Biomarkers for diagnosis of Alzheimer's
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Simple, non-invasive tests for an early detection of degenerative dementia by use of biomarkers are urgently required. However, up to the present, no validated extracerebral diagnostic markers (plasma/serum, platelets, urine, connective tissue) for the early diagnosis of Alzheimer disease (AD) are available. In disease stages with evident cognitive disturbances, the clinical diagnosis of probable AD is made with around 90% accuracy using modern clinical, neuropsychological and imaging methods. Diagnostic sensitivity and specificity even in early disease stages are improved by CSF markers, in particular combined tau and amyloid beta peptides (Abeta) and plasma markers (eg, Abeta-42/Abeta-40 ratio). Recently, a novel gene/protein - ALZAS (Alzheimer Associated Protein) - with a 79 amino acid sequence, containing the amyloid beta-42 fragment (Abeta-42), the amyloid precursor protein (APP) transmembrane signal and a 12 amino acid C-terminal, not present in any other known APP alleles, has been discovered on chromosome 21 within the APP region. Reverse transcriptase-PCR revealed the expression of the transcript of this protein in the cortex and hippocampal regions as well as in lymphocytes of human AD patients. The expression of ALZAS is mirrored by a specific autoimmune response in AD patients, directed against the ct-12 end of the ALZAS-peptide but not against the Abeta-sequence. ELISA studies of plasma dectected highest titers of ALZAS in patients with mild cognitive impairment (presymptomatic AD), but only moderately increased titers in autopsy-confirmed AD, whereas low or undetectable ct-12 titers were found in cognitively intact age-matched subjects and young controls. The antigen, ALZAS protein, was detected in plasma in later clinical stages of AD. It is suggested that ALZAS represents an indicator in a dynamic equilibrium between both peripheral and brain degenerative changes in AD and may become a useful "non-invasive" diagnostic marker via a simple blood test. J Cell Mol Med. 2008 Mar 19

Vitamin A may suppresses type 1 diabetes

High levels of vitamin A may curb the onset of type 1 diabetes by protecting against the attack of insulin-producing beta cells, according to an animal study by American scientists.

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Oral drug candidate for Alzheimer's disease
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EPIX Pharmaceuticals, Inc., a biopharmaceutical company focused on discovering and developing novel therapeutics through the use of its proprietary and highly efficient in silico drug discovery platform, announced that Tom Megerian, M.D., Ph.D, executive director, clinical research of EPIX, is scheduled to present an oral presentation entitled "Results of a Phase 2A Study of a Novel 5HT4 Agonist for the Treatment of Alzheimer's Disease" at the Keystone Symposia Alzheimer's Disease Meeting in Keystone, Colorado on Friday, March 28, 2008 at 8:00 a.m. MDT. EPIX previously announced the compelling results of a Phase 2a clinical trial of PRX-03140 as a single agent and in combination with Aricept® in patients with mild Alzheimer's disease. Dr. Megerian's presentation will focus on these previously reported data.
PRX-03140 is part of EPIX's strategic partnership with GlaxoSmithKline. The companies have been working together to design and initiate the Phase 2b clinical program. EPIX recently announced that this proof of concept program consists of two clinical trials - PRX-03140 as monotherapy and PRX-03140 in combination with donepezil. EPIX expects to initiate these trials in the first half of 2008, and both trials will address a larger patient population and a longer duration of therapy than the successful two-week Phase 2a trial.

PRX-03140 is a novel, oral investigational drug candidate for Alzheimer's disease. It is selective for the 5-HT4 receptor in the brain and is believed to stimulate both acetylcholine production/release - which enables symptomatic improvement in Alzheimer's patients - and the alpha-secretase pathway - which slows Alzheimer's disease progression. Recent Phase 2a results indicated that patients receiving daily oral 150 mg doses of PRX-03140 as monotherapy achieved a mean 3.6 point improvement on the Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog) versus a 0.9 point worsening in patients on placebo (p= 0.021). The ADAS-cog endpoint is the current standard for evaluating drug efficacy for cognition in Alzheimer's disease and is an established and accepted registration endpoint. In three Phase 1 trials and the Phase 2a trial, with more than 180 patients and healthy subjects, PRX-03140 has been well-tolerated. In a 14-day Phase 1b clinical trial, treatment with PRX-03140 resulted in changes in brain wave activity in Alzheimer's patients that are consistent with those seen in clinical trials with currently approved drugs for Alzheimer's disease. In preclinical studies, PRX-03140 has shown to improve cognitive function through increasing levels of acetylcholine, and has led to increased levels of soluble amyloid precursor protein (sAPP) and brain-derived neurotrophic factor (BDNF) in regions of the brain known to be important for memory. http://www.medicalnewstoday.com

Health continues to dominate bakery trends
The trend for healthy and functional foods will continue to dominate the bakery market this year, resulting... http://www.nutraingredients.com

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The dangerous effects of abdominal obesity on the brain
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People in their 40s with larger stomachs have a higher risk for dementia when they reach their 70s.

Previous studies have looked at central obesity (as determined by waist circumference) and body mass index in the elderly and its link to dementia risk. In addition, previous studies have shown that a large abdomen -- in midlife -- increases the risk of diabetes, stroke, and coronary heart disease. This is the first time researchers have demonstrated a longitudinal association between midlife belly fat and the risk of dementia. Capturing abdominal obesity in midlife may be a much better indicator of the long term metabolic dysregulation that leads to dementia risk, said study author Rachel Whitmer, PhD, a research scientist at the Kaiser Permanente Division of Research in Oakland, CA. Measuring abdomen size in older age people may not be as good an indicator because as people age they tend to naturally lose muscle and bone mass and gain belly size, she explained.

"Considering that 50 percent of adults in this country have abdominal obesity, this is a disturbing finding. It is well known that being overweight in midlife and beyond increases risk factors for disease. However, where one carries the weight - especially in midlife - appears to be an important predictor for dementia risk," she said. "Autopsies have shown that changes in the brain associated with Alzheimer's disease may start in young to middle adulthood, and another study showed that high abdominal fat in elderly adults was tied to greater brain atrophy. These findings imply that the dangerous effects of abdominal obesity on the brain may start long before the signs of dementia appear." She explained that additional research needs to be completed to determine the underlying mechanisms that link abdominal obesity in midlife to dementia risk.

Researchers studied 6,583 people age 40 to 45 in northern California who had their abdominal density measured. Belly fat was measured by using a caliper to determine the distance from the back to the upper abdomen, midway between the top of the pelvis and the bottom of the ribs. Belly density is highly correlated with visceral fat tissue, the fat tissue that is wrapped around the organs, according to the researchers. An average of 36 years later, 16 percent of the participants had been diagnosed with dementia. The study found that those who were overweight and had a large belly were 2.3 times more likely to develop dementia than people with a normal weight and belly size. People who were both obese and had a large belly were 3.6 times more likely to develop dementia than those of normal weight and belly size. Those who were overweight or obese but did not have a large abdomen had an 80-percent increased risk of dementia.

Having a large abdomen increased the risk of dementia regardless of whether the participants were of normal weight overall, overweight, or obese, and regardless of existing health conditions, including diabetes, stroke and cardiovascular disease. Non-whites, smokers, people with high blood pressure, high cholesterol or diabetes, and those with less than a high school level of education were more likely to have abdominal obesity.

As with all observational studies, it is possible that the association of the abdominal obesity and dementia is not driven by the abdominal obesity, but rather by a complex set of health-related behaviors, for which abdominal obesity is but one part. http://www.medicalnewstoday.com

New study backs satiety benefits of PinnoThin
A new study has shown that pine nut oil can help reduce food consumption, providing additional weight to the satiety benefits of Lipid Nutrition's PinnoThin ingredient. http://www.nutraingredients.com

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Baby boomers will develop Alzheimer's disease
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The American Health Care Association and National Center for Assisted Living (AHCA/NCAL) said that findings in a new study from the Alzheimer's Association, which estimates ten million U.S. baby boomers will develop Alzheimer's disease in their lifetime, underscores the urgent need for Congress and the Bush Administration to ensure Medicaid has both the future capacity and the financing necessary to compassionately and effectively treat what will be an older, sicker, cognitively-impaired patient population.

"This is a significant, disturbing and timely study from the Alzheimer's Association because it demonstrates in stark definable terms why Medicaid must remain financially viable to ensure we have the ability to care for the influx of Baby Boomers who will require increasingly high levels of care," stated Bruce Yarwood, President and CEO of AHCA/NCAL "The study also signals to our policy makers that critical Medicaid 'reforms' cannot lead us down a road that will further weaken the financial underpinnings of this already unstable program."

Currently, at least 5.2 million Americans suffer from Alzheimer's disease, including 200,000 to 250,000 people under age 65. The Alzheimer's report estimates that by 2010, there will be 500,000 new cases of the disease each year and nearly one million new cases annually by 2050.

Yarwood reiterated AHCA/NCAL's position on Medicaid reform proposals, stating that it is essential for Congress and the Administration to focus on how they would impact care capacity at the state level, and how simply eliminating revenue would decimate the ability to enhance staffing, improve quality, and bolster facility infrastructure and capacity as demand for more care and therapies is on the rise.

"The long term care stakeholder community must work together in an intelligent, realistic manner to ensure the Medicaid safety net does not fray in the critical years ahead and that the rising numbers of Alzheimer's patients are not relegated to a status unworthy of our great nation," concluded Yarwood. http://www.medicalnewstoday.com

Apples may help ward off colon cancer

Apple pectin and polyphenol-rich apple juice have an anticarcinogenic effect on the colon, encouraging the production of suspected chemopreventative metabolite butyrate, say researchers. http://www.nutraingredients.com

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Obesity's influence on dementia
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As populations age, all cognitive disorders, including dementia, become more common. Dementia affects 6–10% of people aged 65 years or older; two-thirds of whom have Alzheimer's disease (AD) (1). In fact, AD currently ranks as the eighth leading cause of death among the elderly in the United States (2) and a pooled analysis for mortality risk by dementia status yielded a risk ratio of 2.63 (2.17, 3.21), independently of age, sex and education (3). Despite its strong association with age (1,4), dementia is still considered a potentially preventable condition with a large number of possible modifiable risk factors. Dementia, particularly of the vascular type (VaD), is conceptually linked with cardiovascular complications. Recent research efforts have included AD as a potential outcome for poor cardiovascular profile (5). One group of risk factors is adiposity, particularly body mass index (BMI in kg m⁻²), obesity (BMI ≥ 30) and central obesity as measured by waist circumference (WC). However, there is still no consensus as to their direct impact on dementia, independently of associated cardiovascular factors, such as type 2 diabetes, hypertension and dyslipidaemia. Findings from recent cohort studies from diverse populations are mixed. Our meta-analysis suggests an independent effect of obesity on dementia in general and incident AD in particular, but the associations are moderate and overweight is not found as a significant risk factor. While the effect of BMI on dementia is a U-shaped one, reducing the prevalence of obesity is a promising strategy in preventing progression from normal ageing into AD. Future cohort studies should attempt to disentangle the effect of BMI from other components of the MetS, address residual confounding by other covariates such as physical activity and depressive symptoms and attempt to fully understand the related biological mechanisms. http://www.blackwell-synergy.com

Prebiotics going strong despite price rise

Prebiotic fibre specialist BENEO-Orafti says demand for its chicory root-derived ingredients has been unaffected by price hikes it implemented at the end of last year. http://www.nutraingredients.com

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Alzheimer's generates burdens mainly in speech, ambulation, dexterity, and cognition

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In an aging society, an understanding of the physical and psychological burdens associated with aging is crucial for the efficient delivery of health and social services, particularly for those who are at risk for burdens prevalent among the elderly. Assessing the health-related quality of life (HRQL) in the population with age-related health conditions enables decision makers to recognize the true physical and psychological burdens this population faces. Therefore, it is important that the validity of outcome measures be evaluated in target chronic conditions before they are used in clinical, population health, and economic decision-making processes.

Health Utilities Index Mark 3 (HUI3) is a generic, multiattribute, utility-based measure that assesses health status and HRQL. The HUI3 consists of a multiattribute health status classification system and utility-based scoring functions. The multiattribute health status classification system consists of eight attributes: vision, hearing, speech, ambulation, dexterity, emotion, cognition, and pain, with five or six levels in each attribute. Single-attribute scoring function generates scores that range between 0.00 (most impaired) and 1.00 (no impairment) for each attribute. The multiattribute scoring function generates overall HUI3 scores ranging from −0.36 (most impaired, the all-worst HUI3 health state), to 0.00 (being dead) to 1.00 (perfect health) [1]. HUI3 has been used in population health surveys to assess health status and HRQL for a number of chronic conditions [2], [3], [4] and [5]. However, some of previous studies are based on samples, which may not be representative of the entire population. HRQL for patients/people with cataracts (CA) has been assessed previously [4], [5] and [6], although the construct validity of HUI3 in people with CA has not been established.

The paper assessed the cross-sectional construct validity of the HUI3 system by testing hypotheses about the ability of HUI3 to capture the burdens associated with disparate, but important conditions in older adults: Alzheimer Disease (AD), arthritis (AR), and CA. We explored two research questions: (1) are overall HUI3 utility scores of individuals with AD and/or CA and/or AR lower than scores for those without any of the three conditions, and (2) are HUI3 single-attribute utility scores able to detect burdens specific to different chronic conditions? We hypothesized that AD generates burdens mainly in speech, ambulation, dexterity, and cognition; AR mainly affects ambulation, dexterity, emotion, and pain; and CA mainly affect vision and emotion. http://www.sciencedirect.com

Fruit and veg linked to kids' school performance, study
Fruit and vegetable consumption and dietary fat intake were found to play an important role in children's academic performance, highlighting yet again the need for balanced diets at an early age. http://www.nutraingredients.com

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Beta-amyloid accumulation and oxidative stress

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Alzheimer's disease (AD) is associated with beta-amyloid accumulation, oxidative stress and mitochondrial dysfunction. However, the effects of genetic mutation of AD on oxidative status and mitochondrial manganese superoxide dismutase (MnSOD) production during neuronal development are unclear. To investigate the consequences of genetic mutation of AD on oxidative damages and production of MnSOD during neuronal development, we used primary neurons from new born wild-type (WT/WT) and amyloid precursor protein (APP) (NLh/NLh) and presenilin 1 (PS1) (P264L) knock-in mice (APP/PS1) which incorporated humanized mutations in the genome. Increasing levels of oxidative damages, including protein carbonyl, 4-hydroxynonenal (4-HNE) and 3-nitrotyrosine (3-NT), were accompanied by a reduction in mitochondrial membrane potential in both developing and mature APP/PS1 neurons compared with WT/WT neurons suggesting mitochondrial dysfunction under oxidative stress. Interestingly, developing APP/PS1 neurons were significantly more resistant to beta-amyloid 1-42 treatment, whereas mature APP/PS1 neurons were more vulnerable than WT/WT neurons of the same age. Consistent with the protective function of MnSOD, developing APP/PS1 neurons have increased MnSOD protein and activity, indicating an adaptive response to oxidative stress in developing neurons. In contrast, mature APP/PS1 neurons exhibited lower MnSOD levels compared with mature WT/WT neurons indicating that mature APP/PS1 neurons lost the adaptive response. Moreover, mature APP/PS1 neurons had more co-localization of MnSOD with nitrotyrosine indicating a greater inhibition of MnSOD by nitrotyrosine. Overexpression of MnSOD or addition of MnTE-2-PyP(5+) (SOD mimetic) protected against beta-amyloid-induced neuronal death and improved mitochondrial respiratory function. Together, the results demonstrate that compensatory induction of MnSOD in response to an early increase in oxidative stress protects developing neurons against beta-amyloid toxicity. However, continuing development of neurons under oxidative damage conditions may suppress the expression of MnSOD and enhance cell death in mature neurons. http://www.ncbi.nlm.nih.gov/pubmed/18353561?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

Fish oil could reduce inflammation, finds study
Daily intake of essential fatty acids could help reduce the need for painkillers in patients suffering from rheumatoid arthritis (RA), according to a new study. http://www.nutraingredients.com

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One in every eight will develop Alzheimer's

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A new report released today by the Alzheimer's Association suggests that 10 million American baby boomers, that is one in every eight, will develop Alzheimer's in their lifetime. The report also estimates that as many as 5.2 million people are living with Alzheimer's in the United States, including up to 250,000 under the age of 65.

The report is a "comprehensive statistical abstract of US data on Alzheimer's disease", giving facts and figures on disease prevalence, mortality, the costs of care and family caregiving. There is also special coverage on lifetime risk. In the US, a person develops Alzheimer's every 71 seconds (set to be every 33 seconds by 2050), said the report, which places the disease as the seventh leading cause of death for all Americans, and the fifth leading cause for those over the age of 65. The disease affects not only individuals but those around them; 70 per cent of people with Alzheimer's and other dementias live at home, and are looked after by family members and friends.

The total cost of Alzheimer's and other dementias, including direct (eg Medicare, Medicaid) and indirect (eg caregiver lost wages and out-of-pocket expenses, and decreased business productivity costs) is estimated to be more than 148 billion dollars a year. This excludes the estimated 10 million caregivers who provide about 89 million dollars a year in upaid services to people with Alzheimer's.

According to a report in the Washington Post, Stephen McConnell, the Alzheimer's Association's vice president for advocacy and public policy, said while most of the cargivers are spouses, "there's evidence that 250,000 of these caregivers are children 8 to 18". "So you get the sense of an expanded circle of people who are affected by this disease. It's not just the person with the disease. It's not just their immediate caregiver: it's the children and grandchildren," said McConnell.

The reports estimated that 14 per cent of all Americans over the age of 71 have Alzheimer's: it affects 16 per cent of women and 11 per cent of men. There were 411,000 new cases of Alzheimer's diagnosed in the US in the year 2000. This figure is estimated to grow to 454,000 new cases a year by 2010, and by 2050, it will have increased to 959,000 Americans diagnosed with Alzheimer's every year, said the report, which estimates the total prevalence will be in the region of 11 to 16 million persons by then.

The second most common form of dementia is vascular dementia, caused by vascular lesions in the brain, usually from strokes. Alzheimer's Disease is the most common form of dementia, responsible for 60 to 80 per cent of cases in the US. The disease has no cure, and the only treatment is drugs that slow it down for a short time. Alzheimer's begins with mild memory loss and confusion but gradually develops into complete memory loss and inability to take care of oneself.

The causes of Alzheimer's are not clear. It is characterized by increasing brain atrophy caused by a gradual build up of amyloid protein plaques and neurofibrillary tangles that destroy neurons and synapses. Although some doctors are concerned that there won't be enough trained medical professionals to deal with the growth in Alzheimer's patients when the baby boomers start to get it, there are those who think the projections in the report could be too high.

Director of geriatric psychiatry at Montefiore Medical Center in New York City, Dr Gary Kennedy, told the Washington Post he thought that because baby boomers were healthier, more active, better educated and better off than their parents, this may slow the disease down sufficiently that it won't affect them until the end of their natural life. Also, new medications are helping to manage the disease more effectively, said Kennedy http://www.medicalnewstoday.com

Datamonitor highlights confectionery novelties
Recent innovations in novel confectionery products include an energy-giving lollipop in a can, chocolate flavoured sea salt, and edible whole flowers, according to new data released by Datamonitor. http://www.nutraingredients.com

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of AD in the children of spouses with Alzheimer's

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Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by deposition of extracellular amyloid plaques, formation of intracellular neurofibrillary tangles and neuronal dysfunction in the brain. A growing body of evidence indicates a central role for biometals such as copper in many critical aspects of AD. The amyloid beta (Abeta) peptide and its parental molecule, the amyloid precursor protein (APP) both modulate Cu and Zn metabolism in the brain. Therefore, aberrant changes to APP or Abeta metabolism could potentially alter biometal homoestasis in AD, leading to increased free radical production and neuronal oxidative stress. Modulation of metal bioavailability in the brain has been proposed as a potential therapeutic strategy for treatment of AD patients. The lipid permeable metal complexing agent, clioquinol (CQ), has shown promising results in animal models of AD and in small clinical trials involving AD patients. Moreover, a new generation of metal-ligand based therapeutics is currently under development. Patents now cover the generation of novel metal ligand structures designed to modulate metal binding to Abeta and quench metal-mediated free radical generation. However, the mechanism by which CQ and other metal complexing agents slows cognitive decline in AD animal models and patients is unknown. Increasing evidence suggests that ligand-mediated redistribution of metals at a cellular level in the brain may be important. Further research will be necessary to fully understand the complex pathways associated with efficacious metal-based pharmaceuticals for treatment of AD. http://www.ncbi.nlm.nih.gov/pubmed

Two's a crowd for probiotic cytokine production
Finnish researchers have found single strains of probiotic bacteria have... http://www.nutraingredients.com/

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