Alzheimer's Disease : New Treatments

by National Institute on Aging

(Page 11 of 16)

Research over the last two decades has revealed many pieces of the Alzheimer's disease puzzle. Using recent advances in genetics and molecular biology, scientists have begun to put these pieces into place. In doing so, they've vastly increased our understanding of Alzheimer's Disease and opene many avenues that could lead to effective treatments.

It has become clear that there probably isn't a "magic bullet" that will, by itself, prevent or cure AD. However, scientists may be able to identify a number of interventions that can be used to reduce risk and treat the disease. Today, it is estimated that the National Institute on Aging, other NIH Institutes, and private industry are conducting clinical trials (studies involving humans that rigorously test how well an intervention works) on around 30 compounds that may be active against AD. These studies focus on three main areas: helping people with Alzheimer's Disease maintain their mental functioning, slowing the progress of AD, delaying its onset, or preventing it, managing symptoms.

Helping People with Alzheimer's Disease Maintain their Mental Functioning

In the mid-1970s, scientists discovered that levels of a neurotransmitter called acetylcholine fell sharply in people with Alzheimer's disease. This discovery was one of the first that linked AD with biochemical changes in the brain.

Scientists have found that acetylcholine is a critical player in the process of forming memories. It is used by neurons in the hippocampus and cerebral cortex, which are areas of the brain important to memory function.

By late 2003, the Food and Drug Administration (FDA) had approved five medications to treat AD symptoms. Of these, four are known as cholinesterase inhibitors and are prescribed to treat mild to moderate Alzheimer's Disease symptoms. The first, tacrine (Cognex), has been replaced by three newer drugs - donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne® (formerly known as Reminyl®)). They act by stopping or slowing the action of acetylcholinesterase, an enzyme that normally breaks down acetylcholine. These drugs improve some patients' abilities to carry out activities of daily living, may improve certain thinking, memory, or speaking skills, and can help with certain behavioral symptoms. However, these medications will not stop or reverse AD and appear to help patients only for months to a few years.

The fifth medication is memantine (Namenda), which can be prescribed to treat moderate to severe AD symptoms. This drug appears to work by regulating excess glutamate in the brain. Glutamate is another chemical involved in memory function. Like the cholinesterase inhibitors, memantine will not stop or reverse Alzheimer's Disease. Studies have shown that memantine may delay loss of daily functions in patients with moderate to severe AD.

Helping people with AD carry out their daily lives and maintain their mental abilities is one of the most important goals of Alzheimer's Disease treatment research. Many investigators are working to develop new and better drugs that can preserve this critical function for as long as possible.

Slowing, Delaying, or Preventing Alzheimer's Disease

Understanding how AD develops-from beginning to end-is vital for finding drugs or other factors that may slow, delay, or even prevent the disease.

Investigators are looking at a number of possibilities for drug treatments. For example, inflammation of tissue in the brain and overproduction of free radicals are two processes that are thought to be a feature of AD. Clinical trials in both of these areas are looking at whether specific anti-inflammatory agents and agents that protect against oxidative damage can slow or prevent the development of Alzheimer's Disease.

Scientists are also conducting clinical trials to see if substances already used to reduce cardiovascular risk factors also help lower AD risk or delay progression of the disease. These trials are testing whether supplementation with folic acid and vitamins B6 and B12 can slow the rate of cognitive decline in cognitively normal men and women, women at increased risk of developing dementia, and people diagnosed with AD. A study of statins, the most common type of cholesterol-lowering drug, is also underway to see whether these drugs can slow the rate of disease progression in Alzheimer's Disease patients.

Estrogen is a hormone produced by a woman's ovaries during her childbearing years. Over the past 25 years, laboratory and animal studies, as well as observational studies in women, have suggested that estrogen has some positive effects on brain activity. These findings have created scientific interest in the relationship among estrogen, memory, and cognitive function.

Studies of estrogen in postmenopausal women with mild to moderate AD did not find estrogen beneficial. But, even if estrogen does not slow the progression of the disease in women already affected with AD, scientists thought perhaps menopausal hormone therapy might in some way affect age-related cognitive decline or protect a woman from developing Alzheimer's Disease. Two types of such therapies have been investigated-the use of estrogen alone in women who have had a hysterectomy and the use of estrogen plus progestin, which reduces the risk of thickening of the lining of the uterus and endometrial cancer, in other women.

About the Author

www.nia.nih.gov
NIA, one of the 27 Institutes and Centers of NIH, leads a broad scientific effort to understand the nature of aging and to extend the healthy, active years of life. In 1974, Congress granted authority to form NIA to provide leadership in aging research, training, health information dissemination, and other programs relevant to aging and older people.