Alzheimer Related News Items

News as of 2/06/11

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Top Items

New Therapies for Prevention and Treatment of AD Identified - A Blanchette Rockefeller Neurosciences Institute (BRNI) study published in the Journal of Neuroscience reveals underlying causes for the degeneration of synapses in AD and identifies promising pharmaceutical solutions for this devastating condition. The BRNI study is the first to achieve fundamental molecular understanding of how synapses are lost in AD before the plaques and tangles develop. At the same time, it is the first study to demonstrate the comprehensive benefits of synaptogenic compounds in treating AD. The BRNI study marks an important shift in our understanding of how AD is caused and should be treated. By preventing the loss of synapses, BRNI’s new therapeutics prevent the progressive symptoms of AD. “AD is not primarily a disease of plaques and tangles as many had previously concluded, it is most importantly a disease of synapses,” said Dr. Daniel Alkon, the scientific director of BRNI and co-author of the study, “This study found that treatments that target the loss of synapses in the AD brain, can virtually eliminate all other elements of the disease -- elevation of the toxic protein, A Beta, the loss of neurons, the appearance of plaques, and loss of cognitive function; the animals’ brains were normalized.” The study utilized mice genetically engineered to express the symptoms and pathology of human AD in two different strains. BRNI used a difficult training regimen for the mice in order to reveal that significant cognitive deficits occurred five months before plaques were detected in their brains, providing evidence that plaques and tangles are not at the root of the disease. Treatments of Bryostatin and similar compounds synthesized at BRNI that target the enzyme PKCe, which controls the creation of synapses at the molecular level, were administered for twelve weeks during the study. While the compounds promoted the growth of new synapses and preservation of existing synapses, they also stopped the decrease of PKCe and the increase of soluble β amyloid, meaning that the treatments could be used to prevent the familiar hallmarks of AD, the plaques and tangles. BRNI has received approval to move forward with Phase II clinical testing for Bryostatin to treat AD, which is set to begin within the next several months. The target of the synaptogenic compounds is the same molecule identified as a biomarker for early diagnosis of AD in clinical trials conducted by BRNI and published in Neurobiology of Aging in 2010. As a result of that study, researchers at the Institute are now working to develop a skin test for identifying AD in its early stages before significant progression. Science Daily 1/14/11 Journal of Neuroscience, Jan.12, 2011; 31(2): 630-643

Drugs

Diabetes Drug AC253 Shows Potential in AD Treatment - A Canadian researcher may be making strides in the ongoing fight against AD, using a drug originally intended to treat diabetes. Dr. Jack Jhamandas, a researcher in the University of Alberta’s Faculty of Medicine and Dentistry, discovered during lab tests that the drug AC253, which was developed to treat diabetic patients but never actually made it to market, could be used instead to prevent and treat AD. In tests conducted by Jhamandas’ six‑person research team using living human brain cells grown in a lab, the drug was found to block the dangerous effects of a protein that is found in the brains of AD patients. “This protein causes a dysfunction and the death of nerve cells in the brain that are involved in memory and cognition,” Jhamandas said. For years, researchers have speculated about a link between diabetes and AD, but the specific nature of that connection isn’t fully understood. A protein similar to the one found in the brains of AD patients is also found in the pancreas of diabetic patients, which is what set Jhamandas and his team, funded by the Canadian Institute of Health Research, on their research path. “We had the notion that perhaps if this compound shares some similarities with the brain protein that’s found in AD patients, we could block that,” he said. “And lo and behold, it turns out that brain cells that are exposed to this amyloid (protein) that normally die, are protected.” Jhamandas said the finding is an important achievement - - one that can give the approximately 400,000 Canadians who suffer from the disease a sense of hope that a cure will be found. “This is a very exciting discovery and one that gives AD patients hope for development that will be much more definitive, rather than treating symptoms, which is what we do right now,” he said. The findings were published in the January issue of the American Journal of Pathology. Now the team is testing the drug on lab mice that have been genetically engineered to develop the debilitating disease, both before the mice have developed symptoms, and after they begin to suffer the effects of the disease. “This is very exciting because I think that it gives us an opportunity to develop drugs that are based on these sorts of compounds with a view of preventing or treating AD,” Jhamandas said. “And we’re fairly confident that we’re going to find that, based on what we have ascertained so far.” If they’re right and the tests prove successful in preventing the effects of the disease in the brains of lab mice, human clinical trials could be underway in about five years, Jhamandas said. “I think the advantage we have with a drug like this, is it was investigated before in the context of diabetes,” he said. “So we know a little about this drug in terms of what it does to the human body.” Jhamandas credited his research team for their ingenuity in seeing the possible benefits of the drug. “It takes good scientific principles, a team of good people in the lab and a dose of serendipity,” he said. By Mariam Ibrahim, Postmedia News 2/4/11 American Journal of Pathology, 178(1): 140-149 Jan. 2011

Genes & Genetic Issues

Second Member in AD Toxic Duo Identified - Like two unruly boys who need to be split up in class, a pair of protein molecules work together to speed up the toxic events of AD. Researchers at the UT Health Science Center San Antonio on 2/3/11 announced the discovery of the second molecule and said its identification could lead to drugs that disrupt the interaction, and thereby block or slow AD onset or progression. Many AD patients have brain lesions called amyloid plaques, which consist of protein fragments called amyloid‑beta. Small aggregates of amyloid‑beta are thought to contribute prominently to the degeneration of brain cells in AD. The discovery involves an amyloid beta fragment which is an APP intracellular domain or AICD. Scientists have known that AICD controls expression of genes that contribute to AD, but how it did so was unclear - - until now. “We discovered a protein molecule [MED12, an RNA polymerase II transcriptional Mediator] that communicates with AICD to turn on target genes,” said Thomas G. Boyer, Ph.D., professor of molecular medicine at the Health Science Center. “We hope to exploit this knowledge to identify compounds or drugs that can disrupt these signals, leading to a novel and effective treatment for this disease.” Eureka Alert 2/4/11 EMBO Reports advanced online publication 4 Feb. 2011; doi:1038/embor.2010.210, published by the European Molecular Biology Organization

Link Between Down Syndrome, AD Discovered - Researchers have discovered that the genetic mechanism which destroys brain cells is responsible for early development of AD in people with Down Syndrome and for development of AD in general population. This discovery by researchers at the University of British Columbia and Vancouver Coastal Health Research Institute provides a potential new target for drugs that could forestall dementia in people with either condition. The research, led by Dr. Weihong Song, Canada Research Chair in AD and a professor of psychiatry in the UBC Faculty of Medicine, found that excessive production of a protein, called Regulator of Calcineurin 1 (RCAN1), sets in motion a chain reaction that kills neurons in the hippocampus and cortex in people with Down Syndrome (DS) and AD. “Neuronal death is the primary reason for the memory loss and other cognitive impairments of AD, and it’s the main reason people with Down Syndrome develop AD long before most people, usually in their 30s, said Song, a member of the Brain Research Centre at UBC and the Vancouver Coastal Health Research Institute (VCHRI), and Director of Townsend Family Laboratories at UBC. People with DS have an extra copy of the gene that produces RCAN1, thus leading to its excess production. The resulting neuronal death ‑ with symptoms that mirror those of AD patients ‑ is one of the prime reasons for the shortened lifespan of people with DS. The research team discovered that some AD patients have similarly elevated levels of the RCAN1 protein, despite having two copies of the responsible gene. It’s still unknown why, though Song speculates that the gene’s overexpression might be triggered by stroke, hypertension or the presence of a neurotoxic protein, called beta amyloid, that typically collects into clumps in the brains of people with AD ‑ what he describes as a vicious cycle in which one destructive factor exacerbates another. The findings have been published online in the Journal of Biological Chemistry. ANI 1/13/11 published online before print Jan. 7, 2011 Journal of Biological Chemistry, doi:10.1074 jbc.M110.177519

Heavy Doses of DNA Data, With Few Side Effects - When companies tried selling consumers the results of personal DNA tests, worried doctors and assorted health experts rushed to the public’s rescue. What if the risk assessments were inaccurate or inconsistent? What if people misinterpreted the results and did something foolish? What if they were traumatized by learning they were at high risk for AD or breast cancer or another disease? The what‑ifs prompted New York State to ban the direct sale of the tests to consumers. Members of Congress denounced the tests as “snake oil,” and the Food and Drug Administration has recently threatened the companies with federal oversight. Members of a national advisory commission concluded that personal DNA testing needed to be carefully supervised by experts like themselves. But now, thanks to new research, there’s a less hypothetical question to consider: What if the would‑be guardians of the public underestimated the demand for their supervisory services? In two separate studies of genetic tests, researchers have found that people are not exactly desperate to be protected from information about their own bodies. Most people say they’ll pay for genetic tests even if the predictions are sometimes wrong, and most people don’t seem to be traumatized even when they receive bad news. “Up until now there’s been lots of speculation and what I’d call fear‑mongering about the impact of these tests, but now we have data,” says Dr. Eric Topol, the senior author of a report published last week in The New England Journal of Medicine. “We saw no evidence of anxiety or distress induced by the tests.” He and colleagues at the Scripps Translational Science Institute followed more than 2,000 people who had a genomewide scan by the Navigenics company. After providing saliva, they were given estimates of their genetic risk for more than 20 different conditions, including obesity, diabetes, rheumatoid arthritis, several forms of cancer, multiple sclerosis and AD. About six months after getting the test results, delivered in a 90‑page report, the typical person’s level of psychological anxiety was no higher than it had been before taking the test. Although they were offered sessions, at no cost, with genetic counselors who could interpret the results and allay their anxieties, only 10 percent of the people bothered to take advantage of the opportunity. They apparently didn’t feel overwhelmed by the information, and it didn’t seem to cause much rash behavior, either. In fact, the researchers were surprised to see how little effect it had. While about a quarter of the people discussed the results with their personal physicians, they generally did not change their diets or their exercise habits even when they’d been told these steps might lower some of their risks. “We had theorized there would be an improvement in lifestyle, but we saw no sign whatsoever,” Dr. Topol says. “Instead of turning inward and becoming activists about their health, they turned to medical screening. They had a significant increase in the intent to have a screening test, like a colonoscopy if they were at higher risk for colon cancer.” The people in the study chose on their own to pay for the tests - - about $225, a steep discount from the retail price at the time - - so they weren’t necessarily representative of the general population. But in another study, published in Health Economics, researchers surveyed a representative sample of nearly 1,500 people and found most people willing to take a test even if didn’t perfectly predict their risks for disease. About 70 percent of the respondents were willing to take even an imperfect test for genetic risks of AD, and more than three‑quarters were willing to take such tests for arthritis, breast cancer and prostate cancer. Most people also said they’d be willing to spend money out of their own pocket for the test, typically somewhere between $300 and $600. A minority of the respondents didn’t want the tests even if they were free, and explained that they didn’t want to live with the knowledge. But the rest attached much more value to the tests than have the experts who have been warning of the dangers. Traditionally, people have had to go through a doctor to get a test, which could mean paying a fee to the physician as well as to a licensed genetic counselor. Buying tests directly from a company like Navigenics or 23andMe can cut out hundreds of dollars in fees to the middlemen. To experts, the tests may seem unnecessary or wasteful when there’s nothing doctors can do to prevent the disease. But consumers have other reasons to want the results. They may find even bad news preferable to the anxious limbo of uncertainty; they may consider an imprecise test better than nothing at all. “We should recognize that consumers might reasonably want the information for nonmedical reasons,” Dr. Neumann says. “People value it for its own sake, and because they feel more in control of their lives.” The traditional structure of American medicine gives control to doctors and to centralized regulators who make treatment decisions for everyone. These genetic tests represent a different philosophy, and point toward a possible future with people taking more charge of their own care and seeking treatments customized to their bodies. “What we have today is population medicine at the 30,000‑foot level,” says Dr. Topol. “These tests are the beginning of a new way to individualize medicine. One of the most immediate benefits is being able to use the genetic knowledge to tweak the kind of drugs people take, like choosing among statins and beta blockers to minimize side effects.” That may be the self‑empowered future, but for now residents of New York still can’t be trusted to buy these tests directly. It’s paternalism run amok, says Lee Silver, a professor of molecular biology and of public policy at Princeton, who is developing another variety of genetic test for consumers. “It seems like a no‑brainer,” Dr. Silver says, “that any competent adult should be free to purchase an analysis of their own DNA as long as they have been informed in advance of what could potentially be revealed in the analysis. You should have access to information about your own genome without a permission slip from your doctor.” The paternalists argue that it’s still unclear how to interpret some of these genetic tests - - and it is, of course. But if you ban these tests, or effectively eliminate them for most people by imposing expensive and time‑consuming restrictions, how does that help the public? When it comes to knowing their own genetic risks, most people seem to prefer imperfect knowledge to perfect ignorance. By John Tierney NY Times 1/17/11 published online before print New England Journal of Medicine doi:10.1056/NEJMoa1011893

Caregivers

Jan’s Story: Love and Early‑Onset AD - Barry Petersen on How the Roadmap of Marriage Is Redrawn by a Disease Affecting Millions for Which There is No Cure. JAN'S STORY is a painful story to tell, particularly for the only man qualified to tell it . . . CBS’s own Barry Petersen. In the 1980s, Jan Chorlton was a promising television reporter. She went on to work for CNN, ABC, even “CBS Sunday Morning.” She was lively, daring, one of those people who celebrated life. But at only 40 years old, the subtle changes began . . . the lapses in memory. Five years ago, when she was 55, she received a diagnosis both awful and heartbreaking. Jan had AD. It has moved so fast that she is now in an assisted living facility, where this once bright, articulate woman struggles to make sense. It can be painful to watch. [This initial text (and the rest of the text ) from CBS Sunday Morning program on Jan. 23, 2011, and the video from the show is available at http://www.cbsnews.com/stories/2011/01/23/sunday/main7274728.shtml]

Testing

F.D.A. Sees Promise in AD Imaging Drug - An advisory committee to the Food and Drug Administration recommended unanimously 1/20/11 that the agency approve the first test - - a brain scan - - that can show the characteristic plaques of AD in the brain of a living person. The approval was contingent on radiologists agreeing on what the scans say and doctors being trained in how to read the scans. The F.D.A. usually follows advice from its advisory committees, and AD experts anticipated that the scans would be approved. The additional requirement would not be a big hurdle, said Dr. Daniel M. Skovronsky, chief executive of the company, Avid Radiopharmaceuticals, that applied to market the scans. “We don’t know exactly what F.D.A. will want,” Dr. Skovronsky said. ABut it should take months to generate this type of data, not years.” The committee vote is “a very positive thing,” said Maria Carrillo, senior director of medical and scientific relations for the Alzheimer’s Association. “This is nothing but a positive for our families.” Plaques are part of the criteria for having AD - - if a person with memory problems does not have plaques, that person does not have AD. But without the scan, the only way to know if plaques were present is to do an autopsy. AD specialists said they expected that if the scan were approved it would come into widespread use. “This is a big deal,” said Dr. Pierre N. Tariot, director of the memory disorders center at the Banner Alzheimer’s Institute in Phoenix. Asked if he would be using the scans, Dr. Tariot replied, “Absolutely.” Dr. Tariot is an investigator in studies by Avid, now a subsidiary of Eli Lilly & Company, and its competitors. The approval would be for a dye that homes in on plaque in the brain, making it visible on PET scans. Such scans would be especially valuable in a common and troubling situation - - trying to make a diagnosis when it is not clear whether a patient’s memory problems are a result of AD or something else. If a scan shows no plaque, the problems are not caused by AD and could be from tiny strokes or other diseases. If a person has AD, though, there is as yet no treatment that can slow or reverse the disease, although new drugs are being tested that are intended to reduce plaque. Nonetheless, doctors said, having a diagnosis is important for planning and for understanding what lies ahead. It also is important for family members to know because they are at increased risk if a mother or father, sister or brother has the disease. And people, they say, often want to know what is wrong with them, even when the news is bad. The panel’s vote “has moved us a monumental step forward,” said Dr. Reisa Sperling, adding that with the scans “we will not just be guessing clinically.” Dr. Sperling, director of the Center for Alzheimer’s Research and Treatment at Brigham and Women’s Hospital in Boston, is an unpaid consultant to Avid Radiopharmaceuticals, which makes the dye, and said she paid her own way to speak at the F.D.A. meeting in White Oak, Md. Some people have plaque without having AD, so if a scan shows plaque, doctors will have to use their clinical judgment, taking into account a patient’s symptoms, in deciding what the scan results mean, noted Dr. P. Murali Doraiswamy, an AD researcher at Duke University and a clinical investigator in the Avid trial. But if a scan shows no plaque, the situation is simpler, Dr. Doraiswamy said. It means the doctor should focus on other causes for the symptoms. “This technique will allow family doctors to feel confident ruling out AD,” he said. “Until now we had to guess whether someone had plaques.” By Gina Kolata NY Times 1/20/11

GE Healthcare Presents Flutemetamol Data for Detection of Amyloid Plaque Linked to AD - New clinical research data suggests that [18F] Flutemetamol could add value to current diagnostic tools used by physicians and provide accurate identification of beta amyloid plaques, considered to be a sign of neurodegeneration linked to AD. Flutemetamol, a GE Healthcare Positron Emission Tomography (PET) imaging agent currently in phase III development, is being studied to identify the uptake of beta amyloid via imaging of the brain tissue in live humans. Currently, beta amyloid is identified from brain samples acquired post‑mortem. Together with other GE Healthcare imaging modalities, this may help physicians detect amyloid deposition and assist in the detection and treatment of AD. “The wealth of data presented this year at the annual HAI meeting fundamentally supports the value Flutemetamol could bring to the AD community,” said Jonathan Allis, MI PET Segment Leader, GE Healthcare Medical Diagnostics. “The ability to make visual assessments of amyloid in AD patients may enable physicians to seek earlier, confirmed diagnosis of AD and make more informed care decisions.” Data highlights from five clinical abstracts from studies of Flutemetamol to be featured at the 5th Annual Human Amyloid Imaging (HAI) meeting in Miami, Florida suggest that: (1) The in vivo PET retention of Flutemetamol and PIB (Pittsburgh Compound B) have comparable patterns of binding; (2) There is a strong concordance between Flutemetamol amyloid imaging and cortical biopsy histopathology using both visual and quantitative methods; (3) The combination of Flutemetamol and structural MRI can provide information that could be useful in understanding other (non‑AD) neuro‑degenerative diseases and in identifying beta amyloid formation; and (4) Flutemetamol scans can be categorized with automated software suitable for use in clinical practice. “At GE Healthcare, our scientists and researchers remain fully committed to developing enhanced diagnostics tools that may help AD patients and their families get accurate information as early as possible,” said Pascale Witz, CEO, GE Healthcare Medical Diagnostics. GE Healthcare is taking a comprehensive approach to understanding AD through its ongoing research to uncover the causes, risks and physical effects of AD. The company’s global commitment to advance clinical knowledge and provide a variety of technologies to aid the fight in this epidemic may assist physicians in the acceleration of diagnosis and improvement of treatment decisions in all stages of the disease. PRNewswire 1/14/11

Prevention

How Does Hypertension Affect Memory? - No matter which way you look at it, hypertension (high blood pressure) is bad for your brain. Hypertension is an important risk factor for cognitive impairment and AD. And if you are diagnosed with AD, hypertension may hasten cognitive decline. What's more, hypertension is the most significant risk factor for strokes, which can lead to dementia by destroying brain tissue. This form of dementia, called vascular dementia, is the second most common type after AD. It is most frequently caused by chronic hypertension, which can result in a series of small strokes. It is the accumulation of damage caused by multiple little strokes that commonly causes vascular dementia. Of course, hypertension can also cause a significant single stroke that can damage a large area of the brain and also cause dementia. How does high blood pressure impact memory? The most obvious way is via stroke. High blood pressure damages blood vessels that carry blood to the brain, and this damage leads to the buildup of plaques, accumulation of inflammatory cells, cholesterol, and other tissue products within blood vessels. When one of these plaques ruptures, it travels through an artery and eventually gets lodged in a place where the diameter of the plaque is larger than the diameter of the blood vessels. This causes a blood clot to form at that spot. If the clot completely cuts off blood supply to brain cells responsible for memory or other cognitive functions, the cells die. The death of these cells then leads to impairments in thinking. About one third of people who suffer a stroke develop serious cognitive problems that interfere with their ability to perform daily activities. Another way that blood pressure affects cognition is its effect on the white matter, the portion of the brain that lies below the surface. White matter is composed of nerve fibers that conduct messages between brain cells and a surrounding myelin sheath that acts as insulation and improves its function as a conduit of electrical and chemical information. Scans show that people with hypertension often have white matter abnormalities, probably because the hypertension produces impaired blood flow that starves nerve fibers of needed oxygen and nutrients. This causes the myelin sheath to decay and results in “demyelination,” which shows up on magnetic resonance imaging (MRI) scans as bright white spots known as white matter hyperintensities (WMHs) or age‑related white matter changes (ARWMCs). Research shows that the greater the amount of white matter changes, the higher the risk of dementia. Reduced blood flow from hypertension can also directly affect cells in such areas of the brain as the hippocampus, which is involved in memory. When these cells do not get enough nutrients and oxygen, they cannot function properly. If this causes the death of cells, those areas of the brain may shrink. In addition, blood flow reduction leads to less efficient removal of waste product from brain tissue. Last, hypertension may compromise the blood‑brain barrier, a relatively impenetrable shield that surrounds the brain. This, in turn, allows toxic substances such as beta‑amyloid (a sticky protein associated with AD) to enter and accumulate in the brain. By Johns Hopkins Health Alert posted in Memory on 1/17/11

Bioidentical Hormones May Help Prevent AD - AD is on the rise in America, but new evidence reveals there is hope. The Shriver Report, published by Maria Shriver with the backing of the Alzheimer’s Association, took an up close and disturbing look at the dreaded disease's impact on women ‑‑ and estrogen’s possible role in preventing it. BodyLogicMD bioidentical hormone physicians know that a woman’s risk of AD increases after menopause. As the largest national network of expert physicians who deal primarily in preventive medicine, they help tens of thousands of women (and men) prevent disease by balancing hormones using bioidentical hormone replacement therapy (BHRT). Scientists report that research is showing some clear connections between declining estrogen and a number of diseases, including AD. The secret may lie in a protein called insulin‑degrading enzyme (IDE). Discovered by Liqin Zhao, Ph.D. and her colleagues at the University of Southern California, IDE degrades beta‑amyloid, a protein fragment strongly associated with AD. What’s more, the researchers also discovered that a decreased level of estradiol, which happens during menopause, reduces the expression of IDE. That, in turn, may reduce the ability of the brain to dispose of beta‑ amyloid. Zhao and her colleagues have proposed further study on how estrogen regulation can influence AD risk, but clear connections have already been proven. “There is significant research into how effective estrogen therapy works to prevent AD,” says Dr. Jennifer Landa, Chief Medical Officer of BodyLogicMD. “Some studies have shown a decrease of AD with estrogen therapy, and researchers are starting to realize that timing of the hormone therapy may have an impact.” Landa points to an article that reviews over a decade of findings from scientific research exploring the HRT (hormone replacement therapy) timing issue. The article, entitled, “Potential role of estrogen in the pathobiology and prevention of AD,” [published at American Journal of Translational Research 2009; 1(2): 131–147] concludes that, when estrogen therapy begins at the onset of menopause, it benefits the brain and actually decreases a women’s risk of developing AD later in life. “When you start hormone therapy in your mid to late 40’s - - basically at the onset of estrogen decline - - you have the most prevention of AD in the long run,” Landa says. “In women who started estrogen therapy at 60 or 65, there was not anywhere near the dramatic prevention effect that was demonstrated in women who were in the late 40s and early 50s.” The research shows that the dosage of HRT is also important. The key is to use naturally occurring estrogen rather than synthetic preparations. Estradiol, the hormone that is showing all this promise, is a potent, naturally occurring estrogen. Studies show that synthetic estrogens may not offer the same benefits as natural estradiol. In fact, Synthetic hormones act as toxins because their chemical makeup cannot be metabolized properly. “Bioidentical estrogen applied through the skin gets much better results in the prevention of AD is than synthetic estrogen taken by mouth,” Landa says. “There is also some strong evidence for bioidentical progesterone. Progesterone protects the brain. The natural form of progesterone has benefits for the brain whereas the synthetic progesterone is actually worse for the brain. In both cases, bioidentical hormones are the best approach.” PR 1/14/11

Dementia Linked to Abstinence, Excess Drinking - When it comes to drinking and brain health, scientists have found it’s a case of darned if you do, darned if you don’t. A Finnish study published in the December issue of the Journal of Alzheimer’s Disease found that people who either abstain from drinking or drink heavily are at greater risk of dementia later in life, according to a press release issued 1/11/11 by the journal. The scientists, led by Jyri Virta of the University of Turku, Finland, found that the pattern of drinking matters as well as the amount of alcohol consumed. When people had the equivalent of a bottle of wine at one sitting just once a month and controlled their alcohol intake the rest of the time, they still raised their risk of dementia, the researchers said. Binge drinking doubled the risk, the study found. Passing out after heavy drinking on a single occasion was enough to raise the risk of cognitive impairment, according to the study. The research relied on the Finnish twin cohort, a study group established in 1974 to explore links between the environment and chronic diseases. “Our finding is significant as the changes typical of AD ‑ the most common dementia syndrome ‑ are thought to start appearing two to three decades before clinical manifestation and therefore identification of early risk factors is imperative,” Virta said in the statement. Those who abstained from alcohol were found to be more at risk of cognitive impairment than moderate drinkers. The finding adds to evidence that abstaining can raise some health risks. Previous research found that non‑drinkers were four times more likely to develop rheumatoid arthritis than moderate drinkers. The researchers relied on questionnaires in which people rated their own drinking habits, which may have skewed the results. Some of the benefit to moderate drinkers may be explained by the fact that people who drink in moderation tend to lead healthier lives overall, Virta said. By Marthe Fourcade Bloomberg News 1/12/11 Journal of Alzheimer’s Disease 2010, 22(3), pp 939-948

Other Items

Researchers Close in on Causes of AD - We are getting closer to understanding the causes of AD, a devastating condition first described by Alois Alzheimer at the beginning of the 20th century. AD develops when clumps of amyloid‑beta protein and tangles of threads in nerve cells caused by the protein tau accumulate in the brain as plaques. There is not a direct correlation between the number of these plaques in the brain and the degree of dementia. A number of genes have been implicated in the development of AD, suggesting that, like diabetes, a number of different conditions may lead to a similar end point. Amyloid‑beta is an interesting protein. We have recently shown that in low concentrations, it actually improves memory. However, too much amyloid‑beta is toxic. Excessive accumulation of amyloid‑beta is caused by its overproduction and the body’s failure to clear it from the brain. Many years ago we showed that amyloid‑beta produces memory disturbances when injected directly into the brain. This protein causes an increase in free radicals that eventually leads to the death of nerves. Amyloid‑beta also damages the blood‑brain barrier, decreasing the ability of excess amyloid‑beta to escape the brain. It also turns on a process that leads to the formation of cell‑killing neurofibrillary tangles. Eventually, the accumulation is deposited in clumps in the brain, producing the amyloid plaques. At St. Louis University, we have developed a number of compounds, called antisenses, which block the production of the protein that makes amyloid‑beta protein. We have shown in mice that these compounds improve memory, decrease brain damage due to free radicals and improve the ability for the amyloid‑beta to escape from the brain. This area of research could hold promise as we continue to explore AD. By Dr. John Morley www.STLtoday.com 1/19/11

Course Correction Needed For AD Therapies, Experts Warn - Misaligned research, medical challenges and harsh economics are thwarting efforts to slow the destructive course of AD in the United States, according to a trio of nationally regarded AD researchers writing a “Perspective” in the 1/27/11 issue of the journal Neuron. The foremost obstacle is that the most promising preventive strategies are being tested in patients firmly in the grip of AD ‑ the ones least likely to be helped. The approach would be similar to testing statins ‑ drugs widely used to prevent heart disease ‑ in patients who are already in cardiac arrest, according to Dr. Todd Golde, director of the UF College of Medicine=s Center for Translational Research in Neurodegenerative Disease. With Dr. Edward Koo of the University of California, San Diego, and Dr. Lon S. Schneider of the Keck School of Medicine at the University of Southern California, Golde pointed to a lack of alignment between studies in human volunteers, which focus on treatment, and preclinical laboratory studies, which are aimed at prevention. “If we do the right types of clinical studies, we have the ability to move toward prevention, which would have a huge impact on this disease,” said Golde, a professor in the department of neuroscience at UF’s McKnight Brain Institute. “But we have to overcome our ‘prevention versus treatment’ dilemma. We already have more than 5 million people affected, and half of people in nursing homes, or more, have AD. As society ages, we are just going to continue to see AD drain the economy and the quality of human life.” Without medical breakthroughs, a projected 7.7 million patients in the U.S. will have AD by 2030, according to the Alzheimer’s Association. That number will grow to between 11 million and 16 million by 2050. Researchers say solving the treatment‑prevention problem will require the development of biomarkers ‑ - substances in the body that point to a disease ‑ - to identify patients before they show the symptoms associated with AD. With biomarkers, it may be possible to test AD drugs in pre‑symptomatic volunteers. “The dilemma is, can you treat people as if they have AD if they do not?” said Koo, co‑director of the Shiley‑Marcos AD Research Center at UC San Diego. “That’s the catch‑22.” Most proposed AD therapies target so‑called “brain plaques” ‑ proteins that clog the spaces between brain cells. Experimental models suggest that therapies targeting these proteins, known as amyloid beta‑peptide, may be effective. Approximately 90 experimental therapies intended to slow or stop the progression of the disease are under way, many of them targeting AD hallmark brain plaques, according to the Alzheimer’s Association. The problem is the strategies are likely to be much less effective when tested in patients who are already experiencing confusion, memory loss or personality changes. But simply placing more emphasis on prevention has its own complications, the researchers say. To date, no drug candidates have been found to be effective at prevention or suitably safe enough for a patient to take for a lifetime. And even if such a drug were found, clinical testing would take well more than a decade and cost pharmaceutical companies millions of dollars. If the drug were successful ‑ and there is no guarantee ‑ the company’s patent would expire before it had a chance to recover its expenses.“It is important to find ways to ensure that the commercial sector will invest in prevention trials that may take 10 years or more to complete,” Koo said. The authors said they are not the first to point out misalignment between clinical and preclinical studies, or summarize current therapeutics, or critique how trials are conducted. But by presenting the issues in a comprehensive way, they hope to spur discussion among members of the research community, pharmaceutical companies and regulatory bodies to address the challenges. “What we’ve done is collect those points and suggest what has to happen to help patients who are suffering from this awful disease,” Golde said. Medical News Today 1/27/11 Neuron, 69(2), 203-213, 27 Jan. 2011

Protein IGF-II Is Found to Boost Memory - The hunt for a substance that can improve memory took a promising turn 1/26/11, as researchers said they had found a method that appears to reduce forgetting in rats. According to a study published in the journal Nature, scientists from Mount Sinai School of Medicine in New York showed for the first time that a molecule that occurs naturally in the human brain during memory formation appeared to help rats enhance the strength and duration of some types of memories. Researchers said that when the substance - - known as IGF‑II, a protein like molecule important for cell growth and development as well as tissue repair - - was blocked from the brain, the rats didn’t remember what they had learned. The findings are notable in part because they showed improvement in an area of memory known as declarative memory - - the ability to remember places, facts and things. Declarative memory is affected in AD and other forms of dementia, and researchers have long sought ways to improve or preserve it. It is too early to say whether IGF‑II will be useful in humans, but the substance may hold more promise than molecules that have been studied up to now, according to Elizabeth Phelps, a cognitive neuroscientist at New York University who studies human learning and memory. Dr. Phelps, who wasn’t involved in the study, called the Nature research “rigorous” and thoroughly conducted. One advantage of IGF‑II is that it can cross the blood‑brain barrier, so it could potentially be administered through the bloodstream or as a vapor through the nose, rather than injected directly into the brain. And because it exists in the body already, it’s unlikely to be toxic. However, researchers will watch for unwanted effects on other cells in the body, said Cristina Alberini, a neuroscience professor at Mount Sinai and the senior author of the paper. Certain proteins and molecules are needed to build and strengthen connections between nerve cells in the brain to form new long‑term memories, and IGF‑II appears to be one of those molecules. But more research is needed, according to Dr. Alberini. “The more we know, the more we’re going to uncover what are the steps that make memory strong,” she said. “Then we’ll get ideas for other [molecular] targets.” In the study, the rats were placed in a two-compartment cage where they would receive a mild foot shock at one end. They quickly learned to avoid that area. Some rats were then given an injection of IGF‑II, in a part of their brain called the hippocampus. Even weeks later, rats that had received the IGF‑II exhibited greater avoidance of the location than rats that had a control injection of another growth factor or saline solution. The effect was seen only in certain parts of the brain. IGF‑II didn’t appear to improve memory in the amygdala, which deals more with memories of emotional reactions like fear. The next step is to administer IGF‑II to the entire body to see if it can produce the same memory-boosting effects as direct injection into brain regions, Dr. Alberini said. By Shirley S. Wang Wall Street Journal 1/27/11 Nature 469, 491-497 (27 Jan. 2011)

Did Reagan Have AD in Office? When Ron Regan, President Regan’s son, suggests in his new book that Ronald Reagan may have suffered from AD in office, I have to assume that he’s being as objective as he always was back in the days when we became friends. I can only say now, as I wrote in 1999, that I never saw any signs of dementia during the years that I observed Reagan in action, from May 1985 through his departure from the White House in January 1989. Old age I saw; extreme fatigue, often; diplomatic occasions when his genius for telling the right joke at the right time deserted him; important meetings during which he read from cue cards like an obedient schoolboy. During one unhappy period, when the Iran-contra scandal coincided with prostate problems, the president was so withdrawn and confused that papers were surreptitiously drawn up by staffers concerned that he might have to be declared “disoriented” and disabled under the 25th Amendment. But thereupon, Ronald Reagan exhibited astonishing powers of recovery. Whenever there was a crisis that taxed his leadership, he snapped to and became authoritative. I quote from my notes for March 2, 1987, as reproduced in Dutch: “Before lunch in the Cabinet Room today, [incoming chief of staff Howard] Baker and his aides position their chairs so that they can check RR’s behavior from all angles. In walks [yesterday’s] depressed, somnolent, prostatically challenged President, moving with his usual fluid grace, tall, beaming, apple‑cheeked, amethyst‑eyed, tailored, giving off waves of benign power. Even before they sit down they realize ‘the Gipper is back’ YThe Twenty‑Fifth Amendment is shelved.” In further proof that Reagan retained his smarts through the end of his presidency, I would cite the diary entries he patiently made every night until he left office. I can testify that although they were mostly boring, they were composed in sequential sentences as lucid as the entries he penned in 1981. By Edmund Morris Newsweek 1/23/11 Morris is the author of Dutch: A Memoir of Ronald Reagan.

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Ron Reagan Clears Up AD Claim, Again – It’s hard to visit Washington without addressing a recent political controversy, so Ron Reagan did that just when appearing at the Jefferson Hotel on 1/24/11 for a fete celebrating his new book “My Father at 100.” Reagan recently got roasted for suggesting that his father had AD while in the White House. He explained to partygoers and to former Newsweek editor Jon Meacham, who was interviewing him in front of the roomful of guests, that his point was more subtle. “I admit that at times, on occasions during the presidency, I did think that I noticed something that seemed just slightly off with him and I’ve described it as watching a TV that shifts out of focus ever so slightly and then snaps back, I didn’t know what it was at the time,” he explained. “Nowhere in the book do I diagnose him with AD while he was in office, I just admit that it was one of the things I worried about.” By Nikki Schwab and Katy Adams Examiner Staff Writers 1/25/11

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