First tool to study image brain function at the cellular level
Carnegie Mellon University neuroscientist Alison Barth has developed the first tool to identify and study individual neurons activated in a living animal.
This advance, described in the July 21 issue of The Journal of Neuroscience, ultimately could lead to the development of targeted drugs that directly affect specific neurons involved in neurological diseases that alter behavior, learning and perception.
While neuroscientists have made great strides in identifying the general areas of the brain that perform certain tasks, these methods have worked at the gross level and with poor resolution, according to Barth, an assistant professor of biological sciences at the university's Mellon College of Science. To overcome these limitations, Barth created a transgenic mouse that couples the green fluorescent protein (GFP) with the gene c-fos, which turns on when nerve cells are activated. Using this method, researchers can see specific neurons glow as they are activated by external stimuli such as sensory experience or drug treatment.
"Our transgenic mouse is a novel tool that can be used to visualize, in living brain tissue, a single neuron that has been activated in response to an animal's experience," Barth said, who is part of the Center for the Neural Basis of Cognition, a joint Carnegie Mellon-University of Pittsburgh initiative.
Barth used the fosGFP mice to identify neurons that are activated during a specific rearing condition—experiencing the world through one whisker. By locating a cluster of glowing neurons, she was able to precisely identify the area of the brain involved in processing sensory input from the single whisker. Once the neurons of interest had been located, Barth then examined each neuron to determine how its electrophysiological and synaptic properties changed in response to sensory input. Her results are the first to show alterations in the rate at which neurons transmit electrical signals after increased sensory input in vivo.
Barth's technology is based on the decades-long understanding that a neuron must turn on new genes to firmly encode memories in the brain. Each time c-fos is activated in Barth's transgenic mouse, so is GFP. The result is an animal whose neurons literally glow when they are activated by stimuli.
"The fosGFP mice offer better access than ever before to the specific neurons that have been activated by an animal's experience," Barth said.
Although scientists can detect c-fos expression using another technique, it requires disrupting membranes and disturbing connections between nerve cells. Barth's method circumvents these drawbacks, allowing scientists to study living neurons at the cellular level.
Using the fosGFP mouse to identify a discrete area of the brain involved in inputting sensory information from a single whisker, Barth found that the electrical properties of neurons in the area stimulated by sensation were different than those of neurons deprived of sensation. Specifically, she discovered that neurons in the sensory-stimulated area underwent changes that made them less likely to send a signal to surrounding neurons.
"These changes are hypothesized to be part of a dynamic interplay between forces that maintain neural firing within an optimal range and those that strengthen particular connections between cells, thought to underlie learning," Barth said.
The fosGFP mouse is a broadly applicable tool for many neuroscientists, according to Barth, who has patented the mouse and licensed it commercially.
The fosGFP mouse should help scientists see which neurons are active in different neurological diseases and has broad implications for rational drug design in the treatment of schizophrenia as well as many other psychiatric diseases, according to Barth. For instance, the drug Clozapine, which is used to treat schizophrenia, is effective at relieving symptoms associated with the disease, but it isn't clear which part of the brain or which specific neurotransmitter receptors are being affected by the drug. Using the fosGFP mouse to study Clozapine's mechanism of action may provide a better understanding not only of which neurons are activated by the drug, but also how they change on continued exposure
"The medications currently used to treat Alzheimer's disease only treat the symptoms," senior author Dr. Daniel L. Alkon, from Blanchette Rockefeller Neurosciences Institute in Rockville, Maryland, said in a statement. The PKC activators, by contrast, treat the cause and the symptoms, he added.
This occurs because PKC, an enzyme, appears to play a role in both Alzheimer's memory loss and in the protein buildup that causes the disease, according to the report in the Proceedings of the National Academy of Sciences.
In the study, Alkon's team evaluated the effects of two PKC activators -- benzolactam and bryostatin -- in cell cultures and in mouse models of Alzheimer's disease.
In cell cultures, the drugs produced chemical changes that could have beneficial effects in patients with Alzheimer's disease. In mice, the drugs reduced protein build-up in the brain, helped prevent premature death, and improved behavioral outcomes, the report indicates.
Bryostatin is currently being investigated as an anticancer agent in humans, the authors note. "Given its...relatively low toxicity, and current use in humans," the agent may be a candidate for development as an Alzheimer's treatment, they add.
by Helen Pilcher (Nature.com)
Intelligence linked to size of key brain regions.
Grey matter in key areas of the brain seems to be linked to intelligence. Size may matter after all, when it comes to IQ. A brain imaging study suggests that human intellect is based on the volume of grey matter in certain brain regions, challenging alternative views about the basis of intelligence.
Researchers have been trying to pinpoint the biological roots of intelligence for decades. More than 25 years ago, a weak correlation was found between IQ and overall brain size. Others have suggested that level of intelligence is due to the size of the frontal lobe. Now, however, a common view is that more subtle characteristics are likely to be involved, such as the speed at which nerve impulses travel in the brain, or the number of neuronal connections present.
This study challenges that idea, suggesting that the volume of certain brain regions may have an effect after all.Richard Haier from the University of California, Irvine, and colleagues used magnetic resonance imaging to measure the amount of grey matter in the brains of 47 adults, who also took standard IQ tests.
Scoring the brain
The researchers divided the brain into sections and imaged the amount of grey matter in each one. Grey matter is a diffuse network of brain regions thought to be involved in information processing.
It is rich in nerve cell bodies and looks grey to the naked eye.They found that people with high IQ scores had significantly more grey matter in 24 of the regions than people with lower scores. Many of the areas, which are spread throughout the brain, are known to be related to memory, attention and language. Their results are reported online in Neuroimage1.
Haier believes that different aspects of intelligence might depend on the amount of grey matter in these different brain regions.
"This may be why one person is quite good at mathematics and not so good at spelling, and another person, with the same IQ, has the opposite pattern of abilities," he says. However, Haier and his colleagues also found that only about 6% of the total grey matter in the brain seems to be related to IQ. Nerve cells in these particular areas may work to allow the brain to process information more efficiently, suggests Haier.
"There is a constant cascade of information being processed in the entire brain, but intelligence seems related to an efficient use of relatively few structures, where the more grey matter the better," he says.
The finding is intriguing, according to Robert Plomin, who studies intelligence at the Institute of Psychiatry, King's College London.
Out of all the possible brain characteristics that could be linked to intelligence, "it's surprising to find that the simplest of all these measures, brain-region size, is the most highly correlated," he says. That said, the correlation is not huge, he adds. Intelligence researcher John Duncan from the Cognition and Brain Sciences Unit at Cambridge adds a further note of caution, pointing out that it is still possible the correlation the researchers saw is due to chance. "It's difficult to say exactly what the study means," he says.
Researchers are establishing a gene bank to help target people at highest risk for the disease.
By Susan J. Landers, AMNews staff. Aug. 2, 2004 issue
Washington -- There are barriers to conducting an Alzheimer's disease prevention trial that researchers would like to see at least lowered before the incidence of the disease swells with the aging population and overwhelms the health care system.
Prevention studies in general are costly, typically priced at about $20 million. Those for Alzheimer's carry additional burdens. First, they require the recruitment of thousands of elderly participants. They also involve numerous site visits for extensive psychosocial testing over several years.
Thus, researchers urgently are seeking ways to trim costs and size requirements. The bottom line: People are living longer, and nearly half of those older than 85 will have the disease that now affects more than 4.5 million Americans.
"We are right at the beginning of an epidemic of Alzheimer's disease," said William Thies, PhD, vice president for medical and scientific affairs at the Alzheimer's Assn. "We don't have time to do four sequential 10-year trials because that will be 40 years out, and you are going to have so many people with Alzheimer's disease that you will have bankrupted the health care system."
Researchers for the Alzheimer's Disease Anti-inflammatory Prevention Trial -- ADAPT -- are very familiar with the obstacles facing trial enrollment. ADAPT, which began in 2000, is attempting to enroll 4,000 individuals older than 70 who have a family history of Alzheimer's-like dementia but who themselves are not cognitively impaired. These participants must also be physically healthy enough to participate in a long-term trial and potentially be exposed to two nonsteroid anti-inflammatory drugs. It's a tall order.
"Recruitment has been much slower and much more difficult than anticipated," acknowledged study leader John Breitner, MD, MPH, professor of psychiatry and behavioral science at the University of Washington. "But no one had ever done this before, particularly not with these treatments," he said. "We had nothing to go on but 'guesstimates' as to how much time and effort would be involved for this recruitment."
4.5 million Americans have Alzheimer's disease.
So far, 2,500 people have been enrolled, and Dr. Breitner and colleagues are applying for another five-year National Institute on Aging grant to continue the pursuit.
Next will come the expense of bringing people in for exams. "We're giving people drugs like ibuprofen and naproxen that are widely believed to be potentially quite nasty. So that means that people will have to come in for medical evaluation."
However, so far, the smaller doses of NSAIDS being given to randomized groups of enrollees seem to result in few instances of gastrointestinal harm. Researchers are hoping they will eventually be able to reduce the frequency of medical visits.
Looking for follow-up options
The Prevention Instrument Project is also exploring more cost-effective ways to evaluate Alzheimer trial participants, perhaps using questionnaires filled out at home, phone interviews or even computer-based evaluations. This project is part of the NIA-supported Alzheimer's Disease Cooperative Study, a network that conducts clinical trials.
"We're trying to find out if we can reduce the need for the participants to come in to the clinic," said Steven Ferris, PhD, director of the Silberstein Institute for Aging and Dementia at New York University School of Medicine and the effort's principal investigator. Fewer visits would result in considerable savings in time and expense.
50% of Americans older than 85 will get Alzheimer's.
Some early findings from the project, presented at the recent International Conference on Alzheimer's Disease and Related Disorders, showed that the home-based tests were valid compared with those delivered in the clinic.
Another approach to trimming the number of enrollees needed is to select people who are at the greatest risk for developing the disease, said Dr. Ferris. They could be individuals with a close relative who developed Alzheimer's or those older than 80.
Under this approach, instead of enrolling 5,000 people and following them for five years, researchers might be able to enroll 1,500 people and follow them for two or three years and still end up with a statistically significant result, said Dr. Ferris.
Identifying people most at risk via genetic testing or neuroimaging are other methods under investigation. The Alzheimer's Disease Genetics Study is a nationwide push supported by the NIA and the Alzheimer's Assn. to find genes that play a role in late-onset Alzheimer's, the disease's most common form.
The study's aim is to establish a large bank of genetic material, cell lines and data from families in which at least two siblings have late-onset Alzheimer's. Scientists will use the data bank of about 1,000 families -- 350 have been enrolled so far -- to uncover the risk-factor genes that contribute to late-onset Alzheimer's.
The use of advanced imaging technologies are also being employed to detect functional and structural changes in the brain that might indicate early development of Alzheimer's. Scientists hope that the measurements may be able to identify those most at risk before they develop symptoms in order to more effectively assess the efficacy of drug treatments.
Dr. Thies is eager to see that some promising research identified in animal and epidemiological studies proceed to human clinical trials. This includes suggestions that risk factors for Alzheimer's are similar to vascular disease risk factors such as a high-fat diet, sedentary life style, high cholesterol, high blood pressure and diabetes.
New research out of the University of Miami School of Medicine suggests exercises that train the brain could help those in the disease's early stages retain or, in some cases, temporarily regain their ability to do everyday tasks.
And those skills could allow them to lead normal lives longer and stay out of nursing homes -- results that study co-author Dr. David Loewenstein says signal promise for the future of what's called "cognitive retraining" or "cognitive rehabilitation."
"I think the writing is on the wall that retraining will become a big part of Alzheimer's disease treatment. If we can delay decline for six months or a year, the quality of life the person has and the savings to society are enormous," said Loewenstein, who developed the training regime with Dr. Amarilis Acevedo.
Both are clinical neuropsychologists based at the Wien Center for Alzheimer's Disease and Memory Disorders at Mount Sinai Hospital in Miami Beach, where Loewenstein is the research director
Twenty-five Alzheimer's patients had retraining sessions twice a week for 12 weeks in their clinic. Drills included ways to associate names with faces, how to make change, "memory notebooks" that tracked appointments and exercises designed to increase the speed at which the brain processes information. At the same time, a control group of 19 patients did mental stimulation activities such as crossword puzzles and computer games -- the things commonly used to help Alzheimer's patients and older adults with memory problems >> Read More
Research with twins offers hope the disease can be delayed, perhaps prevented
New research conducted on twins provides compelling evidence that lifestyle plays a greater role than genetics in developing Alzheimer's.
The study found that if one identical twin developed Alzheimer's, there was a 40-per-cent chance that the other twin (whose genes are virtually identical) would do the same.
Among fraternal twins, there was a 20-per-cent chance of both developing the devastating neurological condition.
The study, presented yesterday at the International Conference on Alzheimer's Disease and Related Disorders in Philadelphia, involved more than 200 pairs of twins who were veterans of the Second World War.
A second study, using data from the Swedish Twin Registry, found similar results.
Among identical twins, if one twin developed Alzheimer's, 59 per cent of the time the other twin did as well. For same-sex fraternal twins, 32 per cent both got the disease, while among boy-girl fraternal twins, the incidence was 24 per cent.
"These results mean that environment must be helping to explain why one twin develops dementia and the other does not," said Margaret Gatz, a professor of psychology and aging at the University of Southern California in Los Angeles. She conducted the Swedish research.
Brenda Plassman, director of the epidemiology of dementia program at Duke University Medical Center in Durham, N.C., said the new findings are not just a curiosity. Rather, they provide real hope that Alzheimer's can be delayed, and perhaps prevented.
Dr. Plassman cited earlier research that showed delaying the onset of Alzheimer's by just five years could reduce the number of cases by half during the next 50 years.
"Data from these World War II veterans suggest that, even barring any conscious effort to change the course of Alzheimer's, there are environmental factors at work that can affect the age of onset by that critical five-year margin," she said.
Alzheimer's disease is a degenerative brain disorder that destroys vital brain cells. It is characterized by the buildup of plaque in the brain. About 354,000 Canadians suffer from the disease, according to the Canadian Alzheimer Society.
Beyond genetics, a number of factors are believed to contribute to Alzheimer's and related dementias. They include other medical conditions like diabetes and cardiovascular disease, obesity, poor nutrition and head injuries. People with low income, and in certain occupations, are far more likely to develop Alzheimer's. Studies have also shown that people who are mentally active -- doing crossword puzzles, reading and playing games -- are at lower risk.
As the twins are followed into old age, Dr. Plassman said, the weight of these various risk factors will become clearer.
However, the importance of socio-economic determinants of health is already emerging from the new twins research. In particular, researchers found that the higher a person's level of education, the lower the risk of developing Alzheimer's.
"The reason that low education is related to higher risk of Alzheimer's disease appears to a great extent to relate to environmental influences," Dr. Gatz said. In other words, people with higher education are more likely to have a higher income, have a better diet and live in better housing. They are also likely to have more "mental stimulation," Dr. Gatz said, and that may prove to be a key prevention measure.
The conference featured dozens of new studies on factors that influence Alzheimer's. Some of the highlights include:
Eating a diet rich in green vegetables like spinach and broccoli seems to reduce the risk of women developing Alzheimer's, likely because the vegetables are rich in folic acid and antioxidants;
The well-known risk factors for cardiovascular disease -- such as obesity, high blood pressure and high cholesterol -- all appear to also increase the risk of developing Alzheimer's;
Being obese (meaning your body mass index exceeds 30) in middle age more than doubles your risk of developing Alzheimer's later in life;
Stress seems to increase the production of plaque in the brain, and increase the severity of Alzheimer's symptoms;
Almost 40 per cent of elderly people who had not been diagnosed with dementia before they died had changes in their brain characteristic of Alzheimer's disease, a finding that confirms the disease develops many years before symptoms arise;
People with Alzheimer's seem to be less likely to develop cancer.
Alzheimer's is largely age-related: About one in 13 people over the age of 65, and one in four over the age of 85, develop the condition. Two of every three people diagnosed with the disease are women.
There is no single known cause for Alzheimer's disease, and no cure.
Remembering Ronald Reagan on America's Flagship
While I have generally avoided stories with a direct personal relevance, researching for today's earlier post got me thinking about the impact of President Reagan. Here is a man who had a tremendous impact on America, and Americans from all walks of life. Following the failure of Desert One to successfully rescue the hostages held in Tehran, an event which ocurred for me while in grammar school in Hawaii, and one of the first actions of U.S. foreign policy that I can recall, a general malaise seemed to take hold.
For us, this was lifted in a direct way when President Reagan visited the USS Constellation and gave the ship a presidential citation, naming the vessel America's Flagship. My father was one of the officers briefing the President, along with the CO of the ship and the Commander of the Battle Group. For him, shaking the president's hand and chatting with him, (and it is clear that President Reagan treated every one he met like an old friend, and was sincere about it) was one of the highlights of his career.
The following excerpt from the USS Constellation's web site comments on the event:
Constellation began her 13th deployment in October 1981, returning to San Diego in May 1982. Before the deployment, in late summer 1981, the carrier played host to President Ronald Reagan. During this visit, Mr. Reagan presented a Presidential Flag to the ship and proclaimed her "America's Flagship." While operating in the Gulf of Oman, Secretary of Defense Caspar Weinberger and the Chief of Naval Operations paid Constellation a visit."
Whatever side of the political spectrum one resided, Mr. Reagan made people believe again in the promise of America with his can-do spirit and untiring optimism. Facing an increasing new threat...
Progress on Alzheimer's Dramatic: says Alzheimers Assn's Dr. William Thies
Thu Jul 22, 5:58 PM ET
By Jon Hurdle
PHILADELPHIA (Reuters) - A cure for Alzheimer's disease (news - web sites) is unlikely in the near future, but big advances are coming soon in the treatment and prevention of the fatal brain illness, a leading researcher said on Thursday.
Researchers have made strides in learning about causes and possible therapies, and just in time, too, as the burden of Alzheimer's threatens Medicare, said Dr. William Thies, vice president for medical and scientific affairs at the Alzheimer's Association.
"We will see drastic improvements in ways of treating and preventing the disease," Thies said in an interview at the end of an international Alzheimer's conference. "It might be three, five, seven, 10 or 12 years away -- something like that."
Thies said researchers have made a "staggering amount" of progress on finding causes, developing medications that have the potential to treat it, and identifying preventive steps, particularly lifestyle changes that may delay the onset of the brain-wasting disease.
Research presented at the conference suggests, for example, that risk factors for heart disease may also lead to dementia. A study in Sweden and Finland found that participants who were obese in middle age were twice as likely to develop dementia in later life.
Another study from Harvard Medical School (news - web sites) found that women who ate vegetables such as spinach and broccoli in middle age preserved more of their cognitive abilities as they entered their 70s.
Drug trials presented to the conference appear to show that beta-amyloid, the abnormal protein that is a prime suspect as the cause of Alzheimer's, can be broken down in the brain using medication, slowing the process of cognitive decline.
16 MILLION CASES
Such preventive measures could help cut the number of Alzheimer's cases in the United States, which is expected to hit 16 million by the middle of this century -- almost four times the current number -- as the baby boom generation ages and lives longer.
That number could be even greater because of the higher incidence of Alzheimer's in the U.S. black and Hispanic populations, which are growing faster than the white population, Thies said.
The financial burden of treating the expected increase in Alzheimer's sufferers threatens to bankrupt the U.S. health care system, Thies said. Alzheimer's patients often have other illnesses, and the cost of treatment to Medicare -- the state-federal health insurance system for the elderly -- averages $13,207 per patient per year.
That amount is more than three times the average for other Medicare patients, according to the Alzheimer's Association.
Seeking to avert a crisis, the association is asking for a 32 percent increase in federal research funding, to $1 billion a year.
The association's campaign have been helped by the Alzheimer's-related death of former U.S. President Ronald Reagan (news - web sites), whose widow Nancy has called for more government support to fight the disease.
"Congress would like to recognize the contribution of Mr. Reagan, and rather than putting his face on a $20 bill, funding to find a cure for this awful disease would be the right decision," Thies said.
The toll of prominent Americans and people worldwide diagnosed with Alzheimer's continues to advance. The latest: the winningest coach (408-165-14 in 57 seasons) in College Football History, Grambling University's Eddie Robinson, has been diagnosed with the disease.
You can read more here:
Eddie Robinson struggling with Alzheimer's - Seattle Times
Grambling Legend's Condition Worsening - ESPN
Early detection is now more important than ever.
Boston University Research: Revealing genetic Alzheimer's link can ease fears
By Kay Lazar
Thursday, July 22, 2004
If you are carrying the gene that signals a higher risk of developing Alzheimer's disease, would you want to know?
Ironically, knowing one's genetic risk can ease anxiety, say researchers at Boston University School of Medicine.
In a new study of 162 adult children of people with Alzheimer's, two-thirds of those who turned out to have a genetic marker for the disease said they did not become more anxious after finding out, and 10 percent said their anxieties actually lessened.
For those who found out the tests revealed no genetic risk, nearly three-quarters said their anxieties eased, and a quarter said they stayed the same.
"Everyone came in expecting bad news and when they got good news it made them feel better,"said Dr. Robert Green, a BU genetic epidemiologist and co-author of the study.
With scientists already testing medications that could slow or halt the progression of Alzheimer's, Green said more and more people will face the decision of whether to find out their genetic risk.
If you had a treatment, and it's costly and it might have side effects, you are not going to want to give it to everyone," Green said. "You will need measures of who is at risk and who is not."
Green said many experts are still hesitant about encouraging Alzheimer's genetic testing or disclosing results for fear of traumatizing patients. But he said his study also included counseling for patients to help them understand the results. For instance, patients who had the marker were assured that it did not guarantee they would get the disease, only that it increased their risk.
Most Alzheimer's drugs treat the symptoms of dementia. But a new tool may soon predict who will develop the disease even before symptoms occur.
Like it or not, our brains start shrinking at around age 40. But an accelerated type of brain shrinkage occurs in people who go on to develop Alzheimer's disease or other types of dementia. Now, research is revealing that the rate of brain volume loss may help identify those with mild cognitive impairment who are at risk for developing dementia.
"Mild cognitive impairment refers to people who are in a transition stage between normal cognition and being demented," explains Deniz Erten-Lyons, a neurologist at Oregon Health and Science University. "They have memory complaints, but these are not severe enough for clinicians to make a diagnosis of dementia. Dementia is a general word for people with problems in brain functions—memory problems, language problems-to a degree that it affects their ability to function in their day to day living."
Erten-Lyons says magnetic resonance imaging (MRI) brain scans may predict who will progress from mild cognitive impairment to full-fledged dementia. Her lab compared the scans of 55 volunteers over the span of 14 years; none of the subjects suffered from mild cognitive impairment at the beginning of the study. Each person was examined twice a year, given tests to place them into three categories: intact cognition, mild cognitive impairment that was considered stable, and mild cognitive impairment that progressed into Alzheimer's disease.
"We looked at the whole volume loss and the loss of brain cells overall in the whole brain as well as within different regions of the brain," says Erten-Lyons. "And we compared these shrinkage rates, how fast the whole brain and the different parts of the brain were shrinking between these groups."
Of the 55 participants, 18 didn't develop mild cognitive impairment and 37 did. Of that 37, 13 remained stable while the other 24 subjects progressed to Alzheimer's disease. Brain scans revealed that brain tissue shrinkage was faster for those who developed Alzheimer's disease than those with mild cognitive impairment. "People who had higher rates of brain shrinkage, whose brains were shrinking faster before the symptoms started and who were in the transition stages, were likelier to develop dementia compared to those in the transition stages," says Erten-Lyons. "Those who get actually get dementia faster do have faster rates of brain shrinkage even before they have symptoms, which means that whatever is going on in the brain in Alzheimer's disease actually starts way before you show any symptoms."
Erten-Lyons points out that not all people with mild cognitive impairment go on to develop Alzheimer's disease. "We know that they a much higher risk of developing Alzheimer's disease, but we also know that some people in these transitional stages can flip back to going back to normal," she says. "This is what we're trying to figure out: What is it that makes these certain people stay at these transitional stages for longer periods of time, and can we actually treat them while they are in this stage and prevent them from entering Alzheimer's disease."
George Bartzokis, professor of neurology at UCLA's David Geffen School of Medicine, director of the UCLA Memory Disorders and Alzheimer's Disease Clinic and Clinical Core director of the UCLA Alzheimer's Disease Research Center, agrees the best way to combat Alzheimer's is early detection. "Because we can measure it with a technology like MRI, then basically we should be able to slow down and therefore delay or get rid of Alzheimer's disease," says Bartzokis.
Still, Erten-Lyons stresses that there is no cure for Alzheimer's disease yet. "Alzheimer's disease is not like a cancer, where if you detect it presymptomatically, you'll take it out and it will be gone and you’ll be cured," she says. "We don't have any treatments available yet."
Erten-Lyons' research was presented at the 56th annual meeting of the American Academy of Neurology and was funded by the U.S. Department of Veterans Affairs and the National Institute on Aging of the National Institutes of Health.
Staying trim, eating well and social networking help
By Amanda GardnerHealthDay Reporter
MONDAY, July 19 (HealthDayNews) -- Can staying trim, eating lots of leafy greens and maintaining healthy blood pressure and cholesterol levels -- all while doing a little gardening or concert-attending -- stave off Alzheimer's?
Increasingly, the evidence seems to suggest "yes."
Three studies presented Monday at the International Conference on Alzheimer's Disease and Related Disorders in Philadelphia, which runs from July 17 to 22, indicate that modifiable lifestyle factors such as physical activity and social networking can help reduce the risk of cognitive decline including Alzheimer's.
"This really represents the beginning of more research in this area," Marilyn Albert, chairwoman of the Alzheimer Association's Medical and Scientific Advisory Council, said at a news conference in Philadelphia on Monday.
"The Alzheimer's Association's ultimate goal is to prevent the disease entirely," added Albert, who is director of the division of cognitive neuroscience in the department of neurology at Johns Hopkins University School of Medicine. "Now is the time to think about risk."
"It seems like common sense, but there's some evidence that these are the important things to do," added Neil Buckholtz, chief of the Dementias of Aging Branch at the National Institute on Aging.
After following a group of nearly 1,500 elderly subjects for more than 20 years, researchers in Sweden and Finland found those who were obese in middle age were twice as likely to develop dementia when they were older. "Obese" was defined as a body mass index (BMI) of more than 30.
High cholesterol and high blood pressure each also increased the risk twofold. All three of these factors had an additive effect, increasing risk six times when they were all present in one person, said study author Dr. Miia Kivipelto, who is with the Karolinska Institute in Stockholm, Sweden.
Obesity, high cholesterol and high blood pressure are also risk factors for cardiovascular disease, and there is increasing evidence that dementia and cardiovascular problems are somehow linked. Not only can cardiovascular disease lead to certain types of dementia, it now seems plausible that separate factors such as cholesterol could contribute to Alzheimer's as well.
This is a good news-bad news scenario. While the prevalence of obesity is increasing globally, "BMI is easy to monitor so it represents as modifiable risk factor," Kivipelto said. "It seems possible that by reducing obesity, we can modify vascular risk factors and modify the risk for Alzheimer's disease."
Researchers at Harvard Medical School found women who ate cruciferous or other green, leafy vegetables in middle age had better cognitive abilities as they aged.
More than 13,000 women aged 70 to 81 who were part of the Nurse's Health Study filled out 116-item questionnaires on what foods they ate and how often.
Overall, there was no association between fruit and vegetable intake and cognitive decline.
There was, however, an inverse association between green, leafy vegetables (such as romaine lettuce and spinach) and cruciferous vegetables (such as cabbage), both of which have high levels of antioxidants and folates.
Women who ate at least eight servings (half a cup each) per week were essentially 1.7 years younger in terms of cognitive aging compared to women who only ate three servings a week. Similarly, women who ate five servings a week of cruciferous were about 1.3 years "younger" in terms of cognition than those who ate only two servings, said study author Jae Hee Kang.
"We're talking really modest differences," Kang said. "But it could be a significant public health benefit."
While both of these studies looked at the effects of activities undertaken in middle age, a third study looked at the effects of activities undertaken in old age.
The study, led by Dr. Laura Fratiglioni, also of the Karolinska Institute, found that leisure activities that combine social, mental and physical components are the most likely to prevent dementia.
"Combination activities are important," Fratiglioni said. Such activities could include gardening, walking or taking a course.
While there are no answers to the big question of whether nature or nurture is more important in the onset of Alzheimer's, environment does seem to be taking a more prominent role. "Even subjects with a genetic predisposition [to Alzheimer's] can have modulation of genetic susceptibility," Fratiglioni speculated.
Kivipelto added that the risk associated with high blood pressure and high cholesterol was, in fact, higher than that associated with the apoE genes.
"The pathology for Alzheimer's disease develops over a very long period of time, 10 years or longer," Albert said. "If they are going to be concerned, they should start as early in life as possible, but certainly by middle age."
As baby boomers age, an avalanche of cases expected
Updated: 9:51 a.m. ET July 19, 2004
PHILADELPHIA - Regulators, researchers and drug companies must work quickly to develop faster and less expensive trials for treatments to prevent and treat Alzheimer’s disease, scientists said.
Promising medications are in the works, but human trials are time-consuming and costly, and an avalanche of Alzheimer’s cases is expected as the baby boom generation ages, they told a conference.
“We need to reduce the time it takes to do these studies, cut the costs involved, and find ways to conduct effective studies with fewer numbers of participants,” said Dr. Marcelle Morrison-Bogorad, an associate director at the National Institute on Aging.
The disease, which helped kill former U.S. President Ronald Reagan last month, affects some 4.5 million Americans and touches one in 10 U.S. families.
The number of cases in the United States has doubled since 1980 and is expected to nearly quadruple to 16 million by 2050.
Symptoms of Alzheimer’s start out with memory loss, difficulty performing familiar tasks, problems with language and loss of initiative. Patients eventually become totally dependent on caregivers.
Medicare costs of the disease are projected to rise 55 percent to $49.3 billion by 2010. The average lifetime cost of care for someone with Alzheimer’s is $170,000, the Alzheimer’s Association said.
Alzheimer's is a degenerative brain disease that usually begins gradually, causing a person to forget recent events or familiar tasks. How rapidly it advances varies from person to person, but the disease eventually leads to confusion, personality and behavior changes and impaired judgment. Communication becomes more difficult as the disease progresses, leaving those affected struggling to find words, finish thoughts or follow directions. Eventually, most people with Alzheimer's disease become unable to care for themselves.
One in 10 people over 65 and nearly half of those over 85 suffer from Alzheimer's disease. Today, 4 million Americans have the condition. That number could jump to 14 million by the year 2050 unless prevention methods are developed.
Scientists still are not certain of the disease's cause. Advancing age and family history are risk factors. Researchers are exploring the role of genetics in the disease, but most agree it's caused by a variety of factors.
There is no single, comprehensive diagnostic test for Alzheimer's disease. Instead, doctors rule out other conditions through a process of elimination. They usually conduct physical, psychological and neurological exams and take a thorough medical history. Diagnosis is about 90 percent accurate, but the only way to confirm it is through autopsy.
There is no medical treatment currently available to cure or stop the progression of Alzheimer's disease. There are currently five FDA-approved Alzheimer's drugs – Namenda, Cognex, Aricept, Exelon and Reminyl -- that may temporarily relieve some symptoms of the disease. Several other drugs are in development.
Common symptoms of Alzheimer's disease include:
-Memory loss that affects job skills
-Difficulty performing familiar tasks
-Problems with language
-Disorientation to time and place
-Poor or decreased judgment
-Problems with abstract thinking
-Placing items in inappropriate places
-Rapid changes in mood or behavior
-Dramatic changes in personality
-Loss of initiative
One current trial focusing on the ginkgo biloba leaf involves more than 3,000 participants aged 75 and older for at least six years at a cost of more than $24 million.
Another is looking at whether two non-steroidal anti-inflammatory drugs, or NSAIDS, can help prevent Alzheimer’s in healthy people. It has so far enrolled about 2,500 of an intended 4,000 participants at a cost of some $25 million.
The use of NSAIDS, a drug category that includes aspirin and ibuprofen as well as COX-2 inhibitors, has potential, said Dr. John Breitner of the University of Washington, who leads a trial of the drugs naproxen and Pfizer’s Celebrex, known generically as celecoxib.
“The preliminary data that NSAIDs can prevent Alzheimer’s is very encouraging, but the treatments have known side effects and there are real difficulties with administration of these or other biologically active compounds to seniors in trials over several years,” Breitner told reporters.
Study: Drug delays onset of Alzheimer's
A project led by Dr. Steven Ferris of the New York University School of Medicine is trying to develop more efficient methods such as home-based testing, using fewer participants.
“We’re trying to find out if we can reduce the need for the participants to come in to the clinic,” Ferris said. “We can save considerable time and expense if the participants don’t have to come in so often.”
Meanwhile, researchers reported mixed results from tests on whether the cholesterol-lowering statin drugs can also help prevent Alzheimer’s. Scientists at the University of Alabama at Birmingham found that aging mice treated with simvastatin -- marketed by Merck and Co. as Zocor -- regained their ability to navigate mazes after being injected with the drug.
But another trial at Duke University involving 30,000 people without dementia has found no evidence yet that any statin protects against cognitive decline.
Small trials of the popular Alzheimer’s drug Aricept show mixed results on whether it can prevent the disease. The latest study presented at the Philadelphia conference suggests its use can delay the worst symptoms by about 18 months.
By Jia Lynn Yang, Times Staff Writer
WASHINGTON - Thirty years ago, no one talked much about Alzheimer's disease - its symptoms were seen as part of a psychological disorder or generic dementia. Twenty years ago, it gained enough notice that President Reagan designated an Alzheimer's Disease Month. Ten years ago - about the time Reagan was diagnosed with the disease - the government was committing about $300 million a year to research, but not getting very far. Today, there is an urgency about Alzheimer's that puts it in the headlines almost daily.
The amount spent on research could soon climb to $1.4 billion a year. And what scientists can and cannot do as they search for a cure is at the center of a national ethics debate. Reagan's death last month has spurred lawmakers and advocates to say that more research into the ailment has never been more crucial, with scientists now poised to make major breakthroughs as more of the 77 million baby boomers approach retirement age. The disease currently afflicts 4.5 million Americans and experts predict that number will triple by 2050.
"Certainly the moon and the stars are beginning to line up to give another increase to Alzheimer's funding," said Stephen McConnell, senior vice president for advocacy and public policy at the Alzheimer's Assn., the world's largest private funder of Alzheimer's research. Public support for Alzheimer's research is so strong that it is renewing attention to the use of embryonic stem cells, which some researchers think could reap advances in the treatment of Alzheimer's and other diseases.Although some scientists acknowledge that the potential benefits of stem cell research for treating Alzheimer's in particular - as opposed to diabetes and Parkinson's, for instance - have been exaggerated to the public, Nancy Reagan's emergence this spring as a supporter of stem cell research has ushered Alzheimer's even further into the political limelight.
On June 16, less than two weeks after the former president's death, a bipartisan group of lawmakers introduced the Ronald Reagan Alzheimer's Breakthrough Act, which would double research funding from about $700 million annually to $1.4 billion. Sen. Barbara A. Mikulski (D-Md.), who lost her father to Alzheimer's in 1987, called the initiative "a living memorial" to the former president."
President Reagan lived his life with vigor. And we have to attack the Alzheimer's situation with the same vigor," she said. A budget boost would provide relief to scientists at the National Institute on Aging, the primary NIH organization for research on Alzheimer's, who say that lately the money for research keeps coming up short."We're making very difficult decisions all the time. More than 80% of the [grant] applications that come into the institute aren't funded," said Marcelle Morrison-Bogorad, the National Institutes of Health's associate director for neuroscience and neuropsychology of aging. "You worry that one of these grants is the one you ought to have funded."Funding for Alzheimer's research for fiscal year 2005 is estimated at $700 million.
By comparison, more than $5.7 billion is spent on cancer research and about $2.9 billion on HIV and AIDS research."The message of this big increase is: 'Goodness, we have to do something about this problem,' " said Denis Evans, director of the Rush Institute for Healthy Aging in Chicago. "We as a society are going to be in a lot of trouble if we don't do something. This is a very persuasive argument for dealing with it now."Evans, who specializes in tabulating Alzheimer's populations, said that about 440,000 Californians are living with the disease. By 2010, that number could increase to 480,000. According to a report released June 23, Alzheimer's could choke the economy unless the government invested more in research. Medicare beneficiaries with Alzheimer's account for 34% of Medicare spending, but they make up only 12.8% of the population over age 65.
The study, sponsored by the Alzheimer's Assn. and conducted by Lewin Group, a healthcare consulting firm in Falls Church, Va., showed that research breakthroughs could save $149 billion in Medicare and Medicaid costs by 2025 and result in nearly 3 million fewer Americans with the disease.Morrison-Bogorad at NIH warns, though, that funding more research, although welcome, is about increasing the chance for a cure in the long term. Even clinical trials that are seeing promising results will not be completed until 2007 or 2008.Nonetheless, techniques for diagnosing Alzheimer's have improved in the last 15 years.
The Centers for Medicare and Medicaid Services, part of the Department of Health and Human Services, announced June 15 that it would expand coverage of positron emission tomography, or PET, scans(and MRI, magentic resonance imaging) for those suspected of having Alzheimer's if all other diagnostic tools had been exhausted. Although "the gold standard for diagnosis is autopsy," said Dr. Sean Tunis, chief medical officer of the Medicare and Medicaid office, "a clinical evaluation, tests of mental function, a physical examination and a good clinical history of a patient's pattern of symptoms are a highly accurate way of diagnosing the disease. PET scanning potentially adds a little more on top of that."In another convergence of events, there was a flurry of activity among advocates for stem cell research in the days just before Reagan's death, suggesting that even without the revived attention on Alzheimer's, public support for stem cell research had been growing. On June 3, a California initiative that would fund $3 billion of embryonic stem cell research - independent of NIH and the federal government - qualified for the state's November ballot.
On June 4, 58 senators, including 14 Republicans, wrote to President Bush, asking him to review his August 2001 decision to restrict embryonic stem cell research to a small number of existing cell lines. Their letter mirrored one sent two months earlier by 206 House members. Stem cells are coveted for their ability to develop into many different cell types, which is why scientists think such research could shed light on a wide array of illnesses, and an April 2004 poll by Peter D. Hart Research Associates indicated that nearly all Americans had a personal connection to at least one of them.
Another Hart survey conducted in the days after Reagan's death showed that 72% of respondents were more likely to support stem cell research, including 64% of conservatives.Picking up on the widening support for stem cell research, the presumed Democratic presidential nominee, Sen. John F. Kerry of Massachusetts, has invoked Reagan's name at campaign stops. "As America said goodbye to Ronald Reagan, we also honored the devotion and love of his wife, Nancy. Her pleas for stem cell research joined the pleas of millions across this country and reinforces in all of us the need to tear down every wall today that keeps us from finding the cures of tomorrow,' Kerry said June 21 at a stop in Colorado.
Two days later, 142 patient groups, universities and scientific societies sent yet another letter to Bush, and senators introduced a bill to expand the federal policy on stem cell research. And on July 4, Sen. Orrin G. Hatch (R-Utah), a strong supporter of stem cell research, noted that there were moves toward a compromise on the administration's stem cell policy. "I think that the Bush administration and all of us will get together and try to find some way that this great research can go on," Hatch told CNN's "Late Edition," noting that more than 60 senators were prepared to vote in support of expanded embryonic stem cell research."We need to support this," he said. "Nancy Reagan happens to be right on this." During his first term as president, Reagan designated November as Alzheimer's Disease Month. "
The emotional, financial and social consequences of Alzheimer's disease are so devastating that it deserves special attention," Reagan wrote in 1983, more than a decade before his own diagnosis. "Right now, research is the only hope for victims and families."
MY VIEW: ALL ARE AT RISK FOR GETTING ALZHEIMER'S?
BY JAN MEAD
Every time I realize I've forgotten something important, I catch my breath.
People I tell this to say, "What's the big deal? You're just busy and have too much to remember." They don't understand that forgetfulness is a big deal to me.
My mom has Alzheimer's disease, and I've been living with it every day for five years now. And every single one of those days, I've asked myself what kind of horrible disease this is that would steadily take away her mind piece by piece until one day, she won't be herself at all.
If you met my mom and talked with her very briefly, you would think she was "pretty good" for an 82-year-old. That would last about five minutes -- maybe. Then she would ask you the very same questions she asked only a minute earlier: "What are you doing today? How's the family?" And if you stayed with her 15 minutes, you would have heard and answered those questions over and over and over.
While this disease has been brutal to my mother, it hasn't been all that kind to me. I have been forced to become my mother's mother, a role I never wanted.
I make decisions for her -- big decisions such as where she is going to live, how she is going to spend her money, what doctor she will go to, where she will go on her one weekly outing from the nursing home. I'm even second in line to God to say when she will die, because my signature is on an order related to her end-of-life medical care.
I also get to make not-so-big decisions -- what she will eat for lunch when we are together, what brand of underwear she will be most comfortable in, what she wants to give her children and grandchildren for Christmas and birthdays.
And yet I am so lucky. My mom took $50,000 she inherited when my dad died 30 years ago, invested it conservatively and lived very frugally. That $50,000 grew to $150,000, which, combined with her own retirement and Social Security benefits, allows her to live in the finest of long-term care facilities. I can't even imagine what life is like for those who care for loved ones 24/7.
I hope that Ronald Reagan's death has given us more awareness and reminded us that no one is exempt from this horrible illness. Not doctors, not teachers, not former presidents of the United States. Money, status, knowledge -- none of these prevents Alzheimer's.
Let's join Nancy Reagan in her fight against Alzheimer's. Let's raise money and push for research. Let's put an end to Alzheimer's -- or at least slow it down.
Jan Mead lives in Wichita.
SENDAI, Japan (Reuters) - Sachiko Murase is a changed woman. A year ago, Alzheimer's disease was so advanced in her that she could hardly recognize a pencil. Now, after having an increasingly popular treatment in Japan called "Learning Therapy," her once blank expression is punctuated with smiles.
"You see it's not only me. We're all having fun," said a beaming Murase, 83, at a nursing home in the city of Sendai, 190 miles north of Tokyo.
Alzheimer's, a brain disease whose causes are not fully understood, can start with mild forgetfulness but gradually ravages the memory and makes it hard to think and use language.
Murase is one of an estimated 1.5 million afflicted among the 24 million Japanese over the age of 65.
She is not cured of the disease, however, and no one is pretending to be able to turn back the clock.
But thanks to methods developed by Professor Ryuta Kawashima of Tohoku University in Sendai and backed up by an army of volunteers and textbooks from Kumon Institute of Education Co. - Japan's largest private education company - she has regained an ability to communicate and interact with people.
The "Learning Therapy" method consists of meeting regularly in classes to perform simple calculations and read aloud passages from essays or novels.
Advocates say it works like a mental exercise to rehabilitate the frontal cortex, part of the brain thought to be important for higher-level functions, memory, reasoning and judgment.
According to Kawashima, who began his research in the Sendai nursing home, a majority of Alzheimer's patients who regularly performed these simple tasks showed improvements in their scores in a test used to determine the severity of Alzheimer's disease.
Even those who did not improve saw little or no deterioration in their mental state during the time they were tested, he said.
While a range of remedies from crossword puzzles to berries has been claimed to help prevent Alzheimer's, Kawashima says this is a full treatment that has been thoroughly researched with a salvo of medical tests.
For staff at the Evergreen nursing home, the improvements have been very noticeable.
"In the past we used to have many behavioral problems because many of our patients had severe symptoms," nurse Rika Murakami said as she checked responses from one of the elderly women attending a recent session.
"But what we've seen since is that they've begun smiling more and many have become more serene," she said.
SIMPLE IS BEST
But the course is far from guaranteeing a full recovery, and the spotlight remains on prevention.
"Even after three years we found that there was no way we could return them to their old selves," Kawashima said. "So the next step then was to think about prevention."
Thus began courses for healthy and less elderly seniors.
These experimental classes began in Sendai, where twice a week some 40 people aged 70 and over gather at a local school to perform tasks that are similar to but slightly more difficult than those done in the nursing home. "The course would probably be easy even for my grandchildren," grumbled one participant, Takao Kumagaya, 74.
"But that's OK. That's how it should be," he added. "Simple subjects like these are what stimulate the brain to keep it young."
These concepts have caught on in Japan like wildfire. Even local governments have taken notice.
In the Shinagawa district of central Tokyo, plans are in place to start similar classes to those in Sendai. Another Tokyo district and one other prefecture are following suit.
Officials at Shinagawa, which like the rest of the country has seen a rapid increase in retired people who need extra medical care, say they fear the day when the increase in elderly patients stretches their welfare support system to the limits.
"Our greatest concern right now is preventing elderly people from being marginalised in our society," said Mari Niimi, head of Shinagawa Welfare and Senior support department.
"So there is great interest in the prevention of Alzheimer's as the care of elderly people with this disease is very difficult," she said. "If we can truly prevent this, it would be revolutionary."
In the meantime, please check back for articles and posts. We will be offering a story on the treatment of memory loss in Japan, which will be posted by this evening - our news reporting is unaffected by the maintenance activity!
Thanks for your support.
We did receive this in the mail from a concerned member, which we thought we should share:
I BETTER NOT HEAR OF ANYONE BREAKING THIS ONE OR SEE DELETED
This is a ribbon for soldiers fighting in Iraq. Pass it on to everyone and pray.
The study in the Journal of Neurology, Neurosurgery, and Psychiatry points out that severe niacin deficiency is known to cause dementia. However, the researchers note that it is unclear if more subtle variations in niacin intake influence the risk of mental deterioration.
"There have been no epidemiologic studies to look at the association between dietary niacin and Alzheimer's disease or cognitive decline," lead author Dr. Martha C. Morris, from the Rush Institute for Healthy Aging in Chicago, told Reuters Health.
Moreover, "animal studies and other studies have really focused on the effects of very high therapeutic dose levels of niacin," not amounts found in a standard diet.
To investigate, the researchers asked several thousand elderly people living in a Chicago community about the types and amounts of food they ate and tested their mental abilities.
The study focused on 815 randomly selected subjects who were free from Alzheimer's disease at the start of the study. After an average of nearly four years, 131 of the participants were diagnosed with Alzheimer's disease.
A high level of total niacin intake seemed to protect against both Alzheimer's disease and cognitive decline. The association was stronger for niacin intake from foods than for niacin taken in vitamin supplements.
"We were surprised to see a fairly strong association between niacin intake from foods and Alzheimer's disease," Morris said. Compared with the lowest intake, the highest intake "was linked to an 80 percent reduction in risk."
In the overall study population, high niacin intake was also linked to a reduced risk of cognitive decline.
Although the finding are provocative, Morris concluded, they will require verification before any changes to current dietary guidelines can be recommended.
Mary Putnam, 82, is in the early stages of Alzheimer's disease.
Right now she can be cared for in the Visalia home of her daughter, Jacqueline Baker, her son-in-law and her four grandchildren.
But Alzheimer's is a progressive disease that over time reduces the memories and reasoning abilities of its victims until they are unable to care for themselves in even the simplest ways.
So while her mother doesn't need that much supervision now, Baker says she knows that could change. Caring for her mother could become an all-consuming task.
It would be a big help, Baker said, if she could find caregivers who could step in for her when she runs errands or goes shopping -- or when she just needs a break.
Pastor Larry Dodson and his congregation at New Life Community Church in Tulare are working to provide just that. Church leaders have been developing a plan to open and operate an adult day-care center for people suffering from Alz-heimer's and other forms of dementia.
"People who don't want their loved ones in a [care] facility 24/7, this is a benefit for them," Dodson said. "They need respite and to know their loved ones are cared for."
Dodson is acutely aware of what Alzheimer's patients and their families endure. His mother-in-law, who suffers from the neurodegenerative disease, lives with him and his family.
He also knows how badly day-care programs for Alzheimer's are needed in Tulare County. The only such program in the north end of the county, the Alzheimer's Day Care Resource Center in Visalia that operated five days a week, closed its doors June 30.
Yvonne Pinal-Wahlstrom, who ran the center during its two years of operation, could not be reached for comment.
Only an Alzheimer's respite program that operated for four hours on Tuesdays at the Visalia Senior Center remains open.
The Tulare Senior Citizens Center had offered a similar Friday-only program, but it stopped in April when it lost state funding. Organizers said they expect to have it running again some time in August.
With the closure of the Resource Center, the nearest day-care programs for adults with dementia are in Porterville and Hanford. And while another adult day-care program is in the works for Lindsay, it's still up to two years away.
None of those is a practical option for people in the north end of Tulare County, said Dodson, "Who from Visalia or Tulare is going to drive people 30 miles? That's why we want to open one [here]. ... We have the program on paper, and we have the staff lined up."
All the church needs is about $15,000 in "seed money," which would come from donations, he said. After that, once the program is on its feet, the plan is to pay for it through client fees -- $7 an hour or less depending on incomes -- with donations and grants, Dodson said.
One other thing Dodson and his fellow New Life officials would have to decide is where to house the center. Dodson said he would like to take over the lease on the Resource Center in Visalia, but the landlord is asking more than the $1,100-a-month rent that his church can afford.
If the church can't negotiate a break in the rent, Dodson said it's likely a new center would be set up in Tulare with an eye toward possibly opening another in Visalia some time later.
Of course, either plan depends on New Life raising the money.
"I wish somebody would take [the Resource Center] over, because it's needed," said Barbara Anderson, who ran the Alz-heimer's respite program at the Visalia Senior Center for nearly 10 years.
She said having a place to socialize is important to Alzheimer's patients.
Besides improving the quality of their lives, many people say they believe such activities help slow the progress of the disease, which mostly strikes people over the age of 65 and becomes more prevalent as people get older.
Cheryl Perkins, the adult services division manager for the county's Health and Human Services Agency, and others who deal with families of Alzheimer's sufferers, said caring at home for a patient is physically and mentally demanding.
The care can range from feeding and changing adult diapers to calming people panicked because they can't recognize their own homes and the people around them, to ensuring that loved ones don't wander off and injure themselves.
As such, experts say without periodic respite, families can quickly burn out, some -- particularly elderly spouses or relatives -- ending up in even worse medical shape than the people for whom they were caring .
Velma McMafter, 81, of Visalia knows that problem all too well. Her husband, Bill, 85, was diagnosed with Alzheimer's nine years ago, and she has primarily cared for him.
When it started, "It was very frustrating. He would get lost. He couldn't find his way home.. He would forget people. He forgot where his barber was. ... Now he forgets everything. He still remembers me. He knows his immediate family. But friends, he will forget. I have to be with him all the time.
"It's very difficult. Initially I got very depressed. I got so depressed, I had to go to the doctor. I didn't care of I lived or died. I didn't want to get out of bed," she said.
But medication has helped alleviate her depression, McMafter said, and, "Now I can handle anything -- but I still need to take a break."
She took Bill to the Resource Center once a week before it closed as well as every other week to the Visalia senior center's respite program.
"With a city our size ... we need this," she said of respite programs. "It's just as important for [Bill] as it is for me," adding that her husband was like a child excited to go to kindergarten each time he went to the Resource Center.
"I know when I told him we couldn't go there anymore, they're closing, he said, 'That's too bad.' "
Two new studies highlight how brain scans can tell whether someone will go on to develop Alzheimer's, and how quickly the person will decline mentally.
As people get older, it is not normal to have a decline in cognitive function or the ability to think and remember.
Any change is abnormal, and these studies show changes, on brain MRI, can be powerful predictors of who is at risk, allowing the patient and family to be better prepared.
The two new research studies, in the Journal Neurology, showed MRI brain scans can tell how quickly a person will decline if diagnosed with Alzheimer's, and who, even among those with mild forgetfulness, will develop full blown Alzheimer's dementia.
The MRI should be a standard part of the workup of anyone with any suggestion of mental decline, said Dr. Jeremy Koppel, a neurologist with Long Island Jewish Medical Center.
"We have a better chance at improving quality of life and sustaining quality of life," Koppel said.
The new research also found evidence of cerebrovascular disease in the brains of those more likely to progress. This means the same cholesterol plaques that clog brain arteries, and lead to strokes, also increases the odds of Alzheimer's progression.
"It's very important to identify patients with high blood pressure, diabetes and atrial fibrillation," Koppel said. "Any illness that might contribute to cerebrovascular disease should be picked up in patients as quickly as possible and be treated to decrease the likelihood that they'll progress to Alzheimer's disease."
He knows just how to wrestle with his 8-year-old twin grandsons, Kevin and Devin. He's perfect at playing Chased by the Monster, to the delight of Ben, his 3-year-old grandson. He remembers all the funny little clucking noises that draw coos from granddaughter Kennedy Warme and great-grandson Caden Thayer, both 3 months old.
"He hasn't forgotten that," says his wife, Valerie.
To most of his 19 grandchildren, who range in age from 30 years to 3 months, Fred is "just grandpa, the way he has always been," she says.
Only, he is not.
Fred Luckau has Alzheimer's Disease, and the adults in his family are painfully aware of what the youngest grandchildren are not: The 76-year-old, retired computer technician has begun the long fade into the forgetting.
Approximately 4.5 million people in the United States have Alzheimer's, including 28,000 Utahns. Experts say the latter count may be about to explode, given the healthy lifestyles of Utahns, which leads to longer life spans. The state's population that is 85 and older -- half of whom are likely to develop dementia or Alzheimer's -- is expected to increase 38 percent by 2015.
That means many more families will, like the Luckaus, face the many sad tasks required when caring for a loved one with the disease.
Among them: helping grandchildren understand what is happening.
"Children just don't know what's going on," says Cheryl Ward, development director for the Utah Chapter of the Alzheimer's Association. "They may see a grandparent become violent, ignore them, say the same thing over and over, wander off. If it's a teen, it may be embarrassing. If it is a younger child, they may just be befuddled by it.
"If parents aren't explaining it to them, what are they to think?" Ward says -- particularly when the first thing grandchildren may experience is their own parent struggling to accept the bad news.
"When we first learned it was Alzheimer's, it really broke my heart," said Shahara Thomas, one of Fred and Valerie Luckau's seven children. "I was really sad, I just cried. The kids were like, 'What is going on?' "
Thomas, like her siblings, discussed their father's diagnosis with her older children.
"We've told them that he might say things that don't sound right and that it's going to be hard sometimes," says Shahara Thomas, whose four children range in age from 8 to 15.
Sue and Collin Cowley of Salt Lake City had a similar conversation with their three children, ages 10, 8 and 5, after Collin's mother Patty was diagnosed with early-onset Alzheimer's in her 50s.
"We explained on a kid level that she had a disease that was hurting her memory and making it harder and harder for her to remember things and how to do things," said Sue Cowley, whose oldest child was born about the time her mother-in-law developed the disease.
Because Fred Luckau is the pleasant, cheerful and affectionate man his family has always known, there has been little need to fill in the younger ones.
The little grandchildren simply take in stride his memory foibles -- laughing along with him when he repeats a sentence or delighting when he decides, as he did last week, to have ice cream for breakfast.
"They don't notice that as being strange," says Valerie. "To them, it's 'Hey, that is a wonderful idea.' "
Charles "Chick" and Lula Ruoti have had custody of their granddaughter, now 5, since she was about 3 months old -- long before Alzheimer's attacked Lula, 71.
"Our granddaughter accepts her for what she is," says Chick Ruoti. "Sometimes she'll say, 'Oh, grandma, you keep forgetting.' You try to talk to her [the granddaughter] and explain what's going on, but when they are her age, you're not sure whether you get through."
Read more of Brooke Adams article from the Salt Lake Tribune>>
Alzheimer's - a topic for National and Global Focus
What do we mean? We would love to hear your thoughts on the topic.
The Congressional Task Force on Alzheimer's Disease is
hosting a panel discussion followed by Q&A on how the federal
government can better accelerate the development of
More than 4.5 million Americans have Alzheimer's disease today
and this number is expected to reach 6.5 million in 2025 and
13.4 million in 2050. This condition is taking an increasingly
tremendous toll on American families as well as our public
health system. Recent data shows that, if left unchecked,
Medicare costs for patients with Alzheimer's disease and
related dementias will reach $294 billion by 2025 and exceed
$1 trillion by 2050.
The impact of this epidemic - on America's families and
healthcare system - can be significantly reduced by slowing
the onset and progression of Alzheimer's disease. Medicare
alone could achieve savings of $126 billion by 2025 and $444
billion by 2050.
U.S. Reps. Ed Markey (D-MA) and Chris Smith (R-NJ), co-chairs
of the Congressional Task Force on Alzheimer's Disease
Dr. Stephen Potkin, Department of Psychiatry and Human
Behavior, University of California, Irvine
Dr. James Shipley, Praecis Pharmaceuticals, Inc.
Alan Bennett, Ropes & Gray
'Smart pills' make headway
By Rita Rubin, USA TODAY
You can rub Rogaine into your scalp to try to regain the hairline of your youth. You can inject Botox into your forehead to smooth time's inroads, at least temporarily. And, some scientists predict, you'll eventually be able to pop a pill to freshen up the inside of your head as well.
Someday soon, if someone jokingly asks you if you remembered to take your smart pill, you can answer yes — seriously.
Thanks to recent strides in understanding how the brain works, it's only a matter of time before medications specifically designed to improve mental ability, or cognition, hit the market.
"The hallmark of these drugs is they don't create more memory," says John Tallman, CEO of Helicon Therapeutics of Farmingdale, N.Y., which plans to begin testing its most promising brain drug in humans later this year. "What these drugs really do is enhance the conversion process of short-term to long-term memories."
Besides Helicon (for the mountain in Greek mythology where Apollo played with the Muses), companies with such evocative names as Sention (apparently a play on sentient, which means conscious or aware) and Memory Pharmaceuticals are focusing on medications to treat patients whose brains are impaired by disease or injury.
But the real market for such drugs might be healthy people who would simply like to be a little quicker on the uptake.
Americans already spend $1 billion a year on dietary supplements claiming to boost brainpower, even though there's little evidence that they work, notes an article in the May issue of Nature Reviews Neuroscience. From vitamin B12 to ginkgo biloba to "BrainQUICKEN" capsules — "used by top students at every Ivy League institution," according to the product's Web site — health-food stores and the Internet are rife with products promising to enhance memory and learning. (Related story: Who should getting a boost in brainpower?)
Once the Food and Drug Administration allows a drug on the market to treat, say, Alzheimer's disease, doctors could prescribe it "off-label" for any purpose they like, including sharpening healthy minds dulled by age or fatigue. And Internet shoppers would have their pick of Web sites selling the drugs without even requiring a prescription.
To an extent, it's already happening. Though it's not clear how widespread the practice is, high school and college students who don't have attention deficit-hyperactivity disorder are taking Ritalin to help cram for exams. Scientists have been known to pop Provigil, approved only to treat narcolepsy, to increase alertness before speaking at professional meetings.
"People are already using a wide range of medical drugs to improve their own performance," says Sention CEO Randall Carpenter, citing Viagra's popularity with men who don't have erectile dysfunction as one example. "It's almost impossible to stop people if they want to do that."
'Normal' cognitive decline
On its Web site, Memory Pharmaceuticals of Montvale, N.J., acknowledges that the potential market for its compounds, one of which is being tested in humans, might extend far beyond patients with Alzheimer's and other memory-robbing ailments. Though 37 million people worldwide have Alzheimer's disease, the company says, more than 180 million — or half of all people over 65 — are experiencing "age-associated cognitive decline."
"This decline is not clearly linked to a definable disease condition and may be a 'normal' part of the process," the company says on its Web site.
Memory Pharmaceuticals raised $35.4 million in its initial public offering this year. President and chief science officer Axel Unterbeck says the medical need alone "would be worth the entire investment" in developing drugs to improve cognition. But he acknowledges that healthy people will seek them out. "This indeed will be a very interesting trend to look at," he says.
Tallman says older people are "very, very concerned about their memories, because their memories are what make them human. No honest person would ever say to you, 'I would never take the drugs.' "
Still, there's no guarantee drugs that work in people impaired by disease would also benefit healthy people who would simply like to recall names more quickly.
For example, first-generation Alzheimer's drugs Cognex and Arricept block the breakdown of acetylcholine, one type of neurotransmitter, a substance that enables nerve cells to communicate with each other. Alzheimer's patients have a shortage of acetylcholine, but people with normal brains do not, so it's not clear what effect the drugs would have on them, says Steven Rose, a director of the Brain and Behavioural Research Group at the Open University in England.
And even if such drugs did enhance cognition in average individuals, Tallman says, "highly functioning people would have probably limited benefit."
Duke University researchers have found that the nicotine patch, approved only to help smokers break the habit, boosts brain function in people with mild to moderate Alzheimer's disease and adults with ADHD and schizophrenia. But earlier tests in healthy volunteers found only a modest effect, says Edward Levin, a professor in Duke's psychiatry and behavioral science department.
Even in Alzheimer's patients, Levin cautions, the nicotine patch's benefits aren't worth the risks. Side effects include an elevated heart rate and blood pressure, sleep disturbances, nausea and dizziness.
The nicotine patch points out another obstacle toward developing "smart drugs" for normal brains. "It has to be as safe as water," Carpenter says. "That's a very daunting task that few people want to try to accomplish."
Perhaps somewhat surprisingly, Stanford University researchers including Dr. Jerome Yesavage found that nicotine gum as well as Aricept, used to treat patients with mild to moderate Alzheimer's, did improve healthy, middle-aged pilots' performance in flight simulators. However, Aricept also can cause side effects that would be pretty undesirable in a pilot, such as dizziness, fainting and vomiting, says pharmacologist Martin Mumenthaler, who led the study.
"The issue is: How do you specifically alter such a complex organ as the brain without affecting anything else?" asks biologist Robert Gerlai, a memory researcher at the University of Hawaii. "The brain doesn't just work on learning and memory. It has all kinds of other functions." In addition, Gerlai and others in the field point out, there is the potential risk that memory-enhancing drugs would work too well, preventing users' brains from distinguishing between important and trivial information.
Some scientists say Helicon's leading drug, aimed at activating a protein involved in the formation of long-term memories, might interfere with short-term memory, Tallman acknowledges.
Animal "memory models are pretty good, but it's hard to really get a total read on human memory without doing human trials," he says. Although Helicon has not yet begun testing its drug in people, Tallman says he suspects that any adverse effects on memory would be transient.
A mental 'jump-start'
Phase I trials, designed to assess the safety of experimental drugs, are conducted in healthy volunteers. So besides monitoring the volunteers for side effects, Sention, of Providence, and Memory Pharmaceuticals are administering tests to assess their drugs' effects on learning and memory.
Mark Bear, a Massachusetts Institute of Technology neuroscientist and Sention co-founder, emphasizes that the Phase I studies were too small to yield robust data about the drugs' effectiveness. Still, he says, "I would be willing to say that the results were very encouraging."
Though it would be unethical for Bear, 46, to test his company's drugs on himself, he does occasionally partake of a medication that might be the first safe and effective smart drug on the market.
Modafinil, sold as Provigil, was approved in 1999 for the treatment of daytime sleepiness in narcolepsy patients. It's not cheap. Web sites sell 30 100-milligram tablets for around $200.
In a small study of healthy men published last year, Barbara Sahakian of the University of Cambridge found that modafinil safely improved performance on tests of memory and attention.
Sahakian says she and her collaborators limited their study to men to eliminate the potentially confounding effect of women's menstrual cycles. But, she says, there's no reason to think that modafinil wouldn't work the same in women.
"It's probably the first smart drug that I've seen," says Sahakian, one of the co-authors of the Nature Reviews article on cognitive enhancers.
Bear says he takes modafinil "to jump-start myself across time zones," not to enhance his mental performance.
He first asked his doctor for a prescription before traveling to a scientific meeting in India. "I had to arrive and give a seminar in the same day. I said to my doctor, 'Look, I'm going halfway around the world. I simply would not be able to function' " without the drug.
Though Bear took modafinil to keep from nodding off in the middle of his presentation, he acknowledges that "anything that increases alertness will increase cognition."
And anyone who has downed a double espresso — or two or three — while studying for an exam or writing a report would probably drink to that.
Although it's bite can be deadly, doctors say the gila monster could help diabetics.
When school principal Marcia Parker was diagnosed with type 2 diabetes, she couldn't lose weight. Eventually, she joined a study that used the lizard's spit to control insulin levels and weight.
"I lost about 15 pounds," she said.
Doctors discovered that a hormone in the lizard's saliva could fight diabetes and obesity. It stabilizes blood sugar levels.
By producing the same hormone synthetically in an injection, physicians help diabetics control their insulin levels without other injections or changes in diet.
The gila monster isn't the only creature scientists are turning to for development of new treatments. Species from blowfish to leeches are being used to fight Alzheimer's, even arthritis.
The vampire bat carries a protein in its saliva that dissolves blood clots which cause strokes and could rival the current best treatment which must be given within three hours of the stroke.
"The current treatment for dissolving blood clots is called TPA. It has to be given within three hours typically and causes a certain percentage of bleeding in the brain. The bat saliva has the benefit of being effective as long as six to nine hours, which is a big improvement," said Dr. John Cochran.
The experimental drugs are still in clinical trials. Even if successful, they are several years away from your pharmacy.
The gila monster's spit may do more than just fight diabetes. Recent studies have shown that the lizard's saliva also contains a chemical which acts on part of the brain the affects memory loss.
Doctors hope it could eventually lead to a treatment for Alzheimer's.
The regional government of the Balearic Isles is (here is a map) to provide the islands' senile dementia and Alzheimer's disease sufferers with around 3,000 mobile tracking devices through its Public Health Commission. The project, which has a budget of around 48,000 euros, will be launched in July.
Martes, 6 julio 2004
The project was approved by the Commission, which will permit the authorisation for the grant for the project to be published at the end of June.
The device will make it possible to track persons with Alzheimer's-related problems who are in the first and second stages of the disease and still possess a certain degree of mobility.
These devices have a button which the person presses if they get lost, which puts them in contact with the emergency services. Families must have an income below the level of the Official Minimum Wage to qualify for the device.
GPS and GSM, the perfect combination for tracking patients
The future of systems for tracking patients lies in the conjunction of mobile technologies such as GPS and GSM, which provide almost perfect triangulations to determine the exact position and track a certain group of patients.
Numerous projects have been presented based on the use of mobile technologies, but the groundbreaking feature of this project is that it uses the GPS communication system, which uses GSM when the former cannot be used.
Both systems are used for reasons of efficiency since GPS is much more effective and precise in obtaining locations, but requires an aerial that is pointed at the sky. This can be problematic in cities where there are a large number of obstacles that cast a shadow over the generator. In these cases the transmitter device changes signal and begins operating in the same way as any mobile that transmits messages - such as traditional text messages - to a main computer which indicates the street location of the user if they are in a city and reports their exact coordinates if they are in a rural environment. In this way the patient is always supervised because it only requires coverage.
Persons affected by dementia suffer a progressive deterioration in their thought processes and behavioural changes that make it difficult for them to continue with their daily routine. Their behaviour also changes. The most common symptoms are memory loss, orientation problems and difficulty in taking precautions
With baby boomers entering their 50s and 60s, society can expect to see an explosion in the number of people with Alzheimer's disease within the next 50 years unless prevention or a cure is found, said an executive of the Alzheimer's Association recently.
According to an Alzheimer's Association fact sheet, 11.3 million to 16 million people could be afflicted with the disease by 2050. Since people can live an average of eight years -- some as many as 20 years -- after symptoms appear, the national cost of long-term care will run into the billions.
"With the baby boomers approaching their 60s and the death rates declining -- it's not a maybe -- we're going to be in it," said William Fisher, CEO of the Alzheimer's Association of Northern California and Northern Nevada, which recently hosted a conference on the disease at Stanford.
Advocates such as Fisher say a cure can be found, and researchers are at the cusp of new information that might be the key to prevention.
"There's a growing body of data that relates cardiovascular health to Alzheimer's disease," Fisher said. "By improving cardiovascular health -- watching your cholesterol, weight, blood pressure, getting enough exercise and not smoking -- you minimize the overall risk of getting Alzheimer's."
In the future, people might be immunized to prevent AD, and molecular genetic studies are decoding the processes that lead to the disease. Equally compelling are the advancements in improving the quality of life for both the patient and the family members who care for them.
Four drug treatments have been approved by the Food and Drug Administration: Aricept, Exelon, Reminyl and Namenda. Although the drugs do not cure the disease or get people back to work, they do help to improve memory, attention and concentration. They also help to minimize delusions, anxiety, and mood swings, Fisher said.
Alzheimer's disease is not a normal part of aging, although people who have the disease tend to be older than 65. They often have other chronic diseases such as heart arrythmia, diabetes, osteoporosis, and asthma. Prescription drugs -- taken for 5 to 10 years -- are a major portion of their health care costs.
Advocates are calling for discount medications and changes in Medicare's re-imbursement policies that allow more units of time for office visits. It takes time for patients with Alzheimer's to describe pain, respond to cues and answer questions.
Also experts say family members, who are usually the primary caregivers, need improved insurance coverage for fatigue and stress-related illnesses that come from caring for someone 24/7.
Fisher said doctors are getting better at making referrals. There are a myriad of reasons why doctors are reluctant to manage patients with Alzheimer's for the long haul. They aren't always compliant in taking medications or following directions; nor do they show up consistently for follow-up.
"Old people are expensive to treat," said Fisher, whose grandmother died of Alzheimer's. "You need special re-imbursement from Medicare, and there's no cure."
Staff Writer, San Mateo County Times