Alzheimer Related News Items

News as of 1/05/03

For more info on these abstracts write/call Ed Cabic (edcabic@comcast.net or 410-992-7197)

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Copies of these reports are posted there

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Top Items

High-Fat Diets Not Linked to Dementia - A study by researchers from the Erasmus Medical Center in Rotterdam, The Netherlands, found no link between high-fat diets or elevated cholesterol and the development of dementia. The researchers followed 5,395 men and women with a mean age of 68 for six years, analyzing their intake of dietary fat and their blood cholesterol levels. Over the course of the study, 197 people developed dementia. The researchers caution that more research needs to be done to confirm the findings. “We think it is premature to conclude from our observational study that cholesterol or cholesterol-affecting fats are not associated with risk of dementia,” write the authors. “Larger, prospective studies with longer follow-up periods are needed to confirm our findings.” In a comment on the study by Jose Luchsinger and Richard Mayeux at the Alzheimer Research Forum (ARF) posted 12/24/02 they note there is one large omission in the study. The effect of the ApoE-e4 allele on the association between dietary fats and incident dementia is not considered. Previous studies have found an association between high intake of fats and incident AD in individuals with the ApoE-e4 allele, and the ApoE gene has been reported to modulate the effects of dietary exposures. Judgment on the findings of this study should be withheld until analyses stratified by the presence of the ApoE-e4 allele are reported. In another comment by Benjamin Wolozin posted 12/24/02 he notes the literature on the relationship between cholesterol and AD is quite confusing, and at times contradictory. Analysis of the biology of cholesterol suggests a potential reason explaining why measurements of serum cholesterol might not show a strong association with AD. AD is thought to be caused, at least in part, by the accumulation of aggregated Ab in the brain. If true, this suggests that the most important site for regulating Ab production is also in the brain. This logic is important because cholesterol in the brain is synthesized de novo. Little, if any, cholesterol comes from the blood. The independence of serum and brain cholesterol could readily account for the lack of any clear association between serum cholesterol and AD. If cholesterol in the brain is the critical issue, how might it affect Ab? There are several possible scenarios. One possibility is that reducing neuronal cholesterol reduces the production of Ab because the g- or b-secretase complex requires a high-cholesterol environment to be active. A second possibility is that statins or cholesterol-lowering diets (in mice) lower apolipoprotein E levels. Whether cholesterol is truly important in AD, and whether statins are actually beneficial as an anti-AD therapy remains to be determined. By Jennifer Thomas HealthScoutNews Reporter 12/23/02 Neurology 2002;59:1915-1921 and “Rotterdam Study Questions Links between Fat and Dementia Risk” at ARF 12/24/02 http://www.alzforum.org/new/detail.asp?id=734



Drugs

Exelon(R) May Be Effective in Treating Patients With Subcortical Vascular Dementia (VaD) - In a 22-month open-label study, Exelon(R) (rivastigmine tartrate) treatment was evaluated in treating various aspects of mental functioning (cognitive, daily, and executive) and behavior in patients with subcortical VaD. Caregiver stress was also measured. “This is the first study to evaluate the safety and efficacy of rivastigmine in patients with subcortical vascular dementia, a common condition for which there are currently few therapeutic options,” said Rita Moretti, M.D., lead author of the study and a Neurologist at Cattinara Hospital at the University of Trieste in Italy. “These findings are promising because they suggest that rivastigmine provides benefits in these patients, and also may reduce stress levels among the patients’ caregivers.” Subcortical VaD is one of the major subtypes of VaD and is associated with poor blood circulation in the subcortical area of the brain (multiple sites of the inner parts of the

brain). Currently, there are no approved treatments for VaD. Traditionally, the approach has been treatment of the risk factors associated with vascular diseases. AScribe Newswire 11/18/02 Journal of the Neurological Scineces vols. 203-204, 15 Nov. 2002, 141-146                         


Genes & Genetic Issues

Bone Marrow Stem Cells Used to Create Brain Cells - Stem cells from a person’s own bone marrow can be used to generate brain cells and other nervous system cells that, when put back into the body, may be a way to treat diseases like brain cancer or AD, researchers said on 12/20/02. Using renewable stem cells culled from bone marrow solves the dilemma surrounding the use of embryonic and fetal stem cells in medical research as well as potential problems with tissue rejection and uncontrolled growth of stem cells cultivated in a lab dish, said Dr. John Yu, co-director of the brain tumor program at Cedars-Sinai Medical Center in Los Angeles and the study’s senior author. Yu and his researchers were able, for the first time, to generate neural progenitor cells from whole adult bone marrow. Using modified viruses as transporters, researchers were able to transfer specific genes into neural stem cells -- cells that have the potential to differentiate into any of several types of cells of the central nervous system. They then confirmed that the new cells expressed the proteins that had been encoded and established that the stem cells were capable of differentiating into astrocytes, neurons and oligodendroglia. A long-term objective of this research is to determine if these neural stem cells can be transplanted to treat stroke, brain tumors and neurodegenerative disorders. This capability would give physicians a renewable source of neural progenitor cells, available from a patient’s bone marrow instead of the brain, and without the ethical and tissue-rejection issues associated with the use of fetal stem cells. By Deena Beasley Reuters 12/20/02 Experimental Neurology vol 178, issue 2, December 2002, Pages 288-293 and PR 12/20/02


Congress May Take Up Cloning Dilemma - There is broad support in Congress for an overt ban of cloning to produce babies. But many senators are not averse to cloning embryos solely for research that could cure diseases such as AD or diabetes, and they blocked passage of legislation that would ban that type of cloning, too. Now the question is whether the uproar over an alleged cloned baby will break that stalemate - - and if so, whether Bush and his allies would succeed in also banning the cloning of embryonic cells for medical research. There are two issues: cloning to make babies, and cloning of embryos to cull a special cell type, called stem cells, for medical research. The House last year passed a bill, backed by Bush, that would ban both types. But in the Senate, Sens. Edward Kennedy, liberal Massachusetts Democrat, and Orrin Hatch, a conservative Utah Republican, partnered to push a bill that would ban only reproductive cloning, arguing that research cloning was crucial. Neither proponents of a total ban or of the compromise could get enough votes to pass their bills. Sen. Sam Brownback, R-Kan., pledged 12/27/02 to quickly introduce legislation for a total cloning ban when Congress returns. Neither side yet appears to have enough votes to settle the issue, and lobby groups geared up for a big fight. Even if Congress succeeds in banning cloning for medical purposes, those cells still could be culled from embryos left over from fertility treatments. Indeed, California this fall passed a law requiring fertility clinics to tell women they can donate their embryos to research. By Lauran Neergaard, AP Medical Writer 12/28/02


Scientists Map Largest Chromosome to Date - French and American scientists have mapped chromosome 14, the longest sequenced to date and the site of more than 60 disease genes, including one linked to early onset AD. The feat enlisting nearly 100 researchers marks the fourth of the 24 human chromosomes mapped so far as part of an international effort. Scientists at Genoscope, the French national sequencing center, said the chromosome is comprised of more than 87 million pairs of DNA, all of which have been sequenced so that the chromosome’s map includes no gaps. The project was led by Genoscope, with contributions from scientists at Seattle's Institute for Systems Biology and the Washington University School of Medicine in St. Louis. Although the accomplishment is noteworthy, it does not mean science is any closer to conquering AD, said Bill Thies, vice president for medical and scientific affairs for the Alzheimer’s Association in Chicago. He said the chromosome 14 gene linked to early onset AD accounts for only a fraction of cases of the degenerative brain disease. Several genes, as well as environmental factors, are known to play a role in a person’s risk of developing AD, Thies said. By April, researchers around the globe hope to complete the sequencing of the remaining 20 chromosomes, said Mark Guyer, director of the division of extramural research at the National Human Genome Research Institute. By Rick Callahan, AP Writer 1/2/03 Nature 2003; doi:10.1038/nature01348


Caregivers

IBM Takes Heart Monitor a Step Further - A tiny device that reads a heart rate monitor and automatically sends a warning call to a predetermined cell phone number if the user is in distress could soon aid people at high risk of cardiac problems. The device uses radio frequency wireless technology, such as short-range Bluetooth technology, to read a heart monitor. When a predetermined heart rate that signals possible cardiac distress is reached, the device automatically sends a text message alert via cell phone to any pre-programmed cell phone number, such as a physician, care-giver or the emergency services. A team from IBM Engineering and Technology Services has successfully tested the relay device and is actively seeking a customer to turn it into a consumer product, the company said. “Our device is the size and shape of a few sticks of chewing gum,”said Bill Striemer, a development engineer for IBM and one of the inventors. The user must have a cell phone and it must be turned on to automatically transmit the crucial information. Striemer is working on incorporating global positioning technology into a version of the device that would enable an elderly person or someone suffering from AD who became lost or confused to send their whereabouts to their children or a designated care-giver’s cell phone. No price structure has been determined for the device, but a spokesman for IBM Engineering and Technology Services said they were determined to make it affordable for the average consumer. By Bill Berkrot Reuters 12/17/02



Prevention

An Active Mind May Keep AD at Bay - A new study of Chicago residents shows that people who participate in intellectually stimulating activities such as reading, listening to the radio and playing games like checkers and cards are less likely than their peers to develop AD. In the study, Dr. Robert S. Wilson of the Rush AD Center in Chicago, Illinois and colleagues looked at 842 black and white city residents whose average age was 76. All the participants performed well on memory tests at the beginning of the study, and the researchers followed up with them an average of four years later. They found that those who participated in mentally challenging activities had a lower risk of AD than those who rarely engaged in such activities. Participation in other types of activities--such as physical exercise--did not seem to affect AD risk. “On average, a person with infrequent cognitive activity was two times more likely to develop disease than a person with frequent cognitive activity,” the authors report. Reuters Health 1/2/03 Neurology 2002;59:1910-1914


Deterring Dementia - There presently is a five-year Ginkgo Evaluation of Memory Study, or GEMS, in progres which is the first dementia-prevention trial. Besides ginkgo, other measures include non-steroidal anti-inflammatory drugs (NSAIDs) such as naproxen; vitamin E; cholesterol-lowering statin drugs; and estrogen. Some of them, such as estrogen, have been tested as treatments for people who already have dementia, but so far they have failed to show any benefit. But that doesn’t necessarily mean they can’t prevent or at least delay the onset of the disease in people who do not yet have symptoms. Possible preventatives have been gleaned from observational studies in which scientists examine what happens to people who on their own decided whether to, say, take vitamins or go on estrogen. Unfortunately, measures that look promising in observational studies don’t always pan out in randomized trials. One need only look at postmenopausal hormone therapy, which appeared to be heart-healthy in observational studies. Apparently, though, something about women who chose to go on hormones, not the hormones themselves, deserved the credit. Subsequent trials found a higher risk of heart problems in women who took hormones. An observational study of 4,615 older Canadians, published in the September issue of the American Journal of Epidemiology, found that NSAIDs, coffee and wine consumption and regular physical activity were associated with a reduced risk of AD. But no one should start drinking wine or popping ibuprofen in the hope it will keep dementia at bay, says lead author Joan Lindsay, an epidemiologist with the University of Ottawa and Health Canada. “I would first start out by recommending regular physical activity, because it’s known to be good for so many other things,” she says. Indeed, there’s an overlap between steps that might prevent dementia and those known to reduce heart disease risk. Physical activity can help control high blood pressure, which appears to be a risk factor for both AD and heart disease. Ginkgo biloba and vitamin E are antioxidants, compounds thought to help keep fatty deposits from accumulating in coronary arteries. Some observational studies have linked a low-fat diet and statin drugs with lower AD risk. AD also tends to be less common in people with severe arthritis who take large doses of NSAIDs. Inflammation might be a factor in the development of plaques found in the brains of people with AD. Some, but not all, observational studies of long-term NSAID use suggest it can cut the risk of AD. By Rita Rubin USA TODAY 12/30/02

Evidence Mounting That Moderate Drinking Is Healthful - Thirty years of research has convinced many experts of the health benefits of moderate drinking for some people. A drink or two a day of wine, beer or liquor is, experts say, often the single best nonprescription way to prevent heart attacks better than a low-fat diet or weight loss, better even than vigorous exercise. Moderate drinking can help prevent strokes, amputated limbs and dementia. Some studies called “feeding studies” have supplemented the diets of laboratory animals with alcohol and found less narrowing of their coronary arteries, thus less chance for blockage. People fed alcohol experimentally for a few months have changes in their serum lipids that lower their risk for heart disease. But the most compelling evidence for alcohol’s benefits comes from large population studies, which have had impressive results. Meanwhile, though, other studies were examining the drinking habits of individual subjects, a technique scientists usually consider more reliable than examining population averages. These studies found similar sizable benefits from a few drinks a day among Italian wine-drinkers, Japanese and German beer drinkers, and Americans who preferred hard liquor. “If you step back, the data shows that alcohol is beneficial in all three beverages,” said Dr. Eric Rimm, an associate professor of epidemiology and nutrition at the Harvard School of Public Health. “If there is any differential it is very small.” The key to maximizing the benefits from any form of alcohol may be to take small quantities regularly “like any drug,” Dr. Rimm said a glass with every evening meal, rather than half a dozen glasses only on Saturday nights. A large study from the Netherlands reported in The Lancet medical journal early this year showed that moderate drinkers over age 55 had about a 40 percent lower risk of developing dementia than nondrinkers, possibly because they were spared the multiple small strokes, which can mimic AD in the elderly. [NOTE - see ARNI February, 2002, in the Prevention section ] But for every one of alcohol’s health benefits there is an equal and opposite risk if a single glass turns into three or four. By Abigail Zuger The New York Times 12/30/02



 

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