Alzheimer Related News Items

News as of 2/8/09

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Top Items

Gene Variant May Hike Women’s Risk of AD - Scientists have discovered a gene variant on the X chromosome that appears to increase the risk of developing AD. The risk was most pronounced in women with the variant on both X chromosomes, although both women and men with just one variant of the gene were also at greater risk. “What you have in a nutshell is the first study showing a gene on the X chromosome and the first sex-specific effect [for AD],” said Dr. Steven Younkin, senior author of the paper published online Jan. 11 in the journal Nature Genetics. “It does not mean women are at increased risk for AD. Although the presence of the mutation offers strong evidence of a heightened risk, further research needs to be done to determine how big of a risk,” added Younkin, who is the George M. Eisenberg professor of neuroscience at the Mayo Clinic College of Medicine in Jacksonville, Fla. Dr. Anton Porsteinsson, director of the AD Care, Research and Education Program and the Memory Disorders Clinic at the University of Rochester School of Medicine, called the finding intriguing. “To me, the fact that it’s X-linked is intriguing because of the fact that there are more women than men with AD,” he said. According to background information in the paper, late-onset AD is the most common cause of dementia in older people, affecting about 10 percent of those aged 65 or over. A mutation in the APOE 4 gene is the only genetic risk factor that has been “solidly” linked to the risk of late-onset AD, Porsteinsson said.Other genes have been linked to early onset disease. “The effort to find additional genetic variants has been difficult,” Younkin said. For the study, Younkin and his colleagues scanned hundreds of thousands of genes in 844 people with AD and 1,255 healthy people who served as “controls.” There was nothing genetic in the first pass that the researchers could say unequivocally was associated with AD. But a second pass, this one on even more patients and controls, uncovered a strong association between a mutation on the PCDH11X gene and AD. “It was significant enough to convince us we had something real,” Younkin said. The findings were given added weight because the researchers examined autopsies on participants who had died to confirm the diagnosis of AD. Clinical diagnoses are about 90 percent accurate anyway, Porsteinsson said. Women with two copies of the gene had a 75 percent increased risk for AD. Women with only one copy of the gene had a 26 percent increased risk, while men with one copy had an 18 percent increased risk. The gene is part of a family of genes linked with the nervous system and are involved in cell adhesion. “We’re basically looking at a finding that seems to encode a gene that has something to do with central nervous system development,” Porsteinsson said. “And AD is ultimately a central nervous system disease.” It’s unclear how the gene may actually work to increase the risk of AD. Once that is known, however, the search for new treatments could be accelerated, the researchers said. “It’s trite but true - - the reason we all search for genes is that every one opens a door to identify people at risk, and every one opens a door to identify potential therapies if we can understand how it works,” Younkin said. But first, these findings need to be replicated. “This just means a lot of work ahead,” Porsteinsson said. By Amanda Gardner Health Day Reporter 1/12/09 Nature Genetics 41, 191-198 (2009)

Insulin Protects Brain from AD - US Study - Insulin appears to shield the brain from toxic proteins associated with AD, U.S. researchers said on 2/2/09, supporting a theory thatAD may be a third form of diabetes. And they said GlaxoSmithKline’s diabetes drug Avandia, or rosiglitazone, which increases sensitivity to insulin, appeared to enhance this protective effect. “Ourresults demonstrate that bolstering insulin signaling can protect neurons from harm,” William Klein of Northwestern University, whose study appears in the Proceedings of the National Academy of Sciences, said in a statement. Klein saidthe findings support a new idea that AD is a type of diabetes of the brain. “In Type 1 diabetes, your pancreas isn’t making insulin. In Type 2 diabetes, your tissues are insensitive to insulin because of problems in the insulin receptor. Type 3 is where that insulin receptor problem is localized in the brain,” Klein said in a telephone interview. In some people, this can occur with age, he said. “As you get older, some individuals start to have less effective insulin signaling, including in the brain,” he said, making the brain more vulnerable to toxins that cause AD. Large sticky plaques of amyloid beta protein are a hallmark of AD, which causes memory loss, confusion, the inability to care for oneself and eventually death. Recent studies by Klein and others have suggested that short strands of the protein, known as amyloid beta-derived diffusible ligands or ADDLs, attack memory-forming brain cells, causing memory loss. Klein and colleagues treated rat nerve cells with insulin. “It blocked all of the effects of ADDLs,” Klein said. The effect was amplified when they added the drug rosiglitazone, which increases insulin sensitivity. Several studies have found that diabetics have a higher risk of getting AD than the general population. Last July, researchers at Mount Sinai Medical Center in New York reported that diabetics who take insulin plus a diabetes pill have a lower risk of developing AD than diabetics who only take insulin. That study included a range of anti-diabetic medications, including an older pill known as a sulfonylurea. Klein said the findings suggest that measures to protect people from diabetes -- including a healthy diet and exercise -- are also important for avoiding AD. By Julie Steenhuysen Reuters 2/2/09 Proceedings of the National Academy of Sciences published online before print February 2, 2009 doi:10.1073/pnas.0809158106

Drugs

Pfizer Gambles on Building an AD Empire - With a 1/26/09 $68 billion bid to acquire Wyeth, pharmaceutical giant Pfizer is setting itself up to potentially dominate the AD treatment market for years to come. But in making such a big bet on one of society’s most pressing unmet medical needs, the pharmaceutical giant may also face increased government scrutiny and possibly some resistance from its key partners. Pfizer and the Japanese drug maker Eisai, currently co-market Aricept, the leading AD drug today with worldwide sales of more than $2 billion. But Aricept loses patent protection at the end of next year, which is one reason why Pfizer has decided to invest heavily in new AD drug research. Last September, Pfizer acquired worldwide commercial rights to Dimebon, an experimental AD drug currently in phase III studies. Pfizer paid Medivation, Dimebon’s owner, $225 million up front for the rights, making it one of the largest drug partnership deals of 2008. Pfizer also has four AD drugs in its own pipeline, most of which are in the early stages of clinical trials. This includes an experimental AD drug acquired in 2006 when Pfizer bought privately held Rinat Neuroscience. Wyeth has 10 AD drugs in clinical trials, both internally and through partnerships, the most important of which is with Irish drug maker Elan. The two companies share development efforts and marketing rights to bapineuzumab, which is being studied in four phase III clinical trials. If the acquisition of Wyeth announced 1/26/09 closes as is, Pfizer would boost its AD drug pipeline from five drugs in clinical trials to 15, including two of the four drugs currently in pivotal phase III studies. (Eli Lilly and Baxter own the other two phase III AD drugs.) Any new drug that could potentially stop or even reverse the loss of memory or cognitive decline that makes AD such a devastating disease would be a mega-blockbuster. Actual sales estimates vary and are conditional on the efficacy and safety profile of the drug, but it’s not out of bounds to forecast a groundbreaking AD drug achieving peak sales of well over $10 billion, perhaps even $20 billion a year. By Adam Feuerstein The Street 1/27/09

How is AD Treated? - In Great Britian the National Institute for Health and Clinical Excellence (NICE), the government body that advises doctors about which treatments should be available on the NHS, has published guidance for doctors on certain drugs used to treat AD. The drugs are donepezil (in the US sold as Aricept), galantamine (in the US sold as Razadyne) and rivastigmine (in the US sold as Exelon). * The drug treatment should be started by a specialist doctor, but may be continued by the patient’s GP. * People who are started on the drug should be checked every six months, usually by a team of specialists. * The check-up should usually include a test called the Mini-Mental State Examination (MMSE). Doctors should also look at how the patient behaves and how well he or she copes with daily life. * Doctors should find out the caregiver’s view of the patient’s condition at the start of treatment and at check-ups. * The drug should be stopped if it is not working, or if the person’s score on the MMSE falls below 10. In some cases, the Mini-Mental State Examination may not be helpful, for example if the person has hearing difficulties or finds speaking difficult because of a stroke. Doctors are advised to use other methods to judge how severe the person’s disease is in those cases. The guidance also says that a fourth drug, called memantine (sold in the US as Nemenda) should not be prescribed unless it is being used in a clinical trial. However, patients already taking donepezil, galantimine or rivastigmine for mild AD, or memantine for moderate or severe AD, should be able to carry on having treatment. Treatment should continue until the patient, his or her carer, or a specialist doctor decide it is the right time to stop. The Guardian News and Media and British Medical Journal The Report is National Institute for Health and Clinical Excellence. Donepezil, galantamine, rivastigmine (review) and memantine for the treatment of AD. September 2007. Technology appraisal guidance 111. Available at http://guidance.nice.org.uk/ta111(accessed on 7 October 2008).

Stroke Drug Might Be a Memory-Booster - Fasudil, a drug used for a decade to safely treat people with vascular problems in the brain, appears to improve some learning and memory abilities in middle-aged rats, a new study says. The findings, published in the February issue of Behavioral Neuroscience, give researchers hope of finding a way to combat the normal decrease in cognitive function experienced by humans as they age. Rats injected with hydroxyfasudil, the active ingredient in Fasudil, performed better on a maze that tested their spatial learning and working memory than those given a placebo. The rodents given higher doses of the drug did better than those given a lower dose. “Fasudil shows great promise as a cognitive enhancer during aging,” study co-author Heather Bimonte-Nelson, of Arizona Alzheimer’s Consortium and Arizona State University, said in a news release issued by the journal’s publisher. “The effects in our aging animal model were robust, showing enhancements in both learning and two measures of memory. The possibility that these findings may translate to benefits to human brain health and function is very exciting.” Fasudil is often prescribed to help stroke victims recover by treating vascular problems in the brain. The drug dilates blood vessels to help blood flow. Health Day News 2/2/09 Behavioral Neuroscience vol 123(1), Feb 2009, 218-223

Advertising Veils Science, True Impact of AD - Advertisements promoting drugs to thwart AD make the disease appear to be merely a manageable setback. Along with, perhaps, hemorrhoids or a winter cold. On the television screen, a wife nuzzles her husband, the lovable dementia patient. In another tender moment this romantic couple, joined by friends, motors toward a lakeside resort. Life here is picture-perfect.To words leap to mind: 1) dishonest and 2) harmful. Plainly, the intent is to sell drugs. Prescription medicines that medical science confirms will not alter the inevitable outcome -- death. Here is what we do understand of the dreaded AD: the “mind-robbing” anomaly, a type of dementia, is without proven cause or known cure . . . and it’s always fatal. AD follows a downward progression lasting, on average, seven to 10 years. Now, as a cheerleader for the aging, I am uncomfortable in the role of negativist. However, where AD is the issue, I am a zealot after the truth, and I’m not alone. Author Charles P. Pierce, whose father was an AD victim, writes how “the great enemy of this disease is the truth. Emotional truth . . . even scientific truth.” In Hard To Forget (Random House; 2000), Pierce charges that AD “festers in euphemism” and “wounds through politesse” (Examples: Grandpa is a little “off” today, or Grandpa has some hardening of the arteries, that’s all.) Pierce further states, “If all the world is a stage, then AD is a burlesque magic castle, with trapdoors and mirrored hallways, and staunch absurdity.” Turn next to author Dede Bonner, Ph.D., writing in The 10 Best Questions for Living with AD (A Fireside Book; 2008): “There is no known treatment for AD that either prevents or reverses the progression of brain cell death.” Alleged improvement always is minimal -- and temporary. In one sense, it’s false hope, a rope thrown to a drowning man. Ms. Bonner suggests that “doing nothing” is a viable option, especially when cost is a consideration. Meanwhile, an Associated Press story in early January told of a study concluding that “AD drugs double the risk of death.” The reference was to anti-psychotic medications, used heavily to treat elderly residents in nursing homes and hospitals. The study’s lead author writes, “For the vast majority of AD patients, taking these drugs is probably not a worthwhile risk.” Finally, comfort, albeit small, comes in the knowledge the world’s most brilliant neuroscientists are hard at work. AD one day will be thwarted, surely delayed, and perhaps cured. Just not any time soon, no matter what those television images portray. By Bard Lindeman Orlando Sentinel 2/1/09

Genes & Genetic Issues

AD: in Your Genes? - According to the National Institutes of Health, three-quarters of those who develop AD have no family history of the disease; butfor the rest, researchers say several genes may contribute to their disorder. AD is an irreversible and progressive condition. It is characterized by inflammation and buildup of amyloid plaque and neurofibrillary tangles in the brain, leading to nerve cell damage. There are two types ofAD:early-onset and late-onset, both of which have genetic links. LATE-ONSET: THE GENETIC LINK: According to the Alzheimer’s Association, late-onset is the most common form of AD and occurs in individuals 65 or older.The most common gene linked to this type of AD is apolipoprotein E (APOE). There are three APOE variations of the gene. APOE e2 occurs least often and appears to reduce the risk of AD. APOE e3 is the most common variant and is not believed to affect a person’s risk of getting the disease. APOE e4, however, appears to contribute to AD. A person may carry two different types of the APOE gene, inheriting one from their mother and another from their father. Therefore, a person can have two APOE e4 genes, which puts them at an even greater risk of developing AD. Other studies link late-onsetAD to the gene SORL1. One study shows a variation of SORL1 is associated with a three times greater risk of developing AD in Dominican families. Certain variations of the SORL1 increase the production of amyloid-beta, which contributes to the formation of amyloid plaques in the brain. No specific mutation has been identified so far, but researchers say a potential treatment could be to target the gene and increase the production of the SORL1 receptor. In June of 2008, researchers discovered another gene that increases the risk of late-onset AD. Having one copy of calcium homeostasis modulator 1 (CALHM1) increases the chance of developing late-onset AD by 44 percent, while having two copies increases it by 77 percent. According to Philippe Marambaud, Ph.D., study author and an assistant professor at The Feinstein Institute for Medical Research in Manhasset, N.Y., roughly a quarter of the population has one copy of the gene.The CALHM1 gene regulates specific calcium channels in the brain, which permit electrically charged calcium molecules to enter cells and trigger production of beta amyloid proteins. Drugs that target calcium channels currently exist; however, none are designed to target the channels the CALHM1 gene controls. EARLY-ONSET: THE GENETIC LINK:Less than 10 percent of AD sufferers have the early-onset variety, of which three genes have been linked to. Inheriting just one of these mutated genes almost guarantees the disease will strike before you turn 65. Amyloid precursor protein (APP), presenilin 1 (PS1) and presenilin 2 (PS2) all cause too much amyloid-beta peptide to be produced in the brain. Roughly half of early-onset patients don’t present any of these three genetic abnormalities, which means the aggressive version of AD may be caused by other genetic mutations that haven’t been discovered. Reported by Roxanne Stein www.wptv.com2/5/09

Obama Wrongly Claims Embryonic Stem Cell Research Will Cure AD in this Editorial by Steven Ertelt - Over the weekend of 1/19/09, incoming president Barack Obama talked about how he’ll make Congress overturn President Bush’s stem cell research policy. In his comments, Obama wrongly indicated embryonic stem cell research can cure AD even though scientists say that’s not the case. In his comments to CNN, he said that “on embryonic stem cell research ... there is a moral and ethical mechanism to ensure that people with Parkinson’s disease and AD can actually find potentially some hope out there.” However,leading scientists say that embryonic stem cell research will likely never yield a cure for AD. “AD is a more global disease, with an effect on numerous kinds of cells,” Steve Stice, a stem cell researcher at the University of Georgia, told the Atlanta Journal-Constitution newspaper previously. “That makes it much more difficult for a cell therapy to be effective.” In a patient afflicted with AD, clumps of protein called amyloid build up within the brain and begin attacking various types of cells and the connections between cells. Other researchers agree that potential cures, if they come about, won’t happen soon. “I think the chance of doing repairs to AD brains by putting in stem cells is small,” stem cell researcher Michael Shelanski, of Columbia University Medical Center in New York, told the Washington Post in June 2004. “I personally think we’re going to get other therapies for AD a lot sooner.” Huntington Potter, a brain researcher at the University of South Florida in Tampa, also told the paper: “The complex architecture of the brain, the fact that it’s a diffuse disease with neuronal loss in numerous places and with synaptic loss, all this is a problem.” Marilyn Albert previously told the Associated Press, “I just think everybody feels there are higher priorities for seeking effective treatments for AD and for identifying preventive strategies.” Albert, a Johns Hopkins University researcher who chairs the Medical and Scientific Advisory Council of the Alzheimer’s Association, says there are more promising efforts to treat the disease than waiting on the decades it could take to see results from embryonic stem cells. Marcelle Morrison-Bogorad, associate director of the National Institute on Aging’s neuroscience and neuropsychology of aging program, concurs. “There’s an awful lot going on right now that perhaps holds a little bit more immediate promise for trying to slow the disease, or even cut off its development,” Morrison-Bogorad explained. By Steven Ertelt LifeNews.com Editor 1/19/09

Caregivers

Vision Problems and AD - A recent study of visually-impaired nursing home residents living with AD found that nearly one-third of them are not getting their vision corrected. This can aggravate symptoms of dementia, according to the study, which is published in the July issue of the Journal of the American Medical Director’s Association. “Many nursing home residents are losing out on stimulation,” said James M. Koch, MD, of St. Louis University. “They may not be able to see the television, read books or interact appropriately.” This loss of visual stimulation may cause disorientation, limit mobility and increase the risk of falls, added Koch, who found that 25 of the 80 residents he and colleagues studied lost their eyeglasses, damaged them or didn’t wear them because the prescription expired. “These patients may become so sensory deprived that they are virtually shut off from the outside world,” Koch continued. A cohort study of 85 patients with AD residing within two private, skilled nursing homes in the St. Louis area (only 80 were visually impaired), its findings were determined through patient, family and staff interviews, as well as considering each patient’s visual history and use of eyewear before and after admission. Researchers report that of the 25 visually impaired residents not wearing their glasses, nine were too cognitively impaired to ask for them, eight had damaged or misplaced them and eight had prescriptions that were too weak. Three specific recommendations to address this problem were offered by researchers: 1.Label eyewear to provide rapid identification in the event of misplacement. 2.Recommend a spare pair of glasses be made in case the current pair is lost or damaged. 3. Ensure that all residents have annual or biannual eye exams. Advance for LPNs 1/19/09 The citation to the July issue of the Journal of the American Medical Director’s Association is not correct.

Testing

Researchers Track Dementia Warning Signs with RFID - Researchers from the University of South Florida are experimenting with a Radio Frequency Identification Technology (RFID) solution to detect early warning signs of dementia. The study uses RFID-enabled bracelets to track the walking patterns of patients, looking for telltale signals of cognitive decline. Current treatments for AD and other forms of dementia involve medications that can only slow, not reverse, the progression of the disease; so the earlier the onset of dementia is detected, the better. The most common forms of testing for dementia, such as a series of questions administered by a doctor, may not catch the issue as early as is preferable. Researchers are exploring a number of possible early detection methods, including brain scans or checking for biomarkers. The experimental RFID solution can be used in a natural setting and in a relatively unobtrusive manner. In the study,residents in assisted-living homes wear RFID-enabled wristbands. Receivers placed around the home track the band’s RFID signals, creating a 3D map of the wearer’s movements, to an accuracy of 10 inches. Researchers can examine the records for signs of cognitive decline, including a tendency to wander, veer suddenly, or pause repeatedly. RFID News 2/3/09

Prevention - Remember: What is good for the heart is good for the brain

Apple Juice Can Delay Onset Of AD, Study Suggests - A growing body of evidence demonstrates that we can take steps to delay age-related cognitive decline, including in some cases that which accompanies AD, according to a study published in the Journal of Alzheimer’s Disease. Thomas B. Shea, PhD, of the Center for Cellular Neurobiology; Neurodegeneration Research University of Massachusetts, Lowell and his research team have carried out a number of laboratory studies demonstrating that drinking apple juice helped mice perform better than normal in maze trials, and prevented the decline in performance that was otherwise observed as these mice aged. In the most recent study Shea and his team demonstrated that mice receiving the human equivalent of 2 glasses of apple juice per day for 1 month produced less of a small protein fragment, called “beta-amyloid” that is responsible for forming the “senile plaques” that are commonly found in brains of individuals suffering from AD. Dr. Shea commented that “These findings provide further evidence linking nutritional and genetic risk factors for age-related neurodegeneration and suggest that regular consumption of apple juice can not only help to keep one’s mind functioning at its best, but may also be able to delay key aspects of AD and augment therapeutic approaches.”Science Daily 1/22/02 Journal of Alzheimer’s Disease, 16, No. 1:167-171 January 2009

Blood Pressure Linked to AD - Better treatment of high blood pressure could halve the number of people who develop AD. New Australian research has drawn a clear link between the degenerative mental condition and high blood pressure, also known as hypertension, which afflicts 70 per cent of older Australians.Hypertension is known to increase the risk of heart attack, but Sydney’s Dr Michael Valenzuela saysit’s now clear sufferers also have a heightened chance of developing AD in later life. “I think there is a fundamental link between AD and cardio-vascular disease ... high blood pressure reduces blood flow to the memory part of the brain,” Dr Valenzuela says. “Any kind of reduction of blood flow is going to be negative for brain cells, they are not going to have enough nutrients or ability to get rid of waste products.” He says this could cause breakages in the tiny blood vessels in the hippocampus, the part of the brain responsible for memory, leading to ``micro-bleeding that may kick off the AD process.” Dr Valenzuela, a research fellow at the University of New South Wales School of Psychiatry, has reviewed 10 years of global dementia-related research, drawing on clinical and also population- based studies. One of the studies involved a trial of more than 4500 people aged over 60 who had high blood pressure. The incidence of later onset of AD was halved among those in the group who were on anti-hypertensive drugs. Dr Valenzuela says further studies confirmed the link. He says the research shows how government and health authorities can move to address projected rising rates of dementia. “I believe that addressing blood pressure in the community in a more focused way, in a more effective way, I’d expect that dementia rates would correspondingly fall,” he says. Australian Associated Press 2/27/09

Dementia More Likely in Some Isolated and Inactive Seniors, Study Finds - The latest news from researchers exploring whether people with certain personality traits are more likely than others to develop dementia is that you really ought to get out more. Past studies consistently have shown that worriers -who get stressed easily and are prone to anxiety and depression - are more likely to develop dementia later in life. Now a new report from Sweden suggests that neurotics can shape their destiny to some extent, because lifestyle also plays a role. The study appeared in the journal Neurology 1/20/09. Scientists at the Karolinska Institute in Stockholm followed a group of 506 people ages 78 and older who had no dementia at the beginning of the study. The subjects completed a personality questionnaire and were interviewed about their lifestyles, and then were monitored for several years, with medical exams at three years and again at six years. After six years, 144 adults in the group had developed dementia. The researchers analyzed the accumulated data for possible associations between cognitive function, neuroticism and other characteristics, as well as lifestyle factors. Very neurotic people were more likely to have developed dementia over time than were people who were calmer, more relaxed and self-satisfied, but only if they were also socially isolated and inactive, the researchers discovered. The subjects with all these risks were three times more likely to have suffered dementia compared to participants who were not neurotic but just as isolated and inactive, the study found. When the elderly participants were physically and mentally active and had rich social networks, it didn’t much matter whether they were neurotic or not, the scientists also found. In this group, neuroticism was associated with only a slightly increased risk of dementia. “This is indicating that an active lifestyle can buffer the effects of high neuroticism,” said Dr. Hui-Xin Wang, the lead author of the study, said. “That’s a good thing, since lifestyle is something one can change.” The associations between personality, lifestyle and dementia risk may be explained by psychological stress, Dr. Wang said, since stress hormones are associated with damage to the hippocampus, the part of the brain involved in forming new memories. Studies have demonstrated that when animals are placed under constant psychological stress, their brains undergo physical changes and they develop memory problems, said Robert Wilson, a professor of neuropsychology at Rush University Medical Center in Chicago who has also studied the link between neuroticism and dementia. Dr. Wilson said the new finding is not altogether surprising, since both neuroticism and an inactive lifestyle have been linked to an increased risk of dementia. He noted that personality traits play a very small overall role in predicting the risk of dementia. “Thegood news is that even if you have the bad personality traits, if your lifestyle is active and integrated, you’re probably okay,” he said. “The extra risk associated with these personality traits is only playing out in people whose lifestyle is already putting them at somewhat risk”.By Roni Caryn Rabin New York Times 1/23/09 Neurology 2009;72:253-259

Exercise Helps Keeps Brain Fit, Slows AD - It has only been a decade since scientists discovered that brain cells could be increased and made more active through exercise, not just lost through disease -- and Brian Christie, a University of Victoria neuroscientist, was part of that groundbreaking research team at the Salk Institute in California. Granted, the studies were on mice. He’s still looking at ways to help regenerate neurons in the adult brain and isn’t waiting for the research on humans. “Exercise creates new cells and changes old cells for the better,” says Christie, who bikes or runs two kilometres to and from UVic each day. “Even if you’re diagnosed with AD, if you exercise, the progression of your disease will slow considerably. As little as 20 minutes of brisk exercise three times a week -- if you just do that, it really produces a lot of benefits.” Backing that up is a 2008 study by Dr. Jeffrey Burns of the University of Kansas medical school that found only one-fourth the brain shrinkage in fit people with AD compared to less-fit participants.Getting blood to the brain is what counts, and a brisk walk rather than a brutal run can do that. It’s especially important because brain volume and the production of new neurons decline with age and even more so with diseases such as AD, Christie says. “If the elderly got out for 20 minutes a day, it would be fantastic.” He’s one of a huge team of scientists from Canada, the U.S. and Europe looking at exercise under the microscope rather than in the gym. In his Salk days, genetically identical mice were divided into two groups -- one with food and water; the other with food, water and a running wheel. Mice with a wheel ran five kilometres a night. Six weeks later, they found a hidden platform significantly more easily than the inactive mice. Examination of their brains showed they had grown more cells than sedentary mice from the same litter, and those cells were largely neurons capable of transmitting messages throughout the brain. To cover your bets, make it physical exercise and mental exercise, Christie advises. Walk, run or bicycle. Learn to throw a baseball or play piano. Do a sudoku or crossword puzzle. Try some creative writing, the more elaborate the better. But beware of hype about exercise. “You’re not going to take someone with serious damage to their brain and rebuild the brain with exercise.” By Katherine Dedyna, Times Colonist, Calgery Herald 1/26/09

Coffee Linked to Lower Dementia Risk - Drinking coffee may do more than just keep you awake. A new study suggests an intriguing potential link to mental health later in life, as well. A team of Swedish and Danish researchers tracked coffee consumption in a group of 1,409 middle-age men and women for an average of 21 years. During that time, 61 participants developed dementia, 48 with AD. After controlling for numerous socioeconomic and health factors, including high cholesterol and high blood pressure, thescientists found that the subjects who had reported drinking three to five cups of coffee daily were 65 percent less likely to have developed dementia, compared with those who drank two cups or less. People who drank more than five cups a day also were at reduced risk of dementia, the researchers said, but there were not enough people in this group to draw statistically significant conclusions. Dr. Miia Kivipelto, an associate professor of neurology at the Karolinska Institute in Stockholm and lead author of the study, does not as yet advocate drinking coffee as a preventive health measure. “This is an observational study,” she said. “We have no evidence that for people who are not drinking coffee, taking up drinking will have a protective effect.” Dr. Kivipelto and her colleagues suggest several possibilities for why coffee might reduce the risk of dementia later in life. First, earlier studies have linked coffee consumption with a decreased risk of type 2 diabetes, which in turn has been associated with a greater risk of dementia. In animal studies, caffeine has been shown to reduce the formation of amyloid plaques in the brain, one of the hallmarks of AD. Finally, coffee may have an antioxidant effect in the bloodstream, reducing vascular risk factors for dementia. Dr. Kivipelto noted that previous studies have shown that coffee drinking may also be linked to a reduced risk of Parkinson’s disease. The new study, published this month in The Journal of Alzheimer’s Disease, is unusual in that more than 70 percent of the original group of 2,000 people randomly selected for tracking were available for re-examination 21 years later. The dietary information had been collected at the beginning of the study, which reduced the possibility of errors introduced by people inaccurately recalling their consumption. Still, the authors acknowledge that any self-reported data is subject to inaccuracies. By Nicholas Bakalar New York Times 1/24/09 The Journal of Alzheimer’s Disease, 16, No. 1: 85-91 January 2009

Living Near Big Power Line May Up AD Risk - Older people living within 50 meters (164 feet) of major power lines are at increased risk of dying from AD or senile dementia, research from Switzerland shows. The risk increased steadily with the amount of time a person had been living in close proximity to a 220-380 kV power line, Dr. Anke Huss of the University of Bern and colleagues found. These are extra-high voltage lines used for long-distance transmission of large amounts of electricity. Huss and colleagues were able to look at census and mortality data for over 95% of the Swiss population, which strengthens the power of the findings. Nevertheless, the researcher told Reuters Health,the results should be interpreted with caution because this is the first study to link residential magnetic field exposure to AD mortality. Huss said she would like to see other research teams, preferably in other countries, look into the issue. Extremely low-frequency magnetic fields are produced by electrical appliances and wiring as well as by power lines. The World Health Organization has stated that these magnetic fields are possible human carcinogens. In 2007, WHO concluded that there was not enough evidence to link extremely low-frequency magnetic fields to AD, but called for the relationship to be a “key research priority,” Huss and her team note in the American Journal of Epidemiology. Overall, Huss and her colleagues found, people living within 50 meters of a 220-380 kV power line were 1.24 times more likely to die of AD than those living at least 600 meters away from these power lines. At present, the researcher added,there is no accepted biological mechanism to explain why magnetic fields might increase AD risk. Given the consistency of the findings, she added, “There might be something going on even if we don’t know what it is.” By Anne Harding Reuters Health 2/6/09 American Journal of Epidemiology 2009 169 (2): 167-175

Other Items

Inside the Brain: An Interactive Tour - The Alzheimer’s Association has a great Interactive

Brain Tour which explains how the brain works and how AD affects it. Taking the tour: there are 16 interactive slides. As you view each slide, roll your mouse over any colored text to highlight special features of each image. Then, click on the arrow to move to the next slide. Go to http://alz.org/alzheimers_disease_4719.aspand click on Start Tour. 

Brain Study Indicates Why Some Memories Persist - A new study appears to explain why people with AD often remember events from the distant past - - but not things that happened recently. The research, published in the Journal of Neuroscience,looked at a structure deep in the brain called the hippocampus. Scientists know that when disease or injury damages the hippocampus, people have trouble forming new memories or retrieving recent memories. Scientists also know that areas of the brain near the hippocampus are usually the first to be affected by AD. “That’s why AD tpically begins with memory problems,” says Larry Squire, a brain researcher at the University of California, San Diego and the Veterans Affairs Medical Center in San Diego. But it’s been something of a mystery how the brain protects older memories. So Squire studied 15 healthy people in their 50s and 60s. A scanner monitored their brains while they tried to answer questions about news events from the past 30 years. “What we found was that the hippocampus was most active when subjects were recalling memories about new events that occurred just a year or two earlier,” Squire says. “The hippocampus became less active as subjects recalled memories that were five years or 10 years old.” As people tried to remember older events, the scientists saw more and more activity on the surface of the brain. The results suggest thatthe hippocampus is necessary to form new memories and to retrieve recent memories, says Russell Poldrack, a brain scientist at UCLA.But it plays little or no role once memories are a few years old. “This is the clearest demonstration yet of what happens as memories get older,” Poldrack says. “It’s pretty compelling evidence.” Poldrack says the study explains why people in the early stages of AD are “more likely to forget where they put their keys yesterday than to forget something that happened back when they were in high school.” By Jon Hamilton National Public Radio 1/29/09

Journal of Neuroscience, January 28, 2009, 29(4):930-938

Getting Diabetes Before 65 More Than Doubles Risk For AD - Diabetics have a significantly greater risk of dementia, both AD - - the most common form of dementia - - and other dementia, reveals important new data from an ongoing study of twins. The risk of dementia is especially strong if the onset of diabetes occurs in middle age, according to the study. “Our results . . . highlighted the need to maintain a healthy lifestyle during adulthood in order to reduce the risk of dementia late in life,” explained Dr. Margaret Gatz, who directs the Study of Dementia in Swedish Twins. In a study published in the journal Diabetes, Gatz and researchers from Sweden show that getting diabetes before the age of 65 corresponds to a 125 percent increased risk for AD. Nearly 21 million people in the United States have diabetes, according to the American Diabetes Association, which publishes the journal. This risk of AD or other dementia was significant for mid-life diabetics - - as opposed to those who develop diabetes after 65 - - even when controlling for family factors. In other studies, genetic factors and childhood poverty have been shown to independently contribute to the risk of both diabetes and dementia. “Twins provide naturally matched pairs, in which confounding factors such as genetics and childhood environment may be removed when comparisons are made between twins,” explained Gatz, professor of psychology, gerontology and preventive medicine at the University of Southern California and foreign adjunct professor of medical epidemiology and biostatistics at the Karolinska Institute in Sweden. Indeed, the chances of a diabetic developing AD may be even greater in real life than in the study, the researchers write. They identify several factors that might have led them to underestimate the risk of dementia and AD among those who develop diabetes before the age of 65.Diabetes usually appears at a younger age than dementia does, the researchers note. Diabetes is also associated with a higher mortality rate, which may reduce the size of the sample of older adults. In addition,approximately 30 percent of older adults with diabetes have not been diagnosed. The results of the study implicate adult choices such as exercise, diet and smoking, as well as glycemic control in patients with diabetes, in affecting risk for AD and diabetes, according to the researchers. The sample for the study was 13,693 Swedish twins aged 65 or older in 1998, the year tracking for dementia began. Information about diabetes came from prior surveys of twins and linkage to hospital discharge registry data beginning in the 1960s. Science Daily 1/28/09    Diabetes 58:71-77 2009

Headway In Understanding AD - Scientists at UC Santa Barbara have discovered that a protein called BAG2 is important for understanding AD and may open up new targets for drug discovery. They are ready to move from studying these proteins in culture to finding out how they work with mice. In a recently paper published in the Journal of Neuroscience, the scientists describe important activities of BAG2 in cleaning up brain cells. The protein tau is normally found in brain cells, but scientists don’t know why it clumps into tangles in people with AD. Senior author Kenneth S. Kosik, co-director of UCSB’s Neuroscience Research Institute, and Harriman Chair in Neuroscience, has been involved in the study of neurons that develop neurofibrillary tangles, one of the hallmarks of the disease, since he was a postdoctoral fellow. “Early on in my career, we were one of several labs to discover that tau was in the neurofibrillary tangles,” said Kosik. Kosik’s team recently started to work on BAG2 to find out how it may be involved in the removal of tangled tau. “It turns out that when you put this protein into the cell, it clears away the damaged tau very nicely,” said Kosik.It doesn’t clear away all the tau; it goes for the damaged tau protein and removes it. For unknown reasons, when tau accumulates in a neurofibrillary tangle, the cell can’t get rid of it. “All cells including neurons have an elaborate, sophisticated, elegant system for disposing of proteins,” said Kosik. “Proteins have a certain turnover; sometimes they get damaged. The cell has its own trash can called the proteosome, and damaged proteins are deposited there. We’ve done this experiment many ways,” said Kosik. “We’ve discovered a bit about how BAG2 works. We’ve turned it on to remove tau. We’ve turned it off to increase tau. We’ve really done a lot of manipulations using cell culture.”So BAG2 is a new player, a new protein that may be a good target for study in the research of AD. There is nothing about a drug or a treatment in any of these findings; however, the first step in fighting any illness is finding what you want to target the drug to,” said Kosik. “This is a protein that is involved in neurofibrillary tangles, so now we have a new target for drug discovery. This is not a drug or a treatment, just a new target. The new target is BAG2.” Kosik is looking forward to studying BAG2 in mice. Kosik explained that we all have these proteins in our cells; however, they can go awry. Their levels can be off, or they may malfunction in another way. The same normal protein can begin to malfunction. “It may be that BAG2 is not doing its job right; it may be that BAG2 is overwhelmed, because sometimes tau is building up, and there is not enough BAG2 there,” said Kosik. “We cannot conclude from this that BAG2 is the fundamental problem in the disease state. It is only a possible target that can help us find our way out of the disease.” Science Daily 2/5/06 Journal of Neuroscience to be published 2/18/09

New Pathway Is Common Thread In Age-related Neurodegenerative Diseases - How are neurodegenerative diseases such as AD initiated, and why is age the major risk factor? A recent study of a protein called MOCA (Modifier of Cell Adhesion), carried out at the Salk Institute for Biological Studies, provides new clues to the answers of these fundamental questions. Under normal circumstances, MOCA is a key member of the squadron charged with keeping AD at bay. A team of researchers led by Salk professor David Schubert, Ph.D., demonstrated what happens when MOCA goes on furlough. In the process Schubert identified a novel pathway with broad implications for both AD and other age-related neurodegenerative diseases. Their findings, reported in the current issue of the Journal of Neuroscience, show how neurodegenerative disease starts, initiating in the nerve ending and inducing gradual changes, like a chain reaction over a long time. The animal model used in the study also will allow scientists to better understand the processes behind the formation of the protein aggregates that are common to most neurodegenerative diseases. In addition, it will provide new opportunities to target the earliest steps for therapy. MOCA was initially identified as a protein that binds to presenilin, a molecule that when mutated causes familial AD. MOCA is only found in neurons and regulates the expression of the beta amyloid protein responsible for the AD plaques that are the hallmark of the disease. To better understand MOCA’s function, Qi Chen, Ph.D., a senior scientist in Schubert’s laboratory,created a line of mice genetically engineered to lack the gene for MOCA.“Because of the initial studies in cultured cells that we had done,we expected these mice to develop plaques,” explains Schubert. “What we found was that they develop ataxia - - a motor coordination problem - - as they age.” Chen then studied the pathology of these mice and found that it reflected a common feature of most age-related neurological diseases, not just AD. The main problem turned out to be the degeneration of axons, the long projections that conduct impulses away from neurons. The axonal degeneration was caused by the accumulation of protein aggregates. Although the mice were not born with the problem, they acquired it, along with the ataxia, as they aged, and the ataxia worsened over time. The aggregates started out small, initially causing few or no symptoms,but as they built up in the axons, they began to destroy the cytoskeleton, the internal framework of the cells, increasingly interfering with the transmission of signals from the nerve cells. Eventually the affected axons died, followed by the death of the nerve cell itself. “Protein aggregates are common features of most age-related neurological diseases,” says Chen, the first author of the study. “So is axon degeneration; we see it in AD, ALS, and Huntington’s disease. Motor problems such as ataxia may be the most obvious manifestation because the aggregates appear in the long axons of the spinal cord. But the axonal aggregates also appear in the brain and may be the first step in the events that lead to age-associated neurological disease.” After documenting the sequence of physiological and behavioral events that characterize the axon degeneration, Chen then sought to piece together the molecular pathway behind it, starting with MOCA and connecting findings from disparate studies that previously had identified parts of the pathway. He ended up with a single, step-by-step process for axon degeneration that for the first time linked together a number of diseases and conditions, including a form of mental retardation in humans. “We had known that MOCA affected the cytoskeleton for some time, but no one had put together clear evidence showing how the sequential age-associated changes in the cytoskeleton of the nerve take place. Dr. Chen was able to do this, thereby connecting the disease pathology with the molecular biology,” says Schubert. “Now we know that MOCA is essential to the functional integrity of axons and have defined a complete pathway for axon degeneration.” Science Daily 1/31/09 Journal of Neuroscience, January 7, 2009, 29(1):118-130

New AD Network - The Alzheimer’s Disease Cooperative Study (ADCS), in collaboration with the National Institute on Aging, has developed a nationwide information network of people who are interested in learning more about AD and dementia. The purpose of the AD Information Network is to educate the public about AD research and upcoming clinical research studies through a monthly e-newsletter. “The only way we will ever find a cure or prevention for AD is to study every viable avenue for therapeutic treatment,” says Paul Aisen, M.D., director of the ADCS. “To date we have investigated 23 therapies and have several more in the pipeline. The drugs currently on the market that help improve symptoms got there because people were willing to help us study these therapies. The only way to move forward is through clinical trials, and for this we need volunteers willing to help us test new ideas.” To become part of this information network and receive regular e-mail alerts announcing new clinical studies as well as updates on research and treatment, please go to http://www.adcs.org/Research/registry.aspxFor more information on the ADCS, visit the ADCS website at http://www.adcs.org/knox.com blog 1/30/09

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