Alzheimer’s disease is a progressive brain disorder that gradually destroys a person’s memory and ability to learn, reason, make judgments, communicate and carry out daily activities. As Alzheimer’s progresses, individuals may also experience changes in personality and behavior, such as anxiety, suspiciousness or agitation, as well as delusions or hallucinations. Although there is currently no cure for Alzheimer’s, new treatments are on the horizon as a result of accelerating insight into the biology of the disease. Research has also shown that effective care and support can improve quality of life for individuals and their caregivers over the course of the disease from diagnosis to the end of life.

The greatest known risk factor for Alzheimer’s is increasing age. Most individuals with the disease are 65 or older. The likelihood of developing Alzheimer’s doubles about every five years after age 65. After age 85, the risk reaches nearly 50 percent.

Most researchers say a protein called beta-amyloid is at the root of Alzheimer’s. The protein appears to build up into plaques in the brain and progressively kill neurons, or nerve cells, in a process known as the “amyloid cascade.” Many of the drugs being studied aim to interrupt this cascade.

Following links are helpful to know more about this disease.

Alzheimer’s Association

National Institute of Aging

Medline Plus

Developments to watch:

Scientists are exploring several promising avenues in drug research that could strengthen the battery of weapons used to slow the scourge of Alzheimer’s disease. A handful of drugs — some originally approved for other diseases — are showing some success in clinical trials at slowing the cognitive decline that is the hallmark of Alzheimer’s. A few, including a prostate-cancer drug, a diabetes drug and a medicine derived from an old class of anti-inflammatory drugs, are in late-stage trials. Their makers say they expect to seek regulatory approval for the treatment of Alzheimer’s within a few years. Other compounds, including cholesterol-lowering statins and antibodies that bolster the immune response against the disease, are also showing promise.

If approved for Alzheimer’s, the drugs could be a huge breakthrough because they seek to modify the brain processes that cause Alzheimer’s, even though those processes aren’t fully understood. In contrast, none of the currently approved medicines attack the underlying mechanisms of the disease, offering only limited relief from some symptoms. The four drugs currently approved for Alzheimer’s — Aricept, Exelon, Razadyne and Namenda — are a huge business.

Alone, sales of Aricept, co-marketed in the U.S. by Pfizer Inc. and Eisai Inc., totaled $1.06 billion in the year ended March 31. But typically, patients gain only modest cognitive improvement for less than 18 months. Then, they start to deteriorate again.

Some of the most promising results to date involve Flurizan, which is derived from an anti-inflammatory and is being tested by Myriad Genetics Inc. The drug targets an enzyme, called gamma secretase, that is believed to play a role in the build-up of amyloid. The company is scheduled to finish its final U.S. study in the spring of 2008, and hopes to apply to the Food and Drug Administration that summer, says Executive Vice President Bill Hockett.

Some researchers think that the best approach may turn out to be a cocktail of different compounds. Different drugs may also work better for different patients, depending on gender and genetics. For example, leuprolide, the prostate-cancer drug that is being tested in Alzheimer’s patients by Voyager Pharmaceuticals Inc. of Raleigh, N.C., has appeared more effective in women than in men. Leuprolide, approved as Lupron for prostate cancer, targets luteinizing hormone, a pituitary hormone believed to promote the production of beta-amyloid.

The diabetes drug Avandia is believed to play a role in how brain cells metabolize glucose, a process that GlaxoSmithKline researcher Allen Roses believes will eventually prove to be the culprit in Alzheimer’s. Dr. Roses says he is “optimistic” that Phase III trials now getting under way will pave the way for approval of the drug for Alzheimer’s. Those trials will enroll about 2,800 patients in the U.S. and 32 other countries, according to a Glaxo spokesman.

Cholesterol-lowering statin drugs are also showing some promise. Through the National Institute on Aging, the NIH has funded a recently completed study to test whether the statin Zocor, from Merck & Co., can stall Alzheimer’s in patients with normal cholesterol levels. “The idea is that lipid lowering seems to also lower the amount of amyloid in the brain,” says Mary Sano, director of the Alzheimer’s Disease Research Center at Mount Sinai Hospital in New York. In addition, Pfizer is recruiting patients for a study of Lipitor in Alzheimer’s patients.

While these drugs are already on the market for other conditions, doctors and researchers say it would be unwise to prescribe or use any medicines “off-label” for Alzheimer’s. The patients who are taking them now are in the controlled environment of a clinical trial with heavy oversight, researchers note, and problems could still crop up, even during the last rounds of testing.

New Drugs for Alzheimer Disease:

• Researchers also tout Alzhemed, a drug being developed by a Canadian company, Neurochem Inc., in a Montreal suburb. In an earlier study, patients with mild Alzheimer’s remained stable for 20 months. Some patients who participated in an extended study have been getting the medication for three years and “have stayed the same,” says spokeswoman Lise Hebert.

• Some researchers are looking at ways to stimulate the immune system to fight the disease. Researchers at Eli Lilly & Co. are in the early stages of trials of an antibody that binds to beta-amyloid and prevents it from building up. That study is still recruiting patients. Lilly investigators are further along in trials of a drug that moderates the activity of an enzyme that appears to promote the production of amyloid, says company researcher Eric Siemers.

• Wyeth, Madison, N.J., is working with Elan Pharmaceuticals Inc. to develop an injectable protein that would prevent the build-up of beta amyloid.

Update on Dec 18, 2006 — Detect Alzheimer Early:

The amount of cholesterol in the blood is usually a good indicator of a person’s risk of suffering heart disease. Now scientists are making headway in developing a similar test to detect the earliest stages of Alzheimer’s disease.

Over the past two years, rival scientists in the U.S. and Europe have identified a series of proteins, known as biomarkers, whose presence in blood or spinal fluid may indicate whether a patient has Alzheimer’s, the most common form of dementia. In the short term, that could lead to better and earlier diagnosis of Alzheimer’s patients. In the longer term, it could yield more-effective drugs and even reduce the cost of developing them.

The search for Alzheimer’s biomarkers “is a hot field, and the goal is a very big one,” says Simon Lovestone, a professor of geriatric psychiatry at King’s College London, who led a team that recently found two such biomarkers in blood. “It’s a step along the way to better treatment.”

Both the European Commission and the U.S. National Institutes of Health are funding large-scale projects on Alzheimer biomarkers. In a new paper appeared in the Annals of Neurology, researchers from Cornell University in Ithaca, N.Y., and Weill Cornell Medical College in New York describe how they have identified 23 biomarker proteins for Alzheimer’s in a trial of nearly 100 patients. The results need to be replicated in a larger clinical trial — and plenty of challenges remain before the findings can become the basis for a reliable clinical test.

Still, the study is a “good start,” says Susan Molchan, who leads a new $60 million project at the NIH’s National Institute on Aging, which is also seeking to identify Alzheimer’s biomarkers. “We want to identify patients earlier and treat them earlier,” she adds. Dr. Molchan has read the Annals of Neurology paper but wasn’t involved in the research.

Diagnosing Alzheimer’s can be tricky, especially in the early course of the illness when many of its symptoms — such as mild forgetfulness — resemble those of other maladies, such as depression or stress, or the natural aging process. That’s why most neurologists can only diagnose “possible” or “probable” Alzheimer’s. The only foolproof way to verify the existence of the disease is to study the brain after death.

A biomarker-based test holds the promise of an early diagnosis for Alzheimer’s. It would enable patients to be treated at the initial stages of their illness, when they are most likely to respond. Families would also have the chance to discuss care options with patients while they are still able to participate in the decisions.

A biomarker protein is a telltale chemical fingerprint that can be detected in parts of the body, such as blood or spinal fluid. If biomarkers for Alzheimer’s are found in a person’s spinal fluid, for example, they can confirm a diagnosis of the disease. Better yet, “if you know how these markers change as the disease progresses, you might be able to alter them” with a drug, thus stalling or reversing the course of the illness, says Norman Relkin, a professor at Weill Cornell Medical College and a co-author of the latest study.

For several years, doctors in European countries — especially Sweden — have extracted spinal fluid from symptomatic patients and tested it for three biomarker proteins that appear to indicate the existence of Alzheimer’s. At the same time, they use brain scans and other tests to exclude other cognitive disorders.

In February 2006, Swedish scientists published a five-year study in the journal Lancet Neurology, describing how the relative progression to Alzheimer’s disease in patients with mild cognitive impairment was significantly increased if their spinal fluid contained abnormal amounts of the same three biomarker proteins, known as b-amyloid, total tau and phosphorylated-tau.

In October 2006, researchers from King’s College London and their collaborators, Proteome Sciences PLC, said they had discovered 15 protein biomarkers associated with Alzheimer’s in patients’ blood.

Two of these proteins, involved in an inflammation response, may play an especially significant role in the disease, the researchers say. Their findings, based on blood tests from 500 U.K. patients, appeared in the journal Brain. The next step: The scientists hope to verify the data in a larger trial and see whether the two proteins can be used to predict how Alzheimer’s disease progresses.

Researchers in the U.S. are also involved in the quest for Alzheimer biomarkers. In February 2005, scientists at Northwestern University claimed that they had become one of the first to detect a significant biomarker for the disease in living patients. They found tiny amounts of a toxic protein, ADDL, in the spinal fluid of living Alzheimer’s patients. Previous research had suggested that ADDL may accumulate at the beginning of the illness and block memory function. The findings appeared in the Proceedings of the National Academy of Sciences. Nanosphere Inc., a biotechnology firm in Northbrook , Ill. , hopes to use the results to develop a diagnostic test.

The new paper appeared in the Annals of Neurology may be the farthest-reaching one so far. Researchers compared 2,000 proteins in patients with Alzheimer’s and in those without. As a result, they homed in on 23 proteins that seemed strongly associated with the disease.