Alzheimer Related News Items

News as of 02/06/05

For more info on these abstracts write/call Ed Cabic (edcabic@comcast.net or 410-992-7197)

For more AD information, see Alzheimer Information athttp://www.connext.net/~seniors/infoad.htm

Copies of these reports are posted there

This web page was started at the Florence Bain Senior Center in Columbia MD

Top Items

Mouse Experiment Offers AD Hope - Brain cells in mice recovered rapidly after brain plaques characteristic of AD were removed, offering hope that plaque-clearing treatments could benefit patients with the disease, Washington University researchers said 1/20/05. Plaque is a prime suspect for the cause of AD and several companies are developing drugs to target the buildup. Researchers at Washington University injected mice with an antibody that cleared plaque in parts of the brain. Where the plaque was cleared, swelling on nerve cell branches disappeared quickly, the researchers said. They cautioned that while encouraging, more studies are needed to determine if similar effects might occur in people. Removing the plaque “often led to rapid recovery of normal structure over a few days,” said Dave Holtzman, senior author of the study and head of the Department of Neurology at Washington University. He said that confirmed benefits of plaque-clearing treatments and “also gets us rethinking our theories on how plaques cause nerve cell damage.” Holtzman was among scientists who previously regarded plaque damage to nerve cells as something that happened once and was irreversible. Instead, the results suggest that plaques might not just cause damage but actively maintain it, he said. By Jim Salter, AP Writer1 /21/05 Journal of Clinical Investigation 115: 428-433 (2005)

Drugs

Safety Concerns Reported on J.& J. AD Drug - Regulators are reviewing the safety of the AD drug Reminyl after data from two clinical trials indicated that people taking the drug had a much higher death rate than those taking a placebo. The review was announced 1/21/05 by Johnson & Johnson, which said it was in discussions with the Food and Drug Administration and regulators in Europe and Canada. The trials, which involved about 2,000 patients in 16 countries, were looking at whether Reminyl could be used to treat mild cognitive impairment, a form of memory loss that is often a precursor to AD disease. Reminyl is approved in 69 countries as a treatment for mild to moderate AD but not for mild cognitive impairment. In the trials, which lasted two years, 15 patients taking Reminyl died compared with 5 taking the placebo. There were various causes of death but many were from heart attacks and strokes, a company spokeswoman, Carol Goodrich, said. The company said no regulatory applications have been submitted for the potential use of REMINYL® for the treatment of mild cognitive impairment anywhere in the world, nor are any planned. By Andrew Pollack NY Times 1/22/05 and PR 1/21/05

No Magic Pill for Treating Dementia Symptoms - Many of the drugs commonly prescribed to treat agitation, delusions and other symptoms that can accompany dementia are not effective, researchers from Wake Forest University Baptist Medical Center and colleagues report 2/2/05. “Our review of 29 research studies found that drug therapies are not particularly effective for managing symptoms such as agitation, wandering and delusions that are observed in most patients with dementia at some point in the illness,” said Kaycee Sink, M.D., lead researcher. “There is no clear standard of care, and treatment is often based on local prescribing customs.” While the primary symptoms of AD and other forms of dementia involve memory deficits, other symptoms, including agitation, aggression, delusions, hallucinations, repetitive vocalizations and wandering have been observed in 60 percent to 98 percent of patients. “Dementia-related behaviors are very distressing to both caregivers and medical professionals,” said Sink, a geriatrician. “It was discouraging to find that we currently don’t have good drug therapies for them.” PR 2/1/05 Journal of the American Medical Association 2005;293:596-608

Jefferson Scientists Help Explain Statins’ Effects in AD - Scientists at Jefferson Medical College and the Farber Institute for Neurosciences at Thomas Jefferson University in Philadelphia have taken another step in understanding the potential effects of anti-cholesterol drugs on AD. They have identified a biochemical pathway that explains the activity of statins, particularly their ability to break down an early form of the protein amyloid that clusters and forms sticky plaques in the AD brain. The results may eventually help provide new targets for anti-amyloid drugs to help treat AD. Some epidemiological studies have found a link between people taking statin drugs to lower blood cholesterol and a lower incidence of AD. Statins work by inhibiting an enzyme involved in cholesterol production, and currently is being tested in clinical trials for their possible effects in slowing the progression of AD. The researchers found evidence suggesting that an enzymatic pathway called Rho/ROCK may play an important role in the metabolism of APP (amyloid-beta peptide precursor protein), which is an early form of amyloid, and in turn, the ability of statins to break down a form of APP. According to the reseaarchers, APP can be broken down in two ways: “Bad cleavage” releases toxic amyloid-beta; “good cleavage” destroys it. Evidence shows that when the pathway ROCK1 is active, less good cleavage occurs. Statins, however, reduce ROCK1 activity, making it more likely that good cleavage will be in effect. “This reveals an unsuspected pathway linking statins and amyloid metabolism,” says Dr. Sam Gandy. “This may help unravel statin action in AD as well as point the way toward novel anti-amyloid drugs.” PR 1/10/05 Public Library of Science Medicine 1/11/05 Jan 2005, Vol 2, Issue 1 e18.

Myriad Genetics Initiates Phase 3 Clinical Trial of Flurizan in AD - Myriad Genetics, Inc. announced 1/12/05 that it has initiated enrollment in a Phase 3 human clinical trial of its lead therapeutic candidate, Flurizan (MPC-7869), in patients with AD. The Phase 3 trial is designed to determine Flurizan’s ability to alter the course of cognitive decline and behavioral change in patients with AD. The trial will be conducted in approximately 750 patients with mild to moderate AD, at approximately 100 centers in the United States. “There is a critical need for drugs that modify the underlying disease mechanism and progression of AD,” said Dr. Schneider. “MPC- 7869 has the potential to do this with its effect on reducing amyloid beta levels. We hope to confirm this in a large, well-controlled clinical trial.” Flurizan has been shown to modulate gamma-secretase and selectively lower levels of Amyloid beta 42, a toxic peptide that is believed to be a chief culprit in the cause of AD. In transgenic mouse studies, Flurizan has demonstrated the ability to reduce brain amyloid levels and prevent memory loss. Flurizan was selected during preclinical testing to avoid cyclooxygenase inhibition and its related side effects. PRNewswire 1/12/05

Cortex to Begin Phase II AD Trial - Neuroscience company Cortex Pharmaceuticals has received FDA permission to begin pilot phase II trials of CX717, a potential treatment for cognitive dysfunction arising from neuropsychiatric conditions such as AD, ADHD and sleep disorders. The first study of CX717 in the US will be a double-blind, placebo-controlled study using positron emission tomography (PET) imaging to determine the response of patients with AD, as well as healthy elderly volunteers, to CX717. In a similar study paradigm in primates, CX717 demonstrated specific activity in the prefrontal cortex, hippocampus and visual cortex, which are the key brain regions needed to improve memory, cognition and attention. PR 1/1/05

AD Drug for Brain Injury Resulting from Accidents and Serious Falls - The drug boosts the function of a key brain chemical called acetylcholine. The researchers believe that drugs called cholinesterase inhibitors, which block the breakdown of this chemical in the brain, may prove to be an effective treatment. Currently, cholinesterase inhibitors are used to treat the early symptoms of AD. Researcher Dr Claire Salmond from Cambridge University said: “We are very excited that this study may point the way to an effective treatment for this type of cognitive deficits.” Martin Wakeling, communications director of the head injury Headway, said: “The link between drugs for the treatment of AD and the treatment of brain injury has been made before but this new research adds to an important body of knowledge.” BBC News 1/15/05 Brain 2005 128(1):189-200

Genes & Genetic Issues

AD Gene Affects Even Healthy Seniors - Even if they’re healthy, older people with the higher-risk genotype for AD can suffer major problems with prospective memory -- the ability to remember what they need to do in the future, such as take medications or make a doctor’s appointment, a new study says. People who carry the high-risk e-4 allele on both of their ApoE genes are eight times more likely to develop AD as non-carriers. People with the high-risk allele on only one ApoE gene are three times more likely to develop AD than non-carriers, according to the research. University of New Mexico researchers studied a group of 32 healthy, dementia-free adults between 60 and 87 years old. Half of them carried the e-4 allele and half did not. The study participants were asked to do a prospective memory task that required them to remember to write a specific word when they saw a target word. Far more often than the non-carriers, the e-4 carriers forgot to remember to write down the specified word when they were supposed to, meaning they forgot to do what they meant to do, when they meant to do it. The findings counter the prevailing view that the e-4 allele has only subtle, undetectable effects on a carrier’s cognition, the researchers said. In light of the study results, doctors might consider helping even healthy e-4 carriers to improve their prospective memory, the study authors said. The study also suggests that testing prospective memory may prove useful as an early diagnostic tool for AD. “Our sample of carriers were healthy as far as we could tell, but our assessments were not as sensitive as some of those used at the major AD research centers. It might well be that some of our carriers were in early AD stages that were not yet detected,” study co-author Mark McDaniel said in a prepared statement. HealthDayNews 1/24/05 Neuropsychology 2005 vol 19(1) 28-34

Bush Signals Tougher Embryo Research Limits - President Bush plans to press for even stricter limits on human embryo research and has no intention of softening restrictions on stem cell research, a senior administration official said on 2/3/05. In the State of the Union address he said “I will work with Congress to ensure that human embryos are not created for experimentation or grown for body parts and that human life is never bought or sold as a commodity.” Supporters of embryonic stem cell research studied the brief comment for some signal of change in the policy, which limits the use of federal funds for embryo research to a few batches that existed as of August 2001. But there was none, the official said, adding that the White House would pursue limits on other research conducted by what she called “rogue scientists.” She referred to a 2003 experiment by Dr. Norbert Gleicher of the Foundation for Reproductive Medicine in Chicago, whose team injected male cells into female embryos. “This would prohibit that type of experimentation as well,” the official said, adding Bush plans to lay out a detailed, broader bioethics agenda in the near future. Reuters 2/3/05

Caregivers

Surf City, Here She Comes - Sometimes the residents of the Kensington Park Retirement Community in Kensington don't know quite what to make of Carolyn Layton. While her peers spend their days sitting in the sunroom downstairs, Layton reads six daily newspapers online, instant-messages her grandson in Maine and downloads bits of animation to attach to e-mails.Layton thinks her neighbors, some of whom suffer from early AD, would benefit from time spent online. “Half the people here are bored,” she said. Surfing the Internet “would keep their synapses firing.” Some claim that technology is the key to maintaining not only the health of mature adults, but also their social lives and their minds. For example, retirement homes built with high-speed Internet connections; about souped-up caller ID that not only identifies who is calling but reminds you of the people you know in common and the subject of your last conversation. Also “smart houses” that tell your daughter how many times you opened the refrigerator or got up off the sofa during the day, so she can call or stop by if she thinks something is wrong. As the oldest boomers approach 60, the distinction between youngsters and oldsters and information technology will diminish to the vanishing point. “This is a population that has had a longer interaction with technology -- and an expectation that technology makes life better,”said Beth Mynatt, lead researcher for the Aware Home initiative at Georgia Tech. While computing technology gave people a new way to communicate and access information, in the future it may help them stay out of an assisted living or nursing home setting for as long as possible. Delaying such a move “can make a big economic difference, as well as a personal one, for older adults,” Mynatt said. By Annys Shin Washington Post Staff Writer 1/30/05

Testing

Nanoscale Diagnostic Sets Sights On AD - Using their novel bio-bar-code amplification (BCA) technology, researchers analyzing fluid from around the brain and spinal cord have detected a protein linked in recent studies to AD. If proven successful in further clinical studies, the procedure could become the first tool for early diagnosis of AD, and the first test to conclusively identify the disease in living patients. Chad Mirkin and William Klein of the National Science Foundation (NSF) Nanoscale Science and Engineering Center (NSEC) for Nanopatterning and Detection Technologies at Northwestern University, and their colleagues, announce their findings in the week of 1/31/05. Because of the extreme sensitivity of the BCA process that Mirkin’s team developed, the researchers were able to detect within each fluid sample a miniscule amount of proteins called amyloid ß-derived diffusible ligands (ADDLs). The goal is to detect and validate infinitesimal amounts of the biomarkers in blood. Research by Klein and his colleagues suggests that ADDLs first appear in the earliest stages of AD. If the BCA process can identify the markers before symptoms develop, doctors may be able to combat the illness in its nascent form when treatments may be most effective. According to the researchers, BCA is about 1 million times more sensitive than the next best thing – standard enzyme-linked immunoassays (ELISAs). ELISAs do not have the sensitivity required to detect ADDLs in cerebrospinal fluid. Science Daily 2/2/05 Published online 2/9/05 in Proceedings of the National Academy of Sciences 10.1073/pnas.0500024102

Weight Loss May Be An Early Sign Of Dementia In The Elderly - Dementia-associated weight loss begins before the onset of the definite dementia symptoms and accelerates by the time of the diagnosis, according to a study in the January issue of the Archives of Neurology. Weight loss in old age is common and may be related to various diseases, according to background information in the article. “It has long been observed that weight loss is common in AD, but this has been documented in people who already have dementia.” Robert Stewart, M.D., From the Institute of Psychiatry, London, and colleagues analyzed data from 1,890 men (aged 77-98 years) who were participants in The Honolulu-Asia Aging Study. In conclusion the authors write: “An important consideration arising from research in this area is the extent to which weight loss may be prevented or minimized in dementia. Poor nutrition and frailty frequently complicate later stages of dementia, causing falls, poor wound healing, and increased physical dependence. ...The results presented here suggest that weight change and nutritional state in people with dementia should be taken seriously at least from the time of diagnosis if not at earlier stages of more mild cognitive impairment.” Science Daily 1/20/05 Arch Neurol. 2005;62:55-60

New Nicotine-like Imaging Agent Holds Promise in Pet Studies, May Help Diagnose AD - The chemical nicotine--a main ingredient in tobacco--may hold promise in the early diagnosis of AD, give insight into therapeutic interventions for nicotine addiction and possibly complement the diagnosis of certain forms of lung cancer, according to a study in the January issue of the Society of Nuclear Medicine’s Journal of Nuclear Medicine. Researchers are examining nicotine’s cognitive, behavioral and addictive actions, and, by looking at targets in the brain where nicotine acts, researchers hope to address several major health problems. Jogeshwar Mukherjee, Ph.D., at the Brain Imaging Center, at the University of California at Irvine (UCI) and a team of researchers from UCI and the Kettering Medical Center in Dayton, Ohio, found that imaging studies with a new fluorine-18 labeled imaging agent, nifrolidine, complement other ongoing positron emission tomography (PET) studies currently underway with nicotine-like PET imaging agents. Nifrolidine was developed to specifically bind to a receptor (protein) that is present in the human and nonhuman brain; this receptor is involved in several brain functions, particularly cognition and certain aspects of learning and memory. By binding at the same place as nicotine, nifrolidine helps to measure how and where nicotine acts. PET studies can be performed with nifrolidine to provide information on the receptor present in various regions of the brain. “Research has shown that with AD there is a gradual loss of these receptors; therefore, there is a potential of early diagnostic value in nifrolidine-PET imaging,” he said. The availability of a good PET imaging agent for this receptor will allow preclinical and clinical studies, leading to better understanding of different medical conditions and eventually helping in their diagnosis and treatment, said the researchers. PR 1/31/05 Journal of Nuclear Medicine 2005:46:130-140

Harvard Brain Images: Cat Versus Rat - Researchers at Harvand University have captured images from living animal brains, a milestone in trying to understand how neurons interact with each other inside the brain. Ultimately, the technique could be used to analyze neurodegenerative diseases like AD. Time lapse images released earlier in January 2005 provide a close-up of the neural circuits that produce vision in cats and rats. The subject animals were shown different pictures of black and white stripes in horizontal, vertical and diagonal patterns. The different patterns caused different groups of neurons to fire, represented by lights blinking off and on in the images. “This technique allows us to see the brain seeing,” R. Clay Reid, a professor of neurobiology at Harvard Medical School , said in a statement. Scientists have captured images of live neurons in the past but typically could only view a few cells at a time. This new technique, which can create images of larger tissue regions, could help researchers understand how--on a large scale--neurons work together to coordinate higher-level functions. It will also give researchers a deeper understanding of brain structure. By Michael Kanellos Cnet news.com 1/31/05

Prevention

Doctors Debate Value of Vitamin E - Doctors and other health professionals defended on 1/27/05 the safety of vitamin E, and reported on continuing studies that they said show its potential benefits in treating a variety of health problems. The conference followed the release of a John Hopkins study in November that found elderly, ill patients who took vitamin E daily at doses of 400 International Units (IUs) or more suffered a 6 percent increase in mortality compared to those who took placebos. One of the criticisms of the Hopkins study expressed by doctors at the conference, sponsored by the supplement industry and held in New York City, was that the conclusions were based on a group of older, ill patients, and these findings aren’t necessarily applicable to the general population. The doctors also criticized the statistical method used by the researchers -- called a “meta-analysis.” A meta-analysis is the use of statistical methods to combine results of separate studies. “Meta-analysis is not a great way to do a study because not everyone agrees on the end-point,” said Dr. Gerald M. Lemole, chief of cardiac surgery at Christiana Health Care Services in Newark, Del. “Also, you can’t say these results apply to the general population.” Dr. Edgar R. Miller, an associate professor of medicine at Johns Hopkins and lead author of the study, defended his statistical methods as the standard way to pool analyses. The study results were representative of those people who most often take vitamin E -- older individuals seeking health benefits and longevity. “Supplement trials focus on those with disease,” Miller said, and people in their 20s, 30s and 40s aren’t generally suffering from these illnesses. “Our study showed a slightly increased risk of mortality, but certainly showed no benefit,” he said. “There was a hint, however, which we noted in the study, that in the low dose -- 200 IUs or less -- there was protection,” he said. “Maybe we need to reexamine what dose we’re giving people.” Miller pointed to approximately 15 NCI trials under way looking into the efficacy of vitamin E. “We should let those studies run their course so we can answer this most definitively,” he said. By Janice Billingsley HealthDay Reporter 1/28/05 Forum “Vitamin E – Impact on Health and Disesase” NY City 1/27/05

U of Minn. Researchers to Study Effects of Vitamin E on AD Sufferers - Researchers at the University of Minnesota will receive $8.1 million to study the effects of vitamin E on people suffering from mild to moderate AD. In addition to vitamin E, the four-year study will look at the effects of a drug called memantine, which has been used to treat patients with more severe cases of the disease. Maurice Dysken, the Veterans Affairs Medical Center Geriatric Research, Education & Clinical Center director and University psychiatry professor said memantine and vitamin E have already proven effective in people with moderate to severe AD. He said the study will test the drug and vitamin both independently and combined on patients with mild to moderate AD who are already on standard treatments. “The study is designed for definitive evidence that these medications will be helpful,” Dysken said. By Naomi Scott The Minnesota Daily ½5/05

Drink a Day May Keep Older Women Sharp - Not only red wine but also white wine, beer and hard liquor appear to protect against mental decline in older women, two new studies have found. The studies are the latest to find a benefit from moderate drinking. In one, researchers at Harvard University and Brigham and Women’s Hospital published in NEJM followed alcohol consumption among more than 11,000 women enrolled in the Nurses’ Health Study, one of the largest investigations into the risk factors for major chronic illnesses in women. The researchers identified women in the study who were 70 or older. Women who consumed about a drink a day (up to 15 grams of alcohol, or about half an ounce), the researchers found, had significantly better test results - so much so that in their mental performance, they scored about a year and a half younger than the nondrinkers and those who drank 15 to 30 grams a day. A second paper, published in The Am. J. of Epidemiology, reported similar results in a group of 4,461 women.

The study, by Dr. Mark Espeland and his colleagues at Wake Forest University Baptist Medical Center in Winston-Salem, N.C., used different tests of mental abilities and found that women who had one drink a day scored higher than those who did not drink at all. The reason that alcohol seems to have this beneficial effect is not entirely clear, but it is probably connected to the significantly lower rates of cardiovascular disease among moderate drinkers, a phenomenon that has been known for some time. Alcohol appears to raise levels of H.D.L. cholesterol, the so-called “good cholesterol,” and to lower levels of blood clotting agents like fibrinogen. This may help prevent not only heart attacks, but also the small, subclinical strokes that cause vascular damage in the brain and lead to mental deterioration. By Nicholas Bakalar NY Times 2/1/05 1^st study The New England Journal of Medicine 352:245-253. 2^nd study The American Journal of Epidemiology 161:228-238

Evidence Mounts That Keeping the Brain Fit Could Ward off AD - Minds in motion stay sharp. At 87, Katie Johnson is convinced she has a surefire way to ward off AD: the fox trot.

Research suggests those nights spent whirling around the dance floor and days motoring around town in her snappy car probably are increasing Johnson’s chances of avoiding the dreaded disease of debilitating memory loss. The best AD prevention might be this simple: Go have fun. Such familiar leisure activities as book groups and Friday night poker clubs might help keep the brain sharp and decrease the odds of developing AD, according to research at the Albert Einstein College of Medicine in New York and the Karolinska Institute in Stockholm, Sweden. The Albert Einstein study found that the most active seniors, both mentally and physically, reduced their risk of developing dementia by 63%, compared with the least active seniors. Researchers are now finding the best activities are those that challenge the brain, are done with other people and might even involve a good workout, such as a fast spin around the dance floor. “Retirement is no excuse for an idle brain,” says Murali Doraiswamy, an AD expert at Duke University.”'If you’re not active, then you’re more susceptible to the onslaught of AD.” USA TODAY 1/25/05

Reduced Calorie and Carbohydrate Diet Slows Progression of AD in Mouse Model - Researchers found that a low carbohydrate diet that reduced total caloric intake by 30% prevented the development of a fundamental feature of AD in a strain of mice genetically engineered to develop the disease. The diet eliminated amyloid plaque development, which is the underlying pathology in AD. The study is the first to demonstrate that a change in diet can slow and possibly prevent AD. “While it is far too early for us to make specific recommendations for human diets,” said Giulio Maria Pasinetti, MD, PhD, Professor of Psychiatry, Neurosciences and Geriatrics and Adult Development at Mount Sinai School of Medicine and primary investigator on the study, “these findings provide the first solid evidence that dietary changes may provide a new approach to treatment and prevention of this devastating disease.” Dr. Pasinetti and his colleagues found that mice did not develop the physiological markers of the disease when they were fed a reduced carbohydrate diet that provided 70% of the calories eaten by similar mice who were allowed to eat ad-libitum. PR 1/12/05 Published online1/13/05 in The FASEB Journal doi:10.1096/fj.04-3182fje

Other Items

Constant Worry May Increase AD Risk - People who have a tendency to worry or feel very stressed out may be more likely to develop AD later in life, new research reports. The relationship between stress and AD also appears to be much stronger in whites than in African-Americans, the authors note in the journal Neurology. The nature of the connection between a tendency to worry and the memory-robbing disease is still unclear, study author Dr. Robert S. Wilson of Rush University Medical Center in Chicago told Reuters Health. However, he said that he suspects that chronic elevations of stress hormones may damage regions of the brain that regulate both behavior under stress and memory. Wilson emphasized that this study only connects stress and AD, and does not prove that one causes the other. The report “does not establish that distress causes dementia,” Wilson noted. But while it’s too soon to recommend that people reduce their stress to help avoid AD, there are many other healthy reasons to relax, he added. “The tendency to experience psychological distress is a trait that we all have to greater or lesser degrees,” Wilson noted. “Family or friends concerned about a loved one who is chronically unhappy should encourage the person to see a qualified mental health professional.” By Alison McCook Reuters Health 2/4/05 Neurology 2005 ;64:380-382

NPH Strikes Senior Citizens, Often Mistaken for AD, Parkinson’s - The NBC Today Show featured a segment 1/26/05 on NPH (Normal pressure hydrocephalus), a treatable brain disorder caused by blockage of the flow of cerebrospinal fluid, that primarily strikes senior citizens and is often confused with AD or Parkinson’s. It may result in loss of any or all brain functions controlled by the area of the brain which is compressed by enlargement of the ventricles within the brain. Normal pressure hydrocephalus (NPH) can be a reversible or treatable disorder. It is thought to account for about 5% of all dementias. The incidence is 1 out of 100,000 people. NPH can occur at any age, although primarily occurs in people over 60. The onset of symptoms is often gradual. NPH is a form of hydrocephalus, also known as “water on the brain,” which means there is too much fluid compressing the brain. It can occur without identifiable cause, or it may be caused by any condition where there is an obstruction to the flow of cerebrospinal fluid (CSF). The CSF is produced in normal amounts in this condition, but it is prevented from being normally re-absorbed. There are three classic symptoms of NPH: difficulty walking, mild dementia, impaired bladder control. The diagnosis of NPH can be difficult because the symptoms are also associated with illnesses like AD and Parkinson’s disease as well as with the normal aging process. People often assume they must live with these changes so they don’t seek help. Patients presenting the three primary symptoms should be referred to a neurologist or neurosurgeon for a complete neurological work-up including clinical assessment, computerized tomography (CT) and/or magnetic resonance imaging (MRI) scans, cerebrospinal fluid flow studies and others. Although NPH cannot be cured, it can often be controlled. Successful candidates for treatment are identified during diagnostic testing. Treatment for NPH involves surgery and the placement of a shunt by a neurosurgeon to drain excess cerebrospinal fluid (CSF) from the brain and divert it to another part of the body where it is reabsorbed into the bloodstream. Senior Journal.com 1/16/05

Blacks More Prone to AD - AD is a silent epidemic striking black Americans, who seem more susceptible to the brain-wasting condition than any other group of Americans, new research finds. One possible explanation: Black Americans are at greater risk of vascular disease, such as high blood pressure and high cholesterol levels. And studies have found that people with a history of either high blood pressure or high cholesterol are twice as likely to succumb to AD, according to the Alzheimer’s Association. Statistics are hard to come by because black Americans aren’t well represented in studies on AD. But recent research has found dementia is anywhere from 14 percent to 100 percent more prevalent among the black American population than among whites, according to Stephanie Johnson, a research associate at Duke University Medical Center's Bryan AD Research Center. And, she added, nearly half -- 44 percent -- of first-degree relatives of black AD patients are at risk for the disease. “Highlighting the racial difference in prevalence rates for AD wasn’t really on the radar screen because of all the other health disparities we focus on. But when you start to put the pieces of the puzzle together, it makes sense,” said Johnson, who is also a clinical associate professor at Duke’s department of psychiatry. Most telling, she said, is the high rate of vascular disease among black Americans, a known risk factor for AD. “Hypertension, type 2 diabetes and high cholesterol, which are highly prevalent among African-Americans, are significant risk factors for the development of AD,” Johnson said, and could be the reason first-degree relatives are at high risk for the disease as well. By Janice Billingsley HealthDay Reporter 1/30/05

Progress Toward a More Targeted Treatment of AD - Scientists from the Flanders Interuniversity Institute for Biotechnology (VIB) connected with the Catholic University of Leuven have shed a little more light on AD. They’ve gone deeply into the operation of γ-secretase, a crucial factor in the origin of the disease. Their research has revealed that the action of γ-secretase is not homogeneous - as previously assumed - but quite differentiated. This discovery opens up perspectives for new medicines that will have fewer undesired side effects than current medicines do. AD involves a kind of plaque that forms in the brain cells. A major role in this process is played by γ-secretase, an enzyme that cuts proteins in a particular place. Sometimes the γ-secretase cleavage goes wrong, causing the creation of a by-product that sticks together and precipitates - thus forming the plaque. In their quest for new medicines, scientists are investigating this key role of γ-secretase to try to find substances that are able to block the formation of plaques. A thorough understanding of γ-secretase is therefore critical. γ-secretase is divided into several entities, but until now scientists have assumed that the complex acts as a homogeneous unit. However, Lutgarde Serneels and Bart De Strooper now show that γ-secretase’s various sub-units exhibit very diverse, tissue-specific activity. They have deduced this from research in which they inactivate one or more sub-units in mice. The effect of this inactivation turns out to be very specific for each sub-unit: in one instance, the mice embryos were not viable; but the inactivation of another sub-unit led to adult mice in which the activity of γ-secretase was significantly reduced. This opens up new possibilities for the development of medicines that focus on the inactivation of γ-secretase. Because current methods prevent the action of the entire complex, they also cause a lot of undesired side effects. The findings of the Leuven researchers should make it possible to develop medicines that are targeted on a single sub-unit and thereby have a much more specific action. PR 2/1/05

Thinning Bones Linked to AD Risk - People with low bone mineral density (BMD) are at increased risk of developing AD, researchers report. Low BMD is also associated with all-cause dementia in women, but not men. “Some, but not all studies have suggested that estrogen replacement therapy has a beneficial effect on cognition in postmenopausal women,” Dr. Zaldy Sy Tan, of Beth Israel Deaconess Medical Center, Boston, and colleagues write in the Archives of Neurology. “BMD is a potential surrogate marker for cumulative estrogen exposure.” In a community-based study, the researchers examined whether low BMD in almost 1000 mentally intact elderly patients increased their risk of AD. The subjects had bone density measured at several places in their body between 1988 and 1989. During 8 years of follow-up, 95 participants developed dementia. Of these, 75 were classified as having AD. Overall, 35 of the 243 patients in the lowest category of hipbone density developed dementia, classified as AD in 27. After adjusting for age, smoking, estrogen use, sex, stroke, education and other factors, women with the lowest BMD had twice the risk of developing AD and dementia, the researchers found. These findings, Tan’s group concludes, suggest that women with low BMD “may benefit from estrogen replacement therapy” -- despite the well-known increased risk of other complications. Reuters Health 1/26/05 Archives of Neurology 2005;62:107-111

AD Affects the Sexes Differently: Study - Researchers studying the changes AD triggers in human brains say the disease affects men and women differently. The same disease causes more shrinkage in the brains of men, and less in women -- results that surprised the Canadian scientists doing the research. “We thought women would show more atrophy than men because women are more vulnerable to AD than men,” said Dr. Sandra Black, a neurologist with Sunnybrook & Women’s College Health Sciences Center. “The surprising thing was that the opposite was found. Actually the men showed more atrophy.” The study is the first to examine specific sex differences in the portion of the brain believed to handle emotions and memory. It examined the brains of 40 men and women with probable AD, as well as 40 control subjects. Researchers have already shown that the brains of both men and women with AD tend to have similar differences in comparison to brains of people without the disease. So, this latest study was designed to identify whether there were differences in the size of, or blood flow in, male and female patients’ brains. By controlling for other factors, such as differing levels of education and head size, the researchers say the biological mechanism behind the sex difference remains the subject of speculation. But it could lead to new diagnostic tests and perhaps even different forms of drug treatments for men and women. “What we suspect is that it will be important to have separate analysis for men and women,” Black said. “So that you are treating them not together, but as separate groups when you are looking at how they respond to treatment.” CTV.ca 1/26/05

MetLife Foundation Recognizes Scientists for Research in AD - The MetLife Foundation Awards for Medical Research in AD were presented in Washington, D.C. today to William E. Klunk, M.D., Ph.D. and Chester A. Mathis, Ph.D., of the University of Pittsburgh School of Medicine; John C. Morris, M.D., of the Washington University School of Medicine in St. Louis, and Ronald C. Petersen, M.D., Ph.D., of Mayo Clinic. The awards recognized the scientists for their clinical research on early detection and diagnosis of AD. $700,000 was shared by the winners to further work in AD research. Drs. Klunk and Mathis have developed experimental non-invasive methods of detecting and creating images of amyloid-beta proteins - plaques that form in the brain tissue of AD sufferers - using dyes to make the plaques visible through the use of medical imaging equipment. The ability to see amyloid deposits in living patients will allow researchers to directly measure the effects of anti-amyloid therapies now being developed. Dr. Morris was recognized for his work in developing clinical methods to identify the earliest symptomatic stages of AD, evaluating new drug therapies in the treatment of dementia, and establishing phenotypes for inherited forms of AD and other dementia. Dr. Petersen, Director of Mayo Clinic’s AD Research Center and neurologist to President Ronald Reagan, focuses his research in the area of mild cognitive impairment and predictors of progression to AD. Those past the age of 65 with mild cognitive impairment are found to be at an increased risk of developing AD than otherwise healthy individuals the same age. Business Wire 2/2/05

D:\AD18\adn0205.htm