Biological Psychology Links

By Bruce Bower Mental exercise lets seniors outrun Alzheimer’s disease — for a while. Then the race takes a tragic turn for the sharp-minded, a new study finds, as declines in memory and other thinking skills kick into high gear. After age 65, regular participation in mentally stimulating activities, including doing crossword puzzles and reading, delays intellectual decay caused by Alzheimer’s disease, say neuropsychologist Robert Wilson of Rush University Medical Center in Chicago and his colleagues. But when this debilitating condition finally breaks through the defenses of a mentally fortified brain, it rapidly makes up for lost time, the scientists report in a paper published online September 1 in Neurology. “The benefit of delaying initial signs of cognitive decline by keeping mentally active may come at the cost of more rapid dementia progression later on,” Wilson says. His team also found that mental stimulation slows cognitive declines typically experienced by seniors with healthy brains but offers no protection against the onset of memory and thinking problems that fall short of Alzheimer’s disease. Several recent studies have pointed to a delayed but sharp drop in thinking skills among mentally active people who develop Alzheimer’s disease, remarks neuropsychologist Yaakov Stern of Columbia University College of Physicians and Surgeons in New York City. Unlike the new report, though, those studies did not compare mentally active adults who developed Alzheimer’s disease with those who remained healthy or lost some mental function. © Society for Science & the Public 2000 - 2010

By GINA KOLATA 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. The work involves laboratory experiments and studies with mice — it is far from ready for the doctor’s office. But researchers, still reeling from the announcement two weeks ago by Eli Lilly that its experimental drug turned out to make Alzheimer’s worse, not better, were encouraged. Copyright 2010 The New York Times Company

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 disease or 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? Copyright 2010 The New York Times Company

By John Biemer, Special to the Chicago Tribune Catholic nuns are known for their acts of charity, but Sister Adrienne Schmidt has found a way to give beyond the grave: She will donate her brain to science. First, though, she is exercising it in an annual battery of memory tests administered by researchers at Chicago's Rush University. Schmidt, 82, repeats two-digit numbers, then three, four, five, six and seven digits. She names as many animals as she can in a minute. She listens to a 30-second story about a school cafeteria cook who is robbed of $56. Half an hour later, she must repeat as many details as she can. The yearly tests are designed to provide a history of how her brain is aging. When the time comes, Schmidt's brain will join hundreds of others in 38 cooling units in a laboratory at the school's medical center. Schmidt is one of the original participants in Rush University's Religious Orders Study, which began in 1993. It is one of a handful of studies nationwide that uses donated brains with a rich and detailed clinical history gleaned from years of memory tests and physical exams. Funding for the study is slated to run out next year, but researchers are preparing a federal grant proposal in hopes of extending the study five years, because it continues to yield a bounty of results. Copyright © 2010, Los Angeles Times

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 breach the blood-brain barrier and reduce levels of beta amyloid in the brain. And, company studies showed, it did reduce amyloid production. Copyright 2010 The New York Times Company

By John von Radowitz, Mid-life stress can increase the risk of women developing Alzheimer's disease, a study has shown. Women who reported repeated episodes of stress and anxiety in middle age were up to twice as likely to develop dementia than those who did not, a team of Swedish scientists found. The majority of those affected were diagnosed with Alzheimer's, the most common form of dementia. Researchers followed the progress of 1,415 women between 1968 and 2000. Three surveys in 1968, 1974 and 1980 were carried out to assess levels of psychological stress experienced by the women, who were aged between 38 and 60 at the start of the study. Stress was defined as a "sense of irritation, tension, nervousness, anxiety, fear or sleeping problems" lasting a month or more. During the course of the study, 161 of the women taking part developed dementia, mainly in the form of Alzheimer's disease. Dementia risk was 65% higher in women who suffered frequent stress in middle age. ©independent.co.uk

By GINA KOLATA In 2003, a group of scientists and executives from the National Institutes of Health, the Food and Drug Administration, the drug and medical-imaging industries, universities and nonprofit groups joined in a project that experts say had no precedent: a collaborative effort to find the biological markers that show the progression of Alzheimer’s disease in the human brain. Now, the effort is bearing fruit with a wealth of recent scientific papers on the early diagnosis of Alzheimer’s using methods like PET scans and tests of spinal fluid. More than 100 studies are under way to test drugs that might slow or stop the disease. And the collaboration is already serving as a model for similar efforts against Parkinson’s disease. A $40 million project to look for biomarkers for Parkinson’s, sponsored by the Michael J. Fox Foundation, plans to enroll 600 study subjects in the United States and Europe. The work on Alzheimer’s “is the precedent,” said Holly Barkhymer, a spokeswoman for the foundation. “We’re really excited.” The key to the Alzheimer’s project was an agreement as ambitious as its goal: not just to raise money, not just to do research on a vast scale, but also to share all the data, making every single finding public immediately, available to anyone with a computer anywhere in the world. Copyright 2010 The New York Times Company

By LARA SALAHI Researchers claimed to have identified markers for early Alzheimer's disease in some patients by analyzing results of a spinal tap, according to an article published Monday in the Archives of Neurology. Their results, they claim, are nearly 100 percent accurate in predicting Alzheimer's in some patients. But many experts are quick to question how reliable these results may be. "The test is an advance and has tremendous research potential. This is sure," said Karl Herrup, chair of Cell Biology and Neuroscience at Rutgers University in Piscataway, N.J. But, he added, "a dangerous, though unintended, consequence of the '100 percent accuracy' descriptor is that people who may not be on the fast track to Alzheimer's will end up frightened unnecessarily from a positive test result." "[T]he fear of [Alzheimer's disease] is so strong in our population that feeding it any way seems not in our best overall interest." And ABC News Senior Health and Medical Editor Dr. Richard Besser said the test is not yet ready for prime time. "This test isn't ready to be used on healthy, normal people," Besser said on "Good Morning America. It will be useful for research, doing drug trials in a group of people who may be at high likelihood to go on for Alzheimer's disease." © 2010 ABC News

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 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. Copyright 2010 The New York Times Company

By GINA KOLATA Will Alzheimer’s disease, a terrible degenerative brain disease with no treatments and no clear guidelines for diagnosis before its end stages, become like heart disease? That might mean early markers of risk, analogous to high cholesterol levels, that predict who is likely to get it. And it might mean drugs that actually prevent it. That is the hope behind new diagnostic guidelines being proposed by the National Institute on Aging and the Alzheimer’s Association. In July, when the groups first announced their proposed guidelines, they were met with some skepticism and anger. Why suggest ways of diagnosing the disease before a person even has symptoms? Why tell people they are doomed? And are those early diagnosis guidelines just a sop to pharmaceutical companies so they can start marketing expensive, and perhaps not very effective, new drugs? So the Alzheimer’s Association, with participation from the National Institute on Aging, held a conference call on Wednesday to clarify their position. They wanted, in particular, to explain why they advocated using so-called biomarkers, like scans for amyloid plaque in the brain, a unique feature of Alzheimer’s, and tests of cerebrospinal fluid. Such brain scans are still experimental. Copyright 2010 The New York Times Company

by Shaoni Bhattacharya I HAVE lost myself," cried Auguste Deter to her physician. Deter was trying to write her name, scrawling "Mrs" in a spidery script, only to forget the rest every time. "What are you eating?" the doctor asked Deter on her second day at the hospital for the mentally ill in Frankfurt, Germany, as the confused 51-year-old lunched on cauliflower and pork. "Potatoes," she replied. That was in 1901. When Deter died five years later, an autopsy revealed that her brain was riddled with strange tangles and plaques of a fibrous material containing the remnants of dead brain cells. She became the first described case of a form of dementia now known by the name of her doctor - one Alois Alzheimer. Over a century later, research into Alzheimer's disease still revolves around efforts to understand those mysterious plaques and tangles. Despite decades of work, no effective treatment exists, never mind a cure. The world's population is ageing, so that search is becoming more urgent. Alzheimer's disease is now recognised as the most common form of dementia, with over 25 million people living with the disease worldwide, and that number is expected to pass 100 million by 2050 (see diagram). Yet today, even definitively diagnosing the disease can still only be done at autopsy. The situation is starting to change, however. Thanks to a new imaging technique, the plaques can now be seen in the brains of living people. Not only could this allow early diagnosis, it is helping to overturn the long-standing orthodoxy over the causes of Alzheimer's and paving the way for effective treatments. © Copyright Reed Business Information Ltd.

By Karen Weintraub A leading antiaging researcher, Leonard Guarente, believes he has found a potential new approach for treating Alzheimer’s disease. For more than 15 years, the MIT biology professor has been researching proteins called sirtuins, which slow an animal’s aging clock during times of scarcity — stalling the animal at a younger and more fertile stage until food becomes more plentiful and reproductive success is more likely. Drug companies, including Cambridge-based Sirtris Pharmaceuticals Inc., a subsidiary of GlaxoSmithKline PLC, have been developing medications for diabetes and metabolic disorders based on this idea. In a paper published in the current issue of the journal Cell, Guarente and several students have shown that amping up one of the sirtuins, known as SIRT1, appears to treat Alzheimer’s in mice. Guarente, who cochairs Sirtris’s scientific advisory board, said his paper suggests that companies like Sirtris should be investigating whether sirtuins could be used against Alzheimer’s in people. “This would give us another completely new shot on goal, so I hope drug companies do try to develop such drugs,’’ he said. “Neurodegenerative diseases are now on the table.’’ © 2010 NY Times Co

By Caroline Parkinson Health reporter, BBC News People who stay in education for longer appear to be better able to compensate for the effects of dementia on the brain, a study suggests. A UK and Finnish team found those with more education were as likely to show the signs of dementia in their brains at death as those with less. But they were less likely to have displayed symptoms during their lifetime, the study in Brain said. Experts said scientists now had to find out why the effect occurred. Over the past decade, studies on dementia have consistently shown that the more time you spend in education, the lower the risk of dementia. But studies have been unable to show whether or not education - which is linked to higher socio-economic status and healthier lifestyles - protects the brain against dementia. The researchers in this study examined the brains of 872 people who had been part of three large ageing studies. Before their deaths they had also completed questionnaires about their education. The researchers found that more education makes people better able to cope with changes in the brain associated with dementia. Post-mortems showed the pathology - signs of disease - in the brains of people with and without long educations were at similar levels. But the researchers found those with more education are better able to compensate for the effects of the condition. It also showed that, for each year spent in education, there was an 11% decreased risk of developing dementia. (C)BBC

By NICHOLAS WADE A potentially promising approach to treating Alzheimer’s disease has been developed by researchers studying sirtuin, a protein thought capable of extending lifespan in laboratory animals. Using mice prone to developing Alzheimer’s, the researchers showed that activating sirtuin suppressed the disease and that destroying sirtuin made it much worse. The finding was made by Gizem Donmez, Leonard Guarente and colleagues at the Massachusetts Institute of Technology, who say it raises the hope of treating Alzheimer’s, and possibly other neurodegenerative diseases like Parkinson’s and Huntington’s, with drugs that activate sirtuin. Researchers not involved in the study agreed. “We think it is a scientifically compelling story that ties the sirtuins to the biology of Alzheimer’s disease,” said Dr. Dennis J. Selkoe, an Alzheimer’s expert at Harvard Medical School. But the therapeutic implications, Dr. Selkoe added, “remain quite up in the air.” Another expert, Dr. Juan C. Troncoso of Johns Hopkins University School of Medicine, said the finding “opens a very good avenue, but it’s not without a lot of technical challenges.” Drugs that activate sirtuin already exist, including resveratrol, a minor ingredient of red wine and other foods, and small-molecule chemicals designed to mimic resveratrol. Sirtris, the company that developed the drugs, is testing them against diabetes and other diseases. This generation of drugs does not cross the blood-brain barrier so would not work against Alzheimer’s. Copyright 2010 The New York Times Company

By GINA KOLATA Marilyn Maldonado is not quite sure why she is at the Memory Enhancement Center in the seaside town of Oakhurst, N.J. “What are we waiting for?” she asks. About 10 minutes later, she asks again. Then she asks again. She is waiting to enter a new type of Alzheimer’s drug study that will, in the boldest effort yet, test the leading hypothesis about how to slow or stop this terrifying brain disease. The disease is defined by freckles of barnacle-like piles of a protein fragment, amyloid beta, in the brain. So, the current thinking goes, if you block amyloid formation or get rid of amyloid accumulations — plaque — and if you start treatment before the disease is well under way, you might have a chance to alter its course. On Tuesday, that plan got a new push. The National Institute on Aging and the Alzheimer’s Association proposed new guidelines for diagnosis to find signs of Alzheimer’s in people who do not yet have severe symptoms, or even any symptoms at all. The guidelines are needed for the new approach to Alzheimer’s drug development. Just about every pharmaceutical company and many biotechnology companies have experimental drugs to block amyloid — there are more than 100 in the pipeline. And the companies would like to show that if they give their drugs early, they can slow or stop the disease. Copyright 2010 The New York Times Company

By Tina Hesman Saey Aging and wisdom are supposed to go together, but it turns out that a molecule that prevents one may actually play a role in the other. Researchers have discovered a new role for the famous antiaging protein SIRT1. It not only fends off aging, but also aids in learning and memory, a new study published online July 11 in Nature shows. Sirtuins, a family of proteins that includes SIRT1, help to regulate gene activity and have been implicated in governing metabolism and many of the biological processes that lead to aging. In the new study, Li-Huei Tsai, a neuroscientist and Howard Hughes Medical Institute investigator at MIT, finds that SIRT1 also plays a critical role in protecting learning and memory, at least in mice. Tsai and her colleagues had an inkling that SIRT1 might play some role in the brain from earlier experiments showing that resveratrol, an activator of sirtuins, could help neurons survive a mouse version of Alzheimer’s disease. Resveratrol also improved the animals’ ability to learn and remember. Since resveratrol can act on all seven of the sirtuins found in mammals and also affects other biological processes (SN Online: 6/28/10), the researchers didn’t know what role, if any, SIRT1 played in the process. To find out, Tsai and her colleagues put mice genetically engineered to lack SIRT1 in their brains through a series of learning and memory tests. The mice had trouble remembering the location of a submerged platform in a water maze, couldn’t tell the difference between a new object and an old one placed in their cages, and did poorly on other memory tests. “The ability for these animals to learn is clearly impaired,” Tsai says. © Society for Science & the Public 2000 - 2010

By GINA KOLATA A small company with a new brain scan for detecting plaque, the hallmark physical sign of Alzheimer’s disease, presented its results on Sunday at an international conference in Hawaii, and experts who attended said the data persuaded them that the method works. Until now, the only definitive way to diagnose Alzheimer’s has been to search for plaque with a brain autopsy after the patient dies. Scientists hope the new scanning technique, described June 24 in The New York Times’s series “The Vanishing Mind,” will allow doctors to see plaque while the patient is still alive, improving diagnosis and aiding research on drugs to slow or stop plaque accumulation. Neurologists have known about plaques ever since Alzheimer’s disease was first described in 1906. They are microscopic bumps made up of a protein, amyloid beta, appearing on the surface of the brain in areas involved with learning and memory. They are so characteristic of Alzheimer’s that they are required for a definitive diagnosis of the disease. Of course, doctors do not wait for a brain autopsy to diagnose Alzheimer’s. They use memory tests and evaluations of patients’ reasoning and ability to care for themselves. Yet with autopsy, even doctors at leading medical centers have been wrong as often as 20 percent of the time: people they said had Alzheimer’s did not have plaque. Copyright 2010 The New York Times Company

by MARILYNN MARCHIONE MILWAUKEE, Wisconsin — Scientists are reporting advances in detecting and predicting Alzheimer's disease at a conference in Honolulu this week, plus offering more proof that getting enough exercise and vitamin D may lower your risk. There are better brain scans to spot Alzheimer's disease. More genes that affect risk. Blood and spinal fluid tests that may help tell who will develop the mind-robbing illness and when. But what is needed most — a treatment that does more than just ease symptoms — is not at hand. "We don't have anything that slows or stops the course," said William Thies, the Alzheimer's Association scientific director. "We're really in a silent window right now" with new drugs, he said. Several promising ones flopped in late-stage tests — most recently, Pfizer Inc.'s Dimebon. Results on several others won't be ready until next year. Still, there is some progress against Alzheimer's, a dementia that afflicts more than 26 million people worldwide. Highlights of the research being reported this week: Prevention. Moderate to heavy exercisers had half the risk of developing dementia compared with less active people, researchers from the long-running Framingham Heart Study reported Sunday. Earlier studies also found exercise helps. Copyright 2010 The Associated Press.

Exercise has previously been linked to possible benefits in staving off dementia, but a new look at the topic suggests the earlier the better. The prevalence of cognitive impairment was significantly lower in women aged 65 and older who reported they were physically active as teens than in those who were inactive in their teen years, the study found. "If we want to optimally prevent dementia, it's important to start physical activity as early in life as possible," said principal investigator Laura Middleton of the Heart and Stroke Foundation Centre for Stroke Recovery at Sunnybrook Health Sciences Centre in Toronto. "More and more people are starting to recognize physical activity as one of the most promising means to prevent cognitive impairment and dementia. And what this study adds is that it's not only important in mid and late life — that we really have to start as early as possible." The study was published Wednesday appears in the July issue of the Journal of the American Geriatrics Society. Middleton worked on the project while she was at the University of California in San Francisco, and used data from the Study of Osteoporotic Fractures. She analyzed the responses of 9,704 women in four U.S. cities: Baltimore, Minneapolis, Portland, Ore., and Monongahela Valley, Pa. © CBC 2010

By PAM BELLUCK No one who knows Justin Kaplan would ever have expected this. A Pulitzer Prize-winning historian with a razor intellect, Mr. Kaplan, 84, became profoundly delirious while hospitalized for pneumonia last year. For hours in the hospital, he said, he imagined despotic aliens, and he struck a nurse and threatened to kill his wife and daughter. “Thousands of tiny little creatures,” he said, “some on horseback, waving arms, carrying weapons like some grand Renaissance battle,” were trying to turn people “into zombies.” Their leader was a woman “with no mouth but a very precisely cut hole in her throat.” Attacking the group’s “television production studio,” Mr. Kaplan fell from his hospital bed, cutting himself and “sliding across the floor on my own blood,” he said. The hospital called security because “a nurse was trying to restrain me and I repaid her with a kick.” Mr. Kaplan’s hallucinations lifted as doctors treated his pneumonia. But hospitals say many patients are experiencing such inexplicable disorienting episodes. Doctors call it “hospital delirium,” and are increasingly trying to prevent or treat it. Disproportionately affecting older people, a rapidly growing share of patients, hospital delirium affects about one-third of patients over 70, and a greater percentage of intensive-care or postsurgical patients, the American Geriatrics Society estimates. Copyright 2010 The New York Times Company

Links for keyword: Alzheimers