Potential Alzheimer's Treatments

Many potential treatments for Alzheimer's disease are being investigated in laboratories and tested in human clinical trials. Scientists continue basic research on therapies that could potentially clear the protein plaques in the brain. The safety and efficacy of possible treatments are being tested on humans, including drugs that could remove plaques, immunotherapy with beta amyloid antibodies, non-steroidal anti-inflammatory drugs (NSAIDs) and statins (drugs used to lower cholesterol). The protective effects of estrogen, antioxidants (Vitamins A, C and E), ginkgo biloba and omega-3 fatty acids (found mainly in fish such as tuna and salmon) are also being tested in trials. To date, no consistent results have emerged from various studies, but further research and future data from rigorous trials should help clarify the benefit of these and other treatments.

In this section, you will find information on:

• Antioxidants
• Alzheimer’s Vaccine
• Non-steroidal Anti-inflammatory Drugs (NSAIDs)
• Statins
• Estrogen
• Ginkgo Biloba
• Omega-3 Fatty Acids

Antioxidants

The body’s cells undergo normal chemical reactions during a process called oxidation; free radicals are often a byproduct of this process. These free radicals are highly reactive, unstable molecules that attack other molecules, harming cells and tissue. This oxidative stress is believed to be at least partially responsible for brain cell damage in Alzheimer’s disease. Antioxidants, including vitamins C and E, and beta carotene (vitamin A), protect against free radical damage. They are found in certain foods as well as dietary supplements.

Alzheimer's disease: Some studies suggest that the use of vitamin E supplements could postpone or prevent the cognitive decline associated with Alzheimer's disease, but other investigations have produced conflicting results. One clinical trial is currently testing whether vitamins E and C, and two other antioxidants, alpha lipoic acid and coenzyme Q, can slow disease progression. Another clinical trial is examining whether vitamin E and/or selenium can prevent Alzheimer's disease or cognitive decline.

Mild cognitive impairment (MCI): People with MCI experience memory problems, but are able to function independently; however, MCI is often a transitional stage that leads to the serious cognitive decline of Alzheimer's disease. In April of 2005, the New England Journal of Medicine published results of a study that compared the use of vitamin E, Aricept® (donepezil - an Alzheimer's disease treatment) and a placebo in delaying progression from MCI to Alzheimer’s disease. The study found that over the course of three years, none of the treatments affected the advance of the disease.

Further rigorous scientific research is needed to determine the role of antioxidants in protecting against Alzheimer’s disease.

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Alzheimer's Vaccine

Scientists have succeeded in eradicating many deadly diseases through vaccination, and some day this same approach might prevent or cure Alzheimer’s disease. 

Researchers generally agree that a build up of beta amyloid protein in the brain plays an important role in Alzheimer’s disease. Thus, prevention or clearing of the protein accumulation could be an effective treatment. In 1999, studies revealed that injection of the beta amyloid itself, called active immunization, caused laboratory mice to produce antibodies against the protein and reduced its accumulation. Spurred on by the potential of immunotherapy, some pharmaceutical companies started human clinical trials. In 2001, Elan and Wyeth began actively immunizing over 300 Alzheimer’s patients with beta amyloid. The trials were halted in 2002 when about six percent of participants developed a potentially serious side effect, acute encephalitis (inflammation in the brain).  Several participants later died from other causes. Autopsies revealed that a large amount of beta amyloid had been cleared from their brains, their brain volume was lower, and lower levels of tau, another protein related to Alzheimer’s disease, were found in their spinal fluid. Further, for the living trial participants who developed antibodies, there was evidence of better memory, attention and concentration.

In 2007, further human trials testing the efficacy and safety (Phase II) of passive immunotherapy were initiated. In passive immunotherapy, antibodies to a protein rather than the protein itself are given to the recipient. By using this form, researchers believe they can avoid the side effects that resulted from earlier trials of the active vaccination. Data from Phase II data of these trials is expected for release in 2008, and Phase III clinical trials that will involve more participants are also planned.

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Non-steroidal Anti-inflammatory Drugs (NSAIDs)

Studies suggest that brain inflammation may play a role in damage due to Alzheimer’s disease, and early observations indicated that NSAIDs could potentially slow disease progression. However, studies and human clinical trials have produced conflicting results. A trial of three NSAIDs, Aleve® (naproxen), Vioxx® (rofecoxib) and Celebrex® (celecoxib) showed that these drugs did not delay the advance of the disease. Trials of naproxen and Celebrex were suspended before completion due to concerns about an elevated risk of stroke and heart attack for participants. In early 2008, researchers examining data from the U.S. Veterans Affairs Health Care System found that long-term (5-year) NSAID use, particularly the use of ibuprofen, appeared to protect against Alzheimer’s. Another study looking at results from six previous investigations suggested that naproxen, ibuprofen and aspirin may reduce the risk of Alzheimer’s disease. However, experts do not currently recommend NSAID treatment for Alzheimer’s. More clinical trials will be necessary as researchers continue to explore the role of anti-inflammatory drugs in the treatment or prevention of Alzheimer’s.

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Statins

Several clinical trials are underway to test whether various types of statins (cholesterol-lowering drugs) can help slow the progression of Alzheimer’s disease. Past studies have produced conflicting results, and further human clinical trials will be necessary before any statin therapy is recommended. In 2007, researchers at the Boston University School of Medicine examined data from the U.S. Veterans Affairs Medical System, and found that a statin called Zocor® (simvastatin) appeared to reduce the incidence of Alzheimer’s. However, in January 2008, data obtained from Catholic clergyman by scientists at the Rush University Medical Center showed no relationship between statins and cognitive decline. In April 2008, Pfizer, a pharmaceutical company that manufactures Lipitor® (atorvastatin calcium), reported no significant difference between clinical trial participants given Lipitor and Aricept®, and those given Aricept and a placebo.

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Estrogen

Research suggests that estrogen taken to manage the symptoms of menopause may also protect the brain. Therefore, scientists have been interested in whether estrogen could reduce the risk or slow the advance of Alzheimer's. However, clinical trials of those already diagnosed with the disease, showed that estrogen had no impact on its progression. Other studies indicate that women who begin using estrogen after age 60 to 65 are at increased risk of developing dementia, as well as heart attack and stroke. Estrogen is now only recommended for short term use to treat menopausal symptoms.

Recent research has helped clarify the neuroprotective role of estrogen taken by younger women before menopause. According to a study published in August 2007, scientists from the Mayo Clinic found that women who had one or both ovaries removed prior to menopause had an increased long-term risk of dementia or cognitive impairment. However, those who underwent ovary removal, but also had estrogen treatment until at least age 50 did not experience this higher risk. These findings suggest that if taken before menopause, the neuroprotective benefits of estrogen may outweigh the risks of side effects, such as heart problems, stroke and cognitive impairment.

Women of any age should consult with a physician about the individual risks and benefits of undergoing or considering hormone replacement therapy.

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Ginkgo Biloba

Ginkgo biloba, an extract from the leaves of the ginkgo tree, is said to have antioxidant and anti-inflammatory properties. It may also increase blood flow in the brain. However, the results of a large multicenter clinical trial led by the University of Pittsburgh School of Medicine, and published in the Journal of the American Medical Association in November of 2008, found that Ginkgo biloba does not reduce the risk of developing Alzheimer’s disease or dementia in either healthy older individuals or in those with mild cognitive impairment. A similar clinical trial is underway in Europe.

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Omega-3 Fatty Acids

Omega-3 fatty acids are found mainly in “oily” fish such as salmon and albacore tuna, but are also present in certain nuts and oils. Scientists believe they may have a protective effect on the brain. Clinical trials are underway to test whether these fatty acids can slow the both cognitive and functional decline in those with mild to moderate Alzheimer's.

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Source: The information provided above was obtained in part from the National Institute on Aging and the Mayo Clinic.

Last Reviewed On: 09/26/08