Let's Toast to an Alzheimer's-Free New Year

With 2006 fast approaching, it's a good time to step back and look back at some of the progress made in the past year. The good news is, scientists continue to show that a few simple lifestyle changes can go a long way in keeping the mind sharp and alert as we age. While there are many factors that we can't control, such as the genes we inherit, here are six simple steps that may help to prevent Alzheimer's years down the road.

1. Eat some fish.

Eating fish at least once a week, particularly oily fish such as salmon rich in “good” fats called “omega-3s,” may benefit both the heart and brain. Researchers at Rush University Medical Center in Chicago found that men and women aged 65 and up who ate fish one or more times a week had, on average, a 10 percent slower rate of cognitive decline as they aged compared to those who rarely ate fish. Over time, the benefits added up to the equivalent of being three to four years younger mentally, the researchers estimate.

2. Maintain a healthy weight.

Middle-aged and seriously overweight? You may be setting the stage for Alzheimer's disease later in life, a large new study found. Researchers from Sweden report that compared to individuals who maintain a healthy weight during their middle years, men and women who are obese at midlife have an increased risk for Alzheimer's disease as they age.

3. Get some exercise.

Regular exercise during your middle years may lower your risk of developing Alzheimer's disease in old age, say researchers from Sweden. Men and women aged 65 to 79 who, in their middle years, exercised during their free time at least twice a week were 60 percent less likely to develop Alzheimer's disease compared to sedentary men and women who exercised less than twice a week. The active individuals were also 50 percent less likely to develop other forms of dementia and memory loss.

4. Get your folic acid.

Folic acid, a B vitamin critical for brain and nerve health sold in supplements and found in green vegetables, beans, whole grains, fortified cereals, and orange juice, was in the news in 2005. University of California at Irvine researchers report that men and women age 60 and up who regularly consumed the recommended daily allowance (RDA) of 400 micrograms (mcg) of folic through foods and supplements cut their risk of developing Alzheimer's by over 50 percent. It is still too early to say, however, whether folic acid—also called folate—or other nutrients may actually prevent the onset of Alzheimer's disease.

5. Sip green tea.

Green tea, the popular beverage drunk by millions in Asia and, increasingly, by many in the U.S. as well, may have benefits against Alzheimer's disease, researchers from the University of South Florida report. The beverage contains a compound called EGCG that appears to reduce the formation of beta-amyloid, a toxic protein that builds up in the brains of those with Alzheimer's disease. Although the studies were carried out in mice and may not apply to humans, scientists are motivated to continue research into the possible benefits of green tea and other types of tea for people suffering from memory loss.

Finally — toast to a healthy new year!

Ring in the New Year with a toast – but don't go overboard. Low to moderate alcohol consumption, just a drink or so a day, may be good for the brain, a large and rigorous Harvard study of nurses revealed. Women who consumed a drink a day or less, on average, tended to perform better on memory tests than those who abstained from alcohol entirely or drank more heavily. The benefits appeared to persist for at least several years, according to the study, which appeared in the prestigious New England Journal of Medicine.

For more on these and other stories, visit alzinfo.org, The Alzheimer's Information Site. The Fisher Center for Alzheimer's Research Foundation offers regular updates and in-depth reports on keeping the mind and memory sharp and fit. Visit alzinfo.org often throughout the year for valuable tips and the latest news. To make a year-end donation to support Alzheimer's Research, click here http://www.alzinfo.org/donations. Your contributions make a real difference in the search for a cure for Alzheimer's disease.

Mechanism Tying Obesity to Alzheimer’s Disease

If heart disease and diabetes aren’t bad enough, now comes another reason to watch your weight. According to a study just released, packing on too many pounds can increase the risk of developing Alzheimer’s disease.
A team led by researchers at the Farber Institute for Neurosciences at Thomas Jefferson University in Philadelphia and Edith Cowan University in Joondalup, Western Australia has shown that being extremely overweight or obese increases the likelihood of developing Alzheimer’s. They found a strong correlation between body mass index and high levels of beta-amyloid, the sticky protein substance that builds up in the Alzheimer’s brain and is thought to play a major role in destroying nerve cells and in cognitive and behavioral problems associated with the disease.
“We looked at the levels of beta-amyloid and found a relationship between obesity and circulating amyloid,” says Sam E. Gandy, M.D., Ph.D., director of the Farber Institute for Neurosciences. “That’s almost certainly why the risk for Alzheimer’s is increased,” says Dr. Gandy, who is also professor of neurology, and biochemistry and molecular biology at Jefferson Medical College of Thomas Jefferson University. “Heightened levels of amyloid in the blood vessels and the brain indicate the start of the Alzheimer’s process.” The scientists reported their findings this month in the Journal of Alzheimer’s Disease.

Can Pound Scum Compound Fight Alzheimer's?

29 Dec 2005

A compound isolated from a cyanobacterium, a type of blue-green algae known as Nostoc, shows promise of becoming a natural drug candidate for fighting Alzheimer's and other neurodegenerative diseases, according to an in vitro study by researchers in Switzerland. It is believed to be the first time that a potent agent against Alzheimer's has been isolated from cyanobacteria, commonly known as 'pond scum.'

Cyanobacteria and other marine natural products have been increasingly found to be a promising source of drug candidates for fighting a variety of human diseases, including cancer and bacterial infections, but their chemistry has been largely unexplored, experts say. Now, a common marine organism could lead to yet another potential health benefit. There is no cure for Alzheimer's at present, although cholinesterase inhibitors have shown promise for delaying or preventing the symptoms of mild to moderate forms of the disease. The newly isolated compound, nostocarboline, was shown to be a potent inhibitor of cholinesterase -- a brain chemical thought to be important for memory and thinking -- whose breakdown has been associated with the disease's progression. The natural compound's potency is comparable to galanthamine, a cholinesterase inhibitor already approved for the treatment of Alzheimer's, the researchers say. As with any promising structure, it could be many years before the new compound is tested as a drug candidate in humans, the scientists caution.

Brain Cell Activity Increases Levels Of Key Ingredient In Alzheimer's Plaques

Washington University School of Medicine in St. Louis
Increased communication between brain cells increases levels of amyloid beta, the key ingredient in Alzheimer's brain plaques, scientists at Washington University School of Medicine in St. Louis have found.
Through a series of these experiments, researchers linked increased amyloid beta levels to the release of synaptic vesicles, small packets containing chemical messengers known as neurotransmitters. The primary way nerve cells send messages to each other is to release the vesicles waiting at the synapse, a structure where the arms of two nerve cells almost touch. The neurotransmitters cross the synapse and bind to receptors on the surface of the receiving nerve cell. Normal brain physiology produces amyloid beta and naturally clears it from the brain, so they conducted a series of follow-up experiments to try to get a sense for whether increased synaptic vesicle release was affecting amyloid beta production or clearance.
"It's probably not clearance, and the effect on production is probably pretty small," they say. "Instead, it appears that synaptic activity is regulating the amount of amyloid beta that gets released from inside brain cells, where amyloid beta is produced. We're going to follow up with studies of whether particular neurotransmitters can be linked to changes in amyloid beta levels."

Activity-dependent synapse modulation and the pathogenesis of Alzheimer disease.

Curr Alzheimer Res. 2005 Dec;2(5):497-506
Authors: Nelson PG

During normal development of the nervous system, a major reduction occurs in the initially excessive number of neurons and synapses. This "pruning" process is heavily influenced by patterns of electrical activity in the synaptic circuits being pruned. Many of the cell biological and molecular mechanisms involved in this activity-dependent modification of nervous system structure and function have been explicated, and the area is one of intense study. Similarly, an explosive increase has occurred in knowledge about the molecular pathogenesis of Alzheimer disease (AD). There are significant mechanistic commonalities between the normal neurodevelopmental process and development of AD. We hypothesize that abnormalities in neural activity patterns, or in the coupling between neural activity and maintenance of neurons and synaptic circuits, may be a key determinant in the pathogenesis of AD that is late in onset, sporadic in nature, and in which the genes for the presenilins and the beta amyloid precursor protein are normal. Behavioral data suggests that an active, socially engaged life-style may be associated with a reduced risk for AD. If so, mechanisms linking neural activity with synaptic circuit integrity are probably involved and provide a target for ameliorative pharmacological intervention.

Two aspects of impaired consciousness in Alzheimer's disease.

Prog Brain Res. 2005;150:287-98
Authors: Salmon E, Ruby P, Perani D, Kalbe E, Laureys S, Adam S, Collette F

Alzheimer's disease (AD) is a degenerative dementia characterized by different aspects of impaired consciousness. For example, there is a deficit of controlled processes that require conscious processing of information. Such an impairment is indexed by decreased performances at controlled cognitive tasks, and it is related to reduced brain metabolic activity in a network of frontal, posterior associative, and limbic regions. Another aspect of impaired consciousness is that AD patients show variable levels of anosognosia concerning their cognitive deficits. A discrepancy score between patient's and caregiver's assessment of cognitive functions is one of the most frequently used measures of anosognosia. A high discrepancy score has been related to impaired activity in the superior frontal sulcus and the parietal cortex in AD. Anosognosia for cognitive deficits in AD could be partly explained by impaired metabolism in parts of networks subserving self-referential processes (e.g., the superior frontal sulcus) and perspective-taking (e.g., the temporoparietal junction).
We hypothesize that these patients are impaired in the ability to see themselves with a third-person perspective (i.e., being able to see themselves as other people see them).

Fat linked to losing your mind

MAINTAINING a healthy weight may significantly reduce a persons risk of Alzheimers disease, Australian research suggests.
A pilot study of 18 mentally fit West Australians, aged between 23 and 64, showed those overweight or obese had higher levels of a protein known as beta amyloid in their blood, the same sticky substance found in high concentrations in the brains of Alzheimers patients.
Population-based research has previously shown a strong link between being overweight or obese in middle age and an increased risk of Alzheimers, but the Australian study is the first evidence to offer an explanation.
Although lead researcher Ralph Martins stressed the study was only preliminary, he said the results were “very striking”, clearly showing the more overweight a person is, the higher the levels of beta amyloid in the blood.
Prof Martins said of the two types of beta amyloid, the more toxic form of the protein known as beta amyloid 42, was the one found in more elevated concentrations in those who were overweight or obese.
Results of the pilot study have been published in the latest edition of the Journal of Alzheimers Disease.
The study has been extended to involve 300 mentally healthy West Australians who will have full body scans in a bid to determine whether higher concentrations of body fat in certain areas, such as around the abdomen, put people more at risk of Alzheimers.
Prof Martins said a Wisconsin study presented at a recent scientific meeting found men with beer bellies who were the children of Alzheimers sufferers had altered levels of beta amyloid in the fluid surrounding their brains.
The ultimate aim of the Australian research is to develop strategies to help people prevent, or at least delay, the onset of the disease.
Prof Martins said research in mice with high levels of beta amyloid had found treadmill exercises had markedly reduced the amount of the protein in their brains.
“We want to see whether we can implement exercise or weight loss programs to alter the beta amyloid levels in humans,” he said.

Synaptic Activity Regulates Interstitial Fluid Amyloid-beta Levels In Vivo.

Neuron. 2005 Dec 22;48(6):913-922
Authors: Cirrito JR, Yamada KA, Finn MB, Sloviter RS, Bales KR, May PC, Schoepp DD, Paul SM, Mennerick S, Holtzman DM

Aggregation of the amyloid-beta (Abeta) peptide in the extracellular space of the brain is central to Alzheimer's disease pathogenesis. Abeta aggregation is concentration dependent and brain region specific. Utilizing in vivo microdialysis concurrently with field potential recordings, we demonstrate that Abeta levels in the brain interstitial fluid are dynamically and directly influenced by synaptic activity on a timescale of minutes to hours. Using an acute brain slice model, we show that the rapid effects of synaptic activity on Abeta levels are primarily related to synaptic vesicle exocytosis. These results suggest that synaptic activity may modulate a neurodegenerative disease process, in this case by influencing Abeta metabolism and ultimately region-specific Abeta deposition. The findings also have important implications for treatment development.

Immunotherapy of Alzheimer's disease
Autoimmun Rev. 2006 Jan;5(1):33-9
Authors: Geylis V, Steinitz M

The deposition of amyloid beta (Abeta) protein is a key pathological feature in Alzheimer's disease (AD).

In murine models of AD, both active and passive immunization against Abeta induce a marked reduction in amyloid brain burden and an improvement in cognitive functions. Preliminary results of a prematurely terminated clinical trial where AD patients were actively vaccinated with aggregated Abeta bear resemblance to those documented in murine models. Passive immunization of AD patients with anti-Abeta antibodies, in particular human antibodies, is a strategy that provides a more cautious management and control of any undesired side effects. Sera of all healthy adults contain anti-Abeta IgG autoimmune antibodies. Hence antigen-committed human B-cells are easily immortalized by Epstein-Barr virus (EBV) into anti-Abeta secreting cell lines.

Two anti-Abeta human monoclonal antibodies which we recently prepared bind to the N-terminus of Abeta peptide and were shown to stain amyloid plaques in non-fixed brain sections from an AD patient. It is anticipated that specifically selected anti-Abeta human monoclonal antibodies could reduce and inhibit deposits of amyloid in brain while avoiding the cognitive decline that characterizes AD. In the future, this type of antibody may prove to be a promising immune therapy for the disease.

Effects of Testosterone on Cognition and Mood in Male Patients
Arch Neurol. 2005 Dec 12

Authors: Lu PH, Masterman DA, Mulnard R, Cotman C, Miller B, Yaffe K, Reback E, Porter V, Swerdloff R, Cummings JL

CONTEXT: There is a compelling need for therapies that prevent, defer the onset, slow the progression, or improve the symptoms of Alzheimer disease (AD).

OBJECTIVE: To evaluate the effects of testosterone therapy on cognition, neuropsychiatric symptoms, and quality of life in male patients with mild AD and healthy elderly men.

DESIGN: Twenty-four-week, randomized, double-blind, placebo-controlled, parallel-group study.

SETTING: Memory disorders clinics as well as general neurology and medicine clinics from University of California medical centers at Los Angeles, San Francisco, and Irvine.

PARTICIPANTS: Sixteen male patients with AD and 22 healthy male control subjects. Healthy elderly control men were recruited from the community through advertisements as well as through the university-based clinics.Intervention Testosterone and placebo, in the form of hydroalcoholic gel (75 mg), were applied daily to the skin of the participants.

RESULTS: For the patients with AD, the testosterone-treated group had significantly greater improvements in the scores on the caregiver version of the quality-of-life scale (P = .01). No significant treatment group differences were detected in the cognitive scores at end of study, although numerically greater improvement or less decline on measures of visuospatial functions was demonstrated with testosterone treatment compared with placebo. Testosterone treatment was well tolerated with few adverse effects relative to placebo.

CONCLUSIONS: Results suggest that testosterone replacement therapy improved overall quality of life in patients with AD. Testosterone had minimal effects on cognition.

Dementia “set To Quadruple”

18 Dec 2005

A new case of dementia arises every seven seconds with the number of people with dementia set to double every 20 years, says a report in the Lancet today. The report, produced for Alzheimer's Disease International (ADI), comes 100 years after the first description of Alzheimer's disease and estimates that 24.3 million people currently have dementia, with 4.6 million new cases annually. By 2040 the number will have risen to 81.1 million. The study highlights that most people with dementia live in developing countries: 60% in 2001 rising to 71% by 2040. The rate of increase is predicted to be three to four times higher in developing regions than in developed areas.
Already, many more people with dementia live in China and its neighbours (6 million) than in either Western Europe (4.8 million) or North America (3.4 million). By 2040 there will be as many people with dementia in China alone as in the whole of the developed world put together. These alarming new figures are a call to action for governments worldwide. “We are faced with a ticking time bomb,” explained ADI's chairman Orien Reid. “Governments must start to plan policy, and allocate health and welfare resources for the future. Another cause for concern is that millions of these cases of dementia are going undiagnosed meaning that, through ignorance and stigma, people aren't receiving the care and services that they so desperately need.” “There is already a great need for community based services, welfare and support and these new figures show that pressure on governments for dementia services will increase dramatically in the next few years. This need has to be addressed now,” said Professor Martin Prince, who co-ordinated the study with Dr Cleusa Ferri. The report concluded that there needs to be a climate for change, but this must start by correcting a fundamental lack of awareness among policymakers, clinicians and the public.
“The Centenary year is an opportunity to bring attention to the worldwide implications of these new figures,” said Michael Lefevre, Executive Director of ADI. The experts reached agreement, based on the evidence, on the proportion of the older population likely to be affected by dementia in each region. These proportions were then applied to UN population estimates to arrive at the total numbers of people with dementia. Researchers used UN population estimates to produce prevalence figures for both men and women in five age bands from 60 to 84, and for those aged 85 and over. The research includes all types of dementia -it does not break down prevalence for Alzheimer's disease, vascular dementia and so on.
The countries and areas with the largest number of people with dementia are:
China - 5 million
European Union - 5 million
USA - 2.9 million
India - 1.5 million
Japan - 1.1 million
Russia: - 1.1 million
Indonesia: - 1 million
Alzheimer's Disease International is the international federation of 75 Alzheimer associations around the world. ADI was founded in 1984 and is based in London. ADI has been in official working relations with the World Health Organization since 1996. The president of ADI is Princess Yasmin Aga Khan, daughter of Rita Hayworth, who had Alzheimer's disease. Dementia is a progressive degenerative brain syndrome which affects memory, thinking, behaviour and emotion. Alzheimer's disease is the most common cause of dementia. Declining memory, especially short-term memory is the most common early symptom of dementia. Other symptoms include difficulty performing familiar tasks, disorientation to time and place, poor or decreased judgment and changes in personality. World Alzheimer's Day is celebrated on 21 September each year. The day was launched with the support of the World Health Organization in 1994. ADI co-ordinates events as well as the production and distribution of materials around the world.

Statin therapy in the treatment of Alzheimer disease: what is the rationale?

Am J Med. 2005 Dec;118 Suppl 12A:48-53
Authors: Dekosky ST

Alzheimer disease (AD) is a chronic neurodegenerative disorder that is manifested by cognitive decline, neuropsychiatric symptoms, and diffuse structural abnormalities in the brain. Its prevalence is predicted to rise 4-fold in the next 50 years.

AD is characterized pathologically by deposition of extracellular beta-amyloid and accumulation of neurofibrillary tangles. Neuronal death and specific neurotransmitter deficits also are part of the pathologic picture. Strategies to delay symptom progression have focused on addressing the neurotransmitter deficits. Strategies to delay the onset or biologic progression of AD largely have targeted the plaques formed by the deposition of beta-amyloid. AD and cardiovascular disease share common risk factors, notably hypercholesterolemia, and occur together more often than expected by chance. Therapy with the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) is the first-line treatment option for hypercholesterolemia, and observational studies have suggested that the risk of AD is reduced in patients who receive statin therapy in midlife. This reduction in risk of AD observed with statin therapy may be due to statins reducing beta-amyloid formation and deposition or to their known anti-inflammatory effects.

Two randomized double-blind statin trials in patients with AD to assess the potential for statins to slow disease progression are currently under way. If successful, statin AD primary prevention trials may be developed.

Huge Increase in Alzheimer's, Dementia Predicted
(HealthDay News)

Experts are now predicting that the global incidence of Alzheimer's disease and other forms of dementia will soar in the next few decades, especially in developing countries. That prediction is made by an international group of 12 experts, two of them American, who were provided with "a systematic review of published studies on dementia" by Alzheimer's Disease International, a London-based organization.
"We estimate that 24.3 million people have dementia today, with 4.6 million new cases of dementia every year," the experts report in the Dec. 17 issue of The Lancet. "The number of people [with dementia] will double every 20 years, to 81.1 million by 2040," they added. The number of cases will double by 2040 in developed countries such as the United States, but will more than triple in India, China and other countries in south Asia and the western Pacific, the experts wrote. "We believe that the detailed estimates in this paper constitute the best currently available basis for policymaking, planning and the allocation of health and welfare resources," they said.
The prediction is very much in line with the forecast made two years ago for the United States by the Alzheimer's Association, said Maria Carrillo, the organization's director of medical and scientific affairs. "We have 4.5 million cases now," Carrillo said. "We predict a huge increase, to 6.5 million in 2025. That will overwhelm our economy and health-care system, and needs to be addressed in the next five to 10 years by research." The Alzheimer's Association is currently seeking a $300 million increase in its funding for dementia research, she said. The exact causes of Alzheimer's disease remain unknown, although it is thought to be related to a gradual build-up of amyloid beta protein plaques within the brain. Cerebrovascular changes have also been linked to increased risk for Alzheimer's, and stroke is a major contributor to other forms of dementia. The Alzheimer's Disease International experts are recommending public health measures that focus on reducing risk factors for cerebral blood vessel damage, such as high blood pressure, smoking, diabetes and cholesterol.
The U.S. Alzheimer's Association agrees with that approach, Carrillo said. "A lot of research has shown that leading a healthy lifestyle can help preserve mental function," she said. "You should be physically active, mentally active and socially active." Mental activity is an important element, but physical activity counts as well, said Colin Milner, chief executive officer of the International Council on Active Aging, based in Canada. "Learning a foreign language, juggling, playing ping-pong, you need to engage your mind and your body," he said. The numbers in the Lancet paper "aren't really a great surprise, because people aren't living healthy lives," Milner said. "Look at diabetes. They're predicting a 165 percent increase over the next five to 10 years. You need to be aware of the impact that not doing something can have on your mind and body."

Disease link to water poisoning

A toxic chemical was tipped into the wrong tank at the Lowermoor worksA post-mortem test on a woman who drank water during the Camelford water poisoning incident has found abnormally high levels of aluminium in her brain.
It is the strongest evidence yet of a possible link between the poisoning and a disease similar to Alzheimer's.
Water in the Cornish town was contaminated with 20 tonnes of aluminium sulphate in 1988.
Hundreds of people said they became ill after the toxic chemical was put into the wrong tank at a treatment works.
Inquest adjourned
West Somerset Coroner Michael Rose released the post-mortem examination results on Thursday.
He asked leading neuropathologist Prof Margaret Esiri to examine the woman's brain and spinal cord following her death in Musgrove Park Hospital, Taunton, in February last year.
Further research will be needed before the significance of the elevated brain aluminium concentration... can be clarified
Michael Rose, coroner
The woman was living in Camelford at the time of the incident.
It was discovered that she died from beta amyloid angiopathy, a form of cerebrovascular disease usually associated with Alzheimer's disease, which could be connected to an abnormally high level of aluminium in her brain.
Mr Rose said: "Further research will be needed before the significance of the elevated brain aluminium concentration in this case can be clarified.
"A scientific report on the case has been submitted for publication. The inquest will stand adjourned until the completion of further research."

Key Brain Antioxidant Linked To Alzheimer's And Parkinson's

A study conducted at the San Francisco VA Medical Center has identified a protein found in both mice and humans that appears to play a key role in protecting neurons from oxidative stress, a toxic process linked to neurodegenerative illnesses including Alzheimer's and Parkinson's diseases.
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The study, led by Raymond Swanson, MD, chief of neurology and rehabilitation services at SFVAMC, identified the protein – known as EAAC1 in mice and as EAAT3 in humans – as the main mechanism through which the amino acid cysteine is transported into neurons. Cysteine is an essential component of glutathione, which Swanson terms "the most important antioxidant in the brain."
It had been thought previously that the main function of the protein was to remove excess glutamate, a neurotransmitter, from brain cells.
"It's known that neurons don't take up cysteine directly, and it's never been clear exactly how it gets there," says Swanson, who is also professor and vice chair of neurology at the University of California, San Francisco. "This study provides the first evidence that EAAC1 is the mechanism by which cysteine gets into neurons – and that transporting cysteine is probably its chief function."
Study findings are currently available in the Advance Online Publication section of Nature Neuroscience.

A Pocketful Of Help For Alzheimer's Sufferers And CaregiversCategory

14 Dec 2005

Florida Tech Professor of Psychology, Dr. Frank Webbe, and Dr. Annie Becker, director of the Florida Tech National Center for Small Business Information, received $200,000 from the Alzheimer's Association (in partnership with Intel Corporation and Agilent Technologies) to study the use of PocketPC and Web technologies to promote quality of life for Alzheimer's patients and caregivers. The project is one of four funded internationally under the Alzheimer's Association's program for "Everyday Technologies for Alzheimer's Care." The researchers will develop a portable caregiver support system called PocketBuddy. The system would issue audio and text reminders to the caregiver, which could include medication information, appointment reminders and automated checklists for daily support. Also embedded could be such information as bill paying instructions, the location of important documents and emergency contact names. Family and friends might access information about patients and caregivers via a Web log, a "Buddy Blog," linked to the PocketPC. This technology could bridge the time and space barriers, which often separate loved ones.
"Combining expertise in psychology and information systems/computer science, we hope to ease the burden and reduce the isolation of Alzheimer's caregivers who care for their family member at home," said Webbe. Becker brings the technology skills to the interface appearance and system usability. She will also supervise the creation of the software that will control the device.

Men With Mild Alzheimer's May Benefit From Testosterone Therapy

13 Dec 2005

Testosterone replacement therapy may help improve the quality of life for elderly men with mild cases of Alzheimer's disease, according to a study posted online today that will appear in the February 2006 print issue of Archives of Neurology, one of the JAMA/Archives journals. "There is a compelling need for therapies that prevent, defer the onset, slow the progression, or improve the symptoms of Alzheimer disease (AD)," the authors provide as background information in the article. They note that hormonal therapies have been the focus of research attention in recent years since male aging is associated with a gradual progressive decline in testosterone levels. "The gradual decline in testosterone level is associated with decreased muscle mass and strength, osteoporosis, decreased libido, mood alterations, and changes in cognition, conditions that may be reversed with testosterone replacement." The authors add that the age-related decline in testosterone is potentially relevant to AD as previous studies have found significantly lower concentrations of the hormone in middle-aged and elderly men who developed AD. Po H. Lu, Psy.D., from the David Geffen School of Medicine, University of California, Los Angeles, and colleagues conducted a 24-week, randomized study to evaluate the effects of testosterone therapy on cognition, neuropsychiatric symptoms, and quality of life in 16 male patients with mild AD and 22 healthy elderly men who served as controls. The study participants were randomized to receive packets of gel to apply on their skin that either contained testosterone or a placebo. Standardized tests were administered at least twice (baseline and end) during the study for the assessment of cognitive functions and quality of life. "For the patients with AD, the testosterone-treated group had significantly greater improvements in the scores on the caregiver version of the quality-of-life scale," the researchers report. "No significant treatment group differences were detected in the cognitive scores at end of study, although numerically greater improvement or less decline on measures of visuospatial functions was demonstrated with testosterone treatment compared with placebo. In the healthy control group, a nonsignificant trend toward greater improvement in self-rated quality of life was observed in the testosterone-treated group compared with placebo treatment. No difference between the treatment groups was detected in the remaining outcome measures." "In conclusion, the present results should be considered preliminary and do not warrant routine treatment of AD and healthy control men with testosterone. Future studies with larger sample sizes are needed before clinical decisions regarding testosterone therapy can be rationally based. For men with compromised quality of life, as reflected on the type of measure employed in this study, and who suffer from low serum T [testosterone] levels, testosterone therapy may be a reasonable consideration."

Alzheimer's Disease Market in the Seven Major Markets is Worth

12/12/2005 10:10:00 AM EST

Research and Markets (http://www.researchandmarkets.com/reports/c1616) has announced the addition of Alzheimer Disease - New Drugs, Markets and Companies to their offering.

Alzheimer's disease remains a challenge in management. With nearly 8 million sufferers from this condition in the seven major markets of the world and anticipated increases in the future. Considerable research is in progress to understand the pathomechanism of the disease and find a cure. The only drugs approved currently are acetylcholinesterase inhibitors but they do not correct the basic pathology of the disease, beta amyloid deposits and neurofibrillary tangles. Several new approaches emphasize neuroprotection as well.
Early diagnosis of Alzheimer's disease is an important first step in management. Several biomarkers in cerebrospinal fluid, blood and urine can detect the disease. They provide a valuable aid to the clinical examination and neuropsychological testing which are the main diagnostic methods supplemented by brain imaging. Genotyping, particularly of ApoE gene alleles is also useful in the evaluation of cases and planning management.
The current management of Alzheimer's disease is reviewed and it involves a multidisciplinary approach. Acetylcholinesterase inhibitors are mostly a symptomatic treatment but some claims are made about a neuroprotective effect. Currently the only approved neuroprotective therapy in Europe is memantine which is awaiting approval in the US. Management of these patients also require neuroleptics for aggressive behavior and antidepressants. There is an emphasis on early detection at the stage of mild cognitive impairment and early institution of neuroprotective measures. The value of mental exercise in delaying the onset of Alzheimer's disease is being recognized.
Research in Alzheimer's disease still aims at elucidating the basic pathomechanisms. Animal models are important for research, particularly in testing some of the potential therapeutic approaches. There is considerable research in progress at the various centers, some of which is funded by the National Institute of Aging of the National Institutes of Health.
Over 130 different compounds are at various stages of development for the treatment of Alzheimer's disease. These are classified and described. There are non-pharmacological approaches such as vagal nerve stimulation and cerebrospinal fluid shunting, which are in clinical trials. Various clinical trials are listed including those that failed in the past.
Alzheimer's disease market in the seven major markets is worth $6.1 billion in the year 2005 and will increase to $ 7.8 billion by the year 2010. The share of currently approved drugs specifically for AD is expected to be $3.1 billion in the year 2005 and $4.1 billion by the year 2010 provided all of them stay in the market. Several new therapies are expected to be in the market and the shares of various types of approaches are estimated for the future up to the year 2015. As a background to the markets, pharmacoeconomic aspects of care of Alzheimer disease patients and patterns of practice are reviewed in the seven major markets.
Profiles of 127 companies involved in developing diagnostics and therapeutics for Alzheimer's disease are presented along with their collaborations. The bibliography contains over 500 publications that are cited in the report. The report is supplemented with 38 tables and 10 figures.

A descriptive national survey of 166 Alzheimer health networks

Presse Med. 2005 34(9):637-9
Authors: Nubukpo P, Le Bruchec M, Clément JP

OBJECTIVE: Assess and describe the organization, operation, and aims of Alzheimer health networks in France.
METHODS: Questionnaire sent by post or handed to physicians in France identified as involved in management of Alzheimer patients by Novartis Pharma sales representatives.
RESULTS: 166 networks managing Alzheimer's disease (2/3 primarily gerontological and 1/3 specializing specifically in Alzheimer's). In 61.9% of the cases, the physician supervising the network was a hospital staff physician, often a geriatrician (48%). The other member physicians were essentially general practitioners. Several paramedics and social workers also participated. Most networks were organized as not-for-profit organizations. Financial support most often came from the relevant ministries and the health insurance funds. The number of active cases handled by the networks could not be globally assessed. The operating tools for the networks included membership charters, management guidelines and protocols, and shared medical files, but fewer than 30% of the networks used any one of these. The networks had as their primary objectives training and information, patient follow-up and gerontological coordination. These aims were consistent with the goals they felt that had come closest to attaining, i.e., improving the quality and organization of care, sharing information with and training other health professionals, and providing information to the public. Barely one third of the networks had developed an assessment procedure. Among the obstacles to network operations were the participants' lack of availability, the absence of collaboration between professionals, and financial problems.
CONCLUSION: Despite the disparity in the quality and exhaustiveness of the data collected, our survey confirmed the diversity and dynamism, but also the lack of formal structure and the difficulties confronted by the Alzheimer networks in France.

Cholesterol and Alzheimer's disease-is there a relation?

Mech Ageing Dev. 2005 Dec 2;
Authors: Sjцgren M, Mielke M, Gustafson D, Zandi P, Skoog I

The predominating theory on the pathophysiology of Alzheimer's disease (AD) concerns the mis-metabolism of amyloid precursor protein (APP). As a result of this mis-metabolism, there is an increased production of the 42 amino acid form of beta-amyloid (Abeta42) that rapidly will form oligomers that initiates a cascade of events leading to the accumulation of amyloid plaques.

Commonly recognised as vascular factors, hypertension, hypercholesterolemia and diabetes and the inheritance of the varepsilon4 allele of the APOE gene, are also risk factors for AD. These risks have been found to promote the production of Abeta42. An association between cholesterol and the development of AD was suggested in the early 1990s and ever since, an increasing amount of research has confirmed that there is a link between cholesterol and the development of AD.

A high cholesterol levels in mid-life is a risk for AD and statins, i.e., cholesterol-lowering drugs, reduce this risk. Statins may not only inhibit enzymes involved in the endogenous synthesis of cholesterol but also affect enzymes involved in Abeta metabolism, i.e., alpha-secretase and beta-secretase. This normalises the breakdown of APP thereby promoting the non-amyloidogenic pathway.

Alzheimer's disease prevention may be easier than cure

Current hypotheses suggest that it is the accumulation over time of amyloid beta peptide 1–42 (Abeta42) that triggers changes in the brain that lead to cognitive dysfunction in Alzheimer's disease. The reduction of amyloid levels is therefore a major therapeutic objective. Todd Golde and colleagues from the Mayo Clinic Jacksonville report evidence to suggest that prevention of amyloid deposition may be easier than curing established Alzheimer's disease. Their results will appear online on December 8 in advance of print publication in the January 2006 issue of the Journal of Clinical Investigation.
The authors use transgenic mice genetically predisposed to accumulate amyloid deposits in their brain to show that an immunization strategy targeting Abeta42, or a second form of Abeta known as Abeta40, prevents the onset of amyloid deposition in these mice at a young age. In contrast, the anti-Abeta42 or anti-Abeta40 monoclonal antibodies were not effective in altering Abeta deposition in mice with modest levels of preexisting Abeta deposits, nor were they capable of clearing existing deposits. The results suggest that it may be easier to prevent Abeta deposition than to alter Abeta once deposited. This method may be an effective strategy to prevent amyloid deposition prior to the onset of Alzheimer's disease, but may have limited benefit in a therapeutic setting where amyloid deposits are already well established within the brain.

Gladstone Researchers Identify New Drug Target For Alzheimer's

Disease12/1/2005
Source: Gladstone Institutes

Researchers at the Gladstone Institute of Neurological Disease have identified a potential new way to stop brain cell death related to Alzheimer's disease.
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Working with cell cultures, the scientists investigated how amyloid beta proteins, which build up in the brain tissue of people with Alzheimer's disease, kill neurons. The cell cultures were established from brain tissue of laboratory rats. Study findings showed that amyloid beta could be prevented from causing neuronal cell death with a compound called resveratrol, which is also found as a natural ingredient in red wine.

A new tool in the battle against Alzheimer's disease and aging: ex vivo gene therapy.

Rejuvenation Res. 2005;8(3):131-4
Authors: Ebert AD, Svendsen CN

Alzheimer's disease (AD) is the most common cause of severe dementia in the aging population and is caused by a loss of many different neural systems throughout the brain associated with memory. Amongst the many neural systems affected, large cholinergic projection neurons that innervate large regions of cortex are particularly vulnerable. Thus, boosting cholinergic neuronal function and survival has been a focus of the few drugs currently available for this disorder. Nerve growth factor (NGF) is the archetypical protein discovered in the 1960s that is able to both increase survival and functioning of cholinergic neurons. However, the blood-brain barrier does not allow penetration of this protein into the brain. A phase 1 clinical trial recently published in the journal Nature Medicine utilized a unique ex vivo gene therapy approach to deliver NGF directly to the basal forebrain of AD patients. Despite the need for further testing, their report illustrated a mild but significant therapeutic benefit of NGF for the treatment of AD and provided important data concerning the safety and efficacy of ex vivo gene therapy in humans.

Alzheimer's disease has been studied for nearly a century.
As Germany was enjoying an industrial boom before World War I, Alois Alzheimer, a neurologist in Munich, first identified the disease. He interviewed a woman who was losing her memory and spatial skills. Before she died a few years later, the woman had started hallucinating and had lost the ability to write.
Alzheimer performed an autopsy on her brain in 1906. He found protein plaques, clumps of tiny biological molecules, and also found that parts of the nerve cells in her brain had become tangled. Those clumps and tangles have come to define Alzheimer's disease.
Like Alzheimer, scientists today still do not know what causes the disease. Some believe the clumps and tangles are a result of Alzheimer's, not its cause. But many studies have shown that the clumps and tangles cause brain decay. Alzheimer's research is therefore often aimed at reducing the number of clumps in the brain.
There is no cure for Alzheimer's disease, nor is there a way to stop it from progressing. The few drugs that are available mostly help ease some symptoms of the disease, such as insomnia, anxiety and depression. The nationwide study now under way aims to determine whether lowering the cholesterol in Alzheimer's patients is enough to slow the progress of the disease by slowing the accumulation of clumps in the brain.
The clumps are formed from the biological molecules, called beta-amyloid particles, that float around in the brain. Because the particles are slightly sticky, they eventually start clinging to each other. Studies have shown that high levels of cholesterol can trigger the brain to produce lots of beta-amyloid particles, which occur naturally in the brain but become dangerous when clumped together - "Like when you are cooking spaghetti and it all sticks together," said William Seavey, a geriatrician and internist at the University of Califoria-Davis who has also been involved in the nationwide study.
But at this point, Seavey said, "I wouldn't go out and take a cholesterol-lowering drug simply to prevent Alzheimer's disease. But I think there is a lot of reason to take care of your brain and your heart to avoid Alzheimer's."

Safety and Acceptability of the Research Lumbar Puncture.
Alzheimer Dis Assoc Disord. 2005

October/November/December;19(4):220-225

Authors: Peskind ER, Riekse R, Quinn JF, Kaye J, Clark CM, Farlow MR, Decarli C, Chabal C, Vavrek D, Raskind MA, Galasko D

Three hundred forty-two subjects underwent 428 research lumbar punctures for studies of cerebrospinal fluid (CSF) biomarkers. Subjects were 67 Alzheimer disease or mild cognitive impairment (AD/MCI) patients and 275 cognitively normal adults aged 21 to 88. Lumbar puncture was performed in the lateral decubitus or sitting position using the Sprotte 24g atraumatic spinal needle. Up to 34 ml of cerebrospinal fluid were collected. Anxiety and pain experienced during lumbar puncture were rated on a visual analog scale. The frequency of any adverse event (11.7%), clinically significant adverse events (3.97%), and typical post-lumbar puncture headache (PLPHA) (0.93%) was low. Risk of post-lumbar puncture headache was unrelated to age, gender, position during lumbar puncture, ml of cerebrospinal fluid collected, or minutes of recumbent rest following lumbar puncture. The frequency of post-lumbar puncture headache was lower in AD/MCI (P = 0.03) than any other subject group. Anxiety and pain ratings were low. Younger subjects reported more anxiety than old (P = 0.001) and AD/MCI subjects (P = 0.008) and more pain than older normal subjects (P = 0.013). Pain ratings for women were higher than those for men (P = 0.006). Using the Sprotte 24g spinal needle, research lumbar puncture can be performed with a very low rate of clinically significant adverse events and with good acceptability in cognitively impaired persons and cognitively normal adults of all ages.

A new tool in the battle against Alzheimer's disease and aging: ex vivo gene therapy.

Rejuvenation Res. 2005;8(3):131-4
Authors: Ebert AD, Svendsen CN

Alzheimer's disease (AD) is the most common cause of severe dementia in the aging population and is caused by a loss of many different neural systems throughout the brain associated with memory. Amongst the many neural systems affected, large cholinergic projection neurons that innervate large regions of cortex are particularly vulnerable. Thus, boosting cholinergic neuronal function and survival has been a focus of the few drugs currently available for this disorder. Nerve growth factor (NGF) is the archetypical protein discovered in the 1960s that is able to both increase survival and functioning of cholinergic neurons. However, the blood-brain barrier does not allow penetration of this protein into the brain. A phase 1 clinical trial recently published in the journal Nature Medicine utilized a unique ex vivo gene therapy approach to deliver NGF directly to the basal forebrain of AD patients. Despite the need for further testing, their report illustrated a mild but significant therapeutic benefit of NGF for the treatment of AD and provided important data concerning the safety and efficacy of ex vivo gene therapy in humans.

What does the language of Alzheimer patients have to do with the language of Paul Celan?

Z Gerontol Geriatr. 2005 Oct;38(5):354-9
Authors: Rösler A, Schwerdt R, von Renteln-Kruse W

Being in touch with severely demented patients requires a fundamental transformation in communication habits in medicine and in nursing. There is a need of reorientation away from an interpreting and often deficit-oriented aspect of communication towards attentive observance of unusual verbal and nonverbal signals and resources of the patient. Spontaneous and open communication with the patient outweighs the importance of a goal-oriented exchange of information and poses a significant challenge for all health and social professions.The well-being of persons with dementia depends mainly on the quality of communication and on the design of the milieu and the quality of everyday life. Interaction in nursing seems to be the crucial issue, including both spontaneity and creativity in the interaction partners, while respecting the personal boundaries of both the patient and the nurse in the necessary intimacy of the care environment.

This essay shows important aspects and strategies of adequate communication with people with dementia from the perspective of medicine and of nursing. Ways to improve communication skills are shown, referring, among others, to the approaches by Kate Allan and John Killick (research fellows at Dementia Services Development Centre, University of Stirling).

Exercise keeps ‘Alzheimer’s Away’

London: Regular exercise can keep Alzheimer’s disease at bay according to a recent study done in the UK. Exercise flushes out the toxic chemical that causes this degenerative disease of the brain in the elderly population. Exercise replaces the toxic molecules with beneficial ones that protect the nerve cell.

Mark Mattson, a researcher at the National Institute on Aging in Baltimore, Maryland, said that the findings were encouraging and that they could prove to play an important role in finding the cure to Alzheimer's disease. "It's initial data but I think it has potential to be very relevant to people," he said. However, Paul Adlard, a neuroscientist at the University of California, who has also studied the brains of mice in a different model of Alzheimer's disease, maintained that according to the data he had collected, exercise did not boost levels of the protective insulin-like grow.

Currently Alzheimer's disease affects millions of the people above the age of 50 years across the globe and treatment for them is only minimally effective.

http://www.medindia.net

Micronutrients and Alzheimer's disease.

Proc Nutr Soc. 2005 Nov;64(4):565-70
Authors: Staehelin HB

The current high life expectancy is overshadowed by neurodegenerative illnesses that lead to dementia and dependence. Alzheimer's disease (AD) is the most common of these conditions, and is considered to be a proteinopathy, with amyloid-beta42 as a key factor, leading via a cascade of events to neurodegeneration. Major factors involved are oxidative stress, perturbed Ca homeostasis and impaired energy metabolism. Protection against oxidative stress by micronutrients (including secondary bioactive substances) has been shown in transgenic Alzheimer model systems to delay AD. Epidemiological evidence is less conclusive, but the vast majority of the evidence supports a protective effect on cognitive functions in old age and AD.

Thus, a diet rich in fruits and vegetables but also containing meat and fish is the most suitable to provide adequate micronutrients.

The strong link between cardiovascular risk and AD may be explained by common pathogenetic mechanisms mediated, for example, by homocysteine and thus dependant on B-vitamins (folate and vitamins B(12) and B(6)). However, micronutrients may also be harmful. The high affinity of amyloid for metals (Fe, Al and Zn) favours the generation of reactive oxygen species and triggers an inflammatory response.

Micronutrients in a balanced diet have a long-lasting, albeit low, protective impact on brain aging, hence prevention should be life long.

Evidence Grows That Alzheimer's Is A Type Of Diabetes

Article Date: 03 Dec 2005

Researchers at Rhode Island Hospital and Brown Medical School have discovered that insulin and its receptors drop significantly in the brain during the early stages of Alzheimer's disease, and that levels decline progressively as the disease becomes more severe, leading to further evidence that Alzheimer's is a new type of diabetes. They also found that acetylcholine deficiency, a hallmark of the disease, is linked directly to the loss of insulin and insulin-like growth factor function in the brain. The study, published in the November issue of the Journal of Alzheimer's Disease (http://www.j-alz.com), is the first to look at insulin levels early in the course of the disease. The authors' previous work published earlier this year primarily focused on the late stages of Alzheimer's. "Insulin disappears early and dramatically in Alzheimer's disease. And many of the unexplained features of Alzheimer's, such as cell death and tangles in the brain, appear to be linked to abnormalities in insulin signaling. This demonstrates that the disease is most likely a neuroendocrine disorder, or another type of diabetes," says senior author Suzanne M. de la Monte, a neuropathologist at Rhode Island Hospital and a professor of pathology at Brown Medical School in Providence, RI.

Beat Alzheimer's with exercise.

Charlotte Schubert

Exercise helps to flush a toxic molecule from the brain and causes a beneficial one to move in and protect nerve cells, research on mice shows. The discovery might help to explain why staying fit and keeping mentally active seem to fend off Alzheimer's disease in humans. "Our experiments support the idea that exercise is a good approach to all types of problems in the brain and that a sedentary lifestyle is a risk factor," says Ignacio Torres-Aleman, who led the study at the Cajal Institute in Madrid.Torres-Aleman and his colleagues were intrigued by previous studies showing that exercise slows mental decline in mice engineered to mimic Alzheimer's disease. They set out to discover the reason.They found that exercise doubled the levels of a protein that helps to flush molecules thought to underlie Alzheimer's disease out of the mice's brains and into their blood. The protein, called megalin, ejects a potentially destructive protein called amyloid-beta. In Alzheimer's patients, amyloid-beta accumulates in clumps throughout the brain.
Megalin also binds to a beneficial molecule in the blood, called insulin-like growth factor, and transports it to the brain. This growth factor is perhaps best known for bulking up muscles after exercise, but it also helps to keep nerve cells healthy.

Experiments support the idea that exercise is a good approach to all types of problems in the brain. Running could keep the brain as well as the body healthy.

New drug target for Alzheimer's identified

SAN FRANCISCO,

Scientists at the Gladstone Institute of Neurological Disease have identified a potential new way to stop brain cell death related to Alzheimer's disease.

Working with cell cultures, the scientists investigated how amyloid beta proteins -- which build up in the brain tissue of people with Alzheimer's disease -- kill neurons. The cell cultures were established from brain tissue of laboratory rats.
Study findings showed amyloid beta could be prevented from causing neuronal cell death with a compound called resveratrol, which is also found as a natural ingredient in red wine.
"Our study suggests that resveratrol and related compounds may protect against neuronal loss associated with Alzheimer's disease," said senior author Li Gan, a staff research investigator at San Francisco institute and an assistant professor of neurology at UCSF. "This could certainly open up new avenues for drug development."
The research is reported in the Dec. 2 issue of the Journal of Biological Chemistry.

US Eastern Timezone Humanetics - Oral Agent to Combat Alzheimer's Disease

MINNEAPOLIS--(BUSINESS WIRE)
--Dec. 1, 2005--
Humanetics Corporation today announced that it has entered into an exclusive license agreement with Mount Sinai School of Medicine in Manhattan, NY to further develop and commercialize an oral agent, referenced as NIC5-15, to combat Alzheimer's disease. This compound has been shown in pre-clinical studies and animal models to be effective in preventing the formation of beta amyloid plaques, which are believed to be a cause of Alzheimer's disease. Humanetics also announced that it has entered into a clinical research agreement with investigators at Mount Sinai to test the effect of the compound in humans. The Principal Investigator on the study is Giulio Maria Pasinetti, M.D., Ph.D., in the Department of Psychiatry and Department of Neurosciences at Mount Sinai.

AT A GLANCE

-- Caffeine exerts a positive effect on short-term memory and reaction times.
-- fMRI showed that 100 milligrams of caffeine (about two cups of coffee) increased activity in regions of the brain associated with working memory and attention.
-- The increased activation patterns in the brain had a direct effect on performance in a memory task.

University of Washington: estrogen replacement therapy may protect against Alzheimer's disease

Among its many salutary effects, estrogen seems to protect the brain against the ravages of Alzheimer's disease: numerous clinical studies support that finding. But how does it accomplish this feat? Researchers at the University of Washington in Seattle are involved in a number of basic-science studies that are beginning to provide answers.Post-menopausal women have somewhat higher rates of Alzheimer's than men. Scientists think the incidence in women is related to the sudden loss of natural estrogen to the brain, as the ovaries cease production during menopause. In men, testosterone converts to estrogen in the brain, where it apparently performs a similar protective function. However, men do not experience the same sudden decrease in hormone levels at midlife.Estrogen replacement therapy (ERT) restores estrogen levels to those of younger women. Various studies show that ERT protects against Alzheimer's (including the Baltimore Longitudinal Study of Aging, which showed that women on ERT have about half the chance of developing Alzheimer's compared to women not on ERT). But there have not been definitive answers to the question of how estrogen protects neurons (brain cells).Researchers led by Dr. Daniel Dorsa, UW professor of psychiatry and pharmacology and interim associate dean of medicine for scientific affairs, are examining estrogen's effects at basic cellular levels, studying rat brains and cell cultures.They are looking for the mechanisms by which estrogen protects against the assaults of Alzheimer's disease, which gradually destroys neurons, leading to dementia and eventual death. They are looking at both the neurotrophic effects of estrogen (its ability to promote neuron survival) and its neuroprotective effects (its ability to protect neurons from toxic substances).The UW research suggests that estrogen acts on neurons differently from its action on cells in other parts of the body.Among its neurotrophic effects, estrogen may promote the expression of certain neurotransmitter genes by activating an enzyme called protein kinase A. This enzyme promotes a chemical modification of a molecule called CREB (cyclic AMP-response element binding protein), found in the nucleus of brain cells, activating it and allowing certain genes to be expressed in the brain.Thus, estrogen may increase the amount of particular neurochemicals used by neurons to communicate with one another, such as vasopressin and acetylcholine, known to facilitate learning and memory.Among the hormone's neuroprotective effects, when neurons are placed in cultures, the addition of estrogen protects them from cell death from toxic agents such as beta amyloid, a protein found in the brains of Alzheimer's patients, which is thought to kill neurons.As part of this neuroprotective effect, estrogen may mimic or amplify the effects of growth factors produced in the brain. "We know that hormones have a dramatic effect on the viability and growth of the developing brain of the fetus," said Dorsa. "We find the same effects in the aging brain."UW studies just published in the journal Endocrinology, using chemically modified estrogen that cannot enter cells, suggest that the action may take place at the level of the cell membrane."These and other studies are letting us begin to understand at the cellular level how estrogen may act in the brain to reduce the incidence and/or progression of Alzheimer's disease," said Dorsa.The UW studies, now in their third year of five, are funded by the National Institute on Aging. Besides Dorsa, UW researchers are Cherie A. Singer, Pamela J. McMillan, Jyoti J. Watters, Patricia A. Pang, Dorcas J. Dobie, Keith L. Rogers, Tamara M. Strickland, Jean S. Campbell, Matthew J. Cunningham and Edwin G. Krebs.