Beta-carotene may protect cognitive decline

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Cognitive performance declines naturally with age, but genetics does play a part in the complex progression of Alzheimers. Indeed, in 1993 scientists reported that people with a gene that codes for the blood lipoprotein, apolipoprotein E4 (apoE4) have a higher risk of developing Alzheimer's disease at an earlier age than people with apoE2 or apoE3.

The new study, by researchers at UCLA School of Medicine, the University of Southern California, and the National Institute on Aging, used data from a seven-year cohort study of older people to investigate if serum beta-carotene levels had an effect on cognitive decline in people with differing ApoE 4 genotypes (homo- or heterozygous). Out of the sample population of 455 people, the researchers report that nine people were ApoE4 homozygous, and 97 were ApoE4 heterozygous. Serum beta-carotene levels were measured at baseline, and cognitive function assessed using a 9-item Short Portable Mental Status Questionnaire (SPMSQ). During the seven years of follow-up, cognitive decline (as measured by falling SPMSQ scores) was documented in 249 people. Hu and co-workers reported that the presence of at least one ApoE 4 allele was linked to a higher risk and larger decline in SPMSQ scores.

The researchers report that high serum beta-carotene levels was associated with a 89 per cent reduction in the risk of cognitive decline in people with at least one APOE 4 allele. For those with no ApoE4 alleles, high serum beta-carotene levels were associated with only a modest 11 per cent reduction in the risk of cognitive decline.

Although the mechanism of Alzheimer's is not clear, more support is gathering for the build-up of plaque from beta-amyloid deposits. The deposits are associated with an increase in brain cell damage and death from oxidative stress. It is against the oxidative stress that beta-carotene may offer protection. In 1999 researchers from Washington University School of Medicine in St. Louis reported that apoE4 may be a risk factor for Alzheimer's because it is not as efficient as ApoE3 in preventing the build up of beta-amyloid deposits (Journal of Clinical Investigation, Vol. 103, pp. R15 to R20).

More research is needed to further investigate the potential link between beta-carotene and lower risk of Alzheimer's disease.

Warning Signs of Alzheimer's Disease

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A recent New York Times article reported that more than five million Americans have Alzheimer's disease. Citing the recent estimates released by the Alzheimer's Association, the times also reports that this is a 10 percent increase from the last official number, reported five years ago, and a number expected to more than triple by 2050.

The telephone survey took place between January 9 and February 6 and included responses from 655 adults. Sixty-seven percent of black caregivers and 63 percent of Hispanic caregivers said they did not know enough about Alzheimer's to recognize the symptoms, compared with 49 percent of other caregivers. The study also found that almost 70 percent of black and Hispanic families who have relatives with Alzheimer's disease dismiss their symptoms as part of aging.

"Alzheimer's disease is a devastating illness that is by no means a normal part of aging," Faison said. "My deep concern is that caregivers who consider the disease normal and don't know how to recognize its symptoms are not going to be able to make the best health-care decisions for their loved ones with the disease and themselves as caregivers." The study also found that patient concerns about the stigma associated with Alzheimer's delayed the diagnosis in many cases. "Those of us working with Alzheimer's disease patients are not surprised by the new disease estimates published by the Alzheimer's Association," said David Bachman, M.D., MUSC Professor of Neurosciences and co-director of the ARCP. "We must find some way as soon as possible to prevent this impending public health catastrophe."

The ARCP program, developed by MUSC Geriatric Psychiatry and the Department of Neurology, serves as a statewide resource for patients, families and physicians. The program provides access to comprehensive inpatient and outpatient diagnostic and treatment services, clinical drug trials and other types of research studies and educational opportunities. A wide range of clinical drug trials and other types of research studies are offered for older adults with Alzheimer's disease, other types of dementia, and Alzheimer's-related behavioral disturbances. Cognitive testing, medical monitoring and study medications are offered at no cost to qualified participants of clinical drug trials. Research staff members collaborate closely with the patient's primary care physician. Research is conducted at the Alzheimer's Research & Clinical Programs office, which is conveniently located off Interstate 26 in the North Charleston area. For more information about current and upcoming research and clinical trials, call 843-740-1592.

Warning Signs of Alzheimer's Disease
1. Memory Loss
2. Difficulty performing familiar tasks
3. Problems with language
4. Disorientation to time and place
5. Poor or decreased judgment
6. Problems with abstract thinking
7. Misplacing things
8. Changes in mood or behavior
9. Changes in personality
10. Loss of initiative

A growing body of studies is reporting protective effects of calcium-rich dairy foods for colorectal cancer, a condition that accounts for nine per cent of all new cancer cases and kills half a million people every year worldwide.

Immune Cell Action In Alzheimer's

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The immune system's response against amyloid-beta, the protein that forms plaques in the brains of patients with Alzheimer's disease, appears to protect the brain from damage in early stages of the devastating neurological disorder. A report from Massachusetts General Hospital (MGH) researchers finds that lack of a protein required for recruitment of the brain's primary immune cell led to increased amyloid-beta deposits and earlier death in a mouse model of Alzheimer's disease.

While it has been known that the immune system reacts against amyloid-beta in the brain, the relation of that response to the pathology of Alzheimer's disease has not been clear. Within the brain and central nervous system, the inflammatory process is controlled by immune cells called microglia, known to accumulate around amyloid-beta plaques. Some evidence has suggested that microglia break down and remove amyloid-beta, but the cells also release factors that could contribute to neurodegeneration. The current study was designed to clarify the role of microglia in Alzheimer's and identify factors involved in the immune cells' accumulation at amyloid plaques.

The research team focused on a molecule called CCR2, a receptor on the surface of microglia and other immune cells that is known to help direct them from the bloodstream to sites of inflammation within the brain. Since CCR2 is known to bind chemokines, proteins that attract immune cells and are elevated in brains affected by Alzheimer's, the receptor could be important for the movement of microglia to the site of amyloid-beta deposits. To test that possibility, the investigators used a mouse model of Alzheimer's disease and generated strains in which one or both copies of the CCR2 gene had been deleted. They found that mice lacking CCR2 had significantly more amyloid-beta in their brains than did the Alzheimer's-model mice that retained the molecule. These deposits were primarily found in small blood vessels – similar to a condition called cerebral amyloid angiopathy, which is associated with an increased risk of cerebral hemorrhage. In addition, CCR2-deficient mice had significantly shortened life spans. By 130 days of age, 85 percent of mice in which both copies of the CCR2 gene had been deleted had died, as had 60 percent of those with one copy. This compares with 30 percent of the Alzheimer's-model mice with two copies of CCR2 and only 1 percent of normal mice.

"By showing that microglia have a protective role in helping remove amyloid-beta from the brain, our findings suggest that enhancing the accumulation of these cells may be beneficial to patients with early-stage Alzheimer's disease," says Andrew Luster, MD, PhD, director of the MGH Center for Immunology and Inflammatory Diseases and senior author of the report.

Nutrition to halt Alzheimer's

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The research gives great hope to a dietary/nutritional approach to improve brain health and curb the rise in Alzheimer's and dementia around the world.
“This is exciting because antioxidants may prove to be a good therapeutic approach to [prevent] Alzheimer's disease and ameliorate human neurodegeneration,” said lead author Dora Dias-Santagata in a statement.

Although the mechanism of Alzheimer's is not clear, more support is gathering for the build-up of plaque from proteins deposits. The deposits are associated with an increase in brain cell damage and death from oxidative stress.

However, whether oxidative stress is a cause or a result of disease is not clear, said the researchers behind the new study.

“In this study, we provide substantial in vivo evidence supporting a causative role for oxidative stress in tau [protein]-induced neurodegeneration,” wrote Dias-Santagata in The Journal of Clinical Investigation.

Currently, about 12 million people in the US plus the EU suffer from Alzheimer's, with some estimates predicting this figure will have tripled by 2050. The direct and indirect cost of Alzheimer care is over $100 bn (€ 81 bn) in the US alone. The direct cost of Alzheimer care in the UK was estimated at £15 bn (€ 22 bn).

Such is the interest in dietary approaches to improve brain health the world's largest food company, Nestlé, recently signaled its intention to get a head start on the competition with the signing of an agreement in November 2006 with the Swiss Federal Institute of Technology (EPFL) to investigate the role of nutrition in cognitive function.

The agreement with the EPFL, Nestlé's largest collaboration with a university of research institute, will see the company contributing up to CHF 5 million (€ 3.1 million) every year for five years, with a review after four years to potentially extend the project further.

The fundamental research, by scientists from Brigham and Women's Hospital and Harvard Medical School in Boston and Howard University in Washington, used genetic and pharmacological approaches to change the genetic expression of transgenic fruit flies so that they would express a disease-related mutant form of human tau protein.

Two different approaches was used by the researchers - on one hand they manipulated genes responsible for the production of anti-oxidant proteins and on the other hand administered the potent anti-oxidant vitamin E to the mutant flies.

The US-based researchers report that reduction in the activity of two anti-oxidant proteins - superoxide dismutase (SOD) and thioredoxin reductases (Trxr) – as a result of their genetic manipulation led to increasing neurodegeneration in the brain of the mutant flies, while administration of vitamin E reversed the effect.

Control flies that did not express the human tau protein did not show any signs of neurodegeneration, they said.

Both results are said to indicate that oxidative stress plays an important role in neurodegenerative dementias, at least in those where the tau protein is involved, and could therefore offer a nutritional/ dietary approach to improving brain health.

“Our results suggest that increased levels of oxidative stress play an active role in enhancing tau-mediated neurodegeneration, possibly through cell cycle activation, underscoring the therapeutic potential of targeting antioxidant pathways and cell cycle mechanisms for the [prevention] of AD,” concluded the researchers.

It must be stressed that significant further research is necessary to study this effect and whether such a mechanism is also observed in humans.

Increasing numbers of studies are reporting that a diet rich in antioxidants from vegetables, and fruit like berries and pomegranate, are associated with a significantly decreased risk of cognitive decline and dementia.

Pinpoint Causes Of Alzheimer’s Diseases

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A study published in this week’s Federation of European Biochemical Societies (FEBS) Journal offers – for the first time – a model for the complex process of aggregation of a protein known as alpha-synuclein, which in turn leads to harmful ring-like or pore-like structures in human membranes, the kind of damage found in Parkinson’s and Alzheimer’s patients.

The researchers at SDSC and UC San Diego also found that the destructive properties of alpha-synuclein can be blocked by beta-synuclein – a finding that could lead to treatments for many debilitating diseases. The current journal’s cover features an image from the research that helps illustrate the scientists’ work.

“This is one of the first studies to use supercomputers to model how alpha-synuclein complexes damage the cells, and how that could be blocked,” said Eliezer Masliah, professor of neurosciences and pathology at UC San Diego. “We believe that these ring- or pore-like structures might be deleterious to the cells, and we have a unique opportunity to better understand how alpha-synuclein is involved in the pathogenesis of Parkinson’s disease, and how to reverse this process.”

Igor Tsigelny, project scientist in chemistry and biochemistry at UC San Diego and a researcher at SDSC, said that the team’s research helped confirm what researchers had suspected. “The present study – using molecular modeling and molecular dynamics simulations in combination with biochemical and ultrastructural analysis – shows that alpha-synuclein can lead to the formation of pore-like structures on membranes.” In contrast, he said, “beta-synuclein appears to block the propagation of alpha-synucleins into harmful structures.”

The complex calculations for the study were performed on Blue Gene supercomputers at SDSC and the Argonne National Labs.

Food, Mood and the Brain

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From East to West, groundbreaking science has reached the same conclusion. Top experts, researchers and household names such as Unilever, Nestlé, Yakult and Glico, have established that not only can certain foods improve mental health and general mood, but also how the links between nutrition, mood and brain work. Hardly two decades after the beginning of functional foods, we are about to witness the development of a new market and this is a key trend set to be one of 2007’s biggest.

It’s altogether a new category in the functional food and drink arena that is emerging. Products offering mental boost and mood enhancement benefits such as stress-free and improved mind and body functions, are gradually appearing on supermarket shelves around the world and are becoming increasingly popular with consumers. Although it is already a vibrant and active market in Japan. But, looking at past experience, the success of such products in the West ought to be considered in a different way. In the early 90s, when functional foods were first introduced from Japan, the Western markets suffered a number of product failures. These were mainly due to marketing difficulties like high price, ingredients and claims too complex for the consumer to understand as well as poor sensory quality. The industry has overcome most of these challenges and the timing is perfect to initiate the development and success of the Mood Food market.

Covering the markets and trends for energy, mental boost and mood enhancement products, the Food, Mood and the Brain conference held on 24th April 2007 at Leatherhead Food International, will offer a unique opportunity to explore this relatively young market, the rewards and the challenges of launching such products, understanding consumers needs and branding and communication issues.

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Alzheimer's Disease: A Guide for Patients and Families

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The American College of Physicians (ACP) has released "Alzheimer's Disease: A Guide for Patients and Families" and "Guide to a Restful Sleep." Available for free to ACP member physicians to distribute to patients and their families, each topic includes a DVD and guidebook.

Alzheimer's Disease: A Guide for Patients and Families

"It can be difficult for patients to find out they have Alzheimer's disease," said Patrick C. Alguire, MD, FACP, ACP's director of education and career development. "By learning more about Alzheimer's disease, patients and their families can understand what to expect and plan for the future."

Sponsored by Ortho-McNeil Neurologics, "Alzheimer's Disease: A Guide for Patients and Families" is designed to help patients and their families understand possible warning signs of Alzheimer's disease; who is at risk; how it is diagnosed; the stages of the disease; treatment and support options; and how to plan for future care, including living arrangements, money management, transportation, and legal arrangements.

The Alzheimer's disease guidebook includes a workbook section that provides questions to discuss with family members and caregivers. The DVD is narrated by television broadcaster and journalist Deborah Norville, whose grandmother had Alzheimer's disease.

Guide to a Restful Sleep

If someone has difficulty falling asleep, difficulty staying asleep (trouble returning to sleep after awakening), waking up too early, or poor quality of sleep (not feeling refreshed after sleep), it could be insomnia.

"It is normal to have trouble sleeping now and then," Alguire said. "Over time, however, getting too little sleep can lead to serious problems such as daytime fatigue, trouble concentrating, bad moods, poor work performance, and depression. Fortunately, there is a lot you can do to help improve your sleep."

Sponsored by Sanofi-aventis, "Guide to a Restful Sleep" is designed to help people improve their sleep by understanding insomnia and its causes, providing tips for sleeping better, and working with their doctor and exploring treatment choices.

The restful sleep guidebook includes a workbook section that provides suggested questions to ask a doctor and a chart to record sleep patterns. The DVD is narrated by actress Finola Hughes, who suffered from insomnia.

ACP members can order the Alzheimer's disease and restful sleep programs for free at http://www.acponline.org/catalog/campaign/pated_videos.htm. The guidebooks also can be downloaded from the ACP Web site http://www.doctorsforadults.com/.

Restriction For Alzheimer's Drugs May Be Attempt To Undermine Its Processes

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According to an editorial written by a senior health economist in this week's British Medical Journal (BMJ), a legal challenge against *NICE (National Institute for Health and Clinical Excellence) over its decision to limit the use of drugs for Alzheimer's disease could well be an attempt to undermine its processes.

NICE faces a judicial review over its refusal to make part of its modeling data for the dementia drug donepezil (Aricept) available to the pharmaceutical industry. NICE insists it is crucial to protect the intellectual property rights of external assessment groups, such as the Southampton University's Health Technology Centre. Alan Maynard, Professor of Health Economics at York University, says that NICE's protection of just this part of the assessment process may be unwise - even though this lack of transparency has never been challenged before.

Maynard says that this conflict may be an attempt by the pharmaceutical industry to improve its profits from a marginally cost effective drug, and could also be part of a more subtle drive to undermine processes of assessing health technology, which are designed to make sure taxpayers receive effective treatment which is good value for money. Similar attempts to undermine the process have also taken place in Australia, which has a similar system of assessing the cost-effectiveness of drugs and devices. NICE is essential for improving the efficiency of the NHS. He adds that NICE's processes are generally sensible and transparent. He also writes that the constraints under which it works can be improved.

Maynard writes "Surely it would have been better to have compensated Southampton for its loss of property rights in its model of treatment for Alzheimer's disease rather than become entangled in litigation. With the NHS seeking to control expenditure and target the use of drugs to improve the health of the population in a cost effective manner, and industry wanting to maximise its profits, conflict is inevitable. It is essential that the trade off between health and wealth is managed with transparent and good science by all participants - both public and private."

5 million people with Alzheimer's

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The report, titled "2007 Alzheimer's Disease Facts and Figures", is issued to coincide with the Alzheimer's Association's annual Public Policy Forum, which started yesterday in the nation's capital with a gathering of hundreds of advocates from across the US. It was released at a hearing chaired by Senator Barbara Mikulski, who with Senator Christopher Bond and Representatives Edward Markey and Christopher Smith have introduced bipartisan legislation to address issues highlighted in the report.

The estimate of 5 million people with Alzheimer's this year includes 4.9 million, or 1 in 8 people, over the age of 65 and half of those over the age of 85. And there is a surprising number between 200,000 and 500,000 of people under 65 with early onset Alzheimer's and other dementias.

The number of younger Alzheimer's suffereres is something the Association feels is "drastically underreported," said Dr Bill Thies, the medical director of the Association. An example is a person in their 50s showing behaviour changes at work that could be early signs of Alzheimer's such as forgetting deadlines or missing appointments. Increasing age is the greatest risk factor for Alzheimer's. And as 78 million baby boomers are now in their 60s, the estimated prevalence is set to go up to 7.7 million by 2030 . By mid-century the report estimates 16 million people will have Alzheimer's, which is more than the combined current population of New York City, Chicago, Houston and Los Angeles.

Alzheimer's is now the seventh leading cause of death in the US and the fifth leading cause of death for the over 65s. One of the reasons the disease is on the rise is because of success in reducing deaths due to the other big killers. "we're keeping people alive so they can live long enough to get Alzheimer's disease," is how the Alzheimer's Association vice president, Steve McConnell, put it. According to the Centers for Disease Control and Prevention (CDC), between 2000 and 2004, death rates have come down for heart disease by 8 per cent, stroke by 10.4 per cent, breast cancer by 2.6 per cent, and prostate cancer by 6.3 per cent. But deaths due to Alzheimer's, according to the CDC, have risen by 33 per cent in the same period.

Harry Johns, President and CEO of the Association explains that the report, "shows the tremendous impact this disease is having on the nation; and with the projected growth of the disease, the collective impact on individuals, families, Medicare, Medicaid, and businesses will be even greater". However, he says it is not all doom and gloom and there is hope. There are 9 promising drugs in phase 3 trials which aim to slow the disease's progress, which with better diagnostic tools hold "the potential to change the landscape of Alzheimer's". This could mean significantly reducing costs of care and increasing the quality of life for Alzheimer's sufferers and their families.

AV-1 binds avidly to β-amyloid

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Avid Radiopharmaceuticals, Inc. (Avid), a product-focused molecular imaging company, today announced the presentation of the first results from a clinical study of 18F-AV-1/ZK (AV-1) a novel radiopharmaceutical for positron emission tomography (PET) imaging of amyloid plaques in patients with Alzheimer's disease. Principal investigator Dr. Christopher Rowe from Austin Hospital of Melbourne, a leading investigator in the field of molecular imaging of Alzheimer's disease, presented the results at the 8th International Conference on AD/PD in Salzburg Austria. The goal of this first clinical study was to examine whether PET imaging with AV-1 could be used to distinguish patients with Alzheimer's disease from those with normal cognitive function. AV-1 binds avidly to β-amyloid, the chief constituent of amyloid plaques, which accumulates abnormally in the brains of people with Alzheimer's disease.

Dr. Rowe reported that PET imaging with AV-1 clearly distinguishes AD from healthy elderly subjects, and may be used to quantify amyloid burden. AV-1 PET scans showed high levels of signal in the Alzheimer's patients, particularly in areas of the brain known to contain amyloid plaques. In contrast there was no retention of AV-1 in the cerebellar cortex, an area where amyloid plaques do not accumulate.

This is the first scientific report of a clinical trial with an 18F-compound designed for specifically imaging amyloid plaques in AD. The wide availability of 18F allows for the possibility of amyloid imaging at a large number of clinical sites worldwide. "We are extremely encouraged by the results of this clinical study with Avid's first compound, AV-1. These data have provided the rationale for Avid's next generation compounds for amyloid imaging, which are now in clinical trials in the United States.", said Daniel Skovronsky, MD, PhD, CEO of Avid.

AV-1 is one of a series of novel compounds discovered in the laboratory of Dr. Hank Kung from the University of Pennsylvania and exclusively licensed to Avid for development and commercialization. The results presented represent a collaborative effort between scientists at Austin Health, the University of Melbourne, Neuroscience Victoria, Avid Radiopharmaceuticals, the University of Pennsylvania, and Bayer Schering Pharma. Amyloid imaging may help in identifying those patients who will benefit from these emerging treatments.
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Investigators confirmed PiB binds to amyloid plaques

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A team led by Massachusetts General Hospital (MGH) investigators has confirmed that the imaging agent Pittsburgh Compound B (PiB) binds to the protein in amyloid plaques that characterize Alzheimer's disease in the human brain. Their report in the March Archives of Neurology describes the first postmortem neuropathological study of a dementia patient who had previously participated in a PET imaging study using PiB.

"This report is an essential validation of the use of PET imaging with PiB to identify amyloid-beta deposits in the brain and as a marker of disease progression that could be used to track the benefit of new treatments," says John Growdon, MD, director of the MGH Memory Disorders Unit, the paper's senior author. "It also indicates that the interpretation of PiB PET scanning needs to be done in the context of a patient's clinical symptoms and other diagnostic studies."

Alzheimer's disease is characterized by plaques within the brain of amyloid-beta protein, which is toxic to brain cells. Previous studies have shown that PiB, invented by researchers at the University of Pittsburgh School of Medicine, binds to amyloid-beta in the brains of mice and can be detected by PET scan in the brains of human patients with a diagnosis of probable Alzheimer's disease. But since a definitive Alzheimer's diagnosis can be made only on autopsy, there had been no confirmation that PiB in human brains was detecting amyloid-beta deposits.

"The distribution of amyloid seen at autopsy matched the overall distribution seen in the PiB imaging study; levels were higher in the cerebral cortex than in other areas of the brain," says Matthew Frosch, MD, PhD, of the MassGeneral Institute for Neurodegenerative Diseases (MGH-MIND), a study co-author. "Features of Alzheimer's pathology, amyloid plaques and neurofibrillary tangles, were observed, but not at a level that would support a separate diagnosis of Alzheimer's disease."

The European ice-cream sector has been stagnant for many companies due to a maturation of the sector, health concerns and growing competition from cheaper private-label products, according to analysts. As a result companies are moving into the market for more premium products and unusual combinations of flavours. Danisco's goats milk ice cream formulation is made with fresh, organic goat's milk.

Alzheimer's Among African-American And Hispanic

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Alzheimer's disease is a progressive, degenerative disorder that attacks the brain's nerve cells, resulting in loss of memory, thinking and language skills, and behavioral changes. An estimated one in 10 persons over age 65 and nearly half of those 85 or older have Alzheimer's disease. Alzheimer's disease currently strikes approximately five million Americans; published reports project that by 2050 this number could more than triple to more than 16 million people in the United States.

Alzheimer's disease occurs significantly more frequently among African American (10.5%) and Hispanic (9.8%) individuals than among Caucasian (5.4%) individuals. Moreover, the proportion of African American and Hispanic individuals reaching ages 65+ in the U.S. is increasing more rapidly than the proportion of Caucasian individuals (2).

Symptoms of moderate Alzheimer's disease can include difficulty identifying familiar people, places, or things, restlessness, sleep disturbances, poor judgment or difficulty with reasoning, aggression or agitation, inappropriate behavior, increased difficulty with everyday activities, losing touch with reality, suspiciousness or paranoia, and hallucinations.
African-American and Hispanic caregivers (1) of people with Alzheimer's disease are significantly more likely than caregivers of other races to consider the disease a normal part of the aging process and dismiss its symptoms as part of getting older, according to the Alzheimer's Foundation of America's (AFA) second ICAN: Investigating Caregivers' Attitudes and Needs survey. This gap in understanding sheds light on the reasons for delay in diagnosis and treatment, which is an unnecessary setback for caregivers and individuals with the disease alike.

"Facing Alzheimer's disease is never easy, but getting a diagnosis and taking advantage of support services are crucial steps to treating and managing the disease," said Eric J. Hall, Chief Executive Officer of the Alzheimer's Foundation of America. "We encourage everyone touched by Alzheimer's disease to reach out for assistance - help is out there."

The survey was conducted by Harris Interactive® on behalf of AFA, a national nonprofit organization providing care and services to individuals with Alzheimer's disease and related dementias, and their families.

According to the survey released today, African-American and Hispanic caregivers surveyed were significantly more likely (37% versus 33%) than caregivers of other races (23%) to believe that Alzheimer's disease is a normal part of the aging process. In fact, Alzheimer's disease is a progressive, neurodegenerative illness. Compounding the problem, African-American (70%) and Hispanic (67%) caregivers were also significantly more likely to dismiss the symptoms of Alzheimer's disease as old age than other respondents of other races (53%). Additionally, African-American (67%) and Hispanic (63%) caregivers were significantly more likely to report that they did not know enough about the disease to recognize the symptoms compared to caregivers of other races (49%).

The survey also found that African-American (33%) and Hispanic (26%) caregivers were also more likely than caregivers of other races (12%) to recognize that they are at a higher risk for Alzheimer's disease.

"Alzheimer's disease is a devastating illness that is by no means a normal part of aging," explained Warachal E. Faison, M.D., Assistant Director of the Institute for Research Minority Training on Mental Health and Aging, and Clinical Director of the Alzheimer's Research and Clinical Programs at the Medical University of South Carolina. "My deep concern is that caregivers who consider the disease normal and don't know how to recognize its symptoms are not going to be able to make the best healthcare decisions for their loved ones with the disease and themselves as caregivers. The fact is, it's crucial for caregivers to be able to identify symptoms and bring their loved one to a doctor without delay for proper diagnosis and treatment."

Homocysteine is a risk factor for Alzheimer's

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Elevated plasma levels of homocysteine are a risk factor for Alzheimer's disease. Because high homocysteine levels can inhibit methyltransferases, Sontag et al. pursued a trail of posttranslational protein modifications that might link homocysteine to tau and amyloid precursor protein (APP). Here's their rationale. The likelihood of amyloidogenic APP increases with its phosphorylation, a state reversed by protein phosphatase 2A (PP2A), which itself is affected by methylation. Previous studies have also reported downregulation of neuronal PP2A methyltransferase (PPMT) and reduced PP2A methylation in brain tissue from Alzheimer's patients. In neuroblastoma cells, the authors found that S-adenosylhomocysteine reduced PP2A methylation probably by inhibiting PPMT. In these same cells, phosphorylation of tau and APP was enhanced. In mice prone to high homocysteine levels, a high-methionine, low-folate diet also led to increased brain S-adenosylhomocysteine, downregulation of PPMT, reduced PP2A methylation, and enhanced phosphorylation of tau and APP.
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B-vitamin boost in fight against mental decline
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Imaging Amyloid-Beta In Human Brain

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A team led by Massachusetts General Hospital (MGH) investigators has confirmed that the imaging agent Pittsburgh Compound B (PiB) binds to the protein in amyloid plaques that characterize Alzheimer's disease in the human brain. "This report is an essential validation of the use of PET imaging with PiB to identify amyloid-beta deposits in the brain and as a marker of disease progression that could be used to track the benefit of new treatments," says John Growdon, MD, director of the MGH Memory Disorders Unit, the paper's senior author.

Alzheimer's disease is characterized by plaques within the brain of amyloid-beta protein, which is toxic to brain cells. Previous studies have shown that PiB, invented by researchers at the University of Pittsburgh School of Medicine, binds to amyloid-beta in the brains of mice and can be detected by PET scan in the brains of human patients with a diagnosis of probable Alzheimer's disease. But since a definitive Alzheimer's diagnosis can be made only on autopsy, there had been no confirmation that PiB in human brains was detecting amyloid-beta deposits.

The Archives of Neurology report describes the case of an elderly man with symptoms that could indicate several neurological disorders. He was evaluated numerous times over a period of three years, including a standard PET scan that produced results suggesting Alzheimer's disease. His eventual diagnosis was dementia with Lewy bodies, a condition that can exist along with Alzheimer's. He also enrolled in a research study involving PiB imaging, and the results of his scan showed the imaging compound had been taken up throughout the cerebral cortex, the outer layer of the brain. Three months after participating in the imaging study, the patient died at the age of 76 following a head injury, and an autopsy was performed.

The researchers note that, while their results confirm that uptake of PiB indicates the presence of amyloid in the brain, a positive PiB PET scan cannot be equated with a definitive Alzheimer's diagnosis. "About 15 percent of control participants in previous PiB studies, people with no cognitive impairment, had some level of PiB uptake," says Brian Bacskai, PhD, of MGH-MIND, the paper's lead author. "Some participants who probably had Alzheimer's had low uptake, and uptake levels varied for those with a diagnosis of mild cognitive impairment. Once a safe and effective drug for removing amyloid from the brain or preventing its accumulation is developed, it will be important to see how closely PiB PET scans can track those effects."

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Phase 2a Trial Of MEM 3454 In Alzheimer's Disease

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Memory Pharmaceuticals Corp. announced the dosing of the first subject in a randomized, double-blind, placebo-controlled Phase 2a clinical trial of MEM 3454, the company's lead nicotinic alpha-7 receptor partial agonist, in Alzheimer's disease. The trial is designed to assess the safety, tolerability and cognitive effects of three doses of MEM 3454 in subjects with mild to moderate Alzheimer's disease. MEM 3454 is a partial agonist of the nicotinic alpha-7 receptor, a highly specialized receptor found in the CNS. Compounds acting on this receptor could be beneficial in the treatment of Alzheimer's disease and schizophrenia, as well as other psychiatric and neurological disorders. MEM 3454 is the Company's lead drug candidate from its nicotinic alpha-7 agonist program. Memory Pharmaceuticals is developing MEM 3454 as potential therapy for Alzheimer's disease and is considering developing the compound as a treatment for schizophrenia as well as other disorders that affect cognition.

"MEM 3454 showed promising cognitive effects in its Phase 1 clinical trial and we're excited about evaluating its efficacy in a disease setting," said Stephen R. Murray, M.D., Ph.D., Vice President of Clinical Development. "We now have two drug candidates, with two distinct mechanisms of action, in clinical trials for the treatment of Alzheimer's disease, and we expect to report top-line results from both trials in the fourth quarter of this year."

The trial will enroll approximately 80 subjects with mild to moderate Alzheimer's disease at multiple sites in the United States. Subjects will be randomized to receive 5 mg, 15 mg or 50 mg of MEM 3454 or placebo once daily for a period of eight weeks. The primary objective of the trial is to assess the effect of MEM 3454 using the Quality of Episodic Secondary Memory (QESM) factor score from the Cognitive Drug Research (CDR) battery. Secondary objectives include assessing the safety, tolerability, and pharmacokinetics of multiple doses of MEM 3454 and the drug candidate's effect on additional psychometric test items from the CDR battery and the Alzheimer's Disease Assessment Scale -- Cognitive subscale (ADAS - cog). Under the terms of the Company's nicotinic alpha-7 agonist collaboration with Roche, the Company leads the development of MEM 3454 through Phase 2a clinical trials, and following the completion of these trials, Roche has the right to obtain an exclusive license to MEM 3454. Roche maintains this right through the development process by making payments to Memory Pharmaceuticals upon its achievement of certain predefined development milestones. For additional information, please visit our website at http://www.memorypharma.com.

The effects of a fatty acid on patients with Alzheimer's

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The Indiana University Center for Alzheimer's disease and Related Disorders seeks volunteers for a clinical study on the effects of a fatty acid on patients with Alzheimer's.

The fatty acid, docosahexaenoic acid or DHA, which is found in small amounts in the diet, is essential for normal brain and eye development. Center researchers want to evaluate whether chronic use of DHA changes the progression of Alzheimer's. This research will help physicians learn more about the usefulness of DHA for future prevention and treatment of the disease.

Volunteers, who must have been diagnosed with Alzheimer's disease, will participate in the study for 18 months and will be seen approximately six times during the course of the study at the IU Medical Center. Study medication, procedures, exams and compensation for time and travel are provided.

Genetic Risk Factors For Alzheimer's

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Cardiff University researchers have found evidence for new genes involved in the development of Alzheimer's disease.

The study, to be published in the next issue of the journal Human Molecular Genetics, tested more than 17,000 gene variants in 4,000 volunteers.

Several genes were found to show evidence of contributing to Alzheimer' disease, the most interesting gene being 'GALP' which could affect the development of tangles within brain cells, a hallmark of Alzheimer's disease.

Professor Julie Williams, School of Medicine, who leads this project with Professor Micheal Owen said: "Whilst these genes are likely to make modest contributions to disease more work needs to be done to test their strength in other samples of volunteers."

Professor Owen, School of Medicine said: "Identifying susceptibility genes for Alzheimer's disease provides a knowledge base for the development of potential new treatments and diagnostic tests. This study is just the first in series we are undertaking using new technology to look comprehensively at every gene in the human genome in Alzheimer's Disease and we hope that there are other exciting findings to come."

There is no known cure or preventative treatment for Alzheimer's disease, which affects one in 20 people over the age of 65 and one in five over the age of 80 in the UK and more than 12 million people worldwide. The disease causes a distressing, irreversible and progressive loss of brain function and memory.

The School of Medicine's Department of Psychological Medicine has established a bank of more than 3,000 volunteers in South Wales, and elsewhere in the UK, to identify possible genetic risk factors for Alzheimer's Disease.

"This is one of the largest studies of its kind and involves many Welsh families " said Professor Julie Williams. "It is by virtue of the support given to us by Alzheimer's sufferers and their carers that we are able to understand factors involved in the disease process. Many genes will be linked with Alzheimer's disease and our current programme of research is designed to identify them."

Step Towards Better Diagnosis Of Alzheimer's

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Dementia diseases develop insidiously and are generally discovered when the memory has already started to deteriorate. New research from Karolinska Institutet shows, however, that approaching Alzheimer's can be detected several years before the symptoms manifest themselves.

Dementia involves a serious deterioration of mental function caused by some kind of dementia disease of the brain, of which Alzheimer's is the most common. Although there is currently no cure for Alzheimer's, it is possible to inhibit its development if the treatment is given early enough. However, with today's diagnostics, it is very difficult to identify people with early Alzheimer's.

A new doctoral thesis by Johanna Lind, Karolinska Institutet in Sweden, now shows that genetic mapping and brain imagery can be used to identify people who will develop dementia even before any clinical symptoms appear.

"This is a crucial step towards the better diagnosis of Alzheimer's," she says. "If the method is developed it can help us find the people who'd benefit most from treatment in good time."

The method is based on the well-established fact that the APOE protein affects the risk of developing Alzheimer's. APOE is a lipid-transporting protein important in, amongst other things, the repair of cerebral neurons. Roughly one person in five carries a genetically determined variant of APOE that is associated with an increased risk of Alzheimer's.

In her study, Johanna Lind was able to show that some of the people in this risk group had reduced parietal lobe activity, detectable using an MR camera, and that these same people were the ones who went on to suffer memory deterioration two to three years later.

"It's surprisingly difficult to diagnose Alzheimer's with any certainty, but things are made easier if you know who runs the greatest risk," she says. "If genetic mapping, MRI and cognitive tests all suggest approaching Alzheimer's, it might be an idea to start a course of treatment."

Clinical Trial of Dimebon

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Dimebon is a weak inhibitor of cholinesterases, and has selectivity for butyryl cholinesterase over acetylcholinesterase, which may be of some concern for GI side effects.
The first clinical trial of Dimebon (by Medivation, conducted in Russia) demonstrated efficacy in five independent measures of cognitive improvement. The study randomized 183 patients to two groups: Dimebon, 20 mg. orally tid or placebo. Patients had mild to moderate Alzheimer disease (MMSE 10-24) and were not taking other medications to treat AD. Compared with patients receiving placebo, patients treated with Dimebon demonstrated highly statistically significant improvement on the study's primary efficacy endpoint, the ADAS-cog; 4.0 point improvement in the mean change from baseline to week 26 as compared to placebo; and on the key secondary efficacy endpoint, the Clinical Interview-Based Impression of Change, as well as statistically significant improvements on all three of the other secondary efficacy endpoints: the Activities of Daily Living, the Neuropsychiatric Inventory, and the Mini-Mental State Examination. In addition to these improvements in comparison to placebo, Dimebon-treated patients also showed statistically significant improvement over baseline on all five efficacy endpoints used in this study. By contrast, placebo-treated patients deteriorated from baseline on all five endpoints (Medivation disclosure).
In a recent 6-month trial (in Russia, concluded in July 2006) Dimebon was well-tolerated. There were fewer serious adverse events in the Dimebon-treated patients than in the placebo-treated patients. The most common adverse event was dry mouth. All other gastrointestinal side effects were uncommon, occurring in less than 3 percent of patients (Medivation disclosure). Toxicological studies performed in the former Soviet Union in rats, guinea pigs, or dogs showed that administration of Dimebon at doses up to 100 times therapeutic dose did not produce physiological or pathological changes in major organs, including embryogenesis in rats.

Anesthetics Accelerate Appearance Of Brain Plaque

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Every year over 100 million people undergo surgery worldwide, most under general anesthesia with an inhaled drug. These drugs clearly affect cognitive ability at least in the short term, but the growing concern is that inhaled anesthetics may affect a person well beyond the perioperative period, even permanently. Several factors appear to play a role in this subtle loss of cognitive ability, most notably age.
A specific effect of these drugs on dementias like Alzheimer's disease, though suspected for many years, has only been recently supported by data. In 2003, Eckenhoff's group showed that the inhaled anesthetics enhance the aggregation and cytotoxicity of the amyloid beta peptide. Just last month, a study reported that these drugs also enhance the production of amyloid beta in isolated cells. But these protein and cell culture studies are a long way from showing that an effect occurs in vivo. This new study provides the first evidence that the predicted effect occurs in animals.
"This animal study data suggests that we have to at least consider the possibility that anesthetics accelerate certain neurodegenerative disorders," said Eckenhoff. "In the field of Alzheimer's research, most effort is focused on delaying, not curing the disease. A delay in the onset of Alzheimer's disease of only three to five years would be considered a success. Therefore, if commonly used drugs, like anesthetics, are accelerating this disorder, even by a few years, then a similar success might follow even small changes in the care of the operative patient."
Mice don't naturally get Alzheimer's, so the animals in this study were genetically engineered to express the human protein responsible, called amyloid beta. "These mice develop a syndrome with many features of the human disease," explains Eckenhoff. Post-doctoral fellow and first author Shannon Bianchi, MD, exposed "middle-aged" Alzheimer mice to anesthetics at low to moderate concentrations for two hours a day over a total of five days, not unusual for a clinical scenario. The cognitive abilities of the mice were then analyzed using standard behavioral tests, and their brains were examined for plaque and cell death.
"Compared to controls, the anesthesia did not appear to worsen cognitive ability, which was already considerably compromised at this age, but it did accelerate amyloid beta aggregation and plaque appearance," said corresponding author Maryellen Eckenhoff, PhD. "We need to test whether anesthetic at earlier, presymptomatic stages, might accelerate both cognitive loss and plaque." This is the main cause of concern because a large fraction of clinical patients receiving inhaled anesthetics during surgery are older, but presymptomatic individuals. http://www.med.upenn.edu/

Omega-3s Improve Mood

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Omega-3 fatty acids, found in fatty fish like salmon, are associated with increased grey matter volume in areas of the brain commonly linked to mood and behavior according to a University of Pittsburgh study.

Animal research has shown that raising omega-3 intake leads to structural brain changes. In a separate study presented by Dr. Conklin at the society’s meeting last year, Pitt researchers reported that people who had lower blood levels of omega-3 fatty acids were more likely to have a negative outlook and be more impulsive. Conversely, those with higher blood levels of omega-3s were found to be more agreeable and less likely to report mild or moderate symptoms of depression. In the study being presented today, the researchers sought to investigate if grey matter volume was proportionally related to long-chain omega-3 intake in humans, especially in areas of the brain related to mood, helping them attempt to explain the mechanisms behind the improvement in mood often associated with long-chain omega-3 intake.
Researchers interviewed 55 healthy adult participants to determine their average intake of long-chain omega-3 fatty acids. Grey matter volume was evaluated using high-resolution structural MRI. The researchers discovered that participants who had high levels of long-chain omega-3 fatty acid intake had higher volumes of grey matter in areas of the brain associated with emotional arousal and regulation – the bilateral anterior cingulate cortex, the right amygdala and the right hippocampus.
While this finding suggests that omega-3s may promote structural improvement in areas of the brain related to mood and emotion regulation – the same areas where grey matter is reduced in people who have mood disorders such as major depressive disorder – investigators note that more research is needed to determine whether fish consumption actually causes changes in the brain.

Potential of blocking apoE/A in Alzheimer's disease

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The accumulation of amyloid-beta (A) peptides is an important stage in the early pathogenesis of Alzheimer's disease (AD), and the binding of A peptides to apolipoprotein E (apoE) has a key role in the sequestration of A in the CNS and in the formation of A deposits. Hence, blocking the apoE/A interaction might constitute a novel therapeutic approach for AD. Now, researchers in New York, NY, have demonstrated the potential of this approach in vivo.
A number of studies have demonstrated that short synthetic peptides corresponding to the apoE binding site on the A peptide can bind to human apoE and block its effect on A accumulation. Sadowski et al. developed a blood–brain-barrier-permeable, nontoxic, nonfibrillogenic synthetic peptide, A12–28P, which binds apoE with high affinity. Systemic administration of A12–28P to two transgenic mouse models of AD resulted in marked reductions in A plaque and cerebral amyloid angiopathy burdens, along with a reduction in the absolute A level in the brain. Behavioral testing with the radial arm maze demonstrated that A12–28P treatment prevented memory deficit; at age 17–18 months, transgenic AD mice given A12–28P performed comparably to wild-type mice, whereas placebo-administered transgenic AD mice showed significantly worse performance than wild-type or A12–28P-treated AD mice (P <0.001 style="font-weight: bold; font-style: italic;" size="1">Sadowski MJ et al. (2006) Blocking the apolipoprotein E/amyloid- interaction as a potential therapeutic approach for Alzheimer's disease. Proc Natl Acad Sci USA 103: 18787–18792

MRI measurements identify Alzheimer's disease

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To date, studies attempting to discriminate patients with Alzheimer's disease (AD) from healthy controls on the basis of brain MRI scans have reported a wide range of accuracy rates. Lerch et al. have suggested that in some cases poor experimental design, small sample sizes and failure to use independent validation cohorts have confounded these results. In response, they have evaluated the capacity of fully automated MRI measurements of cortical thickness to discriminate patients diagnosed with probable AD (n = 19) from healthy elderly controls (n = 17).
The discriminatory ability of the cortical thickness measurements varied depending on the region of the brain under scrutiny. Areas of the brain classically associated with AD had the best predictive capacity (>90% accuracy for the medial temporal lobes and other limbic structures), whereas the primary motor cortex had the poorest accuracy. Multivariate discriminant analysis of 25 cortical structures revealed 100% accuracy with 6 different 2-structure combinations, all of which included the parahippocampal gyrus. All validation was performed internally, using a jack-knife or leave-one-out approach to prevent overtraining of the discriminant models.
The authors conclude that automated MRI measurements of cortical thickness could be used to improve the clinical diagnosis of probable AD. They suggest that further evaluation of advanced computational techniques applied to MRI in patients with mild cognitive impairment or very early AD would enable imaging to be used as a diagnostic tool across the clinical spectrum of dementia.
Lerch JP et al. (2006) Automated cortical thickness measurements from MRI can accurately separate Alzheimer's patients from normal elderly controls. Neurobiol Aging [doi: 10.1016/j.neurobiolaging.2006.09.013]