Alzheimer's Club

"Alzheimer's disease may be due to abnormalities in the regions of the brain that operate the "default state", a term used to describe the cognitive state people defer to when musing, daydreaming, or thinking to themselves, according to new research. Researchers from Howard Hughes Medical Institute (HHMI) used five different medical imaging techniques to study the brain activity of 764 people, including those with Alzheimer's disease, those on the brink of dementia, and healthy individuals.

"The default activity patterns of the brain may, over many years, augment a metabolic- or activity-dependent cascade that participates in Alzheimer's disease pathology," said the lead author of the study, Randy Buckner, a HHMI investigator at Washington University in St. Louis. "The regions of the brain we tend to use in our default state when we are young are very similar to the regions where plaques form in older people with Alzheimer's disease. This is quite a remarkable convergence that we did not expect."

Buckner says the new findings are important because they could help scientists and clinicians identify and understand the beginnings of what is probably a cascade of events that ultimately leads to Alzheimer's. Researcher Randy Buckner: "The regions of the brain we tend to use in our default state when we are young are very similar to the regions where plaques form in older people with Alzheimer's disease."The most common form of dementia among older people, Alzheimer's is characterized outwardly by the erosion of language, thought and memory. Within the brains of people with Alzheimer's disease, abnormal clumps of plaque and tangled bundles of fibers form and characterize the physical manifestation of the disease, which may affect as many as 4.5 million Americans. The causes of the disease are unknown.

The availability of powerful imaging techniques and the ability to merge different sets of imaging data through new bioinformatics and statistical methods enabled Buckner and his team to construct a picture of Alzheimer's from molecular changes to the structural and functional manifestations of the disease. In the process, the team unexpectedly observed that the regions of the brain that light up when we slip into comfortable patterns of thought are the same as those that, later in life, exhibit the disabling clumps of plaque characteristic of Alzheimer's, a disease that most frequently manifests itself after age 60. That remarkable correlation, said Buckner, suggests that dementia may be a consequence of the everyday function of the brain. The study is published in the current issue of the Journal of Neuroscience"

Source: Nick Gibbens. Daydreaming linked to Alzheimer's. www.999today.com (30 August 2005) [FullText]

"New evidence says many devastating brain diseases may share the same cause—clumps of protein debris that clog the circuitry. It could lead to new drugs for millions of aging Americans.

Brain diseases lay waste to their victims in many different ways, most of them fatal. Alzheimer's robs patients of memory. Parkinson's ravages brain regions that coordinate movement. Huntington's unleashes uncontrollable spasms. Lou Gehrig's disease vanquishes the nerve cells that control the muscles. Researchers have long assumed the causes of these and other degenerative disorders are as disparate as their symptoms.

But that assumption is being turned upside down, a stunning development with profound implications for the 6 million Americans with these ailments—and the millions more to come as baby boomers age. Many researchers now believe most of these disorders share a common origin: clusters of deformed proteins that pile up in the brain over the years, slowly poisoning brain cells. Like globs of molecular glue, the protein debris wreaks havoc inside brain cells, clogging communication channels and gumming up nutrients and other necessary chemicals.

The new thinking provides crucial clues to devising the first treatments to attack the molecular origins of Alzheimer's and other brain diseases. Instead of having to start drug development from scratch for every disease, researchers hope they can recycle similar therapeutic strategies to treat several brain disorders.

"The convergence is incredible. Everything is falling into place. I'm hoping not to be working on these diseases in 10 or 15 years," says Harvard Medical School chemist Peter Lansbury, who studies Parkinson's and Alzheimer's. He envisions a day when people will routinely get genetic tests to spot the threat of brain decay, followed up with brain scans every few years for those at risk. At the first hint of trouble patients could preemptively take cluster-blocking drugs, just as millions take cholesterol drugs to prevent heart disease.

Little biotechs and pharmaceutical giants alike are racing to devise drugs to block the deadly clusters. They are focusing first on Alzheimer's, by far the brain's most common degenerative disorder. Praecis Pharmaceuticals, in Waltham, Mass., has crafted a compound dubbed Apan, now in early human tests, which prevents toxic bundles from forming by latching on to them like Velcro. Canada-based Neurochem has designed a drug to block sugarlike structures called glycosaminoglycans, which help protein fragments form bundles; the compound prolongs survival of mice with Alzheimer's-like symptoms and is in early human testing.

"There is a new air of hopefulness after a long time without much hope," says Zach Hall, president of EnVivo Pharmaceuticals and former head of the National Institute of Neurological Disorders and Stroke.

But devising new drugs may take a decade or more, and it will be difficult to target such a delicate organ without causing side effects. This winter Elan Corp. had to halt trials of its Alzheimer's vaccine after it was linked to brain inflammation in 15 of 360 patients.

Nor is there proof that protein clusters cause brain-cell death rather than result from it; the evidence is especially sketchy for amyotrophic lateral sclerosis, or Lou Gehrig's disease. It isn't known why the brain is so vulnerable to protein globs, which presumably form in other organs, too. Researchers figure the brain is more sensitive because most neurons are created in childhood and are never replaced, whereas in most other organs cells constantly turn over.

"We have so little knowledge that we may be being dangerously simplistic," cautions Mihael Polymeropoulos, a geneticist at Novartis.

The toxic-cluster theory arises from the sudden confluence of several independent lines of research. Some of the most powerful evidence comes from studies of patients with inherited forms of Parkinson's, Alzheimer's, Lou Gehrig's, Huntington's and related diseases. Over the past decade gene hunters have identified a dozen mutant genes that cause these diseases. Most times the mutant gene codes for a protein that boosts the formation of globs of protein debris.

The first hints about cellular debris came almost a century ago, when psychiatrist Alois Alzheimer studied the brains of demented patients after death and found them clogged with strange deposits he dubbed amyloid plaques. A few years later, similar deposits, called Lewy bodies, were found in autopsied brains of Parkinson's victims. No one knew quite what to make of these odd clumps. For decades the plaques and Lewy bodies were viewed merely as by-products of brain disease. Doctors came up with all sorts of theories, blaming Alzheimer's on factors as varied as aluminum in the water supply and a lack of key brain nutrients, and attributing Parkinson's disease to pesticide exposure or drug abuse.

In the late 1980s circumstantial evidence condemning the role of Alzheimer's amyloid plaques began to build when Harvard biologist Bruce Yankner showed, in test tubes, that the amyloid protein poisoned brain cells. Exactly why and how amyloid might harm the brain was unclear.

By the early 1990s the amyloid theory attracted the interest of chemist Peter Lansbury, who was then at MIT doing basic research on how proteins fold into their complex final structures. His chemist colleagues viewed Alzheimer's research as a dead end, but Lansbury switched his lab's focus to plaques.

Other researchers had identified several related protein fragments, called beta-amyloid, inside the amyloid plaques, but they didn't know which proteins were the bad ones. In 1993 Lansbury showed that when he put a smidgen of beta-amyloid-42 into a mixed solution of free-floating amyloid particles, it immediately caused them to coalesce into clumps. He proposed that 42 was the pathological form of amyloid and that excess amounts of it would accelerate the buildup of unnatural, toxic clusters in the brain's memory centers. Sure enough, geneticists discovered that patients with rare gene mutations that cause them to produce high levels of the 42 form usually get Alzheimer's at a young age.

At the University of California, San Francisco, neurologist Stanley Prusiner was amassing evidence that deformed proteins played a key role in another class of fatal disorders: Creutzfeldt-Jakob disease, the human version of Mad Cow; and a related malady in sheep known as scrapie.

These diseases are even more insidious than Alzheimer's because they are infectious; people contract Mad Cow disease by eating tainted beef. Scientists had long assumed these disorders must be caused by a virus, but Prusiner had proposed back in 1982 that deformed proteins called prions were the culprit. That violated the dogma that an infectious agent must contain DNA to replicate; proteins have no DNA. But Prusiner gradually proved his case, nailing down the precise molecular identity of the infectious prion in 1993, just as Lansbury was publishing his amyloid-42 work.

Prusiner proved that prions are a deformed version of an otherwise harmless protein called PrP. The bad prion form is chemically identical to the good form except that it has morphed into a highly toxic shape, like an X-Acto knife stuck in the open position. (Prusiner won the Nobel Prize in 1997 for his work.)

Lansbury noticed parallels between his Alzheimer's theory and Prusiner's prions. He showed that just as the bad amyloid-42 sped the formation of amyloid clusters, a small number of pathological prions could convert good prions to the dark side, at least in test-tube experiments. There is still debate as to whether single prions or clusters are the villains.

His idea, ahead of its time, was greeted with a yawn by biologists. "I was a wacky chemist, an outsider," he says. But Harvard neurologist Dennis Selkoe, an early champion of the amyloid theory of Alzheimer's, took notice and lured Lansbury to Harvard Medical School in 1996.

In the late 1990s the toxic-cluster theory was extended to a third major disease: Parkinson's. Geneticist Mihael Polymeropoulos, then at the National Institutes of Health, pinpointed a gene that causes a rare inherited form of the disease by spawning mutations in a protein called alpha-synuclein. When researchers then looked inside Lewy bodies, the mysterious globs in the brains of Parkinson's patients, they found abundant synuclein.

The gene findings showed Parkinson's might also result from the buildup of brain debris, in this case globs of synuclein. Lansbury's team helped build the case, proving in 1998 that the mutant synuclein proteins formed clusters more easily than normal synuclein. Meanwhile, researchers had discovered the gene for Huntington's, a fatal inherited disorder that currently afflicts 30,000 Americans. It, too, creates mutant proteins that build up into globs inside neurons.

These days Lansbury, Selkoe and other proponents of the cluster theory are suddenly in the mainstream, as the circumstantial evidence has become difficult to ignore. The biggest unanswered question is why protein globs are so deadly. The answer may lie in their unusual structure. Healthy proteins coil up into precise ball-like structures that ensure they interact only with their intended targets. Prions, beta-amyloid and synuclein, by contrast, are full of sticky structures called beta-sheets that react willy-nilly with crucial proteins.

As patients age, genetic mutations or unknown environmental factors may boost the production of deformed proteins. Or old brain cells simply may get worse at disposing of debris. Stanford University biologist Ron R. Kopito recently showed that clumps of the Huntington's protein can clog up the cell's waste disposal system. "You get these diseases because the garbage collectors go on strike," he says, "or because the in-laws move in and double the amount of garbage you produce."..."

Source: Robert Langreth. Dirty Minds. Forbes.com (15 April 2002) [FullText]

"Northwestern University researchers say they've found a way to detect and estimate size and structure of a protein suspected of causing Alzheimer's disease. The findings, researchers say, might help scientists better understand the underlying mechanisms of the disease and lead to the development of new treatments to slow or arrest its progression.
They said their findings might also potentially be used to diagnose Alzheimer's disease in living people instead of during an autopsy, said Amanda Haes, a co-author of the study. At present, Alzheimer's can only be accurately diagnosed by examining the brain after death. Haes, a postdoctoral researcher at the Naval Research Laboratory in Washington, conducted the study while she was a graduate student at Northwestern under the direction of Richard Van Duyne.

The findings were presented Wednesday during the 230th annual meeting of the American Chemical Society."

Source: New Alzheimer's disease research reported. UPI, ScienceDaily.com (31 August 2005) [FullText]

"Q: I've heard aluminum cookware is associated with a number of health problems. We have a set of premium aluminum pans. I'm wondering if this poses similar problems, and whether I should replace it. I've even noticed that this company's product literature has dropped the word aluminum and just says that their cookware is "hard-anodized."

A: This question about potential dangers from aluminum cookware has come up periodically during the 15 years that I have been writing this column. It continues to be a fear based on circumstantial evidence rather than a situation with scientific proof of cause and effect.

There is no question that the concern is serious, as it involves Alzheimer's disease -- an as-yet incurable, progressive loss of mental faculties brought about by a breakdown in brain tissue. The circumstantial evidence is that brain tissue from Alzheimer's patients contains an abnormally high concentration of aluminum -- 30 times greater than an individual without the disease. There is, however, no real evidence that exposure to aluminum through diet is what's responsible for this incurable disease. An alternative explanation would be that the accumulation of aluminum is a result of a disease process brought on by other factors that are independent of what type of cookware you use and how much aluminum is in the diet. At present, it appears as though the latter explanation is the case.

One part of the puzzle is that the level of aluminum in the blood, hair and skin remains normal in Alzheimer's patients. This would seem to indicate that we are not dealing with aluminum "toxicity" as much as a malfunction in brain tissue that results in aluminum accumulation.

It is also important to consider that aluminum is present throughout our environment. In fact, it's the third-most-common element in the earth's crust, and naturally occurs in plants and animals. It's contained in a number of food additives and is also found in medications such as popular antacids, as well as in deodorants. To put this in perspective, a study in the journal Food Additives and Contaminants (Jan.-Feb. 1995) reported that if you were to take an entire day's food supply, store it in aluminum containers, prepare it in aluminum cookware and wrap it in aluminum foil, the daily aluminum intake would be approximately 6 milligrams. The tolerable weekly intake set by a joint Food and Agriculture Organization/World Health Organization expert committee is 7 milligrams per kilogram of body weight. This is the equivalent of 68 milligrams of aluminum per day for a 150-pound adult.

To answer your specific question, the new breed of hardened (anodized) aluminum is considered safe for all foods, including high-acid foods. This means that little or no aluminum is brought into the food irrespective of the type of food prepared in such cookware. This effectively moves hardened-aluminum cookware even further down the suspect list. I cannot really comment on the change in advertising literature, but it may be the company's desire to distinguish its product from other forms of aluminum cookware -- even though the connection between eating foods prepared with aluminum cookware and the risk of disease has yet to be established.

Q I have been curious about the number of calories it takes for the human body to heat up the water it consumes and why a person could not burn up calories -- and thus lose weight -- by drinking cold water. As I recall, a calorie is the amount of heat it takes to raise one gram of water one degree Celsius. If a person drank a cup (227 grams) of cold water that was at 5 degrees C (41 degrees F), and the natural functions of the body raised the temperature of the water to 37 degrees C (98.6 degrees F), then wouldn't the body burn up 7,264 calories (227 times 32) in this way? With the hot summer here, I was hoping to lose some weight this lazy way. Why can't I?

A That would have to be the ultimate diet: snack on a few ice cubes and watch the calories melt away. It is true that the body seeks to maintain its normal operating temperature of about 98.6 degrees F (37 degrees C), the temperature at which most chemical reactions are designed to take place. Also true is that calories are expended heating up water or any other cold food. The downside is that the amount used in this task is not the amount you projected -- your diet hopes fall victim to the big "C"/little "c" caloric confusion.

The calorie (note the lowercase "c") is a unit of energy in the metric system, and it is defined as the amount of heat required to raise one gram of water one degree Celsius. The calorie used for food energy or physical activity is actually a kilocalorie, or 1,000 of the small "c" calories. It should be indicated by a capital "C" at the start of the word. Nutrition-facts labels correctly use the uppercase "C," but the distinction is often lost on the public. Add to this the fact that common parlance has blended the two together, and in the minds of average consumers a calorie is a Calorie is a calorie. Scientists use the term "kilocalorie" to avoid confusion.

The bottom line is that your water-heating exercise would use up approximately 7,264 calories (again, note the small "c"), but this is the equivalent of just 7.264 big "C" Calories, which is less than a gram of fat. Sorry to put such a chill on your revolutionary diet plan.

Q: We are having a chicken dispute. Does removing the skin from chicken before you eat it get rid of the cholesterol? Also, I grill the chicken with the skin on to keep it from drying out, having the option of removing it before the meal. How does this compare with removing the skin prior to cooking?

A There is a small amount of cholesterol in the skin and fat of chicken, though most is found in the light and dark meat. This holds true for beef, pork and lamb as well. Buying leaner cuts does little to reduce the cholesterol in the meal.

But don't be too concerned. Research points to the level of fat in the diet -- especially partially hydrogenated fat and saturated fat -- as having more of an effect on our blood cholesterol than the amount of cholesterol we eat. Staying active while making sure your diet is well-balanced with fruits, vegetables, grains, nuts and seeds is the best move.

Regarding grilling, having tried it both ways, I favor keeping the skin on during grilling for flavor and to prevent dryness. The skin can be removed, if desired, once cooking is completed. Avoid overcooking, of course, keeping in mind that the food continues to cook once removed from the grill.

E-mail inquiries for Kensington resident Ed Blonz to cctimes@blonz.com. Blonz, Ph.D., is a nutrition scientist and the author of "Power Nutrition" (Signet, 1998)."

Source: Ed Blonz: On Nutrition. No connection between Alzheimer's and aluminum in food preparation. (17 August 2005) [FullText]

"Description
Alzheimer's disease – after heart disease, cancer and stroke – is the fourth leading cause of death in the United States of America and the most common form of dementia.

This incurable brain disease was named after the German physician Alois Alzheimer, who identified it in 1907. The disease, marked by a progressive degeneration of brain tissue, primarily affects people over the age of 65. In such cases it is known as late-onset Alzheimer’s disease. It has also been reported among people in their 50s, 40s and – rarely – 30s (early onset). Nearly all people with Down syndrome will develop this disease if they live into their 40s.

Eventually, people suffering from Alzheimer’s disease lose the ability to think, reason and co-ordinate movement, and become incapacitated over the course of five to eight years. 10% of people over the age of 65 years and 20% of those over 75 suffer from this or another form of dementia.

Cause
The causes of Alzheimer’s disease are not fully known and scientists continue to investigate this area. So far, research into the causes of this brain disease has found two main forms of neural damage or abnormalities that can be linked to the disease and its progression.
Genetic studies have shed new light on possible causes of Alzheimer's disease, but these must be researched further. Aluminium and zinc as causes were the topics of controversial studies and are discussed in less detail.

Tangled nerve cell fibres (neurofibrillary tangles)
Microscopic study of the brain of a person who has died from Alzheimer’s disease reveals tangled nerve cell fibres in certain areas of the brain. (Nerve cell fibres are typically found inside nerve cells.) As the nerve fibres become tangled, protein deposits called plaques build up in the affected tissue. A protein called tau is found in the tangles. Scientists are not sure how these neurofibrillary tangles are formed, but they are characteristic of the condition.

Senile or neuritic plaques
These patches are situated outside the nerve cells and are surrounded by dying neurons (nerve cells). The plaques contain a sticky protein, beta amyloid, which cause malfunctioning of nerve cells that eventually results in death of these cells. The plaques are made of amyloid precursor protein (APP) molecules, which are usually essential components of the brain. Plaques are formed when an enzyme takes APP apart at a specific location and leaves the fragments (beta amyloid) in brain tissue, where they deposit abnormally. The presence of neuritic plaques may be linked to a reduction in acetylcholine, an important chemical that is instrumental in relaying messages in the brain.

Genetics
The association between Down syndrome and Alzheimer's disease has led scientists to look for genetic factors on chromosome 21, the chromosome involved in Down syndrome. Chromosomes are found in each cell in the body and carry the hereditary information (genes). Other chromosomes that scientists have studied in relation to Alzheimer’s disease include chromosomes 14 and 19. The study of chromosome 19 is the most significant. It was on this chromosome that scientists discovered the ApoE-e4 gene, a well-known marker for heart disease that is commonly found in people who developed Alzheimer's disease at age 65 years or older. The gene was less likely to be found in people who did not have Alzheimer's disease. These findings led scientists to believe that people with this gene might be more susceptible to Alzheimer's disease, although it is not a definite indicator that such people will develop the disease.

Aluminium
Some researchers found increased levels of aluminium, mercury and other metals in the brains of victims of Alzheimer’s disease. This led to a controversial theory suggesting that the ingestion of small particles of one of these metals, especially aluminium, may lead to the development of Alzheimer's disease. However, much more research is necessary to determine whether aluminium build-up is a cause or a result of Alzheimer’s disease and to better understand the exact role of this and other metals in the development of the disorder.

Zinc
Zinc is the focus of another controversial theory about the possible causes of Alzheimer's disease. Studies suggesting a link between zinc and improved mental alertness in the elderly led scientists to give Alzheimer's disease patients zinc supplements in a 1991 study. However, after only two days the patients’ mental abilities deteriorated rapidly. A few years later, laboratory tests revealed that zinc could make proteins form clumps similar to the plaques found in the brains of Alzheimer's disease sufferers. This needs to be further investigated, as scientists are not sure yet whether the plaques actually cause the disease or whether they are a result of it.

Symptoms
Symptoms of Alzheimer's disease vary greatly from person to person, but a few general symptoms can be distinguished. The symptoms are closely related to the various stages of the disease.

Early stage
During this period, usually the first two to four years, symptoms are slow and gradual and can be mistaken for the normal ageing process. Early signs of memory loss characterise this period and may include forgetting names or events. Affected people may also have difficulty following directions and be disoriented. Changes in their normal behaviour and personality can be noted and they are no longer able to perform routine tasks.

Later stage
In this stage, people may suddenly lose their inhibitions, no longer be able to solve simple problems and have trouble with figures. Adapting to simple changes becomes a problem and the afflicted may become confused and disoriented, not knowing what month or year it is and not being able to describe accurately where they live or recall correctly the name of a place recently visited.
Emotionally, Alzheimer sufferers become increasingly suspicious and paranoid. They can no longer control their anger, frustration or inappropriate behaviour and become increasingly quarrelsome, irritable and agitated. They can also no longer dress appropriately and neglect their personal appearance.

Final stage
Severe impairment of intellectual abilities are typical of the final stage of the disease. Physical functioning deteriorates and sufferers become incontinent (unable to control bowel and bladder function). They can no longer engage in conversation, are erratic and inattentive and appear unco-operative. In the final stage they become incapable of looking after themselves and become bedridden or wheelchair-bound. They are often not able to feed themselves and have to be fed. Death is usually the result of pneumonia or another illness that occurs when health has deteriorated severely.

Prevalence
The prevalence of Alzheimer's disease is closely linked to age and dramatically increases with age. 10% of all persons older than 65 years have Alzheimer's disease and 50% of those older than 85 years. It strikes three times as many women as men.

Course
The average duration of the illness is nine years, but it can run its course in just a few years or take as long as 20 years.

Risk Factors
Increasing age is the main risk factor for Alzheimer's disease.
Other risk factors include a family history of dementia and previous head trauma.

When to see a doctor
If a family member or friend displays signs of Alzheimer’s disease over time, you must call your doctor. The person may have a lack of insight that is characterised by not knowing that he or she has the disease and denying the assistance of other people. Thus, the affected person may have to be persuaded to visit a doctor for help.

Diagnosis
It is most important that a doctor should diagnose Alzheimer’s disease, as many other treatable conditions (such as hypothyroidism, vitamin deficiency, hypoglycaemia, anaemia and depression) have symptoms similar to Alzheimer's disease. Other causes of Alzheimer's disease-like symptoms include an adverse reaction to prescribed medicine or a harmful combination of medicines.
To check whether a person has Alzheimer’s disease, the doctor will first do a memory test and then a physical examination in order to eliminate other possible causes of the patient’s mental impairment. Therefore the clinical diagnosis of Alzheimer's disease is a diagnosis by exclusion. Verbal tests, as well as interviews with family members may be the next step, although these methods will not yield definitive results.

Other tests to diagnose possible Alzheimer's disease should include:

Blood tests
Brain scan
Electrocardiogram (ECG, a recording of the electric activity of the heart)
Electroencephalogram (EEG, a recording of the electric activity of the brain)
Brain scans can provide valuable information about the brain. These include:
Computerised axial tomography (CAT) – to exclude disorders with similar symptoms to Alzheimer's disease. CAT scans may reveal changes that are characteristic of the disease.
Magnetic resonance imaging (MRI) – this type of scan provides information about physical structure and chemicals, distinguishes between moving blood and static brain tissue and may add diagnostic information.
Positron emission tomography (PET) – a new instrument that researchers can use to learn more about the brain. It can provide information about blood flow in the brain, metabolic activity and the way that specific receptors are distributed in the brain.
Single photon emission computerised tomography (SPECT) – another instrument available to researchers to help them look for the abnormalities typical of Alzheimer’s disease.
Treatment
There is no cure for Alzheimer's disease. Certain medicines can improve memory and slow the progression of the disease in the early stages, and others can alleviate mood changes and other behavioural problems associated with the disease. The goal of treatment in Alzheimer's disease is to manage the symptoms as far as possible.
Medication
Aricept (donepezil hydrochloride), Exelon (rivastigmine) and Reminyl (galanthamine) work by slowing the breakdown of acetylcholine, the chemical that helps the neurons communicate with one another. It may help improve memory to some extent in people with mild to moderate Alzheimer’s disease.
A number of drugs can alleviate specific symptoms. Antidepressant and antianxiety medications can be prescribed.

Home
The immediate environment of the Alzheimer's disease sufferer can play an important role in helping him or her cope with the disease. It is important that family members who are looking after the person in the final stages of the illness take note of this and modify the surroundings to reduce stress from environmental factors.
Family members of people with Alzheimer's disease can do the following:

Provide balanced nutrition and plenty of fluids.
Keep pills and poisons away.
Keep instructions simple and short.
Promote a feeling of safety. Keep the living environment familiar and stable by sticking to a routine.
Keep visual clues to time and place, such as calendars, clocks and pictures of the season.
If you have to leave the house, leave reminder notes and simple directions which your relative can easily follow and remember.
Label objects.
An ID bracelet with a phone number is indispensable for people with Alzheimer's disease because they are inclined to wander and get lost.
As long-term memory is better than short-term memory in the early stages of the disease, the person may enjoy reminiscing about pleasant past memories. Use family photo albums, old magazines and favourite family stories to bring these memories to the fore.
Looking after an Alzheimer's disease patient can be an emotionally draining experience for family members. If you are caring for someone with Alzheimer's disease, relief from ordinary day-to-day chores in the home may help you cope with the deterioration of a loved one. The role of support groups and social workers cannot be overemphasised in this regard.

Prevention
Prevention of Alzheimer's disease is very difficult, as there is no known cause. Although genetics is a possible cause, this does not mean that if Alzheimer's disease has claimed some members of a family that all the other members will develop it.

If you are concerned about developing Alzheimer’s disease, the best thing to do is to have a healthy lifestyle. Eat a balanced diet and exercise regularly to keep your body, including your brain’s nerve cells, in shape. Studies suggest that highly educated or mentally active older people are less likely to fall prey to this debilitating disease. If possible, avoid cigarette smoke and air pollution. Avoiding these substances minimises your exposure to free radicals (highly reactive molecules) that have been implicated in the formation of plaques.

Vitamin E has been shown to delay disease progression in the later stages of Alzheimer's disease and this effect can be ascribed to the anti-oxidant properties of this vitamin. Some centres recommend a dose of 400 IU per day as a possible preventative measure.

Ginkgo biloba and omega-3 fatty acids may also have some preventative role in Alzheimer’s disease.

Do not limit your daily intake of zinc in accordance with the theory that explores a link between this mineral and Alzheimer’s disease. Zinc is an important mineral and although you should not take an overdose of it, restricting your intake to below the recommended daily allowance (15 mg for men and 12 mg for women) will do more harm than good.

Recent studies have highlighted a link between oestrogen and Alzheimer's disease, suggesting that this hormone may have a protective effect against Alzheimer's disease in that it may help preserve and even stimulate the production of acetylcholine, a chemical that helps to transmit messages in the brain. It seems that women who took oestrogen in the past or who are taking it have a lower risk of developing the disease than other women have.

Reviewed by Dr Frans Hugo, MBChB, M.Med Psychiatry."

Source: Alzheimer's disease. Reviewed by Dr Frans Hugo. Health24.com (last viewed 25 August 2005) [FullText]

"Knowing they'll need a nest egg for later years, sensible middle-aged adults may put their stockbroker on speed-dial and keep 401(k) updates handy.

But how about building a "cognitive reserve" account their brain can draw on at older ages when memory problems are most serious?

It's more than just a clever idea. Animal studies and rapidly growing human evidence suggest that adults might be able to delay or prevent severe cognitive decline, says Molly Wagster, who directs research on normal brain aging at the National Institute on Aging. "There are no guarantees yet, but it's really looking like some of these things could work."

Possible resources for the brain include:

• Mental stimulation.
• Higher education.
• Leisure activities.
• Aerobic exercise.
• Antioxidant-rich foods such as blueberries and spinach.

There's also "overwhelming evidence" of a link between high blood pressure or diabetes and dementia, says Zaven Khachaturian, senior science adviser to the Alzheimer's Association.

Cutting-edge research on the payoffs of planning ahead for people who may live to be 80 or longer will be reported at the American Psychological Association meeting starting today in Washington, D.C.

"We've been surprised to find out how malleable the brain is," says psychologist Randy Buckner of Washington University in St. Louis.

The evidence that mentally challenging lives boost brain power comes from large, worldwide samples of people who have been followed over time. Scientists compare those who maintain good mental function with those who don't. Very few controlled clinical trials have been done, so conclusive evidence on preventing dementia does not exist.

However, animal research, some newer types of brain scans and human autopsy findings tend to support the population findings, Wagster says.

"What we have is fairly compelling and worth paying attention to now," says neurologist David Bennett of Rush University Medical Center in Chicago. "Don't wait till you're 80."

His long-running study of Catholic nuns, priests and brothers shows that the more formal education a person has, the more amyloid plaques — clumped protein fragments typical of Alzheimer's — it takes to produce a given level of memory impairment.

"This doesn't mean you should quit your job and go get a Ph.D.," he says. "Education probably relates to how you use your brain throughout life — your job and leisure activities that stretch the mind."

Additionally, the more plaques found at autopsy, the bigger the difference education made on the person's cognitive test scores.

Leisure pursuits also matter. Several studies have found that stimulating fare such as doing crossword puzzles, going to museums and reading helps stave off memory problems.

Just keeping busy seems to tune the brain, says neuropsychologist Yaakov Stern of Columbia University College of Physicians and Surgeons. Stern followed 1,800 older adults for up to seven years. The more leisure pursuits they engaged in — even just visiting friends, playing cards or going to the movies — the lower their risk of developing Alzheimer's. From the start, he accounted for scores on memory tests, strokes, high blood pressure, diabetes and other health limitations to make sure poor health or memory wasn't the cause.

Stern also conducted studies using high-definition PET brain scans of adults with the same cognitive ability scores and found greater physical changes linked to Alzheimer's disease in those with better educations. In other words, better-educated people can sustain more brain damage before they lose mental ability.

"I'm convinced they have resources that provide a reserve," Stern says.

Adults who lead stimulating lives may develop more neurons, more connections between neurons or more efficiency in using their brain cells so they need fewer, Bennett says. They also may create needed detours around brain blockages in response to the demands of daily life, much in the way a commuter is able to find quicker routes home. Bennett's team is now counting neurons and the links between neurons in brains of deceased study participants to shed more light on what's happening.

Exercise plays a role

Mental and social stimulation is not the whole story in preserving brain function. There's evidence that aerobic exercise is beneficial.

Walking 45 minutes three times a week for six months significantly improved mental ability of older adults with no dementia; a randomly selected control group that did stretching and toning had no change, says study leader Arthur Kramer, a psychologist at the University of Illinois.

Brain scans taken before and after show growth in two regions of the walkers' brains that typically shrink with aging and work less efficiently. "They looked two to three years younger in brain volume after six months," Kramer says.

Nobody knows exactly why aerobic exercise affects the brain. In animal studies, exercise increases proteins that multiply the connections between neurons and even prompt the birth of new brain cells. Aerobic activity also improves the functioning of chemicals that help neurons to communicate with each other, Kramer says.

And exercise helps brain function by reducing blood pressure and the risk of diabetes.

Add diet to the mix

Animal studies suggest that diet also can make a difference: antioxidant-rich foods apparently help. But a stimulating environment combined with antioxidants works even better, Wagster says.

At UCLA, psychiatrist Gary Small is betting a program combining nutrition with mental and physical exercise will improve memory. His two-week "boot camp" combines dietary changes with physical activity, mental "aerobic" exercises, memory strategies and stress relief techniques.

Brain scans taken before and after show participants have more efficient cell activity in a part of the brain that controls everyday, or "working," memory, Small says.

One of his success stories is 46-year-old Michele Rubin of Beverly Hills, who scored average on memory for her age at the start but scored average for a 20-year-old after the program.

Rubin, a former pharmacist, is raising three teenagers and doing hospital volunteer work.

"A few years ago, I started feeling like I wasn't as sharp as I used to be, she says. "I was forgetting things. I'm very busy, but I basically did nothing for myself — not reading, not taking care of my mind was just part of it."

Rubin calls last fall's program "life-altering." She started going to a gym, eating a lower-fat, more nutritious diet, using memory strategies and reading serious non-fiction. She's buying crossword puzzles at the airport now and forcing herself to help the children with algebra.

"I feel like I'm stretching my mind, and I'm remembering more," she says.

Rubin won't take calls at her busy home when many others are in the room and she's apt to be interrupted. She goes into her home office.

"I wasn't concentrating, so I'd forget things. ... I feared I was about to be committed to some old-age home," she says. "Now I feel much better about myself."

That sense of control alone could bode well for staying mentally fit. Adults who believe mental decline is not inevitable as they age are much more likely than fatalists to use helpful strategies on memory tests, says Margie Lachman, chairman of the psychology department at Brandeis University.

"Anybody who uses these strategies would do better," she says. Her lab tests adults 25 to 85 years old. "Over 40, beliefs make more of a difference in test scores. Older adults with negative beliefs just give up quicker, they don't persist, and they don't do as well."

Even as many pine for their youthful brains, they may not be needed to function well at 70. Brain scan studies show that mentally sharp older people more often recruit different areas of their brains than younger adults to do the same mental task, says cognitive neuroscientist Roberto Cabeza of Duke University.

"The older brain can reorganize to cope with changes," he says.

Never too late?

It's not even hopeless for sedentary people in their 70s. University of Illinois psychologist Denise Park conducted an eight-week program teaching digital photography or quilting to elderly adults. On completion, they improved significantly on mental ability tests, compared with a control group that did nothing new.

The potential for preventing or delaying dementia by building brain reserve earlier in life is tantalizing, Park says.

Population studies show that 40% to 50% of people older than 85 have Alzheimer's disease, according to Rush University Medical Center epidemiologist Denis Evans, who specializes in the disease. About 76 million baby boomers are headed there.

Says Park: "Even very modest delays of mental decline could have a huge impact on public welfare.""

Source: Want Alzheimer's free Mind for Your Golden Years? Start Now. USA Today. (17 August 2005) [FullText]

"The fraternity brothers of the Northwest Missouri State University and Missouri Western State University Chapters of Tau Kappa Epsilon International Fraternity are going to have a warmer run and an earlier start this year, when they will team up once again to hold their seventh annual "Running Past the Rivalry" Football Run to raise money for the Reagan Research Institute for Alzheimer's disease.

The run began six years ago as a brainstorm between the two Chapters to increase the contribution they could make to the recognized philanthropy of TKE. In 2001, the international fraternity adopted the Alzheimer's Association as its newest philanthropy to commemorate and honor former U.S. President and key alumni of TKE Ronald Reagan, who announced his affliction with the disease in November 1994 and passed away from complications with Alzheimer's on June 4, 2004.

Alzheimer's disease is a heart-wrenching disease that affects an entire family. Over four million Americans have Alzheimer's disease, and it is estimated that 14 million Americans will have the disease by the middle of this century unless either a cure or better methods of prevention are found.

The Reagan Research Institute for Alzheimer's disease was developed by Tau Kappa Epsilon International Fraternity in 2002 with the fraternity pledging to raise $240,000 to aid Alzheimer's research. TKE Chapters across the country raise money to this end. The Reagan Research Institute is a portfolio of funded projects within the Alzheimer's Association Grant Program that serves as a paradigm for one key principle of the entire research effort - a commitment to innovate basic science by exploring the broadest possible spectrum of approaches in developing Alzheimer's treatments.

On September 17, prior to the game, members of the Northwest Missouri State University Chapter of TKE will be running the football 43 miels from Rickenbrode Stadium on the Northwest Missouri State University campus to Spratt Stadium on the Missouri Western State University campus. Both chapters will then present the game ball to game officials and announce their total amount raised, giving credit to generous donors to the event.

Combined together, the two chapters have a goal of raising $2,000 this year for Alzheimer's. They hope to reach half of that goal with Football Run donations alone.

In the past, TKE has raised thousands of dollars for both the Special Olympics and the Alzheimer's Association through these efforts.

For more information, or to make a contribution, contact Jordan Lenger, President of the Northwest Missouri TKE Chapter at (660) 541-1438 or s255771@mail.nwmissouri.edu, Jeremy Funk, President of the Missouri Western TKE Chapter at (816) 294-9640 or funkster31@yahoo.com, or TKE Football Run Coordinator Fred Cline at (660) 535-4458 or fac2706@missouriwestern.edu."

Source: Northwest, Mo. West fraternities to hold 'Running Past the Rivalry' Football Run. Maryville Daily Forum - Maryville,MO,USA (last viewed 24 August 2005) [FullText]

"Irvine, Calif. - Adults who eat the daily recommended allowance of folates -- B-vitamin nutrients found in oranges, legumes, leafy green vegetables and folic acid supplements -- significantly reduce their risk of developing Alzheimer's disease, according to results from a long-term National Institute on Aging study of diet and brain aging.

The study also found that folates appear to have more impact on reducing Alzheimer's risk than vitamin E, a noted antioxidant, and other nutrients considered for their effect as a brain-aging deterrent.

Maria Corrada and Dr. Claudia Kawas of UC Irvine's Institute for Brain Aging and Dementia led the effort, which analyzed the diets of non-demented men and women age 60 and older. They compared the food nutrient and supplement intake of those who later developed Alzheimer's disease to the intake of those who did not develop the disease. It is the largest study to date to report on the association between folate intake and Alzheimer's risk and to analyze antioxidants and B vitamins simultaneously.

Results appear in the inaugural issue of the quarterly peer-reviewed research journal, Alzheimer's & Dementia: The Journal of the Alzheimer's Association.

"Although folates appear to be more beneficial than other nutrients, the primary message should be that overall healthy diets seem to have an impact on limiting Alzheimer's disease risk," said Corrada, who like Kawas started with the study while at Johns Hopkins University in Baltimore.

The researchers used data from the Baltimore Longitudinal Study of Aging to identify the relationship between dietary factors and Alzheimer's disease risk. Between 1984 and 1991, study volunteers provided detailed dietary diaries, which included supplement intake and calorie amounts, for a typical seven-day period.

Ultimately, 57 of the original 579 participants developed Alzheimer's disease. But the researchers found that those with higher intake of folates, vitamin E and vitamin B6 shared lower comparative rates of the disease. And when the three vitamins were analyzed together, only folates were associated with a significantly decreased risk.

In turn, no association was found between vitamin C, carotenoids (such as beta-carotene) or vitamin B-12 intake and decreased Alzheimer's risk.

"The participants who had intakes at or above the 400-microgram recommended dietary allowance of folates had a 55-percent reduction in risk of developing Alzheimer's," said Corrada, an assistant professor of neurology. "But most people who reached that level did so by taking folic acid supplements, which suggests that many people do not get the recommended amounts of folates in their diets."

Folates have already been proven to reduce birth defects, and research suggests that they are beneficial to warding off heart disease and strokes. Although folates are abundant in foods such as liver, kidneys, yeast, fruits (like bananas and oranges), leafy vegetables, whole-wheat bread, lima beans, eggs and milk, they are often destroyed by cooking or processing. Because of their link to reducing birth defects, folates have been added to grain products sold in the U.S. since 1998. But even with this supplement, it is thought that many Americans have folate-deficient diets.

Recent research is beginning to show relationships between folates and brain aging. Earlier this year, Dutch scientists showed that adults who took 800 micrograms of folic acid daily had significant improved memory test scores, giving evidence that folates can slow cognitive decline.

"Given the observational nature of this study, it is still possible that other unmeasured factors also may be responsible for this reduction in risk," said Kawas, the Al and Trish Nichols Chair in Clinical Neuroscience. "People with a high intake of one nutrient are likely to have a high intake of several other nutrients and may generally have a healthy lifestyle. But further research and clinical studies on this subject will be necessary."

Judith Hallfrisch of the U.S. Department of Agriculture, Denis Muller with the National Institute on Aging and Ron Brookmeyer with Johns Hopkins collaborated on the study, which was originally undertaken at the Gerontology Research Center of the NIA and the Department of Neurology at Johns Hopkins. Study funding came from the Extramural Programs of the NIA.

Begun in 1958 by the NIA, the Baltimore Longitudinal Study of Aging is America's longest-running scientific study of human aging. BLSA scientists are learning what happens as people age and how to sort out changes due to aging from those due to disease or other causes. More than 1,400 men and women are study volunteers. For more information, see: www.grc.nia.nih.gov/​branches/​blsa/​blsa.htm.

The original news release of 12 August 2005 can be found here."

Source: Folates More Effective In Limiting Alzheimer's Disease Risk Than Antioxidants, Other Nutrients. ScienceDaily.com (17 August 2005) [FullText]

"HAMPTON - The Hampton University School of Pharmacy will use a $400,000 federal grant to work on a blood test that could help diagnose Alzheimer's disease at an earlier, more treatable stage. HU scientists plan to study a specific protein in blood - called the abeta peptide - that appears to damage brain cells and cause a loss of memory and function. With money from the National Institute of General Medical Sciences, HU will partner with the Alzheimer's Disease Research Center at Baylor College of Medicine in Texas.

Because there's no simple or single test available to diagnose Alzheimer's, primary-care doctors often don't recognize the progressive brain disorder in people with mild or even moderate dementia. They have to rely on cognitive tests and reports of behavior changes such as anxiety, forgetfulness, confusion and sudden mood swings. "The problem is that by the time a change in behavior is observed, the protein has already damaged the neurons, and treatment is not as effective," said Dr. Chengan Du, an assistant professor at the HU School of Pharmacy and principal investigator on the grant.

Using advanced blood-testing tools, Du said, "we plan to develop an analytical method to measure the concentration of amyloid beta (Abeta) protein." If there's a clear link between high levels of Abeta protein and development of symptoms, doctors could run blood tests and, if appropriate, immediately start medicine to stall the disease.

"We hope our research ultimately leads to the identification of biomarkers" for Alzheimer's, said Corrine Ramaley, an assistant professor at HU and co-investigator on the grant. Alzheimer's disease affects an estimated 4.5 million Americans, a number that has more than doubled since 1980 as the population continues to age. The illness gradually destroys memory and the ability to learn, reason, communicate and carry out daily activities.

There's no cure, but drugs and lifestyle changes can improve quality of life.

For more information about Alzheimer's research at the HU School of Pharmacy, call 728-6791 or 728-6683."

Source: Alison Freehling. HU gets $400,000 grant to develop Alzheimer's test. DailyPress.com (17 August 2005) [FullText]

"The first hints of impending Alzheimer's include not just forgetfulness but lags in attention and other subtle problems that can show up 10 years before an official diagnosis, a study out Monday says.

The new report underscores the scientific view that Alzheimer's begins to injure the brain years before the hallmark symptoms of severe memory loss appear, says William Thies, spokesman for the Chicago-based Alzheimer's Association. Very early identification of Alzheimer's could become even more important in the future if researchers develop therapies that delay this degenerative brain disease, he says.

Such therapy is urgently needed: The population of Alzheimer's victims is expected to rise from 4.5 million to as many as 16 million people by the year 2050.

Alzheimer's warning signs

• Serious memory loss. People with Alzheimer's frequently forget appointments, telephone numbers and important information.
• Difficulty performing everyday tasks. They might not remember how to complete a familiar routine.
• Problems with abstract thinking. Those with Alzheimer's can't do simple math; they might forget what the numbers represent.
• Confusion. They can get lost coming home from a familiar place.
  Source: William Thies of the Alzheimer's Association. For more information, call 800-272-3900.

Lars Bäckman of the Karolinska Institute in Stockholm and his colleagues grouped together the findings from 47 scientific studies. They found a pattern of subtle thinking deficits that seemed more common in people destined to get Alzheimer's. The team homed in on 1,207 older people who had been given cognitive tests years before getting a diagnosis. They compared them with 9,097 older people who had been given the same tests but who stayed healthy.

The team's meta-analysis, a powerful statistical method that culls results from many studies, revealed that the people who would later develop Alzheimer's showed small deficits in memory, a finding that fits with what is known about the way Alzheimer's affects the brain.

Full-blown Alzheimer's attacks the hippocampus, the brain's memory region, Bäckman says. But at very early stages, the disease has yet to produce serious damage: Thus forgetfulness is minor, he says. For example, people might have trouble remembering what they had for breakfast but can still keep track of important appointments.

The team also found a raft of other difficulties, a finding that suggests the disease attacks other brain regions as well. For example, people destined to get Alzheimer's scored poorly on tests of executive function, the ability to plan ahead or multitask.

The people who ended up with Alzheimer's also took longer to solve problems and did a little worse on tests of verbal ability, Bäckman and his colleagues report in the July Neuropsychology.

But the slight deficits in memory and speed could easily be written off as an age-related decline, Bäckman says. Old age itself can produce minor lapses in memory and a slowdown in mental agility, he says.

Researchers have yet to develop a test that reliably identifies people who will develop Alzheimer's in the future, says Ronald Petersen, an Alzheimer's expert at the Mayo Clinic in Rochester, Minn.

Drugs available now do not slow the disease, so there is no rush to find people at this preclinical stage. But that may change if therapies in the pipeline pan out, Petersen says. Then an early diagnosis combined with treatment could stop the disease before a great deal of damage occurs.

"We want to give people lots of time to aggressively treat this disease that makes your brain rot," Bäckman says."

Source: Kathleen Fackelmann. Signs found 10 years in advance of Alzheimer's. USA Today (31 July 2005) [FullText]

"WESTON, Mass. (17 August 2005) According to an article in the Summer 2005 issue of Activities Directors' Quarterly, individuals in the beginning to middle stages of Alzheimer's disease greatly benefit from a daily, structured activity program.

The Smiles Club, a program for Sisters of St. Joseph, was designed to create a structured environment of enjoyment and activity for Alzheimer's patients. Participants meet daily for five-and-a-half hours of dynamic programming that utilizes the interests of staff members. Daily activities include memory box, painting, crossword puzzles, and singing.

After one year in the program, seventy percent of participants either improved or remained stable. A daily, structured activity program of activities is one of the most powerful, effective interventions for Alzheimer's disease. Participation in such programs slows functional decline and improves patients' quality of life.

These findings underscore the need for more research in this area."

Activity Directors' Quarterly,
470 Boston Post Road,
Weston, MA 02493,
USA
(781) 899-2702
http://www.activitiesdirectors.com

Also see this Press Release at PRNewswire.

"Several cholesterol-related genes, not just the APOE one, have been implicated in Alzheimer's disease and may eventually be used to predict who is going to develop the illness.

The e4 variant of the APOE gene has been strongly linked with susceptibility to Alzheimer's disease. Indeed, one-fourth of the population is estimated to carry this variant. What fewer people are aware of, however, is that the APOE gene is also known to be the major transporter of cholesterol in the blood and central nervous system and a risk factor for coronary disease.

Now a number of other genes involved in cholesterol metabolism appear to be involved in Alzheimer's susceptibility as well, a new study suggests. However, the APOE gene still seems to be the biggest culprit.

The study was led by Andreas Papassotiropoulos, M.D., a psychiatrist and research professor at the University of Zurich in Switzerland. Results appeared in the July Journal of Clinical Psychiatry.

Papassotiropoulos and his colleagues enrolled more than 500 older persons from Switzerland and Greece. Half had been diagnosed with Alzheimer's disease; the other half did not have the illness. The researchers then analyzed DNA samples from these subjects to assess 12 single nucleotide polymorphisms—that is, variants in genetic material—from 11 genes related to cholesterol metabolism and previously linked to Alzheimer's disease. One of the single nucleotide polymorphisms was the APOE e4 variant.

The scientists also examined the DNA samples to see whether they contained 48 single nucleotide polymorphisms that had never been linked with either cholesterol or Alzheimer's.

Finally, they looked for links between any of the single nucleotide polymorphisms and the presence of Alzheimer's.

They found that nine of the 12 single nucleotide polymorphisms previously implicated in cholesterol metabolism and Alzheimer's were also significantly associated with Alzheimer's in their study.

In contrast, they were not able to find any association between Alzheimer's and the 48 single nucleotide polymorphisms not previously tied to cholesterol and Alzheimer's.

Moreover, they found that some of the nine single nucleotide polymorphisms were more strongly associated with Alzheimer's than the others were. The APOE e4 gene variant headed the list. Then came material from a gene called SOAT1. Then came material from the APOE promoter.

"This study is potentially important for several reasons," Eric Reiman, M.D., a professor of psychiatry at the University of Arizona and deputy editor of the Journal of Clinical Psychiatry, asserted in an editorial accompanying the report. For example, "It implicates a cluster of genes, including, but not limited to, the APOE e4 allele, in the susceptibility to late-onset Alzheimer's disease."

Also, he added, "It provides further support for the role of higher cholesterol levels in the pathogenesis of Alzheimer's disease and the potential role of cholesterol-lowering strategies in the treatment and prevention of this disorder."

However, as Reiman cautioned in an interview with Psychiatric News, the findings will not be used clinically any time soon to predict Alzheimer's for several reasons—they have not yet been replicated, "they do not predict with sufficient certainty whether or when a person might develop symptoms," and "they don't yet tell the person what he or she might be able to do to prevent the disorder."

In fact, he said, testing for the APOE e4 variant alone to predict Alzheimer's risk is not recommended for clinical use at this point because of the danger of triggering false alarms or creating false reassurances, and because no preventive measures are available.

Josepha Cheong, M.D., an associate professor of psychiatry at the University of Florida and chair of the APA Council on Aging, told Psychiatric News that the study impressed her for several reasons. For one, the researchers attempted to identify the interplay of a cluster of genes that may be involved in the etiology and clinical presentation of Alzheimer's disease instead of looking for the effect of a single gene at a time, which is more common. For another, she believes that the study "represents a continuation in the discovery of genes involved in the pathogenesis of Alzheimer's disease." And finally, whereas the "research results may not be acutely clinically relevant, they portend significant possibilities for diagnosis and treatment."

Meanwhile, Papassotiropoulos said, "I anticipate that several genetics groups will attempt to replicate the findings, among others Dr. Jonathan Prince from the Karolinska Institute in Sweden. There are [also] several [other] lipid-related genes to be looked at. In addition, it will be important to combine this genetic information with data on brain activation patterns by means of PET or fMRI."

The study was funded by the Swiss National Science Foundation, the Early Diagnosis of Alzheimer's Disease and Related Dementia Program in Switzerland, and the National Center for Competence in Research in Switzerland.

"A Cluster of Cholesterol-Related Genes Confers Susceptibility for Alzheimer's Disease" can be accessed online at by searching on the article title in the July issue."

Source: Joan Arehart-Treichel. Clinical & Research News: Cholesterol-Alzheimer's Link Backed by New Data. Psychiatric News (19 August 2005) Vol. 40, No. 16, p.17 [FullText]

"The Burnham Institute will receive $3 M over the next three years from the National Institutes of Health ("NIH") to develop an "Exploratory Center for Human Embryonic Stem Cell Research". The grant provides funds to support research that will advance understanding of the fundamental biology of human embryonic stem cells ("hESCs"), as well as facilities for supporting the work and training of other investigators in the basic methods of growing and using human stem cells.

The Burnham Institute is the only NIH exploratory stem cell center in California and the southwestern United States. The Institute was one of three exploratory center sites selected by NIH: Mt. Sinai School of Medicine in New York and Albert Einstein College of Medicine, also in New York, received the other two grants. NIH has funded a total of six exploratory stem cell centers to date, including three centers named in 2003 when the program was initiated: University of Washington, University of Wisconsin, and University of Michigan.

The field of hESC biology is in its infancy and is part of the burgeoning broader field of human stem cell biology. "If we are to realize the tremendous potential of stem cells, we urgently need more fundamental knowledge about their basic biology and more scientists trained to work with them," said Jeremy M. Berg, Ph.D., director of the National Institute of General Medical Sciences ("NIGMS") at the NIH.

NIGMS is addressing these critical needs by providing a total of $9M to the three new Exploratory Centers for Human Embryonic Stem Cell Research over the next three years. The centers will use this funding for research on stem cell lines that are listed on the NIH's Human Embryonic Stem Cell Registry, so-called "NIH approved" stem cell lines.

"These centers are a crucial step in establishing the infrastructure for scientists to address essential questions about human development and cell differentiation," said Marion M. Zatz, Ph.D., program director for the center grants.

During its first year, the Burnham's exploratory stem cell center will fund pilot studies to develop imaging technology that will allow "real time" observation of stem cells, studies on the molecular signals that enable self-renewal and specialization of stem cells, and ongoing studies to improve on methods for growing and maintaining cells.

"Our primary goal in establishing a stem cell center at The Burnham is to facilitate collaborative research on the basic biology of hESC and encourage new researchers to enter the field. This NIH funding will enable new and established investigators to develop the utility of hESC as a model system for a diverse range of biological and medical problems," said Evan Snyder, M.D., Ph.D., Principal Investigator and Co-director of the Stem Cell Center.

"Training new investigators and sharing information are principal goals of the Stem Cell Center", added Jeanne Loring, Ph.D., co-Principal Investigator and co-director of the Stem Cell Center. The grant will support short workshop courses in hESC technology for visiting scientists and provide infrastructure for an intensive NIH-supported training course initiated in 2004 as a joint effort between Dr. Philip Schwartz of the Children's Hospital of Orange County ("CHOC") and Drs. Loring and Snyder of the Burnham Institute.

The Burnham Institute already serves the worldwide stem cell research community through several other programs. The Southern California Stem Cell Consortium is a group of about 100 scientists from academic and industry organizations who meet monthly at the Burnham to discuss issues in human ES cell biology. The Burnham also sponsors a series of symposia exploring the ethical issues surrounding stem cell biology, and hosts an informational website, called The Stem Cell Community (stemcellcommunity.org). Burnham Institute scientists are producing a definitive human ES cell laboratory manual that will be published in 2006 by Elsevier, a leading publisher of scientific literature.

The Burnham Institute, founded in 1976, is an independent not-for-profit biomedical research institution dedicated to advancing the frontiers of scientific knowledge and providing the foundation for tomorrow's medical therapies. The Institute is home to three major centers: the Cancer Center, the Del E. Webb Neuroscience and Aging Center, and the Infectious and Inflammatory Disease Center. Since 1981, the Institute's Cancer Center has been a member of the National Cancer Institute's prestigious Cancer Centers program. Discoveries by Burnham scientists have contributed to the development of new drugs for Alzheimer's disease, heart disease and several forms of cancer. Today the Burnham Institute employs over 700 people, including more than 550 scientists. The majority of the Institute's funding derives from federal sources, but private philanthropic support is essential to continuing bold and innovative research. For additional information about the Institute and ways to support the research efforts of the Institute, visit http://www.burnham.org.

Contact: Nancy Beddingfield, nbeddingfield@burnham.org , 858-646-3146, Burnham Institute, http://www.burnham-inst.org"

Source: NIH selects Burnham Institute for Exploratory Center for Human Embryonic Stem Cell Research. MedicalNewsToday.com (11 August 2005) [FullText]

ReGen Therapeutics Announces Grant of U.S. Patent on Use of Colostrinin(tm) to Promote Induction of Cytokines

"LONDON (10 August 2005) - ReGen Therapeutics Plc ('ReGen' or the 'Company'), a company whose product Colostrinin(tm) has shown efficacy as a potential treatment for Alzheimer's disease, announces that a patent on the use of Colostrinin(tm) as an inducer of cytokines has been granted by the United States Patent and Trademark Office. The patent is owned by the Board of Regents of the University of Texas System and is based upon long term research at the University of Texas Medical Branch (UTMB) at Galveston, which has been sponsored by ReGen. UTMB has licensed the patented technology to ReGen under the world wide exclusive license agreement that exists between the two parties.

The new patent covers the use of Colostrinin(tm), its constituent peptides and analogues to promote cytokine induction. Cytokines are molecules that are involved in communication between cells.

Potential utility of this patent is expected to be welcomed by people with Alzheimer's disease, because 'the induction of cytokines can modulate the immune response in those patients' said Dr. Kruzel, Scientific Consultant to ReGen and Adjunct Professor at the UT Medical School at Houston.* He also added that the present invention provides a method of modulating an intracellular signalling that leads to reduction of cell damaging reactive oxygen species (ROS). Both are important in the context of Alzheimer's disease and may go some way to explain the clinical benefits shown to be associated with ColostrininTM in clinical studies'.

The grant of this patent adds further strength to the intellectual property portfolio owned by or licensed to ReGen. ReGen now holds rights to 5 different patents relating to Colostrinin(tm); one for the use of Colostrinin(tm) in Alzheimer's disease and other neurodegenerative conditions (granted in 10 countries), one for its use as a dietary supplement in combination with other substances (granted in UK) and 3 UTMB 'mode of use' patents (granted in USA).

The Company has filed a number of other patent applications in relation to Colostrinin(tm) its constituent peptides and analogues and these are currently being evaluated by the relevant patent authorities.

Commenting on the latest patent grant, Chairman Percy Lomax said 'This is now the third granted US patent to come from our long standing association with UTMB and represents further progress in our development programme. It remains a pleasure to collaborate with such an excellent team of scientists.'

*Dr. Marian Kruzel is a faculty member at the Department of Integrative Biology and Pharmacology, the University of Texas, Medical School at Houston. He is an internationally recognized immunologist with an established interest and expertise in inflammation and age-related pathophysiology. He is the recipient of numerous grants and a participant in NIH funded projects. Also he serves as a reviewer on several scientific journals, including Clinical and Experimental Immunology, Cellular and Molecular Biology Letters, and Journal of Experimental Therapeutics and Oncology. He is a former chairman of the board of the Cancer Coalition of America.

Through a consultancy agreement with the Company Dr. Kruzel is responsible to the Board for scientific research and development and management of the scientific aspects of future clinical development on behalf of the Company."

For more information, please contact Andrew Marshall, Marshall Robinson Roe, Tel No 020 7960 6007

Full Text of this Press Release is available at this link

"The Alzheimer's Association, the first and largest Alzheimer voluntary health organization, is celebrating its 25th anniversary of incorporation by leading the fight against the disease and bringing hope to uncover its mysteries, prevent and treat its effects, and find better ways to support and care for those affected by this disease.

When a group of family caregivers founded the Association in 1980, Alzheimer's disease was rarely diagnosed, and no treatments or services were available. The Greater Wisconsin Chapter became part of the Alzheimer's Association in 1985 determined to change the way people think about Alzheimer's disease. This commitment sparked a generation of unprecedented progress as the Alzheimer's Association assumed an ever-growing role as the catalyst and leader in Alzheimer research and local care and supportive services."

Source: 25th anniversary of Alzheimer's Association Chetel Alert (10 August 2005) [FullText]

Also see: Biased Grant Review by Alzheimer's Association?

"MONTREAL (10 August 2005) Neurochem Inc. (NASDAQ: NRMX; TSX: NRM) today announced results for the second quarter ended June 30, 2005. The Company reported a net loss of $18.7 million ($0.54 per share) for the quarter, compared to $14.1 million ($0.47 per share) for the same period the previous year. For the six-month period ended June 30, 2005, the net loss amounted to $35.7 million ($1.08 per share), compared to $23.2 million ($0.77 per share) for the same period the previous year. The increase is mainly due to research and development (R&D) expenses which amounted to $12.9 million this quarter compared to $7.0 million for the same period last year. For the six-month period, R&D expenses were $24.9 million compared to $12.6 million for the corresponding period of the previous year. The increase in expenses was primarily a result of patient recruitment activities which were concluded on schedule in June 2005 for the North American Phase III clinical trial for Alzhemed(TM), Neurochem's investigational product candidate for the treatment of Alzheimer's disease (AD), efforts performed in relation to the launch of the European Phase III clinical trial for Alzhemed(TM) later in the year, as well as the advance of the Fibrillex(TM) program for the treatment of AA Amyloidosis.

At the end of the quarter the Company reported cash, cash equivalents and marketable securities of $75.7 million, up from $29.2 million on December 31, 2004. Following the close of the quarter, Neurochem received additional proceeds of approximately $8.8 million from the exercise of warrants by Picchio Pharma Inc. (Picchio Pharma).

"Having achieved significant milestones during this past quarter, we are pleased with the progress being made with regard to the clinical development of our key products," said Francesco Bellini, Neurochem's Chairman, President and CEO. "We will initiate the filing of a NDA (New Drug Application) with the U.S. FDA (Food and Drug Administration) for Fibrillex(TM) during the third quarter. As well, we expect to start patient recruitment in Europe in the fall for the Phase III clinical trial for Alzhemed(TM). I am proud to lead a Company of this caliber and potential, with a team so dedicated to bringing our product candidates to market," he concluded.

Recent Developments

Following the end of the quarter, Neurochem was informed that it has been included as a founding member of the NASDAQ Health Care Index, a market value weighted index containing NASDAQ-listed companies classified as "Health", "Pharmaceutical" or "Biotechnology". According to NASDAQ, the new index provides market participants with new opportunities to own shares in the Company through additional investment vehicles.

Conference Call

Neurochem will host a conference call Thursday, August 11, 2005, at 8:30 A.M ET. The telephone numbers to access the conference call are 1-416-695-6370 or 1-877-461-2815. A replay of the call will be available until Thursday, August 18, 2005. The telephone numbers to access the replay of the call are 1-416-695-5275 or 1-866-518-1010. Please mention that you are calling for the Neurochem conference replay.

Consolidated Financial Results Highlights

The following information should be read in conjunction with the unaudited consolidated financial statements for the six-month period ended June 30, 2005, as well as the audited consolidated financial statements for the year ended December 31, 2004. For discussion regarding related-party transactions, contractual obligations and commercial commitments, critical accounting policies, recent accounting pronouncements, and risks and uncertainties, refer to the Management's Discussion and Analysis of Consolidated Financial Condition and Results of Operations as well as the Annual Information Form for the year ended December 31, 2004. All dollar figures are Canadian dollars, unless specified otherwise.

Results of operations

For the three-month period ended June 30, 2005, the net loss amounted to $18,694,000 ($0.54 per share), compared to $14,072,000 ($0.47 per share) for the corresponding period last year. For the six-month period ended June 30, 2005, the net loss amounted to $35,664,000 ($1.08 per share), compared to $23,236,000 ($0.77 per share) for the same period last year.

Revenues from collaboration agreement amounted to $822,000 for the current quarter ($2,027,000 for the six-month period) and consist of the revenue earned under the agreement with Centocor, Inc. (Centocor) in respect of Fibrillex(TM). Revenue recognized is in respect of the non-refundable upfront payment received from Centocor, which is being amortized over the remaining estimated period to the date the regulatory approvals of the investigational product candidate are anticipated. The estimated period is subject to change based on additional information that the Company may receive periodically.

Reimbursable costs revenue amounted to $213,000 for the current quarter ($657,000 for the six-month period) and consists of costs reimbursable by Centocor in respect of Fibrillex(TM) related activities. The Company does not earn any margin on these reimbursable costs.

Research and development expenses, before research tax credits and grants, amounted to $12,897,000 for the current quarter ($24,862,000 for the six-month period), compared to $7,008,000 for the same period last year ($12,585,000 for the six-month period). The increase is due primarily to expenses incurred in relation to the development of Alzhemed(TM) for the North American Phase III clinical trial and preparation for the European Phase III clinical trial. For the quarter and six-month period ended June 30, 2005, R&D expenses also include costs incurred to support the on-going Fibrillex(TM) Phase II/III open-label extension study, the on-going
Alzhemed(TM) Phase II open-label extension study, as well as on-going drug discovery programs.

Research tax credits amounted to $532,000 this quarter ($941,000 for the six-month period), compared to $309,000 for the corresponding period last year ($621,000 for the six-month period). Research tax credits represent refundable tax credits earned under the Quebec Scientific Research and Experimental Development Program. The increase is due to higher eligible expenses during the current period.

General and administrative expenses totaled $5,917,000 for the current quarter ($11,082,000 for the six-month period), compared to $4,624,000 for the same quarter last year ($8,589,000 for the six-month period). The increase is attributable to the expansion of the corporate infrastructure to support growth and higher legal fees incurred in respect of the dispute with Immtech International, Inc. (Immtech). The expansion of corporate infrastructure includes an increase in operating costs related to the facilities acquired during the second quarter of 2004 and other corporate agreements and matters.

Reimbursable costs amounted to $213,000 for the current quarter ($657,000 for the six-month period) and consist of costs incurred on behalf of Centocor in respect of Fibrillex(TM) related activities and reimbursable by Centocor.

Stock-based compensation amounted to $2,292,000 for the current quarter ($3,062,000 for the six-month period), compared to $2,239,000 for the corresponding quarter last year ($2,663,000 for the six-month period). This expense relates to employee and director stock options and stock-based incentives, whereby compensation cost is measured at fair value at the date of grant and is expensed over the award's vesting period. For the quarter and six-month period ended June 30, 2005, stock-based compensation also includes expenses of $1,441,000 relating to 140,000 common shares to be issued to the Chairman, President and Chief Executive Officer, pursuant to an agreement signed in December 2004. Regulatory and shareholders' approval were obtained during the current quarter.

Special charges amounted to nil for the quarter and six-month period ended June 30, 2005, compared to $2,085,000 for the quarter and six-month period ended June 30, 2004, and were related to the relocation to facilities acquired from Shire Biochem Inc. in May 2004.

Depreciation and amortization amounted to $575,000 for the current quarter ($1,145,000 for the six-month period), compared to $499,000 for the same quarter last year ($867,000 for the six-month period). The increase reflects the depreciation and amortization associated with the acquisition during the past year of additional property and equipment, including the facilities acquired in the second quarter of 2004, and the increase in patent costs.

Interest and bank charges amounted to $133,000 for the current quarter ($254,000 for the six-month period), compared to $24,000 for the same quarter last year ($48,000 for the six-month period). The increase is due to interest expense on the $10,500,000 revolving decreasing term credit facility entered into by the Company to finance the acquisition of the facilities in 2004.

Interest income amounted to $633,000 for the current quarter ($884,000 for the six-month period), compared to $253,000 for the same quarter last year ($575,000 for the six-month period). The increase results from higher average cash balances in the current period compared to the same period last year, due to proceeds received from the public offering in March 2005. Refer to the Liquidity and Capital Resources section for details.

Foreign exchange gains amounted to $1,406,000 for the current quarter ($1,632,000 for the six-month period), compared to $1,650,000 for the same quarter last year ($2,091,000 for the six-month period). Foreign exchange gains or losses arise on the movement in foreign exchange rates related to the Company's net monetary assets held in foreign currencies, primarily US dollars. The decrease is attributable to lower foreign exchange gains realized in the current quarter compared to the same period last year on the conversion of US dollars into Canadian dollars.

Other income amounted to $296,000 for the current quarter ($347,000 for the six-month period), compared to $85,000 for both the quarter and six-month period ended June 30, 2004. Other income consists of non-operating revenue, such as rental revenue.

Variable interest entities

On January 1, 2005, the Company adopted the recommendations of the CICA Accounting Guideline 15 - Consolidation of Variable Interest Entities (VIE). This guideline requires the Company to identify VIEs in which it has an interest, to determine whether it is the primary beneficiary of such entities and, if so, to consolidate the VIEs. The implementation of AcG-15 resulted in the consolidation of the Company's interest in a holding company that owns Innodia Inc.'s shares, starting January 1, 2005. The effect of the implementation of this accounting guideline was to adjust the net carrying value of the long-term investment and the opening deficit by $2,501,000 at January 1, 2005. The revised carrying amounts of the long-term investment and non-controlling interest at January 1, 2005 were $3,359,000 and $1,439,000, respectively. The implementation of this accounting guideline resulted in the consolidation in the current quarter of a share of loss in a company subject
to significant influence of $824,000 ($1,579,000 for the six-month period) and non-controlling interest of $245,000 ($470,000 for the six-month period), in the Consolidated Statement of Operations.

Litigation

In connection with an agreement concluded in 2002, Immtech brought claims against the Company in legal proceedings filed on August 12, 2003, with the Federal District Court for the Southern District of New York, U.S.A. The dispute is now before an arbitral tribunal convened in accordance with the rules of the International Court of Arbitration. A hearing has been scheduled by the arbitral tribunal for mid-September 2005.

Immtech has claimed monetary damages which, to date, it has estimated at between a total of US$18 million and US$42 million, which includes an estimated valuation for equitable relief. The Company counterclaims damages which, to date, it has estimated at no less than US$3.5 million, which includes an estimated valuation for equitable relief. The outcome of this matter, or the likelihood and the amount of loss, if any, is not determinable. No provision for possible loss has been recorded by the Company in connection with this matter. The Company has, and will continue to, vigorously defend itself against claims brought by Immtech.

LIQUIDITY AND CAPITAL RESOURCES

As at June 30, 2005, the Company had available cash, cash equivalents and marketable securities of $75,727,000, compared to $29,173,000 at December 31, 2004. The increase is primarily due to proceeds received from the issue of additional share capital during the first quarter of 2005 (as described below), net of funds used in operations and in investing activities.

On March 9, 2005, the Company completed a public offering of its common shares in the United States and in Canada. The Company issued four million common shares at a price of US$15.30 per share. Total proceeds from the offering were $74,495,000 (US$61,200,000) and the issue costs totaled $4,955,000. Certain funds raised from the share issuance were denominated in U.S. dollars. The Company maintains a significant U.S. dollars position to serve as a natural hedge of exchange rate fluctuations with respect to planned U.S. dollar denominated research and development expenditures primarily relating to its phase III clinical programs. Net proceeds will be used to fund the clinical trials of the Company's product candidates (primarily Alzhemed(TM)), other research and development programs, advancing Fibrillex(TM), working capital and general corporate purposes.

On July 25, 2005, Picchio Pharma exercised a warrant previously issued pursuant to a July 2002 private placement, generating total proceeds to the Company of $8,764,000 and the issuance of 2,800,000 common shares from treasury.

At July 31, 2005, the Company had 37,379,393 common shares outstanding, 220,000 common shares issuable to the Chief Executive Officer upon the achievement of specified performance targets, 2,324,485 options granted under the stock option plan and 1,200,000 warrants issued and outstanding.

For Consolidated Financial Information and Press Release Full Text please follow this links.

"For a state with so many senior citizens, Florida was treated more like a toddler when it came to its efforts to cure Alzheimer's disease. The National Institute on Aging, which oversees federally funded Alzheimer's research, has designated seven Alzheimer's research centers in California. New York has three. Until recently, Florida had none. It was a noticeable slight for a state with an estimated 430,000 Alzheimer's patients - enough to fill Raymond James Stadium more than six times.

That changed in April, when a consortium led by the Johnnie B. Byrd Sr. Alzheimer's Center & Research Institute and the University of South Florida became the first Alzheimer's Disease Research Center based in Florida. NIA awarded the consortium $7.3 million in federal funding over 5 years. For the Byrd Institute, created in the tough world of Tallahassee politics, the recognition conferred big-league status. What some once dismissed as the pet project of former state House Speaker Johnnie Byrd Jr. is now a national player in Alzheimer's research.

As Creighton Phelps, who directs NIA's Alzheimer's Disease Research Centers program, put it, ``We were willing to invest in it because we thought the potential was there.'' Phelps said NIA was impressed with a number of things - the Byrd Institute's statewide team of researchers, a $15 million-a-year state commitment and the quality of the research it is doing. Byrd Institute discoveries are receiving national attention, most recently a study released in July in which their researchers and a team from the University of Helsinki showed that a naturally occurring protein called KDI tri-peptide may protect the brain and spinal cord from injury.

The institute's location at USF also will pay dividends for Bay area Alzheimer's patients and their families. The institute is participating in four clinical trials of experimental Alzheimer's drugs, in which about 40 people from the Bay area are enrolled. Seven more clinical trials are scheduled to start in the fall.

Honoring His Father

Before all of this, though, Byrd fought bruising battles with fellow lawmakers over funding for the center. His fight to build an institute, to help Floridians with Alzheimer's and honor his late father, who had the disease, held up passage of the state budget in 2003. Relations between Byrd and then-Senate President Jim King Jr., who wanted the state to create a biomedical research center to honor his parents, were so strained that the leaders dispensed with the usual handkerchief drop at the end of the 2004 session, a time-honored Tallahassee nicety that takes place in the state Capitol Rotunda signaling no hard feelings between the two chambers.

Byrd made no secret of his desire to see an Alzheimer's institute based at USF.

``Politically, they always say, `Don't ever let anybody know what you really want,' '' Byrd said. ``But I couldn't help it. That's what I wanted, to help 400,000 people [in Florida] who have Alzheimer's. Everybody had my number. I was wearing my heart on my sleeve.'' In the end, Byrd's persistence made an Alzheimer's research center at USF a reality. In 2002, lawmakers authorized a statewide Alzheimer's institute and included $20 million for a building.

In 2004, the Legislature renamed the institute in memory of Byrd's late father. The legislation also included $15 million a year from the state's alcoholic beverages and tobacco trust fund. The institute, based in a Tampa Palms office building, is building a state-of-the-art research facility and clinic at USF, scheduled to open in 2006. The Byrd Institute would not have been created without Byrd's vision and ``absolute dedication,'' said Huntington Potter, the institute's chief executive officer and scientific director. ``There was no other person who was going to take up this standard and push it,'' said Potter, a Harvard-trained biochemist and molecular biologist.

By weaving a groundbreaking network of Alzheimer's researchers across the state - USF, the Wien Center for Alzheimer's Disease & Memory Disorders at Mount Sinai Medical Center in Miami Beach, the Mayo Clinic in Jacksonville, the University of Florida and the University of Miami - the bid succeeded where previous bids for ADRC status had failed. ``That partnership is a very compelling and positive move,'' said John Morris, who directs the Alzheimer's Disease Research Center at Washington University in St. Louis. ``I think they can be an enormous force.''

The $15 million a year from the state also makes the Byrd Institute stand out. ``It's good funding,'' said Sid Gilman, program director for the Alzheimer's Disease Research Center at the University of Michigan, which doesn't receive state funding. ``They should be able to do a lot with that.''

Living With Alzheimer's

If you want to know what finding a cure for Alzheimer's would mean, ask Diane Ringer of Brandon. Ringer's husband, Tom, learned he had the disease in 2000. The experience has turned Ringer into an Alzheimer's activist. She leads a support group in Brandon and belongs to a second group. Against a backdrop of family photos in her den, Ringer smiles when she speaks of Tom, her husband of 54 years and the light of her life.

They were just a couple of young Michigan kids when they were married in 1951. Diane was 19. Tom, 24, a Navy veteran with dark hair and movie-star looks, was just starting with the Royal Oak Police Department. ``He was the handsomest cop in the department,'' said Diane, 73. They raised two children. Diane worked as a travel agent. Tom rose to the rank of commander of the uniform division in the department. They retired and moved to Florida. Tom enjoyed an active retirement, walking two or three miles a day and riding his bike regularly. Then, he showed signs of slowing down that turned out to be more than normal aging.

Tom shied away from golf because he had difficulty keeping track of his golf strokes. It was the beginning of Alzheimer's. These days, Diane visits Tom, 77, in the Brandon nursing home where he lives. He is in the final stages of the disease. ``Tom doesn't know me anymore,'' Diane said. ``He knows I'm somebody he likes, but he really doesn't know who I am.'' Diane said that had Tom's condition not been so advanced, he would have been eager to participate in clinical trials at Byrd Institute. ``He would have jumped in with both feet,'' Diane said.


Died On Election Day

Johnnie Byrd Sr. was what his son calls ``this Greatest Generation kind of guy.'' Byrd Sr., a high school valedictorian, had the smarts but not the money for college. He went off to World War II as a pilot and built a grocer's life as the owner of the Piggly Wiggly in rural Brewton, Ala. Byrd Sr. developed Alzheimer's in the early 1990s. He died on Election Day in 1998, the day his son was re-elected as a state representative. ``In a quiet moment on that day, I said I'd do whatever I could to save other people from that fate,'' Byrd said. Legislative leaders typically have their own priorities, causes for which they are willing to spend the coin of leadership.

For Byrd, a Plant City Republican, who served as speaker during the 2003 and 2004 sessions, his priority was building an Alzheimer's institute to fight the memory-stealing disease that claimed his dad. But even after Gov. Jeb Bush signed legislation in 2004 naming the institute after Byrd's father and allocating $15 million a year, there were legislative assaults.

In 2005, after Byrd's term as speaker, the state Senate passed a bill that would have made the Byrd Institute compete for the $15 million with other Alzheimer's researchers. The bill was not taken up by the House. ``It shouldn't be a monopoly by one institute,'' said Mike Fasano, R-New Port Richey, who sponsored the bill. Had that happened, the Byrd Institute never would have received Alzheimer's Disease Research Center status, said Potter, its chief executive. asano's bill also would have stripped Byrd's father's name from the center and replaced it with that of former President Reagan, who had Alzheimer's.

Fasano said he proposed the name change because a Reagan connection would give the institute national exposure and because many of his colleagues wouldn't back an institute with the Byrd name on it. ``You don't want to play politics with finding a cure for such a horrible disease,'' Fasano said. Byrd is diplomatic when asked how he felt about efforts to remove his father's name from the institute. ``They're in charge now, so I trust them to do what's right,'' he said. ``That's their job. They're the ones who have to decide what what to do.'' Byrd is the second powerful Tampa Bay area lawmaker to leave a lasting imprint on the area's health scene.

H. Lee Moffitt, a former House speaker from Tampa, fought his own battles to make a state-funded cancer center in Tampa a reality. He understands the battle Byrd waged. ``It takes a whole lot of perseverance,'' Moffitt said. ``There are so many obstacles, so many naysayers, so many people who, for political reasons, don't want it to happen.'' Being speaker gave Moffitt the leverage to help a cause dear to his heart, he said. ``You have the power that goes along with that position,'' Moffitt said. ``They listen to you more. You have the ability to influence the outcome that you don't have if you're a rank- and-file legislator.'' The H. Lee Moffitt Cancer Center & Research Institute at USF opened to patients in 1986.

Byrd says his vision is to eradicate Alzheimer's. ``When my seventh-grader says, `What was polio all about?' and you try to describe that to him, I hope one day our grandchildren will ask, `What was this thing called Alzheimer's?' ''"

Source: Gary Haber. Alzheimer's Center Brings Hope Closer. TBO.com News [FullText]

"Elevated insulin levels may contribute to the development of Alzheimer's disease, and investigators hope this new finding will lead to more effective treatment strategies, according to a report in the August 8 issue of the Archives of Neurology. Researchers at the University of Washington in Seattle raised blood insulin levels in 16 healthy older adult volunteers and then measured changes in the volunteers' levels of inflammatory markers and beta-amyloid (a protein associated with Alzheimer's disease) in their cerebrospinal fluid and plasma.

"Moderate peripheral hyperinsulinaemia (increased levels of insulin) provoked striking increases in CNS (central nervous system) inflammatory markers," the study authors wrote. "Our findings suggest that insulin-resistant conditions such as diabetes mellitus and hypertension may increase the risk for Alzheimer's disease, in part through insulin-induced inflammation." The research team concluded: "Although this model has obvious relevance for diabetes mellitus, hyperinsulinaemia and insulin resistance are widespread conditions that affect many nondiabetic adults with obesity, impaired glucose tolerance, cardiovascular disease and hypertension. Our results provide a cautionary note for the current epidemic of such conditions, which, in the context of an ageing population, may provoke a dramatic increase in the prevalence of Alzheimer's disease.""

Source: Insulin, Alzheimer's link. Health24.com (South Africa) (10 August 2005) [FullText]

"Anti-inflammatory Function Of Alzheimer's Disease Drugs Revealed

The mechanism in anti-Alzheimer's disease drugs that inhibits the production of a destructive, inflammation-causing protein in the brain has been revealed by researchers at the Hebrew university of Jerusalem.

Their work, described in a recent issue of the American journal, Annals of Neurology.
is likely to lead to the development of more efficient drugs than are currently in use for treating Alzheimer's Disease as well as other neurological conditions resulting from infections, autoimmune diseases such as multiple sclerosis, or brain inflammation resulting from trauma or stroke.

The research team working on this project was headed by Prof. Raz Yirmiya of the Psychology Department at the Hebrew University, Dr. Yehuda Pollak, a post-doctoral fellow in Prof. Yirmiya's laboratory; and in cooperation with Hermona Soreq, the Charlotte Slesinger Professor of Cancer Studies at the Silberman Institute of Life Sciences at the Hebrew University, and Prof. Tamir Ben-Hur of the Hebrew University Faculty of Medicine.

Alzheimer's Disease is a degenerative disease of the brain, characterized by a deterioration of both cognitive and physical abilities. It first affects memory and the ability to carry out complex, coordinated tasks. It also can bring on depression, inattention and outbursts of anger. In a more progressive stage, the disease can cause difficulties in the ability to perform even simple tasks such as speaking and comprehending, eating and sleeping. The affected person can even forget his name and identity.

The medicines administered today to Alzheimer's Disease patients focus on preventing the breakdown of acetylcholine, a chemical produced by brain cells which transmits information within the brain and is vitally involved in cognitive processes that include memory, attention and thought. Because acetylcholine-producing cells are among the first to die in Alzheimer's Disease patients, drug-induced elevation of acetylcholine levels partially attenuates the cognitive deterioration.

In recent years it has been shown that another pathological process that occurs in the brain of Alzheimer's Disease patients is excessive immune activation and inflammation, which are induced by overproduction of an inflammation-producing protein called interleukin-1, as well as a few other related compounds. This process can impair the functioning of nerve cells and can even lead to their death. Furthermore, genetic alterations in the interleukin-1 gene have been associated with increased risk for the appearance and severity of Alzheimer’s Disease symptoms.

The Hebrew University researchers found that anti-Alzheimer’s Disease drugs currently in use not only block the activity of the enzyme responsible for breaking down acetylcholine but also cause a marked reduction in the production of interleukin-1. Furthermore, they describe the use of a novel drug (EN101), developed by Prof. Soreq’s team, which produces these effects in a more efficient way than known heretofore by destroying the molecular antecedent (messenger RNA) of the enzyme, rather than simply blocking the enzyme’s activity.

In a series of experiments, conventional anti-Alzheimer’s Disease drugs, as well as the novel drug EN101, were injected into mice with brain inflammation. It was found that these injections reduced significantly the activity of the enzyme that breaks down acetylcholine and blocked almost entirely the production of interleukin-1.

“These findings suggest a new role for acetylcholine in the brain,” said Prof. Yirmiya. “When the anti-Alzheimer’s Disease drugs block the enzyme which breaks down acetylcholine, the level of this chemical in the brain goes up, and there is a reduction of the production of the inflammatory material, interleukin-1, and its destructive influence in the brain.”

“The discovery of this mechanism in the anti-Alzheimer’s Disease medicines points the way towards development of new forms of these medicines which will block even more efficiently and specifically the inflammatory and destructive activity of inteleukin-1,” Prof. Yirmiya stressed. “Beyond that, it is likely that the drugs that are currently used for treatment of Alzheimer’s Disease, and particularly the new drug EN101, will also be effective in dealing with other inflammatory illnesses.”

Original news release can be found here.

Please note: The above story (available at this link) has been adapted from a news release issued by The Hebrew University of Jerusalem. It is available here.

"When evangelical Christians held their first "Justice Sunday" national political rally in April, Senate Majority Leader Bill Frist, R-Tenn., was one of the featured speakers. The same religious coalition is running a "Justice Sunday II" rally 10 days from now in Frist's hometown of Nashville, but Frist has conspicuously not been invited.

Frist, a renowned heart-lung transplant surgeon with presidential ambitions, committed the sin of allowing respect for science to trump the absolutist dogma of religious politics. He endorsed embryonic stem cell research.

This instantly improved chances for medical research that could benefit millions. But it enraged activists who regard the research as the taking of life because embryos ­ fertilized eggs ­ are destroyed in the process.

When the Senate returns from its summer recess, it is expected to take up a House-passed bill that would loosen the Bush administration's restrictions on federal funding for such research. Scientists say embryonic cells could yield new ways to treat devastating spinal-cord injuries, Alzheimer's disease, diabetes and other ailments.

Because stem cells derived from embryos have the unique ability to develop into any kind of tissue in the body, researchers hope they can be manipulated into replacing diseased or injured tissues. Four years ago, President Bush allowed federal funding for stem cell research but limited it to those stem cell colonies, or "lines," already in existence at that time. He reiterated his position this week after Frist's speech.

Bush's approach initially seemed reasonable, but scarcely one-fourth of those lines turned out to be viable for research. And all are tainted by animal products used to help them grow in the laboratory; they might be useless or even dangerous in treating humans. Meanwhile, foreign countries have moved ahead. States, private researchers and major universities have begun to create their own stem cell institutes, but the lack of federal support is hampering the research effort at home.

The pending legislation would allow government support for research using stem cells, taken from surplus embryos at fertility clinics, that would otherwise be discarded. In a speech the day the Senate quit for a five-week recess, Frist endorsed the bill.

"The limitations put into place in 2001 will, over time, slow our ability to bring potential new treatments for certain diseases," he said. "It isn't just a matter of faith. It's a fact of science."

Indeed it is. Frist's support could be crucial to overcoming a threatened Senate filibuster, or to rallying the two-thirds vote needed to override a threatened presidential veto.

Respect for life should dictate removal of barriers to potential life-saving research, particularly when the material involved does not resemble life as most people think of it. Recent polls show majorities favor easing restrictions on stem cell research or having no limits on funding.

Frist's critics labeled his speech a politically motivated flip-flop. Perhaps it was. Even so, mindless consistency to an outmoded position is no virtue..."

Source: Shift brings new hope. USAToday (3 August 2005) [FullText]

"Today's obesity epidemic may be tomorrow's Alzheimer's disease epidemic, a new study shows.

People with diabetes are at particularly high risk of Alzheimer's disease. But now there's strong evidence that people with high insulin levels — long before they get diabetes — already are on the road to Alzheimer's disease.

As the body becomes more and more overweight, it becomes more and more resistant to the blood-sugar-lowering effects of insulin. To counter this insulin resistance, the body keeps making more insulin. If it continues, this escalating cycle of insulin resistance and insulin production end in type 2 diabetes.

Drug Holds Off Alzheimer's Disease

Insulin Triggers Amyloid Buildup. High insulin levels are known to cause blood vessels to become inflamed. Inflamed tissues send off chemical warning signals. These warning signals set off an avalanche of tissue-damaging effects.



But insulin doesn't just cause inflammation in the lower body. It also causes inflammation in the brain, find University of Washington researcher Suzanne Craft, PhD, and colleagues.

One dangerous effect of this insulin-caused brain inflammation is increased brain levels of beta-amyloid. Beta-amyloid is the twisted protein that's the main ingredient in the sticky plaques that clog the brains of people with Alzheimer's disease.

"What was striking was the magnitude of the effect," Craft tells WebMD. "Inflammation can be a result of amyloid elevations but can also create an environment in which amyloid is made more readily. Inflammation can be both the result and cause of amyloid production."

Marijuana Ingredient May Help Alzheimer's

Brave Volunteers. Craft's research team signed up 16 very brave volunteers. These men and women, ranging in age from 55 to 81, let research doctors give them two-hour infusions of both insulin and sugar. This kept their blood sugar at normal levels while creating the same kind of high insulin levels seen in people with insulin resistance. The volunteers then let the researchers give them a spinal tap so they could analyze their spinal fluid.

Just this brief rise in insulin levels had what Craft calls "striking" effects:

It set off inflammation in the brain.

The spinal fluid had increased levels of a compound called F2-isoprostane. Alzheimer's patients have unusually high brain levels of F2-isoprostane.

Brain levels of beta-amyloid increased.

Except for the spinal tap, many Americans already are undergoing the same experiment as the study volunteers did. And they are doing it for a lot longer than two hours.

Because they are overweight and inactive — and because they may have genetic risk factors — many people have high insulin levels. It's not good for their hearts. And it's not good for their brains, says Samuel Gandy, MD, PhD. Gandy, chairman of the Alzheimer's Association's medical and scientific advisory committee, is director of the Farber neuroscience institute at Thomas Jefferson University, Philadelphia.

"I think this reinforces the idea that it's wise to maintain your brain," Gandy tells WebMD. "Controlling blood sugar and body weight — all those things we know are good for your heart health are also really good at preventing Alzheimer's disease. So there are more and more reasons not to be slouchy about getting these things under control."

Craft and colleagues report their findings in the October issue of Archives of Neurology.

Sources: Fishel, M.A. Archives of Neurology, October 2005; vol 62: early online edition. Suzanne Craft, PhD, University of Washington School of Medicine and Veterans Affairs Puget Sound Health Care System, Seattle. Samuel Gandy, MD, PhD, chairman, medical and scientific advisory committee, Alzheimer's Association; and director, Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia.

Source: Daniel J. DeNoon, reviewed by Brunilda Nazario, MD. Prevent Alzheimer's With Healthy Living. Foxnews.com (9 August 2005) [FullText]

"Even moderately elevated insulin levels may increase the risk of developing Alzheimer's disease, according to a small study by investigators at the University of Washington here.

They measured inflammatory markers in plasma and cerebrospinal fluid in 16 adult volunteers who were given infusions to mimic insulin resistance, and found that a moderate increase in peripheral insulin produced "striking" increases in central nervous system inflammatory markers.

"Our findings suggest that insulin-resistant conditions such as diabetes mellitus and hypertension may increase the risk for Alzheimer's disease, in part through insulin-induced inflammation," wrote Mark A. Fishel, M.D. and colleagues in the online version of the Archives of Neurology. The study is scheduled for publication in the October print edition. The results, if confirmed, suggest that the current epidemic of diabetes and insulin resistance syndromes could cause an upsurge in the prevalence of Alzheimer's in the future, the authors contended.

Many researchers suspect that inflammation plays a key role in the development of Alzheimer's, as suggested by the presence in CSF levels of Alzheimer's patients of interleukin 6 (IL-6), an inflammatory cytokine, and F2-isoprostane, a lipid peroxidation marker. In addition, laboratory and animal studies have pointed to an interaction between inflammation and beta-amyloid processing and deposition. Abnormal accumulation of beta-amyloid protein is a diagnostic hallmark of Alzheimer's.

To test whether insulin resistance could elevate markers of inflammation, the investigators recruited 16 cognitively normal adults ages 55 to 81 years. All were in good health and none were taking medications known to have CNS or gluco-regulatory effects. On separate mornings one week or more apart, the fasting participants randomly received infusions of saline for a baseline and insulin with variable dextrose levels to raise their plasma insulin levels while maintaining normal glycemia. The result was an approximation of the physiologic state of patients with insulin resistance following a meal.

The investigators then measured changes in plasma and CSF levels of the inflammatory markers IL-1 , IL-1 , IL-6, F2-isoprostane, and tumor necrosis factor- (TNF- ); inflammatory modulators (transthyretin, apolipoprotein E, and norepinephrine); and beta-amyloid. They found that during hyperinsulinemia, there were increased CSF levels of all the interleukins, TNF- and F2-isoprostane, but cytokine levels in plasma did not change reliably in response to insulin. Insulin also increased both plasma and CSF levels of beta-amyloid42, and these changes were predicted by increased cytokine and F2-isoprostane, and by decreased transthyretin levels; transthyretin normally binds beta-amyloid and shuttles it out of the brain and into the periphery.

The increase in inflammatory markers that they observed was modulated by insulin-induced changes in CSF levels of apoE and norepinephrine. The investigators hypothesize that insulin's inflammatory effects may be due to its influence on CNS cells that express insulin receptors, such as the endothelial cells in the blood brain barrier, glial cells in the brain, and neurons. Alternatively, insulin may have an indirect effect on CSF cytokine levels by modulation of CSF and beta-amyloid42 plasma levels.

"Although this model has obvious relevance for diabetes mellitus, hyperinsulinemia and insulin resistance are widespread conditions that affect many nondiabetic adults with obesity, impaired glucose tolerance, cardiovascular disease, and hypertension," wrote Dr. Fishel and colleagues. "Our results provide a cautionary note for the current epidemic of such conditions, which, in the context of an aging population, may provoke a dramatic increase in the prevalence of Alzheimer's disease.""

Source: Neil Osterweil, Senior Associate Editor. Elevated Insulin Increases Alzheimer's Disease Risk. MedPage Today (8 August 2005) [FullText]

"It's common knowledge that a proper exercise regimen can do wonders for the body. Only recently, however, have psychologists and gerontologists aggressively applied the same principle to the mind.

Among people who work with older adults, the concept of "cognitive fitness" has become a buzzword to describe activities that stimulate underutilized areas of the brain and improve memory. Proponents of brain-fitness exercises say such mental conditioning can help prevent or delay memory loss and the onset of other age-related cognitive disorders.

Broadband Stories. What's your story? "Most people's idea of fitness stops at the neck," said Patti Celori, executive director of the New England Cognitive Center. "But the brain is the CPU of our body, and most people don't do much to keep it as fit as possible."

The NECC runs one of a growing number of programs that work with older adults to improve cognitive abilities. Activities include computer programs designed to stimulate specific areas of the brain, replication of geometric designs using boards with pegs and rubber bands, and visual and auditory memory exercises.

Some of the other programs are Maintain Your Brain, initiated a year ago by the Alzheimer's Association; Mind Alert, run by the American Society on Aging; and other regional programs such as the Center for Healthy Aging in Kent, Ohio.

For do-it-yourself types, a plethora of books have been published on getting the brain in shape. Paula Hartman-Stein, a geropsychologist at the Center for Healthy Aging, recommends The Better Brain Book, by David Perlmutter and Carol Colman, and The Memory Bible by Gary Small.

One purpose of mental exercises is to reinforce the idea that "in aging, not everything is downhill," said Elkhonon Goldberg, a Manhattan neuropsychologist and author of The Wisdom Paradox, which examines how some people grow wiser with age.

"There are gains that are subsequent and consequent to a lifelong history of mental activity and mental striving," Goldberg said. He also believes brain exercises can benefit adults suffering from mild cognitive impairment, and he has developed computer puzzles designed to help them stimulate different areas of their brain.

It's not clear how much targeted brain exercises can prevent the onset of cognitive disorders in older adults. But some findings indicate that high cognitive ability is tied to a lower risk of Alzheimer's.

One of the most extensive and widely cited investigations on the subject, the landmark Nun Study, tracked 100 Milwaukee nuns who had written autobiographies in the 1930s. More than 50 years later, scientists gave them cognitive tests and examined the brain tissue of nuns who died. Those who demonstrated lower linguistic ability in the autobiographies were at greater risk for Alzheimer's disease.

A similar study published in the Journal of the American Medical Association surveyed 801 older Catholic nuns, priests and brothers. The results linked reading newspapers and participating in other brain-stimulating activities with a reduced risk of Alzheimer's.

A 2000 National Research Council report commissioned by the National Institute on Aging found some brain exercises were worthy of government funding.

But skeptics question whether beginning an active regimen of brain teasers late in life will do much to prevent brain disorders.

Research to date provides scant evidence that mental exercise can stave off dementia, wrote Margaret Gatz, a psychology professor at the University of Southern California, in an article published by the Public Library of Science.

Gatz wrote in an e-mail that she would be more convinced if researchers randomly assigned cognitive training, then followed study subjects over several decades.

She also said she was concerned that too much emphasis on the benefits of mental fitness could stigmatize Alzheimer's patients.

"If mental exercise is widely believed to prevent (Alzheimer's disease), then individuals who do become demented may be blamed for their disease on the grounds of not having exercised their brains enough," she said.

Still, supporters of cognitive-fitness programs are pushing for greater recognition from the federal government. During December information-gathering sessions leading up to the White House Conference on Aging, conference representatives said several speakers have made a case that brain health ought to be promoted in much the same way that physical fitness is today.

Few people see much downside in pursuing brain-stimulating activities, said Nancy Ceridwyn, special-projects director at the American Society on Aging. Puzzles, spelling practice, memory exercises or book discussions don't pose much harm.

That said, Ceridwyn isn't convinced that all the brain exercises being offered today are practical. She wonders whether workbooks that ask adults to do pages of math problems to get their brains in gear might be unnecessarily torturing people in their twilight years..."

Source: Institute, Brain Workouts May Tone Memory. Wired.com (4 August 2005) [FullText]

"Forget about a magic panacea for longevity. "There are clearly no pills or potions that have yet been established to increase longevity, and in fact for many of such pills and potions out there, there are real concerns about adverse effects," said Richard Hodes, director of the National Institute on Aging (NIA). He's talking about: HGH, testosterone, antioxidants and dietary supplements.

"People spend a lot of money on one kind of anti-aging remedy or another, and they have for thousands of years," said Peter Whitehouse, Case Western Reserve University professor of neurology and biomedical ethics, who studies age-related cognitive decline.

75% of Our Longevity is Determined by Environment

Alas, aging is still the fundamental fact of the life cycle, and the human mortality rate remains 100 percent. But we can, if we're fortunate, exercise some control over the timing of our death and what our life is like until that day comes. Hodes says studies have shown that about 25 percent of how we age is determined by genetics; the other 75 percent, by the environment. Which is to say, by tending to our environment and what we do within it, we can shift the odds of a longer and better life in our favor, at least a bit. Of course, the best life practices won't prevent that proverbial bus from running you down this afternoon, or some cruel cancer appearing on your liver in September. But if those things don't intrude, there are a few key lifestyle choices you can make that science has connected with long and healthy tenure on this earth. And they are fairly well established to reduce risk substantially for early onset of the diseases most likely to kill or disable you: heart disease, stroke, diabetes, dementia and some cancers. After all is said and done, exercise is the most potent elixir for a longer and healthier life.

Exercise Leads the Way

Recent research reinforces the fact that regular physical activity retards bodily decline, though the precise mechanism by which it might do that remains a mystery. Rigorous activity helps circulate blood throughout the body's tissues and organs, delivering nourishment and removing impurities. Exercise also helps maintain weight in a healthy range. Epidemiological studies associate a BMI of 27 or greater (27.8 for men and 27.3 for women) with increased sickness and death.

Calculate Your BMI

Some good research connects aerobic capacity with living longer. A 2002 study in the New England Journal of Medicine looked at 6,213 men with and without coronary artery disease. It showed a 12 percent improvement in survival for every unit of metabolic capacity increased through endurance training.

In a 1999 study in the Journal of the American Medical Association (JAMA), low levels of fitness increased men's risk of death from cardiovascular disease by about five times; overall risk of death from all causes increased about three times.

Experts also know muscle strength and balance can help protect against falls and related injuries that can compromise independence and, in the very old, lead to death.

More definitive data on fitness's protective benefits on life span is expected. NIA is developing a randomized trial to study how exercise affects people's risk for disabilities. This will be the first direct test of its kind to show "whether we can actually prevent decline in the living community," said Hodes.

Until that study's findings appear, make sure you get the Surgeon General's recommended 30 minutes of vigorous exercise daily. And read today's Lean Plate Club column for thoughts about incorporating strength training into your life..."

Source: Suz Redfearn Exercise Leads The Way For A Longer And Healthy Life. Washington Post (3 August 2005) [FullText]

"Ireland-based Elan Pharmaceuticals, Inc. (Elan), whose expertise in the neuroscience field is highly respected [AC: Make sure you read footnote below], has teamed up with the Institute for the Study of Aging (ISOA) in New York City to establish new grants to catalyze and accelerate the global discovery and development of new drugs for Alzheimer’s disease. The objective of this Request for Proposal (RFP) program is to support the development of lead compounds through preclinical in-vitro and in-vivo evaluation, including pharmacology, toxicology, pharmacokinetics, formulation chemistry and the conduct of pre-clinical “proof of concept” studies. Four 1-yr grants are available for $130K/yr. Applicants must hold an M.D. or Ph.D. degree. Applications and supporting materials must be received by October 14, 2005. See more details on the ISOA web site."

Source: AlzForum web site (last viewed 5 August 2005) [FullText: Link 1 Link 2 Link 3 (Doc file) ]

Footnote: Make Sure You Know that Elan Directors were in preslump shares sales a year before the company publicly announced poor results in its' trial of amyloid-based Alzheimer's disease treatment with a vaccine. See Ireland The Business Post publications for further details: 18 August 2005 and 11 August 2005 . The non-disclosure of competing interest by Elan Director and Harward Professor Dennis Selkoe (and other scientists in Alzheimer's field) could well led to sad storied of Alzheimer's patients families, such as the one described in the article "Good buy came early".

"This week scientists of the Flanders Interuniversity Institute for Biotechnology (VIB) will once again publish a breakthrough in their research regarding Alzheimer's disease. The researchers, this time connected to the Catholic University of Leuven, discovered the function of one of the most important proteins related to Alzheimer's disease. They have indicated that the protein stimulates the growth of nerve paths in the brain, which is essential for recovery after brain damage. The results are published in the authoritative journal EMBO Journal.

The normal function of the amyloidal precursor protein or APP clarified

It has been known for several years that APP is relevant in Alzheimer's disease. APP is the precursor of the amyloidal-â protein that causes the typical 'plaques' in the brains of patients. The normal function of APP was, however, not known. Maarten Leyssen and his colleagues have indicated that APP stimulates the development of nerve paths. Intact nerve paths are essential for the proper functioning of the brain. These connections can be damaged after traumatic brain damage resulting in the improper functioning of the brain. APP is responsible for stimulating the development of new nerve paths.

APP and Alzheimer's disease

These results also aid better understanding of certain aspects of Alzheimer's disease, where APP plays a major role. The fruit fly - an ideal model to study the brain's action - indicates that APP increases considerably after brain damage, namely in areas where new nerve paths need to be formed. Because more APP is made, more plaques can develop in the brain, a typical symptom of Alzheimer's disease. For the first time the results of VIB researchers explain the strong link between brain damage and Alzheimer's disease: not only do patients with major brain damage have more chance of developing Alzheimer's disease later on in life, their brains also often show plaques that strongly resemble those of Alzheimer patients."

Contact: Ann Van Gysel (ann.vangysel@vib.be , 32-9-244-66-11) VIB, Flanders Interuniversity Institute of Biotechnology, http://www.vib.be

Source: Link between Alzheimer's disease and traumatic brain damage clarified. Vib.be Press Release (3 August 2005) [FullText]

"SYDNEY, Aug 4 (Reuters) - Australian scientists say they have identified a toxin which plays a key role in the onset of Alzheimer's, raising hope that a drug targeting the toxin could be developed to slow the degenerative brain disease.

The toxin, called quinolinic acid, kills nerve cells in the brain, leading to dysfunction and death, the scientists said. "Quinolinic acid may not be the cause of Alzheimer's disease, but it plays a key role in its progression," Alzheimer's researcher Dr Karen Cullen from the University of Sydney said in a statement. "It's the smoking gun, if you like." "While we won't be able to prevent people from getting Alzheimer's disease, we may eventually, with the use of drugs, be able to slow down the progression."

Alzheimer's is a brain-destroying disease that affects millions of people around the world. As the population gets steadily older, experts estimate numbers will balloon to as many as 16 million in the United States alone by 2015. More than 200,000 people have Alzheimer's disease in Australia and the number is expected to rise to 730,000 by 2050. Outward symptoms start with memory loss, which progresses to complete helplessness as brain cells are destroyed. In the brain, neurons die as messy plaques and tangles of protein form.

The Alzheimer's research team from Sydney's St Vincent's Hospital, the University of Sydney and Japan's Hokkaido University found quinolinic acid neurotoxicity in the brains of dementia patients. Quinolinic acid is part of a biochemical pathway called the kynurenine pathway which is also found in other brain disorders, including Huntington's disease and schizophrenia. The scientists said there were several drugs in an advanced stage of development for other conditions which targeted this pathway and that these drugs, which still need to be tested, could be used to complement other treatments for Alzheimer's..."

Source: Alzheimer's toxin may be key to slowing disease. Reuters (4 August 2005) [FullText]

"VERNON HILLS, Ill. - Aug. 3, 2005 - A diagnostic test developed by Applied NeuroSolutions, Inc. (OTCBB:APNS)(www.appliedneurosolutions.com) to detect the early onset of Alzheimer's disease was the subject of a "Healthwatch" story on WCBS-TV in New York last week, the company said.

The story, which aired last week on CBS2 News in New York at 5:00 pm and is being picked up by CBS affiliates across the country, called the cerebrospinal fluid (CSF) test assay "a promising new test for Alzheimer's" and noted the importance of detecting the disease early on, when it may be possible to stall or slow the progression of the disease. The story can be viewed by accessing the following link: http://wcbstv.com/video/?id=79071@wcbs.dayport.com

Dr. Peter Davies, founding Scientist of Applied NeuroSolutions and the Judith and Burton P. Resnick Professor of Alzheimer's Disease Research at Albert Einstein College of Medicine (AECOM), was quoted throughout the piece and noted that the company's test is "very good, (with) 85-95 percent agreement with the clinical diagnosis."

Applied NeuroSolutions has a long-term agreement with AECOM that gives it the exclusive licensing rights to commercialize Dr. Davies' Alzheimer's related discoveries.

Dr. John DeBernardis, President and CEO of Applied NeuroSolutions, said, "We are very pleased that the media is taking note of the importance of our diagnostic test to detect Alzheimer's disease. This is especially important because there are no diagnostic tests currently available, and the disease is so often confused with other neurological disorders." Dr. DeBernardis continued, "We are hoping to finalize a deal with a clinical reference laboratory in order to make our test available under a CLIA exemption. This would make the test available as a research tool prior to FDA approval. We anticipate starting our clinical trials, leading towards FDA approval, before year end."

Applied NeuroSolutions, Inc. is developing products to diagnose and treat Alzheimer's disease based on a novel hypothesis of AD pathology. In partnership with Dr. Peter Davies and a scientific team at Albert Einstein College of Medicine, Applied NeuroSolutions has developed a cerebrospinal fluid (CSF) test to detect Alzheimer's disease at a very early stage with 85%-95% accuracy in more than 3,000 patient samples.

The company is also developing a blood serum-based screening test, as well as a new class of therapeutics to treat AD. Alzheimer's disease currently afflicts over 4 million Americans, and the market for AD therapy is expected to grow to 21 million patients by 2010 in the seven major pharmaceutical markets (USA, France, Germany, Italy, Spain, U.K. and Japan) according to BioPortfolio, Ltd.

There are currently no FDA-approved diagnostic tests to detect Alzheimer's disease."

Source: Applied NeuroSolutions' Diagnostic Alzheimer's Disease Test Focus of Story on CBS News TV Stations. BusinessWire (3 August 2005) [FullText]

"Fierce competition to find a drug that could delay onset of or prevent Alzheimer's disease is a relatively recent phenomenon. Why was this potential blockbuster shunned for so long?

...Now, as the baby boom generation starts to inch past middle age, a new contender has emerged for that unappealing label: Alzheimer's disease (AD).
An estimated 4.5 million Americans already have the neurodegenerative condition, and that number could more than triple by 2050. Devastating to both those afflicted and their caregivers, the illness exerts a $100-billion-a-year drain on the U.S. economy, according to the Biotechnology Industry Organization.

...So when Science looked for a condition that illustrates the challenges confronting the pharmaceutical industry--and the opportunities that beckon--AD was an obvious candidate. A drug that slows the disease could be especially lucrative because it presumably would need to be taken well before the first symptoms are likely to appear, and then for life. "Everyone recognizes that this is a great, unmet medical need. The drug company that succeeds here will be a very successful company," says Peter Boxer, associate director of central nervous system (CNS) pharmacology at Pfizer Global Research and Development in Ann Arbor, Michigan.

That recognition is fairly new, however. Academic and federal scientists had to lobby hard in the late 1980s to get Parke-Davis to conduct the first major clinical trial of an Alzheimer's drug. Although that drug, tacrine, and related compounds known as acetycholinesterase inhibitors rang up about $3 billion in sales for AD therapy in 2003, they are less than ideal medicines. They don't halt the underlying progression of the disease, and their slowing of cognitive decline is temporary.

But even a less-than-perfect AD drug could still be a blockbuster for companies. It would also be a boon for society: Because the prevalence of Alzheimer's disease increases exponentially with age, drugs that provide a modest 5-year delay in the onset of symptoms would reduce the number of affected people by as much as 50%.

Industrial nihilism

Although drug development for AD is a relatively young endeavor, the condition was identified nearly a century ago by German neuropathologist and psychiatrist Alois Alzheimer. In 1906, he gave a lecture on a 51-year-old woman who had died with dementia. An autopsy found that her brain was littered with extracellular masses (plaques) and intracellular clumps (neurofibrillary tangles) that have since become the diagnostic hallmark of the disease that now bears his name. But for decades, because it wasn't diagnosable until after death, AD remained an obscure condition, and study of the illness was a scientific backwater. "No one wanted to get into [AD research] because it was seen as an unpromising career path leading to a scientific dead end," recalls Zaven Khachaturian, former director of the Office of Alzheimer's Disease Research at the National Institute on Aging (NIA).

The same pessimism about AD held true in industry. "There was very little interest because the disease could not be diagnosed, and the prevailing wisdom considered it an untreatable normal consequence of aging," says Khachaturian

...In the absence of hard evidence, a few vague theories took root. Some researchers argued that the dementia in general stemmed from inadequate blood flow within the brain, giving a slight boost to a class of drugs called cerebral vasodilators. Similarly, compounds that promoted learning and memory in animals--drugs known as nootropics, which means "growing the mind"--were also suggested as dementia treatments...

The scientific hook

Drug development for AD didn't truly get started until the cholinergic hypothesis emerged in the late 1970s, largely through the efforts of British neuroscientists such as Peter Davies, now at Albert Einstein College of Medicine in New York City [AlzClubC: and Applied NeuroSolutions]. In 1976, for example, he and a colleague reported that compared to normal brains, those from several people who had had the brain disorder had decreased levels of an enzyme that helps make the neuro-transmitter acetylcholine. Those data, combined with earlier evidence that drugs blocking the cholinergic system produced memory problems in people, led Davies and others to argue that the core defect in AD was a lack of acetylcholine.

Image: Double trouble. The pathological hallmarks of Alzheimer's disease are extracellular brain deposits of amyloid called plaques (large blue oval in corner) and intracellular clumps of tau known as tangles (smaller blue masses).

"Until that time, dementia was primarily looked at as an amorphous mental disorder," says Khachaturian. "The cholinergic hypothesis was the first scientific hook that could provide a clear path to understand the underlying neurochemistry of AD. It also gave us a plausible scientific rationale for developing treatments because so much was known about the cholinergic system." That knowledge, says Dunbar, "meant we were in neuropharmacology that the industry understood." There was also an obvious therapeutic road map to follow. It drew from work a decade earlier showing that the symptoms of Parkinson"s disease stemmed from the death of dopamineproducing neurons and that L-dopa, a dopamine precursor, could bring about miraculous recoveries in patients. Could curing AD, researchers asked, be as simple as replacing acetylcholine?

Not quite. Efforts to deliver acetylcholine precursors to the brain met with little success. In 1986, however, a different strategy grabbed the spotlight. A research team reported remarkable benefits for a few AD patients taking the well-studied compound oral tetrahydroaminoacridine, also called tacrine, which blocks the activity of an enzyme that breaks down acetylcholine.

Quickly deciding to push for a validation study on the efficacy of tacrine, Khachaturian and the directors of the recently created, NIA-funded network of Alzheimer's Disease Research Centers sought a company to formulate the compound, which was off-patent, into various doses and quantities needed for a full-scale trial. They found an advocate in Elkan Gamzu at Parke-Davis. "Having a person inside that company lobbying for an efficacy study was very important to getting that first drug to go," says Khachaturian.

Parke-Davis, a division of Warner-Lambert Co. that later became part of Pfizer, started its tacrine study in 1987. But the drug, marketed as Cognex, failed to pass muster with a Food and Drug Administration (FDA) advisory board in 1991. After further trials with higher doses, the drug won FDA approval in 1993, albeit not without controversy. "The scientific community was not very enthusiastic about it because the benefits were marginal and it had a lot of side effects," says Khachaturian.

Still, its approval validated the cognitive tests that had recently been developed to gauge drug efficacy for the disease and provided clear guidelines on how to conduct clinical trials for AD. "If the FDA had set the bar very high and not approved it, then that would have been the kiss of death. No other company would have gotten into developing [AD] therapies," says Khachaturian. "Once tacrine was approved, a lot of other companies jumped on the bandwagon" to develop safer and more potent acetylcholinesterase inhibitors, notes Boxer. (Six of the seven drugs currently approved in the U.S. for AD are in this class.)

Image: Keep apart? Now in phase III study, the drug Alzhemed blocks proteoglycan molecules from helping amyloid form fibrils.

The quick follow-up to tacrine by other drugs targeting the same enzyme illustrates an important principle of drug development. Even before a company with a head start on a target proves the value of a class of drugs, other firms will generally have similarly acting "me, too" drugs with improved properties in their pipeline. For competition's sake, says Boxer, "you can't wait for other companies' clinical data."
The acetylcholinesterase inhibitors spurred research into other ways of tweaking the cholinergic system. Acetylcholine operates through two classes of receptors, muscarinic and nicotinic, and major pharmaceutical companies vigorously pursued muscarinic agonists until troublesome side effects slowed their development. "Big pharma is still plugging away at the muscarinic hypothesis," says Dunbar. That has left room for his current firm, Targacept, to develop AD drugs that target nicotinic receptors.

The amyloid hypothesis

Still, halting the decline of the cholinergic system in AD is not the same as curing, preventing, or even slowing the actual pathology of the illness. In fact, the benefits of acetycholinesterase inhibitors are so questionable that a government panel evaluating drugs for the U.K. health care system recently issued a preliminary opinion that the drugs aren't worth buying, a viewpoint the makers of the drugs have strongly challenged.

Most companies seeking more fundamental treatments for AD are focusing on a protein fragment called amyloid, which in 1984 was shown to be the primary component of the brain"s plaques. That discovery spawned the amyloid hypothesis, which holds that the buildup of amyloid causes AD by harming or killing brain cells. In 1991, scientists found that several families plagued by an early-onset form of AD had mutations in the gene encoding amyloid precursor protein (APP), from which amyloid is derived. A few years later, similar disease-causing mutations were found in genes encoding proteins called presenilins that were subsequently shown to affect APP processing into amyloid.

The amyloid hypothesis provided a bounty of new targets and potential strategies. Some companies tried to prevent -amyloid molecules from clumping together, for example, while others began testing whether known drugs, such as statins and nonsteroidal anti-inflammatories, alter -amyloid production.

The novel hypothesis opened the door for small biotech companies, too. Neurochem, which was founded in 1993 in Laval, Canada, drew upon research licensed from Queen's University in Kingston regarding proteoglycan molecules in the brain that bind to amyloid and promote the formation of the amyloid fibrils that make up plaques. The company has developed small organic molecules that mimic these proteoglycans, occupying their binding sites on amyloid and preventing fibrils. Earlier this year, Neurochem launched a phase III trial of its lead Alzheimer's treatment, Alzhemed, seeking to become the first to bring an amyloid-modifying drug to market.

Few firms are trying to directly block -amyloid molecules from aggregating, notes Dennis Garceau, senior vice president of drug development at Neurochem. "Big companies like to target enzymes; it's a more conventional target," he says. Indeed, the fiercest competition has been to develop secretase inhibitors, compounds that block the enzymes that cut APP into the smaller -amyloid fragment.

The race began in 1999 when a secretase that acts upon APP was identified. (After the initial published report by Amgen, several other firms quickly revealed that they too had identified the same potential secretase, perhaps setting the stage for a patent fight.) "Everyone went after that target right away. It was such a rational target," says Boxer, who recalls hearing that another company had launched a major effort to inhibit the enzyme within a week of the announcement of its discovery.

The identified secretase was a particularly inviting target because it belonged to the same family of enzymes as HIV's protease. Several protease inhibitors had already been approved as AIDS drugs, allowing companies to draw on those experiences.

It takes two cuts to make amyloid out of APP, however. Drug companies weren't ignoring the other key enzyme, secretase, but they just weren't clear what it was. A theory that presenilins were secretases took several years to be accepted after its 1999 proposal. Still, even without a clear identification of the enzyme, several firms had developed in vitro systems displaying -secretase activity upon which they could test potential inhibitors.

Image: PET project. Using a compound developed at the University of Pittsburgh, researchers can now use PET scans to image the amount of amyloid in brains of people with (left) or without (right) Alzheimer's disease. Such an ability could help drug companies monitor whether a drug is helping a person with Alzheimer's disease.

Current efforts to develop secretase inhibitors remain shrouded in corporate secrecy. Bristol-Myers Squibb reportedly began clinical testing a gamma-secretase inhibitor in 2001 and stopped because of side effects, but it has never publicly reported those results. Eli Lilly has also just begun clinical testing of a gamma-secretase inhibitor. The challenge in developing such drugs seems to be blocking their action on enzymes needed for activities other than cutting up APP. Gamma secretases also cleave a protein called Notch, for example, that's important in development and the immune system. As a result, companies must find compounds that more specifically affect APP processing.

A surprise vaccine

While the amyloid hypothesis has offered drug researchers a number of obvious targets and strategies, it also led to the most surprising attempt to thwart AD. In the late 1990s, long after his colleagues at Elan had tested their most promising compounds, Schenk suggested injecting a few mice with amyloid itself. His goal was to raise an antibody or other immune response against plaques. "No one thought it would work. Even after the experiment was done, the results weren't analyzed for a while," recalls Schenk.

The results were stunning. The immunization slowed or prevented the development of -amyloid plaques in young mice and even wiped away preexisting ones in older mice. The episode illustrates how one person's idea can change the direction of a company or a field. "Dale was really brave," says John Trojanowski of the University of Pennsylvania School of Medicine in Philadelphia.

How does big pharma react when a disease-treating strategy such as the Elan vaccine comes out of the blue? Most large companies working on CNS drugs have experience with small-molecule drugs, not antibodies, says Boxer. And although firms can always tweak an enzyme inhibitor to make a better drug and carve out some market share, vaccines tend to either work or not. "We look at this stuff and go, 'Huh?'" says Boxer. "Where is your unique drug?" As result, he says, most companies have conceded the vaccine approach to Elan.

The unexpected emergence of the Elan vaccine illustrates the importance and limitations of animal models. For several years, companies pursuing the amyloid hypothesis were largely stuck in vitro. Attempts to genetically engineer mice that overproduced APP seemed fruitless; there was even a notable fraud case in which a researcher published a picture of a human plaque as evidence that his mice had developed -amyloid clumps. "The entire field was trying to make a mouse model," says Schenk.

Then a failing biotech company trying to sell off its assets approached Elan and saved the day, ultimately setting the stage for the vaccine's proof of principle. The struggling company's transgenic rodents were greatly overexpressing APP, and when Elan scientists checked out the mice, they found numerous brain plaques. Elan acquired the rights to the mice and quickly began testing its compounds. The company eventually allowed the -amyloid vaccine strategy to be tested. Without that animal model, the idea might have faded away.

Having animal models reduces the risk, and thus the cost, of developing drugs. For small companies such as Neurochem, they can also be a lifeline to continued funding from venture capitalists and other sources. "Until we got proof of concept in vivo, people were a little bit skeptical," says Garceau.

...Yet animal models also reveal the risks of drug development. Elan's vaccine approach seemed to work well in mice, but brain inflammation in a few patients triggered an abrupt halt to the clinical trial. Elan, together with its partner Wyeth, is now conducting clinical trials with plaque-targeting immunotherapy strategies such as passive administration of antibodies to amyloid.

But how can a company pursuing amyloid-based therapies for AD know if its drug or treatment is working? Showing that people maintain the same cognitive and memory skills, or improve such skills, can be difficult and time-consuming. Unfortunately, there are no well-accepted AD biomarkers, like cholesterol levels for heart disease or viral load for AIDS. A lack of animal models and biomarkers are "two difficult issues for developing a drug," says Boxer.

The biomarker obstacle has led companies such as Pfizer, Merck, Eli Lilly, and Elan to partner with the Alzheimer's Association, NIA, the National Institute of Biomedical Imaging and Bioengineering, and FDA to identify ways of measuring progression of mild cognitive impairment and AD in people. Industry will pick up one-third of the cost of the $60 million, 5-year effort, known as the Alzheimer's Disease Neuroimaging Initiative, that will test various ways of imaging brain plaques and tangles as well as measuring levels of proteins in blood, urine, and cerebrospinal fluid. "It's so difficult [to develop an Alzheimer's treatment without biomarkers] that the drug companies are collaborating," says Boxer.

What about tau?

It's sometimes forgotten that the effort to develop amyloid-based treatments represents a huge and costly gamble on a single, unverified theory of AD. There are many other hypotheses being explored by small numbers of scientists or a handful of tiny biotech firms. One is the second major theory of AD, which involves tangles, the intracellular brain lesions identified by Alois Alzheimer.

In the early days, Alzheimer's researchers were divided over whether plaques or tangles were more important. The identification of amyloid in plaques and disease-causing mutations in the APP gene relegated tangles and their primary constituent, a hyperphosphorylated form of a protein called tau, to a sideshow. "We were the token other pathway at every meeting," recalls Trojanowski; he and his wife Virginia Lee have been the most vocal proponents of tangles and tau research.

For companies, that lack of interest was partly a matter of simple economics. "Even big pharma can only pick a certain number of targets," says Dunbar, noting that Bristol-Myers Squibb, where he used to direct clinical development of CNS drugs, has never had a tau program to his knowledge. Tau is now drawing more attention, in part because of a 1998 paper in which researchers showed that mutations in a gene encoding one of the human versions of tau lead to a rare form of dementia that bears some similarities, such as tau tangles, to AD. "It launched studies that should have been done in the early 1990s," says Trojanowski.

Trojanowski contends that tau, when it becomes overloaded with phosphate groups, can no longer bind to and stabilize cellular filaments called microtubules. That change disrupts the ability of neurons to transport molecules down the long extensions known as axons. Back in 1994, his team proposed that microtubule-stabilizing compounds, such as the cancer drug Taxol, might treat AD. And earlier this year, in the 4 January Proceedings of the National Academy of Sciences, they offered a proof of concept in mice genetically engineered to overproduce a human version of tau.

These rodents suffer from a neurodegenerative disorder that includes tanglelike masses of hyperphosphorylated tau and impaired axon function. As hypothesized, the administration of Taxol sped up the animals' axonal transport and ameliorated their motor problems. Trojanowksi and his colleagues are now working with Angiotech Pharmaceuticals in Vancouver, British Columbia, and other firms are sniffing around. "I know pharma is interested," he says. "My phone rings more often."

Partnerships and future

Will the next significant drug for AD come from a small biotech company or big pharma? Given the economics of drug development, it's likely that the Davids and Goliaths will end up working together. "It's very difficult for a small company to take a drug all the way to market," notes Targacept's Dunbar. His company's strategy, for example, is to push a drug only through phase II trials and then "outsource it to big pharma." And Neurochem says it would be open to partnerships with bigger companies given the right deal.

...Still, the search for Alzheimer's drugs should leave room for many companies, small and large, to prosper. "This disease will need a cocktail of treatments," predicts Neurochem's Garceau."

Source:John Travis. Saving the Mind Faces High Hurdles. Science. Vol 309, Issue 5735, p. 731 (29 July 2005) [FullText]

"One-quarter of the population will be at high risk for cognitive impairment and Alzheimer's disease by 2025."

Source: Big market seen in neurotech field. Contra Costa Times - CA,USA (July 2005) [FullText (subscription required)]