Alzheimer Related News Items

News as of 09/04/05

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 Top Items

Next-generation Vaccine Trial under Way - Elan Corp. plc and Wyeth Pharmaceuticals have launched a Phase II clinical trial of their second-generation AD vaccine AAB-001. The trial will enroll about 180 individuals age 50 to 85 with mild to moderate AD at study centers nationwide. Participants are allowed to take currently approved AD drugs if they have been on a stable dose for at least four months. Full details and a list of study sites are posted on http://ClinicalTrials.gov . AAB-001 contains monoclonal antibodies, synthetic, laboratory-produced molecules engineered to zero in on a specific target. AAB-001 targets beta-amyloid, a sticky protein fragment considered a prime suspect in disabling and destroying brain cells in AD. Monoclonal antibodies can be given in set doses like any other drug because they do not stimulate the immune system to produce its own antibodies. AAB-001 is given by intravenous injection. The developers hope the lack of impact on the immune system will help AAB-001 avoid triggering inflammation of the brain and spinal cord. Brain inflammation emerged as a serious side effect that prematurely ended studies of AN-1792, the first AD vaccine ever to reach clinical trials. AN-1792, also developed by Elan and Wyeth, was a form of beta-amyloid, designed to stimulate the immune system to produce its own antibodies to beta-amyloid. Www.alz.org 7/15/05

Nasal Vaccine Might Slow AD - Researchers think they are close to devising a deceptively simple way to prevent the progression of AD: a nasal spray vaccine. Although it has so far only been tested on mice, the vaccine is a combination of two medications -- Protollin and glatiramer acetate, which has already been approved to treat other conditions, such as multiple sclerosis (MS). The spray targets what many researchers suggest is the most probable cause of AD -- the abnormal build-up in the brain of a sticky substance called beta-amyloid plaque. “This is a vaccine in the scientific sense of the word, in that I’m very hopeful it could stimulate the immune system to reduce this build-up among people with early signs of AD as well as for those in later stages of the disease,” said study co-author Dr. Howard L. Weiner, co-director of the Center for Neurologic Diseases at Brigham and Womens Hospital in Boston. Weiner and his colleagues took a different approach from the traditional vaccine design that sought to provoke the development of antibodies to eliminate amyloid, by designing a vaccine -- administered via drops in the nose -- that would initiate an amyloid-cleansing process by triggering the immune system without provoking antibody development. The researchers targeted a specific type of amyloid-eating cell known as a microglial cell -- stimulating the cells into action to essentially gobble up the amyloid build-up. The authors found that, overall, amyloid plaque levels in the vaccinated mice were reduced by 73 percent. None of the vaccinated mice showed any evidence of encephalitis or other toxic side effects. By Alan Mozes HealthDay Reporter 8/11/05 Journal of Clinical Investigation 115:2423-2433 (2005)

Drugs

Study Questions Statins’ Value Against AD - Cholesterol-lowering drugs called statins have been linked to a decreased risk of AD and other dementias, but a new study questions that association. According to the results of this latest study, use of statins and other lipid-lowering drugs showed no association with reductions in the risk of AD or other types of dementia in older adults. Statins may reduce the risk of heart disease by blocking the production of cholesterol or by serving as an anti-inflammatory, experts say. Both these mechanisms may also play a part in the development of AD and other dementias. In their study, Dr. Thomas D. Rea, of the University of Washington, and colleagues collected data on nearly 2,800 people 65 or older enrolled in the Cardiovascular Health Study. After accounting for other risk factors, Rea’s team found that, compared with people who never took statins, those who did showed no reduction in their risk of developing AD or any other dementia. The reasons for the finding may include the length of time patients were taking statins, Rea’s group noted. “Several factors may explain why statin use was not associated with a lower risk of dementia,” they wrote. “Participants were on average 75 years of age, and statin use was assessed for a median of five years. Statin exposure may need to occur earlier in adulthood or for longer periods to prevent dementia, although analyses that stratified the duration of statin use did not suggest a duration-dependent association.” By Steven Reinberg HealthDay Reporter 7/11/05 Archives of Neurology 2005;62:1047-1051 (July)

Scientists Discover That Three Molecules May Be Developed into New AD Drugs - A team of scientists has discovered three molecules –– from a search of 58,000 compounds –– that appear to inhibit a key perpetrator of AD. Each of the three molecules protects the protein called “tau,” which becomes hopelessly tangled in the brains of patients with AD. The finding is promising news for the development of drugs for the disease. Ken Kosik, co-director of the Neuroscience Research Institute at the University of California, Santa Barbara, headed the effort to find these molecules. “Tau goes wrong and becomes pathological when it becomes intensely phosphorylated,” said Kosik. “This means that many phosphate groups attach to tau--modify it--and cause it to become dysfunctional.” The culprit is an enzyme, called CDK5, that attaches the phosphate to the tau protein, facilitating the disease process. The researchers set out to find a way to inhibit this enzyme, to keep it from putting any phosphate on tau. Small molecules are preferred because they are more easily used as a drug since they can get through the body and into cells. It is also important to find molecules that will cross the blood brain barrier. They then set up a test of nearly 400 small molecules that fit their criteria. The test results showed three small molecules that can inhibit the enzyme. These are candidates for development as drugs. Kosik explained that proteins are strings of amino acids folded into small globs. All proteins that happen to be an enzyme involved in phosphorylation have one thing in common. They have a pocket that is almost always in the same place and this is where the phosphate attaches to the enzyme, in this case CDK5. To get a molecule that specifically prevents the enzyme from binding at the pocket is difficult. Of the three compounds that the research group found, the scientists were able to locate where they bind. They found that one binds in the pocket, another binds at the edge of the pocket, and a third appears to bind completely outside the pocket. The scientists are most interested in the second and third compounds. “This is the first demonstration that we can find small molecules that can more specifically affect the phosphorylation of tau by CDK5,” said Kosik. PR 7/22 Chemistry and Biology 12:811-823, July 2005

More Effective AD Drugs Are on the Way - Researchers at The Hebrew University of Jerusalem have explained how drugs against AD inhibit the production of a destructive, inflammation-causing protein in the brain. The team working on this project was headed by Prof. Raz Yirmiya of the psychology department and Dr. Yehuda Pollak, a post-doctoral fellow in Yirmiya’s lab. Medicines administered today for AD focus on preventing the breakdown of acetylcholine, a chemical which transmits information within the brain and is vitally involved in cognitive processes such as memory, attention and thought. Because acetylcholine-producing cells are among the first to die in AD patients, drug-induced elevation of acetylcholine levels slows cognitive deterioration. In recent years, researchers have shown that another pathological process occurs in the brain of AD patients – excessive immune activation and inflammation, which are triggered by overproduction of an inflammation-producing protein called interleukin-1, as well as a few other related compounds. This process can impair the functioning of nerve cells and can even lead to their death. In addition, genetic alterations in the interleukin-1 gene are linked with increased risk for the appearance and severity of AD symptoms. The researchers found that anti-AD drugs currently in use not only block the activity of the enzyme responsible for breaking down acetylcholine, but also cause a marked reduction in the production of interleukin-1. They also describe the use of a novel drug (EN101) which produces these effects in a more efficient way – by destroying the “messenger RNA” of the enzyme rather than simply blocking the enzyme’s activity. In a series of experiments, conventional drugs for AD, as well as the novel drug EN101, were injected into mice with brain inflammation. These drugs significantly reduced the activity of the enzyme that breaks down acetylcholine, and almost completely blocked production of interleukin-1. “These findings suggest a new role for acetylcholine,” said Yirmiya. “When the anti-AD drugs block the enzyme that breaks down acetylcholine, the level of this chemical in the brain goes up, and there is a reduction in production of the inflammatory material, interleukin-1, and its destructive influence in the brain.” By Judy Siegel-Itzkovich, the Jerusalem Post 7/24/05 Annals of Neurology 57,5:741-745

New Liquid Form of AD Drug Namenda Approved By FDA - A drug that fights mild to severe AD has been approved by the Food and Drug Administration for liquid oral forms. Forest Laboratories, Inc. announced 8/19/05 that an oral solution formulation of Namenda (memantine HCl), is now available to physicians, patients, and pharmacies nationwide. Oral solution offers an alternative that may make the ingestion of Namenda easier for those patients who have trouble swallowing tablets. Namenda is the first in a class of medications approved by the FDA with a unique mechanism of action that focuses on the glutamate pathway, a target for the treatment of AD. By Douglas Maher All Headline News Staff Reporter 8/20/05

AD Toxin May Be Key to Slowing Disease - Australian scientists say they have identified a toxin which plays a key role in the onset of AD, raising hope that a drug targeting the toxin could be developed to slow the degenerative brain disease. The toxin, called quinolinic acid, kills nerve cells in the brain, leading to dysfunction and death, the scientists said. “Quinolinic acid may not be the cause of AD, but it plays a key role in its progression,” AD researcher Dr Karen Cullen from the University of Sydney said in a statement. “It’s the smoking gun, if you like.” “While we won’t be able to prevent people from getting AD, we may eventually, with the use of drugs, be able to slow down the progression.” Quinolinic acid is part of a biochemical pathway called the kynurenine pathway which is also found in other brain disorders, including Huntington’s disease and schizophrenia. The scientists said there were several drugs in an advanced stage of development for other conditions which targeted this pathway and that these drugs, which still need to be tested, could be used to complement other treatments for AD. “Building on what we’ve found and others have found, it’s likely that they would have significant effect,” said Professor Bruce Brew, director of neurology at St Vincent’s Hospital. Reuters 8/4/05 Neuropathology and Applied Neurobiology 31,4:395-404

Hope for AD Blossoms with Daffodils - A substance found in the Welsh national flower, which could offer hope for sufferers of AD, is being supported for large scale manufacture by Cardiff University’s Manufacturing Engineering Center (MEC). Certain species of daffodil, which thrive in the Black Mountains of South Powys, produce galanthamine, a leading drug in the alleviation of memory loss symptoms. The University’s Manufacturing Engineering Center is now helping a company Alzeim Ltd to develop the agricultural potential of the daffodil as a medicinal plant along with the Institute of Grassland and Environmental Research at the University of Wales, Aberystwyth. The Center is providing support from harvesting in the field to marketing the pharmaceutical product. This includes assisting with the science of developing crops more than once a year and helping growers to assess when the best time to harvest the crop. Medical New Today 8/3/05

Eisai Submits Application to FDA for Aricept for Treatment of Severe AD - Eisai Co., Ltd. and Eisai Inc. announced 9/1/05 that they have submitted a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration for Aricept (donepezil HCl tablets) for the treatment of severe AD. Aricept, is co-promoted in the United States by Eisai Inc. and Pfizer Inc, and is currently approved for treatment of mild to moderate AD. PR 9/1/05

UK Wants More Proof on Value of AD Drugs - The UK’s watchdog for cost-effectiveness in medical treatments has asked drugmakers for more evidence about the benefits of their AD medicines, prolonging a bitter row over whether the drugs should be paid for by the state.  The National Institute for Health and Clinical Excellence (NICE) said on 7/19/05 its experts still believed the pills should not be prescribed routinely, but that there might be a sub-group of patients for whom they worked particularly well. The decision leaves in limbo the future of four drugs, including Pfizer Inc and Eisai Co Ltd’s market leading product Aricept, users of which are currently reimbursed on the state health service and are widely used around the world.

Although they do not work for everyone, the drugs can improve memory and delay the progression of AD by between six to 12 months, according to Clive Ballard, director of research at the Alzheimer’s Society. Ballard said NICE’s failure to back the products was “outrageous” and its request for more information on effectiveness made no sense, since the medicines had already been assessed in more than 30 clinical trials. NICE will consider any fresh evidence from companies at the next meeting of its appraisal committee in October. By Ben Hirschler Reuters 7/19/05

Forest Labs to Keep Studying Its Neramexane AD Drug - Forest Laboratories said 7/14/05 that a new clinical trial of an experimental AD drug has encouraged the company to continue working on it. The drug is neramexane for moderate to severe AD. Eleven months ago, Forest reported that a late-stage clinical test of neramexane failed to meet its goals. In that test, patients receiving a combination of neramexane plus standard AD drug called acetylcholinesterase inhibitors didn’t do any better than patients getting one of the standard drugs. In the latest study, Forest compared neramexane patients vs. patients receiving a placebo. The company said the test “showed sufficient clinical activity, safety and tolerability to continue development of the compound.” Forest has viewed neramexane as an important building block in its AD efforts. It already sells Namenda, a member of the same class of drugs as neramexane, for patients with moderate to severe AD. Both drugs are licensed to Forest from the German drug company Merz Pharmaceuticals. By Robert Steyer TheStreet.com Staff Reporter 7/14/05

Possible Pathway to Development of AD Drugs - A new research approach to understanding the cellular processes of degenerative brain diseases could lead to the development of new drugs to treat these illnesses. Amyloid formation, or the twisting of cellular proteins into abnormal shapes, is linked to AD, Huntington’s, Parkinson’s and other degenerative diseases but has left scientists puzzled as to how it kills the cells and leads to disease. Researchers, including Ratnesh Lal, a scientist from the Neuroscience Research Institute at the University of California, Santa Barbara, examined the three-D structure of several different proteins associated with the diseases. They noticed misfolded proteins in the cell membrane -- resembling ion channels -- and changes in the electrical properties of cells. The researchers found that the proteins were capable of producing electrical currents when embedded into artificial membranes, confirming their similarity to ion channels. It was previously known that abnormal ion balance disrupts cell function and causes degeneration, proving the possibility that amyloid formation may lead to the cellular destruction associated with neurodegenerative diseases. “These ion channels could serves as a model system for designing preventive and therapeutic drugs,” said Lal. “You don’t need large aggregates of these amyloid proteins, the plaque, to have this disruption. Rather, small aggregates, when in contact with membrane, form ion channels and allow passage of ion current. By controlling activity and designing specific drugs to regulate these channels, we might be able to prevent and/or treat various diseases related to the amyloids.” Ivanhoe Newswire 7/13/05 Proceedings of the National Academy of Science, 2005;102:10427-10432

Scientists Investigate Drugs for Treatment of AD - Scientists are investigating a class of pharmaceuticals that may well improve memory function, including those with AD, and address some of the underlying causes of memory loss rather than today’s drugs that simply treat symptoms. Cortex Pharmaceuticals is testing and developing a second-generation class of pharmaceuticals classified as ampakine compounds. Its lead compound, CX-717, is expected to treat the memory and thinking disorders associated with Mild Cognitive Impairment, and AD as well as other disorders. It is believed that loss of connections between brain cells is responsible for memory loss. Ampakine compounds are said to increase the signal strength at those connections. (See http://www.cortexpharm.com for more detail.) Ampakines are designed to compensate for deterioration of AMPA-receptor mediated brain activity in patients with AD and other disorders. Ampakines may also increase the amount of certain growth factors in the brain, which, in turn, may help treat the underlying causes of conditions like AD. Cortex Pharmaceuticals also recently announced that it began enrollment in the second and third AMPAKINE CX717 Phase IIa studies: one in Attention Deficit Hyperactivity Disorder (ADHD) and the other in mild to moderate AD. PR 8/18/05

FDA Deals Forest Labs a Setback - Forest Laboratories said the Food and Drug Administration rejected the company’s application to expand the coverage of its AD drug Namenda. Although Namenda is the only product approved in the U.S. for moderate to severe AD, the FDA turned down Forest’s request that it also be approved for treating mild AD. Namenda was approved for treating moderate to severe forms of the disease in October 2003. Forest said it plans to discuss the rejection with the FDA. By Robert Steyer TheStreet.com Staff Reporter 7/25/2005

Nymox AD Test Not Proven - US Experts - A U.S. Food and Drug Administration advisory panel rejected Nymox Pharmaceutical Corp.’s urine test for AD in a 5-2 vote on 7/15/05. The company’s study did not prove the test, called AlzheimAlert, was effective, the panel of outside experts said. The FDA, which refused to approve the test in 2004, usually follows its panels’ advice. AlzheimAlert aims to detect levels of neural thread protein, a brain protein found in high levels in AD patients in a urine sample. Reuters 7/15/05

Genes & Genetic Issues

Embryonic Stem Cells Found to Acquire Mutations - Human embryonic stem cells, treasured by researchers because of their potential to help rejuvenate ailing organs, do not remain as ageless and perpetually unblemished as scientists once thought, according to a new research report. Like ordinary cells, stem cells accumulate significant numbers of mutations over time, including several that could cause them to become tumors. The findings, reported by an international team of scientists 9/4/05, could bolster those who have been calling upon President Bush to allow the use of federal money to create fresh stem cell colonies. Researchers hoped to harvest batches of the cells periodically from master colonies and turn them into various kinds of tissues for transplantation into patients. But the longer stem cells are cultivated -- and the more cell divisions they undergo -- the more mutations build up in their genes, Aravinda Chakravarti of Johns Hopkins Medical Institutions and his colleagues reported in the journal Nature Genetics. By Rick Weiss Washington Post Staff Writer 9/5/05 Nature Genetics published online: 4 September 2005; doi:10.1038/ng1631

Skin Cells Converted to Stem Cells - Scientists for the first time have turned ordinary skin cells into what appear to be embryonic stem cells -- without having to use human eggs or make new human embryos in the process, as has always been required in the past, a Harvard research team announced 8/21/05. The technique uses laboratory-grown human embryonic stem cells -- such as the ones that President Bush has already approved for use by federally funded researchers -- to “reprogram” the genes in a person’s skin cell, turning that skin cell into an embryonic stem cell itself. The approach -- details of which are to be published in the journal Science is still in an early stage of development. But if further studies confirm its usefulness, it could offer an end run around the heated social and religious debate that has for years overshadowed the field of human embryonic stem cell research. By Rick Weiss Washington Post Staff Writer 8/22/05 Science 309:1369-1373 Aug 26, 2005

New Technology Could Lead to AD Cure - New technology for mass-producing nerve stem cells, which can grow into all kinds of nerve cells, has been developed. According to a research report published in the recent issue of PLoS-Biology, a U.S. science journal, a joint research team at the universities of Edinburgh and Milan succeeded in experimenting with the divisional proliferation of nerve stem cells in test tubes without differentiating them into nerve cells. Until now, stopping nerve stem cells from differentiating into nerve cells in test tubes has been a major obstacle for scientists. Since it is now possible to make nerve stem cells from human embryo stem cells and mass produce them in the test tube, the solutions for curing degenerative nerve diseases such as AD and Parkinson’s will be available earlier than expected because new drugs can be tested without limit using the mass produced cells. “Mass producing pure nerve stem cells is an important progress in developing a treatment based on transplanting stem cells for damaged organs,” said Professor Austin Smith of the University of Edinburgh Stem Cell Research Institute. By Ho-Gab Lee Donga.com 8/18/05 web site is www.plosbiology.org - then do a search. PLoS Biology Vol. 3, No. 9, e283 DOI: 10.1371/journal.pbio.0030283

Scientists Link Vascular Gene to AD - Scientists at the University of Rochester Medical Center have discovered a link between a prominent developmental homebox gene and neurovascular dysfunction in AD. The gene plays a major role in the growth and remodeling of vascular systems. But, in brain cells of people with AD, expression of the gene is low, the scientists found, revealing a new piece of the AD puzzle. In laboratory studies, the scientists also showed that restoration of the gene expression level in the human brain cells (1) stimulated the formation of new blood vessels. It also (2) increased the level of a protein that removes amyloid beta peptide, the toxin that builds up in brain tissue in AD. In further studies, the scientists, led by Berislav Zlokovic, M.D., Ph.D., deleted one copy of the gene in mice, creating echoes of the damage of AD including (1) reduced ability to grow blood vessels in the brain and (2) impaired clearance of amyloid beta. The gene targeted in the research is a homeobox gene known as MEOX2 and also as GAX. A homeobox gene encodes proteins that determine development. Zlokovic calls it a “big boss.” The scientists studied human brain endothelial cells taken from autopsy samples from people with AD. They found that expression of MEOX2, or mesenchyme homeobox 2, is low in the cells of those with AD. “The cells with low levels can’t form any kind of vascular system or any kind of network,” Zlokovic said. “They just start dying.” In restoring expression of the gene, the Rochester scientists showed for the first time that it suppresses a specific transcription factor. When the expression of MEOX2 is low, the factor “rampages” and allows apoptosis or programmed cell death in the brain vascular system, Zlokovic said. When MEOX2 expression is low, the research also showed that a protein that helps with the clearance of amyloid beta is suppressed. Zlokovic views his findings reported in Nature Medicine as support for his belief that AD is a neurovascular disease. Medical News Today 8/15/05 Nature Medicine 11, 959-965 (2005)

Scientists Hope Gene Chips Hold Key to Solving Brain Disorders - A black cartridge about the size of credit card called a gene chip contains the entire human genome and, thanks to new federal funding, thousands of neuroscientists around the country now have access to it to study the way brain disorders behave at the molecular level. “If you take your car to the mechanic, he has to identify the problem before he can fix it,” said Shrikant Mane, a gene chip researcher at Yale. “This tells you what the problem is.” Scientists need to know how genes act and interact, how the healthy body functions and how diseases affect each gene. Unlike simple traits such as hair color or freckles, a complicated disease such as depression may involve more than 1,000 genes, Mane said. Understanding how these genes behave is paramount to finding a cure, he said. While some scientists caution against overly high expectations, others believe the gene chip, also called a microarray, holds the key to many cures. Scientists start with two chips, each containing the genetic blueprint for a human. One is injected with healthy genetic material, the other with diseased material. The two chips react differently. Some genes are turned on, others off. By comparing the chips, scientists hope to see exactly what a disease is doing. Some see this as a step toward individualized medicine, in which doctors might tailor drugs to a patient’s DNA. By Matt Apuzzo AP Writer 8/14/05

With Help from Mice, Lexicon Fights Disease - The heart of Lexicon Genetic’s business is its Genome5000 project, which unlocks the traits of some 5,000 human genes by studying the removal of those same genes in mice. Although the human genome consists of about 20,000 genes, researchers believe that diseases are associated with just 5,000 of them. The process is highly complicated, but generally Lexicon scientists using mouse embryonic stem cells create genetically engineered mice that are each missing a particular gene. Then, they study those mice against normal mice that still contain the missing gene. Among Lexicon’s most exciting mice are the LG-617s. After having a specific neurological gene knocked out, these mice scored twice as well on a battery of learning and memory tests than normal ones who were not missing the same gene, Arthur Sands co-founder and CEO said. “These are mice of superior cognitive abilities,” said Sands, adding that the discovery of this target gene’s functions has huge implications for the treatment of AD. By Anne Belli Houston Chronicle 7/15/05

Pinpointing a Culprit Molecule in AD - The clipping of amyloid precursor protein (APP) produces two types of amyloid beta peptide – one 40 amino acid units long (Ab40) and one 42 units long (Ab42). Circumstantial evidence has suggested that Ab42 is the “stickier” of the two forms, and underlies the pathology of AD. Now, researchers led by Eileen McGowan and Todd Golde of the Mayo Clinic College of Medicine report definitive proof that Ab42 is, indeed, the culprit molecule. In their experiments, they created transgenic mice that overproduced either Ab40 or Ab42 in the absence of overproduction of APP. Thus, they could precisely study the role of each of these molecules in AD pathology. Their studies of the mice revealed that the Ab40 mice showed little amyloid disease pathology in the animals’ brains, while the Ab42 mice showed extensive accumulation of amyloid plaque and resulting neural damage. What’s more, when the researchers crossed the Ab42 mice with those producing mutant APP, they saw a massive increase in amyloid deposition that was more than the additive effect of the two mutations. PR 7/20/05 Neuron 47, 7/21/05: 191-199

Caregivers

Missing Eyeglasses Make Life A Blur For A Third Of Nursing Home Patients With AD -

One in three nursing home residents who have AD are not getting their vision corrected so they can see clearly, according to new Saint Louis University research reported 7/21/05. “Many nursing home residents are losing out on stimulation. They may not be able to see the television, read books or interact appropriately,” said James M. Koch, M.D., principal investigator and a resident in the department of internal medicine at Saint Louis University. The research is some of the first to examine the effect of visual impairment on AD patients in nursing homes, said George T. Grossberg, M.D., director of the division of geriatric psychiatry at Saint Louis University School of Medicine and a co-author of the study. Koch interviewed nearly 100 nursing home patients and determined that one third of them were not using or did not have glasses that were strong enough to correct their eyesight. They had either lost their glasses, broken them or had prescriptions that were no longer sufficient. Several of the patients were too cognitively impaired to ask for help. Vision problems make it difficult for a person to function and can aggravate symptoms of dementia, Koch said. “The loss of visual stimulation may cause disorientation, limit a patient’s mobility and increase the risk of falls. Everyday activities such as reading or watching television may also be difficult. These patients may become so sensory deprived that they are virtually shut off from the outside world.” The research recommends (1) labeling eyewear so it can be returned to its owner in case it is misplaced, (2) having a spare pair of glasses to replace a missing pair and (3) ensuring all nursing home residents receive annual or biannual eye exams. Sciencedailey.com 7/21/04 Journal of the American Medical Directors Association 6(4) July-Aug 2005: 233-237

Testing

Altered Sense of Smell May Point to AD - A 10-item smell identification test seems to be useful for finding out if people with mild mental impairment are at increased risk of developing AD, according to investigators. “Our work, and that of other groups, has shown that problems with identifying common smells can be an effective early marker of the disease,” Dr. Matthias H. Tabert of Columbia University College of Physicians and Surgeons, New York, told Reuters Health. Starting with the 40-item University of Pennsylvania Smell Identification Test (UPSIT), Tabert and his colleagues tested 147 patients with mild cognitive impairment, 100 with AD and 63 healthy controls. The aim was identify particular odors connected to a risk of AD. The result was a 10-item test featuring scents of menthol, clove, leather, strawberry, lilac, pineapple, smoke, soap, natural gas and lemon. The 10-item test performed as well as the larger UPSIT panel in identifying patients at increased risk of AD. “Narrowing the list of odors allows screening for smell deficits to occur in less than 5 minutes and thus makes it feasible for physicians to include this type of testing as part of their standard clinical work-up for patients at risk for AD,” Tabert pointed out. Other testing also showed that incorrect responses to the 10 odors were consistently associated with the risk of AD. Given further positive findings, the researchers conclude that the 10-item approach “may in combination with other diagnostic tests help to improve early detection of AD.” By David Douglas Reuters Health 8/2/05 Annals of Neurology 58,1:155-160

Skull Scanner Reveals AD - Technology that’s now used to monitor patients in the operating room could become the first accurate way to diagnose AD before death. Early test results indicate that a brain-wave analysis device can accurately detect the beginning stages of the deadly illness and even help to diagnose depression. The technology, developed by Aspect Medical Systems, converts the data from an electroencephalogram, or EEG, into a numerical value between 0 and 100 indicating the amount of electrical brain activity. If the technology gains FDA approval for diagnosing AD, doctors could gain new insight into how the disease begins, which could lead to earlier treatment and help researchers find a cure. By John Gartner Wired News 8/30/05

Early Warning Signs of AD Show Up Across Cognitive Areas Years Before Official Diagnosis - By combing through dozens of AD studies, psychologists have gained a clear picture of cognitive problems in people who will develop the degenerative brain disease. The meta-analysis reveals that people can show early warning signs across several cognitive domains years before they are officially diagnosed, confirming that AD causes general deterioration and tends to follow a stable preclinical stage with a sharp drop in function. Researchers at the Karolinska Institute and Stockholm Gerontology Research Center, affiliated also with the Max Planck Institute for Human Development and the University of South Florida, crunched the data from a decade’s worth of studies: Published reports that met stringent criteria had records on 1,207 people with preclinical AD (they later developed the disease) and 9,097 controls who stayed healthy. The authors studied 47 peer-reviewed studies published between January 1985 and February 2003. The year 1985 marked the introduction of more systematic and reliable diagnostic criteria for AD. The analysis showed that no matter what kind of study, people at the preclinical stage showed marked preclinical deficits in global cognitive ability, episodic memory, perceptual speed, and executive functioning; along with somewhat smaller deficits in verbal ability, visuospatial skill, and attention. There was no preclinical impairment in primary memory. The generalized nature of the problem is consistent, say the authors, with recent observations that multiple brain structures and functions are affected long before the AD diagnosis. They remind readers that the deficits seen in preclinical AD mirror quite closely those seen in normal aging, such as impairments in episodic memory, executive functioning, and cognitive speed. Still, says lead author Lars Backman, PhD, these problems are exacerbated in those who will go on to be diagnosed with dementia. The data also supported the emerging consensus that AD’s preclinical period is characterized by an early onset followed by relative stability until a few years before diagnosis, when functioning plummets. Medical Research News 8/4/05 Neuropsychology vol. 19, no. 4 ,520-531. Full 12 page copy in pdf at http://www.apa.org/journals/releases/neu194520.pdf

Scientists Find New Ways To Detect AD - Dr. Elizabeth Edgerly is an area director of the Alzheimer’s Association. “The aging of our population is such that we are seeing more and more people with AD and when the baby boomers hit their senior years, which is just now starting, we are going to see a dramatic increase by the number of people affected by AD.” To cope with that growth of AD, scientists are working on early detection devices. One of these devices is a PET, or position emission tomography. PET scans, which are still in the experimentation process, are given to healthy middle-aged patients to determine potential AD warning signs. Dr. Edgerly explains that, “We may be able to see the changes in brains through brain scans and imaging decades before the person actually develops symptoms. Why that is particularly exciting is that it opens a window of opportunity for us to intervene even before the damage has taken place in the brain to the extent that symptoms appear.” The tests are 85 percent accurate in detecting which patients will get AD or other memory illnesses. But scientists caution that more testing has to be done before PET detection scans can be widely available. By Barry Unger VOA News 7/27/05

New Dye Could Offer Early Test for AD - MIT scientists have developed a new dye that could offer noninvasive early diagnosis of AD, a discovery that could aid in monitoring the progression of the disease and in studying the efficacy of new treatments to stop it. “Before you can cure AD, you have to be able to diagnose it and monitor its progress very precisely,” said Timothy Swager, leader of the work and a professor in MIT’s Department of Chemistry. “Otherwise it’s hard to know whether a new treatment is working or not.” Swager and colleagues developed a contrast agent called NIAD-4 that would first bind to the protein deposits, or plaques, in the brain that cause AD, and then fluoresce when exposed to radiation in the near-infrared range. The new dye could allow direct imaging of AD plaques through a patient’s skull. Swager says fluorescing dyes like NIAD-4 could be ready for clinical trials in the near future. PR 8/25/05 Angewandte Chemie 44(34) 5452-5456

Biosensor Reveals New Information about Suspected Cause of AD - Chemists and biologists at Northwestern University have found a way to detect and estimate the size and structure of a miniscule toxic protein suspected of triggering AD. The findings, researchers say, could help scientists better understand the underlying mechanisms of the disease and lead to the development of new treatments that could slow or possibly arrest its progression. The researchers developed a method to detect small harmful proteins in cerebrospinal fluid using nanoscale optical biosensors. The proteins, known as ADDLs ( amyloid β-derived diffusible ligands ) are so small that they can’t be detected by conventional diagnostic tests. They are usually less than 5 nanometers wide and are found in extremely low concentrations. “It’s becoming more evident that the size of β-amyloid ( ADDL ) molecules matters - that only ADDLs of a certain size cause problems for neurons in the early stages of AD,” said Amanda Haes who presented the work to the national meeting of the American Chemical Society on 8/31/05. “These nanoscale biosensors may one day allow us to determine, based on size, if an individual has ADDLs that will affect his or her cognitive function. However, there are still many hurdles that must be overcome before we can use it as a diagnostic tool.” PR 8/31/05

Medical Software Offers New Tool vs. AD - Dr. Charles Duffy, a geriatric neurologist at the University of Rochester Medical Center, has turned his understanding of AD into a new company, Cerebral Assessment Systems LLC, or CAS. The company has patented a software-based technology meant to improve early detection of AD and streamline clinical trials forAD drugs. Duffy hopes to develop a more user-friendly version of the technology’s core software and bring it to the burgeoning AD care market. The software is intended to diagnose, monitor and guide therapy for AD by compiling and analyzing data on specific areas of the brain, Duffy explained. It can thereby measure the effectiveness of AD drugs using quantitative data, providing a more objective way to assess clinical trials of the drugs, he said. “It’s better because it gives a quantitative analysis of how the brain analyzes information,” Duffy says. “It’s faster because clinical trials are usually paper- and-pencil tests that take a long time for interpretation. We create data that are practically real-time analyzed.” By Nishad Majmudar Staff writer Democrat & Chronicle 8/1/05

Prevention

Healthy Gums May Help Fight AD - Brushing your teeth may be one of many ways to help keep your mind healthy and lower the risk of AD. A new study shows that lifetime exposure to inflammation, including gum disease, may have a significant impact on the risk of developing AD. Researchers studied sets of twins in which one twin developed AD and the other didn’t. They found that the twin with AD was four times more likely to have had gum disease by middle age. They say the results show that certain preventive measures, including practicing good oral health habits, can reduce the risk of AD and dementia. “While genetic factors are significant in explaining why some people develop dementia and others do not, our research suggests that there are certain risk factors over which an individual may be able to exert some influence earlier in his or her life,” says researcher Margaret Gatz, professor of psychology at the University of Southern California, in a news release. “And these aren’t risk factors that are unique to dementia. Many of these are also risk factors for other disorders.” The results of the study were presented 6/20/05 at the Alzheimer’s Association 1st International Conference on Prevention of Dementia. Researchers say their results indicate an inflammatory burden early in life, such as chronic gum disease, may have a significant impact on the later risk of AD and dementia. Previous studies have also linked inflammation to heart disease and stroke risk. By Jennifer Warner WebMD 6/20/05

Daily, Structured Activity Program Effective for AD Patients - According to an article in the

Summer 2005 issue of Activities Directors’ Quarterly, individuals in the beginning to middle stages of AD greatly benefit from a daily, structured activity program. The Smiles Club, a program for Sisters of St. Joseph, was designed to create a structured environment of enjoyment and activity for AD patients. Participants meet daily for five-and-a-half hours of dynamic programming that utilizes the interests of staff members. Daily activities include memory box, painting, crossword puzzles, and singing. After one year in the program, seventy percent of participants either improved or remained stable. A daily, structured activity program of activities is one of the most powerful, effective interventions for AD. Participation in such programs slows functional decline and improves patients’ quality of life. These findings underscore the need for more research in this area. PR 8/17/05 website for the Quarterly is http://www.activitiesdirectors.com

Folate May Reduce Risk of AD - Diets high in folate may help reduce the risk of AD.

During a nine-year study, researchers showed that older adults whose diets were high in folate reduced their risk of AD by half compared with those whose diets contain less than the Recommended Dietary Allowances (RDA). Using information gathered from the Baltimore Longitudinal Study of Aging, researchers identified the relationship between diet and AD risk. Foods rich in folate include oranges and bananas, leafy green vegetables, asparagus, broccoli, liver, and many types of beans and peas, as well as fortified bread. They concluded that older adults whose total folate intake (diet and supplement) equaled or exceeded the 400 microgram RDA reduced their chances of developing AD by 55%. “Although folates appear to be more beneficial than other nutrients, the primary message of our study should be that overall healthy diets seem to have an impact on limiting AD risk,” says Maria Corrada, assistant professor of neurology at the University of California in Irvine, in a news release. By Patti Connor WebMD Medical News 8/15/05 Alzheimer’s and Dementia 1,1:11-18 (July 2005)

Teen IQ and Mental Activity Linked to Dementia Risk Later on - A new study by researchers at the University Memory and Aging Center, affiliated with Case Western Reserve University (Case) and University Hospitals of Cleveland (UHC), found that persons who were more active in high school and who had higher IQ scores, were less likely to have mild memory and thinking problems and dementia as older adults. Thomas Fritsch, Ph.D., the study’s lead author, said “We found that, controlling for gender and education level, higher adolescent IQ and greater activity level were each independently associated with a lower risk for dementia and mild cognitive impairments. Conversely, those who were lower on the IQ continuum and who participated in fewer activities in high school had a higher risk of cognitive impairments.” The Case researchers used historical data from high school records and yearbooks from the mid-1940s to create a picture of the students’ abilities and interests as teens. A particular strength of the Case study is the use of objective measures of cognitive ability (IQ) collected in the teen years. Also, no study has yet reported on associations between teen activity levels and dementia risk using objective measures (i.e., extracurricular activity participation). According to Fritsch, “Our findings confirm that markers for dementia risk can be found early in life. However, while our research implicates a role for IQ and activity level in youth, many other factors, alone or in combination, also influence who will and will not develop dementia. As we know, some very bright and active people develop dementia, while others who are less gifted and who were inactive as teenagers, do not. This indicates that the causes of dementia are complex and are determined by a host of factors.” According to the Case research team, it is premature to make lifestyle recommendations to teenagers based only on a single study. However, Fritsch commented, “It’s a safe bet that being intellectually engaged, physically active, and socially connected has many health benefits across the lifespan and is to be recommended.” Medical News Today 7/3/05 The Journal of the American Geriatrics Society 53(7):1191-1196 July 2005

AD Workshop Stresses Mind-body Workouts - A new workshop put together by the Alzheimer’s Association says mental, physical and social workouts are the best ways to lower the risk of AD. While new drugs and therapies offer some promise for the brain-destroying disease, there is no cure for AD and not even a good treatment. So the hope is to prevent people from developing it in the first place. “People are really starting to worry,” said Elizabeth Edgerly, who leads a “Maintain Your Brain” workshop for the non-profit association. Detailed on the Internet at http://www.alz.org/maintainyourbrain/overview.asp , the program is a reminder of what studies have shown: People who exercise regularly, who have social connections, who have mentally challenging jobs or hobbies, who eat plenty of fruits and vegetables and who keep a healthy weight have a lower risk of AD. By Maggie Fox, Health and Science Correspondent Reuters 6/20/05

Sheep Milk Protein May Prevent AD - Researchers are hoping a protein, or peptide, found in sheep milk could help prevent AD. Colostrinin can stabilise mental functions, and is being investigated for its preventative health value. Research scientist with Food Science Australia, Louise Bennett, says the substance was detected by researchers in Poland. “A peptide extracted from sheep’s milk, or sheep colustrum, is able to dissolve the plaques that are associated with the development of AD,” she said. “And it’s quite possible that there are similar peptides present in cows milk.” Australian Broadcasting Corp. 7/19/05         

Candy Good for You? Mars to Probe Cocoa Benefits - Mars, the company that made its fortune satisfying chocolate cravings, unveiled plans on 7/25/05 to develop medications that use a component of cocoa to help treat diabetes, strokes and vascular disease. The privately held U.S. company said it hoped to make medications based on flavanols -- plant chemicals with health benefits found in cocoa, as well as red wine and green tea. It is now in talks with several large pharmaceutical companies for a licensing or joint venture agreement to develop medicinal products based on its research. After 15 years and more than $10 million worth of studies, Mars said it had developed hundreds of compounds that copy the aspirin-like blood-thinning properties of cocoa flavanols. “The mounting scientific evidence is extraordinary,” said Dr. Norm Hollenberg, Professor of Medicine at Harvard Medical School, which has collaborated with Mars on cocoa research. “This is a scientific breakthrough that could well lead to a medical breakthrough.” Hollenberg was chairing a two-day seminar with 20 science and medical experts in Switzerland to discuss the newest research on cocoa’s potential health benefits. Two clinical trials have found that cocoa flavanols can boost the flow of blood to key areas of the brain, raising the possibility of treatments for dementia and strokes. Mars has already launched CocoaVia, a nutrition bar containing 80 calories and specially preserved flavanols, which typically get destroyed in usual cocoa processing. By Eleanor Wason Reuters Health 7/25/05

Other Items

Finding May Open New Front in AD Fight - Brain cells poisoned by AD don’t always die right away, says provocative research that suggests it may one day be possible to save those sick cells and recover some memory. Demented mice rapidly regained mental function after they were protected from a mutant protein named tau -- even if a significant number of their brain cells already had died. “We’d always thought the mental impairment was due to the loss of neurons,” said lead researcher Karen Ashe, a University of Minnesota neurology professor. “'What we’re showing is that there are neurons which are affected but not dead.” Stop the poison and at least some of those neurons can recover, she reported 7/14/05 in the journal Science. The study is sure to open a long-awaited new front in AD research. Until now, scientists have focused mostly on a different brain protein, called beta-amyloid, that also wreaks havoc in patients’ brains. Ashe’s work shows they will need to focus on both culprits. The study bolsters the notion that AD patients brains do contain three types of cells: still healthy ones, dead ones and sick ones, said William Thies, scientific director of the Alzheimer’s Association. “If you can actually rescue some of these sick cells, that really brings the possibility of return of some function, which would be of tremendous value,” he said. By Lauran Neergaard AP 7/15/05 Science 2005 309:476-481

Scientists Shed New Light on AD - Proteins called amyloid-B peptides that accumulate in plaques around brain cells are known to contribute to AD. Now, new research suggests that similar peptides accumulating in the blood vessels of the brain contribute to the disease, too. In fact, researchers suspect this blood vessel accumulation may actually lead to plaque formation around neurons -- brain cells -- later on. “What these new studies show is that the accumulation of amyloid-B in blood vessels is also an important contributing factor to the problems that occur in an AD brain,” said William E. Van Nostrand, professor of research medicine at Stony Brook University, New York, and the senior author of one of the two studies, both of which are published in the August issue of the American Journal of Pathology. For years, he said, the general thinking was that amyloid-B accumulates in plaque deposits around the neurons in the brain, leading to problems with memory and other signs of AD. Experts have also long known that amyloid-B is found in the brain’s blood vessels, but that area had not been a prime focus of research. “Everyone thought the plaque was causing all the damage,” he said. What the two new studies show, he said, is that accumulation of amyloid in blood vessels is also an important contributing factor in the disease. Van Nostrand and his colleagues developed a new mouse model genetically engineered to have a mutation in an amyloid protein common to specific AD-prone families. “When the mice made that amyloid protein in their brain, they preferentially accumulated this amyloid-beta protein in their brain blood vessels,” Van Nostrand explained. “When that happens, a lot of inflammation is associated with it. This shows that the blood vessels [not just neurons] can cause some of these problems.” “In the brains of AD patients, you have plaque and blood vessel amyloid,” he said. “In this mouse model, we have just blood vessel amyloid. And when you have just the blood vessel amyloid, you can still have the same things you find in an AD brain -- inflammation and behavioral impairment.” The finding, Van Nostrand said, shows that blood vessels in the brain should be an important target of AD research. In the second study, conducted by researchers from the U.S. National Institute on Aging and other institutions, two strains of mice engineered to develop dense-core plaques and highly concentrated amyloid-B deposits were used to research the association of blood vessels with amyloid-B deposits. The researchers found evidence of vessel damage, resulting in the release of protein through the vessel walls and accumulation of the protein next to the vessels. “What their conclusion shows,” said Van Nostrand, “is that it appears a lot of these amyloids actually start at the level of the blood vessel and lead to formation of the plaque.” By Kathleen Doheny HealthDay Reporter 7/22/05 American Journal of Pathology 2005;167:505-515 and 527-543

Aging: Dementia Is Linked to Blood Flow to the Brain - Low blood flow to the brain may lead to dementia in older people, researchers are reporting 8/30/05. The findings suggest that doctors may be able to reduce the risk of patients’ developing dementia by monitoring how well blood is flowing to their brains and giving treatment if there is a problem, the researchers said. Blood flow to the brain can be restricted by an array of problems, said Dr. Aart Spilt of the Leiden University Medical Center in the Netherlands, the lead author of the study. High blood pressure is one: it can lead to stiffening and narrowing of the arteries. So, on the other hand, is low blood pressure, if the body is unable to compensate for the problem. Heart failure can also be a cause. “Preventing this low blood flow seems important in reducing the risk of dementia,” Dr. Spilt said. “In our opinion,” the researchers wrote, “these observations strongly suggest that decreased cerebral blood flow indeed causes brain damage.” By Eric Nagourney NY Times 8/30/05 Radiology 2005, 236: 990-995

New research Suggests Heart Bypass Surgery Increases Risk of AD - Boston University School of Medicine (BUSM) researchers have discovered that patients who have either coronary artery bypass graft surgery or coronary angioplasty are at an increased risk of developing AD. The research pinpoints stress and trauma of the surgery as the major cause for the increased risk. “The coronary bypass patients had a 70 percent increased risk of developing AD,” said Benjamin Wolozin, MD, PhD, professor of pharmacology at BUSM, co-author of the study. “This increased incidence of neurocognitive degeneration associated with heart bypass surgery provides further incentive for more studies to better characterize the risks of cardiac surgery on the brain.” According to Wolozin, previous studies show some heart surgery patients experience memory problems immediately following the procedure. However, at a one-year follow-up most patients regain cognitive function. Researchers believe this early cognitive impairment is an immediate reaction to the stress of surgery. “Heart bypass surgery represents a traumatic insult to the brain, particularly by reducing oxygen supply to the brain and increasing the stress response,” said Wolozin. “We believe that the compensation that occurs by one year masks an underlying deficit in the central nervous system caused by the heart surgery. As individuals age, this underlying deficit might exacerbate progressive cognitive deficits associated with mild cognitive impairment, a precursory phase before diagnosis of AD.” PR 8/25 Journal of Alzheimer’s Disease 7(4):319-324

Nerve Damage Repair Agent Hope - Scientists say they have discovered a protein that could be injected to repair damaged nerves and brain cells. The protein, KDI tripeptide, works by blocking the harmful effects of a substance present in degenerative brain diseases and spinal cord injuries. By blocking this substance, called glutamate, KDI prevents permanent cell death and helps the body heal itself. The Finnish work from the University of Helsinki is published online by the Journal of Neuroscience Research. So far the researchers have tested KDI in the lab on animals and nerve cells from humans. The findings have been promising and they hope to be able to begin treating people with nerve and degenerative brain diseases, such as AD and Parkinson’s disease, using KDI injections within a year. Since KDI occurs naturally in some form in the body, researchers do not believe it will have major toxic side effects. None have been noted during their work to date. Currently, KDI has to be injected as a solution directly to the damaged area. However, in the future it might be possible to make the treatment as an oral drug or an intravenous injection, said Dr Liesi. BBC News 7/24/05 Journal of Neuroscience Research 81,6:797-804

High Insulin Levels Increase Inflammatory Markers and Beta-amyloids, May Contribute to AD - Moderately elevated levels of insulin increase the levels of inflammatory markers and beta-amyloid in plasma and in cerebrospinal fluid, and these markers may contribute to AD, according to a new study. Mark A. Fishel, M.D., from the University of Washington, Seattle, and colleagues, raised blood insulin levels (while maintaining normal blood sugar levels) in 16 healthy older adults ranging in age from 55 to 81 years, and then measured the changes in levels of inflammatory markers, modulators, and beta-amyloid (a protein associated with AD) in plasma and cerebrospinal fluid. “Moderate peripheral hyperinsulinemia (increased levels of insulin) provoked striking increases in CNS (central nervous system) inflammatory markers,” the authors report. “Our findings suggest that insulin-resistant conditions such as diabetes mellitus and hypertension may increase the risk for AD, in part through insulin-induced inflammation.” “Although this model has obvious relevance for diabetes mellitus, hyperinsulinemia and insulin resistance are widespread conditions that affect many nondiabetic adults with obesity, impaired glucose tolerance, cardiovascular disease, and hypertension. Our results provide a cautionary note for the current epidemic of such conditions, which, in the context of an aging population, may provoke a dramatic increase in the prevalence of AD. More encouragingly, greater understanding of insulin’s role in AD pathogenesis may lead to novel and more effective strategies for treating, delaying, or even preventing this challenging disease,” the authors conclude. PR 8/8/05 Archives of Neurology Online at Arch Neurol, Aug 2005; doi:10.1001/archneur.62.10.noc50112 The study will be published in the October print edition of the journal.

Link Between AD and Traumatic Brain Damage Clarified - It has been known for several years that amyloidal precursor protein or APP is relevant in AD. APP is the precursor of the amyloidal-β protein that causes the typical “plaques” in the brains of patients. The normal function of APP was, however, not known. Maarten Leyssen and his colleagues at the Flanders Interuniversity Institute for Biotechnology (VIB) in Belgium have found that APP stimulates the development of nerve paths. Intact nerve paths are essential for the proper functioning of the brain. These connections can be damaged after traumatic brain damage resulting in the improper functioning of the brain. APP is responsible for stimulating the development of new nerve paths. These results also aid better understanding of certain aspects of AD, where APP plays a major role. The fruit fly – an ideal model to study the brain’s action – indicates that APP increases considerably after brain damage, namely in areas where new nerve paths need to be formed. Because more APP is made, more plaques can develop in the brain, a typical symptom of AD. For the first time the results of VIB researchers explain the strong link between brain damage and AD: not only do patients with major brain damage have more chance of developing AD later on in life, their brains also often show plaques that strongly resemble those of AD patients. PR 8/3/05 EMBO Journal 24, No. 16:2944-2955, 2005

Gender May Play Role in AD - Researchers from the Rush AD Center found that plaques and tangles in the brain, the changes seen in people with AD, are more likely to be expressed as dementia in women than in men. The principal investigator Lisa L. Barnes, PhD, sought to determine whether the relation between levels of AD pathology and clinical symptoms of AD differed in men and women. The researchers studied older Catholic nuns, priests, and brothers in the Religious Orders Study, a longitudinal clinicopathologic study of aging and AD. Barnes found women had more global AD pathology than did men due primarily to more neurofibrillary tangles. “On a global measure of AD pathology that ranged from 0 to three, each additional unit of pathology increased the odds of clinical AD nearly three-fold in men compared with more than 20-fold in women. The findings suggest that AD pathology is more likely to be expressed clinically as dementia in women than in men. Our results suggest that the clinical manifestation of AD is stronger in women than in men.” Barnes says that “Understanding why the association between AD pathology and dementia differs in men and women could yield important clues about the pathophysiology of AD or eventually lead to sex-specific preventive or therapeutic strategies. Another possibility is that women have a relative lack of some protective factor, such as the estrogen deficiency of postmenopausal women, which could increase their vulnerability to AD pathology” Barnes suggests more research is needed to explore these and other possibilities. Medical News Today 7/23/05 Archives of General Psychiatry 2005;62:685-691 June 2005

Study Looks Into Roots of AD - The brain areas involved in daydreaming, musing and other stream-of-consciousness thoughts appear to be the same regions targeted by AD, researchers are reporting 8/24/05 in an unusual study that offers new insights into the roots of the deadly illness. The strong correlation between the two suggests there might be a link between the sort of thinking that people regularly do when not involved in purposeful mental activity and the degenerative disease that is characterized by forgetfulness and dementia, said scientists who conducted the federally funded study. Randy Buckner, a neuroscientist at Washington University in St. Louis, said the implications of the finding are far from clear. It is too early to suggest that daydreaming is dangerous, he said, or that avoiding such musings could affect the risk of AD. Rather, he and others said, the study adds to the evidence that everyday mental and physical activities play an important role in the course of neurological disease. “It suggests an avenue between brain activity patterns and AD that we just hadn’t been thinking about,” said Buckner, who led the study. “It is going to take some time to understand the relative potential of this link.” By Shankar Vedantam Washington Post Staff Writer 8/24/05 Journal of Neuroscience August 24, 2005 25(34):1709-1717

AD More Likely Among Diabetics - Japanese scientists say they’ve found diabetics and prospective diabetics are three times more likely to develop AD than healthy people. The research team from Kyushu University’s Graduate School of Medical Sciences said in 1985 it examined 887 residents of Japan’s Fukuoka Prefecture, aged 65 or older for signs of AD, finding 826 of them were healthy. Fifteen years later, the team performed follow-up tests on the 826, and discovered diabetics and those prone to develop diabetes were 3.1 times more likely to suffer AD. The Japanese scientists noted their results far exceeded findings in similar research performed in the United States. UPI 7/25/05

Enzyme Action Creates Protein Linked to AD - Researchers at UT Southwestern Medical Center have defined a key step in the production of beta-amyloid, a short protein that is thought to be responsible for the development of AD. Understanding this step may aid in the discovery of drugs that could help block the disease from developing. In AD, too much beta-amyloid is produced by an enzyme gamma-secretase that has many other essential roles. As a result, simply blocking the whole enzyme knocks out many of its other functions - which is fatal to the organism. Using cultured human and mouse cells, as well as test-tube assays, UT Southwestern researchers singled out how just one portion of the enzyme, a protein called nicastrin, is involved in the pathway that produces beta-amyloid, thereby leading to AD. They hope next to work on ways to specifically block nicastrin. “The work provides an attractive potential strategy for developing treatment for AD,” said Dr. Gang Yu, assistant professor in the Center for Basic Neuroscience and of cell biology and senior author of the study. Now that nicastrin’s function has been ascertained, it opens a way to block just the splitting of APP, leaving all the enzyme’s other functions intact. For instance, it may be possible to generate chemical compounds that specifically prevent nicastrin from latching on to APP. If APP doesn’t attach to nicastrin, APP remains intact and harmless. Meanwhile, nicastrin would be free to bind all the other essential proteins that it works on. “We want to find a particular way to block the recognition of APP but not the others,” Dr. Yu said. Medical News Today 8/12/05 Cell 122,435-447, 12 August 2005

Program Pairs AD Scientists with Patients - An unusual educational program at Northwestern University pairs researchers and medical students with early-stage AD patients, a group growing in numbers whose needs the medical community is just starting to address. Across town, the University of Chicago has a similar “buddy” program with dual goals -- to give the medical community better insight into AD and keep patients engaged in activities that help them cope. A rare, familial form of the disease that can strike when people are in their 30s and 40s is called early onset AD. Early stage patients have the most common form of the aging-related disease. Dr. David Bennett, an AD specialist at Chicago’s Rush University Medical Center, said that when he began seeing AD patients almost 20 years ago, “it wasn’t unusual for people to come in for their first evaluation very severely impaired. Now it’s actually quite unusual.” Most AD drugs, designed to improve mental function, are designed for use in early stages but do not slow the underlying course of the irreversible disease, Bennett said. Some scientists believe mind-stimulating activities like crossword puzzles and taking classes might help prevent -- but not treat – AD. Researchers are studying whether more structured memory-stimulation programs might help early stage patients learn tasks that might help keep them independent longer, said Neil Buckholtz, head of the dementias of aging branch at the National Institute on Aging. In the meantime, Bennett said programs that keep patients engaged in the community, like the buddy program, “are good things to do even if they don’t impact the course of the disease.”

AP 7/26/05

Alzheimer’s Association Names Harry Johns President and CEO - The Alzheimer’s Association announced 8/16/05 that Harry Johns has been named president and chief executive officer. Johns comes to the Association from the American Cancer Society (ACS), where he most recently served as executive vice president of strategic initiatives. “We are delighted to have the opportunity to benefit from Harry’s vast experience with the nation’s largest non-profit health organization,” said Larry Varnes, the Alzheimers Association’s chairman of the board. “In our 25th anniversary year, our organization is facing many of the growth issues that ACS has encountered. We are on the verge of breakthroughs in science and care and Harry’s leadership will enable us to accelerate our progress, enhance our ability to serve those who suffer from AD and advance our quest for prevention and cure.” PR 8/16/05

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