Alzheimer Related News Items
News as of 2/10/02
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UCLA Researchers Invent First Technique to Image AD Onset - UCLA scientists have created the first technique to image the earliest evidence of AD in the living brain - - before the disorder begins attacking brain cells. The technique will allow doctors to monitor the disease as it unfolds - - speeding diagnosis, intervention and new therapies for the disorder that afflicts 10 percent of people older than 65. UCLA researchers combined a new chemical marker called FDDNP with positron emission tomography (PET) to see for the first time the brain lesions indicative of AD in the living patient. "We have developed the first tracer molecule that visually zeroes in on the brain lesions caused by AD," said principal investigator Dr. Jorge R. Barrio, UCLA professor of medical and molecular pharmacology. "This non-invasive method will help us monitor new vaccines and drugs designed to prevent and treat the brain damage caused by AD," said co-author Dr. Gary Small, Professor of Aging and UCLA professor of psychiatry and biobehavioral sciences. Physicians regard these brain lesions, called amyloid plaques and tangles, as the definitive hallmarks of AD. Experts suspect that the lesions' growth disrupts cell function and kills off brain cells, leading to disorientation and progressive memory loss. Barrio and Small discovered that PET scans of patients injected with FDDNP showed the presence of early brain lesions - - before the plaques are believed to destroy brain cells. If experts' hypotheses about the lesions' role prove accurate, UCLA's technique could identify when medical intervention may still stave off or prevent the onset of disease. "Most forms of dementia clinically look the same," Small said. "But if we can pinpoint the specific form of dementia, we can use the appropriate medication to postpone onset of the disease. This is a major gain." PR 1/9/02 American Journal of Geriatric Psychiatry 10:24-35, February 2002

Drugs
Pfizer to Offer Drug Discount to Low-Income Elderly - Pfizer, the world's largest drug company, said 1/15/02 it would offer its drugs to low-income elderly people for a flat fee of $15 a month for each prescription, a fraction of the average retail price of $65. Pfizer estimated that seven million people could qualify for its program, which will be available to individuals with gross incomes under $18,000 a year and couples with incomes below $24,000. Medicare beneficiaries will have to submit copies of the first page of their tax returns or other proof of income with their applications. People can get applications and information about the program, known as the Pfizer Share Card program, by calling a toll-free telephone number, (800) 717-6005. Patients cannot qualify if they have other drug coverage, through private insurance, Medicaid or state programs. The program will cover some drugs that Pfizer markets jointly with foreign drug companies including Aricept, for people with mild to moderate AD. By Robert Pear and Melody Petersen NY Times 1/15/02

New Compounds Suppress Neuroinflammation of AD - Researchers from Northwestern University and the Université Louis Pasteur in France have synthesized a new class of chemicals which suppress the cellular signaling processes that trigger inflammation of brain cells, a hallmark of AD, stroke and other neurodegenerative diseases. The new compounds inhibit over-activation of glia, important cells of the central nervous system that normally help the body mount a response to injury or developmental change, but which are overactivated in certain neurodegenerative diseases or after traumatic brain injury or stroke. The new compounds selectively block production of interlukin-1 beta (IL-1B), a highly active form of nitric oxide synthase (iNOS) and nitric oxide (NO) by activated glia without diminishing the production of other glial proteins, such as apolipoprotein E, or of COX-2, the target of new anti-inflammatory drugs used in the treatment of arthritis and other inflammatory disorders. The results of this study demonstrate the selectivity of the compounds and suggest that the mechanism of action is different from that of currently available anti-inflammatory compounds that target peripheral inflammation. "The direct linkage of glial activation to disease pathology underscores the importance of understanding the signal transduction pathways that mediate these critical glial cellular responses and of the need for discovery of cell-permeable drugs that can modulate disease-relevant pathways," said study leader D. Martin Watterson. PR 1/2302 Journal of Medicinal Chemistry, 2002;45(3);563-566

Amersham and Pfizer to Work on Personalized Drugs - Anglo-Norwegian healthcare group Amersham Plc said on 1/31/02 it had agreed to a research deal with Pfizer Inc, the world's largest drugs company, aimed at finding ways of making personalized drugs. Different individual responses to drugs is one of the biggest headaches in the healthcare industry, with drug makers, regulators, dispensers and users alike continually struggling to weigh the benefits of a treatment against possible side-effects. Tailoring drugs to individual users is therefore one of the Holy Grails of the healthcare industry. Under the deal, Pfizer will fund research by Amersham Health into finding ways of diagnosing how an individual will respond to a particular drug. The research will rely heavily on Amersham's Positron Emission Tomography technology, a scan that can look into an individual's body down to the molecular level. "The idea is that if we can look at a person's genetic make-up, we can decide how they will respond (to a particular treatment)," a spokeswoman for Amersham Health told Reuters. Amersham, whose contrast-imaging agents help make a medical diagnosis somewhere in the world every two seconds, said its research would initially focus on Pfizer's library of treatments for Parkinson's, AD, lung and heart disease. By Mark Potter Reuters 1/31/02

Genes & Genetic Issues
Risky AD Surgery Could Hold Promise - Surgeons at the University of California at San Diego (UCSD), have implanted genetically modified tissue deep in Lola Crosswhite's brain. She is a pioneering AD patient - only the third in the world to undergo an experimental gene-therapy procedure designed to slow the progression of the disease. The tissue contains proteins called growth factors, which doctors hope will prevent the death of memory and reasoning cells, which typically degenerate in AD patients. "This won't be a cure" says Dr. Mark Tuszynski, the associate professor of neuroscience at UCSD who developed the procedure. "This will, if we are fortunate, slow the decline of the disease." The 11-hour procedure held substantial risks, but Crosswhite says she was willing to take them. She remained awake throughout the entire surgery. Doctors had to insert long needles directly into Crosswhite's brain, which could have triggered bleeding. There was also the possibility that the added tissue could cause tumors, pain and even weight loss if not delivered to the right area. Being off-target by less than a quarter of an inch could render the therapy useless. Adding to the complexity: Doctors had to give Crosswhite two MRI scans to make sure her brain had not been harmed. "I think it's worth trying despite the risk," says AD expert Dr. Leon Thal of UCSD, "because we stand to gain a tremendous amount of information about whether the approach will work. And then if it does, we're going to find simpler ways of trying to deliver the same type of compounds and get the same effect." A month after the surgery, Crosswhite was back on the ski slopes. And although it will be months yet before doctors will be able to tell if the gene therapy is slowing the progression of her AD, Crosswhite says those who know her have noticed a difference already. "People around me seem to feel that my short-term memory is much better than it used to be," she says. "That may be just wishful thinking, but I don't think so." By Rhonda Rowland CNN 1/25/02

Monkey Stem Cells Created Without Viable Embryo - For the first time, scientists have derived embryonic stem cells from a primate without fertilizing the female egg--raising the possibility that human stem cells could be created without destroying viable human embryos. This is because the monkey embryos in this case were created through a process called parthenogenesis, in which an unfertilized egg is coaxed into becoming an early embryo. Unlike the human embryos that have been used for stem cell research, embryos created in this manner cannot become a viable fetus. The technique has been used before in primates, but until now scientists have not been able to derive stem cells lines from the resulting embryo. Despite this new success, however, parthenogenesis is "not the savior for stem cell research," one of the study's authors told Reuters Health. Instead, said Dr. Kent E. Vrana, it offers "another tool" to be used along with embryonic and adult stem cells in research to treat disease. Because stem cells can potentially differentiate into any type of body tissue, scientists believe they can be used to replace the diseased cells that mark conditions such as AD, Parkinson's, heart disease and diabetes. Vrana said that while for those who are concerned about the ethics of destroying potentially viable embryos, parthenogenesis could be an attractive approach to obtaining stem cells, his team is not saying it might replace other techniques. It is possible that, in the future, advances in parthenogenesis and in getting stem cells from adult tissue could "wipe out" the debate over embryonic stem cell research, one bioethics specialist told Reuters Health. By Amy Norton Reuters Health 1/31/02 Science 2002;295:819

Caregivers
Dietitians Issue Nutrition Guide for Elderly - A new Nutrition Screening Initiative, sponsored by the American Dietetic Association and the American Academy of Family Physicians, provides thousands of doctors a guide to nutrition concerns regarding eight chronic diseases: cancer, chronic obstructive pulmonary disease, congestive heart failure, coronary heart disease, dementia, diabetes, high blood pressure and osteoporosis. Their web site, http://www.aafp.org/nsi , links to more comprehensive information and provides a quick test for consumers to check their own nutrition risks. It comes at a time of increased interest in nutrition therapy. In January 2002, Medicare began paying for registered dietitians to help treat more than 7 million seniors with diabetes or kidney disease, illnesses considered among the most influenced by diet. Some 85 percent of seniors have at least one chronic disease that can benefit from nutritional intervent-ions. Yet the societal, economic and physical changes of aging leave them at particular risk of malnutrition. AD makes patients forget to eat. And medications can sap appetite or make eating unpleasant. Antibiotics, for example, can leave your mouth feeling like "aluminum foil with fungus on it," says University of Tennessee dietitian Jane White. The sweet tooth that often accompanies age isn't necessarily bad. If you're trying to fatten up an AD patient who loves doughnuts, provide them -- all calories count to postpone tube-feeding as long as possible. Try bite-size finger foods; they forget how to use a fork. AP 1/22/02 A 12 page chapter on the nutrition guide for dementia is in pdf format at http://www.aafp.org/nsi/manual/chap05.pdf

Early AD Treatment May Cut Costs - As the symptoms of AD worsen, both patient care and caregiver costs rise dramatically, suggesting that treatment to slow progression of the degenerative brain disease may help lower costs, according to a study released on 2/4/02. The UCLA research showed that for a six-month period, costs associated with AD could rise to more than $30,000 per patient, depending on severity of symptoms. "We knew that AD was an expensive illness but I wanted to get a better idea of how the severity of the illness related to the costs," said lead researcher Dr. Gary Small, professor of psychiatry and biobehavioral sciences at UCLA. "We found that, as AD progresses, the cost to society increases and those costs included the direct health care costs as well as lost productivity of caregivers," Small said in an interview. For the six-month period examined, health care costs totaled approximately $20,000 for a high functioning patient--someone recently diagnosed who has memory loss but is still able to conduct some activities of daily life. For patients with severe dementia, the study found that health care costs rose to approximately $35,000 during the same period. The UCLA study was based on a national survey of caregivers representing 1,700 AD patients who are not in institutions or nursing homes. Family members, often a spouse, son or daughter, bear the brunt of the rising costs of caring for AD patients, said Small, who is also director of UCLA's Center on Aging. "If you look at overall costs regardless of severity (of symptoms), the cost of direct care for patients, going to the hospital, visiting physicians, is about $3,000. The cost to caregivers is about ten times greater, about $26,000," Small said. "That's cost translated into missed days at work and hours spent per week caring for patients." In addition to early treatment, more help for caregivers may also help control the costs of AD, said Small. According to his study, caregivers spent an average of 85 hours a week caring for patients. By JoAnne Allen Reuters 2/4/02 Journal of the American Geriatrics Society Feb. 2002

Testing
Early Warning System for AD in the Works - Someday, a yearly brain scan might be as routine for some people as a blood pressure check. A research group at the Harvard Medical School is working on a computerized method for interpreting brain MRI scans, which will look for changes in the shape and size of certain brain regions. The researchers hope the technique will make it simpler and cheaper for physicians to make an early diagnosis of neurodegenerative conditions such as AD, Huntington's disease and schizophrenia. MRI produces a very detailed picture of structures inside the body. Even a highly trained specialist can require a week to analyze an MRI for brain changes that indicate AD or similar diseases, and to distinguish them from the changes that accompany normal aging. To speed things up, a team led by Dr. Anders Dale, a radiologist, is creating computerized "atlases" that show the position, shape and size of brain structures in healthy and diseased brains. With a single computer workstation, these atlases can be compared with a brain MRI in about 30 minutes. Each of 37 different brain regions is labeled and evaluated to determine whether it is normal. As a first step, the researchers have shown that their system is able to distinguish people with AD from healthy people. In 17 patients known to have AD, three regions of the brain were smaller than in 25 healthy people, reflecting the degeneration that is characteristic of the disease. These regions were the hippocampus, which is involved in learning and memory; the amygdala, which is involved in expression of emotions; and the thalamus, which receives almost all of the body's sensory information. The researchers are hopeful that ultimately, their new system "may provide a more accurate and sensitive tool for early diagnosis of brain disorders." Reuters Health 1/30/02 Neuron 2002;33:341-355

Prevention
Moderate Drinking May Cut Dementia Risk -Study - Moderate drinking, regardless of the alcoholic beverage of choice, may reduce an older person's risk of developing dementia, new study results by the Erasmus Medical Centre in Rotterdam, Netherlands suggest. They found that among the 5,400 older adults studied, those who had up to three drinks a day were less likely than non-drinkers to develop any type of dementia, including AD. And it did not matter whether the alcohol was wine, beer, liquor or a fortified wine such as sherry. However, the relatively few who said they had four or more drinks in a day saw no such protective effect. Past research has suggested that enjoying a drink or two a day might help ward off the mental decline that often comes with age. Since evidence also shows light-to-moderate drinking may benefit the heart, investigators have speculated that, similarly, alcohol might help maintain blood flow to the brain by reducing clotting or improving cholesterol levels. Another possibility, the authors add, is that alcohol directly affects mental functioning through the release of the chemical acetylcholine in the brain. They note that "substantial evidence" indicates that acetylcholine affects learning and memory, and rat research has shown that low levels of alcohol stimulate the chemical's release, while higher alcohol levels inhibit it. In addition, a couple of drinks per day showed a protective effect among people who carried the gene variant ApoE4, which is associated with an increased AD risk. The researchers speculate that alcohol, possibly through improving cholesterol levels, might moderate dementia risk among ApoE4 carriers. "Further studies are needed to clarify the relation between (ApoE) and alcohol consumption," Breteler and colleagues conclude. Reuters Health 1/25/02 The Lancet 2002;359:281-286

Good News for Nonagenarians, AD Risk Low - People who live to be well into their 90s appear to be at lower risk of developing the memory-robbing illness AD than their younger counterparts, according to the results of a new study. "If you have made it to your mid- to late-90s and don't have AD, there is a pretty good chance you won't ever get it, even if you live a number of years longer," co-investigator Dr. John C. S. Breitner of Johns Hopkins University in Baltimore, Maryland, told Reuters Health in an interview. This was true even for a few people who inherited two versions of the ApoE-e4 gene variant--one from each parent--who for some reason were spared the illness. People with one copy of ApoE-e4 and particularly those with two copies of this gene variant are known to be at higher risk of developing AD, the researchers note. The ApoE gene codes for a cholesterol-carrying molecule and comes in three versions: e2, e3 and e4. "We studied an unusually large and long-lived population, so we were able to examine a person's chances of coming down with AD at each year of age out to about 100 (years)," Breitner said. The investigation revealed that a person's chance of developing AD doubled every 5 years until somewhere near age 90. "After that, the annual increase slowed," he noted. "The most likely, but not the only explanation, is that there is a subgroup of the population who won't ever get AD," Breitner told Reuters Health. "These people are probably a distinct minority but they're still fairly numerous." In terms of genetics, the study findings indicate that men and women with two versions of the ApoE-e4 gene showed a stronger likelihood of developing AD earlier in life as would be expected based on previous studies. "We need to find out why some people seem to escape this dreaded disease, even in very late old age, while most others seem vulnerable to it," Breitner said. "Genes may be the answer," he added, "but it doesn't appear to be that the ApoE gene - - otherwise an important predictor of risk for AD - - is involved." By Keith Mulvihill Reuters Health 1/29/02 Neurology 2002;58:209-218

In Struggle Against AD, Hope May Be Over the Counter - For people worried about developing AD, a recent study seemed to offer a rare hint of good news. Dutch researchers found that people who took anti-inflammatory drugs like ibuprofen or naproxen for at least two years were only one-sixth as likely to get AD as people who did not take the drugs. The medicines are widely used: ibuprofen is the main ingredient in Advil and Motrin, and naproxen is found in Aleve. The study was not considered definitive, but several other trials are under way, also testing anti-inflammatory drugs in people with or at high risk of developing it. The newer trials, more rigorously designed than the Dutch one, are expected to provide clearer answers about whether the drugs can ward off AD. The studies reflect scientists' growing interest in the idea that a common condition, inflammation, may underlie many chronic and debilitating diseases - like AD, heart disease, osteoporosis and diabetes - and that drugs that fight inflammation may have a role in preventing or delaying those diseases, or at least slowing them down. By Denise Grady NY Times 1/22/02 The New England Journal of Medicine 34:1515-1521 (11/22/02)

Other Items
AD-Linked Fibers Found in Bacteria - Some strains of E. coli bacteria produce the same type of fibers that accumulate in the brains of people with AD, researchers at the Washington University in St. Louis, Missouri report. Studying how the fibers form in bacteria may provide clues to how the abnormal deposits develop in AD, one of the researchers told Reuters Health. Curli are fibers that form outside of E. coli and Salmonella bacteria, according to Dr. Matthew R. Chapman. Besides playing a role during infection, these fibers help form "communities of bacteria" called biofilms, he explained in an interview. When they cluster like this, bacteria are more resistant to some antibiotics, he said. Now, Chapman and his colleagues have found that curli are formed from amyloid, which makes up the brain deposits called plaques that are one of the tell-tale signs of AD. This is the first time that amyloid fibers have been found in bacteria, the researchers report. Until now, amyloid was thought to only be present in more advanced organisms. The discovery of amyloid fibers in bacteria may help scientists better understand how amyloid deposits form in the brains of people with AD, according to Chapman. "We don't understand how they are formed," he said. Proteins in the brain undergo some sort of change to allow them to be stacked into fibers, Chapman explained. Exactly how this process works is a mystery, though, he said. E. coli "is a wonderful model system" for studying the formation of amyloid fibers, according to the St. Louis researcher. By understanding how the fibers form in bacteria "we can make some guesses" about the similar process in people, he said. Besides providing a way to study the formation of amyloid fibers, the research also suggests a possible role for bacteria in amyloid diseases, according to Chapman. The findings provide "a different way to think about" this process, he said. Chapman stressed, however, that any connection between bacteria and amyloid diseases is only conjecture and a topic for future research. By Merritt McKinney Reuters Health 1/31/02 Science 2002;295:851-855

Relative with AD Is Riskier for U.S. Blacks - African Americans who have a close relative with AD are at higher risk of developing dementia by the age of 85 than whites who have family members with the memory-robbing disease, according to a new report which examines the risk of dementia in a large number of white and African-American families. "There are two important findings," said lead author Dr. Robert C. Green of the Boston University School of Medicine, in Massachusetts, during an interview with Reuters Health. "The first is that we have created risk curves that will help clinicians counsel family members who are concerned about their own risk of developing AD," Green explained. "The second is that we have made those risk curves as precise as possible by independently creating them for whites and African Americans," he added. "When we do this, we see that African-American family members of patients with AD are at higher risk for dementia than white family members of patients with AD." The investigators found that blacks with a close relative with AD were 1.6 times as likely as whites with such relatives to develop dementia. Overall, the cumulative risk of developing dementia by age 85 was 44% in blacks with relatives with AD and 27% in their white counterparts. This is the first study to show that while the overall risk of dementia is higher among African-American family members, the impact of gender or having a gene associated with dementia (called APOE e4) on that risk is roughly the same, regardless of ethnicity, he explained. By Keith Mulvihill Reuters Health 1/15/02 The Journal of the American Medical Association 2002;287:329-336

Vitamin C Helps Drugs Pass Blood-Brain Barrier - Vitamin C could provide a key to unlock the blood-brain barrier, which stops many drugs from getting into the brain where they could potentially treat diseases such as AD or epilepsy, according to preliminary findings from researchers at the University of Ferrara in Italy. Dr. Stefano Manfredini and colleagues found that drugs used to treat neurological disorders appear to slip past the blood-brain barrier more easily when a vitamin C molecule is attached. "Ascorbic acid works like a sort of a shuttle. Theoret-ically, it could transport onto the brain any compound," Manfredini told Reuters Health. Potential applications include not only drugs for diseases such as AD, Parkinson's and epilepsy, but also viral infections, including AIDS. Manfredini's group focused on the ascorbic acid SVCT2 transporter, which is believed to play a major role in regulating the transport of vitamin C into the brain. By Rossella Lorenzi Reuters Health 1/15/02 Journal of Medicinal Chemistry 2002 January.

Institute's Research Points to 'Excited' Brain Activity - Researchers at The Burnham Institute say they've made a discovery that could help explain why receptors in the brain get over-stimulated, as occurs in disorders including AD, stroke, epilepsy, Lou Gehrig's disease and AIDS dementia. They reported 1/30/02 the cloning of the seventh and final subunit of the N-methyl-D-aspartate, or NMDA, family of receptors. Researchers are calling the subunit NR3B. By cloning the subunit, researchers found that receptors containing NR3B are activated not by glutamate, as previously believed, but by a different brain chemical known as glycine. Glycine was thought to inhibit the nervous system, rather than excite it, according to Burnham Institute spokeswoman Nancy Beddingfield. The new findings are expected to offer insight into brain disorders associated with "excitotoxicity," which Burnham Institute neuroscience research director Stuart Lipton explains as the process by which "cells excite themselves to death." "This could raise a new field of drugs," Lipton said 1/30/02, noting the potential of the findings may not be grasped for several years. "I think the most important basic research often leads to totally different discoveries." Lipton and Burnham Institute assistant professor Dongxian Zhang led the research, with collaboration by about a dozen researchers at hospitals and universities across the nation over the course of several years. Yahoo.com 1/30/02 Nature APO, Published on line:30 January 2002; DOI: 10.1038/nature715

Study to Look at Possible Benefits of Musical Training on Brain Function in Young and Old - A Canadian study is underway to look at whether musical training gives children an edge over non-musical counterparts in verbal and writing skills AND gives the elderly an edge in preserving cognitive function for as long as possible. It is one of the most ambitious studies to date to look at musical training and its influence on the brain's wiring across the age spectrum. The reseach is lead by neuroscientist Dr. Christo Pantev at The Rotman Research Institute at Baycrest Centre for Geriatric Care in Toronto and will be carried out together with Profs. Larry E. Roberts and Laurel Trainor from McMaster University in Hamilton. The project is funded with a $200,000 US grant from the California-based International Foundation for Music Research. PR 1/9/02

Ronald Reagan's 91st Birthday Marked - Ronald Reagan, the longest-living U.S. president, celebrated his 91st birthday at home with his family and was honored with a proclamation by the governor declaring it "Ronald Reagan Day" across California. Reagan spent his birthday with his wife, Nancy, and daughter Patti Davis, at his Bel-Air home. They served him his favorite cake - - chocolate. Reagan, who has recovered from a broken hip suffered in a fall last year, has remained secluded at the home since announcing in 1994 he has AD. "He's doing as well as can be expected," said Joanne Drake, Reagan's chief of staff. In Time magazine this month, Davis wrote emotionally about her father and his AD. "We will commemorate his birthday, speak of it, but the word 'happy' won't be put in front of it," she said. By Jeff Wilson, AP 2/7/02

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