, correcting and arguing. (6) Use “props” and visual cues to increase recognition. For example, take the person to where the toilet is visible, and point to it before asking if he or she needs to go to the bathroom. Finally, even if you get frustrated, try to keep your voice calm and relaxed. If your words and the way you say them don’t match, it may be confusing. Your nonverbal cues often send a clearer message than what you actually say. Mayo Clinic http://mayoclinic.com/health/alzheimers/AZ00004

Assisted Living, Home Care Costs Climb: Study - Older Americans in need of care face sharp spikes in the cost of increasingly popular assisted living quarters and home health aides, according to a study. The average price tag for a private one-bedroom unit in an assisted living facility rose 7 percent in 2006 to about $33,000 per year, compared with a 5 percent rise in 2005, according to a survey by insurer Genworth Financial Inc. The average hourly rate for most home health aides climbed 19 percent to $22.15 per hour, compared with a 2 percent rise in 2005, the study found. The average cost for a private room in a nursing home, by contrast, rose 2 percent to about $71,000 in 2006, after rising 6 percent in 2005. The increased costs reflect the growing popularity of home health care and assisted living centers, which typically provide meals, help with everyday tasks and provide some medical care. Assisted living centers cost less than nursing homes and attract patients not needing the more greater medical treatment offered by nursing homes. The survey of 9,000 nursing homes, assisted living facilities and home care providers was conducted in January and February of 2006. By Kim Dixon Reuters 3/27/06

Prevention

Vitamins Plus Ibuprofen May Ward off AD - For patients at high risk of AD, taking a combination of vitamins E and C plus ibuprofen significantly reduces their risk, results of a longitudinal study suggest. Specifically, the combination seems to benefit people who carry a variant of the gene for apolipoprotein, APOE-4, which is known to put them at high risk for developing AD. “We found that for people at low risk, taking vitamin C and E alone is sufficient to further reduce their risk,” Dr. Majid Fotuhi told Reuters Health. “But for those with (APOE-4), the combination [with ibuprofen] exerts a synergistic benefit.” Fotuhi, from Johns Hopkins University in Baltimore, and his associates followed nearly 5000 elderly residents of Cache County in Utah for 8 years, taking into account their regular consumption of vitamins C and E, and ibuprofen. They identified 127 subjects who regularly consumed all three agents, Fotuhi reported at the American Academy of Neurology’s annual meeting here in San Diego. Results showed that this group exhibited significantly less decline in mental performance scores. “With this approach, we’ve advanced a two-point attack on the cascade of events that leads to AD pathology,” Fotuhi said. “On the one hand, we reduce inflammation (with vitamins E and C), and on the other hand, we reduce the amount of amyloid in the brain (with ibuprofen), the substrate that causes inflammation.” As noted, APOE-4 carriers experienced the greatest benefit from the triple combination. According to the researchers, this subset of patients in their late 60s or 70s exhibited no decline in cognitive function during the 8-year follow-up when they took all three agents. Subjects who took just one of these agents had worsening memory over time. Fotuhi recommends a dose of ibuprofen no higher than 100 mg per day. By Karla Gale Reuters Health 4/7/06

Midlife Obesity Raises Risk of AD - Being overweight during one’s early 40s increases the risk of AD decades later, new research shows. “We originally thought that once we took into account diabetes and cardiovascular disease, that there would be no effect of overweight on AD, but that turned out not to be the case,” Dr. Rachel A. Whitmer said at a press briefing held at the American Academy of Neurology’s annual meeting in San Diego. Whitmer, from the Kaiser Permanente Foundation Research Institute in Oakland, California, and her colleagues studied data on nearly 9000 men and women who were between the ages of 40 and 45 years old when they were first examined between 1964 and 1973. Body fat was measured in the back and arms using special calipers. During an average follow-up period of 23 years, 221 cases of AD were diagnosed. After factoring in the effects of diabetes, stroke, high cholesterol levels, and high blood pressure, “we observed a strong independent effect for people with high levels of adiposity” [i.e. fat] in middle age, Whitmer said. Subjects with high levels of fat in the arm and back were nearly three times more likely to develop AD than those with low levels. The association was even stronger when taking into account body mass index (BMI), an overall measure of body weight in relation to height, the researcher added. “Doctors need to remind people that they need to think about weight in middle age,” she said. Losing excess weight and body fat in middle age is not just good for the heart, it’s also good for the brain. Whitmer and her team plan to evaluate whether weight loss reduces the risk of AD. Reuters Health 4/6/06

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