Alzheimer Related News Items

News as of 9/08/02
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Top Items
High Fats May Boost AD Risk - A diet high in calories and fat may increase the risk of AD in people who are genetically susceptible to the mind-robbing disorder, new research at Columbia University suggests. The study found that people who consumed the most calories and fat faced double the risk of developing AD. The findings are the latest evidence that lifestyle factors including diet may play a role in AD. Some researchers believe that restricting calories may slow the aging process by reducing production of cell-damaging oxygen molecules called free radicals, formed during the body's breakdown of food. The latest study, though preliminary, suggests that for some people, calorie restriction might lower AD risks by curbing nerve-cell death in the brain. Lead author Dr. Jose Luchsinger said it would be premature to recommend specific diets for reducing AD risks. Study participants whose diets increased the risk had one or two copies of the apolipoprotein-E gene variant known as apoE e-4. People with the e-4 variant are thought to be already prone to the disease. About 20 percent of the U.S. population has one copy and even fewer have two, said William Thies, vice president of medical and scientific affairs for the Alzheimer's Association. In the study, 28 percent of participants had one or two copies of the variant. The gene is involved in transporting cholesterol in the blood. Not everyone with the e-4 variant develops the disease, and the study suggests that diet may influence which people with the variant become afflicted, Thies said. By Lindsey Tanner, AP Medical Writer 8/12/02 Archives of Neurology 2002:59;1258-1263

AD Study May Harm Patients - Critics - A big government-sponsored trial aimed at seeing if painkillers can reduce the risk of AD is not only useless, but dangerous and should be stopped according to Public Citizen, a consumer's group. On 9/7/02 it said the study is using the wrong drugs. The trial, called the AD Anti-Inflammatory Prevention Trial or ADAPT, has enrolled about 1,000 elderly people who have a relative with AD or some other kind of dementia or memory loss. Sponsored by the National Institute of Aging, the trial aims to give the volunteers either one of two analgesic drugs or a placebo, and see who goes on to develop AD. Pharmacia and Bayer are providing the drugs being used in the study -- celecoxib, sold under the brand name Celebrex, and naproxen, sold as Naprosyn. But Public Citizen said there is no reason to believe either drug will work and notes that, like all non-steroidal anti-inflammatory agents or NSAIDS, they can have serious and even deadly side-effects. The worst is stomach bleeding, which kills thousands every year. "Because patients are taking drugs without true informed consent, Public Citizen urges the NIA to immediately stop this unethical trial and provide patients already enrolled in the trial with the information previously denied them on lack of plausible benefit as well as the possible health risks," the group wrote in a letter to Health and Human Services Secretary Tommy Thompson. The group cites studies that show NSAIDS may work against AD not because of their main mechanism of action -- suppression of inflammation via the COX-2 enzyme -- but because of their action on another enzyme called beta-secretase. And the studies showing these effects used other NSAIDS -- ibuprofen, indomethacin and sulindac, the group said. The National Institute on Aging said it was preparing a response to the letter. By Maggie Fox, Health and Science Correspondent Reuters 9/4/02 A copy of the letter is at http://www.citizen.org/publications/release.cfm?ID=7195

Genes & Genetic Issues
Gene Tied to 'Normal' Age-Related Mental Decline - The so-called normal memory loss and mental decline that comes with age may be linked to a gene variant already associated with AD, a new report suggests. Scottish researchers at the Royal Victoria Hospital in Edinburgh found that mental decline among elderly people who did not show signs of dementia was more likely if they carried a particular variant of the gene that encodes the protein apolipoprotein E (APOE). The researchers note the variant, called APOE-e4, is found in 25% of the population and has been tied to higher levels of AD, as well as cardiovascular disease. The new study "took great care" to check that the association between APOE-e4 and relative mental decline over a lifetime was not due to the inclusion of people with unrecognized AD, co-author Dr. John M. Starr said in an interview with Reuters Health. The researchers tested the mental abilities of a group of 80-year-old men and women. All 466 study participants had taken the same test at age 11, and none had been diagnosed with dementia. The test is known as the Moray House Test, Starr said. "It is a general intelligence test, the forerunner of the '11-plus' test which was used to select children for grammar and secondary modern schools in the UK over many years," Starr explained. Those who carried the gene scored worse on the test than those who did not. APOE-e4 is one of several variants of the APOE gene, which helps transport and metabolize cholesterol and other blood fats. However, Starr said, its role in the brain "appears to be distinct" from this. "Current thinking is that it is involved in brain cell repair and that the e4 form is less effective at this than the e2 or e3 forms," the researcher explained. Starr and his colleagues also concluded that the effects of e4 were not due to heart disease or drugs used to treat heart disease. By Linda Carroll Reuters Health 8/28/02 Nature 418,932(2002)

Adult-stem-cell Research Shows Some Limits - Despite earlier research that adult stem cells from bone marrow could successfully change into brain cells, research out today suggests the change isn't as easy as once believed. That could put a damper on hopes that adult cells might take the place of those from embryos in research to cure brain diseases and spinal cord injuries. A team at Baylor College of Medicine in Houston described its futile efforts to get adult stem cells from mouse bone marrow to produce neural cells, which are found in the brain and nervous system. "It may work only under certain experimental conditions," says H. David Shine, of the Center for Cell and Gene Therapy at Baylor and senior author of the study. Over the past three years, several researchers were able to coax mouse bone marrow cells to differentiate into neural cells, but the Baylor team was unable to replicate those findings. By Elizabeth Weise USA TODAY 8/23/02 Science 2002 Aug 23;297(5585)1299

Testing
Verbal Memory Test Best Indicator of Who Will Have AD - Incidence of AD is expected to increase as the population of elderly grows. Early diagnosis and treatment of AD will be the key to lessening the disease's worst effects, but, how to spot the disease before its symptoms become serious (and harm is already done) is a challenge for health professionals. A new study by psychologists of the University of Toronto has determined that the best predictor of future AD type dementia is a verbal memory test. Their study was presented 8/25/02 at the 110th Annual Convention of the American Psychological Association (APA). In a meta-analysis of 31 studies amounting to 1,144 AD patients and 6,046 healthy controls, their findings support the use of the California Verbal Learning Test (long delay recall and percent recall) as the best predictor of AD type dementia, with executive function type measures also being predictive but less so than both the long and short delay memory tests. Changes in the hippocampus were the best volumetric or neuroimaging measure but in general volumetric measures were less sensitive to preclinical stages of the dementia than were the neuropsychological tests. Ironically, while memory assessments were also more predictive of preclinical AD than neuroimaging tests for people with the ApoE gene, the most predictive test for such persons still appears to be an odor identification test. As to how to tell the difference between those elderly with normal memory impairments and those with preclinical AD the answer lies in the magnitude of the memory deficit. Because their study was a meta-analysis of effect sizes, the results allowed them to compare the size of the difference between normal older adults with normal memory decline and older adults with actual dementia. PR 8/25/02

Prevention
Fish and Nuts Are Brain Foods - The essential fats found in fish and nuts help more than your heart. They can also reduce memory loss and strokes, claims a new study. "When we don't have enough omega-3 and omega-6 fatty acids in our system, it can lead to a heart attack or a stroke. You're not getting enough oxygen to your brain, and you are overloading your heart," explains study author Vallie Holloway, a researcher at Loyola University Medical Center in Maywood, Ill. Those two fatty acids, which are found in fish, nuts, seeds and some oils, are needed for a long list of body functions. However, while the human body manufactures most of the fats it needs, it does not make these two elements, requiring people to get them from their diets. A string of recent studies have linked these essential fats to healthy hearts and blood vessels, but Holloway's study also targeted the effects of one of them, omega-6, on brain function. "I would like to either stop or retard AD," says the researcher, who presented her findings on 8/27/02 at the American Physiological Society's convention in San Diego. Holloway studied 180 rats for a year to examine how their diets influenced their blood pressure and memory. Half of the rats were bred to have high blood pressure, and the other half were bred for low blood pressure. While all of the rats were given a normal diet and a regular regimen of maze-running, half of each group also got a supplement of omega-6 fatty acids. The results were striking. The hypertensive rats that didn't get the omega-6 supplement saw their blood pressure increase as their brain function decreased. At four months, the rats had already forgotten part of the maze, and at six months their memory functions were badly deteriorated. By contrast, the hypertensive rats that got the supplement realized a drop in blood pressure and held onto their memory functions much longer. Rather than four months, these rats started forgetting parts of the maze at six months. Holloway explained her results by focusing on the fats that clog blood vessels. In the feeder blood vessels in the brain, plaque buildup can cause clotting, which leads to strokes and AD. At the same time, clogging of the arteries forces the heart to work harder in pumping blood, leading to possible heart failure. Ironically, the body has a mechanism to limit this buildup, but poor nutrition often stands in the way, she says. When the brain senses an increase in the blood pressure, it sends a signal through the blood vessels to dilate the vessel walls, thereby allowing more blood to pass through. However, the process requires omega-6 and omega-3 fatty acids, which are often in short supply in the body, especially in old age. "Basically your body doesn't produce enough of the chemical to dilate the blood vessels," Holloway says. "When we get older we need lots of things, and this is one of them." Ann Yelmokas McDermott, a researcher at Tufts University's Friedman School of Nutrition Science and Policy in Boston, argues the broader issue is finding the proper balance between these two fats. "The omega-6 takes care of one set of problems, and the omega-3 takes care of another set of problems. We need them both. But the ratio has to be correct," McDermott says. "The American diet is very high in omega-6 rather than omega-3 fats. It's thought that it should be the inverse for optimal health." By Ross Grant HealthScoutNews Reporter 8/27/02

Blueberries May Help Old Folks Keep Their Smarts - A cup of blueberries a day may keep "senior moments" away, new findings suggest. A team of Massachusetts and Florida researchers has shown that the fruit reduces aging-related damage in rat brains, and can also prevent mental decline in mice genetically engineered to develop AD-like plaques in their brains. The findings, along with early results from a human study, suggest a healthy diet can go a long way toward preventing the mental decline that often accompanies aging, Dr. James A. Joseph of the Center on Aging at Tufts University in Boston and USDA Human Nutrition Research told Reuters Health. Joseph presented his findings at the American Chemical Society's annual meeting on 8/19/02. Cell-damaging products of normal metabolism known as free radicals can injure tissue, an effect known as oxidative damage. Antioxidants -- found in several fruits and vegetables, including blueberries -- help prevent this damage, which has been implicated in a number of conditions including cancer, AD and heart disease. Oxidative damage is also a factor in aging. Joseph said he believes the berries' brain-protecting power goes beyond its known antioxidant and anti-inflammatory effects. Blueberries seem to "directly influence the way neurons communicate," he told Reuters Health. Preliminary results from a new study, he added, show that people who ate a cup of blueberries a day appeared to be protected from aging-related mental decline. Joseph expects the study will be published late this fall. The next steps, the Boston researcher said, will be to do more tests in transgenic animals, evaluate which chemicals in blueberries find their way into the brain, and study how the fruit might be protecting the brain. By Anne Harding Reuters Health 8/19/02

Sorting Through the Confusion Over Estrogen - This 7 page single spaced piece discusses many factors and the possible risks. In the section on possible benefits the section on the brain has the following discussion. The possibility that estrogen benefits the aging brain is biologically plausible. The brain is loaded with receptors for estrogen, strongly suggesting that it is directly or indirectly vital to brain function. Estrogen affects the survival of brain cells, and it influences chemicals that send messages between brain cells, or neurotransmitters. It also affects the formation of synapses that connect brain neurons and protects against oxygen deprivation. Estrogen increases blood flow, removes cell-damaging compounds called free radicals and increases the dendritic spines needed for nerve cell interactions. Clinically, higher blood levels of estradiol, the most prominent premenopausal estrogen, are associated with better mental performance, and in women with menopausal symptoms, estrogen has improved verbal memory, vigilance, reasoning and the speed of motor responses. But this could be from estrogen-induced improvements in sleep patterns, rather than the direct effects on the brain. Observational studies like the Baltimore Longitudinal Study of Aging found a halving of the risk of AD in women using estrogen, and the large Leisure World study of a retirement community in Southern California found that women who had ever used postmenopausal estrogen were a third less likely to develop AD than those who had never taken the therapy. In addition in the Leisure World study, the risk of AD dropped sharply as the dosage and duration of estrogen use increased. But even short-term estrogen therapy may be beneficial. In a five-year study of 1,124 elderly women, those who took estrogen for less than one year at the time of menopause were half as likely to develop AD, suggesting that neurons may be especially susceptible to damage at the onset of menopause. Still lacking, however, is proof from randomized clinical trials that estrogen can delay AD or improve mental performance in women in the early stages of this disease. Well-designed studies have produced conflicting results. By Jane E. Brody NY Times 9/3/02

The Search for Alternatives to Hormone Replacement Therapy - Many women worried about the latest findings on the possible health risks of long-term hormone replacement are ready to abandon the therapy or have decided not to start it. But how? For those who choose to remain on hormone replacement by mouth or patch, most experts believe that the safest approach is to use the lowest possible dose needed to relieve symptoms. For those who want to get off hormones quitting cold turkey is not the best way to become hormone-free. Dr. Sally McNagny, a former investigator for the Women's Health Initiative study of hormone replacement, suggests gradual weaning over many months. The articles discusses finding substitutes for hot flashes, vaginal dryness, bone loss, and maintaining heart health. As to maintaining brain function "use it or lose it" seems to be as apt a motto for the brain as it is for muscles. Remaining intellectually and socially involved may not prevent AD, but it can help to maintain a sharp mind. Experts on aging recommend doing crossword puzzles, playing bridge, attending lectures, reading books and joining discussion groups. Women seeking more information on hormone alternatives might consult "The Truth About Hormone Replacement Therapy" by the National Women's Health Network (Prima Publishing, 2002, $15.95). By Jane E. Brody NY Times 9/3/02

Doubts Prompt Reviews of Hormone Therapy - Responding to growing doubts about the safety and value of hormone replacement therapy in women after menopause, two federal agencies are reviewing what is known about the drugs and what women and their doctors should be told about them. The National Institutes of Health will hold a public meeting on Oct. 23 and 24 in Bethesda, Md., to discuss questions about the therapy. The Food and Drug Administration is reviewing the labeling of hormones. The goal of the October meeting, said Dr. Vivian Pinn, director of the institutes' Office of Women's Health, is to address confusion in the wake of a federal study last month that found increased health risks from one hormone combination taken by millions of women. Dr. Pinn said participants would also discuss whether recent findings from that study, the Women's Health Initiative, could be generalized to similar products. By Gina Kolata NY Times 8/15/02

Other Items
A Focus on Early AD - MCI - A growing number of medical experts are viewing unusual lapses of memory in an otherwise healthy person -- the kind often passed off as senility -- as a powerful new sign for the earliest stage of AD. This condition, diagnosed by a recent change in memory that affects a person's daily routine, is called mild cognitive impairment, says Ronald Petersen, director of the Mayo Clinic's AD Research Center in Rochester, Minn. What is known from studies conducted so far is that 80% to 90% of cases of MCI progress to AD within six to 10 years. That suggests millions of healthy people with only a troublesome memory loss face up to a decade of uncertainty with the label of AD on their shoulders. The implications for patients, their families, the workplace and the nation's healthcare system are staggering, says Bill Thies, scientific director at the Alzheimer's Association headquarters in Chicago. "This presents a real challenge for people who have to deal with a diagnosis of mild cognitive impairment," Thies says. "But because the diagnosis is coming at a much earlier time, people have more time to work on it. There is a sense now that there will be preventative treatments in the future, probably in a five- to 10-year time window. So you would like to catch people at the very earliest moments in the disease." Catching MCI early and trying to delay, or even arrest, the progression to AD is one of the most active areas of research currently funded by the National Institutes of Health. This year, NIH is spending $594.7 million on AD research. Much of that is aimed at early-stage disease. The National Institute on Aging (NIA) is funding three MCI trials using the three approved AD drugs and vitamin E. The drugs are Aricept, Exelon and Reminyl. Vitamin E may protect aging cells from oxidative damage. NIA also is funding a $25 million study to prove whether the health supplement ginkgo biloba can delay progression. NIH also funds imaging studies that aim to give physicians diagnostic tools in the near future. Early data suggest PET scans and magnetic resonance imaging can detect changes in the brain in people with MCI. Studies of risk factors are revealing that the same risks for heart disease hold true for AD. People who exercise and maintain a healthy weight, have lower cholesterol, drink moderately and don't smoke are at lower risk. "In AD, we have moved from the stage of understanding the disease in the late phases to getting a handle on the very earliest stages," says Marcelle Morrison-Bogard, NIA associate director. "MCI is the epitome of how the field is moving back in time to ask what are the beginnings of this disease biologically and cognitively." But the most important work begins at home, the experts say. People must change their view of AD from the blank stare of the late-stage patient to an active person in the earliest stage of MCI. That means people need to pay closer attention to memory problems and seek medical advice. By Tim Friend USA TODAY 8/20/02

Scientists Improve Memory in Mice - Scientists have boosted learning and memory in mice by blocking a brain enzyme, and they say the result could point to therapy for reducing forgetfulness in older people. They found the enzyme, called PP1, as a key actor in the brain's system for erasing memories. Other scientists said it's unclear if the findings may lead to memory-enhancing therapies for older people, but they called the work important. "This is going to make us think in new and different ways about forgetting," said James McGaugh, director of the Center for the Neurobiology of Learning and Memory at the University of California, Irvine. "It says here we have a molecule in the brain that is constantly making us forget, and when you block that, it slows down the forgetting." The researchers genetically modified mice so they could block PP1 simply by giving the animals food laced with a particular drug. They found that mice in which PP1 was inhibited did better on learning and memory tests than other mice did. The animals were tested on whether they remembered seeing particular objects and whether they could recall the location of an escape platform submerged in a tank of opaque water. Aged mice also did better when PP1 was suppressed, hinting at a possible approach to treating age-related memory loss, said co-author Isabelle Mansuy of the Swiss Federal Institute of Technology in Zurich, Switzerland. "This indicates that in the aged brain the molecular machinery is not completely deteriorated and that these functions can be restored if only one component - PP1- is blocked." By Rick Callahan, Associated Press Writer 8/28/02 Nature 418, 970-975(2002)

Unlocking Key to Nerve Cell Death - Scientists at the Burnham Institute in California have uncovered new information about nerve cell death in people with stroke and neurodegenerative disorders such as AD. Their report outlines a new enzyme pathway to nerve cell death. It involves an ephemeral gas called nitric oxide, which is found in the body and is also an air pollutant. Nitric oxide can activate enzymes on the outside of nerve cells that leads to the death of the nerve cells during stroke and diseases such as multiple sclerosis, AIDS dementia and AD. The enzymes activated by the nitric oxide belong to a group called matrix metalloproteinases (MMPs). When these enzymes are activated in excess, they chew up the outside of the nerve cells and kill them, the report says. "The new work uncovers the mechanism of activation of an enzymatic pathway that leads to nerve cell death," says research team head Dr. Stuart A. Lipton, a neurologist and director of the Center for Neuroscience and Aging at the Burnham Institute. This is the first study to clearly identify this kind of enzyme pathway outside, rather than inside, the nerve cells. It's the first time that scientists have identified the ability of nitric oxide to activate MMPs. "Now that we know about this new pathway to nerve cell death that occurs outside of the cells, we can design drugs to interrupt it, and this is where this work will go in the future," Lipton says. HealthScoutNews 8/15/02 Science 2002 Aug 16 297(5584)1186-1190

Study Finds Link Between Common Neurological Disorder and AD - A study by scientists at The Wistar Institute at the University of Pennsylvania links the genes responsible for neurofibromatosis, a common neurological disorder, to a protein thought to play a role in AD. In establishing a connection between the two diseases, the research opens new lines of thinking for investigators studying both diseases, while also providing basic biological insights into vital cellular processes. The protein shared by neurofibromatosis and AD is kinesin-1, known to be pivotal to protein trafficking, which is the movement of various needed proteins from one part of a cell to another. Neurons are characterized by long arms called processes that extend away from the cell body, and under normal circumstances proteins move along a system of microtubules to reach all parts of the neuron. Problems with the internal transport of proteins can lead to neuronal malfunction and death. "This protein, kinesin-1, is like a locomotive that pulls cargo throughout the cell," says Ramin Shiekhattar, Ph.D., an associate professor at The Wistar Institute and senior author on the study. "In neurons, it pulls its cargo down microtubules, which can be thought of like the rails for the locomotive. Kinesin-1 is vital for efficient protein trafficking within neurons and other cells, and it's of great interest to us to find it linked to the genes that cause neurofibromatosis." Unrelated recent studies have also shown that kinesin-1 interacts with a protein called amyloid precursor protein, of APP, which has been implicated in AD, a major cause of dementia in older people. "If kinesin-1 is the locomotive, then APP's role appears to be to hook the cargo to the locomotive," Shiekhattar explains. "Finding kinesin-1 in protein complexes that also contain the NF1 and NF2 genes of neurofibromatosis clearly ties neurofibromatosis and AD to a common cellular pathway." PR 8/22/02 published electronically 8/20/02 Journal of Biological Chemistry 10.1074/jbc.C200434200

Report: Prominent French Doctor Prescribes Parkinson's Treatment for Pope - The French researcher who co-discovered the AIDS virus, Dr. Luc Montagnier, has prescribed a treatment made from papaya extract to ease Pope John Paul II's symptoms of Parkinson's disease when he met with the pope in mid-June. Montagnier believes that oxidative stress - created when cells convert oxygen into energy - contributes to certain medical conditions, including neurodegenerative diseases such as Parkinson's and AD. "My convictions are shared by a number of biologists," Le Monde, the French newspaper, quoted Montagnier as saying. To fight the effects of oxidative stress, Montagnier prescribed an extract from fermented Asian papayas that contains antioxidants and stimulates the immune system, Le Monde said. He also recommended a similar substance that is produced by a New York company that wasn't named in the Le Monde article. AP 9/1/02

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