Alzheimer’s

Discussion in 'Men's Health Forum' started by Michael Scally MD, Aug 10, 2010.

  1. #1
    Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Spinal-Fluid Test Is Found to Predict Alzheimer’s
    http://www.nytimes.com/2010/08/10/health/research/10spinal.html

    August 9, 2010
    By GINA KOLATA

    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 these tests in finding signs of Alzheimer’s, the study, which will appear Tuesday in the Archives of Neurology, shows how very accurate they can be.

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

    The study, said Dr. John Morris, a professor of neurology at Washington University, “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’re 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.

    The new study is part of a tsunami of recent findings on Alzheimer’s disease. After decades when nothing much seemed to be happening, when this progressive brain disease seemed untreatable and when its diagnosis could only be confirmed at autopsy, the field has suddenly woken up.

    Alzheimer’s, investigators now agree, starts a decade or more before people have symptoms. And by the time there are symptoms it may be to 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 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 slow or stop the relentless brain cell death that robs people of their memories and abilities to think and reason.

    But the PET scans are not yet commercially available, while spinal fluid tests are. So the new results are giving rise to a difficult question: Should doctors offer, or patients accept, commercially available spinal tap tests to find a disease that is, as 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 say it should be up to doctors and their patients. Others say doctors should refrain from using the spinal fluid test in their practices. It is not reliable enough — results can vary from lab to lab — and has only been studied 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 the Massachusetts General Hospital who wrote an editorial accompanying the paper, said that decision is up to doctors and their patients.

    Doctors might want to use the test in cases where they need to be sure a patient with symptoms of severe memory loss and loss of reasoning abilities has Alzheimer’s. And they might want to offer it to people with milder symptoms who really want to know if they have the devastating brain disease.

    One drawback, though, is that spinal fluid is obtained with a spinal tap, and that procedure 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, Dr. Growdon said, there needs to be an education campaign to make people feel more comfortable about having them. He suggested that, since most family doctors and internists are not experienced with the test, there could be special spinal tap centers where they could sent patients.

    The new study included more than 300 patients in their seventies, 114 with normal memories, 200 with memory problems, and 102 with Alzheimer’s disease. Their spinal fluid was analyzed for amyloid beta, which forms plaques in the brain, and for tau, another 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 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 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 get symptoms like memory loss with absolute certainty.

    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 – investigators 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 only be detected 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. “This confirms their accuracy in a very big way.”


    De Meyer G, Shapiro F, Vanderstichele H, et al. Diagnosis-Independent Alzheimer Disease Biomarker Signature in Cognitively Normal Elderly People. Arch Neurol 2010;67(8):949-56.

    Objective - To identify biomarker patterns typical for Alzheimer disease (AD) in an independent, unsupervised way, without using information on the clinical diagnosis.

    Design - Mixture modeling approach.

    Setting - Alzheimer's Disease Neuroimaging Initiative database.

    Patients or Other Participants - Cognitively normal persons, patients with AD, and individuals with mild cognitive impairment.

    Main Outcome Measures - Cerebrospinal fluid–derived ?-amyloid protein 1-42, total tau protein, and phosphorylated tau181P protein concentrations were used as biomarkers on a clinically well-characterized data set. The outcome of the qualification analysis was validated on 2 additional data sets, 1 of which was autopsy confirmed.

    Results - Using the US Alzheimer's Disease Neuroimaging Initiative data set, a cerebrospinal fluid ?-amyloid protein 1-42/phosphorylated tau181P biomarker mixture model identified 1 feature linked to AD, while the other matched the "healthy"status. The AD signature was found in 90%, 72%, and 36% of patients in the AD, mild cognitive impairment, and cognitively normal groups, respectively. The cognitively normal group with the AD signature was enriched in apolipoprotein E 4 allele carriers. Results were validated on 2 other data sets. In 1 study consisting of 68 autopsy-confirmed AD cases, 64 of 68 patients (94% sensitivity) were correctly classified with the AD feature. In another data set with patients (n = 57) with mild cognitive impairment followed up for 5 years, the model showed a sensitivity of 100% in patients progressing to AD.

    Conclusions - The mixture modeling approach, totally independent of clinical AD diagnosis, correctly classified patients with AD. The unexpected presence of the AD signature in more than one-third of cognitively normal subjects suggests that AD pathology is active and detectable earlier than has heretofore been envisioned.
     
    Last edited: Aug 18, 2010
  2. #2
    Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Drug’s Failure Casts Doubt on a Tactic in Alzheimer’s Battle
    http://www.nytimes.com/2010/08/19/health/19alzheimers.html

    August 18, 2010
    By GINA KOLATA

    The failure of a promising Alzheimer’s drug in clinical trials highlights the gap between diagnosis — where real progress has recently been made — and treatment of the disease.

    It was not just that the drug, made by Eli Lilly, did not work — maybe that could be explained by saying the patients’ illness was too far advanced when they received it. It was that the drug actually made them worse, the company said. And the larger the dose they took, the worse were patients’ symptoms of memory loss and inability to care for themselves. Not only that, the drug also increased the risk of skin cancer.

    So when Lilly announced on Tuesday that it was ending its large clinical trials of that drug, semagacestat, researchers were dismayed.

    “Obviously, this is disappointing news, to say the least,” said Dr. Steven Paul, an Alzheimer’s researcher and a recently retired executive vice president at Lilly.

    Beyond the setback for Lilly, the study raises questions about a leading hypothesis of the cause of Alzheimer’s and how to treat it. The idea, known as the amyloid hypothesis, says the disease occurs when a toxic protein, beta amyloid, accumulates in the brain. The idea is that if beta amyloid levels are reduced, the disease might be slowed, halted or even prevented if treatment starts early enough.

    The Lilly drug, like most of the more than 100 Alzheimer’s drugs under development, blocks an enzyme, gamma secretase, needed to make beta amyloid. It was among the first shown to broach the blood-brain barrier and reduce levels of beta amyloid in the brain. And, company studies showed, it did reduce amyloid production.

    “We did get enough in the brain to have an effect,” said Dr. Eric Siemers, medical director of Lilly’s Alzheimer’s disease team. “Unfortunately, the effect was not what we wanted.”

    Now researchers are focused on what went wrong, and why.

    Some, like Dr. Lon Schneider, an Alzheimer’s researcher at the University of Southern California, say the drug’s failure may mean the field is rushing off a cliff in its near single-minded focus on blocking the production of amyloid. Dr. Schneider, like most leading Alzheimer’s researchers, consults for a number of drug companies, including Lilly.

    The Lilly study’s failure, he said, “chips away at that approach to testing the amyloid hypothesis.”

    “We don’t know what the drug targets for Alzheimer’s disease are,” Dr. Schneider said. “We don’t know because we don’t know the causes of Alzheimer’s.”

    At the very least, said Dr. P. Murali Doraiswamy, an Alzheimer’s researcher at Duke University, the Lilly result “clearly tells us that our current views may be too simplistic.”

    Dr. Doraiswamy said he was not abandoning the amyloid hypothesis. But, he said, “this is a time of major soul searching in the field.”

    “What worries me is that we don’t know if this was a toxicity unique to Lilly’s drug and this late-stage population or whether it also applies to similar anti-amyloid therapies given at earlier stages of the disease,” Dr. Doraiswamy said.

    The bad news came on the heels of what researchers see as a resurgence of hope in this challenging field. With new cooperation in research they have made advances in diagnosing Alzheimer’s, a disease that used to be uncertain until autopsy.

    And those new diagnostic tests are still exciting, researchers said.

    PET scans of amyloid plaques in the brain and tests of cerebrospinal fluid can show amyloid accumulation long before people have symptoms of Alzheimer’s disease and, as was recently reported, appear to identify people at high risk of developing the disease. Researchers believe the best time to try to alter the course of the disease is before memory loss — by that time, brain cells are dead or dying and are unlikely to be restored.

    At this point, though, when there is no treatment, those tests are primarily a benefit for companies testing new therapies and researchers trying to understand the disease’s progress.

    The long journey of semagacestat began more than a decade ago, when Lilly scientists discovered it could block gamma secretase in laboratory experiments. Years of work followed, showing it appeared safe, that it got into the brains of people, that it reduced the production of amyloid in the brain.

    Finally, in 2008, Lilly began two large studies of semagacestat, enrolling more than 2,600 people with Alzheimer’s disease. The company did not expect its drug to reverse the disease — patients’ brains were too ravaged for that, said Richard Mohs, Lilly’s team leader in Alzheimer’s research. But it did hope to slow the disease’s progression.

    Now, with the abrupt end of the studies, patients will continue to be followed but no one will be taking any more of the drug.

    “The fact that people got worse means there is biology we don’t understand,” Dr. Mohs said.

    There are several possible explanations.

    One is that the drug altered the functioning of other proteins in the brain and body — it now appears that gamma secretase is involved in the production of about 20 proteins in addition to beta amyloid. Companies, including Lilly, are developing drugs that block gamma secretase from making amyloid but do not have much of an effect on the other proteins.

    One company, Bristol-Myers Squibb, says that is what its drug does. Its drug is now being tested in two clinical trials. In one, the participants have Alzheimer’s. In the other, they have memoryimpairment that falls short of Alzheimer’s dementia and have brain amyloid PET scans and tests of cerebrospinal fluid showing amyloid is accumulating in their brains, indicating that they are likely to go on to develop Alzheimer’s.

    “We still like the amyloid hypothesis,” said Charlie Albright, a Bristol-Myers group director in neuroscience biology. The Lilly drug failure “doesn’t affect our enthusiasm about going forward.”

    Another possibility is that the enzyme is decreasing production not just of a dangerous form of amyloid, known as a beta 42, but also of another form, a beta 40, that may protect the brain. Companies are developing so-called selective gamma secretase inhibitors, Dr. Paul said, which only block the production of a beta 42.

    Companies are also pursuing other ways of reducing amyloid levels in the brain. One, a Lilly drug that uses a monoclonal antibody to block amyloid, is being tested in a large clinical trial.

    And companies are pursuing a more difficult target — blocking a protein, tau, that accumulates in dead and dying nerve cells after the disease is under way.

    But Alzheimer’s experts worry about the future. The research is extremely expensive — Lilly spent hundreds of millions of dollars on its failed drug — and it can take a decade or more to know if a drug works. It can take even longer if drugs are tested in people with mild symptoms of Alzheimer’s disease or in people who are at high risk but have no symptoms yet — a direction many think is necessary to really make a difference.

    “I am certainly concerned that if we see some more failures it will be a harder to convince companies to invest that much money in testing these hypotheses,” Dr. Paul said.

    Dr. Samuel Gandy, an Alzheimer’s researcher at Mount Sinai Medical Center, shares that concern.

    “Failures certainly don’t build energy and enthusiasm,” he said. “The market is still there, but failures do take their toll.”
     
  3. #3
    cvictorg

    cvictorg Member

    Years Later, No Magic Bullet Against Alzheimer’s Disease

    http://www.nytimes.com/2010/08/29/health/research/29prevent.html?hp

    But the jury’s verdict was depressing and distressing. So far, nothing has been found to prevent or delay this devastating disease, which ceaselessly kills brain cells, eventually leaving people mute, incontinent, unable to feed themselves, unaware of who they are or who their family and friends are.

    “Currently,” the panel wrote, “no evidence of even moderate scientific quality exists to support the association of any modifiable factor (such as nutritional supplements, herbal preparations, dietary factors, prescription or nonprescription drugs, social or economic factors, medical conditions, toxins or environmental exposures) with reduced risk of Alzheimer’s disease.”
     
  4. #4
    Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Daviglus ML, Bell CC, Berrettini W, et al. NIH State-of-the-Science Conference Statement: Preventing Alzheimer's Disease and Cognitive Decline. NIH Consens State Sci Statements 2010;27(4).

    OBJECTIVE: To provide health care providers, patients, and the general public with a responsible assessment of currently available data on prevention of Alzheimer's disease and cognitive decline.

    PARTICIPANTS: A non-Department of Health and Human Services, nonadvocate 15-member panel representing the fields of preventive medicine, geriatrics, internal medicine, neurology, neurological surgery, psychiatry, mental health, human nutrition, pharmacology, genetic medicine, nursing, health economics, health services research, family caregiving, and a public representative. In addition, 20 experts from pertinent fields presented data to the panel and conference audience.

    EVIDENCE: Presentations by experts and a systematic review of the literature prepared by the Duke University Evidence-based Practice Center, through the Agency for Healthcare Research and Quality. Scientific evidence was given precedence over anecdotal experience.

    CONFERENCE PROCESS: The panel drafted its statement based on scientific evidence presented in open forum and on published scientific literature. The draft statement was presented on the final day of the conference and circulated to the audience for comment. The panel released a revised statement later that day at NIH Consensus Development Program. This statement is an independent report of the panel and is not a policy statement of the NIH or the Federal Government.

    CONCLUSIONS: (1) Extensive research over the past 20 years has provided important insights on the nature of Alzheimer's disease and cognitive decline and the magnitude of the problem. Nevertheless, there remain important and formidable challenges in conducting research on these diseases, particularly in the area of prevention. There are numerous ongoing or planned investigations which may offer promising new insights regarding the causes and prevention of these diseases. (2) Cognitive decline and Alzheimer's disease are major sources of morbidity and mortality worldwide. They pose a significant burden not only on affected individuals, but also on their caregivers and society in general. (3) Firm conclusions cannot be drawn about the association of modifiable risk factors with cognitive decline or Alzheimer's disease. (4) There is an absence of highly reliable consensus-based diagnostic criteria for cognitive decline, mild cognitive impairment, and Alzheimer's disease, and the available criteria have not been uniformly applied. (5) There is insufficient evidence to support the use of pharmaceutical agents or dietary supplements to prevent cognitive decline or Alzheimer's disease. However, ongoing additional studies including (but not limited to) antihypertensive medications, omega-3 fatty acid, physical activity, and cognitive engagement may provide new insight into the prevention or delay of cognitive decline or Alzheimer's disease. (6) Large-scale population-based studies and RCTs are critically needed to investigate strategies to maintain cognitive function in individuals at risk for decline, to identify factors that may delay the onset of Alzheimer's disease among individuals at risk, and to identify factors that may slow the progression of Alzheimer's disease among individuals already diagnosed with the disease.
     

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  5. #5
    Michael Scally MD

    Michael Scally MD Doctor of Medicine


    Years Later, No Magic Bullet Against Alzheimer’s Disease
    http://www.nytimes.com/2010/08/29/health/research/29prevent.html?hp

    August 28, 2010
    By GINA KOLATA

    BETHESDA, Md. — The scene was a kind of science court. On trial was the question “Can anything — running on a treadmill, eating more spinach, learning Arabic — prevent Alzheimer’s diseaseor delay its progression?”

    To try to answer that question, the National Institutes of Health sponsored the court, appointing a jury of 15 medical scientists with no vested interests in Alzheimer’s research. They would hear the evidence and reach a judgment on what the data showed.

    For a day and a half last spring, researchers presented their cases, describing studies and explaining what they had hoped to show. The jury also heard from scientists from Duke University who had been commissioned to look at the body of evidence — hundreds of research papers — and weigh it. And the jury members had read the papers themselves, preparing for this day.

    The studies included research on nearly everything proposed to prevent the disease: exercise, mental stimulation, healthy diet, social engagement, nutritional supplements, anti-inflammatory drugs or those that lower cholesterol or blood pressure, even the idea that people who marry or stay trim might be saved from dementia. And they included research on traits that might hasten Alzheimer’s onset, like not having much of an education or being a loner.

    It is an issue that has taken on intense importance because scientists recently reported compelling evidence that two types of tests, PET scans of Alzheimer’s plaque in the brain and tests of spinal fluid, can find signs of the disease years before people have symptoms. That gives rise to the question: What, if anything, can people do to prevent it?

    But the jury’s verdict was depressing and distressing. So far, nothing has been found to prevent or delay this devastating disease, which ceaselessly kills brain cells, eventually leaving people mute, incontinent, unable to feed themselves, unaware of who they are or who their family and friends are.

    “Currently,” the panel wrote, “no evidence of even moderate scientific quality exists to support the association of any modifiable factor (such as nutritional supplements, herbal preparations, dietary factors, prescription or nonprescription drugs, social or economic factors, medical conditions, toxins or environmental exposures) with reduced risk of Alzheimer’s disease.”

    “I was surprised and, at the same time, very sad” about the lack of evidence, said Dr. Martha L. Daviglus, the panel chairwoman and a professor of preventive medicine and medicine at the Feinberg School of Medicine at Northwestern University. “This is something that could happen to any of us, and yet we are at such a primitive state of research.”

    She said, “In the end, we concluded that the evidence is the evidence and we have to say what it is.”

    The state of the evidence reflects in part the long time it took before researchers even realized that Alzheimer’s was a disease, said Dr. Richard J. Hodes, director of the National Institute on Aging. Until the mid-1980s, many thought dementia was a normal part of aging, and so serious studies of its causes and prevention did not really begin until then. Scientists have spent the years since searching for factors that might affect risk, checking data from other studies to see if, for example, diet or blood pressure or years of education might be associated with the disease.

    In the meantime, doctors are in a bind. Should they tell people to do things like walk briskly or eat vegetables — activities that might someday be shown to protect against Alzheimer’s and that certainly cannot hurt? Or should they wait for absolute proof, confirmation that a diet or a drug or an exercise regimen prevents Alzheimer’s?

    The Alzheimer’s Association tells people to exercise, challenge themselves mentally, remain socially engaged and keep their hearts healthy. Such measures can only help, says Dr. Maria C. Carrillo, a senior director of the organization.

    But, she said, “The Alzheimer’s Association certainly agrees that there is not enough evidence to say anything definitive about the prevention of Alzheimer’s disease and any kind of intervention.”

    Of course, Dr. Hodes said, there are many reasons to follow practices to improve general health. But, he said, researchers have to be careful about implying that any measures will protect against this degenerative brain disease.

    “We don’t know that yet,” Dr. Hodes said.

    Rating the Quality

    Dr. John W. Williams Jr., head of the Duke group that evaluated the studies, thought the task would not be too arduous. He expected relatively few studies and clear results.

    To its great surprise, the Duke group discovered a vast amount of literature on Alzheimer’s prevention. Instead of coming up empty on many topics, Dr. Williams said, “We came up empty on very few.”

    The problem, the group wrote, was that “the quality of the evidence was typically low.”

    Most studies observed people who happened to use or not use a possible preventive measure and then determined whether they got Alzheimer’s or not.

    Such studies, known as observational ones, are not the gold standard, like those in which people are randomly assigned to take a pill or do something like exercise, or not. Observational studies are useful in generating hypotheses but are not proof. Still, if several well-done studies of this type come to the same conclusion, they can be valuable evidence.

    In the case of Alzheimer’s prevention, though, the studies tended to have problems, Dr. Williams said.

    Often it was not clear precisely what subjects were doing. They might have been using a drug or a supplement at the start of the study but the dose was not specified, nor was it clear whether subjects were taking the same doses, or for how long.

    Some studies of drugs to lower blood pressure used self-reports as opposed to, for example, pharmacy data. A 12-year study asked participants about their use of cholesterol-lowering statins at the start of the study but never did again. A nine-year statin study used pharmacy records but included as users those who took the drugs at any time during the study period.

    Definitions of conditions, like high blood pressure, tended to vary from study to study.

    Descriptions of factors like “strong social support” were vague or idiosyncratic. For example, some studies classified married people as having strong social support for that reason alone, with no evaluation of whether the marriage was good or bad.

    Often, there were vague assessments of Alzheimer’s disease. And often studies did not take into account other differences among subjects, like age or family history of Alzheimer’s, that might have independently led some to get the disease and others not.

    Looking over the piles of studies, the group rated evidence as high, moderate or low, depending on how confident they were in the findings.

    Low confidence did not necessarily mean the measures did not work — it meant the evidence was so faulty that there was no way of deciding.

    In the end, it said it was highly confident in the findings for just one thing, the herb ginkgo biloba. But in that case the evidence pointed in only one direction: it did not prevent Alzheimer’s.

    Moderate evidence, not totally convincing but not worthless, applied to only four factors studied.

    Two were factors that increased risk. They were a particular gene, ApoE4, which, moderate evidence showed, increased risk about threefold, and menopause therapy with a combination of estrogens and progestins, which doubled risk.

    The other moderate evidence indicated that certain things that had been hoped to be protective were not. For instance, there was moderate evidence that vitamin E, found in nuts, vegetable oils, green leafy vegetables and fortified cereals, had no effect on risk. There was also moderate evidence that cholinesterase inhibitors, drugs often used to treat Alzheimer’s symptoms, had no effect.

    Other than that, evidence was poor.

    There is only poor evidence, for example, that keeping your brain active, having a high level of education or exercising has a protective effect. There is also only poor evidence that eating a Mediterranean diet — high in fruits and vegetables, fish and olive oil — will help stave off Alzheimer’s.

    There is only poor evidence that having poor social support or smoking increases risk.

    In a way, it is not surprising that many thought the evidence was stronger than it was, says Dr. James R. Burke, a member of the Duke group and director of the Memory Disorders Clinic at Duke.

    “You remember the positive studies,” Dr. Burke said. “The ones that are more marginal, you tend to put them out of your mind.”

    And many things thought to protect against Alzheimer’s — a healthy diet, vigorous exercise and an active brain — just seem to be common sense. The science jury said it was still possible that those measures might be found to help and urged that better quality studies be done.

    But that may not be so easy if studies have to follow people until they get the disease. Alzheimer’s seems to progress silently in the brain for a decade before the earliest symptoms of memoryproblems surface. It can take another decade until the distinctive signs of Alzheimer’s appear: profound memory loss and an inability to handle the normal activities of daily life like bathing and dressing.

    “Once there is even minimal cognitive impairment, the brain is damaged, inflamed, burning like a bonfire,” said Dr. Caleb Finch, director of the Gerontology Research Institute at the University of Southern California.

    As a result, high-quality studies of possible factors like diet and exercise or mental stimulation before the disease’s onset might have to last for decades.

    In the meantime, patients, like those at Dr. Burke’s Memory Disorders Clinic, and their frightened family members want advice about things they can do now.

    He tells them to do all they can to stay healthy: keep their heart disease risk factors under control, eat a good diet, exercise. He tells them that even if good health cannot prevent Alzheimer’s, it might delay its onset.

    “We don’t have compelling evidence or proof that this will prevent Alzheimer’s disease,” he says. But those measures, he adds, “would improve quality of life.”

    But Dr. Williams, head of the Duke group, said it was also important to keep an open mind; the measures may or may not affect a person’s chances of getting Alzheimer’s.

    “Unfortunately, in medicine,” he said, “things that are logical and make good sense don’t necessarily work out.”

    The Problem, Personified

    Elise Schoux of Washington is facing the prevention problem. She is 53, an age when prevention might make sense — when Alzheimer’s strikes, people usually are in their 70s and 80s — and she is watching her 70-year-old husband’s slow decline into the dread disease.

    Bill Schoux’s memory had been deteriorating for years, but in July 2009, when he got the diagnosis, Mrs. Schoux was devastated.

    “For two weeks, we were at a loss, we would burst into tears,” she said. “How could this be?”

    Mr. Schoux had been an athlete all his life, he ate a healthy diet, he was friendly and outgoing. He had been an expert on foreign aid, traveling around the world, and had certainly had a mentally stimulating career. Mrs. Schoux is not sure how much more her husband could have done to ward off Alzheimer’s. But she wants to do everything she can to protect herself from getting it and to slow the disease in him.

    So Mrs. Schoux now unfailingly goes to the gym with her husband several days a week, lifting weights and spending 30 minutes on a treadmill or an elliptical cross trainer.

    Her husband always worked crossword puzzles. Now she does them, too. She and her husband have a subscription to a local theater. And they read the newspaper every day.

    “It can’t hurt to keep the brain cells moving,” Mrs. Schoux said.

    Mrs. Schoux also tries to eat blueberries, salmon, intensely colored fruits and dark leafy vegetables, in case that helps.

    She knows that much of what she is trying is unproved but feels that it can, at worst, be harmless.

    “I don’t know what the answers are,” Mrs. Schoux said. “I hope they find something. It is a seriously debilitating disease.”
     
    Last edited: Aug 29, 2010
  6. #6
    cvictorg

    cvictorg Member

    http://www.nytimes.com/2010/09/02/health/research/02alzheimer.html?hpw

    Finding Suggests New Aim for Alzheimer’s Drugs

    In a year when news about Alzheimer’s disease seems to whipsaw between encouraging and disheartening, a new discovery by an 84-year-old scientist has illuminated a new direction.

    The scientist, Paul Greengard, who was awarded a Nobel Prize in 2000 for his work on signaling in brain cells, still works in his Rockefeller University laboratory in New York City seven days a week, walking there from his apartment two blocks away, taking his aging Bernese mountain dog, Alpha.

    He got interested in Alzheimer’s about 25 years ago when his wife’s father developed it, and his research is now supported by a philanthropic foundation that was started solely to allow him to study the disease.

    It was mostly these funds and federal government grants that allowed him to find a new protein that is needed to make beta amyloid, which makes up the telltale plaque that builds up in the brains of people with Alzheimer’s.

    The finding, to be published Thursday in the journal Nature, reveals a new potential drug target that, according to the prevailing hypothesis of the genesis of Alzheimer’s, could slow or halt the devastating effects of this now untreatable disease.
     
  7. #7
    Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Smith AD, Smith SM, de Jager CA, et al. Homocysteine-Lowering by B Vitamins Slows the Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial. PLoS ONE;5(9):e12244. PLoS ONE: Homocysteine-Lowering by B Vitamins Slows the Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial

    Background
    An increased rate of brain atrophy is often observed in older subjects, in particular those who suffer from cognitive decline. Homocysteine is a risk factor for brain atrophy, cognitive impairment and dementia. Plasma concentrations of homocysteine can be lowered by dietary administration of B vitamins.

    Objective
    To determine whether supplementation with B vitamins that lower levels of plasma total homocysteine can slow the rate of brain atrophy in subjects with mild cognitive impairment in a randomised controlled trial (VITACOG, ISRCTN 94410159).

    Methods and Findings
    Single-center, randomized, double-blind controlled trial of high-dose folic acid, vitamins B6 and B12in 271 individuals (of 646 screened) over 70 y old with mild cognitive impairment. A subset (187) volunteered to have cranial MRI scans at the start and finish of the study. Participants were randomly assigned to two groups of equal size, one treated with folic acid (0.8 mg/d), vitamin B12(0.5 mg/d) and vitamin B6 (20 mg/d), the other with placebo; treatment was for 24 months. The main outcome measure was the change in the rate of atrophy of the whole brain assessed by serial volumetric MRI scans.

    Results
    A total of 168 participants (85 in active treatment group; 83 receiving placebo) completed the MRI section of the trial. The mean rate of brain atrophy per year was 0.76% [95% CI, 0.63–0.90] in the active treatment group and 1.08% [0.94–1.22] in the placebo group (P = 0.001). The treatment response was related to baseline homocysteine levels: the rate of atrophy in participants with homocysteine >13 µmol/L was 53% lower in the active treatment group (P = 0.001). A greater rate of atrophy was associated with a lower final cognitive test scores. There was no difference in serious adverse events according to treatment category.

    Conclusions and Significance
    The accelerated rate of brain atrophy in elderly with mild cognitive impairment can be slowed by treatment with homocysteine-lowering B vitamins. Sixteen percent of those over 70 y old have mild cognitive impairment and half of these develop Alzheimer's disease. Since accelerated brain atrophy is a characteristic of subjects with mild cognitive impairment who convert to Alzheimer's disease, trials are needed to see if the same treatment will delay the development of Alzheimer's disease.


    Trial Registration
    Controlled-Trials.com ISRCTN94410159
     
  8. #8
    Michael Scally MD

    Michael Scally MD Doctor of Medicine

    World Alzheimer Report 2010
    World Alzheimer Report - Alzheimer's Disease International

    The World Alzheimer Report 2010 provides the clearest, most comprehensive global picture yet of the economic impact of Alzheimer's disease and dementia.

    The report includes an estimate of the worldwide cost of dementia, including direct medical costs, direct non-medical costs and costs of informal (family) care. The estimates are broken down by world region and include analysis of the differences between low and high income countries. The report also contains important policy recommendations and makes clear to key decision-makers that doing nothing is not an option.


    Landmark Report Reveals Massive Global Cost Of Alzheimer's: 1% Of Global GDP - And Growing

    Global Action Needed to Address "Most Significant Health Crisis of the 21st Century"

    A landmark report on the Global Economic Impact of Dementia finds that Alzheimer's disease and other dementias are exacting a massive toll on the global economy, with the problem set to accelerate in coming years. The World Alzheimer Report 2010 - issued on World Alzheimer's Day by Alzheimer's Disease International (ADI) - provides the most current and comprehensive global picture of the economic and social costs of the illness. The Report was jointly authored by Prof Anders Wimo of the Karolinska Institutet, Stockholm, Sweden; and Prof Martin Prince, Institute of Psychiatry, King's College London, UK.

    "This is a wake-up call that Alzheimer's disease and other dementias are the single most significant health and social crisis of the 21st century," said Dr Daisy Acosta, Chairman of ADI. "World governments are woefully unprepared for the social and economic disruptions this disease will cause."

    The Report reveals:

    • The worldwide costs of dementia will exceed 1% of global GDP in 2010, at US$604 billion.

    • If dementia care were a country, it would be the world's 18th largest economy. If it were a company, it would be the world's largest by annual revenue exceeding Wal-Mart (US$414 billion) and Exxon Mobil (US$311 billion).

    • The number of people with dementia will double by 2030, and more than triple by 2050.

    • The costs of caring for people with dementia are likely to rise even faster than the prevalence - especially in the developing world, as more formal social care systems emerge, and rising incomes lead to higher opportunity costs.

    • Reports from individual countries such as the UK suggest that dementia is one of the costliest illnesses - and yet research and investment is at a far lower level than for other major illnesses.

    "The scale of this crisis cries out for global action," said Marc Wortmann, Executive director of ADI. "History shows that major diseases can be made manageable - and even preventable - with sufficient global awareness and the political will to make substantial investments in research and care options."

    "This new Report gives us the clearest, most comprehensive picture yet of the global economic and social costs of dementia," said Prof Anders Wimo. "In this World Alzheimer Report 2010, we merged the best available data and the most recent insights regarding the worldwide economic cost of dementia. This enabled us to provide more detailed estimates than before, by making use of recently available data that considerably strengthens the evidence base."

    The Report combines the most current prevalence data from the World Alzheimer Report 2009 with improved data on low and middle-income countries from the 10/66 Dementia Research Group studies in Latin America, India and China. The Report uses representative population-based samples from developing countries to better quantify the cost of informal care systems that have previously been excluded from impact estimates.

    Co-author Prof Martin Prince urged nations to develop better plans for caring for the millions who have the disease. "The care of people with dementia is not just a health issue - it is a massive social issue," said Prof Prince. "This is particularly true in low and middle income countries which lack adequate systems of formal care. Governments must show greater leadership, working with all stakeholders, to drive solutions to the long term care issue."

    Recommended Actions

    The Report urges the global community to take the following immediate actions:

    • Governments worldwide should act urgently to make Alzheimer's disease a top priority and develop national plans to deal with the social and health consequences of dementia. Several countries have moved forward to develop national plans, including France, Australia and England. It is critical for other governments to follow suit.

    • Governments and other major research funders must increase research funding to a level more proportionate to the economic burden of the condition. Recently published data from the UK suggests that a 15-fold increase is required to reach parity with research into heart disease, and a 30-fold increase to achieve parity with cancer research.

    • Governments worldwide must develop policies and plans for long-term care that anticipate and address social and demographic trends and have an explicit focus on supporting family caregivers and ensuring social protection of vulnerable people with Alzheimer's disease and other dementias.

    • The scale of what is facing us elevates this to a global challenge, which must be addressed as a top WHO priority and on the G-20/G-8 agenda.

    Dementia is a syndrome that can be caused by a number of progressive disorders that affect memory, thinking, behavior and the ability to perform everyday activities. Alzheimer's disease is the most common type of dementia. Approximately 0.5% of the world's total population live with dementia and this will grow exponentially.

    After age 65, the likelihood of developing Alzheimer's roughly doubles every five years. At the age of 85, the odds of a person developing it are close to 50 percent. In the World Alzheimer Report 2009, ADI estimated that there are 35.6 million people living with dementia worldwide, increasing to 65.7 million by 2030 and 115.4 million by 2050.
     
  9. #9
    Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Brain-protecting enzyme may fight Alzheimer's
    Brain-protecting enzyme may fight Alzheimer's | Reuters

    By Julie Steenhuysen
    Sep 22, 2010

    (Reuters) - Restoring levels of a nerve-protecting enzyme offers a new approach to developing treatments for Alzheimer's disease, U.S. researchers said on Wednesday.

    They said the enzyme SIRT1 may help prevent the formation of a toxic form of the protein tau that kills brain cells in people with Alzheimer's disease.

    "This is definitely the first step toward finding new strategies to reduce tau," Li Gan at the Gladstone Institute of Neurological Disease in San Francisco, whose study appears in the journal Neuron, said in a telephone interview.

    She said people with Alzheimer's tend to have low levels of SIRT1, and drugs that boost these levels may keep this toxic form of tau from forming, they said.

    The team studied the link between SIRT1 and a form of tau that is strongly linked with Alzheimer's disease. called p-tau.

    They found that mice genetically engineered to lack the SIRT1 gene were more likely to make the toxic form of tau.

    When they tested a chemical that restores levels of SIRT1, it curbed the formation if p-tau.

    The finding offers a new approach to reducing levels of tau in people with Alzheimer's.

    "We think by modulating this pathway, we will be able to lower the pathogenic form of tau," Gan said.

    Many companies, including GlaxoSmithKline, have been working on drugs that activate SIRT1, which is thought to control many age-related diseases.

    Alzheimer's is a progressive and fatal form of dementia that kills brain cells, causing steady declines in memory and thinking until people lose the ability to care for themselves.

    Current drugs can treat symptoms, but none can close the progression of the disease, which affects 26 million people globally.

    On Tuesday Alzheimer's Disease International projected the worldwide costs of dementia would reach $604 billion in 2010, more than one percent of global GDP output.


    Min S-W, Cho S-H, Zhou Y, et al. Acetylation of Tau Inhibits Its Degradation and Contributes to Tauopathy. Neuron 2010;67(6):953-66. http://download.cell.com/neuron/pdf/PIIS0896627310006872.pdf?intermediate=true

    Neurodegenerative tauopathies characterized by hyperphosphorylated tau include frontotemporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17) and Alzheimer's disease (AD). Reducing tau levels improves cognitive function in mouse models of AD and FTDP-17, but the mechanisms regulating the turnover of pathogenic tau are unknown. We found that tau is acetylated and that tau acetylation prevents degradation of phosphorylated tau (p-tau). We generated two antibodies specific for acetylated tau and showed that tau acetylation is elevated in patients at early and moderate Braak stages of tauopathy. Histone acetyltransferase p300 was involved in tau acetylation and the class III protein deacetylase SIRT1 in deacetylation. Deleting SIRT1 enhanced levels of acetylated-tau and pathogenic forms of p-tau, probably by blocking proteasome-mediated degradation. Inhibiting p300 with a small molecule promoted tau deacetylation and eliminated p-tau associated with tauopathy. Modulating tau acetylation could be a new therapeutic strategy to reduce tau-mediated neurodegeneration. º Tau is acetylated and tau acetylation is elevated at early stage of tauopathy º SIRT1 deacetylates tau, whereas p300 mediates tau acetylation º Tau acetylation slows down its degradation º Enhancing tau deacetylation abolishes pathogenic forms of phosphorylated tau
     
  10. #10
    Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Blood test could diagnose Alzheimer’s disease,
    UT Southwestern researchers find in statewide study
    Blood test could diagnose Alzheimer's disease, <br>UT Southwestern researchers find

    DALLAS – Oct. 6, 2010 – A set of proteins found in blood serum shows promise as a sensitive and accurate way to diagnose Alzheimer’s disease, researchers at UT Southwestern Medical Center have found as part of a statewide study.

    An analysis of the proteins, plus a clinical exam, proved 94 percent accurate in detecting suspected Alzheimer’s and 84 percent accurate in ruling it out in people without the disease, the researchers said.

    “This research uses a novel technology that makes it possible to analyze several biomarkers in a single blood sample in a cost-effective way,” said Dr. Ramón Díaz-Arrastia, professor of neurology at UT Southwestern and senior author of the study which was published in the September issue of the Archives of Neurology.

    Researchers have been seeking a simple blood test for Alzheimer’s for years, Dr. Díaz-Arrastia said, but no single substance, or “biomarker,” has been shown to be useful. Such a test, he said, would be comparable in principle to measuring blood cholesterol as a biomarker of cardiovascular disease.

    Alzheimer’s disease is an incurable degenerative brain disease, which currently afflicts about 5.3 million people over 65 in the U.S., according to the National Alzheimer’s Association. By 2050 that number is expected to reach 11 million or more.

    The disease is difficult to diagnose, particularly in its early stages when it resembles other cognitive problems. Currently, a definitive diagnosis is possible only after examining the brain tissue of deceased individuals. Tests for suspected Alzheimer’s are often expensive or invasive, and not every patient is able or willing to undergo them, the researchers stated.

    A blood test would provide a convenient diagnostic method that could be performed by health care workers nearly anywhere. In addition, a definitive diagnosis is important because treatments specifically targeting Alzheimer’s might not be effective against other forms of neurodegenerative disease or cognitive decline, Dr. Díaz-Arrastia said.

    Researchers associated with the Texas Alzheimer’s Research Consortium, a five-university group funded by the state, carried out the research. In the current study, the scientists analyzed blood samples from 197 Texas patients who had suspected Alzheimer’s and 203 people without the disease.

    The researchers measured more than 100 blood proteins and created a mathematical analysis that could measure a person’s risk of having Alzheimer’s. The analysis, combined with information from a clinical exam, accurately detected Alzheimer’s 94 percent of the time, and correctly ruled out Alzheimer’s 84 percent of the time in people without the disease, Dr. Díaz-Arrastia said.

    Neither the blood test nor a clinical exam alone was as accurate on its own as the blood test and clinical exam combined, the researchers found.

    “Having a diagnosis is an important step, but it’s not the end of the road unless you’ve got a treatment or a cure,” Dr. Díaz-Arrastia said.

    The next step in the work is to determine whether the biomarker test can detect accurately Alzheimer’s in preserved blood serum from patients who have been diagnosed definitively by an autopsy.
     
  11. #11
    Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Low testosterone levels lead to Alzheimer’s
    Low testosterone levels lead to Alzheimer’s - The Times of India

    ANI, Oct 6, 2010

    Older men with low levels of the male sex hormone, testosterone, are more prone to Alzheimer's disease, revealed a new study.

    "Having low testosterone may make you more vulnerable to Alzheimer's disease. The take-home message is we should pay more attention to low testosterone, particularly in people who have memory problems or other signs of cognitive impairment," said Dr. John E. Morley, director of the division of geriatric medicine at Saint Louis University and a study co-investigator.

    Led by Dr. Leung-Wing Chu, who is chief of the division of geriatric medicine at Queen Mary Hospital at the University of Hong Kong, researchers studied 153 Chinese men who were recruited from social centers.

    They were at least 55 years and older, lived in the community and didn't have dementia.

    Of those men, 47 had mild cognitive impairment - or problems with clear thinking and memory loss.

    Within a year, 10 men who all were part of the cognitively impaired group developed probable Alzheimer's disease.

    These men also had low testosterone in their body tissues; elevated levels of the ApoE 4 (apolipoprotein E) protein, which is correlated with a higher risk of Alzheimer's disease; and high blood pressure.

    "It's a very exciting study because we've shown that a low level of testosterone is one of the risk factors for Alzheimer's disease," said Morley.

    The findings corroborate findings in previous studies of older Caucasian men that show low testosterone is associated with impaired thinking and Alzheimer's disease.

    They suggest that testosterone may have a protective value against Alzheimer's disease.

    The next step, Morley said, is to conduct a large-scale study that investigates the use of testosterone in preventing Alzheimer's disease.

    The researchers encourage studying the effectiveness of testosterone replacement in older men who have both mild memory problems and low testosterone in staving off Alzheimer's disease.

    The study was published in the Journal of Alzheimer''s Disease.


    Chu LW, Tam S, Wong RL, et al. Bioavailable Testosterone Predicts a Lower Risk of Alzheimer's Disease in Older Men. J Alzheimers Dis. IOS Press - Journal Article

    There is a paucity of data on the relationship between testosterone and Alzheimer's disease (AD) in older men. The objective of the present study was to investigate the effects of serum total testosterone (TT), bioavailable testosterone (BT), and sex hormone binding globulin (SHBG) levels on the subsequent risk of AD in non-demented Chinese older men. This was a one-year prospective cohort study. 153 ambulatory community-living non-demented Chinese older men, aged 55 years or over, were recruited and followed for one year. Morning serum TT, BT, and SHBG levels were measured at baseline. At one-year of follow-up, assessment for dementia and AD were performed. AD was diagnosed by the NINCDS-ADRDA criteria for probable AD. Overall, the mean age of the subjects was 72.7 (SD 6.9). 6.5% (n = 10) developed dementia (converters), all having AD. 93.5% (n = 143) did not develop dementia (non-converters). Logistic regression analysis for independent predictors of AD~showed that the baseline serum BT level, systolic blood pressure (SBP) and ApoE epsilon4 genotype were significant independent predictors, after adjustment for age, education, BMI, fasting plasma glucose, and serum HDL-C levels. The baseline serum BT level predicted a reduced risk of AD (adjusted relative risk (RR) 0.22, 95% CI: 0.07-0.69)). Baseline SBP and ApoE epsilon4 genotype but not SHBG were independent risk factors, with RRs of 1.04 and 5.04 respectively. In conclusion, the serum level of bioavailable testosterone in late life predicts a lower risk of future AD development in older men.
     
    Last edited: Oct 6, 2010
  12. #12
    zkt

    zkt Member

    Mild cognitive impairment

    [ame="http://en.wikipedia.org/wiki/Memantine"]Memantine - Wikipedia, the free encyclopedia@@AMEPARAM@@/wiki/File:Memantine.svg" class="image"><img alt="" src="http://upload.wikimedia.org/wikipedia/commons/thumb/5/58/Memantine.svg/150px-Memantine.svg.png"@@AMEPARAM@@commons/thumb/5/58/Memantine.svg/150px-Memantine.svg.png[/ame]
     
  13. #13
    Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Panel Calls for Biomarkers in Routine Clinical AD Diagnosis
    Medical News: Panel Calls for Biomarkers in Routine Clinical AD Diagnosis - in Neurology, Alzheimer's Disease from MedPage Today

    Clinicians should try to incorporate biomarker data in their diagnosis of patients with Alzheimer's disease or conditions potentially leading to it, an ad hoc expert panel recommended.

    Levels of beta-amyloid or tau proteins in cerebrospinal fluid (CSF), or data from MRI or PET scans using amyloid-specific tracers, should be part of the differential diagnosis of Alzheimer-related disorders, according to two dozen members of the International Working Group for New Research Criteria for the Diagnosis of Alzheimer's Disease.

    Led by Bruno Dubois, MD, of Salpetriere Hospital in Paris, the group also put forth what it called a "lexicon" to standardize the taxonomy of Alzheimer-related conditions.

    Their recommendations, which would give biomarkers a more prominent role in clinical practice than suggested this summer by a U.S.-based working group, appeared online in Lancet Neurology.

    The lexicon's proposed classification scheme included six diagnostic categories: typical, atypical, mixed, prodromal, and preclinical Alzheimer's disease (AD), and mild cognitive impairment. It also proposed criteria for Alzheimer dementia, not as a separate diagnostic category but rather as a critical milestone in disease progression that distinguishes some of their categories from others.

    Dubois and colleagues contended that biomarker data was good enough for clinicians to use in diagnosing most of these conditions, mainly excepting mild cognitive impairment.

    "This reliable identification of AD biomarkers supports a major change in the conceptualization and diagnosis of AD, because both clinical and in-vivo biological manifestations of the disease can now be integrated into the diagnosis," they wrote. "Laboratory and neuroimaging biomarkers are very highly correlated with the neuropathological lesions of AD."

    In an accompanying editorial, Lon S. Schneider, MD, of the University of Southern California in Los Angeles, disagreed that biomarkers were ready for routine clinical use.

    "Given the importance of biomarkers in this lexicon, it should be remembered that, although several biomarkers have been correlated with neuropathological changes of Alzheimer's disease, clinical symptoms, and disease stage, none has yet been shown to have clear criterion validity," he wrote.

    He said the data on biomarkers do support their use in at least some clinical trials. But, even apart from the currently known biomarkers' diagnostic accuracy, Schneider questioned their clinical utility on practical grounds.

    "Clinicians will assess cognitive function before considering lumbar punctures or brain imaging, and will be unlikely to undertake lumbar punctures when patients are asymptomatic or have no clear clinical findings," he observed.

    "Although this lexicon is well integrated and conceptually attractive, field trials are needed to establish whether the diagnostic criteria will work effectively in clinical or research situations," Schneider concluded.

    The International Working Group's lexicon goes beyond the guidelines proposed in July by another working group assembled by the National Institute on Aging (NIA) and the U.S. Alzheimer's Association (USAA). Those guidelines suggested three broad categories of disease: full-blown Alzheimer's disease, mild cognitive impairment, and a preclinical Alzheimer state.

    The NIA/USAA guidelines stated that brain imaging results and CSF biomarkers can be used clinically to diagnose these conditions -- to "improve the certainty" of clinical evaluations -- but stopped short of suggesting they should be required, as the proposal from Dubois and colleagues would do.

    The international group's lexicon described the clinical presentations that would go along with biomarker findings for each of the six diagnostic categories.

    • Typical Alzheimer's disease: progressive worsening of episodic memory along with less specific abnormalities in executive function, attention, and word-finding.

    • Atypical disease: other well-recognized presentations associated with autopsy-confirmed disease that differ from the typical pattern. "These include non-amnestic focal cortical syndromes, such as primary progressive nonfluent aphasia, logopenic aphasia, posterior cortical atrophy, and frontal variant [disease]," Dubois and colleagues wrote.

    • Mixed disease: features of typical or atypical Alzheimer's disease occurring alongside other sources of dementia such as cerebrovascular disease or Lewy body infestations.

    • Alzheimer dementia: not intended to be separate from the above types of Alzheimer's disease, but included as an entity in the lexicon "to identify the dementia threshold as a severity milestone in the source of the disease," Dubois and colleagues indicated. The onset of frank dementia "adds a set of management issues for clinicians to address," and hence deserves its own diagnostic focus, they argued.

    • Prodromal disease: early episodic memory loss of the hippocampal type, absent a dementia diagnosis but accompanied by Alzheimer-associated biomarkers.

    • Preclinical-asymptomatic disease: clinically normal, but Alzheimer-related CSF or imaging markers are present.

    • Mild cognitive impairment: any clinical presentation involving cognitive changes that may or not resemble prodromal Alzheimer's disease and can be diagnosed if biomarkers are negative. It is also the category for patients with positive biomarker findings and mild cognitive symptoms that do not fit the Alzheimer prodrome.

    Dubois and colleagues acknowledged that the association with biomarkers in some of these categories -- such as atypical disease -- has not been confirmed to the same degree as for classic Alzheimer's disease.

    They also recognized that lumbar punctures and expensive high-tech imaging may not be feasible to use on all patients with cognitive deficits, particularly in the absence of regulatory approvals and the insurance reimbursements that depend on them.

    In general, they said, the recommendations should be more immediately applied in clinical research.

    Still, Dubois and colleagues also indicated that clinicians should follow suit as soon as practical.

    One aim of publishing the lexicon now "is to provide clinicians with a clear view of this evolving field in which use of biomarkers is advancing and might reach regulatory qualification and approval in the foreseeable future."

    It's important, Dubois and colleagues wrote, "to keep the research and clinical view of the disease from becoming too widely separated."

    But Schneider questions how much clinical utility the CSF markers and brain imaging data would actually provide in routine practice, issues of cost and patient acceptance notwithstanding.

    "Data from several cohort studies suggest that more than 70% of patients diagnosed with mild cognitive impairment due to Alzheimer's disease and 90% of patients with Alzheimer's disease dementia had positive amyloid biomarkers, including 90%–100% of the apolipoprotein E epsilon-4 carriers," he pointed out.

    Dubois and colleagues noted that their work was necessarily provisional.

    "This lexicon is a proposal that will require revisions and updating by the scientific community," the researchers stressed.

    One apparent oddity in their scheme was a subgroup they offered within the preclinical category, dubbed "presymptomatic." These are healthy individuals without CSF markers or brain imaging abnormalities but who possess a genetic mutation that inevitably leads to Alzheimer's disease.

    This is currently a hypothetical group, because such a mutation, if one exists, has not yet been discovered in several genome-wide scans of large numbers of individuals. The APOE epsilon-4 variant is strongly predictive of Alzheimer risk but not "fully penetrant" -- a significant minority of homozygous carriers do not develop Alzheimer's disease, indicating that the genotype, by itself, is insufficient to cause the disease.

    In fact, Dubois and colleagues did not include a role for apolipoprotein E genotype status in their diagnostic criteria.

    Some researchers have suggested that additional searches for fully penetrant mutations would likely be fruitless and that any success would apply only to the few individuals who possess such rare mutations.
     
  14. #14
    zkt

    zkt Member

    What is the name of the spinal fluid test and what labs can process it ? If you know or can find out will greatly appreciate it.
     
  15. #15
    Michael Scally MD

    Michael Scally MD Doctor of Medicine

    The Age of Alzheimer’s
    http://www.nytimes.com/2010/10/28/opinion/28oconnor.html?ref=opinion

    October 27, 2010
    By SANDRA DAY O’CONNOR, STANLEY PRUSINER and KEN DYCHTWALD

    OUR government is ignoring what is likely to become the single greatest threat to the health of Americans: Alzheimer’s disease, an illness that is 100 percent incurable and 100 percent fatal. It attacks rich and poor, white-collar and blue, and women and men, without regard to party. A degenerative disease, it steadily robs its victims of memory, judgment and dignity, leaves them unable to care for themselves and destroys their brain and their identity — often depleting their caregivers and families both emotionally and financially.

    Starting on Jan. 1, our 79-million-strong baby boom generation will be turning 65 at the rate of one every eight seconds. That means more than 10,000 people per day, or more than four million per year, for the next 19 years facing an increased risk of Alzheimer’s. Although the symptoms of this disease and other forms of dementia seldom appear before middle age, the likelihood of their appearance doubles every five years after age 65. Among people over 85 (the fastest-growing segment of the American population), dementia afflicts one in two. It is estimated that 13.5 million Americans will be stricken with Alzheimer’s by 2050 — up from five million today.

    Just as President John F. Kennedy, in 1961, dedicated the United States to landing a man on the moon by the end of the decade, we must now set a goal of stopping Alzheimer’s by 2020. We must deploy sufficient resources, scientific talent and problem-solving technologies to save our collective future.

    As things stand today, for each penny the National Institutes of Health spends on Alzheimer’s research, we spend more than $3.50 on caring for people with the condition. This explains why the financial cost of not conducting adequate research is so high. The United States spends $172 billion a year to care for people with Alzheimer’s. By 2020 the cumulative price tag, in current dollars, will be $2 trillion, and by 2050, $20 trillion.

    If we could simply postpone the onset of Alzheimer’s disease by five years, a large share of nursing home beds in the United States would empty. And if we could eliminate it, as Jonas Salk wiped out polio with his vaccine, we would greatly expand the potential of all Americans to live long, healthy and productive lives — and save trillions of dollars doing it.

    Experience has taught us that we cannot avoid Alzheimer’s disease by having regular medical checkups, by being involved in nourishing relationships or by going to the gym or filling in crossword puzzles. Ronald Reagan suffered the ravages of this disease for a decade despite the support of his loving family, the extraordinary stimulation of his work, his access to the best medical care and his high level of physical fitness. What’s needed are new medicines that attack the causes of the disease directly.

    So far, only a handful of medications have been approved by the Food and Drug Administration to treat Alzheimer’s, and these can only slightly and temporarily modify symptoms like forgetfulness, disorientation and confusion. None actually slows the underlying neurodegeneration.

    In the mid-1980s, when our country finally made a commitment to fight AIDS, it took roughly 10 years of sustained investment (and about $10 billion) to create the antiretroviral therapies that made AIDS a manageable disease. These medicines also added $1.4 trillion to the American economy. The National Institutes of Health still spend about $3 billion a year on AIDS research, while Alzheimer’s, with five times as many victims, receives a mere $469 million.

    Most of the medical researchers who study Alzheimer’s agree on what they have to understand in order to create effective drugs: They must find out how the aberrant proteins associated with the disease develop in the brain. They need to model the progression of the illness so they can pinpoint drug targets. And ultimately they must learn how to get drugs to move safely from the blood into the brain.

    A breakthrough is possible by 2020, leading Alzheimer’s scientists agree, with a well-designed and adequately financed national strategic plan. Congress has before it legislation that would raise the annual federal investment in Alzheimer’s research to $2 billion, and require that the president designate an official whose sole job would be to develop and execute a strategy against Alzheimer’s. If lawmakers could pass this legislation in their coming lame-duck session, they would take a serious first step toward meeting the 2020 goal.

    Medical science has the capacity to relegate Alzheimer’s to the list of former diseases like typhoid, polio and many childhood cancers. But unless we get to work now, any breakthrough will come too late to benefit the baby boomers. Whether the aging of America turns out to be a triumph or a tragedy will depend on our ability to fight this horrific disease and beat it before it beats us.

    Sandra Day O’Connor is a retired associate justice of the Supreme Court. Stanley Prusiner, who received the 1997 Nobel Prize in Medicine, is the director of the Institute for Neurodegenerative Diseases at the University of California, San Francisco. Ken Dychtwald, a psychologist and gerontologist, is the chief executive of a company that consults with businesses about the aging world population.
     
  16. #16
    Jeton

    Jeton Member

    great op-ed.

    personally i've been taking minocycline since 2005 specifically for it's potential to prevent or slow AIDS Dementia Complex, and the drug is also studied for a neuroprotective role in Alzheimer's, Huntington's and Parkinson's diseases as well. it's been more promising in some roles than in others, but it does seem promising as it interrupts the macrophage-inflammation cycle that's critical to the formation of various amyloid plaques.

    ScienceDirect - Neurobiology of Disease : Multiple neuroprotective mechanisms of minocycline in autoimmune CNS inflammation

    [ame="http://en.wikipedia.org/wiki/Minocycline"]Minocycline - Wikipedia, the free encyclopedia@@AMEPARAM@@/wiki/File:Minocycline_structure.png" class="image"><img alt="" src="http://upload.wikimedia.org/wikipedia/commons/thumb/8/88/Minocycline_structure.png/220px-Minocycline_structure.png"@@AMEPARAM@@commons/thumb/8/88/Minocycline_structure.png/220px-Minocycline_structure.png[/ame]
     
  17. #17
    zkt

    zkt Member

    Thats good enough for me.
    Thanks, didnt know that..
    Will add it to the memantine-donepezil and see what happens. But I doubt if anything but long-term would be noticed.
    Its good to find someone else interested in this.
    BTW, your avatar is just too freaky.It scares the hell outta me. Who is that? some serial killer or what? Reminds me of Charles Manson

    [ame="http://en.wikipedia.org/wiki/Memantine"]Memantine - Wikipedia, the free encyclopedia@@AMEPARAM@@/wiki/File:Memantine.svg" class="image"><img alt="" src="http://upload.wikimedia.org/wikipedia/commons/thumb/5/58/Memantine.svg/150px-Memantine.svg.png"@@AMEPARAM@@commons/thumb/5/58/Memantine.svg/150px-Memantine.svg.png[/ame]
    [ame="http://en.wikipedia.org/wiki/Minocycline"]Minocycline - Wikipedia, the free encyclopedia@@AMEPARAM@@/wiki/File:Minocycline_structure.png" class="image"><img alt="" src="http://upload.wikimedia.org/wikipedia/commons/thumb/8/88/Minocycline_structure.png/220px-Minocycline_structure.png"@@AMEPARAM@@commons/thumb/8/88/Minocycline_structure.png/220px-Minocycline_structure.png[/ame]


    It seems the spf test isnt quite ready for prime time yet.

     
  18. #18
    Jeton

    Jeton Member

    [:eek:)] ur much too kind...that avy is me about 2 years ago, laying on a couch in a gay club and staring up lustfully at my husband-to-be. we'd met 8 days earlier.

    i think the success of the minocycline would come from NOT noticing any changes over time, while STILL maintaining memory.

    after all, one could perfectly NOT notice anything changing and still become demented...in fact,
    the two could go together quite easily...:D
     
  19. #19
    zkt

    zkt Member

    Now I`m REALLY confused. Did I pay you a complement or insult you ? I`m having a little cognitive dissonance with the Manson thing, but Ill probably forget about it soon . LOL
    Anyway, no, its not me . The wife
    But your right, the progression is often overlooked, untreated and ends badly.
    I should have been on this a few years ago but had to learn about my own issues first. So Id be around to study and treat hers.

     
  20. #20
    Jeton

    Jeton Member

    u did both complement and insult, simply by expressing natural heterosexual male anxiety at confronting the visage of toppy homosexual lust. here's a larger size version of the pic, showing off the lust better, perhaps making u more anxious...


    [​IMG]



    [​IMG]
     

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