Non-drug treatment improves brain
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Non-drug treatment (exercise and occupational therapy) improves brain blood flow in MCIA team led by Seigo Nakano, M.D., Ph.D., at the Fifth Department of Internal Medicine, School of Medicine, Fukuoka University, Fukuoka, Japan evaluated the effects of a non-drug therapy on regional cerebral blood flow in amnestic MCI (MCI with memory loss only) among seniors living in the community.
“I was particularly motivated to examine nondrug therapy to prevent further increases in medical expenses as Japanese society is aging at an extremely rapid pace,” Nakano said.
The scientists evaluated 32 amnestic MCI subjects aged 65 years or above in Ajimu, Japan. Eighteen participants received nonpharmacological interventions, and 14 control subjects did not. The intervention included occupational therapy, which was planning and doing simple tasks, and aerobic exercise of climbing up and down a step. Specifically, those in the intervention group helped with the renovation of an old building. During the course of the project, they did planning and were assigned to simple tasks. They also decided the menu for lunch, did shopping and cooked the meal. The seniors in the intervention group did these tasks once a week from November 2004 to November 2005.
All participants were given tests of memory, attention, verbal fluency, and other measures of mental functioning before and after the intervention; regional cerebral blood flow was measured using SPECT. On the baseline SPECT study, there was no significance between intervention and control groups. After one year of follow-up, the cognitive functions and regional cerebral blood flow were revaluated.
The researchers found that in the participants with MCI who received the therapy, the memory score and verbal fluency score after the therapy were significantly better compared to those who did not receive the therapy. According to the researchers, the cerebral blood flow of all participants before the intervention showed a pattern typically seen in early Alzheimer’s; the blood flow in areas called the posterior cingulate gyri, precuneus and parietal lobules was low. One year later, the researchers observed that, in those who received the therapy, the overall area with low blood flow became smaller and the blood flow in areas usually low in Alzheimer’s was improved.
“In people with amnestic MCI, our nondrug therapy may improve cerebral blood flow in areas that usually decrease in Alzheimer’s,” Nakano said. “This suggests possible effectiveness in preventing them from progressing to Alzheimer’s, which deserves further study.”

Effects Of Meditation On Early Cognitive Impairment
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Researchers at the University of Pennsylvania School of Medicine are examining the effectiveness of meditation on early cognitive impairment. Once this new study is completed, the results could help answer lingering questions over whether or not stress-reducing techniques and mind exercises can lessen or even prevent cognitive decline. This is the first study at Penn's new "Center for Spirituality and the Mind," which evolved from work initiated in Penn's Department of Radiology, to embrace and encourage researchers from the fields of medicine, pastoral care, religious studies, social work, nursing, and bioethics to expand our knowledge of how spirituality may affect the human brain. "We'll be looking at patients with mild cognitive impairment or symptoms of early Alzheimer's disease," explains Andrew Newberg, MD, Assistant Professor of Radiology, Psychiatry, and Religious Studies, who also directs the Center's investigations and is Principal Investigator of this pilot study. "We'll combine their meditation with brain imaging over a period of time to see if meditation improves cognitive function and is associated with actual change in the brain's activity levels. Specifically, we'll be looking for decreased activity in specific areas of the brain." The dementia process causes a decreased function of neurons in the brain and can result in problems with memory, visual-spatial tasks, and handling emotional issues. As it worsens in a patient, it can also eventually lead to the need for round-the-clock care. In this study, investigators want to look at the early symptoms of dementia. Study participants will learn a particular kind of meditation, called Kirtan Kriya, identified as one of the most fundamental types of meditation practice. It's a repeated chanting of sounds and finger movements designed to help the mind focus and become sharper. Study participants will perform this meditation program every day for eight weeks to see if this relaxation technique can change the brain's response to different tasks. "This is a form of exercise for the brain which enables the brain to strengthen itself and battle the unknown processes working to weaken it. We want to keep the mind sharp and work that muscle," Newberg adds. "We might see improvements in baseline activity levels in the brain and these patients might be able to activate their brain in a more robust way in particular. So if this kind of meditation is successful in helping patients with neurological problems, it could then someday become a low-cost additional treatment to current therapy."

Alzheimer's drugs fail to deliver

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Thomas Finucane, a geriatric specialist, tells his Alzheimer's patients and their relatives not to get their hopes up when he prescribes Pfizer Inc.'s Aricept and similar drugs.
“In 10 years we are going to be embarrassed that we were sending billions of dollars to the drug companies for a pill that patients can't distinguish from a placebo,” said Finucane, a professor of medicine at Johns Hopkins University School of Medicine in Baltimore.
Alzheimer's medicines generated $2.16 billion last year, according to IMS Health Inc. Approved in 1996, Aricept became the world's top-selling drug for the disease even amid doubts about its effectiveness and that of similar pills. Today, in one of the largest reviews of clinical data on Alzheimer's drugs, researchers found that all medications in the same class as Aricept, known as cholinesterase inhibitors, offered the same small improvement in mental functioning.
The study by the U.K.-based Cochrane Collaboration analyzed data from 18 clinical trials involving 9,200 patients. Patients taking Alzheimer's drugs showed an average 2.5-point improvement on a 70-point scale measuring cognitive function and activities of daily living compared with those taking a placebo.
The analysis found that 29 percent of patients dropped out of the trials because of side effects, such as nausea, vomiting and diarrhea.
'Don't Expect Miracles'
“The average benefit is very small. It might escape notice,” said lead researcher Jacqueline Birks, a medical statistician for Cochrane's dementia and cognitive impairment group at University of Oxford. “Don't expect miracles.”
“All the current drugs only treat the symptoms, they don't get at the underlying disease process,” Morris said.
Previous clinical trials have shown that more than half of patients show no improvement, and for those that do, the degree of benefit is small, according to the Alzheimer's Association. Findings presented today at the International Conference on Alzheimer's Disease and Related Disorders in Madrid will do little to sway opinion on either side of the debate.
'Not ultimately Satisfying'
“It's not ultimately satisfying to anyone, and I think the manufacturers would agree with that,” said William Thies, vice president of medical and scientific relations for the Chicago-based Alzheimer's Association. “If you put all these studies together you do get a consistent effect. It's modest.”
The marginal efficacy of Alzheimer's drugs also raises the debate about cost effectiveness. A month's supply of Aricept pills costs about $150, according to Drugstore.com. Razadyne costs about $160 per month, and Exelon costs about $170.
Last year, the U.K.'s National Institute for Clinical Excellence, which evaluates a drug's cost against its benefits for the country's National Health Service, recommended against prescribing the drugs, saying they weren't worth the expense.
'No Clear Evidence'
“The reason there is such a dispute is that there is no clear evidence that they have an important clinical benefit or that they make a difference in the lives of patients,” Sidney Wolfe, director of the Washington-based Public Citizen's health research group, said in an interview.
Public Citizen has kept Aricept on its list of “worst pills” since 1999. Exelon and Razadyne are also on Public Citizen's list of medications to be avoided. The group accuses drug makers of playing on the “hope, fear and guilt” of Alzheimer's patients and their caregivers through advertising.
Eli Lilly & Co., based in Indianapolis, is developing drugs to both block the secretion of amyloid and improve the body's ability to clear it out of the brain. Dublin-based Elan Corp. and Wyeth, based in Madison, New Jersey, are developing a similar treatment to remove amyloid deposits, while Switzerland's Novartis is refining a vaccine that would prompt the body's own immune system to destroy the plaque.

Dementia In Older Men Associated With High Estrogen Levels But No Association Observed With Testosterone
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As our population ages, the impact of dementia will grow. By the year 2050, some 13 million Americans could have Alzheimer's disease, which is the most common cause of dementia. Researchers are searching to understand risk factors and some studies have suggested that sex hormones play a role. One large study showed that women receiving estrogen therapy had an increased risk of cognitive impairment and dementia. However, the evidence for how testosterone levels affect men is contradictory. To better understand the role of sex hormones in dementia, researchers led by Mirjam Geerlings, Ph.D. of the University Medical Center Utrecht, studied whether older men's levels of testosterone and estrogen were associated with their risk of cognitive decline and developing dementia, including Alzheimer's disease. They examined data from the prospectively studied population-based cohort of 2974 Japanese-American men aged 70 to 91 who participated in the Honolulu-Asia Aging Study. Participants showed no signs of dementia at baseline in 1991-1993, at which time fasting blood samples were drawn. The researchers measured the levels of testosterone and estradiol, the major estrogen in humans, in the samples and the men were reexamined for evidence of cognitive decline or dementia in 1994-1996 and 1997-1999 using the Cognitive Abilities Screening Instrument (CASI). At each exam, researchers also collected physical, demographic and medical information. A total of 2300 men completed the study and 223 were diagnosed with incident dementia during the follow-up period. 134 men developed Alzheimer's disease, and 44 developed vascular dementia. The researchers used Cox regression analyses, adjusting for age and other covariates, to see if hormone levels were associated with risk of developing dementia "Levels of bioavailable testosterone were not associated with risk of cognitive decline and incident dementia," they report. "In contrast, higher levels of bioavailable estradiol were associated with an increased risk for cognitive decline and Alzheimer's disease." For each standard deviation increase in estradiol level, the risk for the disease went up by 25 percent. Furthermore, compared with the lowest tertile of estradiol, men in the middle and highest tertile had .24 and .28 points lower CASI scores, respectively, for each year increase in age. The researchers hypothesize that the estradiol association could be explained by increased aromatase activity in the brain which may be associated with a neurodegenerative process. It is then possible that the high levels of estradiol are a consequence or early marker of Alzheimer's disease rather than a cause. Some caution is needed when interpreting the results, as, due to death or refusal, some men could not be given a diagnosis of dementia or follow-up cognitive testing. In conclusion, the authors report, "our findings of an increased risk of cognitive decline and Alzheimer's disease associated with higher estradiol are similar to recent findings in postmenopausal women. Further studies are needed to examine whether there are mechanisms by which estradiol may increase risk of cognitive decline and dementia."

Keeping Mind And Body Active Slows Alzheimer's
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Researchers have uncovered the pathways behind the protection offered by environmental stimulation in Alzheimer's disease, further confirming that enhanced mental and physical activity slows neurological decline. The paper by Ambr-e et al., "Reduction of amyloid angiopathy and Aβ plaque burden after enriched housing in TgCRND8 mice: involvement of multiple pathways," appears in the August issue of The American Journal of Pathology. Alzheimer's disease, the leading cause of senile dementia, presents with cognitive and behavioral deficiencies resulting in part from accumulation of -amyloid (A) deposits within the brain (A plaques) and its blood vessels (amyloid angiopathy). Although previous studies have shown that increased mental and physical activity can slow the progression of the disease, how such deceleration occurs has been unclear until now. Dr. Kathy Keyvani's group at University Hospital Muenster examined the effects of environmental stimulation on the brain pathology of TgCRND8 mice. These mice, which express a mutant form of A found in some Alzheimer's patients, develop Alzheimer-like features including A plaques and cognitive deficits. To study the effects of enrichment, mice were housed in either standard cages or enriched cages, similar to the standard but with access to a stimulus cage containing permanent fixtures (rope and gnawing wood) as well as removable items (tunnels, balls, ladders, ramps, and exercise wheels) that were changed on a rotating basis. Following five months of standard versus enriched housing, mouse brains were examined for signs of disease. Mice housed in the enriched environment had fewer A plaques, smaller plaque size, and reduced amyloid angiopathy compared to mice housed in standard cages. Interestingly, there were no differences in the levels of soluble A peptide or the transcriptional/translational expression levels of its precursor protein (APP) or the processing of APP between the two groups. So how did environmental stimulation prevent disease? To answer this question, Ambr-e et al. performed DNA microarray analysis to determine which genes were differentially regulated in mice housed in the enriched environment compared to standard cages. Enriched mice exhibited down-regulation of pro-inflammatory genes but up-regulation of genes related to anti-inflammatory processes, protein degradation and cholesterol binding. These results were confirmed by specifically analyzing gene expression for examples in each category. Together these data suggest that an enriched environment elicits protection via pathways that prevent A accumulation and enhance its clearance. The authors speculate that the altered expression of inflammatory genes may shift the immune response from one that is neurotoxic to one that is phagocytic, i.e., able to clear unwanted debris, such as A. In accordance with this, a significant enhancement of microglial activity was found by Western blot and morphometric analyses of microglia, which often surround and infiltrate A plaques. In addition, activating cellular protein degradation pathways provides another means of removing excess A. Finally, changes in cholesterol homeostasis, elements of which have been shown to correlate with A deposition, may exert beneficial effects by preventing plaque formation in the first place. These data provide strong evidence that an environment rich in mental and physical stimulation slows the progression of Alzheimer-like brain pathology. Further investigation of the pathways and individual elements involved in such protection may provide novel treatment strategies for Alzheimer's disease. Until that time, keep your running shoes and crossword puzzles handy.

Eye Test Can Inspect For Early Dementia

Diabetes Drug Shows Promise In Treating Alzheimer's
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Treatment of high blood sugar may have a scientific connection to memory loss that could, one day, benefit millions of people with Alzheimer's Disease, which affects up to 4.5 million older Americans, bringing with it impaired thinking and memory.
New research at the University of Virginia Health System and Case Western Reserve University shows that a drug approved by the Food and Drug Administration to treat type 2 diabetes may hold promise in treating Alzheimer's as well, without serious side effects. "We believe that the drug may reduce the body's inflammatory reaction to one of the toxic components that builds up in Alzheimer's, called amyloid plaque, " said Dr. David Geldmacher, an associate professor of neurology at UVa.
The drug, called pioglitazone HCl, was tested in a placebo-controlled trial involving 25 people with mild to moderate Alzheimer's. The study assessed the safety of the drug and, although the treatment appeared to reduce Alzheimer's progression, the study was too small for investigators to be sure of the effects on memory and everyday abilities. However, the findings are promising enough, researchers say, to carry out larger studies of pioglitazone.
The research was presented July 16 to the world's largest Alzheimer's conference, ICAD 2006, in Madrid, Spain. It was selected by ICAD organizers to be highlighted because of a growing sense of the relationship between diabetes and Alzheimer's.
"We don't know exactly how pioglitazone works in Alzheimer's, but there are two possibilities," Geldmacher said. "It could be that the drug reduces the body's response to the amyloid protein found in Alzheimer's. Or, it could be that this drug helps brain cells function. The real advantage is that it's a completely novel approach to treating the disease."
In the next few years, Geldmacher and his colleagues hope to study the effectiveness of pioglitazone in a group of 200 to 300 Alzheimer's patients nationwide. "If it works, this treatment might allow people to better hold on to memory and brain function over a period of time, despite having Alzheimer's," Geldmacher said. "It could also complement other treatments and become part of a multi-pronged approach to Alzheimer's treatment." Right now, there are 5 drugs approved by the FDA to treat Alzheimer's, Geldmacher said, but pioglitazone is unrelated to any of the others. The trial of pioglitazone at UVa and Case Western Reserve was supported by the National Institutes of Health and Takeda Pharmaceuticals North America, Inc., which manufactures the drug.

Young Investigators Receive the Boehringer Ingelheim Apopis Awards ...

Once a day pill hope in Alzheimer's fight
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And until now, there's been little to offer patients that might stop the progress of the disease known as "the long goodbye".But sufferers around the world now have a glimmer of hope thanks to some Melbourne scientists who've created a pill that could delay the onset of the degenerative symptoms of the disease.

Researchers in Australia believe the drug could significantly prevent Alzheimer's developing or delay the onset of the brain disease for many years.
Tests on mice showed that levels of Beta-amyloid, also known as Abeta, dropped by 60% within 24 hours of a single dose of PBT2 and memory performance improved within five days.
Studies conducted by Professor Ashley Bush, of the Mental Health Research Institute of Victoria (MHRI), demonstrated that the drug quickly and significantly improved spatial memory, which is an important indicator of cognitive function.
The research team used a water maze test which involved the mice remembering the location of a submerged platform in order to navigate the maze.
Prof Bush said: "This data is compelling and very exciting because it shows that PBT2 not only may facilitate the clearance of Abeta from the brain or prevent its production, but more importantly may improve cognition."
Professor George Fink, head of the MHRI, said the drug could be on the market within four years. He said: "It is a major breakthrough. Though much depends on the next phase of human clinical trials, early results indicate this drug offers hope to people with Alzheimer's disease."
Human studies on the drug will begin in Sweden next month and will be followed by a major international trial next year.
Alzheimer's is a progressive and fatal brain disease. It is the most common cause of dementia and affects around 450,000 people in Britain.

The First Early Blood Test
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DiaGenic ASA today announced that it has achieved important milestones in the development of a diagnostic test for Alzheimer's disease. New scientific data based on gene expression analysis confirms that the development of a simple blood-based test for diagnosing Alzheimer's Disease (AD) is a realistic possibility in the near future, thereby enabling earlier therapeutic intervention. DiaGenic presented its findings at the 10th International Conference on Alzheimer's Disease and Related Disorders (ICAD) in Madrid. ICAD, which is organized by the Alzheimer's Association, is one of the largest gatherings of Alzheimer's disease researchers in the world. “There are currently no direct tests that confirm Alzheimer's disease in a living person, with diagnosis usually relying on subjective means, such as memory tests,” said Professor Bengt Winblad, of the Karolinska Institute, Stockholm, co-founder of ICAD, and renowned AD researcher. “This study clearly demonstrates the potential of DiaGenic's approach towards the development of an early, blood-based diagnostic test with the sensitivity and specificity the AD community is looking and hoping for.” DiaGenic ASA and its collaborative partner, IMGM Laboratories GmbH, Munich, used Applied Biosystems gene expression technology in a research study to identify a gene expression signature characteristic for AD in easily collectable peripheral blood samples. The extensive test set validated study shows clearly that the gene expression signature identified by DiaGenic can distinguish, with high accuracy, individuals with AD from both healthy elderly and younger individuals and also from those with another neurodegenerative disorder, Parkinson disease. In this extensive study, a set of 330 blood samples, including 125 from patients recently diagnosed with AD, was used to generate a gene expression model for the disease and an independent test set was then used to validate the model. This rigorous validation gave an accuracy of 87%.

New hope of curing dementia

Antibodies impede Alzheimer's advance

Eye test 'could spot Alzheimer's'
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Early dementia could be detected with a simple eye test, similar to those used to test for high blood pressure and diabetes, US scientists believe. The test, developed by a team led by Dr Lee Goldstein, of Brigham and Women's Hospital, Boston, uses a non-invasive laser to study the lens of the eye. It checks for deposits of beta-amyloid - the protein found in the brains of those with Alzheimer's disease.
The procedure has worked in a trial in mice, a conference in Spain heard. During the trial, a brief pulse of infrared light into the eyes of four mice with Alzheimer's and four without accurately identified which had the condition.
Dr Goldstein and his team envisage the test could be used to detect the disease at its earliest stages as well as to track disease progression and monitor how people respond to Alzheimer's treatments.
Currently there is no simple test to make a diagnosis of dementia and it can only be confirmed with certainty by looking at someone's brain in a post-mortem examination.
The scientists believe the technology, known as quasi-elastic light scattering, may detect the very earliest stages of amyloid deposits in the lens, even when they appear completely clear to the naked eye.
The amyloid deposits appear as unusual cataracts. These are different from common, age-related cataracts. Dr Goldstein told the International Conference on Alzheimer's Disease and Related Disorders in Madrid: "Amyloid in the lens can be detected using extremely sensitive, non-invasive optical techniques.
"This makes the lens an ideal window for early detection and disease monitoring in Alzheimer's."
The scientists acknowledge that much more work is needed before such a test could be available to use in patients.
Professor Clive Ballard, of The Alzheimer's Society, said: "This exciting study uses a new imaging technique which has enormous potential as a relatively inexpensive and non-evasive way to chart the growth of amyloid, the protein at the core of the plaques which develop in the brain in a person with dementia.
"But we are long way from eye scans being regularly used to diagnosis someone with dementia.
"More research is needed to show exactly how the amount of protein in the eye relates to development of dementia."

Natural antibodies halt Alzheimer's
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Treatment with antibodies naturally produced in the body appears to halt the memory-robbing progression of Alzheimer's disease, according to promising early research that scientists plan to expand over the next year.
Current Alzheimer's drugs provide moderate relief to some patients but do not stop the disease from advancing. By contrast, the antibodies - a treatment already in use for multiple sclerosis and other autoimmune diseases - stopped or slightly reversed the disease in six of eight patients participating in an 18-month preliminary clinical trial.
Scientists from Weill Cornell Medical School in New York reported the findings at the 10th International Conference on Alzheimer's Disease and Related Disorders in Madrid, Spain. The findings are similar to those from an earlier German study of five patients over six months.
"Those people are not just stabilizing; many of them are getting better. That's quite remarkable," said William Thies, vice president for medical and scientific relations of the Chicago-based Alzheimer's Association.
On the basis of these early results, a larger Phase 2 trial with 24 patients has already begun that will compare the antibody treatment to an inert placebo, and a Phase 3 multicenter trial with 210 patients will start next year.
"We're using something which the human body potentially evolved on its own to deal with this disease," said Cornell's Dr. Norman Relkin, also of the New York Presbyterian Hospital, who presented the trial results in Madrid.
Experts say the need for new drugs is critical because the disease affects an estimated 4.5 million Americans and the number may accelerate as a result of new evidence linking type-2 diabetes with an increased risk of Alzheimer's disease. The cost of the disease in the United States is estimated to be $100 billion annually. Diabetes, which is associated with obesity, has reached epidemic proportions in America, affecting an estimated 73 million people.
The patients in the new studies were treated with a product called intravenous immunoglobulin, or IVIg, a concoction of many antibodies collected from blood donated by healthy volunteers. The Food and Drug Administration approved immunoglobulin therapy more than 25 years ago for treating autoimmune diseases.
A single IVIg dose requires the pooled blood of several thousand donors and costs about $3,000. Baxter International Inc. in suburban Deerfield, Ill., produces IVIg and is funding the clinical trials.
Certain immune-system cells circulating in the blood make thousands of different antibodies against germs and other foreign invaders. They also make antibodies to get rid of rogue proteins, which occur as a result of cellular damage or aging.
One of these proteins, beta amyloid, is widely thought to cause the destruction of brain cells that leads to memory loss. Some people are better able to make antibodies against the various forms of beta amyloid, and population studies show they have a lower rate of Alzheimer's disease. People who have low levels of beta amyloid antibodies, meanwhile, are at higher risk for Alzheimer's.
The Cornell researchers believe IVIg works against Alzheimer's because it contains antibodies that neutralize beta amyloid and speeds its elimination from the body.
"We have found that there are multiple types of antibodies against the amyloid molecule in IVIg, some targeting the end of the amyloid molecule and some the middle," Relkin said.
Steve Snyder, the National Institute on Aging's program director for the etiology of Alzheimer's disease, said the IVIg research "certainly does look promising from very early pilot data. There is some improvement in cognition in these patients. That goes hand in hand with what we see in the animal studies."

Alzheimer's antibodies?

A Vaccine for Alzheimer's?
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"It's conceivable that if we detect changes by imaging even when there is substantial memory loss, disease-modifying therapies, such as passive vaccines, will have the most benefit."
John C. Morris, MD
(WebMD) After the widely publicized failure of a potential vaccine for Alzheimer's disease in 2002, new hope may be on the horizon. According to research presented Wednesday at the 10th International Conference on Alzheimer's Disease and Related Disorders in Madrid, Spain, researchers are already making great strides in developing a vaccine for this progressive brain disorder. Affecting about 4.5 million Americans, Alzheimer’s disease gradually destroys a person’s memory and ability to learn, reason, make judgments, communicate, and carry out daily activities, according to the Alzheimer's Association. Alzheimer’s disease is a result of damage to nerve cells in the brain. Plaques of a protein called beta amyloid contribute to the damage and death of brain cells. The antibody therapy tested in this study targeted beta-amyloid protein and amyloid plaques. The older trial was halted in 2002 when 6% of participants developed a dangerous brain inflammation called encephalitis; some also developed brain shrinkage. But two new approaches toward vaccines seem to avoid such problems, explains John C. Morris, MD, director of the Alzheimer's Disease Research Center of Washington University in St. Louis. Passive Immunization One promising approach is known as passive immunization. In a nutshell, a vaccine helps your body create antibodies to fight off disease. An active vaccine marshals the body’s own disease- fighting mechanism to attack the disease. By contrast, a passive immunization strategy is based on treating patients with antibodies that are manufactured. "This is a different way to grow antibodies," Morris explains. "We grow them in test tubes and give them to patients so the patient can then launch an immune response, but since the body is not generating the antibodies on its own, they will not overstimulate their immune system." Latest Studies Currently there are two trials in different stages looking at this approach, Morris says. In one new study presented here, researchers including Eric Seimers, MD, from Eli Lilly and Company of Indianapolis, gave 19 people with Alzheimer's disease an intravenous (IV) infusion of one of four doses of antibodies over a half hour. Side effects were similar across all dosage groups, but in the highest-dose group, people reported mild shaking and dizziness that lasted less than two hours after the infusion. Although there were no changes in mental function among participants, the researchers noted changes in the blood levels of beta-amyloid. "It's possible that the optimal effects would be to introduce vaccines at a time when the changes are just beginning," he says. "It's conceivable that if we detect changes by imaging even when there is substantial memory loss, disease-modifying therapies, such as passive vaccines, will have the most benefit," Morris says. In addition to passive immunization, newer, more targeted vaccines do not seem to have the same side effects as the older vaccines. "Some researchers are working on a more specific vaccine that if given to people will cause antibodies to attack amyloid plaques and will not have inflammation as a side effect," he says. The good news is that "we are now testing treatments that if found to be safe and effective will have the chance to halt the disease process, and we are on the cusp of early detection of Alzheimer's with novel imaging technologies," he says. "Putting the two together is the way to go particularly as baby boomers reach age 65." Gleaning his crystal ball for WebMD, Morris says, "Alzheimer's is complicated and I would be delighted if we could have one or more new effective therapies by 2020."

Studies show Prana compound may improve cognition

News Tips From The Journal Of Neuroscience

Alzheimer's patients may get skin patch
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By LAURAN NEERGAARDAP MEDICAL WRITER
WASHINGTON -- Alzheimer's patients may soon get the first skin patch to treat the creeping brain degeneration, a novel way to deliver an older drug so that it's easier to take and might even work a little better.
The patch, which infuses the drug Exelon through patients' skin, headlines a trio of innovative potential treatments unveiled Wednesday at an Alzheimer's meeting in Spain. Also under study are a prostate cancer drug that may help dementia, too, and an immune therapy to ward off the sticky gunk that is Alzheimer's brain-clogging hallmark.
The Exelon patch is furthest in the pipeline, with maker Novartis Pharmaceuticals Corp. poised to seek U.S. sales approval by year's end.
"It would be good to have an alternative" to oral medication, Dr. Bengt Winblad of Sweden's Karolinska Institute, who led the patch research, said in a telephone interview. "It's a useful approach, a new treatment strategy that would be very appreciated not only by the patients, but the caregivers."
About 4.5 million Americans have Alzheimer's, a toll expected to reach a staggering 14 million by 2050 with the graying of the population. It gradually robs sufferers of their memories and ability to care for themselves, eventually killing them.
There is no known cure or prevention; today's drugs only temporarily treat symptoms. Exelon does that by inhibiting the breakdown of a brain chemical called acetylcholine, which is vital for nerve cells to communicate with each other. The longer acetylcholine sticks around, the longer those cells can call up memories. But it can be hard to get Alzheimer's patients to swallow pills, and Exelon can cause serious nausea and vomiting. Applied once a day, the new skin patch sends Exelon straight into the bloodstream, bypassing the gastrointestinal tract in hopes of fewer side effects and maintaining a consistent daylong dose.
The Novartis-funded study of nearly 1,200 patients compared taking 12 milligrams of Exelon a day by mouth to a low-dose patch - equivalent to 9.5 mg of Exelon daily - or a high-dose patch, equivalent to 17.4 mg.
The low-dose patch was just as effective as the high-dose pills - but pill users suffered three times more nausea and vomiting than patch users, Winblad reported, making the patch a good alternative to today's oral Exelon.
And the high-dose patch users scored slightly better on cognition tests than pill users, with similar side effects. That means the high-dose patch could provide one more option "when the relatives come and say, 'He's declining, what do we do?'" Winblad said. "That's very nice for us as doctors."
The patch clearly improves patients' quality of life, said Dr. Sam Gandy, director of the Farber Institute for Neurosciences at Philadelphia's Thomas Jefferson University and an Alzheimer's Association spokesman. "It's an important alternative in this era where we still have these symptomatic medications," Gandy said. Far better would be drugs that could slow Alzheimer's inevitably worsening brain decay. A chief target is a sticky protein called beta-amyloid that forms clumps that coat and probably kill brain cells.
Two experimental treatments that aim to fight that plaque buildup: -Leuprolide, an anti-hormone drug currently used to treat prostate cancer and uterine disorders.
Doctors noticed that some men with both Alzheimer's and prostate cancer seemed to fare better cognitively while taking leuprolide. If the effect was real, it was puzzling: Leuprolide blocks a hormone that in turn decreases the brain-protective sex hormones testosterone and estrogen. Then newer research suggested leuprolide also could reduce beta-amyloid - in mice, at least.
Wednesday, Voyager Pharmaceutical Corp. presented initial human studies, suggesting leuprolide helped some patients maintain functional capabilities for nearly a year.
The studies tracked just 50 women and 90 men injected with either leuprolide or a dummy drug every three months plus taking regular Alzheimer's pills. And the effects weren't dramatic: 51 percent of leuprolide patients either stayed stable or showed a slight improvement, versus 35 percent of "control" patients.
Still, the results are promising enough that Voyager is recruiting more than 500 U.S. Alzheimer's patients for advanced testing. This time, participants will receive a spaghetti strand-like implant that dissolves as the drug is absorbed, instead of injections.
-Antibodies, immune system cells created to soak up beta-amyloid so it can't clog the brain.
In an initial safety trial, Eli Lilly & Co. gave 19 patients a single intravenous infusion of these so-called monoclonal antibodies. Patients didn't show symptom improvement, but over the next few weeks, the beta-amyloid in their blood rose sharply, Lilly's Dr. Eric Siemers reported Wednesday. Presumably, the antibodies had sucked some of the sticky substance from the brain, sequestering it so the body could break it down.
In 2002, competitor Elan Corp. tested a vaccine designed to spur the body to create its own amyloid-clearing antibodies. That research was halted when some participants developed brain inflammation, even though others seemed to clearly improve. Now Elan and Lilly have both created their own versions of antibodies, a vaccine alternative, and begun second-stage testing.

Deepening Connections Between Diabetes and Alzheimer’s
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Existing diabetes therapies may help fight Alzheimer’s
There is a growing body of scientific evidence that links diabetes with Alzheimer’s, and which may enable already approved diabetes therapies to be quickly tested for effectiveness against the deadly brain disease. New data from drug trials and long-term population studies were reported this week in Madrid at the 10th International Conference on Alzheimer's Disease and Related Disorders (ICAD), presented by the Alzheimer’s Association.
“A connection between Alzheimer’s and diabetes has major public health implications,” said Ronald Petersen, M.D., Ph.D., vice chair of the Alzheimer’s Association’s Medical & Scientific Advisory Council.
“The number of people with Alzheimer’s, and the number that will soon get it, is rising dramatically as the Baby Boomers turn 60, which is approaching the age of highest risk. Will this growth be redoubled by the rising tide of obesity and diabetes?”
Nearly one-third of American adults – perhaps as many as 73 million people – have diabetes or higher than normal blood sugar levels, according to a study from the National Institute of Diabetes and Digestive and Kidney Diseases that was published in the June 2006 issue of Diabetes Care.
“At the same time, drugs and other treatment strategies – such as changes in diet and exercise – already developed for diabetes may prove useful in Alzheimer’s, and, if so, then we’ll have decades of diabetes research and real life experience to bring to the effort to better treat and prevent Alzheimer’s,” Petersen said.
Borderline diabetes linked with increased risk of dementia and Alzheimer’s

Previous studies have consistently shown an association between diabetes and dementia, and the adverse impact of early stage diabetes on cognitive functions. Weili Xu, M.D., and colleagues from the Karolinska Institutet and the Stockholm Gerontology Research Center, Sweden, sought to examine the effects of borderline diabetes on the development of dementia and Alzheimer’s.
For nine years, the investigators followed 1,173 individuals age 75 years and older who were free of dementia and diabetes at baseline; borderline diabetes was identified in 47 subjects. About one in three (397) of the subjects developed dementia during the follow-up, including 307 subjects who developed Alzheimer’s.
After controlling for other major vascular factors, borderline diabetes was associated with an almost 70 percent increased risk of developing dementia and Alzheimer’s disease in this population. Further analysis suggested that such a significant association was present only among non-carriers of APOE e4 allele, a gene that increases risk for the most common form of Alzheimer’s. The risk for Alzheimer’s was especially high when borderline diabetes occurred with severe systolic hypertension (=180 mm Hg).
“Our findings have significant implications for public health because some studies show that impaired glucose regulation can be improved by lifestyle changes,” Xu said. “Our findings also highlight the need to detect borderline diabetes in order to proactively address both type 2 diabetes and dementia.”

Weight Loss Can Precede Alzheimer's Onset
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If an elderly woman loses weight, it is possible she will develop Alzheimer's disease in the coming years, say researchers from The Mayo Clinic, USA, in a study of over 1,000 people. Many people in the study who had dementia had lost weight up to ten years before symptoms of memory loss began to show. The researchers, who presented their findings at an Alzheimer's Conference, Madrid, Spain, stressed that weight loss in an elderly woman does not mean she will get Alzheimer's. A bit like not all fruit are bananas, but all bananas are fruit - not all elderly women who lose weight will develop dementia, but a large proportion of women who developed Alzheimer's had lost weight some years before the onset of the disease. The researchers believe this finding will perhaps provide some clues regarding the brain mechanisms of dementia. The scientists identified two groups of people. 560 had been diagnosed with dementia during 1990-1994. They were compared to another similar-sized group of people, during the same period, who did not have dementia. All the people's weights were observed up to 30 years before 1990-1994. They found that the women with dementia had had similar bodyweights to the women without dementia many decades before 1990-1994. However, about ten years before that 1990-1994, those that went on to develop dementia lost a few pounds, while the women who did not develop dementia did not. The women lost some more weight when the dementia symptoms began to show. Dr David Knopman, Mayo Clinic, said "The weight of those women who developed dementia was drifting downward many years before the onset of symptoms. This illustrates changes that occur before the memory loss and mental decline in dementia. We believe that the brain disease began to interfere somehow with maintenance of body weight, long before it affected memory and thinking." He wondered whether the disease that brings on dementia may cause women to become less interesting in eating food - perhaps even interfering with their sense of taste and/or smell. Another possibility, Knopman added, is that these women began to have an earlier sense of satiety.

Leuprolide acetate helps women with mild-to-moderate Alzheimer's disease maintain functional capabilities for a longer period of time, according to data presented Monday by Voyager Pharm. Co. http://www.medicalnewstoday.com/medicalnews.php?newsid=47484&nfid=al

Donepezil Slows Brain Shrinkage In Alzheimer’s Patients

High Blood Sugar Level Increases Risk Of Alzheimer's Disease

Neuropharma presents new mechanism of action for AD drug
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Neuropharma has developed a new treatment for Alzheimer's Disease, which uses a unique method of attack, incorporating a mechanism of action that targets a little-known enzyme that contributes to the proliferation of the neurodegenerative disease. Alzheimer's disease is a condition affecting more than 27 million people worldwide and figure suggest this number will rise. Current treatments can only treat the symptoms. Little is relatively understood of the underlying cause of the disease.
Symptomatic treatment on average remains effective for 6-12 months, after which the natural evolution of the degenerative process begins to produce a progressive deterioration.
NeuroPharma's lead compound, NP-12, has a new mechanism of action that may slow the neurodegenerative process by inhibiting the GSK-3 enzyme involved in the excessive phosphorilation of the tau protein and in the deposit of neurofibrillary tangles, one of the neurodegenerative lesions associated with neuronal death and correlated with the dementia severity.
“Proof of efficacy in several animal models and the toxicological and safety regulatory studies have shown that NP-12 could be a promising treatment for Alzheimer's disease with an innovative therapeutic approach,” said Ana Martínez, R&D Director of Neuropharma.
Alzheimer's disease, the most frequent cause of dementia in old people, is a serious degenerative disorder produced by a gradual loss of brain neurons. The cause of this illness is not known.
The brain of patients suffering from Alzheimer's disease shows two main lesions: an intracellular lesion, neurofibrillary tangles formed by hyperphosphorylated tau protein, and an extra cellular lesion, senile plaques formed by the aggregation of beta amyloid peptide. Both of them are considered to provoke neuronal death.
Speaking at the 10th International Conference on Alzheimer's Disease (ICAD) taking place in Madrid from 15th to 20th July, NeuroPharma revealed that it had designed the Phase I clinical development (safety assessment and dose escalation) to establish the safety of the compound in humans and define the optimal dose for the Phase II and III trials.

Vision Loss In Seniors Linked To Alzheimer's
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Researchers at Saint Louis University School of Medicine have received nearly half a million dollars from the National Eye Institute to study a protein thought to be linked to Alzheimer's disease and its possible relationship to age-related macular degeneration, the leading cause of blindness in people over 60. Apolipoprotein E (apoE) is a protein component that helps transport cholesterol in the blood between the liver and other tissues, says Steven Fliesler, Ph.D., professor and director of research in the department of ophthalmology at Saint Louis University School of Medicine and lead investigator. It also is present in the brain and other nervous tissues, including the retina. There are three genetically determined forms of apoE (apoE-2, apoE-3 and apoE-4), each encoded by a specific sequence of DNA . Studies suggest that apoE-3 may play a protective role in the nervous system, assisting in the repair of nervous tissue, such as after a brain injury. On the other hand, people who have elevated levels of the apoE-4 version of the protein are at an increased risk for developing the late onset, familial type of Alzheimer's disease. The mystery SLU researchers are now trying to solve is why the reverse seems to be true when it comes to advanced macular degeneration. "Paradoxically, the exact opposite trend seems to prevail," Fliesler says. "ApoE-4 seems to correlate with a reduced incidence of macular degeneration." For the next two years, Fliesler and his team will test whether the presence of one or the other form of apoE slows down, quickens, or does essentially nothing to the rate of retinal degeneration in genetically altered mice that undergo progressive, age-dependent vision loss. Fliesler's team will selectively introduce either the human apoE-3 or apoE-4 gene into the mice and then study what effects this may have on the structure and function of their retinas. "We hope our experiments with transgenic mice will provide some clues as to what apoE is doing in the retina and why one form of apoE versus another would predispose someone to having macular degeneration," Fliesler says. "At this point, it makes no sense to me that the same molecule would have very different actions in the brain versus the retina, both of which are nervous tissue," he says. Macular degeneration, which affects nearly 12 million people in the United States - about one in four older adults - and about 50 million worldwide, is caused by the deterioration of the central portion of the retina, known as the macula. The macula is responsible for focusing central vision in the eye, and it controls the ability to read, drive a car, recognize faces or colors and see objects in fine detail. As people age, their chances for developing eye diseases increase dramatically. Smoking is also a strong risk factor, as it seems to be for other age-related diseases. As the baby boomers get older and the average human lifespan continues to increase, these diseases will have an increasingly significant impact on society, including quality of life for the elderly as well as worldwide escalating healthcare costs, says Fliesler.

Treatment for Alzheimer's may be necessary before 50
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The researchers found that in people genetically prone to Alzheimer's, significant amounts of a brain-clogging protein start moving from the spinal fluid to the brain about age 50 or younger.
"It can be going on for decades before we have an inkling of symptoms," said Dr. Elaine Peskind, associate director of the University of Washington Alzheimer's Disease Research Center at the VA Puget Sound Health Care System in Seattle.
Previous research has indicated that Alzheimer's begins years before symptoms appear. But this latest work by Peskind, the lead scientist, and her colleagues is the first to look at early signs across a wide range of ages -- from 21 to 88. The research is particularly significant because scientists predict a dramatic increase in Alzheimer's in the decades ahead. About 4.5 million people in the United States have the disease, and researchers say that could increase to 16 million by 2050.
Peskind and scientists from five other medical centers analyzed the effects of aging and the presence of a gene connected to Alzheimer's, APOE4, on 184 adult volunteers with an average age of 50 and all mentally normal.
People with the APOE4 gene have a higher Alzheimer's risk because it produces a sticky protein, called beta amyloid, in the form of a plaque that is thought to damage brain cells.
Among the volunteers with the gene, the level of one important form of the protein in the spinal fluid was dramatically lower in participants 50 and older than in the younger ones.
The decline in levels "possibly begins in young adulthood" in those with the gene, the scientists report in the July edition of the Archives of Neurology. Among the volunteers without the gene, the protein levels dropped slowly into old age.
About a quarter of the population has the APOE4 gene, though there are other physical factors that also influence whether a person develops the disease. Because there is no cure or vaccine for Alzheimer's, such tests would be unwise now, because they could affect whether someone could obtain health insurance or long-term-care insurance, she said.
The four prescription drugs now available for Alzheimer's merely ease the symptoms for a few years. Other drugs are under investigation, including two at the University of Washington. One is to remove the plaque. The other is to prevent its production.
But Peskind predicts it will be many years before a major drug will be available to prevent or control the disease. "I think within 10 years, it will definitely be possible," she said.
Test May Detect Alzheimer's Early

New Jewelry Line To Honor Caregivers
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The Alzheimer's Foundation of America (AFA) has introduced a jewelry line that, in addition to being highly fashionable, makes more than merely a fashion statement: it is designed to recognize the heroic act of caregiving and to raise awareness of Alzheimer's disease and related dementias. The line consists of a necklace, bracelet and lapel pin -- each with a sterling silver pendant modeled after AFA's logo of arms embracing a heart. The logo reflects the organization's mission of providing optimal care to individuals with dementia and their families. "Caregivers give from the deepest recesses of their hearts. Our goal is to recognize the selflessness and strength of these exceptional human beings in light of the enormity of their role," said Eric J. Hall, AFA's chief executive officer. AFA expects the jewelry to especially touch caregivers of individuals with Alzheimer's disease or other illnesses, and their families, as well as to have universal appeal due to its artistic look. An estimated five million Americans have Alzheimer's disease, which results in loss of memory and other cognitive functions; the incidence is expected to triple by mid-century. There is an estimated one to four caregivers for each person with the disease. A recent AFA survey of caregivers of individuals with Alzheimer's disease, conducted by Harris Interactive, highlighted caregivers' massive responsibilities: More than 70 percent attend appointments with their loved ones, help plan and organize their lives, and aid in day-to-day activities. The survey also found that 76 percent of caregivers have learned that they are stronger than they thought. Proceeds from the jewelry will support AFA's programs, including grants to member organizations to enhance local services. The Alzheimer's Foundation of America, a nonprofit organization based in New York City, unites hundreds of member agencies nationwide that provide hands-on services to individuals with Alzheimer's disease and related illnesses, and their families.

Spinal Fluid Proteins may Signal Alzheimer's
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Decreases with age in the cerebrospinal fluid concentrations of a specific amyloid-beta protein may help identify the early signs of Alzheimer's disease.
Older cognitively normal patients with the apolipoprotein E 4 (ApoE4) genetic variant, which confers increased risk for Alzheimer's, had significantly greater decreases in levels of amyloid-beta42 protein in their CNS fluid than did older people with low-risk alleles, reported Elaine R. Peskind, M.D., of the VA Puget Sound Health Care System, and colleagues.
Among volunteers in a community-based study who were negative for the ApoE4 allele, mean amyloid-beta42 levels in CSF rose slightly until about age 50, then fell slightly with increasing age.
Among ApoE4 carriers, however, amyloid-beta42 concentrations declined slightly in the younger participants, then dropped off rapidly beginning between the ages of 50 and 60 years, the investigators reported in the July issue of the Archives of Neurology.
The investigators did a single spinal tap for each of 184 volunteers who were from 21 to 88 years old.
These findings have implications for the preclinical diagnosis of Alzheimer's, as well as for treatment," Dr. Peskind and colleagues wrote. "Follow-up of cohorts such as ours will be important to affirm our cross-sectional findings and to assess whether subjects who fall in the lowest part of the age- and ApoE-adjusted range for CSF amyloid-beta42 concentration have the highest risk of developing Alzheimer's."
In an accompanying editorial, Archives of Neurology editor Roger N. Rosenberg, M.D., a neurologist at the University of Texas Southwestern Medical Center in Dallas, wrote that the data "provide the means to identify patients who have the apolipoprotein E 4 allele, potentially have asymptomatic Alzheimer disease, are acquiring the neuropathologic abnormalities of the disease as indicated by abnormal cerebrospinal fluid levels of ab42, and would be ideal candidates for therapeutic intervention."
The amyloid-beta peptide is cleaved by the amyloid precursor protein into fragments ranging between 38 and 42 amino acids in length, hence the amyloid-beta42 designation. Previous studies have shown that decreased levels of amyloid-beta42, but not amyloid-beta4o in CSF is a biomarker for Alzheimer's.
Amyloid-beta42 concentrations may be lower in patients with AD because the protein fragment is taken up by amyloid-beta plaques in the brain, presumably years before symptoms of the neurodegenerative disease develop, the authors suggested.
To get a handle on the interactive effects of normal aging and the presence of the ApoE4 allele on levels of amyloid-beta42 in CNS fluid, the authors recruited 184 volunteers who were from 21 to 88 years old.
The participants, 94 men and 90 women, all underwent detailed clinical and laboratory evaluations and were found to be cognitively normal on the Mini-Mental State Examination and Clinical Dementia Rating Scale, and had no clinical evidence or history of cognitive or functional decline.
Cerebrospinal fluid was collected by spinal tap in the morning following an overnight fast, and concentrations of amyloid-beta42 and amyloid-beta40 were measured by sandwich enzyme-linked immunosorbent assay. The investigators also used restriction digest techniques to determine ApoE genotypes in the volunteers.
They found that concentration of amyloid-beta42, but not amyloid-beta40 decreased significantly with age in all participants.
There was a sharp decrease in CSF amyloid-beta42 concentrations beginning in the 60s in participants who were positive for the ApoE4 allele. The age-associated decrease was significantly greater, and the effect was larger, in those participants who were ApoE4 carriers than among those who did not have the high-risk allele.
"Our results are therefore consistent with differential aggregation and deposition in the brain, clearance, or binding to carrier molecules that selectively affects amyloid-beta42," they wrote.
"These results do suggest that sequestration of amyloid-beta42 in the brain occurs early in ApoE4 allele carriers, bolstering evidence for this as a key initiating factor in AD pathogenesis. Measuring amyloid-beta concentration in CSF provides an indirect estimation of the net effect of production, clearance, aggregation, and deposition; therefore, we cannot determine which of these factors is most important."
Their findings support the results of a recent study which found that asymptomatic adults who were carriers of mutations in the genes encoding for presenilin complexes involved in amyloid-beta precursor-protein cleavage also had low levels of amyloid-beta42 in CSF, "lending further support to a decrease in CSF ab42 concentration as a preclinical biomarker for AD," they added.

Researchers Get Closer To Preventing Alzheimer's Disease

Protein may help detect Alzheimer's
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CHICAGO, July 10 (Reuters) - Sampling spinal fluid for a protein that makes up the plaques that clog the brains of Alzheimer's disease patients may help diagnose the mind-wasting disease, researchers said on Monday.
As plaques build up in the brain, levels of the protein -- A beta 42 -- are thought to decline elsewhere in the body, including the spinal fluid, according to the study appearing in the Archives of Neurology.
Other than giving suspected Alzheimer's patients mental tests, a diagnosis can only be confirmed after death from the tell-tale plaques found in the brain.
One hundred eight-four adults averaging 50 years old and free of Alzheimer's at the start of the study had their spinal fluid tested for the protein found in brain plaques.
In subjects with a genetic predisposition to Alzheimer's disease, protein levels in the spinal fluid declined slightly through adulthood and then dropped sharply between age 50 and 60 -- presumably as plaque formation in their brains accelerated.
In people without the genetic predisposition, protein levels in the spinal fluid rose until age 50, then began declining slowly.
No direct connection was found between levels of the protein and Alzheimer's symptoms, but the mental decline from Alzheimer's is thought to progress only after years of plaque buildup and usually becomes evident in old age, the study said.
"These findings have implications for the preclinical diagnosis of Alzheimer's disease, as well as for treatment," said study author Elaine Peskind of VA Puget Sound Health Care System and University of Washington School of Medicine, Seattle.
"Therapeutic strategies aimed at prevention of Alzheimer's disease may need to be applied in early midlife or even younger ages to have maximal effect on amyloid (plaque) deposition," she added.

A recent study directed by Mount Sinai School of Medicine identifies a faulty molecule in the brain found in cases of mild cognitive impairment (MCI). Researchers say this faulty molecule may be responsible for the progression of MCI to mild Alzheimer's disease (AD) dementia. http://www.medicalnewstoday.com/medicalnews.php?newsid=46754&nfid=al

Researchers Get Closer To Preventing Alzheimer's Disease

Alzheimer's drug test underway at USF

Blood analysis may reveal Alzheimer’s risk
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A blood test might one day predict a person’s risk of developing dementia, a new study suggests. It links certain levels of two proteins in blood samples with a 10-fold increase of developing Alzheimer’s disease and other forms of dementia.
Alzheimer’s disease has no known cure, and its causes are also mysterious. The disease typically progresses over years, gradually robbing elderly patients of memory, language and other crucial mental skills. In very rare cases, people in their 30s or 40s can develop “early-onset Alzheimer’s”.
Notably, those who carry the genetic mutations known to encourage early-onset Alzheimer’s have elevated levels of certain protein fragments, called amyloid fragments, in their blood.
This finding caught the attention of epidemiologist Monique Breteler of Erasmus Medical Centre in Rotterdam, The Netherlands, because the same amyloid fragments form plaques in the brains of patients with Alzheimer’s, regardless of the age at which they develop the disease.
Dementia watch
Breteler and colleagues studied how blood levels of two slightly different amyloid fragments – Beta 1-40 and the slightly longer Beta 1-42 – relate to the risk of dementia among people who do not have early-onset Alzheimer’s.
The team took blood samples from 6713 volunteers over the age of 55 years who showed no signs of dementia. They analysed the blood for levels of the two amyloid fragments, and monitored the cognitive function of 1756 volunteers randomly selected from the sample group over an average of 8.6 years.
Of the closely monitored subgroup, 9% developed dementia. While most of these developed Alzheimer’s, others had dementia relating to other illnesses, such as Parkinson’s disease. To strengthen their analysis, researchers also included data from 230 patients in the initial study group who developed dementia, such as Alzheimer’s.
Dangerous ratio
The study showed that those with the highest Beta 1-40 levels combined with the lowest Beta 1-42 levels were 10 times more likely to develop dementia as those who had the lowest amounts of both fragment types. Subjects with high levels of both amyloid Beta 1-40 and amyloid Beta 1-42 had about the same risk of developing dementia as those with low levels of both.
As a result, Breteler believes it is the ratio of these amyloid fragments that matters. She speculates that lower levels of amyloid Beta 1-42 – the predominant component of Alzheimer’s plaques in the brain – may indicate that this is getting deposited in the brain instead of circulating in the body. Previous studies have suggested that amyloid Beta 1-40 is deposited in plaques during the later stages of Alzheimer’s.
But Breteler admits that it remains “debatable” how much protein levels in the blood reflect those in the brain.
While she says that this is by far the largest study to see how well the ratio of these amyloid fragments in the blood predict dementia, she also cautions that it is too soon to consider the method a reliable test. “I don’t think that we are at a test yet,” she stresses. “I think that’s really the next step.”

Nuns teach aging with grace
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A look inside a well-known Alzheimer's study that began 20 years ago
By TOM DUNKEL

'Down to a system'
That's a lesson worth imparting. America, like the School Sisters, is going gray. Millions of baby boomers are completing their long trip from rock 'n' roller to Social Security recipient -- and potential Alzheimer's patient.
The Nun Study has been the subject of a Time magazine cover story, a Nightline broadcast, radio shows, innumerable articles and one book, ''Aging With Grace,'' written by Snowdon. It has been credited with two landmark findings: establishing a link between vascular episodes -- such as strokes -- and the onset of Alzheimer's, and confirming a belief that intellectual activity helps ward off the disease.
Continuing his rounds, Snowdon taps on Sister Helen Fellenz's open door. She is 94 and taught music at the order's schools in Japan.
''I feel honored for you to come see me,'' Sister Helen says softly.
''Thanks for all you've done being part of the study,'' Snowdon tells her. ''The book just last year was translated into Japanese. How do you say 'thank you' in Japanese?''
''Arigato.''
Before Snowdon can visit her again, Sister Helen will die of heart failure, reducing the number of living Nun Study participants to about 150, less than a quarter of the original total.
Like all School Sisters, Sister Helen received the traditional Mass of Christian Burial, and was laid to rest wearing her SSND pin, a crucifix and rosary. But as a Nun Study sister, she had a parting gift for Snowdon: her brain.
''We have it down to a system,'' says Sister Bernice Feilinger.
Sister Bernice, coordinator for the Nun Study at Villa Assumpta, makes sure the bodies of all sisters in the study are immediately transported to Johns Hopkins Bayview Medical Center. A lab assistant removes each brain, placing it in a container of formaldehyde, where it sits 10 days before being shipped inside a foam-lined cardboard box.
In the Notre Dame community, the School Sisters who have volunteered for the study have a saying: ''When we die our souls go to heaven, but our brains go to Kentucky.''
Snowden stores the brain specimens, chronologically by death, at the University of Kentucky Medical Center in Lexington. It is believed to be the largest, most thoroughly documented collection of its kind: 520 human brains and counting. Snowdon, by training an epidemiologist -- a ''disease detective'' -- is their keeper.
In 1986, while completing his doctorate at the University of Minnesota, Snowdon began a pilot project on aging. For his control group, he chose a community of School Sisters of Notre Dame in Mankato, Minn.
COMING: Cause or effect?

Nuns teach aging with grace
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A look inside a well-known Alzheimer's study that began 20 years ago
By TOM DUNKEL
''How old are you, Sister?''
Sister Agnes Barbara Hettel smiles.
''I'm 92,'' she replies. ''I'm one of the young ones.''
That's an inside joke. Dr. David Snowdon gets it. Probably only God knows more elderly nuns.
Snowdon, a Kentucky neurologist, makes his way through the halls of Villa Assumpta, a converted mansion north of Baltimore that is headquarters -- ''the motherhouse'' -- for the School Sisters of Notre Dame.
About 80 retired nuns live here. Most are former teachers and administrators. In younger days, they taught students in Catholic schools here and shaped careers at the College of Notre Dame. Some keep busy staffing the reception desk or maintaining archives. Some are occupants of the third floor, a licensed medical unit, that is home for sisters with Alzheimer's disease.
That's where Snowdon, 54, is now.
Twenty years ago, Snowdon began research that now encompasses nearly 700 School Sisters across the U.S. As participants in his ''Nun Study,'' these sisters undergo annual physical and mental tests that gauge the effects of aging. Snowdon will track them until the day they die -- and beyond.
Their hope is to unravel the mysteries of Alzheimer's, the creeping dementia that affects 4.5 million Americans and, at a cost of $100 billion annually, ranks among the country's most expensive health problems.
The School Sisters in Snowdon's study left the classroom long ago. Now they're teaching a larger audience what it means to age well and with dignity.

COMING: 'Down to a system'

Study finds clue in preventing Alzheimer's
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NEW YORK, July 6 (UPI) -- Researchers said Thursday that the enzyme IDE -- at low levels in Alzheimer's patients -- may be a key to preventing the illness.
Researchers at the Neuroinflammation Research Center at Mount Sinai School of Medicine in New York set out to test the theory that increasing the amount of IDE in the body with synthetic enzymes as soon as levels start to drop could prevent the onset of Alzheimer's disease. The team saw that IDE levels were low in the memory-crucial hippocampus and entorhinal cortex of the brains of people with mild cognitive impairment, often a precursor to Alzheimer's. IDE breaks down beta-amyloid peptides, which cause amyloid brain plaques if their production is unchecked.
The team hypothesized that low IDE was responsible for the formation of these plaques. To test their theory, they measured beta-amyloid and IDE levels in the postmortem brain tissue of 46 elderly subjects and found that low IDE activity was indeed associated with elevated beta-amyloid peptides in both the hippocampus and entorhinal cortex.
The researchers said they will next determine how soon low IDE levels can be detected in the blood, and whether boosting these levels pharmacologically will prevent the formation of amyloid brain plaques and stop Alzheimer's disease before it begins.
Results of the study can be found in the June 10 online issue of Neurobiology of Aging.

Research Points to Alzheimer's Blood Test

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Vitamins Failed To Slow Mental Decline In Studymore...

Researchers Get Closer To Preventing Alzheimer's
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A recent study directed by Mount Sinai School of Medicine identifies a faulty molecule in the brain found in cases of mild cognitive impairment (MCI). Researchers say this faulty molecule may be responsible for the progression of MCI to mild Alzheimer's disease (AD) dementia. The study, which appeared June 10th online in the journal Neurobiology of Aging, may lead to preventative treatments for AD.
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An estimated 4.5 million Americans have Alzheimer's disease and presently there are no known cures or effective preventive strategies.
"Alzheimer's Disease is a growing health concern that affects millions of people, "says Giulio Maria Pasinetti, M.D., Ph.D., Professor of Psychiatry and Neuroscience, Director of the Neuroinflammation Research Center at Mount Sinai School of Medicine and lead author of the study. "We hope our research provides direction for preventative treatments to delay the onset of AD dementia by eliminating amyloid plaque-causing peptides in the brain."
People with AD exhibit elevated levels of beta-amyloid peptides that cause plaque buildup in the brain (the main characteristic of AD). In the earliest stages of Alzheimer's, beta-amyloid peptides are on the rise, especially in the two connected brain regions critical for memory functions-- the hippocampus and entorhinal cortex.
In this study, Dr. Pasinetti and colleagues at Mount Sinai School of Medicine in New York suggests one reason for that early increase of beta-amyloid peptides: an enzyme that breaks down beta-amyloid peptides, also referred to as an insulin-degrading enzyme (IDE), is not active in the brain in the cases at high-risk for developing AD. To assess possible changes in IDE during MCI, the investigators measured protein levels and enzymatic activity in postmortem brain tissue from 46 elderly subjects.

Vitamin B And Folate Combo Doesn't Sharpen The Mind
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Older people at higher risk of dementia do not benefit from a combination of vitamin B and folate, say researchers from the University of Otabo, Dunedin, New Zealand. Even after two years of taking the vitamins daily, volunteers did not better in cognitive tests than those who were given a placebo. All the participants had high levels of homocysteine, which is associated with a higher risk of dementia and low cognitive performance. Their homocysteine levels, at 16 µmol/L, were not quite high enough for dementia and/or cognitive impairment. In other words, none of the participants had dementia or cognitive impairment. They were all over 65, half of them had university degress. You can read about this study in the New England Journal of Medicine, 29 June, 2006. There were 276 participants in this study. Half took a placebo, while the other half were given 1,000 µg folate, 500 µg vitamin B12, and 10 mg vitamin B6. The researchers had expected homocysteine levels to lower after two years on the vitamin combination. Six months into the study those in the treatment group saw their homocysteine levels go down to 4.23 µmol/L, and stayed down throughout the two years. However, after comprehensive cognitive tests were carried out at the end of the two years, no difference was identified between the two groups. In some parts of the test - Part B of the Reitan Trail Making Test, say the researchers, the treatment group did worse than the placebo group. This part of the test measures the speed at which a person processes information. The researchers concluded that lowering homocysteine levels does not improve cognition in people with high homocysteine levels but without dementia or poor cognitive skills. They added that it would be interesting to find out whether the vitamin combinations may have offered any benefit for patients with mild cognitive impairment or dementia. New England Journal of Medicine.

Immunization with amyloid-beta attenuates Alzheimer-disease-like ...Amyloid-beta peptide (Abeta) seems to have a central role in the neuropathologyof Alzheimer's disease (AD). Familial forms of the disease have been linked ...
Funding for Alzheimer's research is key, scientists saySan Luis Obispo Tribune - San Luis Obispo,CA,USA... that plaques may impede the clearance of amyloid beta from the brain. These findings may be a useful antemortem marker of Alzheimer's, reported Niven and her ...

Foods You Can Eat to Stave Off Alzheimer's Disease
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Antioxidants Come to the Rescue By: Aaron Cummings
" Recent studies, including the study on wine, point to antioxidants for Alzheimer and Dementia risk reduction. " At the present time, one out of ten adults have some form of Alzheimer's disease. According to Dr. Greengard, Director of the Fisher Center for Alzheimer's Research at the Rockefeller University, that number is expected to strike up to three times as many in the coming decades. Alzheimer's is considered a disease of the elderly and with the average lifespan of the US population rising to 74, a solution to the medical problem is being sought.
For Scientists the largest concern is what causes Alzheimer's and how can it be eradicated. For possible victims and their families it is how do we prevent the dreaded affliction or stop it in its tracks once it is diagnosed.
Scientists are in agreement and have narrowed down the contributing factor causing Alzheimer's disease. Most researchers agree that Beta-amyloid is one of the agents thought to cause damage to the brain in Alzheimer's disease. The research is attempting to find a deterrent and is recognizing antioxidants to be significant in protecting at risk patients.
According to the Harvard Medical Center, continuing research and studies are being conducted with some positive results. Even though some studies by the French point to wine as a protectant, the results are considerably controversial. The component in the wine that was indicated to be responsible for the protectant agent is still somewhat ambiguous.
Recent studies, including the study on wine, point to antioxidants for Alzheimer and Dementia risk reduction.
In an Italian study conducted by A. Russo, et.al., it was found that black grape skin extract protected cells in a test tube from oxidative damage and DNA fragmentation when exposed to beta-amyloid. An even more recent study by E. Savaskan, et.al, examined the red wine ingredient resveratrol, and found it to be neuroprotective against beta-amyloid oxidative stress, again supporting an antioxidant mechanism.
What these studies point to is, red wine may have an effect that could provide some protection against Alzheimer's disease, but indication says it is the antioxidant factor that is the hero. This is consistent with the fact that other antioxidants, most notably vitamin E, are being studied with great interest as potential protective agents against Alzheimer's disease. According to Dr. Steve Seiner, of Harvard Medical School, "While the results of these studies do not necessarily suggest that people should drink wine in order to lower their risk of Alzheimer's disease, they do support the potential role of antioxidant treatment in preventing or delaying Alzheimer's disease.
In another study by Robert P. Friedland, MD chief of the neurogeriatrics laboratory at Case Western Reserve University School of Medicine, "If antioxidants prove to protect against Alzheimer's disease, it is probably because they reduce what is called 'oxidative stress' in cells." He went on to say that his team believes free radicals are the culprit of oxidative stress in cells caused by the inappropriate consumption of some foods such as those in high fat content. In this study Friedland is recommending a "to-do" list for those who want to improve their chances of maintaining a healthy brain. He suggests:
Eat a diet high in antioxidants
Eat fish
Take vitamin E
Take B vitamins
Take folic acid
Be mentally and physically active throughout life
Avoid head injuries
When addressing the reduction of free radicals it is essential to recognize the importance of Oligomeric Proanthocyanidins (OPC's) as the most powerful antioxidant known in scientific studies. OPC's are products commonly derived from a combination of grape seed extract, red wine extract and/or pine bark extract. They are very powerful bioflavanoids used as a natural food supplement ready to be absorbed into the body and begin to attack the free radicals.
OPC's are safe and have been used for over 20 years throughout Europe. Extensive studies and laboratory testing reveal no evidence for human toxicity, allergic reactions, birth defects, or carcinogenicity. OPC's work synergistically with other antioxidant vitamins, regenerating the antioxidant properties of vitamin C and vitamin E.
However, Bill Thies, PhD, vice president of medical and scientific affairs for the Alzheimer's Association says although Friedmand's recommendations are probably useful and that he agrees with all of them, he wants to "be very clear that the association is not making any recommendations about ways to prevent Alzheimer's. This is, however, involved in reading and learning about all studies concerning Alzheimer's Disease.
A study conducted in Rotterdam, Netherlands, Dr. Monique Breteler with the Eras UM Medical Center, found the antioxidants beta-carotene, vitamin C, and vitamin E appear to be equally protective as a reducing factor in the fight against Alzheimer's. Her results of the 5,000 volunteers over the past 14 years, confirmed some earlier studies that point to antioxidants as a way to lower risk of dementia. She also said the protective effect of antioxidants was "more pronounced among smokers and among those who are carriers of the Alzheimer's gene."
It was also pointed out that diets rich in antioxidants are helpful, but in order to consume the necessary requirements, a person would have to triple, or more, their current consumption, which Breteler says, is most unlikely. Recommendations for proper amounts of ingestion are through antioxidant supplements including OPC's, vitamin E and vitamin C.