10 warning signs of alzheimer's disease

1.Memory loss. Forgetting recently learned information is one of the most common early signs of dementia. A person begins to forget more often and is unable to recall the information later.

What's normal? Forgetting names or appointments occasionally.

2.Difficulty performing familiar tasks. People with dementia often find it hard to plan or complete everyday tasks. Individuals may lose track of the steps involved in preparing a meal, placing a telephone call or playing a game.

What's normal? Occasionally forgetting why you came into a room or what you planned to say.

3.Problems with language. People with Alzheimer's disease often forget simple words or substitute unusual words, making their speech or writing hard to understand. They may be unable to find the toothbrush, for example, and instead ask for "that thing for my mouth."

What's normal? Sometimes having trouble finding the right word.

4.Disorientation to time and place. People with Alzheimer's disease can become lost in their own neighborhood, forget where they are and how they got there and not know how to get back home.

What's normal? Forgetting the day of the week or where you were going.

5.Poor or decreased judgment. Those with Alzheimer's may dress inappropriately, wearing several layers on a warm day or little clothing in the cold. They may show poor judgment, like giving away large sums of money to telemarketers.

What's normal? Making a questionable decision from time to time.

6.Problems with abstract thinking. Someone with Alzheimer's disease may have unusual difficulty performing complex mental tasks, like forgetting what numbers are for and how they should be used.

What's normal? Finding it challenging to balance a checkbook.

7.Misplacing things. A person with Alzheimer's disease may put things in unusual places: an iron in the freezer or a wristwatch in the sugar bowl.

What's normal? Misplacing keys or a wallet temporarily.

8.Changes in mood or behavior. Someone with Alzheimer's disease may show rapid mood swings for no apparent reason.

What's normal? Occasionally feeling sad or moody.

9.Changes in personality. The personalities of people with dementia can change dramatically. They may become extremely confused, suspicious, fearful or dependent on a family member.

What's normal? People's personalities do change somewhat with age.

10.Loss of initiative. A person with Alzheimer's disease may become very passive, sitting in front of the TV for hours, sleeping more than usual or not wanting to do usual activities.

What's normal? Sometimes feeling weary of work or social obligations.

Source: Alzheimer's Association at www.alz.org

Published daily in Bend, Oregon, by Western Communications, Inc. Copyright 2007.

100 percent juices found as beneficial to health as fruits and vegetables

When it comes to some of today’s health issues, 100 percent fruit and vegetable juices do help reduce risk factors related to certain diseases.

This conclusion is the result of a European study designed to question traditional thinking that 100 percent juices play a less significant role in reducing risk for both cancer and cardiovascular disease than whole fruits and vegetables.

Juices are comparable in their ability to reduce risk compared to their whole fruit/vegetable counterparts say several researchers in the United Kingdom who conducted the literature review. The researchers analyzed a variety of studies that looked at risk reduction attributed to the effects of both fiber and antioxidants. As a result, they determined that the positive impact fruits and vegetables offer come not from just the fiber but also from antioxidants which are present in both juice and the whole fruit and vegetables.

This 2006 review of the literature states, “When considering cancer and coronary heart disease prevention, there is no evidence that pure fruit and vegetable juices are less beneficial than whole fruit and vegetables.” The researchers add that the positioning of juices as being nutritionally inferior to whole fruits and vegetables in relationship to chronic disease development is “unjustified” and that policies which suggest otherwise about fruit and vegetable juices should be re-examined.

The researchers who authored the paper “Can pure fruit and vegetable juices protect against cancer and cardiovascular disease, too? A review of the evidence” suggest that more studies in certain area are needed to bolster their findings. The study was published in the International Journal of Food Science and Nutrition (2006).

“Although this independent review of the literature is not designed to focus on any particular 100 percent juice, it does go a long way in demonstrating that fruit and vegetable juices do play an important role in reducing the risk of various diseases, especially cancer and cardiovascular heart disease,” says Sue Taylor, RD, with the Juice Products Association, a non-profit organization not associated with this research. She adds that appropriate amounts of juices should be included in the diet of both children and adults, following guidelines established by leading health authorities.

Taylor also points to a large epidemiological study, published in the September 2006 issue of the Journal of Medicine, which found that consumption of a variety of 100 percent fruit and vegetable juices was associated with a reduced risk for Alzheimer’s disease. In fact, that study found that individuals who drank three or more servings of fruit and vegetable juices per week had a 76 percent lower risk of developing Alzheimer’s disease than those who drank juice less than once per week.

Journal of Clinical Laboratory Analysis Publishes Positive New Data Bolstering Nymox's AlzheimAlert(TM) Urine Test for Alzheimer's Disease

--(BUSINESS WIRE)--Nymox Pharmaceutical Corporation is pleased to announce the publication of a new peer-reviewed report in the most recent issue of the Journal of Clinical Laboratory Analysis providing further positive data on the accuracy and utility of the Company's urinary AlzheimAlert(TM) test (J Clin Lab Anal. Jan 2007;21:24-33, "Competitive ELISA studies of neural thread protein in urine in Alzheimer's disease"). The paper reports excellent performance in laboratory studies and impressive reproducibility of clinical test results for patients and controls who were re-tested at intervals ranging from 2 days to 4.5 years.

Earlier this month, the successful results of a multi-center double blind independent clinical study of the Company's urinary AlzheimAlert(TM) test were published in the most recent issue of the Journal of the American Medical Directors Association (J Am Med Dir Assoc. Jan 2007; 8:21-30; "A multi-center blinded prospective study of urine neural thread protein measurements in patients with suspected Alzheimer's disease,".Goodman I et al.). The newly published independent peer-review study from 8 prestigious centers across the U.S. found the level of accuracy of the AlzheimAlert(TM) urine test to be over 90%. The study was double-blind and involved expert assessments and state of the art clinical correlations and continued evaluations.

AlzheimAlert(TM) is Nymox's proprietary urine based diagnostic aid for Alzheimer's disease. It is the only proven accurate non-invasive AD test technology available. The test has the CE Mark, allowing it to be marketed in Europe, and is also available to physicians in the U.S. through the Company's national CLIA-certified Clinical Reference Laboratory in New Jersey at a cost of $295. Nymox currently has numerous initiatives underway for the AlzheimAlert(TM) testing technology, including marketing and distribution overseas, and global product development.

There are an estimated 4.5 million people with Alzheimer's disease in the United States alone; by 2050 this number is projected to increase almost three times to 13.2 million. Worldwide estimates of the current number of people with Alzheimer's disease range from 15 to 20 million. The annual national direct and indirect costs of caring for Alzheimer patients in the U.S. alone are estimated at $100 billion. The human toll on patients, families and caregivers is incalculable.

More information about Nymox is available at www.nymox.com, email: info@nymox.com, or 800-936-9669.

This press release contains certain "forward-looking statements" as defined in the United States Private Securities Litigation Reform Act of 1995 that involve a number of risks and uncertainties. There can be no assurance that such statements will prove to be accurate and the actual results and future events could differ materially from management's current expectations. The conduct of clinical trials and the development of drug products involve substantial risks and uncertainties and actual results may differ materially from expectations. Promising early results do not ensure that later stage or larger scale clinical trials will be successful or will proceed as expected. Such factors are detailed from time to time in Nymox's filings with the United States Securities and Exchange Commission and other regulatory authorities.

Role of anesthetics in Alzheimer's disease: Molecular details revealed: Source: University of Pittsburgh Medical Center

Inhaled anesthetics commonly used in surgery are more likely to cause the aggregation of Alzheimer's disease-related plaques in the brain than intravenous anesthetics say University of Pittsburgh School of Medicine researchers in a journal article published in the Jan. 23 issue of Biochemistry. This is the first report using state-of-the-art nuclear magnetic resonance (NMR) spectroscopic technique to explain the detailed molecular mechanism behind the aggregation of amyloid â (Aâ) peptide due to various anesthetics.

Aâ plaques are found in the brains of people with Alzheimer's disease. Many believe that the uncontrolled clumping of Aâ is the cause of Alzheimer's disease and that the similar aggregation of peptides and proteins play a role in the development of other neurodegenerative diseases such as Parkinson's disease.

"Many people know of or have heard of an elderly person who went into surgery where they received anesthesia and when they woke up they had noticeable memory loss or cognitive dysfunction," said Pravat K. Mandal, Ph.D., assistant professor of psychiatry, University of Pittsburgh School of Medicine and lead author of the study. Previous studies by the Pittsburgh researchers found that the inhaled anesthetics halothane and isoflurane and the intravenous anesthetic propofol encouraged the growth and clumping of Aâ in a test tube experiment.

"Our prior research had shown in molecular models that anesthetics may play a role by causing amyloid peptides to clump together—something that is thought to signal the advancement of Alzheimer's disease. In this study, we set out to see why this was happening and to determine if any one form of anesthesia might be a safer option than another," said Dr. Mandal.

In this study the researchers used NMR spectroscopy to determine how the inhaled anesthetics halothane and isoflurane and the intravenous anesthetics propofol and thiopental interact with Aâ influencing the aggregation of Aâ in forms commonly found in the brains of people with Alzheimer's disease. The results were strikingly different between the inhaled and injected anesthetics. The inhaled halothane and isoflurane had the most potent interaction with Aâ peptides causing the highest levels of Aâ aggregation. The injected anesthetic propofol only interacted and caused aggregation at high concentrations—interaction was not evident at lower concentrations. The intravenous thiopental did not cause the clustering of Aâ peptides even at high concentrations. Additionally, the molecular details for the interaction of these anesthetics with Aâ peptide were revealed.

Dr. Mandal noted that if the same thing occurs in humans, anesthetics could lead to more amyloid plaques which may lead to earlier memory problems, warranting further studies of anesthetics with Aâ both in laboratory and clinical settings.

HIGHER FOLATE LEVELS LINKED TO REDUCED RISK FOR ALZHEIMER’S DISEASE

CHICAGO—Individuals who take in higher levels of the nutrient folate through both diet and supplements may have a reduced risk of developing Alzheimer’s disease, according to a report in the January issue of Archives of Neurology, one of the JAMA/Archives journals.

By the year 2047, the prevalence of Alzheimer’s disease is expected to quadruple, according to background information in the article. Delaying the onset of this neurodegenerative disease would significantly reduce the burden it causes. Researchers suspect that elevated levels of the amino acid homocysteine in the blood, which is linked to a higher risk for cardiovascular disease and stroke, may also increase the risk for Alzheimer’s disease. Folate, vitamin B12 and vitamin B6, are important in the body’s processing of homocysteine—therefore, deficiencies in these nutrients increase homocysteine levels and may contribute to cardiovascular disease, stroke and dementia.

José A. Luchsinger, M.D., Columbia University Medical Center, New York, and colleagues examined, interviewed and assessed the diets of 965 individuals without dementia between 1992 and 1994 and then followed them for an average of 6.1 years to see if they developed Alzheimer’s disease. The participants had an average age of 75.8 and 70.2 percent were women, 32.6 percent African-American, 45.3 percent Hispanic and 22.1 percent white.

During the follow-up period, 192 of the participants developed Alzheimer’s disease. When the individuals were divided into four groups based on the total level of folate they took in through food and supplements and the analysis was adjusted for patient characteristics, comorbid diseases and B12 and B6 intake, the risk of Alzheimer’s disease was lower in the groups with higher intake. Neither dietary folate nor supplements alone were significantly linked to Alzheimer’s disease risk; only the two in combination appeared to produce an effect. Levels of the vitamins B12 and B6 were not associated with Alzheimer’s disease risk.

Higher folate intake was modestly correlated with lower homocysteine levels, “indirectly suggesting that a lower homocysteine level is a potential mechanism for the association between higher folate intake and a lower Alzheimer’s disease risk,” the authors write.

Definitive conclusions about the role of folate in the development of Alzheimer’s disease cannot yet be made, they continue. The findings of this study are in contrast to those of some other research, and other compounds (such as hormones) perceived to reduce the risk for dementia in observational studies did not do so in randomized trials. “Thus, the decision to increase folate intake to prevent Alzheimer’s disease should await clinical trials,” they conclude.
(Arch Neurol. 2007;64:86-92. Available to the media pre-embargo at www.jamamedia.org).

Editor's Note: This study was supported by grants from the National Institutes of Health; a grant from the Charles S. Robertson Memorial Gift for research on Alzheimer’s disease; the Blanchette Hooker Rockefeller Foundation; and the New York City Council Speaker’s Fund for Public Health Research. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

For more information, contact JAMA/Archives media relations at 312/464-JAMA (5262) or e-mail mediarelations@jama-archives.org

CAREGIVING FOR THOSE AT END OF LIFE REWARDING DESPITE CHALLENGES, SURVEY FINDS

CHICAGO—Family or friends served as informal caregivers to almost three-quarters of disabled older adults living in the community during their final year of life, according to an article in the January 8 issue of Archives of Internal Medicine, one of the JAMA/Archives journals. More than two-thirds of these caregivers found their role rewarding despite providing more than 40 hours of care per week and making little use of caregiver-focused supportive services.

Family and friends serve as the main providers of care for patients with long-term disabilities and those at the end of life, according to background information in the article. Studies have found that these caregivers provide high levels of assistance and often experience associated emotional, physical and financial strains. It is recognized that these individuals also derive rewards from their caregiving role, but this concept has been little explored in research.

Jennifer L. Wolff, Ph.D., and colleagues at the Johns Hopkins Bloomberg School of Public Health, Baltimore, assessed the dynamics of providing care among 1,149 caregivers who participated in a national survey. The participants and the older adults for whom they provided care completed surveys in 1999. Investigators then monitored the pairs to determine if the older patient died within 12 months. Of the 1,149 caregivers who participated, 182 cared for a person who then died within one year, and 967 for a person who did not.

Among the 11.2 percent of disabled, community-dwelling older adults who died within one year of being interviewed, 72.3 percent were receiving help from an informal caregiver (compared with 48.6 percent of older adults who did not die within one year). Among the caregivers of adults in the last year of life, 41.5 percent were spouses, 39 percent were children and 19.5 percent were other family members or friends; 75.1 percent of them were female, and they had an average age of 64 years. They provided an average of 43 hours of care per week, and 84.4 percent of them provided daily assistance.

Less than 5 percent of caregivers used respite care (in which a temporary caregiver provides a break by caring for the ill individual) or caregiving support groups, while 62.3 percent reported using assistive devices, 37.2 percent used personal or nursing care services and 28.3 percent used home modifications—all interventions designed to help the disabled or ill older adult.

“While end-of-life caregivers reported significant emotional (28.9 percent), physical (18.4 percent) and financial (14 percent) strains, more than two-thirds endorsed personal rewards related to their helping role,” the authors write. About 70 percent agreed that their role “makes me feel good about myself” and “enables me to appreciate life more,” and 76 percent said they felt useful and needed. Many also identified benefits they received from the person for whom they were caring; 65 percent reported that the person kept them company, 26 percent said that they helped financially and 20.8 percent said that they helped with household chores.

“Seriously ill patients have expressed the importance of ongoing daily interactions with family and friends, and the ability to help others as components of a good death,” the authors conclude. “Data from this study indicate that primary caregivers were readily able to identify reciprocated emotional, instrumental and financial exchanges afforded to them by the person to whom they provided assistance.”
(Arch Intern Med. 2007;167:40-46. Available to the media pre-embargo at www.jamamedia.org)

Editor's Note: This study was supported in part by a grant from the National Institute of Aging and an unrestricted grant from Pfizer Inc. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

For more information, contact JAMA/Archives media relations at 312/464-JAMA (5262) or e-mail mediarelations@jama-archives.org

GENETICS AND LIFESTYLE INTERACT TO INCREASE RISK FOR AGE-RELATED BLINDNESS

CHICAGO—The interplay between genetic predisposition and exposure to modifiable risk factors can multiply the risk for age-related macular degeneration, according to a report in the January issue of Archives of Ophthalmology, one of the JAMA/Archives journals.

Age-related macular degeneration (AMD) can cause blindness and is known to have both genetic and environmental risk factors, according to background information in the article. Researchers have previously found that a mutation in the gene for complement factor H (CFH) is associated with AMD, as is a mutation in the gene LOC387715. Because these mutations are common in the white population, it is likely that other factors—such as obesity and smoking—may modify the risk for AMD. “Elucidation of these modifying factors may increase understanding of disease pathogenesis and suggest lifestyle changes that may prevent AMD or delay the disease onset in carriers of predisposing genetic variants,” the authors write.

Debra A. Schaumberg, Sc.D., O.D., M.P.H., of Brigham and Women’s Hospital and Harvard Medical School, Boston, and colleagues compared 457 men and women with AMD (cases) to 1,071 controls who were the same age and sex as the cases but did not have AMD. All of the individuals were part of either the Nurses’ Health Study, a large examination of female registered nurses who were between the ages of 30 and 55 years in 1976, or the Health Professionals Follow-up Study, which includes male U.S. health care professionals who were ages 40 to 75 in 1986. The participants were examined when they enrolled in the studies and completed a follow-up questionnaire every two years; average age at AMD diagnosis was 68.7 years.

Blood samples were also collected for a genetic analysis. Information about CFH was available for 437 AMD cases and 1,015 controls, while information about LOC387715 was available for 445 AMD cases and 1,041 controls. Compared with those who had two normal copies of each gene (alleles), those who had two mutated alleles of both genes were 50 times more likely to develop AMD.

Individuals who carried two mutant alleles of the CFH gene and were not obese were four times as likely as non-obese individuals with two normal alleles to develop AMD. If those individuals also smoked, their risk was 8.69 times as great as non-smoking non-carriers. If individuals were obese and carried two mutant alleles of the CFH gene, their risk increased 12 times as compared with non-obese non-carriers. For LOC387715, risk increased by 6.33 times for those with two mutated alleles who did not smoke and 22.47 times for those with two mutated alleles who did smoke. The genetic risk factors were not affected by other risk factors associated with AMD, including regular aspirin use, fruit intake, fatty acid ratios or alcohol consumption.

Because these genetic mutations are so common, some have questioned the utility of widespread screening for AMD risk, the authors write. “The existence of interactions with modifiable lifestyle factors may provide further impetus for screening individuals who are at potentially greater risk [for AMD], for example, cigarette smokers or the obese,” they continue. “Knowledge of the substantial risk of AMD among individuals homozygous for either or both of these major AMD-associated variants might help motivate these individuals to stop smoking, lose weight, modify other risk factors and have regular eye examinations.”

(Arch Ophthalmol. 2007;125:55-62. Available to the media pre-embargo at www.jamamedia.org).

Editor's Note: This study was supported in part by grants from the National Institutes of Health. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

For more information, contact JAMA/Archives media relations at 312/464-JAMA (5262) or e-mail mediarelations@jama-archives.org

BBC NEWS: Exercise now to cut dementia risk

Exercising for half an hour at least twice a week during midlife can significantly cut a person's risk of dementia later, say researchers.

People in their late 40s and early 50s who do this could reduce their risk of dementia by about 50%, according to a study reported in Lancet Neurology.

Those who are genetically prone to Alzheimer's disease could see a reduction of about 60%, it adds.

The Swedish team said the findings had large disease prevention implications.

Protective effect

"If an individual adopts an active lifestyle in youth and at midlife, this may increase their probability of enjoying both physically and cognitively vital years in later life," they said.

Past studies have also suggested regular exercise might guard against dementia, however, this is one of the first to look at the effects over a long time scale - about two decades.

The authors say this is important because dementia takes many years to develop and is typically quite advanced when it is diagnosed.

This study backs up the evidence so far.

The study involved nearly 1,500 men and women, of whom nearly 200 developed dementia or Alzheimer's disease between the ages of 65 and 79.

The researchers looked back at how physically active the study participants had been up to 21 years earlier, when they would have been in their late 40s and early 50s.

Those who developed Alzheimer's disease or another form of dementia were far less likely to have been active when they were middle-aged than those who remained free of dementia.

Good for the brain.

The amount of exercise that appeared to be necessary to be protective was physical activity which lasted 20-30 minutes at least twice a week and which was enough to cause breathlessness and sweating.

People are generally recommended to take moderate aerobic exercise for 20-30 minutes three to five times a week for a healthy heart and lungs.

Dr Miia Kivipelto and colleagues said there were many reasons why exercise might be good for the brain as well as the rest of the body.

For example, regular exercise could help keep the small blood vessels of the brain healthy as well as protecting against other conditions that might make dementia more likely, such as high blood pressure and diabetes.

Memory

Exercise might also reduce the amount of the protein amyloid that builds up in the brain in Alzheimer's disease.

Physical activity also affects genes and compounds important for maintaining good cognition and memory.

It might be that people who exercise tend to live healthier lifestyles in general, such as drinking less alcohol and refraining from smoking, they said.

However, when they took into account such health risk factors, the findings remained the same, suggesting that exercise per se is beneficial for the brain.

A spokeswoman from the Alzheimer's Research Trust said: "This study backs up the evidence so far.

"Studies seem to suggest that leading a healthy lifestyle - exercising regularly and eating a balanced diet - helps protect against dementia."

She said more research was needed, particularly as the condition was becoming increasingly common since the proportion of older people in society was increasing.

New Imaging Compounds for Detection of Neurodegenerative Diseases To be Developed by Bayer Schering Pharma

To develop novel imaging compounds for the detection of neurodegenerative diseases (Alzheimer's disease, Parkinson's disease and other disorders also associated with neuroinflammation such as multiple sclerosis), Bayer Schering Pharma AG (OTC: SHRGY) has signed a license and option agreement with Taisho Pharmaceutical Co., Ltd., Nihon Nohyaku Co., Ltd., and the National Institute of Radiological Sciences (NIRS), Japan.

Dr. Hans Maier, Head of Business Unit Diagnostic Imaging at Bayer Schering Pharma, stated:

"We are convinced that innovations in molecular imaging have the potential to fundamentally improve the diagnosis of neurodegenerative disorders, particularly Alzheimer's disease.

Bayer Schering Pharma is already pursuing the development of tracers targeting amyloid plaques, a hallmark of this disease. Imaging of neuroinflammation as another important pathology will excellently complement these activities.

This agreement underscores our commitment to Alzheimer patients by developing innovative diagnostic methods for the early detection of the disease."

The terms of the agreement entitles Bayer Schering Pharma to worldwide exclusive rights to develop and market the respective products (a compound class whose patent jointly owned by Taisho Pharmaceutical Co., Ltd., Nihon Nohyaku Co., Ltd. and the National Institute of Radiological Sciences) for use with PET scanning technology.

Find more details from the press release.

Body can 'heal dementia itself'



The scientists used the body's natural defence against disease
Scientists have harnessed the body's own natural defences against infection to make a treatment for dementia.

A German team, from Friedrich-Wilhelms University in Bonn, used proteins or antibodies produced by people against disease.

Five Alzheimer's disease patients treated with the experimental therapy showed improvement in tests.

More work is needed but the results are promising, said the authors in the Journal of Neurology, Neurosurgery and Psychiatry.

Natural defence

People with Alzheimer's disease have 'amyloid' deposits in the brain that are made up of a protein beta peptide.

These deposits get progressively worse and damage the brain tissue, leading to dementia.

Scientists have been looking at ways of blocking the action of beta peptide to prevent the build up of amyloid deposits using vaccines.

Now Dr Richard Dodel and colleagues believe they have found a way to do this, using the body's own natural defence system, in humans.

When the body encounters a disease or infection it produces complex protein molecules called antibodies to seek out and destroy the invasion.

Whilst this is very encouraging, the safety and effectiveness of this specific type of vaccine treatment needs to be carefully examined in a larger trial.

The researchers isolated antibodies against beta peptide and injected these into patients with early Alzheimer's disease on a monthly basis for six months.

To monitor the effect of this experimental treatment, the scientists measured the levels of beta peptide in the cerebrospinal fluid, which bathes the brain, at the beginning and end of the study.

They also tested the patients' brain function for things like memory, which is affected by dementia.

At the end of the six months, levels of beta peptide in cerebrospinal fluid fell by 30%, and the level of beta peptide in the blood shot up 233%, suggesting that the treatment was working.

Although brain, or cognitive function improved only slightly in four patients, it did not worsen, which would have been expected after six months.

Promising start

Also, mental tasks improved in three patients and stayed the same in the other two.

The scientists said although definitive conclusions could not be drawn on the strength of a study of five patients, their findings warranted further detailed investigation, and added weight to the experimental evidence.

In an accompanying editorial, Alzheimer's experts Professor Philip Scheltens and Dr Erik Hack from The Netherlands said: "Larger studies are needed to confirm that this treatment can stabilise or even improve cognitive functions in Alzheimer's disease."

But they said the study highlighted "a novel and interesting" treatment option for Alzheimer's disease which seemed "worthy to be explored".

Future research

Professor Clive Ballard from the Alzheimer's Society said: "Whilst this is very encouraging, the safety and effectiveness of this specific type of vaccine treatment needs to be carefully examined in a larger trial."

He said there had been a lot of excitement about treating Alzheimer's disease using the immune system.

He said an approach which used a vaccine to make the body produce antibodies against amyloid proved to be very effective in animal studies.

This led to a clinical trial involving about 200 people with Alzheimer's disease, he said.

"Unfortunately, although the vaccine appears to clear some of the protein from the brain, a substantial minority of participants in the trial developed a serious complication called encephalitis (inflammation of the brain), with two people dying.

"Therefore a lot of effort has been directed at trying to further develop this vaccine treatment approach to enable it to be used safely," he said.

In the current study, none of the five patients had major side effects.

Dr Dodel said his approach should not encounter these problems because the antibodies are given directly to the patient in a "passive" way rather than encouraging the body to make its own antibodies in an "active" way.

Alzheimer's Vaccine via a Skin Patch Shows Promise



A new study promises to make an Alzheimer's vaccine a reality sometime in future after it was found that skin patches were successful in clearing the brain plaques, which are the standout feature in Alzheimer's disease. The idea of this "transdermal" vaccine is published in this week's issue of the Proceedings of the National Academy of Science.

The vaccine works by stimulating the body's immune system to recognize and act against the plaque build up in the brain. It is commonly accepted that this plaque is the main cause of all cognitive problems associated with Alzheimer's patients.

In the current study, researchers from the University of South Florida tried to develop a needle-free vaccine for Alzheimer's patients.

"While many groups have shown vaccinating against the beta amyloid protein (Ab) can reduce Alzheimer's-like pathology including certain cognitive deficits, this study is the first to demonstrate that immunization using the skin may be an effective way to reduce Ab pathology," said lead researcher Jun Tan, the director of the Neuroimmunology Laboratory at the Institute for Research in Psychiatry.

Earlier trials at developing an Alzheimer's vaccine failed miserably when many patients developed fatal auto immune reactions causing inflammation of the brain. That clinical trial was suspended. The reason for this violent reaction was that the immune system seemed to turn against its own proteins.

However the USF researchers are targeting the skin as a route to deliver a safe vaccine. The researchers are planning additional tests to determine the safety and efficacy in handling senile plaques in mice.

"If those studies show clear cognitive benefits," Dr. Tan said, "we believe clinical trials to evaluate a beta amyloid skin patch or topical cream in patients with Alzheimer's would be warranted."

Learning slows physical progression of Alzheimer's disease - Study suggests keeping brain active may have significant therapeutic value: UNIVERSITY OF CALIFORNIA AT IRVINE


Study suggests keeping brain active may have significant therapeutic value

Irvine, Calif., January 23, 2007

Learning appears to slow the development of two brain lesions that are the hallmarks of Alzheimer’s disease, scientists at UC Irvine have discovered. The finding suggests that the elderly, by keeping their minds active, can help delay the onset of this degenerative disease.

This study with genetically modified mice is the first to show that short but repeated learning sessions can slow a process known for causing the protein beta amyloid to clump in the brain and form plaques, which disrupt communication between cells and lead to symptoms of Alzheimer’s disease. Learning also was found to slow the buildup of hyperphosphorylated-tau, a protein in the brain that can lead to the development of tangles, the other signature lesion of the disease. Scientists say these findings have large implications for the understanding and treatment of Alzheimer’s disease, as it is already known that highly educated individuals are less likely to develop the disease than people with less education.

“This study shows learning can delay the progression of Alzheimer’s neuropathology in mice genetically engineered to develop this insidious disorder, and learning also delays the cognitive decline,” said Frank LaFerla, professor of neurobiology and behavior and co-author of the study. “These remarkable findings suggest stimulating the mind with activities such as reading books or completing crossword puzzles may help delay and/or prevent Alzheimer’s disease in senior citizens.”

The study appears in the Jan. 24 issue of the Journal of Neuroscience.

LaFerla; James McGaugh, research professor of neurobiology and behavior; and postdoctoral researchers Kim Green and Lauren Billings studied hundreds of mice between two and 18 months of age that were bred to develop the plaques and tangles characteristic of the disease. Mice in one group were allowed to “learn” by swimming in a round tank of water until they found a submerged platform on which to stand. These mice received training four times a day for one week at two, six, nine, 12, 15 and 18 months of age, and were evaluated at each session for learning and memory abilities. Other groups of untrained mice were allowed to swim in the tank for just one session before their learning and memory skills were tested and their brains examined for plaques and tangles.

Mice up to 12 months of age that learned on previous occasions had fewer plaques and tangles in their brains, and they learned and remembered the location of the escape platform much better than mice not previously allowed to learn. At the 12-month point, the mice that had learned developed levels of beta amyloid and hyperphosphorylated-tau that were 60 percent less than the mice that had not learned; but, by 15 months of age, the mice that had learned deteriorated and were identical both physically and cognitively to the mice that had not learned.

“We were surprised this mild learning had such big effects at reducing Alzheimer’s disease pathology and cognitive decline, but the effects were not strong enough to overcome later and more severe pathology,” Green said. “We are now investigating if more frequent and vigorous learning will have bigger and longer benefits to Alzheimer’s disease.”

LaFerla and other colleagues developed the transgenic mice used in this study. These mice, bred to develop the brain lesions associated with Alzheimer’s, now are used by scientists worldwide to study the disease.

Alzheimer’s is a progressive neurodegenerative disorder that affects more than 4.5 million adults in the United States. With an aging population, that number could approach 20 million by 2050. Alzheimer’s is the third-leading cause of death, behind cancer and heart disease. Five percent of people older than 65 have Alzheimer’s, and up to one-half of people are affected by age 80.
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News - New Therapy to Treat Patients With Severely Elevated Cholesterol Levels
PHILADELPHIA, PA -- January 11, 2007 -- Researchers at the University of Pennsylvania School of Medicine have demonstrated the potential of a new type of therapy for patients who suffer from high cholesterol levels.

The findings are in the January 11 issue of the New England Journal of Medicine (NEJM). In this study, patients with homozygous familial hypercholesterolemia (FH), a high-risk condition refractory to conventional therapy, had a remarkable 51% reduction in low-density lipoprotein (LDL) or "bad cholesterol" levels.

"Our study shows that targeted inhibition of the microsomal triglyceride transfer protein (MTP) is highly effective in reducing cholesterol levels in these very high risk patients," stated Daniel J. Rader, MD, Director of Preventive Cardiology and the Clinical and Translational Research Center at Penn, and principal investigator of this study. "Furthermore, there are many other patients who have cholesterol levels that are difficult to treat or who are not tolerant to treatment with statins. New therapies are required for these patients as well, and it is possible that after further research MTP inhibition could eventually be used for such patients."

Genetic defects in MTP lead to profoundly low levels of LDL. Using this information, Bristol-Myers Squibb began to search for inhibitors of this protein and discovered the study drug, originally known as BMS-201038. Bristol-Myers Squibb then donated it to Penn for use in clinical trials in patients with severe cholesterol problems. Rader and his team at Penn designed and carried out the current study in homozygous FH patients with support from the Doris Duke Charitable Foundation. Due to the success in this study, Penn has licensed the drug to Aegerion Pharmaceuticals Inc for further development as AEGR-733.

Patients who suffer from homozygous FH typically respond poorly to standard drug therapy and have a very high risk of premature cardiovascular disease.

Homozygous FH is caused by loss-of-function mutations in both alleles of the LDL receptor gene. It is a rare form of hypercholesterolemia affecting approximately one in every million people. Patients with this disorder typically have plasma cholesterol levels of more than 500 mg per deciliter. If untreated, patients develop cardiovascular disease before they are 20-years-old and generally do not live past the age of 30. Because existing cholesterol lowering drugs are relatively ineffective in this patient population, new therapies to reduce LDL levels are needed.

In this study, researchers conducted a dose-escalation study to examine the safety, tolerability and effects on lipid levels of an inhibitor of MTP in six patients with homozygous FH. Patients received the MTP inhibitor at four different doses, each for four weeks, and returned for a final visit after an additional four-week drug washout period. Analysis of lipid levels, safety laboratory analyses, and magnetic resonance imaging of the liver for hepatic fat content were performed throughout the study.

All patients tolerated titration to the highest dose studied. In addition to the 51% reduction in LDL cholesterol, treatment at this dose also decreased total cholesterol levels by 58%, triglyceride levels by 65% and apolipoprotein B levels by 56% from baseline. In contrast to statin drugs, which have relatively little effect on cholesterol levels in homozygous FH patients, the MTP inhibitor was shown to reduce the liver's ability to produce LDL. The most notable adverse events in the study were loose stools and elevation of liver transaminase levels and accumulation of hepatic fat in some but not all of the patients studied.

Rader concluded, "Although our study establishes proof of concept, a longer-term study in more patients will be required to determine the benefits and risks of this approach as a potential new therapy for homozygous familial hypercholesterolemia." Marina Cuchel, MD, PhD, a co-investigator in this study at Penn, is now the principal investigator of a Phase III study for this compound in homozygous FH patients that is funded by the U.S. Food and Drug Administration Orphan Drug program and planned for later this year.

Rader points out that this study is a superb example of "translational research" in which discoveries in basic science are "translated" into use in humans for the development of novel therapies. Rader is an internationally recognized leader in translational research in the areas of cholesterol metabolism and heart disease prevention. Penn recently created a new Cardiovascular Institute that is charged with promoting translational research in the diagnosis, treatment, and prevention of cardiovascular disease. Additionally, Penn was recently awarded a large NIH grant to foster the further development of translational research under the auspices of the newly created Institute for Translational Medicine and Therapeutics.

The results of this study are in The New England Journal of Medicine (http://content.nejm.org). The article is titled "Inhibition of Microsomal Triglyceride Transfer Protein in Homozygous Familial Hypercholesterolemia."

Efficacy and safety of donepezil over 3 years: an open-label, multicentre study in patients with Alzheimer's disease
University of Manchster, Manchester, UK.

OBJECTIVE: This 132-week, open-label extension study assessed the long-term efficacy and safety of donepezil in 579 patients with mild to moderate Alzheimer's disease (AD) who had previously participated in a 24-week double-blind study of 5 or 10 mg/day donepezil vs placebo.

CONCLUSIONS: These results support the conclusion that donepezil is safe and effective for the long-term treatment of patients with mild to moderate AD.

PMID: 17199235 [PubMed - as supplied by publisher]

Lifestyle Affects Genetic Propensity for Age-Related Eye Disorder
The interplay of a genetic predisposition and modifiable risk factors, such as obesity and smoking, increases the risk for age-related macular degeneration, researchers here reported.

The high prevalence of these mutations in the white population, not all of whom will develop the eye disease, suggested that modifiable lifestyle risk factors may alter the underlying genetic risk, said Debra Schaumberg, Sc.D., D.O., of Brigham and Women's Hospital, and Harvard colleagues.

In a comparison of 457 men and women with age-related macular degeneration and 1,071 age- and sex-matched controls in a prospective nested case-control study, those homozygous for both risk alleles at both loci were 50 times more likely to develop age-related macular degeneration (50.48, 95% CI, 10.8-236.6),), although the 95% CI was wide, the researchers reported in the January issue of the Archives of Ophthalmology.

Cigarette smoking and obesity (BMI 30 or greater) multiplied the risk associated with these variants, they reported.MORE

Folate Weakly Linked to Reduced Alzheimer's Disease Risk - CME Teaching Brief - MedPage Today
Folate appears associated with a lower risk of Alzheimer's disease, although the relationship is tenuous, according to an observational study here.

The recommended intake of folate is 400 µg per day for adults, according to the NIH Office of Dietary Supplements.

Furthermore, the finding could have an explanation other than a direct effect of folate on Alzheimer's risk, the researchers reported in the January issue of Archives of Neurology.

The study also found no protective effect for B vitamins against Alzheimer's. But the authors also urged caution in interpreting this result.

"To our knowledge, ours is the first published study to associate homocysteine-related vitamins and Alzheimer's disease in a cohort that is predominantly African American and Caribbean Hispanic," the authors said.

Previous research has suggested that folate and vitamin B deficiencies may lead to elevated plasma homocysteine levels, which in turn may be a risk factor for cardiovascular disease, stroke, and Alzheimer's, they said.MORE