Second Member in Alzheimer's Toxic Duo Identified

Like two unruly boys who need to be split up in class, a pair of protein molecules work together to speed up the toxic events of Alzheimer's disease. Researchers at the UT Health Science Center San Antonio February 4 announced the discovery of the second molecule and said its identification could lead to drugs that disrupt the interaction, and thereby block or slow Alzheimer's onset or progression.

Report: Alzheimer's disease causes global financial burden

The cost of caring for people with dementia around the world tops $600 billion according to a report released Tuesday. "70 percent of the costs occur in Western Europe and North America," according to the report.

With the release of the World Alzheimer's Report 2010, Alzheimer's Disease International (ADI), a consortium of 73 non-profit Alzheimer's groups from around the world, is trying to raise awareness about the global financial burden caused by dementia.

Each year ADI issues a report on September 21, which has been designated as World Alzheimer's Day.

Last year's annual Alzheimer's report estimated that 35.6 million people would be living with some form of dementia in 2010 and predicted that this number would nearly double in 2030 and reach 115.4 million in 2050.

The new report calculates the cost of medical care as well as the cost of formal services and informal services provided by family members. Researchers estimate the total cost of care just for this year will be $604 billion, which they say is equal to the gross domestic product (GDP) of what would be the 18th largest country or about 1 percent of the world's GDP.

The United States ranks highest when comes to the cost of caring for a person with dementia, which comes to more than $48,000 according to the report. Caring for people with dementia is least costly – just $903 according to the new data – in South Asian countries like Bangladesh and India.

In this report, ADI is calling on all governments to do more to recognize dementia as a health priority and invest more in prevention and developing plans for caring for the millions more who will get this disease in the coming decades.

"The U.S. is unprepared to handle the massive human and economic burden that is building as a result of the growing number of people with Alzheimer's disease," Harry Johns tells CNN. Johns is the president and CEO of the Alzheimer's Association, one of the members of Alzheimer's Disease International. He notes that the U.S. government annually spends $6 billion on cancer research, $4 billion on heart disease research, approximately $3 billion on HIV/AIDS, which he says are all good investments and have led to lives being saved. However, when it comes to Alzheimer's research, Johns notes that funding by the National Institutes of Health is only $469 million per year.

ADI suggests in this report that many governments are unprepared to meet the challenges they face with a growing population of people with dementia. The Alzheimer's Association in the United States points out that 6 other countries, including France, England and Australia do have national Alzheimer's plans, but the United States does not. Legislation called the National Alzheimer's Project has been introduced in Congress.

CNN

Lucy’s Revenge Caregiver Chronicles: Ocean Springs Couple Fighting Alzheimer’s With Help of Friends and Family

BY: B. Keith Plunkett

You don’t drown by falling into water. You drown by staying there. -- Robert Allen

Cindi and Jon Braud

When I first met Cindi Braud, she floated into our meeting at a coffee shop at the IP Casino, and never sat down. In fact, I’m not sure she even touched the ground. Cindi has been employed at the Biloxi based casino for five years, and is a ball of energy and purpose. She apologized for being a little late, we exchanged business cards and email addresses, and she hurried away for another meeting. I left thinking my first interview for the Lucy’s Revenge Alzheimer’s Paddling Project was a bust. But, I’ve since conducted the interview, and now I know that the reason Cindi doesn’t stop long to reflect is that she is simply too concerned about getting things done to worry much about cogitation.

For many people, Alzheimer’s is an elderly person’s disease. Sadly, this misconception may be why some people don’t give it the attention it deserves when considering worthy causes to support. Despite her busy schedule at IP, Cindi is out to change all that. Alzheimer's is a disease of the brain that causes problems with memory, thinking and behavior. It is the seventh leading cause of death in the country and the fifth leading cause of death for those over age 65. Contrary to public opinion, it is not a normal part of aging and currently the cause of Alzheimer's disease is unknown. What many people don’t understand is that a growing segment of those diagnosed are much younger than 65. Cindi’s husband Jon is among that group. Jon Braud was diagnosed at the age of 40. He is now 42.

Cindi explains that the diagnosis was not a complete surprise. The Ocean Springs couple knew the genetics were there, and that the disease could touch them as it had prior generations of the Braud family. Jon’s father was diagnosed at the age of 44, a mere 23 months before his death. Likewise, Jon’s Grandmother and a cousin were taken by the disease at the ages of 50 and 51, and a Granduncle died just after turning 40. It was because of these familial reasons that Jon and Cindi decided early on not to have children. The chances were simply too great that the Alzheimer’s disease gene would be passed along. Early Onset Alzheimer’s Disease (EOAD) is more about genetics than any other subset of the disease. The couple made a conscious effort to end the disease in the Braud family with Jon.

The decision the Braud’s made to forego having children is an honorable one and one of necessity. It illustrates how Alzheimer’s is not only affecting individuals and their caregivers, but also generations of entire families. Strides have been made in the past decade to ease the affects of Alzheimer’s symptoms with some success, but there is still no cure. Cindi believes the lack of knowledge keeps medical professionals out of the fight. The Braud’s have visited a few medical facilities with less than supportive results. Just last July, Jon’s Neurologist summed up the current lack of medical resources when he told him, “Its Alzheimer’s, I’m sorry there is nothing I can do for you.”

Other facilities also found reasons not to help the Braud’s. The Lou Ruvo Brain Institute in Las Vegas turned the couple away because they did not live in Nevada. An administrator at the famed Mayo Clinic said, “We’re not the miracle hospital everyone thinks we are.” And, the Pennington Bio-Medical Center in nearby Baton Rouge summed up what those with EOAD face in the competitive research money race. Simply put, they said, “There is no money in saving the 1% with the disease.”

But, if there is one thing Cindi Braud is, it is persistent. She, along with 50 family members and friends, has embarked on a crusade to email every medical facility and doctor associated with Alzheimer’s at every University in the country. 

“I hope that they will be so inundated with emails regarding Jon and us asking for help that someone might be able to.  Squeaky wheel gets the grease,” she said.

Cindi is also hoping to toy with a few egos and the facilities desire to compete for research dollars.  She says it has already worked with UCLA. 

“UCLA told me there was nothing they could do for us and they referred me to a doctor at UCSD. I emailed UCSD, and they replied with a ‘yes’ as they are doing stem cell research,” says Cindi. “When we concluded our conversation (UCSD) copied the doctor at UCLA (on the email).  Within 2 hours I received a phone call from UCLA inviting us out there for research.”

Cindi’s employer has joined in the fight. IP Casino’s Benefits Manager has helped with everything from insurance questions to accommodating Cindi through Family Medical Leave. IP is also donating $10K to the Alzheimer’s Association (ALZ) and will hold signups for teams for an Alzheimer’s Association Memory Walk in November.  In January the company will hold an event to promote awareness and provide information for Gulf Coast residents. 

The Braud’s are not alone in their inability to find resources. Here in Mississippi, an estimated 148,000 caregivers are working tirelessly to provide for the 53,000 loved ones affected by the disease with little or no support. Only now are medical facilities beginning to recognize the dire need across the state, and that the disease takes a toll not only on the patients, but on those working hard to provide care.

“There is no assistance on the Gulf Coast for our situation,” says Cindi. “When I first called ALZ in September 2009 they asked me if I had my financial affairs in order and had I picked out an assisted living facility.  That was unacceptable to me. It’s one of the many reasons I fight so hard.”

“I want to change the way ALZ responds when someone is calling for help,” she added. “When you hear the diagnosis for the first time you already understand the finality of the disease.  Tell me who is willing to fight it, cure it…not, ‘have I picked out his tombstone?’.”

Cindi’s investigation into the disease continues to show the need for more awareness in the medical community. She says that people continue to be “shocked” when she tells them her 42-year old husband has the disease, “Most people, including doctors look at me like I’m crazy.”

Studies have been started and stopped over the years with little sharing of information. Cindi says that at least one University, UAB, destroyed the outcome of a retired doctor’s research on the genetics of EOAD.

Cindi relates the story, “In 1998 UAB was conducting a study on Jon’s family and sent his cousin a letter.  She was shocked to receive the letter and knew nothing about the study.  A med student named Kathryn Hanson came to Baton Rouge to meet with some family members and they never heard from her again.  I contacted UAB to see if anything had been concluded with the study. No one knew who Kathryn Hanson was nor did they know about the study.”

Cindi eventually found an email address for one of the doctors mentioned in the study, and he informed her that since his retirement UAB had destroyed his research.  Further attempts to get the research or have Jon added to clinical drug qualifications have been unsuccessful.

"Any clinical trial drug qualifications start at the minimum age of 50,” says Cindi.  I have yet to find anyone at UAB that can give me any information regarding their study on Jon’s family.”

Jon did not qualify for three other trials at UAB due to his age and they were unwilling to make an exception. The Braud’s have found that going through their doctor and following normal protocol does not get them very far. Yet, they continue to fight.

“My husband’s motto is ‘play to win’,” says Cindi of her former High School and College athlete husband. “It has a new meaning now.  I do not stop thinking about this. It’s 24/7 with me.  What can I do to help him?  Who can I call or write to?”

Despite the numerous setbacks, Cindi’s tenacity has had some pay off. Jon was recently enrolled into the Dominantly Inherited Alzheimer’s Network (DIAN). The world-wide study by Washington University in St. Louis, Missouri is studying Amyloid Beta protein in the brain and the possible connections to Alzheimer’s.  

She continues to fight every day. She fights for what little time she has left with Jon, she fights for disability benefits for her husband, and she fights for a doctor to help him.  One thing is certain: Cindi Braud does not take no for an answer, and in the fight against Alzheimer’s that is a good thing. 

Spinal-Fluid Test Is Found to Predict Alzheimer’s

Researchers report that a spinal fluid test can be 100 percent accurate in identifying patients with significant memory loss who are on their way to developing Alzheimer’s disease.

Although there has been increasing evidence of the value of this and other tests in finding signs of Alzheimer’s, the study, which will appear Tuesday in the Archives of Neurology, shows how accurate they can be. The new result is one of a number of remarkable recent findings about Alzheimer’s.

After decades when nothing much seemed to be happening, when this progressive brain disease seemed untreatable and when its diagnosis could be confirmed only at autopsy, the field has suddenly woken up.

Alzheimer’s, medical experts now agree, starts a decade or more before people have symptoms. And by the time there are symptoms, it may be too late to save the brain. So the hope is to find good ways to identify people who are getting the disease, and use those people as subjects in studies to see how long it takes for symptoms to occur and in studies of drugs that may slow or stop the disease.

Researchers are finding simple and accurate ways to detect Alzheimer’s long before there are definite symptoms. In addition to spinal fluid tests they also have new PET scans of the brain that show the telltale amyloid plaques that are a unique feature of the disease. And they are testing hundreds of new drugs that, they hope, might change the course of the relentless brain cell death that robs people of their memories and abilities to think and reason.

“This is what everyone is looking for, the bull’s-eye of perfect predictive accuracy,” Dr. Steven DeKosky, dean of the University of Virginia medical school, who is not connected to the new research, said about the spinal tap study.

Dr. John Morris, a professor of neurology at Washington University, said the new study “establishes that there is a signature of Alzheimer’s and that it means something. It is very powerful.”

A lot of work lies ahead, researchers say — making sure the tests are reliable if they are used in doctors’ offices, making sure the research findings hold up in real-life situations, getting doctors and patients comfortable with the notion of spinal taps, the method used to get spinal fluid. But they see a bright future.

Although the latest PET scans for Alzheimer’s are not commercially available, the spinal fluid tests are.

So the new results also give rise to a difficult question: Should doctors offer, or patients accept, commercially available spinal tap tests to find a disease that is yet untreatable? In the research studies, patients are often not told they may have the disease, but in practice in the real world, many may be told.

Some medical experts say it should be up to doctors and their patients. Others say doctors should refrain from using the spinal fluid test in their practices. They note that it is not reliable enough — results can vary by lab — and has been studied only in research settings where patients are carefully selected to have no other conditions, like strokes or depression, that could affect their memories.

"This is literally on the cutting edge of where the field is,” Dr. DeKosky said. “The field is moving fast. You can get a test that is approved by the F.D.A., and cutting edge doctors will use it.”

But, said Dr. John Trojanowski, a University of Pennsylvania researcher and senior author of the paper, given that people can get the test now, “How early do you want to label people?”

Some, like Dr. John Growdon, a neurology professor at Massachusetts General Hospital who wrote an editorial accompanying the paper, said that decision was up to doctors and their patients.

Sometimes patients with severe memory loss do not have the disease. Doctors might want to use the test in cases where they want to be sure of the diagnosis. And they might want to offer the test to people with milder symptoms who want to know whether they are developing the devastating brain disease.

One drawback, though, is that spinal fluid is obtained with a spinal tap, and that procedure, with its reputation for pain and headaches, makes most doctors and many patients nervous. The procedure involves putting a needle in the spinal space and withdrawing a small amount of fluid.

Dr. Growdon and others say spinal taps are safe and not particularly painful for most people. But, he said, there needs to be an education campaign to make people feel more comfortable about having them. He suggested that, because most family doctors and internists are not experienced with the test, there could be special spinal tap centers where they could send patients.

The new study included more than 300 patients in their 70s, 114 with normal memories, 200 with memory problems and 102 with Alzheimer’s disease. Their spinal fluid was analyzed for amyloid beta, a protein fragment that forms plaques in the brain, and for tau, a protein that accumulates in dead and dying nerve cells in the brain. To avoid bias, the researchers analyzing the data did not know anything about the clinical status of the subjects. Also, the subjects were not told what the tests showed.

Nearly every person with Alzheimer’s had the characteristic spinal fluid protein levels. Nearly three quarters of people with mild cognitive impairment, a memory impediment that can precede Alzheimer’s, had Alzheimer’s-like spinal fluid proteins. And every one of those patients with the proteins developed Alzheimer’s within five years. And about a third of people with normal memories had spinal fluid indicating Alzheimer’s. Researchers suspect that those people will develop memory problems.

The prevailing hypothesis about Alzheimer’s says that amyloid and tau accumulation are necessary for the disease and that stopping the proteins could stop the disease. But it is not yet known what happens when these proteins accumulate in the brains of people with normal memories. They might be a risk factor like high cholesterol levels. Many people with high cholesterol levels never have heart attacks. Or it might mean that Alzheimer’s has already started and if the person lives long enough he or she will with absolute certainty get symptoms like memory loss.

Many, like Dr. DeKosky, believe that when PET scans for amyloid become available, they will be used instead of spinal taps, in part because doctors and patients are more comfortable with brain scans.

And when — researchers optimistically are saying “when” these days — drugs are shown to slow or prevent the disease, the thought is that people will start having brain scans or spinal taps for Alzheimer’s as routinely as they might have colonoscopies or mammograms today.

For now, Dr. DeKosky said, the days when Alzheimer’s could be confirmed only at autopsy are almost over. And the time when Alzheimer’s could be detected only after most of the brain damage was done seem to be ending, too.

“The new biomarkers in CSF have made the difference,” Dr. DeKosky said, referring to cerebral spinal fluid. “This confirms their accuracy in a very big way.”

NYT

UMC to lead $26M Alzheimer's study

The University of Mississippi Medical Center is poised to become a world leader in Alzheimer's research.
UMC and four collaborating academic centers have received $26 million from the National Institutes of Health to conduct a study to determine risk factors for Alzheimer's disease and related forms of cognitive decline.

UMC will take the lead role in the study.

Also, UMC announced today the creation of a research center that will go along with the study.

"This puts the University of Mississippi Medical Center as one of the world leaders to deal with Alzheimer disease, dementia and memory loss," said Dr. James Keeton, UMC’s Dean of the School of Medicine.

The study will build on data collected from 16,000 individuals over 20 years to determine risk factors from heart disease and stroke.

Some things are already in place, but overall Alzheimer study is expected to kickoff May 2011.

Mostly private funds will be used to operate the new research center. A $9 million fund-raising campaign will go toward the effort.

Clarion Ledger

Drugmakers to share data to speed brain research

(Reuters) - Major drugmakers will share data from their clinical trials for Alzheimer's and Parkinson's disease in an effort to speed the development of new medicines to treat the brain disorders.

The database, a public/private partnership unveiled on Friday, will give academic and industry researchers worldwide access to information from more than 4,000 patients with neurodegenerative diseases.

Bringing the data together, rather than keeping pieces of it within each drug company, will give scientists a larger amount of information on how the diseases progress and how they differ in various patients.

Backers hope the approach will jump start research into treatments for some of the toughest and most common brain disorders. Despite decades of study, doctors still have few effective treatments for Alzheimer's disease, which affects more than 26 million people globally. It is the most common form of dementia.

An estimated four million people worldwide have Parkinson's disease, which causes trembling and other symptoms.

Information in the new database should help drugmakers design more efficient clinical trials of potential treatments, said Dr. Raymond Woosley, president and chief executive of the Critical Path Institute, a nonprofit organization working to improve drug development.

Some patients, for example, develop Alzheimer's in their 80s while for others it starts in their 40s, Woosley said. The disease probably evolves differently in those groups, but companies only have small numbers in each age range to study in their own trials.

"If you have 4,000 patients (in the database), you begin to have enough data to see their real course" and can target a drug to specific types of patients, Woosley said in an interview.

At a news conference to unveil the effort, Woosley said future clinical trials "will be smaller, they'll be shorter and yet far more likely to find successful therapies because of this database."

The project is coordinated by the Coalition Against Major Diseases, an organization of patient groups and 13 drugmakers that is part of the Critical Path Institute.

Companies that have already contributed clinical data are Pfizer Inc, GlaxoSmithKline PLC, AstraZeneca, Johnson and Johnson, Novartis AG Sanofi-Aventis and Abbott Laboratories Inc.

Manufacturers agreed to participate because they realize "innovation no longer happens in one company's laboratory. It happens through constant interaction between scientists in the biopharmaceutical industry, patient advocacy organizations, academia and government," said Dr. Frank Casty, an AstraZeneca vice president.

Officials from the Food and Drug Administration, the National Institutes of Health and the European Medicines Agency serve as advisers.

FDA Deputy Commissioner Joshua Sharfstein said information gleaned from the data will help the agency and outside experts identify the best standards for future clinical trials.

The results "will allow safe and effective treatments to come to market and get to patients more quickly," he said.

Promising new drug target for Alzheimer's disease

ScienceDaily -- Researchers have identified a potential drug target for the treatment of Alzheimer's disease: a receptor that is embedded in the membrane of neurons and other cells. A protein fragment associated with Alzheimer's disease activates this receptor, sparking increased activity in the affected neurons, eventually leading to cell death, researchers report.

Science Daily

Caring for spouse with Alzheimer's increases risk of developing dementia, study finds

Those who care for a spouse with Alzheimer's are six times as likely to develop a form of dementia themselves, according to a new study.

The study from Utah State University, reported in the Journal of the American Geriatrics Society, tracked more than 1,221 couples (2,442 individuals) over 12 years. None of the couples, who had been married for an average of 49 years, had been diagnosed with dementia at the start of the research period.

Twelve years later, 225 couples had been affected by dementia in some way. In 125 of the couples, only the husband developed dementia; in 70 of the couples only the wife was affected. In 30 couples, both spouses were affected.

When other factors, including genetics and social class, were taken into account, having a husband or wife with Alzheimer's emerged as a prominent risk factor - particularly for men.

The physical, mental and emotional challenges of caring for a declining spouse may put the other spouse at risk, researchers suggested. Additionally, couples who live together for many years may be exposed to the same lifestyle risks.

"Two people living the same lifestyle may be exposed to the same risk factors so it could be possible that spouses both develop dementia," said Professor Clive Ballard of the UK Alzheimer's Society in a statement released in response to the study. "However there has been limited research in this area and more is needed to determine which people are the most vulnerable."

New York Daily News

New finding could mark shift in Alzheimer's research

By Steven Reinberg

HealthDay Reporter

THURSDAY, April 29 (HealthDay News) -- New research could change the way scientists view the causes -- and potential prevention and treatment -- of Alzheimer's disease.

A study published online this month in the Annals of Neurology suggests that "floating" clumps of amyloid beta (abeta) proteins called oligomers could be a prime cause of the disorder, and that the better-known and more stationary amyloid-beta plaques are only a late manifestation of the disease.

"Based on these and other studies, I think that one could now fairly revise the 'amyloid hypothesis' to the 'abeta oligomer hypothesis,'" said lead researcher Dr. Sam Gandy, a professor of neurology and psychiatry and associate director of the Alzheimer's Disease Research Center at Mount Sinai School of Medicine in New York City.

The new study could herald a major shift in Alzheimer's research, another expert said.

Maria Carrillo, senior director of medical and scientific relations at the Alzheimer's Association, said that "we are excited about the paper. We think it has some very interesting results and has potential for moving us in another direction for future research."

According to the Alzheimer's Association, more than 5.3 million Americans now suffer from the neurodegenerative illness, and it is the seventh leading cause of death. There is no effective treatment for Alzheimer's, and its origins remain unknown. For decades, research has focused on a buildup of amyloid beta plaques in the brain, but whether these deposits are a cause of the disease or merely a neutral artifact has remained unclear.

The new study looked at a lesser-known factor, the more mobile abeta oligomers that can form in brain tissue. In their research, Gandy's team first developed mice that only form abeta oligomers in their brains, and not amyloid plaques.

Based on the results of tests gauging spatial learning and memory, these mice were found to be impaired by Alzheimer's-like symptoms.

Next the researchers inserted a gene that would cause the mice to develop both oligomers and plaques.

Similar to the oligomer-only rodents, these mice "were still memory impaired, but no more memory impaired for having plaques superimposed on their oligomers," Gandy said.

Another result further strengthened the notion that oligomers were the prime cause of Alzheimer's in the mice.

"We tested the mice and they lost memory function, and when they died, we measured the oligomers in their brains," Gandy said. "Lo and behold, the degree of memory loss was proportional to the oligomer level," he said.

Gandy noted that PET scans are not able to detect oligomers in the human brain, but they do see amyloid plaques. This could help explain why recent trials of the experimental Alzheimer's drug bapineuzumab showed a reduction in plaques, but no improvement in patients' cognitive function, Gandy said.

Bapineuzumab is targeted to amyloid plaques. Whether the drug also affected the oligomers is not known, Gandy said, because the PET scans could not see them. "We don't even know whether bapineuzumab 'sees' them," he said.

The new study could help change the focus of ongoing research. "Our new 'oligomer only' mice may enable the development of imaging agents and drugs that lower oligomer levels without having plaques around to muddy the picture," Gandy said.

Researchers have long been trying to figure out the stages that lead up to plaques and tangles, Carrillo noted. "We [now] know that plaques and tangles are really the end stage of this disease," she said.

Oligomers are "toxic clumps" that could be the cause of Alzheimer's disease, Carrillo said. This study confirms for the first time that these toxic clumps are a cause of memory problems, she said.

Carrillo noted that these results also confirm that the disease starts developing 10 to 15 years before it is diagnosed. This understanding could lead to new ways of diagnosing and treating the illness, she added.

"Perhaps future therapeutics attacking oligomers instead of plaques would be a strategy," Carrillo said.

One expert did have some reservations about that possibility, however.

"The larger unresolved issue is how these oligomers relate to people where plaques accumulate many years prior to disease onset," said Greg M. Cole, professor of medicine and neurology and associate director of the UCLA Alzheimer's Center. "One would expect the little oligomer aggregates to arise prior to the bigger plaque aggregates, that is, decades before important memory problems [surface]."

That could mean that "targeting oligomers may work best for prevention," rather than the treatment of existing disease, he said. "Ongoing efforts to track and specifically target the oligomers in clinical trials with memory deficit patients should soon tell us how much good we can do hitting the oligomers. It may be a huge success or too little, too late."