Monday, January 22, 2007

Alzheimer's Vaccine Patch Works in Mice


The Alzheimer's vaccine being tested works by triggering the immune system to recognize and attack Ab -- a protein that abnormally builds up in the brains of Alzheimer's patients.




Source United Press International


Alzheimer's vaccine patch works in mice





MIAMI, Jan. 22 (UPI) -- A transdermal vaccine shows promise in treating the deadly memory-impairment disorder Alzheimer's disease in mice, say U.S. researchers.

The needle-free approach appeared effective in clearing the Alzheimer's-affected animals of the brain-damaging plaques that mark the disease, said researchers at the University of South Florida.

"While many groups have shown vaccinating against the beta amyloid protein (Ab) can reduce Alzheimer's-like pathology including certain cognitive deficits, this study is the first to demonstrate that immunization using the skin may be an effective way to reduce Ab pathology," said senior study author Jun Tan, director of the Neuroimmunology Laboratory at the Institute for Research in Psychiatry at USF.

The Alzheimer's vaccine being tested works by triggering the immune system to recognize and attack Ab -- a protein that abnormally builds up in the brains of Alzheimer's patients.

"The beauty is that something as simple and non-invasive as a skin patch could potentially be a promising therapy for Alzheimer's disease," said study coauthor Terrence Town.

A transdermal treatment for the disease would also reduce the risk of adverse immune reactions, the researchers said.

The study is published online this week in The Proceedings of the National Academy of Sciences.

Thursday, January 18, 2007

Alzheimer's: Understand and control wandering


One of the questions I am most frequently asked is if I am worried that my mother might wander away and get lost.

Alzheimer's: Understand and control wandering

Wandering is one of the more widely known behaviors of people suffering from Alzheimer’s disease.

This article from the Mayo Clinic explains this behavior and some of the likely causes and remedies.

Monday, January 15, 2007

New Gene Linked to Alzheimer's


"It fits into what we believe is the main mechanism of Alzheimer's already," Gandy said. "This reinforces the idea that we're on the right track with therapies already in the pipeline, while also suggesting a totally new strategy that could be used to target entirely new classes of drugs."




New Gene Linked to Alzheimer's


Source Forbes and

Nature Genetics




SUNDAY, Jan. 14 (HealthDay News) -- Scientists has discovered a major new gene and linked it to the development of late-onset Alzheimer's disease. The researchers found that faulty versions of the gene --known as SORL1 -- are more common among those with the disease than among healthy people of a similar age. The finding is significant, the researchers said, because the study included more than 6,000 people from a wide range of racial and ethnic groups -- white Europeans, blacks, Caribbean-Hispanics and Israeli-Arabs.

Abnormal SORL1 genes seem to set in motion a neurological chain of events that promotes the production of amyloid plaque in the brain -- a development integral to the onset of Alzheimer's.

People with these gene variants also appear to have fewer normal SORL1 genes overall, a dip that the researchers believe could also raise the risk for developing late-onset Alzheimer's.

But, the researchers added that not all people with the faulty SORL1 gene will develop Alzheimer's.

"There are multiple genes and maybe some environmental factors [involved], and it may be that some people carry a risk gene but don't get the disease," explained study co-author Dr. Richard Mayeux, co-director of the Taub Institute for Research on Alzheimer's Disease and the Aging Brain in New York City.

"So, until we map out all of (the) genes involved we're not going to understand exactly how to calculate risk for this disease," he said.

The findings are published in the Jan. 14 online issue of Nature Genetics.

Mayeux made his remarks during a news conference prior to the study's release. He was joined by his co-lead collaborators: Dr. Peter St. George-Hyslop, director of the University of Toronto's Centre for Research in Neurodegenerative Diseases; Lindsay Farrer, chief of Boston University's Genetics Program; and Dr. Steven Younkin, chairman of the department of pharmacology at the Mayo Clinic College of Medicine, in Jacksonville, Fla.

The researchers pointed out that three other genetic variants have been previously tied to the development of early onset Alzheimer's, a relatively rare form of the illness that typically strikes between the ages of 30 and 60.

However, only one other genetic variant has been previously linked to late-onset Alzheimer's, which typically strikes people over the age of 65 and accounts for 90 percent of all cases of the disease. This other variant -- known as ApoE4, and first isolated in 1993 -- is thought to account for about 20 percent of all late-onset Alzheimer's cases. ApoE4 is believed to elevate the risk of disease by between 30 percent and 40 percent, the researchers said.

As for the SORL1 variant, the study authors said it probably accounts for fewer cases of Alzheimer's than the ApoE4 variant.

The researchers based their SORL1 finding on a five-year genetic analysis of blood drawn from 6,000 people from around the globe. They included 500 black sibling pairs with one sibling who had Alzheimer's; 350 families in New York City, Toronto and the Dominican Republic -- totaling 1,800 people -- half of whom had the disease; and elderly residents of a northern Israeli-Arab community.

The researchers divided the entire pool into two groups -- one to establish the presence of SORL1 and the other to establish the gene's role. Describing SORL1 as a "big gene" that may contain as many as 500 variants, the researchers focused on the activities of just 29 -- leaving lots of gene turf yet to till.

None of the 29 variants so far appears to be directly related to an Alzheimer's chain of events.

But, when tallying the overall presence of both normal SORL1 and SORL1 with abnormal variants, the researchers found that in each of the racial and ethnic groups, SORL1 with variants was more common among the Alzheimer's patients than among the healthy men and women. And normal SORL1 was less common among those with the disease.

The researchers concluded that SORL1 clearly plays a role in the late-onset Alzheimer's.

While enthusiastic about the finding, Mayeux said it doesn't represent a smoking gun. "Alzheimer's disease is caused by a complex genetic puzzle, and the finding about SORL1 explains a section of the puzzle," he said. "It is not the entire story."

Mayeux and his colleagues stressed that much more work needs to be done.

Dr. Sam Gandy is chairman of the Alzheimer's Association's Medical and Scientific Advisory Council, and director of the Farber Institute for Neurosciences at Thomas Jefferson University in Philadelphia. He agreed that the new finding is just one step down a long and complicated research road, but he said it could be an important step.

"It fits into what we believe is the main mechanism of Alzheimer's already," Gandy said. "This reinforces the idea that we're on the right track with therapies already in the pipeline, while also suggesting a totally new strategy that could be used to target entirely new classes of drugs."

An estimated 4.5 million people in the United States have either early or late-onset Alzheimer's disease, a number that's expected to double during the next 25 years as the population ages.






Friday, January 5, 2007

Decoding Alzheimer's: After a century, promising treatments at last—and whispers of a cure



This is must reading for all Alzheimer's caregivers.

"After a century, promising treatments at last—and whispers of a cure"


Source Business Week Online

Decoding Alzheimer's

After a century, promising treatments at last—and whispers of a cure


Francesco Bellini hasn't been sleeping lately.
The charged-up chairman of Neurochem Inc. (NRMX ) is just months away from finding out if a drug developed by his Quebec-based company can actually slow the course of Alzheimer's disease. A clinical trial of the drug, Alzhemed, will wrap up in January, with results expected in the spring. "The summation of all our work and research for the last 12 years will happen in the next six months," he says.

Those 12 years have been focused on overcoming one of the toughest challenges in medicine: keeping Alzheimer's disease from slowly, relentlessly destroying the brain, something no drug has yet done. The data on Alzhemed have been promising but scant. In a 2002 study it stabilized the disease in nine patients over six months, but the small sample left plenty of specialists skeptical. Not Bellini, a scientist-entrepreneur who discovered one of the first effective treatments for aids. He bought a third of Neurochem and took the helm the same year the earlier Alzhemed trial was completed. "I started to feel very good about the drug as soon as I saw what it did for humans," he says.

Neurochem quickly moved ahead with a costly late-stage trial, enrolling 1,052 patients with mild to moderate Alzheimer's. There is plenty of debate in the Alzheimer's world over what the results of that trial are likely to be, but a recent follow-up of patients from the previous study found that four were still stable after four years on Alzhemed. In addition, Bellini says every patient who has completed the trial asked to continue the drug—a sign, he says, that it is helping. "I was expecting maybe 30% would ask, but 100%, that's remarkable."

It's not hard to understand why patients would want to continue: They are desperate for hope. Alzheimer's is a frightening trend for an aging population. One in 10 people over the age of 65 develops the disease. Over age 85, the odds rise to one in two. The diagnosis is an agonizing death sentence, as it takes anywhere from 3 to 20 years for Alzheimer's to kill—and it always does. The Alzheimer's Assn. estimates there will be 9 million Americans with the disease by 2020 and 15 million by 2050. If there are no disease-modifying drugs by then, the cost of care will top $1 trillion.

Whether or not Alzhemed works as hoped, its very existence is just one reason the outlook for Alzheimer's drug discovery is turning, finally, more positive than negative. A century after the disease was first identified, scientists are closing in on medicines that can safely delay or reverse its onset. The burden of proof doesn't rest solely on Alzhemed, either. Flurizan, a drug developed by Myriad Genetics Inc. (MYGN ), is also in a late-stage trial, with results expected next summer. A few years behind Alzhemed and Flurizan are promising treatments from Wyeth Pharmaceuticals (WYE ) and Eli Lilly & Co. (LLY ) that provoke an immune response against the disease. Nearly 60 other drugs designed to modify the disease are also in clinical trials, including one from AC Immune of Switzerland that caught the attention of biotech giant Genentech Inc. (DNA ), best known for its cancer treatments. Genentech just announced plans to invest $300 million for the rights to AC Immune's drug. "It's a whole new era," says Dr. Serge Gauthier, director of Alzheimer's research at McGill University's Center for Studies in Aging. "At least some of these medications are likely to work, and once we have disease-modifying drugs, we have opened the door to prevention."

It's particularly striking that the science is advancing despite a long-standing dearth of investment in Alzheimer's research. There are currently 4.5 million Alzheimer's patients in the U.S., and the direct and indirect costs of caring for them total more than $100 billion a year, making Alzheimer's the third most expensive illness after heart disease and cancer. Yet the federal government budgeted only $645 million for Alzheimer's research for 2007, $7 million less than the prior year. In contrast, $2.6 billion was allocated for research into HIV/AIDS, which afflicts one million Americans.

The massive funding pumped into HIV research led to predictable results: AIDS was transformed from a death sentence into a manageable disease in just 10 years. Scientists say the same could happen with Alzheimer's if there were a similar national will. "Look, if we doubled our research output it would halve the amount of time it will take to find a cure," asserts Dr. Leon J. Thal, director of the Alzheimer's Disease Research Center at the University of California, San Diego.

Certainly any disease could benefit from more funding, but with Alzheimer's the need for effective treatments is especially urgent. It is the only major cause of death in the U.S. where the numbers are getting worse, not better. That's because Alzheimer's is a disease of success. As people live longer and benefit from new treatments for common killers such as heart disease and cancer, the odds they will succumb to Alzheimer's increase. Proving the point, Los Angeles County just reported that deaths there from heart disease dropped 29% between 1998 and 2003, and from lung cancer by 19%. But deaths from Alzheimer's soared 220%.

Given the trend lines, any drug that ameliorates the disease is certain to be an instant blockbuster. Investment advisers Cowen & Co. (COWN ) calculate that if just a few of the medicines in clinical trials pan out, U.S. demand for Alzheimer's drugs could reach $10 billion to $15 billion annually, up from about $1.3 billion now.

The market will be even larger if these new drugs are used by millions of senior citizens with faulty memories, a condition called mild cognitive impairment (MCI) that significantly raises the odds of developing Alzheimer's. The hope of every drug developer out there is that a successful Alzheimer's treatment may be able to prevent the disease from occurring in these higher-risk patients. "The MCI market is huge—20 or 30 million people," says Neurochem's Bellini.

The changing outlook for Alzheimer's is particularly striking because, unlike heart disease and cancer, there has been no gradual evolution from good drugs to better. The Food & Drug Administration has approved only five medicines for the disease, led by Pfizer Inc.'s (PFE ) Aricept. All relieve only some memory loss, for some months, in some patients. Until recently, neither large pharmaceutical companies nor venture capitalists showed much interest in funding research into more effective drugs, given the low success rate. With no proven treatment, or even a proven cause, Alzheimer's research seemed just too risky.

The U.S. government has no plans to put together the equivalent of a moon shot to cure the disease. But a critical mass of committed scientists, philanthropists, and maverick entrepreneurs has come together and put forth new scientific approaches and new funding sources to push the field forward. The result: For the first time, scientists are beginning to whisper the word "cure."

PAST AND PRESENT
Rudolph E. Tanzi, a boyish-looking 47, ended up in Alzheimer's research in the early 1980s after he realized he probably wasn't going to make it as a rock star. Having recently graduated from the University of Rochester, he quit his band to work on the genetic causes of brain diseases at Massachusetts General Hospital. He earned a PhD from Harvard University, and in 1987 his team discovered a gene that plays a key role in the start of Alzheimer's, solving a central mystery of the disease.

Today, Tanzi is director of the Genetics & Aging Research Unit at Mass General's Institute for Neurodegenerative Disease, working with some 200 other researchers, several hundred mice, and his wife, Dora Kovacs, who studies the role of inflammation in Alzheimer's. Tanzi has started two companies to develop drugs based on his findings, written dozens of scientific papers, and still found time to pen a layman's history of Alzheimer's research, Decoding Darkness, published in 2000. "I can't imagine a more incredible puzzle to solve," he says.

The solution has been a long time coming. Alzheimer's was first identified at a medical meeting in Germany in 1906 by a Bavarian neurologist, Dr. Alois Alzheimer. He described a patient, Auguste D., whom he started treating for madness when she was 51. She died five years later, and when Dr. Alzheimer autopsied her brain he discovered it was riddled with sticky clumps and fibrous tangles. For the first time, dementia was classified as a distinct disease rather than a form of insanity, and there the science remained for 78 years.

It wasn't until 1984 that scientists figured out that those clumps are made of a protein found throughout the body called amyloid. The discovery gave birth to the amyloid hypothesis, which holds that the accumulation of amyloid plaque in the brain slowly destroys brain cells. This is still very much a theory. Some experts contend that the excess amyloid may instead turn out to be a by-product of some earlier disease process that already took hold of the brain. "Many in the field find the evidence behind the amyloid hypothesis compelling, but we can't exclude the possibility that other targets play an important role," says Dr. Richard A. Hodes, director of the National Institute of Aging (NIA). "It's critical that we not put all of our efforts in that domain."

Nevertheless, drugs targeting amyloid are much further along than any other approach because the amyloid process has been at least partially decoded. The gene discovered by Tanzi 20 years ago starts the process, creating a large protein called APP. Found in almost every cell of the body, APP sticks halfway out of the cell wall. Two scissor-like enzymes cut away a fragment of this molecule, which then floats away to facilitate communications between other cells. But for unknown reasons, these fragments sometimes go awry and become toxic.

In the brain, normal amyloid fragments are 38 to 40 molecules long. But in the mid-1990s scientists discovered that the wayward snips consist of 42 molecules. Those extra two molecules cause the amyloid fragment to fold in on itself until it looks like a bobby pin. As more and more bobby pins are formed, they become entwined, creating clumps called plaque.

The vast majority of Alzheimer's drugs in development target A-beta 42, as this overgrown fragment is known. There is wide variation in their methods, however. Some seek to reduce its production, while others try to keep it from accumulating into plaque. Tanzi and an Australian colleague, Ashley Ian Bush, came up with a "chelating" agent that washes A-beta 42 out of the brain before it can clump together.

Their drug is based on Bush's discovery that traces of zinc, copper, and iron prod amyloid to form into plaque. The two found a compound that removed those metals from the brain and caused amyloid levels to drop in mice. They then teamed up with a pioneering Alzheimer's scientist, Colin Masters, in 1997 to form Prana Biotechnology Ltd. (PRAN ) in Victoria, Australia.

Coming up with the money for a drug startup is never easy, and Alzheimer's is on the bottom of venture capitalists' to-do lists. But Bush had a deep-pocketed friend in Australia who was looking for a new adventure. Geoffrey Kempler, 50, CEO of Prana, made his millions by securing the Australian rights to the Aveda (EL ) line of beauty products. Fueled by a combination of "naiveté and enthusiasm," as he puts it, he spent a few million dollars getting Prana off the ground before its initial public offering in 2000.

Prana's metal-removing drug was tested in 36 patients in 2003, and it successfully lowered amyloid levels. But in April, 2005, problems with the drug's purity forced Prana to stop the program. The share price sank from $4 to $1 within days.

As it happened, Prana was working on a successor treatment designed to be safer than the first. Although still in shock over the blow to the market value, "we actually put our foot on the accelerator," says Kempler. The second drug successfully completed an initial safety study in 2005, and in December Prana started a larger trial with 80 patients in Sweden. If all goes well, the drug could reach the market in five years, says Kempler. The stock price, meanwhile, has risen to around $3 a share.

Tanzi is not counting on Prana alone. Alz-heimer's is such a complex disease that most experts anticipate giving patients a cocktail of drugs, much as they treat AIDS. Tanzi says he is willing to license his discoveries to any company seeking to develop an ingredient of that cocktail. Toward that end, in 2000 he co-founded TorreyPines Therapeutics Inc. (TPTX ) in La Jolla, Calif., to work out a compound that lops off the amyloid fragment at the 38th molecule instead of the 42nd, rendering it harmless.

This year, Tanzi started work on his biggest project yet: identifying all the genes involved in Alzheimer's. He predicts he will have a genetic blueprint in hand within two years and a genetic test within five. Tanzi doesn't have to scrape around for cash this time, either. The Cure Alzheimer's Fund, founded by three Boston area families, pledged $3 million to his lab for this genetic detective work, stepping in where the NIA and venture capitalists refuse to tread.

PHARMA PARTNERS
In 2000, Wyeth CEO Robert Essner bucked a pharma industry trend and made Alzheimer's a research priority. It wasn't his idea. Essner, who came out of the marketing side of the business, was talked into a partnership with Elan Corp. (ELN ) by Wyeth scientists enthralled with the Irish company's vaccine for treating Alzheimer's, which they thought was the most promising treatment out there.

The scientists warned Essner it would take three years and $100 million just to get the treatment into human clinical trials. They also conceded that they couldn't even hazard a guess at the likelihood of success, the odds were so low. Essner took the leap anyway: "Our scientists were so passionate that if I had turned them down, I would have had a mutiny."

Five years on, Essner figures Wyeth has spent more than twice that estimated $100 million. He has also made the concept behind the vaccine—that the immune system can be primed to fight off amyloid—the centerpiece of Wyeth's Alzheimer's program.

In the spring of 2002, Elan and Wyeth scientists were immersed in clinical trials of the vaccine. But in March they were forced to halt the trials when 15 of 300 patients developed encephalitis, a dangerous swelling in the brain. A deep gloom spread through the Alzheimer's research community. The Elan-Wyeth drug was the first to "cure" the disease in mice, but the risk of encephalitis forced doctors to halt human tests.

The researchers didn't give up. When they examined the blood of several patients in the trial, they saw that the vaccine had produced antibodies against the amyloid, as it was meant to do. In the fall of 2003, the companies announced that the autopsied brains of four vaccine recipients who had died of other causes had no amyloid plaque. A few months later, Swiss doctors reported that 19 of 28 patients treated with the vaccine had produced antibodies against amyloid, and 12 of those 19 either improved or stabilized their performance on memory tests—the first proof of principle that clearing amyloid could alter the disease in people.

The vaccine, a safer version of which is now in early-stage trials, calls for a patient to be injected with a tiny piece of the A-beta 42 protein found in deadly plaque. The injected fragment prompts the body to produce antibodies, which seek out and destroy more of the offending A-beta molecules. But tampering with the immune system can stir up unfortunate side effects, such as encephalitis. It's safer to send in some handpicked soldiers instead, otherwise known as monoclonal antibodies. The Wyeth/Elan partnership created such a lab-built antibody to target the same molecule used in the vaccine experiments, A-beta 42.

When injected into a patient, the antibody locates and destroys amyloid fragments without activating the immune system. Data released last spring from the first human trial of the drug, called AAB-001, showed that patients performed significantly better on memory tests, and there was reduced plaque in autopsied brains. Results from an ongoing Phase 2 trial are expected in early 2007. If positive, the company is likely to move into final testing quickly, putting the drug on track for FDA review by 2010. Meanwhile, Wyeth's strategy has attracted the sincerest form of flattery: Eli Lilly, Pfizer, and now Genentech are all developing amyloid antibodies.

There are also dozens of startup companies with intriguing anti-amyloid drugs. "We've got 30 to 50 drugs in Phase 2 and eight or nine in Phase 3," says William Thies, the Alzheimer's Assn.'s vice-president for medical relations. "They've passed an awful lot of hurdles. I believe some will work, and we will keep developing better and better medicines."

SOLDIER WITH FORTUNE
Leonard Lauder, the 73-year-old chairman of Estee Lauder Cos. (EL ), is an elegant man with an elegant office. He works in a robin's-egg-blue room high up on Fifth Avenue with a to-die-for view of Central Park. Around his desk are artworks by Richard Serra, Agnes Martin, and Claes Oldenburg, and his large coffee table is covered with fashion magazines and lavish art books. All this beauty represents his "day job," as he puts it. In off hours, he is determined to find a cure for Alzheimer's. His reason is simple: "Name me one person who sooner or later doesn't worry about getting it."

Lauder is not content to use his fortune, estimated at $2.9 billion, to bolster long-standing Alzheimer's charities. In 1998 he and his younger brother, Ronald, founded the Institute for the Study of Aging solely to turn promising Alzheimer's research into commercial drugs. To date, the institute and an affiliated public charity have funded 167 projects, spending $25.5 million. "We figured that if we put enough money into it and backed enough ideas, we had a pretty good shot at coming up with a cure," says Lauder.

With the meager public funds available for Alzheimer's research, a scientist with a good idea must scramble for money. The Lauders' foundation aims to ease the burden. The two brothers knew how frustratingly slow the hunt has been for an Alzheimer's drug, and thought a venture philanthropy that focused on drug discovery rather than basic research might be able to close the gap between the two. They hired Dr. Howard Fillet, a renowned geriatrician who had treated their mother at Mount Sinai Medical Center in New York (Estee Lauder died of heart failure in 2004) and told him to forget about requiring complex grant proposals. "They gave me an office, a desk, and a pot of money," says Fillet, the institute's director. "I go to meetings, hear an interesting presentation, and tell the scientist, Call me. I'll give you money.'"

That's the story behind Allon Therapeutics Inc. ( NPC.TO ) in Vancouver. Some five years ago, Allon's founding scientist, Ilana Gozes of Tel Aviv University, had collected meager funds from friends and family to finance her research into a protein fragment necessary for brain formation. She had a hunch the fragment might shield neurons from the damage inflicted by Alzheimer's.

Gozes was just starting her company when Fillet learned about her work. Based on a few conversations, he handed her $350,000. "No one else would have made an investment at that point," says Allon CEO Gordon C. McCauley, who came on board in 2004 when his venture capital fund provided the next round of financing. Allon's treatment has since proven safe in people and is about to enter a larger trial. And Allon has enough capital to keep the trials going—the company went public in 2004.

JUST THE BEGINNING
Dr. Paul S. Aisen oversees the care of some 1,000 Alzheimer's patients as director of the Memory Disorders Program at Georgetown University School of Medicine, and there is little he can offer them. Consequently he is willing to test any reasonable-sounding experimental treatment that comes along, and his program is one of the nation's leading centers for Alzheimer's trials.

Unfortunately, clinical trials often turn into exercises in futility, since fewer than 10% of experimental drugs survive the three-stage process to win FDA approval. Aisen knows this all too well. He spent 15 years testing anti-inflammatories such as Aleve and Vioxx against Alzheimer's because studies seemed to show a link between the popular drugs and a lower incidence of the disease. But in 2003 he admitted defeat after a rigorous trial found that anti-inflammatories did no good. He published the results and moved on, searching for something else that would work. "It is the patients' plight that gives everyone on our team a great appreciation for the tremendous need for better treatments," says Aisen.

Today, Aisen is the lead investigator for Alzhemed. His clinic is also running trials on Flurizan, antibodies from Wyeth/Elan and Eli Lilly, and the generic anti-seizure medicine Valproate. But he'll look far afield from advanced biotech labs for treatments. That's why he is testing a drug derived from a Chinese moss that has been used for more than 2,000 years in the Middle Kingdom to treat fevers.

Aisen learned in 1999 that doctors in China had been using the drug, called Huperzine A, for some 20 years to relieve symptoms of Alzheimer's. Now made by Neuro-Hitech Inc. (NHPI ), the drug improves memory in much the same way as Pfizer's Aricept and other existing Alzheimer's treatments, without the gastrointestinal problems associated with these older drugs. But Aisen was most intrigued by evidence that, in mice, Huperzine A protected brain cells from the ravages of plaque and tangles, something the other drugs can't do.

Aisen is now in charge of a mid-stage trial of Huperzine A. But he does not expect it, or any of the drugs he is testing, to be the definitive cure the world craves. Ultimately, scientists and physicians say today's research is laying the groundwork for treatments that can prevent Alzheimer's from taking hold in the first place. "I'm hoping we'll put ourselves out of business in 20 years," says Dr. Reisa A. Sperling, head of Alzheimer's clinical trials at Brigham & Women's Hospital in Boston. "I'm 47, and before I retire, I believe I'll be looking for another disease to study."

Thursday, January 4, 2007

Imaging Method Detects Alzheimer's Risk


An innovative brain-scan technology shows promise in detecting those at risk for developing Alzheimer's disease, years before symptoms become obvious.



Source Photonics

An innovative brain-scan technology shows promise in detecting those at risk for developing Alzheimer's disease, years before symptoms become obvious, by showing in living brains the abnormal protein deposits that can lead to the disease -- something that previously could only be confirmed by autopsy.

Scientists at the University of California, Los Angeles are in the early stages of identifying biomarkers in the blood and spinal fluid to help with Alzheimer's diagnosis, but they said this study is the first to report a real-time "window into the brain" that identifies the major abnormal deposits of the disease, which affects 15 to 20 million Americans, in living people who may not develop it for years to come.

The researchers used positron emission tomography (PET) imaging employing a small molecule invented at UCLA that binds to the abnormal proteins -- amyloid plaques and neurofibrillary tangles -- that may cause the disease. Previously, only an autopsy could determine the existence of these deposits and confirm a definitive diagnosis.

Study results found that the new method was able to track disease progression over a two-year period and was more effective than conventional imaging techniques in differentiating patients with Alzheimer's and mild cognitive impairment from normal study subjects. Mild cognitive impairment is a condition that increases the risk for developing Alzheimer's.

"The study suggests that we may now have a new diagnostic tool for detecting pre-Alzheimer's conditions to help us identify those at risk, perhaps years before symptoms become obvious," said Gary Small, Parlow-Solomon Professor on Aging, lead study author and a professor with the Semel Institute for Neuroscience and Human Behavior at UCLA. "This imaging technology may also allow us to test novel drug therapies and manage disease progression over time, possibly protecting the brain before damage occurs."

The study included 83 volunteers aged 49 to 84. Based on cognitive testing, 25 patients had Alzheimer's disease, 28 had mild cognitive impairment and 30 were normal controls. Researchers performed PET brain scans after intravenously injecting the volunteers with the new chemical marker, called FDDNP, which binds to the plaque and tangle deposits found in Alzheimer's patients. Scientists found distinct differences among people with normal brain aging, people with Alzheimer's and people with mild cognitive impairment.

The PET imaging showed that the more advanced the disease, the higher the FDDNP concentrations in the temporal, parietal and frontal brain regions, where the abnormal protein deposits typically accumulate. Patients with Alzheimer's showed the most FDDNP binding, indicating a higher level of plaques and tangles than other subjects.

"We could see the definitive patterns starting early in patients with mild cognitive impairment and advancing in those with Alzheimer's disease," said Jorge Barrio, a study author and professor of medical and molecular pharmacology at UCLA's David Geffen School of Medicine.

All subjects also received a PET brain scan using a more conventional chemical marker called FDG, which measures the metabolic function of cells and has previously been used in aiding diagnosis for Alzheimer's disease. However, FDG cannot identify the abnormal brain protein deposits that may cause the disease. In addition, 72 subjects received magnetic resonance imaging (MRI) scans, which show brain structure and size.

Scientists found that the FDDNP–PET scan combination differentiated between study subject groups better than the FDG–PET combination or the MRI.

"FDDNP yielded excellent diagnostic accuracy and precisely predicted disease progression and brain pathology accumulation," said Barrio. "FDDNP–PET also delivers the promise of new drug monitoring in human subjects for a more rapid introduction of therapeutic candidates to control or slow progression of the disease."

Researchers performed follow-up scans two years later on 12 research subjects, using FDDNP–PET. Patients whose conditions had grown worse -- declining from normal cognitive function to mild cognitive impairment or from mild cognitive impairment to Alzheimer's disease -- showed a 5 to 11 percent increase in FDDNP binding over their previous brain scans, suggesting an increase in plaques and tangles.

A brain autopsy completed on a follow-up Alzheimer's patient who died 14 months later showed high plaque and tangle concentrations in areas that had previously demonstrated high FDDNP binding values on the PET scan. "This is the first time this pattern of plaque and tangle accumulation has been tracked in living humans over time in a longitudinal study," said Small.

The study was published in the Dec. 21 issue of The New England Journal of Medicine. It was funded by National Institutes of Health,the Department of Energy, General Clinical Research Centers Program and numerous foundations. The DoE funds supported FDDNP synthesis, which was performed at the UCLA Cyclotron Laboratory.

UCLA researchers are now working with Siemens Medical to begin a clinical trial using the new molecular marker to obtain Food and Drug Administration approval. UCLA owns a patent on the approach and has licensed it to Siemens.

For more information, visit: www.ucla.edu



Keeping time with Alzheimer's


The following is an excellent article that I read in the San Francisco Chronicle.
"When guilt catches up with me, I am on the bike path above the creek, ducks swimming along beside me. Guilt rolls off our backs like you know what. Alone at last, I walk at my own pace. Fast. Fast is what Ben can no longer do -- and fast is slow compared with the woman coming toward me as I near the marsh. She is wearing shorts and earphones. She smiles and I smile back. What a good idea this is, walking out in the sun and cold. What could produce better clarity? I don't have to work it out the first day. I don't have to do it right the first time."
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Alzheimer’s Disease What is it? Who gets it? What causes it?


Alzheimer's disease is the most common cause of a condition called dementia. It is named for the German doctor who first described it, Alois Alzheimer. What is it? Who gets it? What causes it?

Also see:

What’s the Difference Between Alzheimer’s and Dementia?

Alzheimer’s Disease

What is it?

Alzheimer’s Disease What is it?  Who gets it?  What causes it?
Alzheimer's disease is the most common cause of a condition called dementia. Dementia is a general decline in mental ability, such as memory, language skills, judgment, and concentration. Alzheimer’s is a progressive disease, which means symptoms occur gradually and become worse over time. It is named for the German doctor who first described it, Alois Alzheimer.

Who gets it?

Alzheimer’s disease most commonly affects those over the age of 65, although it has been diagnosed in people in their 40s and 50s.

Huperzine A Factsheet (Alzheimer's)


I recently read about Huperzine A. The following page contains a fact sheet about the herb. Huperzine A may have cognition-enhancing activity in some Alzheimer's patients.

Huperzine

Americans Fear Alzheimer’s More Than Heart Disease, Diabetes or Stroke


A study by the MetLife Foundation found that Americans fear getting Alzheimer's disease more than heart disease, stroke, or diabetes. Alzheimer's ranks second in the minds of American's only to cancer.

The survey reveals a mismatch between fear of Alzheimer’s and acting on that fear to prepare for the future.

With Alzheimer's, the Caregiver Is a Patient, Too


This is an interesting and thought provoking article that highlights the problems often effecting Alzheimer's caregivers.

With Alzheimer's, the Caregiver Is a Patient, Too

Alzheimer's Disease and other forms of dementia do not affect just the patient. These diseases gradually rob patients of memory and other intellectual abilities, leaving them unable to perform routine tasks. As the disease continues to destroy brain cells, patients increasingly depend on family members or others to carry out simple tasks like shopping and getting dressed. Ultimately, most patients will need complete care, adding to the caregiver's burden.

Alzheimer's disease is the most common form of dementia, affecting up to 4 million Americans - and untold millions of family members and others who care for them. Physicians now recognize that Alzheimer's caregivers themselves often require care and attention, says Diana R. Kerwin, MD, Medical College of Wisconsin Assistant Professor of Medicine in the Division of Geriatrics and Gerontology.

"What we're seeing is that Alzheimer's is not a typical disease model," she says, "precisely because the health and well-being of the caretaker is affected as well as the patient. I know when I assume the care of an Alzheimer's patient, I am also caring for the caregiver."

Caregivers who accompany patients to the Froedtert Senior Health Program's Geriatric Evaluation Clinic, where Dr. Kerwin practices, are screened for "caregiver stress" and see a gerontologic nurse and social worker who will answer their questions, provide information and help create a plan for care of the patient. Caregivers are given a kit with information about support groups and community services, including adult day care, home care agencies, assisted living, skilled nursing facilities and respite care.

Stress, Depression Are Common
According to the Alzheimer's Association, more than 80% of Alzheimer caregivers report that they frequently experience high levels of stress, and nearly half say they suffer from depression. It's not difficult to see why.

The national Family Caregiver Alliance terms caregiver depression "one of today's all-too-silent health crises." The alliance estimates that caregiving spouses between the ages of 66 and 96 who are experiencing mental or emotional strain have a 63% higher risk of dying than people the same age who are not caregivers.

"Alzheimer's causes progressive memory loss, and in the later stages patients can develop behavior problems," Dr. Kerwin says. "It's distressing for the caregiver to suddenly have to cope with their loved one's anger, hallucinations, paranoia, aggression or inappropriate conduct in public. It's upsetting when, as the disease progresses, the patient no longer recognizes the spouse or loved one."

Caregivers often experience feelings of guilt, believing they are not doing enough to help, she adds. Spouses and adult children feel grief and loss, not unlike a death in the family - except that instead of being sudden, it's spread out over years. Alzheimer's is a progressively worsening disease, but the rate of progression from mild to advanced can vary widely, from three to 20 years. As Alzheimer's progresses, the loss of brain function itself will cause death unless the patient has one or more other serious illness.

When the Child Becomes the Parent
For an adult child who cares for a parent with dementia, taking on the role of caregiver is a role reversal and takes some adjustment. "It can be a difficult transition for a child to take on the role of 'parent' and decision-maker," Dr. Kerwin says. "The child often needs to be empowered to step in and begin caring for their ailing parent - making sure their parent takes his or her medication, for instance, or telling their parent they should not drive, and making difficult decisions about when the parent is no longer able to safely live alone."

Those caregivers are often already juggling multiple responsibilities with their own spouses, children and careers. In some cases, adult-child caregivers with siblings feel resentful if they must bear the brunt of their parent's care, Dr. Kerwin says. If the adult-child caregiver is the only sibling living in the same city as the parent he or she often feels isolated, overwhelmed and underappreciated.

And sometimes, whether the caregiver is a spouse or an adult sibling, out-of-town siblings or other family members who see the parent infrequently may think the caregiver is exaggerating the extent of the Alzheimer's patient's decline. The out-of-town family members may feel guilty about not being able to help from a distance, and when they do visit, they may criticize or ask to change the care their parent is receiving.

Caregivers are often fatigued from carrying out their new responsibilities, Dr. Kerwin says. "I see them neglecting their own health. It's not unusual for caregivers to suffer not only depression but also higher levels of hypertension. We recommend they have annual physicals, during which they should be sure to tell their primary care physician that they are caregivers. We also recommend they participate in support groups and learn about the community resources available."

Other concerns caregivers regularly express are loss of concentration due to their caregiving responsibilities and fear that they themselves might eventually get the disease.

Warning Signs for Caregivers What are some warning signs of caregiver stress? According to the Alzheimer's Association, they include:

Anger
Anxiety
Denial
Depression
Exhaustion
Health problems
Irritability
Lack of concentration
Sleeplessness
Social withdrawal
Caregivers who regularly experience these conditions should seek help from their physician, says the Alzheimer's Association.

Financial Strain Heightens Burden
In some families, the presence of Alzheimer's disease also brings financial problems that can add to stress and depression. Caregivers sometimes give up paying jobs for the unpaid one of caring for a loved one. They often find additional responsibilities are thrust on them, such as overseeing medications for their patient, knowing if or when the patient's care should be transferred to a nursing home, and taking on power of attorney duties along with living wills and advanced directives that specify whether terminal patients should undergo extreme measures to keep them alive.

The national Family Caregiver Alliance estimates that approximately 80% of the long-term care in the United States is provided without compensation, sometimes around the clock.

"The responsibilities are vast," Dr. Kerwin notes. "It's important for caregivers to regularly take some time for themselves, away from their caring responsibilities."

Barbara Abel
HealthLink Contributing Writer

For more information on this topic, see the HealthLink articles End-Stage Alzheimer's - the Long Goodbye and Current Research on Alzheimer's, Memory Loss, and Aging.

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Bob DeMarco is the editor of the Alzheimer's Reading Room and an Alzheimer's caregiver. Bob has written more than 1,050 articles with more than 8,000 links on the Internet. Bob resides in Delray Beach, FL.

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James Smith: I'm 46 Years Old, I can't have Alzheimer's


My doctors initially diagnosed it as possible depression. I accepted the diagnosis, and started taking the medications they prescribed. The medications didn’t change the symptoms, even after taking them for several months. Then they told me I had early onset Alzheimer's disease.


Blood Pressure Drug May Offset Alzheimer's


The drug, valsartin (Diovan), is widely prescribed to treat high blood pressure in elderly patients and was identified as being effective in preventing the build-up of beta-amyloid in the brain.


This article discusses the possibility that drugs currently being used to counter hypertension may help prevent cognitive decline. To read the article in its entirety follow the link, Blood Pressure Drug May Offset Alzheimer's Complication.







Dementia Factsheet (Alzheimer's Disease)


I ran across this dementia factsheet from the Milton S Hershey Medical Center. The section entitled,What are the Symptoms, is particularly interesting.

Alzheimer's and Aging


Alzheimer's and Aging

This MetLife website contains lots of useful information on Alzheimer's and Aging. It should be expecially useful to Baby Boomers and Caregivers.

You can also read more on Alzheimer's at the CareGiver.

The CareGiver Blog
Robert T DeMarco
AllAmerican Senior Care
AllAmerican Senior Care Weblog