News as of 7/07/02
For more info on these abstracts write/call Ed Cabic (edcabic@comcast.net or 410-992-7197)
OTE - e-mail address change to new address as of 2/02
For more AD information, see Alzheimer Information at http://www.connext.net/~seniors/infoad.htm
Copies of these reports are posted there
This web page was started at the Florence Bain Senior Center in Columbia MD
NOTE: There are fewer AD stories this month. One reason may be the 8th International
Conference on AD and Related Disorders on July 20-25, 2002, in Stockholm, Sweden.
Researchers may be waiting until then to disclose their latest results.
Top Items
Elevated Levels of Cholesterol Play an Even Greater Role in Development of AD, Study
Shows - Research at Georgetown University Medical Center has led to a deeper understanding of
the role that elevated cholesterol plays in the development of AD. APP, a protein found in
several major organs including the brain and heart, is present in all people. Its normal function in
the body is unknown, but in people with AD, APP is abnormally processed and converted to beta
amyloid protein. When fragments of this protein break off, they become entangled, leading to the
plaques that are one of the characteristic structural abnormalities found in the brains of people
suffering from AD. "Past research has shown that high cholesterol levels appear to increase APP
levels, which in turn leads to increased levels of beta amyloid protein and the risk of
accumulation of amyloid beta peptide," said Vassilios Papadopoulos, PhD, professor of cell
biology and pharmacology. "Our research showed that high cholesterol levels also increase the
rate at which the amyloid beta peptides break off and form the tangles that kill brain cells."
In addition to this discovery, the Georgetown research also found that high cholesterol increases
the production of another protein, apolipoprotein E (APOE), which is mainly responsible for
transportation of cholesterol out of the cell. Researchers discovered that too much APOE results
in the accumulation of free cholesterol, which is toxic to human nerve cells. Papadopoulos
and colleagues found that introducing a certain type of protein, bovine lipoproteins, would
bind with the free cholesterol, allowing it to be transported back to the liver and negating
its harmful effects. "By giving the dangerous free cholesterol something to bind to, we are
paving the way for possible new therapies," Papadopoulos said. "Our study adds to the growing
body of evidence implicating high cholesterol as a significant risk factor in AD, and breaks new
ground in showing the damage caused by excessive levels of cholesterol." Papadopoulos added
that many years of further study are required before any therapy derived from his team's findings
might be tested in humans. PR 6/19/02 This work has been accepted for publication in The
FASEB Journal, the journal of the Federation of American Societies for Experimental Biology
Caregivers
Senate Committee OKs AD Research Bill - The US Senate Health, Education, Labor and
Pensions Committee on 6/26/02 approved a measure calling for more research into AD.
"This legislation will help make sure people with AD and their families have the support they
need, both in the lab and in the community," said Sen. Barbara Mikulski (D-MD), the bill's
sponsor. "Without a cure, the number of AD patients will more than triple in the next 50 years....
If science can help delay the onset of AD by even 5 years, it would improve the lives of millions
of families and save billions of dollars." The bill would, among other things, permanently
authorize the Alzheimer's Disease Prevention Initiative at the National Institute on Aging. The
initiative conducts large-scale trials to test whether therapies like estrogen, vitamin E or ginkgo
biloba can prevent or delay AD's onset. The measure would also establish a new program to look
for new ways to help those who care for AD patients and to determine just how large a toll
caregiving takes. "One in eight AD caregivers becomes ill or injured as a direct result of
caregiving," said Mikulski, "and older caregivers are three times more likely to become clinically
depressed than others in their age group. Research is needed to find better ways to help
caregivers bear this tremendous, at times overwhelming, responsibility." The bill would also
renew a program that demonstrates innovative ways to provide care to those with AD while
providing support to family members. By Julie Rovner Reuters Health 6/27/02
Testing
Urine Test Predicts AD - A urine sample taken at the doctor's office can be the step in
determining your chances of developing AD, according to researchers at the University of
Pennsylvania School of Medicine. They have determined that a urine test can reliably detect
free radical damage associated with people with Mild Cognitive Impairment (MCI) - a
recognized precursor to AD. The test detects isoprostanes, fatty acids that are formed as the
result of free radical damage in the brain - damage that correlates with clinical diagnosis of AD.
"This is the first noninvasive test that can predict a clinical diagnosis of AD," said Domenico
Praticò, MD, assistant professor in Penn's Department of Pharmacology. "Since there is no cure
for AD, physicians could slow the course of the disease if it is caught early enough." "We found
that patients with MCI have increased brain oxidative damage before the onset of AD - damage
that can be detected in the form of isoprostanes in urine, as this study shows," said Praticò. "In
fact, five MCI subjects, all with high isoprostane levels, converted to AD during follow-up." A
urine sample taken in the doctor's office may be a first point of decision in gauging the risk of
developing AD. Further tests could then determine the severity of a patient's condition and
course of treatment. For example, studies have shown that the transition from MCI to AD occurs
fastest in people who have a gene called apoE4 and whose brain's hippocampus region is shown
to be smaller as measured in an MRI scan. "One hypothesis is that, in AD, healthy brain tissue is
damaged by the local formation of large amounts of free radicals," said Praticò. "Isoprostanes are
the byproducts of fats in the human body that were warped by free radical attack. They then
accumulate in CSF, blood, and urine as the body works to get rid of them." Praticò is now
developing a urine test he hopes will be available for clinical use within a year or two. He
predicts it will likely cost about $70 initially, later dropping to about $20. A patient who receives
a positive reading from the test he is devising, Praticò says, may be counseled to start a course of
antioxidants like vitamin E -- compounds that, some researchers believe, may slow the brain
damage associated with MCI and AD. PR 6/13/02 and Suz Redfearn Washigton Post 6/25/02
Archives of Neurology 2002;59:972-76
Prevention
Some Foods May Cut AD Risk - Eating nuts, leafy green vegetables and other foods rich in
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antioxidants such as vitamin E may reduce the risk of AD, two studies suggest. The findings build on growing research into the effects of antioxidants on dementia. The studies seem to suggest that vitamin-rich foods, but not vitamin supplements, have beneficial effects. The researchers, however, said more definitive studies are needed. Antioxidant vitamins have been shown to block the effects of oxygen molecules called free radicals, which can damage cells and are thought to contribute to cancer and heart disease. And lesions typically associated with exposure to free radicals have been found in the brains of AD patients. Previous research suggested that vitamin E pills could slow disease progression in people already diagnosed with AD. The new studies examined people who had not developed the mind-robbing ailment at the outset and suggested no effect from pills. But pill use was somewhat uncommon and of comparatively short duration in both studies. One of the studies found strong effects from vitamins E and C. In the other, results from vitamin E foods were more conclusive, but researchers said there was a suggestion vitamin C also provided benefits. The first Chicago study, funded by the National Institute on Aging, involved 815 Chicago residents 65 and older who had no initial symptoms of mental decline. They were questioned about their eating habits and followed for an average of about four years. AD |
| Eating nuts, leafy green vegetables and other foods rich in antioxidants such as vitamin E may reduce the risk of AD, two studies suggest. The findings build on growing research into the effects of anti-oxidants on dementia. (AP Graphic) | developed in 131 participants. It was diagnosed in 14.3 percent of those with the lowest intake of vitamin E foods, compared with 5.9 percent of those with the highest intake. When factors such as age and education were taken into account, the highest-intake group faced a 70 percent lower risk of developing the disease. Intake of vitamin C, found in foods such as citrus fruits, also appeared to have offer some protection, but those results were not statistically significant, said lead researcher Martha Clare Morris of Rush-Presbyterian-St. Luke's Medical Center in Chicago. Morris said participants with the highest vitamin E intake ate amounts that could be obtained from a diet that includes whole-grain cereal for breakfast, a sandwich with whole-grain bread for lunch and a dinner including a green leafy salad sprinkled with nuts. There was no |
protective effect in participants with a gene variation called apoplipoprotein E-4, which has been linked to the development of AD. The other study, from Erasmus Medical Center in Rotterdam, involved 5,395 people in the Netherlands 55 and older who were followed for an average of about six years. AD developed in 146 participants. Those with high intakes of vitamins E and C were less likely to become afflicted, regardless of whether they had the gene variation. An accompanying editorial noted several limitations in both studies, including relying on participants' memories of their eating habits and not following them longer. By Lindsey Tanner AP Medical Writer 6/26/02 Journal of the Am. Medical Assn 2002;287:3223-3229, 3230-3237, 3261-3263
More Doubt Cast on Estrogen As Post-Menopause Protector - The case for older women to take estrogen pills just got a lot weaker. Research published in the Journal of the American Medical Association on 7/2/02 provides potent evidence that women with heart disease won't avoid heart attacks and cardiac death by taking estrogen after menopause. For decades, women have taken estrogen to ward off heart disease, prevent bone fractures and avoid AD, among other purposes. But an increasing number of studies indicate there is little or no health benefit to hormone therapy. The research showed during nearly seven years, hormone therapy didn't lower the incidence of heart attacks and cardiac death. Other research also published in the same issue showed commonly used pills combining estrogen and the hormone progestin tend to increase the rate of blood clots in veins. The research is the latest and most powerful study to remove the scientific underpinnings supporting estrogen use. "This is probably the next to the last nail" in the coffin of estrogen use, said Deborah Grady, medical professor at the University of California at San Francisco, one of the researchers in the study. She said there are symptoms against which estrogen is helpful -- hot flashes, night sweats and vaginal dryness -- but the hormone is looking weaker and weaker for disease prevention. An editorial in the same issue of JAMA said estrogen could still be shown to protect against the development of dementia, although randomized trials of estrogen in treatment of AD haven't shown that benefit. The editorial also said despite studies showing estrogen prevents bone loss, estrogen in this study didn't appear to reduce the risk of bone fractures. By Thomas M. Burton Wall Street Journal 7/3/02 The Journal of the American Medical Association 2002;288:49-57, 58-66 and 99-101
Exercise Keeps Older People's Brains in Shape - Active octogenarians appear to be more
focused and less easily distracted than their sedentary peers, a study findings suggest. "By leading
an active, involved lifestyle, you may be able to maintain your ability to think and react to
situations well into late life," study author Dr. Walter R. Bixby, of the University of Maryland in
College Park, told Reuters Health. "This is especially important for getting through tasks of daily
living when one considers driving, walking down the street with groceries, following directions,
etc.," he added. The investigators found that those who participated in higher levels of physical
activity scored higher on a test of their focusing abilities, meaning they were better able to focus
on the task at hand despite surrounding distractions, than the less-active seniors. Further, Bixby
noted that the patients were not extremely physically fit. Thus, "a moderate level of physical
activity, not necessarily an exercise training plan per se, but just doing something, may lead
to improvements in one's cognitive ability," he said. In light of the findings, "the main
recommendation for anyone young or old, would be to try and incorporate some form of
physical activity into your life," Bixby said. "Also, try and keep your mind active by reading,
doing crosswords, or trying to learn new or different materials." By Charnicia E. Huggins
Reuters Health 6/27/02
Other Items
MIT Researchers Find New Cellular Target to Thwart AD - A group of existing compounds
with known biological properties -- some already FDA-approved for various uses -- may turn out
to reverse the effects of early- to mid-stage AD, report Professor Vernon M. Ingram and
colleagues at the Massachusetts Institute of Technology. They screened more than 1,500
compounds. They found that in cell cultures, 10 of them reversed a process caused by the
beta-amyloid plaques that attack the brains of AD patients. These "hit compounds have only been
tested on nerve cell cultures grown in a laboratory. But, as potential future drugs, they show
promise for the restoration of cognitive function in the treatment of early and mid-stage AD," the
researchers wrote. They have found a molecular mechanism that explains how toxic beta-amyloid peptides attack brain cells. In one of two papers published simultaneously, the
researchers describe molecular changes that occur in the cell when the clumped peptide - - the
plaque found in the brains of AD patients - - interacts with receiving proteins on the cell's
surface. When a plaque touches the cells, as well as positive calcium ions flooding in, negative
chloride ions flow out, quickly draining the cell of its negative charge, just like a battery
going dead. "If this happens in memory-forming cells, you lose your memory," said Ingram. They
believe the effects they see in the cell culture also occur in the brains of AD victims, leading to
symptoms such as memory loss and disorientation. In the second of the two papers the
researchers screened a library of some 1,500 compounds to discover drugs that might counter the
plaques' negative effects. The screen resulted in 10 compounds able to reduce or eliminate the
effect described in the first paper. Some of these are drugs approved by the US Food and Drug
Administration for conditions, including cancer, unrelated to AD. So far, these drugs have been
tested only on nerve cells. The next steps are to try them on normal mice for possible toxic side
effects, and on mice genetically engineered to develop the memory deficits characteristic of AD,
Ingram said. PR MIT 6/10/02 and Andy Couglan in PR New Scientist 6/12/02 Biochemical and
Biophysical Reserch communications 2293 (2002) 1197-1203 1204-1208. Free copies of the two
articles are available at http://www.idealibrary.com/links/toc/bbrc/293/4/0
Large Study to Begin for Promising Treatment - A new device promises to unclog the brains of people with AD. It worked in a small study. Now it's jumped to a large-scale test. Here's the theory. As people age, the spinal fluid that washes the brain flows less freely. If a person has AD, the flow is twice as slow. The fluid gets stagnant and fills with toxic materials -- including the tangled fibers that clump into the plaque that clogs the brain of AD patients. Increasing the flow is supposed to wash this goop away. One way to do this is to install a drain in the brain called a shunt which is implanted in the brain to divert spinal fluid, which bathes the brain, into the abdominal cavity. "There is something special about AD where the drainage is almost cut in half. Almost like the pipes are backed up," says Dr. Allan Levey of Emory University in Atlanta. With the pipes being backed up, researchers think toxins stagnate in the brain. So the idea is to wash out the toxins with the shunt and slow down memory loss. The procedure sounds easy. After all, doctors have been using shunts for other medical conditions for years. A trial was done with 29 patients with mild to moderate AD. By random selection, 15 of the patients got shunt implants and 14 did not. All continued on their regular AD drugs. After a year, there was a big difference between the two groups. More than a third of the patients who got the shunt had improved mental function. There was no improvement in any patient who didn't get a shunt. Not everyone with a shunt implant got better, but far fewer deteriorated. Deteriorating mental function was seen 60% of the control group but only in 27% of the shunt patients. The next trial sponsored by Eunoe Inc, the makers of the device, called the CogniShunt, is a larger trial that will enroll 250 patients at some 25 U.S. medical centers. Emory is one of those centers. "We are looking for people with typical AD who are stabilized on their medications," Levey tells WebMD. "People have to understand this is a procedure that -- while safe -- has possible complications such as infection. Or the shunt might stop working. There are no promises: this is research. We don't know whether it will work or not." "There certainly are skeptics and they're going to remain skeptics," said Levey. "The more ideas that get tested, the more likely we are to find a cure." By Daniel DeNoon WebMD 3/27/02 and CNN 6/24/02
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