Exercise Protects Against Alzheimer's
NEW YORK -- April 28, 1998
Regular strenuous exercise throughout life appears to protect against the development of Alzheimer's disease, a neurologist at Case Western Reserve University reported at the 50th annual meeting of the American Academy of Neurology, which is underway in Minneapolis, Minnesota. Elderly persons who reported regularly engaging in activities such as running, tennis, racquetball, weight training, ice skating, golf, swimming or biking in their younger years had a lower risk of the disease than their sedentary counterparts, Dr. Robert Friedland reported. Friedland and colleague Dr. Arthur L. Smith studied the exercise patterns between ages 20 and 59 in 126 elderly patients with Alzheimer's, and compared these to activity levels between the same ages in a group of 315 healthy older adults. The mean age of the two groups at the time of the study was 77. The researchers obtained their data from a questionnaire given to the Alzheimer's patients (or their family members) and to the healthy adults. The study results show that the Alzheimer's patients had a much lower score on an activity rating scale than the group of healthy older adults. "The healthy individuals reported significantly more physical activity over the four decades then those with Alzheimer's disease," said Smith, a clinical research fellow at the University Hospitals of Cleveland/Case Western Reserve University in Cleveland, Ohio, in a statement. "The results suggest that lifelong regular exercise may be protective against the development of Alzheimer's disease." "The difference persists even after we correct for age, gender and level of education," Friedland reports. Friedland pointed out that he and others have previously shown that intellectually demanding occupations, higher levels of education, and high levels of social activity are also protective against Alzheimer's disease. "We believe that the brain is just like all the other organs in the body -- that it ages better when it is used," Friedland said. "Alzheimer's disease affects about 4 million people in this country and it is the most common cause of dementia in the United States and Europe. The number of individuals affected by Alzheimer's will likely double by the year 2030," said Smith.
Folic acid, B12 could delay Alzheimer's - study
LONDON -- April 27, 1998
British and Norwegian scientists believe that taking a simple supplement of folic acid and vitamin B12could help prevent or delay the onset of Alzheimer's disease,they reported Tuesday. But the researchers at the Universities of Oxford in Englandand Bergen in Norway called for further studies and stressedthat so far their study has revealed only an association, not adirect cause and effect between diet and the debilitating braindisease. ``These findings are important because they provide atestable hypothesis that it may be possible to prevent or delaythe progression of Alzheimer's disease in a proportion ofpotential sufferers,'' Professor David Smith, chairman of thedepartment of pharmacology at Oxford, said in a statement. ``However, testing this hypothesis will require long andcostly trials,'' he added. Smith and his colleagues studied 76 Alzheimer's patients whotook part in the Oxford Project to Investigate Memory and Aging(OPTIMA). The results were to be presented to an internationalconference on homocysteine metabolism in Nijmegen, in theNetherlands Tuesday. The researchers found that patients with Alzheimer's hadmoderately elevated blood levels of the amino acid homocysteineand lower blood levels of folate and vitamin B12, which controls homocysteine, compared to 108 healthy people of a similar age. A moderate rise of homocysteine in the blood is also a knownrisk for heart disease and stroke. The discovery opens the way for an accurate blood test toidentify people most at risk for the disease -- which is themain cause of senile dementia. ``We need something to go for, and the idea of reducing therisk of Alzheimer's disease by diet is a promising hypothesis,''Professor Helga Refsum, one of the Norwegian researchers, toldthe Sunday Telegraph newspaper. Alzheimer's affects tens of millions of people and althoughthere is no cure, drugs can reduce some of its effects. OPTIMA has been conducting research since 1988 into changes that occur in the brain as part of the aging process. A reportof their latest research is being considered for publication ina medical journal.
Alzheimer's drug candidate shown effective in rats
LOS ANGELES
A California biotech company said Tuesday a treatment it has in development for Alzheimer's disease appeared to work as designed in preliminary tests in rats. NeoTherapeutics Inc., based in Irvine, California, said it plans to start to test the effectiveness of the drug in people, and hopes to have inital results some time next year. Even if they are successful, however, additional tests would be needed and commercialization of the drug could be years away. Still, the findings offered hope of a potential breakthrough in the treatment of Alzheimer's, for which there are currently no highly effective drugs. NeoTherapeutics' drug is a compound known as AIT-082, which is designed to promote regeneration of damaged nerve cells by stimulating the body to produce growth factor. ``We found if we cut the spinal cords of rats and then gave them this drug in their drinking water, within seven days, we had turned on these growth factors in their spinal cords,'' Alvin Glasky, president of NeoTherapeutics said. ``We believe that our drug is working by generating new nerves. In other words, no matter how Alzheimer's disease occurs or how the nerve cells are killed, we are hopeful that our drug will cause new cells to be regenerated,'' said Glasky. He is presenting his findings this week at the Society of Neuroscience annual meeting in New Orleans. NeoTherapeutics' research builds on a breakthrough discovery last year by researchers at the University of California at San Diego, who demonstrated that nerve cells were capable of regenerating. The problem is that the growth factor needed to stimulate them to do so somehow gets turned off in matureadults. ``The capability is built into us but does not getexpressed,'' said Glasky. Since that discovery, researchers have been rushing to find a way to put it into practice. But efforts to inject the missing growth factor into the brain or the site of the injury have resulted in complications like infection or an undesired hyper-growth of nerve cells. NeoTherapeutics' approach is somewhat different: it is an orally administered drug that stimulates the body to produce its own growth factor where it is needed. It has already been shown to be safe and well-tolerated in humans. Existing treatments for Alzheimer's disease are of limited benefit since they do not address the underlying cause of dyingnerve cells. ``If what we are seeing is correct, then in any situation where you have nerve degeneration you should be able to see effects,'' said Glasky. He said the company plans to focus later clinical trials on other spinal cord injuries, and other neurological disorderssuch as stroke
New treatment for deadly brain tumor
DURHAM, N.C. -- May 27
Scientists have doubled the survival time of victims of a deadly brain cancer with radioactive antibodies that attack their tumors. In a study of 34 patients, scientists from the Duke Comprehensive Cancer Center, Durham, N.C., say those given the radioactive antibodies lived an average of 56 weeks. That's about twice as long as most victims of the disease, which is called glioblastoma. Neuro-oncologist Darell Bigner, who led the research team, says that some patients are still alive three to four years after getting the treatment. The patients were seriously ill, fighting against a second round of tumors that had returned after they had had surgery to remove the primary cancer. Bigner says, ''This surprised us. You don't see survival improvements.'' The method is geared to overcoming a major hurdle in treating the disease, says Bigner. External radiation has been used to fight the brain tumors, but the beam has to pass through healthy tissue before it reaches its target. The therapy itself can lead to serious brain damage, he says, so the radiation must be limited. But Bigner says, ''Here we are treating from the inside out.'' The radioactive antibodies are pumped into a cavity left after surgery to remove the cancer, hitting tissues only about one inch (2.54 centimeters) around the margin the tumor. The antibodies, which come from mice, are designed to target a molecule called tenascin, which is found in tumors and around tumor blood vessels. Bigner says the next step to getting approval for the technique will be a trial in which some of the patients get only surgery, others get the antibody without the radioactive tag, and a third group gets the radio-labeled antibody. Bigner says this should show whether the tumor killing capability comes from the radioactive molecules or the antibody itself. If these studies go well, the product could get approval by the U.S. Food and Drug Administration in two to three years, Bigner predicts. Bigner says that his group is refining the technology, and have started experiments with an even more potent form of the radioactive antibody, using an isotope, called Astatine-211, that is five times more powerful than Iodine-131, the isotope used in this study. Glioblastoma strikes about 12,000 people each year, hitting most often when people are in their prime. Bigner says, ''This is one of the worst cancers there is.'' The average survival is about a year, and the disease destroys memory, personality and causes other serious problems, such as uncontrollable epilepsy. Bigner falls short of calling his therapy a cure, even though he has had patients who have survived for years, with no sign of tumor recurrence, following the therapy. But, he says glioblastoma cells tend to migrate, and can pop up on another part of the brain years later. Bigner says, ''For cures, we've have to have a treatment that reaches the entire brain.'' The study appears in Thursday's issue of the Journal of Clinical Oncology.
Hopkins Q&A: Alzheimer's and Genetics Informed opinion from the experts at America's foremost health institution
BALTIMORE -- March 16, 1998
A new genetic location that may play a role in as many as 15 percent of all cases of Alzheimer's disease has been identified, according to a paper recently published in the Journal of the American Medical Association. Researchers found an area on chromosome 12 that seems associated with the development of late-onset Alzheimer's disease, which typically develops after age 65. In this InteliHealth interview, Jason Brandt, M.D., professor of psychiatry at the Johns Hopkins Medical Institutions, says identification of these genetic locations is helping researchers to understand how the disease develops. However, he cautions concerned individuals not to confuse susceptibility genes with the inherited form of Alzheimer's Disease.
Interviewer: How much of Alzheimer's disease is genetic in nature?
Dr. Brandt: Early onset, familial Alzheimer's Disease (AD), appears to be inherited as a dominant trait. However, this accounts for only about 5 percent of Alzheimer's cases. The more common, late-onset AD appears to be related to known genetic factors in about half of cases.
Interviewer: Does having the mutation mean that someone will always develop the disease?
Dr. Brandt: No, it does not. Two genetic factors that may be most influential - the APOE gene on chromosome 19 and the newly-identified gene on chromosome 12 - are susceptibility genes. That means that having a particular form of the gene (known as an "allele") confers an increased risk of developing AD. However, we know that genes are not everything! There are clearly people without any genetic risk factors who develop AD, and there are people with the risk factors who do not. We also know from studies of monozygotic (identical) twins that one twin may get the illness much earlier than the other. This indicates that environmental factors are at work, since identical twins share the same genes. These environmental factors might include diet, use of medications or hormone replacements, exposure to toxins, or other health problems (e.g., head injury). Clearly, more research is needed in this area.
Interviewer: Can people be tested to find out whether they have a genetic mutation related to Alzheimer's disease?
Dr. Brandt: Right now, some centers are testing for the APOE gene, but only in those who are already showing signs of dementia. While this is being done to help confirm the diagnosis, it is not clear that this actually provides the clinician much new information or will lead to different treatment decisions. Testing is not recommended for people who do not show any signs of the disease.
Interviewer: Do you think testing should be offered to anyone who wishes it?
Dr. Brandt: We need to remember that testing provides only a bit of information to the person requesting it; what people do with that information is a very individual matter. For some people, learning that they have a genetic risk factor for AD might lead to years or even decades of anxiety and severe emotional distress. For others, it might result in changes in health behaviors. For example, they might start taking Vitamin E or nonsteroidal anti-inflammatory medications (like ibuprofen), since some studies have suggested these compounds may offer some protection against AD. People might also use their test results in planning for their futures, such as financial arrangements and advanced directives for their later health care.
Interviewer: Since testing is not offered now, should people pay close attention to the development of dementia in their relatives to assess their own risk?
Dr. Brandt: I think people are already doing that. But we need to remember that while susceptibility to AD may be under genetic control, the disease is, for the most part, not an inherited disorder. What I mean is that, in most cases, the disease is not passed down from one generation to the next. There are plenty of people who have a parent with late-onset AD who will never get the disease. As I mentioned earlier, there is an inherited form, but it is extremely rare.
Interviewer: Do you see a day when testing will be available for everyone?
Dr. Brandt: Perhaps when there is a really effective treatment or intervention for AD, testing will be useful. For example, if a medication were developed that could delay the onset of AD for just five years, we could reduce by half the number of people who ever get the disease! If that were the case, and the genetic tests available were highly informative of a person's risk for the disease, a stronger case could be made for testing unaffected people. But, for now, I advise patients to not become preoccupied with whatever genetic mutations they may carry. We all have plenty of them.
Copyright The Johns Hopkins University
HOMOCYSTEINE CONFERENCE: Homocysteine A Possible Risk Factor For Alzheimer's
NIJMEGEN, THE NETHERLANDS -- April 29, 1998
Scientists at the Universities of Oxford and Bergen, Norway, have found an association between pathologically-confirmed Alzheimer's disease and moderately-elevated blood levels of the amino acid, homocysteine. A moderate elevation in blood levels of homocysteine is a known risk factor for heart disease and stroke. Researchers found that 76 patients in the Oxford Project to Investigate Memory and Ageing (OPTIMA) who had pathologically-confirmed Alzheimer's disease had elevated blood levels of homocysteine and lower blood levels of folate and vitamin B12 (the vitamins which control homocysteine levels) than 108 age-matched control subjects. These latest findings, which have yet to be published, were reported April 27, 1998 in Nijmegen, The Netherlands, at the second International Conference on Homocysteine Metabolism. However, the authors of the report, stressed that these biochemical changes in the blood could be a consequence, rather than a cause, of Alzheimer's disease, and that further work is required to distinguish between these two interpretations. In particular, clinical trials over a number of years will be needed to determine if lowering homocysteine levels, by means of dietary supplementation with folic acid and vitamin B12, influences the development of Alzheimer's disease. Individuals should not take extra folic acid without consulting their doctor. "These findings are important because they provide a testable hypothesis that it may be possible to prevent or delay the progression of Alzheimer's disease in a proportion of potential sufferers," said David Smith, chairman of the department of pharmacology at Oxford and head of OPTIMA, said. "However, testing this hypothesis will require long and costly trials." A full paper describing the results of this study is being considered for publication in a medical journal and no further details of the research will be issued until the date of publication.
Scientists probe link between diet and Alzheimer's
LONDON-- April 26, 1998
Scientists will unveil researchthis week that suggests a simple change in diet could protectmillions of people from Alzheimer's disease, British newspapersreported on Sunday. The reports said the international team believes a simplesupplement of folic acid -- which is found in many greenvegetables and can be taken as a vitamin tablet -- could shelterpotential sufferers against the debilitating disease, the maincause of senile dementia. ``It is a very promising finding,'' the Sunday Telegraph quoted one of the research team, Professor Helga Refsum ofNorway's Bergen University, as saying. ``We need something to gofor, and the idea of reducing the risk of Alzheimer's disease bydiet is a promising hypothesis.'' Refsum stressed that the results had so far only revealed anassociation, not a direct cause and effect, and pointed out thatmany older people suffer from conditions that can be exacerbatedby taking folic acid. The research is to be unveiled at an internationalscientific conference in the Netherlands this week. The newspapers said the study of hundreds of Britishpatients revealed a link between Alzheimer's and high levels ofa chemical produced by the body that is known to be affected bydiet. The discovery, made by an international team co-ordinated atOxford University, opens the way to a simple blood test for identifying those most at risk. It also raises the possibility of avoiding the diseasealtogether by cutting levels of a compound known ashomocysteine. This could be brought about by increasing apatient's intake of folic acid. The disease affects 500,000 people in Britain and causesprogressive memory loss. It is the fourth commonest cause ofdeath in the Western world. ``If the interpretation being placed on these results iscorrect, it is potentially dynamite,'' the Sunday Times quotedone senior scientist as saying.
Scientists discover aberrant genes linked to Alzheimer's c. WASHINGTON -- Jan. 9, 1998
A newly identified genetic mutation may be the key to understanding a form of Alzheimer's disease that strikes older people apparently at random, a study in the latest edition of Science magazine says. A Dutch research team has discovered a set of proteins in the degenerating brains of people with non-hereditary Alzheimer's and Down's syndrome which result from a mutation in encoding genes, the study says. The researchers, led by Fred Leeuwen of the Netherland Institute for Brain Research, say this "transcript" mutation contains a form of the beta-amyloid protein known to accumulate in the tangled threads and plaques found in the brains of Alzheimer's victims. "Transcript mutation may thus be a widely occurring phenomenon (and) is likely an important factor in the widely occurring non-familial early- and late-onset forms of Alzheimer's disease," the study says. Alzheimer's disease is the most common cause of dementia in the elderly, progressively destroying memory and eroding the personality of its victim. The non-hereditary form accounts for the majority of cases
U.S. scientists pinpoint role of Alzheimer's genes
BOSTON
A defect in the ability of a cell toproperly parcel out its genetic material when it makes a copy ofitself may be an underlying cause of most inherited cases ofAlzheimer's disease, a new study suggests. Five Harvard University researchers report in Friday's issueof the journal Cell that they have uncovered the tasks performedby two chunks of genetic material, known as presenilin 1 andpresenilin 2. Those genes, which have been implicated in the familial formof Alzheimer's, help govern a cell's ability to make copies ofits genetic material and send a complete copy to opposite endsof the cell just before it splits in two. Alzheimer's, a brain disease that can lead to confusion,memory loss and speech problems, often starts in later middlelife and is estimated to afflict more than 10 percent of those over 65 years of age. When presenilin 1 or presenilin 2 is defective, the geneticmaterial is not divvied up properly and the two cells createdfrom the original may not be able to function normally. The same inability to correctly divide the genetic materialis responsible for Down's syndrome, where an extra copy of oneof the body's chromosomes produces a distinctive pattern of birth defects, including varying degrees of retardation. Huntington Potter, leader of the Harvard team, said he haslong suspected a link between Down's and Alzheimer's becausepeople with Down's syndrome always develop Alzheimer's when theyare in their 30s or 40s. The same chromosome, number 21, responsible for Down'ssyndrome also carries the genetic code for a telltale proteinseen in the brain of Alzheimer's patients. Down's syndrome, which occurs in about 1 in 600 to 650 livebirths, is marked by mental retardation and physical defects. The evidence for Down's syndrome shows up in nearly everycell in the form of a third, unwanted copy of chromosome 21.Potter said the new research supports the idea that peoplewithout Down's syndrome who inherit Alzheimer's disease may developed the extra chromosome in some of their cells but notothers because the defect appears later in the person'sdevelopment. ``Instead of occurring in every cell of the body because thechromosome segregation went wrong during the development of theegg, it occurred during the growth of the individual, so only asmall percentage of cells had three copies of the chromosome,''Potter said. ``This would then cause Alzheimer's disease, but at a laterstage because of the fact that you only have a few cells in thebody that have this genetic defect.'' In a separate preliminary study, Potter and Lisa Geller ofHarvard have found that the number of skin cells with an extracopy of chromosome 21 is three times higher in people withAlzheimer's disease than it is in healthy individuals of thesame age.
Brain Research Links Low Levels of
Fluoride to Alzheimer's and Dementia
April 17, 1998
In a study just published in the Journal of Brain Research the presence of low levels of fluoride in the drinking water of test animals, equal to the amount of elemental fluorine found in fluoridated water, caused changes to the tissue of the brain that the authors identified as similar to the pathological changes found in humans with Alzheimer's and other forms of dementia. In the Introduction of this 52 week study to assess the factors that enhance or inhibit the bioavailability of aluminum and its effects on the nervous system, it is noted that, "One of their most remarkable findings was that animals administered the lowest dose of aluminum-fluoride (0.5 ppm) exhibited a greater susceptibility to illness and a higher incidence of mortality than the animals administered the higher levels (5 ppm, 50 ppm) of aluminum (without the fluoride)." The authors continue, "While the small amount of aluminum-fluoride in the drinking water of rats required for neurotoxic effects is surprising, perhaps even more surprising are the neurological results of the sodium-fluoride at the dose given in the present study (2.1 ppm) (the amount used to achieve 1 ppm of elemental fluorine used in fluoridation). "In most reports of chronic fluoride toxicity, the data provided are usually limited to weight loss, dental and skeletal changes, indicators of carcinogenesis, and damage to soft tissues. "Fluoride has diverse actions on a variety of cellular and physiological functions, including the inhibition of a variety of enzymes, a corrosive action in acid mediums, hypocalcemia, hyperkalemia, and possibly cerebral impairment." The authors summarize, "Chronic administration of aluminum-fluoride and sodium-fluoride in the drinking water of rats resulted in distinct morphological alterations of the brain, including the effects on neurons and cerebrovasculature." While there are numerous studies linking fluoride to increased risk of hip fracture, cancer, genetic damage, bone pathology, and dental fluorosis, as identified in July 1997 by the union which consists of all of the scientists and other professionals at the Environmental Protection Agency, Washington, D.C., this study adds further definition to a series of recent studies that have illuminated fluoride's adverse neurological impact and have anticipated the results from this research that focuses on the hippocampus region of the brain, and interaction with other neurotoxins. A previous study by Mullenix, et al. in Neurotoxicology and Teratology, 1995, documents abnormal behavioral responses by animals exposed to fluoride at various stages of gestation, which resulted in the exposed animals exhibiting either permanent hyperactivity if exposed prenatally, or the rat version of "couch potato" if exposed after birth, with some animals not able to find their way out of a circular maze to the same food source every day. This study of the neurological effects of sodium fluoride, which is commonly touted as perfectly safe, with no adverse health effects when described as an addition to our public water supplies, comes on the heels of a study appearing in the current issue of the Journal of the American Medical Association that reports that 2 million people a year become ill, and more than 100,000 people die, from medicines that are judged by the medical community to be correctly prescribed and correctly administered. The follow-up question should be obvious: In light of this scientific evidence, is it in the best interest of our nation to continue a public policy -- a public policy that has already been rejected by 98% of Europe -- that forces each man, woman, and child to ingest a known cumulative neurotoxin, which is added to our water supply with no control over total intake from all sources, or variances in susceptibility? The science is clear. Media representatives, citizens, agencies charged with the responsibility of protecting the safety of our food and water, please stand up. References Chronic administration of aluminum-fluoride or sodium-fluoride to rats in the Drinking Water: alterations in neuronal and cerebrovascular integrity, Julie A. Verner, Karl F. Jensen, William Horvath, Robert L. Isaacson, Journal of Brain Research, vol. 784, 1998. Neurotoxicity of Sodium Fluoride in Rats, Mullenix et al., Neurotoxicology and Teratology, Vol. 17, no. 2, pp.169-177, 1995.
Drug Therapy Slows Alzheimer's Decline
NEW YORK -- March 16, 1998
Treatment with cholinesterase inhibitors -- drugs that increase levels of the neurotransmitter acetylcholine in the brain -- may help slow the progressive mental decline associated with Alzheimer's disease, Dr. Bruce Kinosian reported at the 21st Annual Symposium of the American Medical Directors Association, held recently in San Antonio, Texas. His study of nearly 3,300 Alzheimer's patients may help "predict outcomes for Alzheimer's disease patients who have been prescribed emerging cholinesterase inhibitors such as (the drug) metrifonate." Metrifonate is not yet approved by the US Food and Drug Administration. However, metrifonate treatment was able to slow the rate of cognitive decline by up to 20% in Alzheimer's patients, reported Kinosian, of the University of Pennsylvania in Philadelphia. The patients were examined in 1984, 1989 and 1992. This could mean an extra year of life for many Alzheimer's patients, he said, and "the probability of patients being institutionalized would be reduced by 5% over a five-year period." Kinosian and his colleagues also looked at various factors to determine the types of decline that were most predictive of long-term Alzheimer's-related disability and death. They found that declines in cognitive function -- including memory and intelligence -- were the strongest predictors of either nursing home placement or death. Kinosian told Reuters that, on average, at "the point at which we could make a diagnosis of Alzheimer disease, the patient's life expectancy is about four years." Kinosian also found that "these patients are spending more time in a nursing home than we would have thought." He said the average Alzheimer's patient spends about a third of his or her postdiagnosis lifespan in a nursing home. The University of Pennsylvania study was funded by the Bayer Corporation, the makers of metrifonate. Brought to you by Mayo Clinic May 1, 1998 The ultimate goal of treatment and management of Alzheimer's disease is to reverse, reduce or retard the mental and behavioral process of dementia. Although headlines may tout the promise of new drugs to treat Alzheimer's disease, most such drugs are still in some stage of testing. And all, including the few currently available, are designed to treat some of the manifestations of the disease. None offers a cure of the underlying illness. Over the past two decades, strides have been made in developing drugs to improve mental abilities, particularly for those in the early and middle stages of the disease. Such medications currently represent the primary drug therapies available for use in Alzheimer's disease. Treating the symptoms of Alzheimer's There are symptoms of Alzheimer's disease that may respond to early treatment when they are caused by medications, alcohol, depression, delirium, heart or lung problems, infection, vision or hearing problems or head injury. As an example, many older adults may have reactions to medications, including over-the-counter drugs, that they're taking. Sometimes adjusting the dose or changing when or in what combinations drugs are taken may improve symptoms. Some medications also affect the behavioral symptoms that often accompany Alzheimer's, including sleeplessness, wandering, anxiety, agitation and depression. Antidepressant medicines, for example, may increase neurotransmitter levels thereby reducing the depression that is common in people with dementia. Improving such symptoms can have a major effect on relieving family and caregiver stress and play a role in determining when to place someone with Alzheimer's in a long-term facility. Several new drugs in clinical trials are being studied for their possible benefits on the mental and behavioral aspects of Alzheimer's disease. As cognitive abilities become impaired with progression of the disease, these drugs are given in an attempt to improve memory, attention and concentration. Tacrine and donepezil The first such drug was approved by the FDA in 1993. Tacrine (Cognex) can slow the loss of mental abilities in about 30 percent of people with mild to moderate Alzheimer's disease by retarding the natural breakdown of acetylcholine in the brain. Acetylcholine is a chemical that plays an important role in memory. Tacrine does not reverse the underlying problem of nerve cell degeneration. This drug has been implicated in causing liver complications and its use has declined. In 1996, the FDA approved donepezil hydrochloride (Aricept) to decrease mild to moderate symptoms of the disease. Aricept is thought to work in the brain by increasing the availability of acetylcholine. The drug, taken once a day at bedtime, may produce side effects, including nausea, diarrhea and fatigue. However, these symptoms are usually mild and of short duration. Aricept is one of a series of drugs called acetylcholine esterase inhibitors being studied that increase the availability of acetylcholine. "For some people with early or middle stages of the disease, these drugs help by alleviating some of the cognitive symptoms," says Ronald C. Petersen, M.D., a neurologist and director of the Mayo Clinic Alzheimer's Disease Center. "However, neither tacrine nor donepezil can stop or reverse the disease. In addition, it remains unclear how long patients should take them or even how long the drugs will be effective in them." Continuing research The aim of drug research is to develop medications that will work on large numbers of patients, be effective for a long time, work in both the early and later stages of the disease and improve patients' daily living activities - all without producing side effects. The ultimate goal is to halt or prevent the disease completely. To accomplish this, research must identify and increase understanding of the processes that cause Alzheimer's. "Research institutions and the pharmaceutical industry are moving toward developing drugs that address the basic mechanisms of the disease," says Dr. Petersen. "Understanding the biology of the disease, including how nerve cells lose their ability to communicate with each other, the reasons some nerve cells die, as well as what constitutes normal brain aging, are major goals of scientific research." Brought to you by Mayo Clinic May 1, 1998 The ultimate goal of treatment and management of Alzheimer's disease is to reverse, reduce or retard the mental and behavioral process of dementia. Although headlines may tout the promise of new drugs to treat Alzheimer's disease, most such drugs are still in some stage of testing. And all, including the few currently available, are designed to treat some of the manifestations of the disease. None offers a cure of the underlying illness. Over the past two decades, strides have been made in developing drugs to improve mental abilities, particularly for those in the early and middle stages of the disease. Such medications currently represent the primary drug therapies available for use in Alzheimer's disease. Treating the symptoms of Alzheimer's There are symptoms of Alzheimer's disease that may respond to early treatment when they are caused by medications, alcohol, depression, delirium, heart or lung problems, infection, vision or hearing problems or head injury. As an example, many older adults may have reactions to medications, including over-the-counter drugs, that they're taking. Sometimes adjusting the dose or changing when or in what combinations drugs are taken may improve symptoms. Some medications also affect the behavioral symptoms that often accompany Alzheimer's, including sleeplessness, wandering, anxiety, agitation and depression. Antidepressant medicines, for example, may increase neurotransmitter levels thereby reducing the depression that is common in people with dementia. Improving such symptoms can have a major effect on relieving family and caregiver stress and play a role in determining when to place someone with Alzheimer's in a long-term facility. Several new drugs in clinical trials are being studied for their possible benefits on the mental and behavioral aspects of Alzheimer's disease. As cognitive abilities become impaired with progression of the disease, these drugs are given in an attempt to improve memory, attention and concentration. Tacrine and donepezil The first such drug was approved by the FDA in 1993. Tacrine (Cognex) can slow the loss of mental abilities in about 30 percent of people with mild to moderate Alzheimer's disease by retarding the natural breakdown of acetylcholine in the brain. Acetylcholine is a chemical that plays an important role in memory. Tacrine does not reverse the underlying problem of nerve cell degeneration. This drug has been implicated in causing liver complications and its use has declined. In 1996, the FDA approved donepezil hydrochloride (Aricept) to decrease mild to moderate symptoms of the disease. Aricept is thought to work in the brain by increasing the availability of acetylcholine. The drug, taken once a day at bedtime, may produce side effects, including nausea, diarrhea and fatigue. However, these symptoms are usually mild and of short duration. Aricept is one of a series of drugs called acetylcholine esterase inhibitors being studied that increase the availability of acetylcholine. "For some people with early or middle stages of the disease, these drugs help by alleviating some of the cognitive symptoms," says Ronald C. Petersen, M.D., a neurologist and director of the Mayo Clinic Alzheimer's Disease Center. "However, neither tacrine nor donepezil can stop or reverse the disease. In addition, it remains unclear how long patients should take them or even how long the drugs will be effective in them." Continuing research The aim of drug research is to develop medications that will work on large numbers of patients, be effective for a long time, work in both the early and later stages of the disease and improve patients' daily living activities - all without producing side effects. The ultimate goal is to halt or prevent the disease completely. To accomplish this, research must identify and increase understanding of the processes that cause Alzheimer's. "Research institutions and the pharmaceutical industry are moving toward developing drugs that address the basic mechanisms of the disease," says Dr. Petersen. "Understanding the biology of the disease, including how nerve cells lose their ability to communicate with each other, the reasons some nerve cells die, as well as what constitutes normal brain aging, are major goals of scientific research." Brought to you by Mayo Clinic May 1, 1998 The ultimate goal of treatment and management of Alzheimer's disease is to reverse, reduce or retard the mental and behavioral process of dementia. Although headlines may tout the promise of new drugs to treat Alzheimer's disease, most such drugs are still in some stage of testing. And all, including the few currently available, are designed to treat some of the manifestations of the disease. None offers a cure of the underlying illness. Over the past two decades, strides have been made in developing drugs to improve mental abilities, particularly for those in the early and middle stages of the disease. Such medications currently represent the primary drug therapies available for use in Alzheimer's disease. Treating the symptoms of Alzheimer's There are symptoms of Alzheimer's disease that may respond to early treatment when they are caused by medications, alcohol, depression, delirium, heart or lung problems, infection, vision or hearing problems or head injury. As an example, many older adults may have reactions to medications, including over-the-counter drugs, that they're taking. Sometimes adjusting the dose or changing when or in what combinations drugs are taken may improve symptoms. Some medications also affect the behavioral symptoms that often accompany Alzheimer's, including sleeplessness, wandering, anxiety, agitation and depression. Antidepressant medicines, for example, may increase neurotransmitter levels thereby reducing the depression that is common in people with dementia. Improving such symptoms can have a major effect on relieving family and caregiver stress and play a role in determining when to place someone with Alzheimer's in a long-term facility. Several new drugs in clinical trials are being studied for their possible benefits on the mental and behavioral aspects of Alzheimer's disease. As cognitive abilities become impaired with progression of the disease, these drugs are given in an attempt to improve memory, attention and concentration. Tacrine and donepezil The first such drug was approved by the FDA in 1993. Tacrine (Cognex) can slow the loss of mental abilities in about 30 percent of people with mild to moderate Alzheimer's disease by retarding the natural breakdown of acetylcholine in the brain. Acetylcholine is a chemical that plays an important role in memory. Tacrine does not reverse the underlying problem of nerve cell degeneration. This drug has been implicated in causing liver complications and its use has declined. In 1996, the FDA approved donepezil hydrochloride (Aricept) to decrease mild to moderate symptoms of the disease. Aricept is thought to work in the brain by increasing the availability of acetylcholine. The drug, taken once a day at bedtime, may produce side effects, including nausea, diarrhea and fatigue. However, these symptoms are usually mild and of short duration. Aricept is one of a series of drugs called acetylcholine esterase inhibitors being studied that increase the availability of acetylcholine. "For some people with early or middle stages of the disease, these drugs help by alleviating some of the cognitive symptoms," says Ronald C. Petersen, M.D., a neurologist and director of the Mayo Clinic Alzheimer's Disease Center. "However, neither tacrine nor donepezil can stop or reverse the disease. In addition, it remains unclear how long patients should take them or even how long the drugs will be effective in them." Continuing research The aim of drug research is to develop medications that will work on large numbers of patients, be effective for a long time, work in both the early and later stages of the disease and improve patients' daily living activities - all without producing side effects. The ultimate goal is to halt or prevent the disease completely. To accomplish this, research must identify and increase understanding of the processes that cause Alzheimer's. "Research institutions and the pharmaceutical industry are moving toward developing drugs that address the basic mechanisms of the disease," says Dr. Petersen. "Understanding the biology of the disease, including how nerve cells lose their ability to communicate with each other, the reasons some nerve cells die, as well as what constitutes normal brain aging, are major goals of scientific research."
Estrogen Reduces Alzheimer's Protein
NEW YORK -- March 31, 1998
Postmenopausal estrogen replacement therapy may prevent Alzheimer's disease by reducing the synthesis of beta-amyloid peptides, the short proteins that make up the brain plaques characteristic of the disease, according to a report in the April issue of Nature Medicine. Estrogen replacement therapy has been theorized to delay or prevent the development of Alzheimer's disease, although the data is still inconclusive. Now, an international team headed by Dr. Sam Gandy of New York University at N.S. Kline Institute in Orangeburg, New York, have discovered that estrogen reduces the generation of beta-amyloid peptides in cultured rodent and human embryonic nerve cells. "The biological basis for the regulation by estrogen of (beta-amyloid) formation... is unknown," the authors write. Nevertheless, they say, "these results suggest a mechanism by which estrogen replacement therapy can delay or prevent Alzheimer's disease." The Alzheimer's Association applauds the work by Gandy and colleagues, according to a statement issued by the organization. However, they note that the effect was seen in cells grown in laboratory dishes, a far cry from the complexity of cells interacting inside a living organism. "We still don't know if they are applicable to living people," according to the association's statement. "In addition, there may be other ways estrogen is involved in nerve cell protection." SOURCE: Nature Medicine (1998;4:447-451)
*MUCH MORE TO COME
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