A new drug discovery tool for Alzheimer's

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An article published in the April issue of the Journal of Alzheimer's Disease presents a detailed characterization of a new drug discovery tool for Alzheimer's disease. It demonstrates that an abnormal form of tau protein, as it occurs in Alzheimer's disease, can be produced in very simple cell models in an unambiguous way. Most importantly, it also shows an example of a chemical compound, found in nature, which is highly effective to completely suppress the abnormal changes of tau.

A simple cellular assay for the pathological modification of tau protein by abnormal hyperphosphorylation, as seen in Alzheimer's disease and a variety of other neurological disorders (tauopathies), has been developed by researchers at Sirenade Pharmaceuticals AG in Munich, Germany. The assay can be used to screen for drugs against these disorders, and the discovery of a very effective small molecule is described as an example.

Tau proteins are a family of neuron-specific proteins believed to play an important role in the organization of the skeleton of nerve cells. This protein has been known to be abnormally modified in degenerating neurons in Alzheimer's disease in a process called neurofibrillary degeneration. This form of neurodegeneration is thought to be a dominant cause of the massive loss of brain mass and function in many dementias, and its inhibition can be expected to change the prognosis of Alzheimer's disease significantly.

Cell models are essential tools to analyze the molecular mechanisms involved in specific disease processes, and also the mechanisms of drugs, which act against them. For the process of tau hyperphosphorylation, credible models with utility for drug discovery have not been established to date. The model developed at Sirenade AG under the leadership of Dr. Hanno Roder, now at TauTaTis, Inc., fills this important gap. http://www.medicalnewstoday.com .

Curcumin may offer diabetes benefits: study
Curcumin, the natural pigment that gives the spice turmeric its yellow colour, could have benefits for diabetics, suggests a joint Korean-American study. http://www.nutraingredients.com

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Alzheimer's and low oxygen

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In studies of human brain cells, the widely-used anesthetic desflurane does not contribute to increased production of amyloid-beta protein; however, when combined with low oxygen conditions, it can produce more of this Alzheimer's associated protein.

Over 200 million people undergo surgery each year, and there has been concern that anesthetic use may contribute to Alzheimer's and other brain disorders. It were subjected human brain cells to 12% desflurane for six hours (mimicking a surgery condition) and observed no changes in either the production of amyloid-beta protein or the rate of cell death. However, when combined with low oxygen levels (18%), desflurane could stimulate these cellular changes associated with Alzheimer's (hypoxia by itself did not induce any changes). The results with desflurane are contrary to the researchers' previous work, which found isoflurane by itself could stimulate both amyloid production and cell death.

The researchers do emphasize that the current findings are from cell culture experiments, and the next critical step will be to confirm these findings in animal models and test the effects of other anesthetic agents. But, these early results suggest that it is important to ensure anesthetic patients maintain sufficient oxygen in their brain. http://www.medicalnewstoday.com .

Study supports lycopene protecting skin from within
Consuming lycopene-rich tomato paste may protect against sunburn and sun-induced skin ageing, British researchers have reported. http://www.nutraingredients.com

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A novel strategy for therapeutic intervention in Alzheimer's

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JADO Technologies GmbH, the leading developer of RAFT intervention therapeutics, has announced he publication of a paper in Science demonstrating a potential novel strategy for therapeutic intervention in Alzheimer's and other diseases by targeting discrete sub-compartments in the cell membrane (RAFTS). The study conducted by JADO scientists together with several academic collaborators will appear in the April 25, 2008 issue of the magazine.

Entitled "Efficient inhibition of the Alzheimer's disease ß-secretase by membrane targeting", the paper describes how ß-secretase, the rate-limiting enzyme in the production of Alzheimer's disease associated ß-amyloid peptide, can be inhibited effectively using compounds anchored to cell membrane RAFTS. Unlike existing approaches for ß-secretase inhibition that do not account for the intracellular location of the target protein or the different conformation that the protein may assume in this context, these RAFT inhibitors are delivered to the exact site where ß-secretase executes its neurotoxic activity.

"Our data provide proof-of principle of a new approach for directing small molecule inhibitors to disease causing RAFT targets in cellular membranes. In this instance, by directing inhibition to the sub-compartment where the enzyme is active, the approach has potential to be used in the design of more effective β-secretase inhibitors for the treatment of Alzheimer's disease," noted Professor Kai Simons, Max-Planck Institute of Molecular Cell Biology and Genetics and co-founder of JADO. "We believe that this novel strategy can be used to design therapeutics against other RAFT targets in a range of other diseases."

ß-secretase is internalized from the cell membrane into intracellular compartments (endosomes) where it cleaves its substrate, Amyloid Precursor Protein (APP). Most soluble inhibitors of ß-secretase do not gain access to this internal location, so the researchers first tested whether anchoring of such a ß-secretase inhibitor to the membrane would confer inhibitory activity upon it by bringing it to the right compartment. A peptide inhibitor of ß-secretase, which inhibited soluble ß-secretase but failed to block the enzyme in a cellular assay, was coupled to a sterol anchor molecule and a potent inhibition of ß-secretase activity demonstrated. Concentrations as low as 100 nM of the anchored inhibitor were sufficient to completely block appearance of amyloid peptide. In an animal model of Alzheimer's disease, the same sterol-coupled inhibitor reduced ß-amyloid formation in the brain by 50% over 4 hours, whereas the free inhibitor was ineffective.

The researchers explained that the advantage of using a sterol anchor was to target and increase the concentration of the inhibitor in the sterol-rich RAFT domains where ß-secretase cleaves APP. Evidence was also provided that the RAFT anchor could not be substituted by any other lipid type and that knowledge of RAFT chemistry is crucial. http://www.medicalnewstoday.com .

Micronutrients show potential against TB recurrence

Daily supplements of micronutrients vitamins A, B-complex, C, E, and selenium may reduce the recurrence of tuberculosis during standard treatment, suggests a new study.

http://www.nutraingredients.com
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Early life experiences contribute to amyloidogenesis

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Alzheimer's Disease (AD) is a progressive, irreversible neurodegenerative disease. Despite several genetic mutations (Haass et al., J. Biol. Chem. 269:17741-17748, 1994; Ancolio et al., Proc. Natl. Acad. Sci. USA 96:4119-4124, 1999; Munoz and Feldman, CMAJ 162:65-72, 2000; Gatz et al., Neurobiol. Aging 26:439-447, 2005) found in AD patients, more than 90% of AD cases are sporadic (Bertram and Tanzi, Hum. Mol. Genet. 13:R135-R141, 2004). Therefore, it is plausible that environmental exposure may be an etiologic factor in the pathogenesis of AD. The AD brain is characterized by extracellular beta-amyloid (Abeta) deposition and intracellular hyperphosphorylated tau protein. Our lab has demonstrated that developmental exposure of rodents to the heavy metal lead (Pb) increases APP (amyloid precursor protein) and Abeta production later in the aging brain (Basha et al., J. Neurosci. 25:823-829, 2005a). We also found elevations in the oxidative marker 8-oxo-dG in older animals that had been developmentally exposed to Pb (Bolin et al., FASEB J. 20:788-790, 2006) as well as promotion of amyloidogenic histopathology in primates. These findings indicate that early life experiences contribute to amyloidogenesis in old age perhaps through epigenetic pathways. Here we explore the role of epigenetics as the underlying mechanism that mediates this early exposure-latent pathogenesis with a special emphasis on alterations in the methylation profiles of CpG dinucleotides in the promoters of genes and their influence on both gene transcription and oxidative DNA damage. J Mol Neurosci. 2008;34(1):1-7

Can flavonoid-rich chocolate protect against heart disease?
A study to be conducted by the University of East Anglia (UEA), UK, will examine whether adding flavonoids found in cocoa to the diet, gives additional protection against heart disease on top of that provided by prescription drugs. http://www.nutraingredients.com
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Alzheimer's has different effects in different racial and ethnic groups

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Hispanic and black caregivers are more likely than other ethnic groups to misinterpret symptoms of Alzheimer's disease as normal signs of aging, according to a recent survey by the Alzheimer's Foundation of America, HealthDay/Washington Post reports. The survey found that 37% of black caregivers and 33% of Hispanic caregivers believed that the disease's symptoms were a normal part of aging, compared with 23% of caregivers from other racial or ethnic groups. The survey also found that black and Hispanic caregivers were more likely to report that they knew little about Alzheimer's.

Misinterpretation of the disease's symptoms "often leads to delays in seeking care, when early treatment might make a difference in the progression" of the condition, HealthDay/Post reports. Experts said the survey's findings indicate a need for more culturally competent education on Alzheimer's disease. Eric Hall, founding CEO of AFA, called the findings "distressing," adding, "In the absence of a cure, care becomes a critical issue to sustain the highest quality of life for the longest time."

According to Angela Geiger, vice president of constituent relations for the Alzheimer's Association, Alzheimer's has different effects in different racial and ethnic groups. For example, the disease is more prevalent in blacks than whites, and Hispanics are more likely to display symptoms earlier. Such differences prompted the organization to create "a series of culturally appropriate publications tailored" to blacks and Hispanics, she said (Doheny, HealthDay/Washington Post, 4/20). http://www.medicalnewstoday.com .

Croda kick starts UK brain food scheme
Croda has become the first ingredient supplier to receive accreditation under UK charity Food for the Brain Foundation's new labelling scheme that recognises products with cognitive benefits.http://www.nutraingredients.com

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Transforming dementia services in Scotland

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Today's Ministerial statement on dementia by Shona Robison MSP is warmly welcomed by Alzheimer Scotland. It confirms that the Scottish Government recognises the scale of the problem of dementia in Scotland, as highlighted by our recent report The Dementia Epidemic - where Scotland is now and the challenge ahead.

The programme has identified the need for changes in service provision for people with dementia across Scotland, including the integration of palliative care as promoted by Scotland's Beyond Barriers project. It also recognises the need to enhance the research into dementia, its causes and potential treatments; a need that has received much attention following the recent comments of Terry Pratchett. Awareness raising and information sharing will be promoted, increasing the understanding of dementia across Scotland. All this gievs substance to the Scottish Government's commitment to making dementia a national priority.

In addition, the announcement of joint funding of £600,000 (over three years) between Alzheimer Scotland and the Dementia Services Development Centre in Stirling will allow the organisation to carry out invaluable work on post-diagnostic support and information initiatives for people with dementia and their carers.

Jim Jackson, Chief Executive at Alzheimer Scotland, said, "This is an important start to work which needs to be done by the Government, NHS, local authorities, voluntary and private sector services. As more people are diagnosed, Scotland will need to be better prepared to provide personalised support for people with dementia. We look forward to working with our partners in the Dementia Forum and transforming dementia services in Scotland." http://www.medicalnewstoday.com .

Vitamin D, calcium combo may cut exercise-related stress fractures

Daily supplements of calcium and vitamin D, long linked to improving bone health, may also reduce the risk of stress fractures during exercise, scientists have reported.

http://www.nutraingredients.com

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Breakthrough in the research into the cause of Alzheimer's

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According to estimates there are 85,000 Alzheimer patients in our country and approximately 20,000 new cases every year. This spectacular increase is due to the increasing ageing population. Unfortunately it is still unclear precisely which ageing process forms the basis of this spectacular rise in the occurrence of the disease. VIB scientists affiliated to K.U.Leuven have discovered an important molecular link between Alzheimer's disease and the development of the typical plaques in the brains of Alzheimer patients. This discovery is an important breakthrough in the fundamental research into the cause of Alzheimer's disease.

Alzheimer's disease, a neurodegenerative disease that slowly and gradually destroys brain cells, is the most common form of dementia in the Western world. The way in which it affects the memory and mental functioning makes it one of the most frightening disorders. Over the last 15 years the amount of research worldwide into this still incurable disease has grown considerably: faster diagnosis of the disease and better treatment are essential. Alzheimer's disease is associated with amyloid plaques i.e. abnormal accumulations of protein fragments that form in the brain cells. A few years ago Bart De Strooper and other researchers unravelled the process by which these plaques develop in the familial form of Alzheimer's disease (less common form). ?-secretase, which cuts proteins at a specific location plays an important role here. Sometimes the secretase cuts in the wrong place, which results in a by-product and thus the formation of plaques. In the most common form of the disorder the same sort of plaques are found, but there is still little known about their development mechanism

In patients with the most common form of Alzheimer's disease the brain cells show an increase in the protein BACE1 or ß-secretase. VIB researcher Sébastien Hébert and colleagues, under the direction of Bart De Strooper and in collaboration with international experts, looked into the cause of this increase. To this end the VIB researchers checked the expression profiles of certain microRNA's, i.e. the short pieces of RNA that regulate protein production. In patients where there was an increase in the BACE1 protein, there was a significant reduction in miR-29a and miR-29b-1. This observation suggests the possible role of certain miRNA's in the increase of BACE1 and in the formation of plaques in the brains of patients with Alzheimer's disease.

On the one hand this research raises hopes for a better diagnostic test. Timely prescription of certain medicines for Alzheimer's disease results after all in a better response, and thus a better quality of life for the patient. On the other hand there is the question of whether these microRNA's could in the future form the basis of a new drug. http://www.medicalnewstoday.com .

Lifelong prebiotic supplements may enhance survival: rat study
Lifelong supplementation with the prebiotics inulin and oligofructose may extend lifespan by over 30 per cent, according to a new animal study from France. http://www.nutraingredients.com

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Immune Globulin Intravenous for the treatment of Alzheimer's

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Presbyterian Hospital/Weill Cornell Medical Center and Baxter International Inc. (NYSE: BAX) announced results of a six-month, placebo-controlled Phase II study of 24 patients treated with GAMMAGARD S/D and GAMMAGARD LIQUID [Immune Globulin Intravenous (IGIV)] for the treatment of mild-to-moderate Alzheimer's disease today at the American Academy of Neurology (AAN) annual meeting in Chicago. The study met the primary endpoint criteria favoring GAMMAGARD LIQUID and GAMMAGARD S/D over placebo on measures of cognitive function and global impression of change, which are common measures of outcome in Alzheimer's disease clinical trials. The study also met secondary endpoints that measured changes in beta-amyloid and anti-amyloid antibody levels in blood and cerebrospinal fluid. Results show findings indicative of potential efficacy and tolerability. Key findings throughout six months included: measurements of clinical outcome, behavioral outcome and cognitive performance in Alzheimer's patients treated with GAMMAGARD S/D and GAMMAGARD LIQUID compared to placebo. Twelve-to-18 month data will be available later this year.

Secondary endpoint results suggest that levels of antibodies against beta-amyloid were observed to have increased in the blood and cerebrospinal fluid of patients treated with GAMMAGARD S/D and GAMMAGARD LIQUID, while the levels of beta-amyloid increased in the blood. Beta-amyloid is a substance thought to contribute to the degeneration of the brain in Alzheimer's disease. Clearing this substance from the central nervous system, therefore is hypothesized to help remove or reduce the building blocks of Alzheimer's.

The primary and secondary endpoint data were reported by the lead researcher for the trial, Dr. Norman Relkin, director of the Memory Disorders Program and behavioral neurologist and neuroscientist at New York-Presbyterian/Weill Cornell Medical Center, and associate professor of clinical neurology at Weill Cornell Medical College in New York City. "This was the first placebo-controlled clinical trial of GAMMAGARD for Alzheimer's disease and the results are clearly promising," Dr. Relkin commented. Baxter supported the study and provided GAMMAGARD LIQUID and GAMMAGARD S/D for the trial. GAMMAGARD S/D and GAMMAGARD LIQUID, marketed as KIOVIG in the European Union, contain a broad spectrum of immunoglobulins (antibodies) and are indicated as an immunoglobulin replacement therapy that boosts the immune system in patients with primary immunodeficiency disorders. The precise mechanisms of GAMMAGARD S/D and GAMMAGARD LIQUID's effects in Alzheimer's disease are not known. "These study results reflect Baxter's support of innovative science and commitment to meeting a critical, unmet medical need," said Hartmut J. Ehrlich, MD, vice president of global research and development for Baxter's BioScience business. "While results of Baxter's mid-stage development work in Alzheimer's disease treatment are promising, further investigation in a larger Phase III study is required." http://www.medicalnewstoday.com .

Season lightly for nutrient-rich tomatoes
Differences between salt and fresh water organisms does not usually extend to land plants, but Italian researchers report that watering tomatoes with diluted seawater can boost their nutrient content. http://www.nutraingredients.com

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Heavy drinkers developed Alzheimer's 4.8 years earlier

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Heavy drinkers and heavy smokers develop Alzheimer's disease years earlier than people with Alzheimer's who do not drink or smoke heavily, according to research that will be presented at the American Academy of Neurology 60th Anniversary Annual Meeting in Chicago, April 12-19, 2008.

"These results are significant because it's possible that if we can reduce or eliminate heavy smoking and drinking, we could substantially delay the onset of Alzheimer's disease for people and reduce the number of people who have Alzheimer's at any point in time," said study author Ranjan Duara, MD, of the Wien Center for Alzheimer's Disease at Mount Sinai Medical Center in Miami Beach, FL, and Fellow of the American Academy of Neurology.

"It has been projected that a delay in the onset of the disease by five years would lead to a nearly 50-percent reduction in the total number of Alzheimer's cases," said Duara. "In this study, we found that the combination of heavy drinking and heavy smoking reduced the age of onset of Alzheimer's disease by six to seven years, making these two factors among the most important preventable risk factors for Alzheimer's disease."

The study looked at 938 people age 60 and older who were diagnosed with possible or probable Alzheimer's disease. The researchers gathered information from family members on drinking and smoking history and determined whether the participants had the epsilon 4 gene variant of the APOE gene, which increases the risk of Alzheimer's disease. People with the epsilon 4 variant also develop Alzheimer's at an earlier age than those who do not have the gene variant.

Seven percent of the study participants had a history of heavy drinking, which was defined as more than two drinks per day. Twenty percent had a history of heavy smoking, which was defined as smoking one pack of cigarettes or more per day. And 27 percent had the APOE epsilon 4 variant.

Researchers found that people who were heavy drinkers developed Alzheimer's 4.8 years earlier than those who were not heavy drinkers. Heavy smokers developed the disease 2.3 years sooner than people who were not heavy smokers. People with APOE epsilon 4 developed the disease three years sooner than those without the gene variant.

Adding the risk factors together led to earlier onset of the disease. People who had all three risk factors developed the disease 8.5 years earlier than those with none of the risk factors. The 17 people in the study with all three risk factors developed Alzheimer's at an average age of 68.5 years; the 374 people with none of the three risk factors developed the disease at an average age of 77 years. http://www.medicalnewstoday.com .

Vitamin D pills for risk groups may be warranted
The benefits of vitamin D for brain health may warrant recommendations for supplements in groups at risk of low levels, leading American scientists say. http://www.nutraingredients.com

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Antioxidant Therapy Against Alzheimer's Disease

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For the first time, new research demonstrates that curbing harmful antioxidant processes in the brain's vasculature can reverse some of the cognitive decline associated with Alzheimer's disease. A natural enzyme of the immune system -- NADPH oxidase -- has been found to have toxic side effects, producing free radicals in the brains of mice. Identification of the enzyme's role in dementia might translate into a new drug target for Alzheimer's disease in humans, according to new findings published in a recent issue of the Proceedings of the National Academy of Sciences. After the offending enzyme was genetically "switched off," mice with a type of dementia mimicking Alzheimer's regained important cognitive abilities, even though the amount of Alzheimer's-linked amyloid plaques in their brains remained unchanged. These results suggest that the enzyme independently influences the progression of dementia.

The researchers, led by Dr. Costantino Iadecola, the George C. Cotzias Distinguished Professor of Neurology and Neuroscience at Weill Cornell Medical College and chief of the Division of Neurobiology at NewYork-Presbyterian Hospital/Weill Cornell Medical Center, also genetically engineered mice that produced a mutated form of NADPH enzyme that did not produce the toxic free radicals.

The result: The formerly "demented" mice regained their healthy, exploratory behaviors, just as non-demented mice do. According to the authors, the findings suggest that neurological damage from Alzheimer's may not be permanent and might even be reversed through antioxidant treatment. http://www.medicalnewstoday.com .

The dangers of selective science

Antioxidants are back under the microscope for all the wrong reasons. But the use of meta-analyses to pool data is controversial, and scientists need to keep perspective before publishing conclusions. http://www.nutraingredients.com

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Dimebon as a treatment for Alzheimer's

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Patients with mild to moderate Alzheimer's disease who were treated with the experimental drug Dimebon from US drugmaker Medivation Inc, showed improvement in key mental skills after a year compared to patients who took the placebo. The patients on the active drug showed clear improvements in memory, language, awareness of time and place, and a more complex process called "praxis", which means having an idea and then actually putting it into practice. Ferris described the improvement observed in the patients who took Dimebon as "broad" as opposed to "selective", because it spanned improved memory, orientation, language and praxis. "This is an important finding given that deficits in memory and thinking are one of the hallmarks of Alzheimer's disease and cause patients and caregivers significant distress," said Ferris. (Dr Steven H Ferris, the Gerald J and Dorothy R Friedman Professor of Psychiatry at New York University (NYU) and director of the NYU Alzheimer's Disease Center). Chief medical officer of Medivation, Dr Lynn Seely, said in a press statement that: "We have recently presented a number of different findings from our first pivotal trial of Dimebon at scientific conferences, demonstrating that this investigational drug has a beneficial impact on the key aspects of Alzheimer's disease; from behavioral symptoms to thinking and memory problems to impairments in daily function." The company said it is pressing forward as rapidly as it can to develop Dimebon as a treatment for mild to moderate Alzheimer's disease. An earlier 12-month, double blind, placebo controlled trial involving 193 patients had already shown that patients on Dimebon showed statistically significant improvements in memory, thinking, daily living activities, behaviour and overall clinical function, compared with patients on placebo. According to the drugmaker, the improvements were already showing after 12 weeks, and were sustained after six months and a year. Also, at the six month point, the patients on the drug showed significantly better function on all five aspects of the disease than they did at the start of the trial. The drugmaker is planning to start a second confirmatory pivotal phase III trial soon, after which it will apply for US and European marketing approval in 2010, said the company in a press statement. http://www.medicalnewstoday.com .

Omega-3 EPA linked to improved gullet health
An increased intake of the omega-3 fatty acid eicosapentaenoic acid.... http://www.nutraingredients.com

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Vitamin E delays the progression of moderately severe Alzheimer's

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An increased intake of vitamin E supplements may improve the survival of people suffering from Alzheimer's disease, researchers report. Regular supplementation with vitamin E was associated with 26 per cent lower mortality rates, according to data obtained from 847 people with Alzheimer's disease presented at the American Academy of Neurology 60th Anniversary Annual Meeting in Chicago.

"Vitamin E has previously been shown to delay the progression of moderately severe Alzheimer's disease. Now, we've been able to show that vitamin E appears to increase the survival time of Alzheimer's patients as well," said lead author Valory Pavlik, PhD., from Baylor College of Medicine. "This is particularly important because recent studies in heart disease patients have questioned whether vitamin E is beneficial for survival."

Talking to NutraIngredients.com, Dr. Pavlik indicated that the results of the study, a long-term follow-up of an Alzheimer's disease patient cohort, are in-line with a randomised, placebo-controlled trial reported in the New England Journal of Medicine (1997, Vol. 336, pp. 1216-22), which showed a beneficial effect of vitamin E (2000 IU total per day) in Alzheimer patients. "We are not aware of any other studies that have examined vitamin E just in relation to all-cause mortality in Alzheimer's disease patients," said Dr. Pavlik. In addition, the study found vitamin E plus a cholinesterase inhibitor may be more beneficial than taking either agent alone. "Our findings show that people who took a cholinesterase inhibitor without vitamin E did not have a survival benefit," said Pavlik. "More research needs to be done to determine why this may be the case."

Alzheimer's disease (AD) is the most common form of dementia and currently affects over 13 million people worldwide. The direct and indirect cost of Alzheimer care is over $100 bn (€ 81 bn) in the US, while direct costs in the UK are estimated at £15 bn (€ 22 bn).

Unilever plucks UK soy drink from shelves
Unilever has withdrawn its soy juice - AdeZ - in the UK, after little more than 18 months on market after consumers failed to connect with its health messaging.http://www.nutraingredients.com

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High mid-life cholesterol and the risk of vascular dementia

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People with high cholesterol in their early 40s are more likely to develop Alzheimer's disease than those with low cholesterol, according to research that will be presented at the upcoming American Academy of Neurology 60th Anniversary Annual Meeting in Chicago, April 12-19, 2008.

"Our findings show it would be best for both physicians and patients to attack high cholesterol levels in their 40s to reduce the risk of dementia," said study author Alina Solomon, MD, with the University of Kuopio in Finland. Solomon collaborated with Rachel Whitmer, PhD, senior author of the study and a research scientist with Kaiser Permanente Division of Research in Oakland, CA.

The study involved 9,752 men and women in northern California who underwent health evaluations between 1964 and 1973 when they were between the ages of 40 and 45 and remained with the same health plan through 1994. From 1994 to 2007, researchers obtained the participants' most recent medical records to find 504 people had a diagnosis of Alzheimer's disease and 162 had vascular dementia. The study found people with total cholesterol levels between 249 and 500 milligrams were one-and-a-half times more likely to develop Alzheimer's disease than those people with cholesterol levels of less than 198 milligrams. People with total cholesterol levels of 221 to 248 milligrams were more than one-and-a-quarter times more likely to develop Alzheimer's disease.

"High mid-life cholesterol increased the risk of Alzheimer's disease regardless of midlife diabetes, high blood pressure, obesity, smoking and late-life stroke," said Solomon. Solomon says conclusions regarding high mid-life cholesterol and the risk of vascular dementia were difficult to formulate as there are several types of vascular dementia that may have slightly different risk factors.

The American Academy of Neurology, an association of more than 21,000 neurologists and neuroscience professionals, is dedicated to improving patient care through education and research. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as Alzheimer's disease, epilepsy, multiple sclerosis, Parkinson's disease, and stroke.

http://www.medicalnewstoday.com

Yellow kiwifruit may boost immune health: study

A puree from gold kiwifruit may enhance the immune response by promoting the production of antibodies in mice, suggests a new study from the home of the fruit.

http://www.nutraingredients.com

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Brain volume is an accurate tool for diagnosing the Alzheimer's

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Scientists in the US discovered that elderly people who had no mental decline had larger brains than Alzheimer's patients, even though their brain tissue showed signs normally associated with the disease. The researchers working at the OHSU Layton Aging & Alzheimer's Disease Center discovered that brain volume and the occurrence of mental decline are linked in people with Alzheimer's.

Autopsy examinations of elderly deceased patients showed that the volume of the whole brain, and particularly the hippocampus (a region that sits at the base of the brain and is thought to be involved with encoding long term memory and emotions) tended to be larger in those patients who had not suffered cognitive impairment when they lived. But the brains of these "healthy" patients still had the characteristic large clusters of protein plaques and tangles normally associated with Alzheimer's.

As co-investigator Dr Deniz Erten-Lyons, an assistant professor of neurology in the OHSU School of Medicine and a staff neurologist at the Portland Veterans Affairs Medical Center explained:"Prior to death, these people did not suffer from mental decline. We also noted that these healthy study subjects had brain volumes that were on average, larger than the brain volumes of the Alzheimer's subjects we studied."

The researchers examined the brains of 36 deceased patients, comprising 12 people who did not have symptoms of Alzheimer's before they died (no cognitive impairment) and 24 who did. Using MRI (magnetic resonance imaging), they found the brains of the "healthy" subjects were about 10 per cent larger by volume than those of the Alzheimer's patients.

Senior scientist on the study, Dr Jeffrey Kaye, who is director of the Layton Aging and Alzheimer's Disease Center and a professor of neurology in the OHSU School of Medicine said:"We are hopeful that this research will help us further understand the structural and genetic ties to Alzheimer's disease and perhaps offer clues that may help us develop new drugs or therapies. We should caution that at this point we do not believe brain volume is an accurate tool for diagnosing the disease. However, in the future, this correlation could be helpful to doctors and researchers alike".

Although the study is quite small, it was well received in some quarters. Professor Clive Ballard from the Alzheimer's Society in the UK, told the BBC the discovery "exciting" and needed "more exploration". Ballard said it was consistent with other studies that showed "people with higher levels of education or cognitive reserve may be protected from some of the effects of dementia". http://www.medicalnewstoday.com

Vitamin D status linked to artery health: study
Increased levels of vitamin D may improve cardiovascular health and reduce the prevalence of peripheral arterial disease (PAD), suggests a new study. http://www.nutraingredients.com

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Depression is an early indicator of the processes that cause Alzheimer's
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Depression may increase the risk of developing Alzheimer's: The Daily Telegraph reports on a study that followed more than 900 Catholic clergy for up to 13 years. It reports on a study that followed more than 900 Catholic clergy for up to 13 years. The study found that those who developed the disease had more symptoms of depression at the beginning of the study.

The main aim of the research was to look at changes in depressive symptoms in the early stages of Alzheimer's. There is a known association between dementia and depression. However, there are different theories as to whether depression causes Alzheimer's or whether they both develop because of a separate cause. By investigating changes in the severity of depression around the time that dementia develops, the researchers hoped to shed some light on the debate.

Their study found no increase in depressive symptoms before Alzheimer's became evident. This suggests that depression is not an early sign of the same processes that cause dementia. The researchers say that this therefore implies that depressive symptoms are a risk factor for Alzheimer's.

This study challenges the theory that depression and dementia are caused by another factor. It therefore adds weight to, but does not prove, the theory that depression is a risk factor for dementia. However, this study has shortcomings, and further research that is free of these should provide a clearer picture. Until more is known, depression sufferers should not be overly worried that they will develop dementia.

http://www.medicalnewstoday.com

Omega-3 EPA linked to improved gullet health
An increased intake of the omega-3 fatty acid eicosapentaenoic acid (EPA) may improve the fatty acid levels composition in the gullet, and reduce the risk of cancer, suggests a new study. http://www.nutraingredients.com

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An alternative way to treat Alzheimer's
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A private clinic in California, USA, appears to be getting dramatic reductions in dementia symptoms by injecting an arthritis drug called etanercept into the neck of Alzheimer's patients.

Using the drug as an "off-label" treatment (that is the drug is approved by the US Food and Drug Administration, but not for this particular use), the doctors at the Institute for Neurological Research, a private medical group based at the University of California, Los Angeles (UCLA), believe they are restoring communication links in the brain. Etanercept is normally used to treat arthritis, where it blocks the action of tumour necrosis factor-alpha (TNF), a chemical that causes painful and swollen joints. However, in the case of Alzheimer's, TNF is also thought to block the communication between brain cells, so using etanercept restores that function, so the researchers suggest.

The Institute for Neurological Research has posted videos and information on its website that describes Alzheimer's patients dramatically improving (within minutes in some cases) after receiving the drug. The drug is injected into the spine, at the neck, and then the patient is tilted up to encourage bloodflow to take the drug into the brain. Many experts say the results are worth investigating further with controlled clinical trials.

The private clinic is currently treating about 50 Alzheimer's patients using what it describes as the Tobinick Method for the treatment of Alzheimer's disease. Edward Tobinick is the professor who pioneered the research. Tobinick said he and his team have observed improvements in patients' thinking and reckoning skills, as well as memory and verbal skills. They have also noticed improvement in mood and in the "gait" of patients where that has been a symptom. However, the improvements are not so great that the patients can be described as returning to normal, he cautioned. Doctors at the clinic said they are getting 90 per cent response rates from the drug, usually within minutes. Some of the patients have been on the treatment for three years, but the typical patient improves week by week, as they receive each dose, and the improvements level out after about three months of being on the medication. One of the videos shows how the treatment affected 82-year old Marvin Miller. Miller can be seen muttering incoherently in response to questions from a nurse. He can't name objects like a pencil or a bracelet.

Miller is then given his first etanercept injection, and according to the video, five minutes later he recognizes and embraces his wife when she comes up to him. Mrs Miller said he had not done this for years, because until that moment he did not know who she was. She appears visibly shocked by her husband's improvement. In another session on the same video Mrs Miller describes her husband's improvements, four weeks after starting the treatment. He makes sense 90 per cent of the time now, and before the treatment he didn't make any sense at all, she said.

Dr Susanne Sorensen, head of research at the UK's Alzheimer's Society, said in a prepared statement that effective treatments for Alzheimer's were urgently needed. The disease affects 400,000 people in the UK alone, and there are millions of carers looking after people with Alzheimer's. The numbers of people affected by the disease are rising dramatically, and: "Investment in dementia research is an essential part of confronting this devastating condition," said Sorensen.

Regarding the apparent success of the Tobinick Method, Sorensen commented that: "On the surface these results are exciting," but she said "there are large gaps in the research, which only involved a small pilot group and we cannot draw any conclusions until a controlled trial is carried out". She said the Society has concerns about the cost and practical problems involved with a treatment where the patient has to be given the drug by injection into the spine, a procedure that requires specialist staff and facilities.

Sorensen concludes on a cautiously optimistic note and calls for more investment in research: "It is very encouraging to see alternative ways to treat Alzheimer's disease being explored. We need to see much wider investment in dementia research in the UK." Dr Clive Holmes, a professor at Southampton University, said on BBC Radio 4 this morning that he was keen to do the research, there was enough evidence from what he had seen on the video footage to make it worth doing a small clinical trial, but there was no funding as yet. http://www.medicalnewstoday.com

Green tea for sports nutrition?
Antioxidant-rich green tea may counter the effects of resistance exercise by reducing the detrimental effects of oxidative stress, suggests a small trial from Brazil. http://www.nutraingredients.com

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Wine provides protection against dementia
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There may be constituents in wine that protect against dementia. This is shown in research from the Sahlgrenska Academy at University of Gothenburg in Sweden.

The findings are based on 1,458 women who were included in the so-called Population Study of Women from 1968. When they were examined by physicians they were asked to report how often they drank wine, beer, and liquor by selecting from seven categories on a scale from 'never' to 'daily.' The researchers know nothing about how much they drank on each occasion, or how correct the estimates were. For each beverage the women reported having drunk more than once a month, they were classified as a consumer of that particular beverage.

Thirty-four years after the first study, 162 women had been diagnosed with dementia. The results show that among those women who reported that they drank wine a considerably lower proportion suffered from dementia, whereas this correlation was not found among those who had reported that they regularly drank beer or liquor. "The group that had the lowest proportion of dementia were those who had reported that the only alcohol they drank was wine," says Professor Lauren Lissner, who directs the study in collaboration with Professor Ingmar Skoog, both with the Sahgrenska Academy.

The researchers nevertheless are reluctant to make any recommendations regarding whether a woman should begin to drink wine, continue to drink wine, or increase their consumption. It's also important to point out that these findings cannot be generalized for men, who have a different pattern of drinking. "We have to be very cautious when we interpret these results, since we can't see in this type of population study what is cause and what is effect. There may be other factors in women who drink wine that provide them with protection against dementia, factors that we can't measure. But the correlation found is a strong one and can't be explained by other factors that we can measure, such as education, BMI, and smoking," says Lauren Lissner.

The researchers already knew that the drinking habits of Swedish women have changed over the last few decades. Today's women drink more wine and liquor, but less beer, than earlier generations did. The study shows, for example, that fewer than 20 percent of middle-aged women drank wine every week in the late 1960s. Today more than half of all women of that age report that they drink wine every week. "These findings, in combination with the fact that women today drink more wine than 40 years ago, show that it is important to continue to do research on this correlation. In future analyses we will be studying the effect on more specific types of dementia, such as Alzheimer's disease. Other research methods will be needed in order to see what role wine and other alcoholic beverages play in the development of dementia," says Lauren Lissner. http://www.medicalnewstoday.com

Canola protein shows anti-diabetes potential

Substituting milk proteins for proteins from rapeseed (canola) could delay the onset of insulin resistance and protect against diabetes, suggests a new study with rats. http://www.nutraingredients.com

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Lovastatin Slows Progression Of Alzheimer's
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High cholesterol levels are considered to be a risk factor for cardiovascular disease including stroke. Therefore, many cholesterol lowering drugs have been developed by pharmaceutical companies in recent years. One class of these drugs, statins, has been found to reduce the incidence of stroke and progression of Alzheimer's disease when prophylactically administered.

In a recent paper published in the Journal of Alzheimer's Disease, Amalia Dolga and co-workers from the University of Groningen show that the statin lovastatin, in addition to lowering cholesterol, can also prevent nerve cells from dying in conditions that occur in Alzheimer's disease. Amalia Dolga discovered a previously unknown cascade of cellular signals in nerve cells that are responsible for this neuroprotective mechanism. This is an important finding because in many diseases such as Alzheimer's or Parkinson's, death of nerve cells is generally thought to be a major cause of the dramatic symptoms that we find in these diseases.

Amalia Dolga found that statins stimulate nerve cells to produce a specific receptor molecule for a protein which plays a central role in the body's immune response: Tumor Necrosis Factor-alpha (TNF-á). Previous studies conducted by Dr. Ulrich Eisel's group in the Department of Molecular Neurobiology (headed by Prof. Paul Luiten) have demonstrated that this specific TNF-á signaling pathway has a strong beneficial effect on nerve cells and can protect nerve cells against death. This finding now demonstrates that a widely given drug like a statin can activate this protective pathway. http://www.medicalnewstoday.com

Vitamin D, calcium's colon benefits pinpointed?
Epidemiological studies supporting vitamin D and calcium for protection against colorectal cancer may be biochemically and biologically plausible, suggests new research. http://www.nutraingredients.com

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Alzheimer's: a simple memory screening test
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Early detection and diagnosis can help delay the onset of Alzheimer's disease and other memory problems. That's why Texas neuropsychologist Samuel Brinkman, Ph.D, developed the GrayMatters® Assessment System (http://www.dementiascreening.com) - to provide a quick, accurate, and affordable tool for identifying Alzheimer's disease and other memory problems. "In some cases, Alzheimer's-like symptoms might be caused by a physical illness or problem that can be treated and even reversed - if detected early," Brinkman said. "Effective screening leads to early detection and appropriate treatment."

GrayMatters® is a simple memory screening test that has been incorporated into an easy-to-use, touch screen computer system. No computer knowledge is needed to take the test. It can be taken during a doctor's office visit, with results available within minutes for the patient's physician to review. Because the test results are analyzed by the GrayMatters® system, routine memory screenings can even be provided by family physicians who have no specialized training in Alzheimer's or dementia diagnoses. If the test reveals symptoms of memory problems, patients can be referred to an expert for further testing and treatment.

Screening is recommended every one to two years for people in their 60s and annually for those ages 70 and older. For people who are at greater risk (with identifiable risk factors such as a parent diagnosed with Alzheimer's), annual screening should begin earlier.

The GrayMatters® Assessment System is designed for use in physician offices and healthcare clinic settings and requires minimal technological expertise for office personnel to set up and use. The system analyzes the test results, then sends a printable report back to the healthcare provider within minutes via a secure Internet connection. Patients require no technical or computer skills and interact easily with the system. The screening takes only about 30 minutes, as the unit cues the patient through each step of the assessment with easily understandable voice narration and visual cues. Patients respond to the instructions by touching the computer screen after each cue. http://www.medicalnewstoday.com

European food groups edging past US rivals in obesity focus
European food groups are ahead of US rivals in providing health and wellness products to consumers, but can do more in the area, a new report claims. http://www.nutraingredients.com

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Alzheimer's: eating blueberries are good for you
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Blueberries and other phytochemical-rich foods could help in increasing memory capacity by reversing age-related deficits in memory, according to a new rat study by UK researchers. The study, conducted by researchers at the University of Reading and the Peninsula Medical School, has not yet been published but is expected to appear in the peer-reviewed journal Free Radical Biology and Medicine within the next few days. After supplementing the diet of rats with blueberries over a 12-week period, the research team said that improvements in spatial working memory tasks emerged within three weeks and continued throughout the period of the study.

Forgetful rats Three groups of adult male rats were used in the study. The first group comprised of 'young' rats, aged 6 months at the start of the testing period, while the remaining rats were all 18 months old and were randomly assigned to either an 'aged' group or an 'aged + blueberry-supplemented' group. Those in the blueberry-supplemented group had powdered blueberries incorporated into the standard rat feed at a level of 2 per cent.

The researchers said that the two intervention diets used contained a defined and characterized amount of flavonoids (anthocyanins and flavanols) and were as far as possible macro- and micronutrient-matched. The two diets were isocaloric and matched for major antioxidant vitamins via the addition of corn starch and vitamin C (2 mg/kg) to the control diet. The mean intake of flavonoids by blueberry-fed animals was approximately 10.5 mg/day (Anthocyanins: 6.68 mg/day; Flavanols: 3.85 mg/day). Rats were tested in cross-maze apparatus, which they had to navigate in order to receive reward pellets. The animals were given a week's training in the apparatus before supplementation began in order to ensure that they ran reliably. The researchers set up an alternate navigation/reward system, which involved rats having to make a choice as to which path to take in order to receive the pellets. For each trial, accuracy and time taken to make a choice were measured.

Old rats get sharp Animals in the 'young' group were found to perform "extremely well and very consistently", scoring an average of 90 per cent correct on each test day. The 'aged' animals were substantially impaired on this task compared to the young animals, with an average score of only 57 per cent correct.

Similarly, the 'aged + blueberry-supplemented' group showed an age-related deficit in performance compared to the 'young' animals at baseline achieving only 60 per cent accuracy of choice. However, three weeks of blueberry supplementation produced a significant increase in performance in these animals, with accuracy rising to 83 per cent by testing in week three. This increase in performance accuracy was maintained throughout the remainder of the treatment period, said the researchers.

Blueberry benefits

"This study not only adds science to the claim that eating blueberries are good for you, it also provides support to a diet-based approach that could potentially be used to increase memory capacity and performance in the future," said researcher Dr Matt Witterman, from the Institute of Biomedical and Clinical Science, Peninsula Medical School.

The beneficial effects of the blueberries are thought to be linked to their flavonoid content - in particular anthocyanins and flavanols. The exact way in which flavonoids affect the brain are unknown, but they have previously been shown to cross the blood brain barrier after dietary intake.

It is believed that they exert their effects on learning and memory by enhancing existing neuronal connections, improving cellular communications and stimulating neuronal regeneration, explained the researchers.

"Scientists have known of the potential health benefits of diets rich in fresh fruits for a long time. Our previous work had suggested that flavonoid compounds had some kind of effect on memory, but until now we had not known the potential mechanisms to account for this," said lead researcher Dr Jeremy Spencer, a lecturer in Molecular Nutrition at the University of Reading. The research team said it plans to extend its findings further by investigating the effects of diets rich in flavonoids on people suffering from cognitive impairment and Alzheimer's disease. http://www.medicalnewstoday.com

Maternal omega-3 again linked to children's coordination
Increased intake of the omega-3 DHA during pregnancy could produce improved motor function in the offspring in later life, suggests a new study from Canada.

http://www.nutraingredients.com

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The risk for dementia associated with small vessel disease
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Alzheimer's disease may be what most people fear as they grow older, but autopsy data from a long-range study of 3,400 men and women in the Seattle region found that the brains of a third of those who had become demented before death showed evidence of small vessel damage: the type of small, cumulative injury that can come from hypertension or diabetes.

Dr. Thomas Montine, University of Washington, presented the study results at Experimental Biology 2008 in San Diego on April 6. His presentation was part of the scientific program of the American Society for Biochemistry and Molecular Biology (ASBMB).

In the autopsied brains of people who had experienced cognitive decline and dementia, 45 percent of the risk for dementia was associated with pathologic changes of Alzheimer's disease. Another 10 percent of dementia risk was associated with Lewy bodies, neocortical structural changes that indicate a degenerative brain disease known as Lewy Body Dementia, believed by some clinicians to be a variant of Alzheimer's and/or Parkinson's disease. But a third of the risk for dementia (33 percent) was associated with damage to the brain from small vessel disease.

Dr. Montine and his colleagues believe that, and are now studying in more detail, this small vessel damage is the cumulative effect of multiple small strokes caused by hypertension and diabetes, strokes so small that the person experiences no sensation or problems until the cumulative effect reaches a tipping point. This may be good news, says Dr. Montine. At a time when prevention and treatment for Alzheimer's remain investigational, methods for preventing complications of hypertension and diabetes are currently available.

These findings are very different from both conventional wisdom and from those of most autopsy studies of brain aging and dementia, says Dr. Montine.

Why such different results? Perhaps because of the broad reach of the population on which the autopsy study was based, says Dr. Montine. Most studies looking at the structural changes on autopsy in brains of persons with dementia have focused on participants in Alzheimer's disease center studies or in populations limited to one gender, ethnic or professional group. Individuals in this study were part of the Group Health Cooperative, one of the oldest and largest managed care programs in the United States.

Members in the group who reach 65 with normal cognitive ability are eligible to volunteer for an Adult Changes in Thought (ACT) study, established by Dr. Eric Larson, director of Research at the Group Health Cooperative. ACT participants undergo cognitive, neurological and psychological tests every two years until their death.

Between 1994 and 2006, the period covered by this study, 3,400 men and women entered the ACT study. They were representative of the Seattle urban and suburban area: white, Asian, African American and Hispanic, with a range of educational and professional levels. During this 12-year period, some participants suffered cognitive impairment and dementia, while others did not. Roughly a third of all participants died, and autopsies were performed on the 221 who had given permission for this to be done.

With 55 percent of the risk for dementia attributable to Alzheimer's and Lewy Body Dementia, these findings underscore the therapeutic imperative for developing new pharmacologic and other means of preventing or delaying the onset of Alzheimer's and Lewy Body disease, says Dr. Montine. But the unexpected finding that a third of the risk for dementia is related to small vessel disease also provides an additional reason to control hypertension and diabetes: not only to protect cardiovascular and renal health but also to protect the health of the brain. http://www.medicalnewstoday.com

Red grape's antioxidant benefits identified
A dietary supplement of red grape juice may reduce the activity of an enzyme linked to cardiovascular disease, suggests a new study said to be first report of its kind in humans.

http://www.nutraingredients.com

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Aluminum as a risk factor for Alzheimer's
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The purpose of the study was to condense existing scientific evidence about the relation between aluminum (Al) exposure and risk for the development of Alzheimer's Disease (AD), evaluating its long-term effects on the population's health. A systematic literature review was carried out in two databases, MEDLINE and LILACS, between 1990 and 2005, using the uniterms: "Aluminum exposure and Alzheimer Disease" and "Aluminum and risk for Alzheimer Disease". After application of the Relevance Test, 34 studies were selected, among which 68% established a relation between Al and AD, 23.5% were inconclusive and 8.5% did not establish a relation between Al and AD. Results showed that Al is associated to several neurophysiologic processes that are responsible for the characteristic degeneration of AD. In spite of existing polemics all over the world about the role of Al as a risk factor for AD, in recent years, scientific evidence has demonstrated that Al is associated with the development of AD. Rev Lat Am Enfermagem. 2008 Feb;16(1):151-157

Vitamin K2 linked to lower prostate cancer risk

An increased intake of vitamin K2 may reduce the risk of prostate cancer by 35 per cent, suggest results from the European Prospective Investigation into Cancer and Nutrition (EPIC). http://www.nutraingredients.com

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Alzheimer's is higher in women than in men
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The prevalence of Alzheimer disease is higher in women than in men. In the age group 65-69 years 0.7% of women and 0.6% of men suffer from the disease with increasing frequencies of 14.2% and 8.8% in individuals aged 85-89 years. The incidence is also higher in demented women. In Austria 74.1% of Alzheimer patients older than 60 years are women. Several studies report more pronounced language, mnestic, semantic and orientation deficits in women, but methodological shortcomings might be responsible for this finding. The validity of results reporting a more rapid cognitive decline in women can also be questioned. Women have a broader spectrum of dementiarelated behavioural symptoms with a predominance of depression, while aggression is more frequent in men than in women. Biological explanations for gender-specific differences in the phenotype of Alzheimer s disease include different brain morphology and function with higher susceptibility for pathological lesions in women and greater cognitive reserve in men. Sex differences were also reported for expression of antioxidative enzymes and post-menopausal hormonal changes. Interactions between gender nd response to treatment, if any, are subtle and have large intra-individual variability. In Austria, two thirds of patients receiving attendance allowance are women. Care takes place in 80% by the families and is provided by women in 78%. The rate of female care-givers in partly institutionalized care units in 91% in nursing homes it is 84%. Neuropsychiatr. 2008;22(1):1-15

Essential oil combinations offer shelf-life prolongation
Combining low levels of essential oils (EOs) could enhance their antimicrobial power and remove adverse taste effects, suggests a new study from Ireland. http://www.nutraingredients.com

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Redox-active iron correlates with Alzheimer's
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Oxidative stress constitutes a hallmark of Alzheimer's disease (AD). Recent studies also point to redox active metals such as iron, copper and zinc in mediating oxidative stress in AD pathogenesis. However, the reactivity of cerebrospinal fluid (CSF) iron and its possible correlation with the severity of cognitive decline in both Alzheimer's patients and subjects with mild cognitive impairment (MCI) is still unknown. Here we show that different stages of cognitive and functional impairment are associated with changes in CSF reactive iron. In this work, we compared CSF samples from {56} elders, classified into 4 groups according to their scores on the Clinical Dementia Rating scale (CDR). Total CSF iron was analyzed by atomic absorption spectrometry. Redox-active iron was analyzed by a novel fluorimetric assay. One-way ANOVA was used to test differences in mean values, and Newman-Keuls Multiple Comparison Test was used for multi group comparisons. No difference in total CSF iron was found between different groups. Significant amounts of redox-active iron were found in CSF and their levels correlated with the extent of cognitive impairment. Redox-active CSF iron levels increased with the degree of cognitive impairment from normal to MCI subjects, while AD patients showed an abrupt decrease to levels close to zero. Given the relevance of oxidative damage in neurodegeneration, it might be possible to associate the development of cognitive and functional decline with the presence of redox-active iron in the CSF. The decrease in redox-active iron found in AD patients may represent a terminal situation, whereby the central nervous system attempts to minimize iron-associated toxicity. J Alzheimers Dis. 2008 Apr;13(2):225-32 Epub 2007 Sep 18

Passion fruit peel may ease breathing for asthmatics: study
A flavonoid-rich extract from purple passion fruit may ease wheezing amongst asthmatics, suggest findings from a randomised, placebo-controlled, double-blind trial. http://www.nutraingredients.com

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Zinc deficiency: a risk factor for Alzheimer's
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The ZnT3 zinc transporter is uniquely expressed in cortical glutamatergic synapses where it organizes zinc release into the synaptic cleft and mediates beta-amyloid deposition in transgenic mice. We studied the association of zinc in plaques in relation to cytoarchitectural zinc localization in the APP/PS1 transgenic mouse model of Alzheimer's disease. The effects of low dietary zinc for 3 months upon brain pathology were also studied. We determined that synaptic zinc distribution within cortical layers is paralleled by amyloid burden, which is heaviest for both in layers 2-3 and 5. ZnT3 immunoreactivity is prominent in dystrophic neurites within amyloid plaques. Low dietary zinc caused a significant 25% increase in total plaque volume in Alzheimer's mice using stereological measures. The level of oxidized proteins in brain tissue did not changed in animals on a zinc-deficient diet compared with controls. No obvious changes were observed in the autometallographic pattern of zinc-enriched terminals in the neocortex or in the expression levels of zinc transporters, zinc importers or metallothioneins. A small decrease in plasma zinc induced by the low-zinc diet was consistent with the subclinical zinc deficiency that is common in older human populations. While the mechanism remains uncertain, our findings indicate that subclinical zinc deficiency may be a risk factor for Alzheimer's pathology. Neuroscience. 2007 Dec 5;150(2):357-69. Epub 2007 Sep 18


Raw milk feta may hold anti-Listeria key, say researchers Feta cheese made from raw milk in Greece may hold secrets that could lead to new methods for battling food poisoning bacteria like Listeria, researchers at the University of Lincoln said yesterday. http://www.dairyreporter.com

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MRI to detect Alzheimer's
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With nearly 10 million baby boomers at risk for developing Alzheimer's disease, researchers are taking a closer look at a condition known as mild cognitive impairment. This is a state between the normal forgetfulness that comes with aging and the more pronounced thinking deficits of dementia. Mild cognitive impairment often progresses to Alzheimer's disease, but some people remain stable and others recover. New technology is improving the ability to determine who might fall into each category, reports the April 2008 issue of the Harvard Mental Health Letter. These developments are promising because they are occurring just as the first disease-modifying drugs for Alzheimer's have reached late-stage clinical testing.

One technology, fluorodeoxyglucose positron emission tomography (FDG-PET), measures blood glucose metabolism in the cerebral cortex. Diminished glucose uptake suggests that neurons are not as active. Clinicians can also measure brain volume changes with volumetric MRI to detect shrinkage, which is typical in Alzheimer's. These techniques are likely to prove most useful when combined with detection of newly discovered proteins believed to be the first signs of Alzheimer's.

If one of these technologies or a combination can reliably predict which people with cognitive impairment are likely to progress to Alzheimer's, scientists might be able to determine who should get the disease-modifying medications now in development. And they might be able to predict which healthy people are most likely to get mild cognitive impairment, and try to prevent it.

The technologies and medications needed to predict and prevent mild cognitive impairment and Alzheimer's are still in the early stages of development, but the Harvard Mental Health Letter says that this research will almost certainly lead to better treatments. http://www.medicalnewstoday.com

Red seaweed extract shows joint health benefits

A natural, multi-mineral ingredient derived from the red seaweed Lithothamnion Corallioides can improve osteoarthritis symptoms by about 15 per cent, say the results of a new pilot study.

http://www.nutraingredients.com

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Alzheimer's away: a cup of coffee a day
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A daily dose of caffeine blocks the disruptive effects of high cholesterol that scientists have linked to Alzheimer's disease. A study in the open access publication, Journal of Neuroinflammation revealed that caffeine equivalent to just one cup of coffee a day could protect the blood-brain barrier (BBB) from damage that occurred with a high-fat diet. The BBB protects the central nervous system from the rest of the body's circulation, providing the brain with its own regulated microenvironment. Previous studies have shown that high levels of cholesterol break down the BBB which can then no longer protect the central nervous system from the damage caused by blood borne contamination. BBB leakage occurs in a variety of neurological disorders such as Alzheimer's disease.

In this study, researchers from the University of North Dakota School of Medicine and Health Sciences gave rabbits 3 mg caffeine each day - the equivalent of a daily cup of coffee for an average-sized person. The rabbits were fed a cholesterol-enriched diet during this time. After 12 weeks a number of laboratory tests showed that the BBB was significantly more intact in rabbits receiving a daily dose of caffeine.

"Caffeine appears to block several of the disruptive effects of cholesterol that make the blood-brain barrier leaky," says Jonathan Geiger, University of North Dakota School of Medicine and Health Sciences. "High levels of cholesterol are a risk factor for Alzheimer's disease, perhaps by compromising the protective nature of the blood-brain barrier. For the first time we have shown that chronic ingestion of caffeine protects the BBB from cholesterol-induced leakage." Caffeine appears to protect BBB breakdown by maintaining the expression levels of tight junction proteins. These proteins bind the cells of the BBB tightly to each other to stop unwanted molecules crossing into the central nervous system. The findings confirm and extend results from other studies showing that caffeine intake protects against memory loss in aging and in Alzheimer's disease. "Caffeine is a safe and readily available drug and its ability to stabilise the blood-brain barrier means it could have an important part to play in therapies against neurological disorders," says Geiger. http://www.medicalnewstoday.com

Wine and tea compounds linked to diabetes benefits
Antioxidant-rich red wine and tea could help regulate blood sugar levels in diabetics, suggests a new study from the University of Massachusetts. http://www.nutraingredients.com

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Gamma secretase modulators shows promise in Alzheimer's
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Gamma secretase modulators (GSMs) have shown promise in Alzheimer's disease animal model efficacy studies, according to research conducted by TorreyPines Therapeutics, Inc. (Nasdaq: TPTX).

Presented by Steven Wagner, Ph.D., the company's Chief Scientific Officer, at the recent Keystone Symposium on Alzheimer's Disease, data demonstrated that GSMs provide a more selective mechanism than gamma secretase inhibitors (GSIs). The in vivo research involved internally discovered and optimized compounds that modulate the g-secretase complex without inhibiting its catalytic activity. These GSMs appear to reduce the formation of the longer pathogenic Ab peptides (e.g, Ab42) and allow the g-secretase enzyme complex to generate the shorter, less fibrillogenic Ab peptides such as Ab38 and Ab37 and to perform its other necessary functions.

"We have identified a series of GSM compounds that are intended to modulate the enzyme's activity without preventing it from performing its normal functions," said Dr. Wagner. "These orally bio-available, small molecule GSMs appear to have addressed some of the pitfalls associated with the GSI compounds, which have been associated with side effects. The significance of our findings is that we may be able to selectively attenuate the pathological functions of this enzyme complex without affecting the other critical physiological functions it performs."

The major pathological hallmark of Alzheimer's disease is the abundance of deposits called neuritic plaques in key areas of the brain that control memory and cognition. These neuritic plaques are largely comprised of aggregations of fibrillar peptides referred to as amyloid b, or Ab peptides. Evidence indicates that individuals genetically predisposed to early-onset forms of Alzheimer's disease make a greater proportion of the longer Ab peptides, especially Ab42, relative to unaffected individuals. All of these Ab peptides, including the pathogenic Ab42 peptide, are derived via proteolysis from a much larger precursor molecule known as the amyloid b precursor protein (APP: 9.55, -0.35, -3.53%).

During normal catabolism, two crucial enzymes, or proteases, are responsible for generating these Ab peptides from APP. The first enzyme, beta secretase (b-secretase), cuts the APP molecule into two major pieces comprised of a soluble extracellular fragment and a membrane-associated fragment. The second enzyme, gamma secretase (g-secretase), then cleaves the membrane- associated fragment into one of several different Ab peptides that vary in length from 34 to 42 amino acids. http://www.foxbusiness.com

Inulin range offers obesity solutions
Cosucra Groupe Warcoing has launched two new ingredients designed to boost fibre and reduce sugar in food and beverage products. http://www.nutraingredients.com

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Anti-psychotic Drugs Bad For Alzheimer's
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A new UK study has found that anti-psychotic drugs, such as (Melleril), chlorpromazine (Largactil), haloperidol (Serenace), trifluoperazine (Stelazine) and risperidone (Risperdal), are bad for patients with Alzheimer's disease - the drugs were found to make their condition worse.

The researchers, from Kings College London and the Universities of Oxford and Newcastle, found that neuroleptics undermined Alzheimer's patients' verbal skills, and offered most patients with mild symptoms of disturbed behavior no long-term benefit. In fact, they found that a deterioration in verbal skills happened within six months of taking the medications. Neuroleptics are drugs used for treating schizophrenia as well as some other serious mental illnesses.

In this study, researchers looked at 165 Alzheimer's patients from four different nursing homes in Oxfordshire, Newcastle, Edinburgh and London. Approximately 60% of UK Alzheimer's patients are given medications to control their often aggressive behavior. There are indications that neuroleptics may also up the death rates of Alzheimer's patients. All the 165 patients had started on neuroleptics and had been on them for three months before the study started. Half of them continued on them for another 12 months while the others were switched to a placebo.

"It is very clear that even over a six-month period of treatment, there is no benefit from neuroleptics in treating the behavior in people with Alzheimer's disease when the symptoms are mild. For people with more severe behavioral symptoms, balancing the potential benefits against adverse effects is more difficult," said team leader Professor Clive Ballard. Many experts are saying that in light of this study neuroleptics should only be used long-term for dementia patients who have severe behavioral problems, after other treatments have failed.

Neil Hunt, Chief Executive of the Alzheimer's Society (UK), wrote -"The overprescribing of antipsychotics to people with dementia is robbing people of their quality of life and is a serious breach of human rights. Paul Burstow MP's report illustrates the scale and severity of the important issue. Inappropriate use of antipsychotics in people with dementia can cause devastating side effects, such as excessive sedation, parkinsonism symptoms, accelerated cognitive decline and an increased risk of stroke. This abuse has got to stop. Antipsychotics have got to stop being a quick fix. There are over 700,000 people with dementia in the UK and more than half of these will experience behavioral symptoms. Alzheimer's Society research has shown that basic dementia training can help staff deal with behavioral symptoms and reduce the use of antipsychotics drugs by 50 per cent." http://www.medicalnewstoday.com

Salmonella study to build prebiotics knowledge
Studies are underway to investigate the use of galacto-oligosaccharides to protect animals from salmonella infection, both to reducing the risk of the bacteria entering the food chain and increase knowledge on prebiotics' benefits. http://www.nutraingredients.com

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Slow the progression of Alzheimer's by inhibiting gamma-secretase
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Alzheimer's disease is a progressive neurodegenerative condition that is the most common cause of dementia in patients over 65 years of age. Estimates show that 6-8% of people over age 65 are affected by Alzheimer's disease, totaling approximately 5 million people in the United States alone. Every 72 seconds, an American is developing Alzheimer's disease, and it is the seventh-leading cause of death in the United States. The direct and indirect health care costs associated with Alzheimer's disease in the U.S. are estimated to be about $150 billion. The total cost globally in 2005 was estimated at $315.4 billion.
As life-expectancy grows, without the availability of medicines that delay or prevent the onset of Alzheimer's disease, the number of affected people is expected to at least triple by the year 2050 in developed nations. The average duration between onset of symptoms and death due to complications of Alzheimer's disease is about 8-10 years. The burden to caregivers and health care costs can increase dramatically in the late stages of Alzheimer's disease, when patients cannot maintain independent function and are frequently bedridden.
Eli Lilly and Co has started a Phase III Clinical Trial of LY450139, an investigational gamma secretase inhibitor for the treatment of patients with mild/moderate Alzheimer's disease. The trial aims to see whether it can slow the progression associated with Alzheimer's by inhibiting gamma-secretase. Gamma-secretase is an enzyme that can create amyloid beta - a sticky protein.
The current theory goes that subtypes of amyloid beta stick together and form plaques - these plaques play a key role in killing off brain cells. If the gamma secretase can be blocked less amyloid beta is formed, and subsequently plaques are formed and fewer brains cells are killed off. Patients whose Alzheimer's progression is slowed down may be able to preserve independent functioning and quality of life in the milder disease stages. Also, it is hoped that LY450139 may delay the onset of the severe stages of Alzheimer's.

To date, there are no Alzheimer's disease treatments which have a documented effect on amyloid beta. At best, current treatment may provide modest improvements in symptoms, but have no impact on slowing down the underlying disease process. To more completely characterize the disease-modifying effects of LY450139, a number of optional biomarker sub-studies will be available to patients. These optional sub-studies will utilize new brain-scanning techniques to determine the amount of amyloid beta plaque in the brain, employ other, more established scanning techniques to examine brain structure and function, and evaluate a number of additional biochemical measures of Alzheimer's disease. By determining the effect of LY450139 on these objective biomarkers, a more complete understanding of the effect of LY450139 on underlying Alzheimer's disease pathology is possible. http://www.medicalnewstoday.com

Green tea shows superbug-battling potential
Green tea can boost the potential of antibiotics to battle superbugs and other bacterial strains and even make previously antibiotic-resistant bacteria susceptible to treatment, according to "surprised" Egyptian scientists. http://www.nutraingredients.com

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