Rising Numbers

 Health care costs for the roughly 4.5 million Americans with Alzheimer's disease (AD) exceed $100 billion a year, according to the Alzheimer's Association. As baby boomers age during the next few decades, the number of victims and the dollar costs of care are expected to almost quadruple.

As age increases, so does the risk of getting AD. For each five-year age group beyond 65, the percentage of people with AD doubles, according to the National Institute on Aging (NIA). Nearly half of those over age 85 have it. A small number are diagnosed with "early-onset Alzheimer's," which can strike people in their 30s, but most AD cases are among older people. A person with AD lives an average of eight years after the onset of symptoms, but some live as long as 20 years.

A Disease of the Brain

 AD is a brain disorder that occurs gradually. It starts with mild memory loss, changes in personality and behavior, and a decline in thinking abilities (cognition). It progresses to loss of speech and movement, then total incapacitation and eventually death. It is normal for memory to decline and the ability to absorb complex information to slow as people get older, but AD is not a part of normal aging.

Researchers aren't exactly sure what causes AD, but they do know that people with the disease have an abundance of two abnormal structures in the brain: plaques and tangles. Plaques are dense, sticky substances made up of accumulations of a protein called beta-amyloid. Tangles are twisted fibers caused by changes in a protein called tau. The beta-amyloid plaques reside in the spaces between the billions of nerve cells, or neurons, in the brain, and the neurofibrillary tangles clump together inside the neurons. Plaques and tangles block the normal transport of the electrical messages between the neurons that enable us to think, remember, talk and move. As AD progresses, nerve cells die, the brain shrinks, and the ability to function deteriorates.

Healthy nerve cells in the brain (neurons) have support structures called microtubules, which guide nutrients and molecules from the cell's body down to the ends and back. A special kind of protein, tau, makes the microtubules stable. Tau is changed chemically in people with Alzheimer's disease. It begins to pair with other threads of tau and they become tangled up together. When this happens, the microtubules disintegrate, collapsing the neuron's transport system. This may result first in communication malfunctions between neurons and later in cell death.

Treating the Symptoms

 There is no cure for AD, but there are drugs to treat some of the symptoms. The Food and Drug Administration has approved four prescription drugs for people with mild-to-moderate AD: Cognex (tacrine), Aricept (donepezil), Exelon (rivastigmine), and Reminyl (galantamine). "All of them work by the same mechanism," says Russell Katz, M.D., director of the FDA's Division of Neuropharmacological Drug Products. The drugs increase the level in the brain of acetylcholine--a chemical that nerves use to communicate with each other. "People with AD are deficient in this neurotransmitter, and the drugs work by inhibiting an enzyme called cholinesterase that breaks down the acetylcholine," says Katz. "These cholinesterase inhibitors have an effect on the symptoms, but we have no evidence that they have any effect on the underlying progression of the disease. During treatment, as far as we know, the nerve cells are still dying and the various plaques and tangles are still forming."

"There's healthy debate about whether these drugs actually affect the course of the illness," says Trey Sunderland, M.D., chief of the Geriatric Psychiatry Branch of the National Institute of Mental Health (NIMH). According to the data, says Sunderland, "If people are on the cholinesterase inhibitors, they tend to go to nursing homes later than people who are not on the inhibitors." Some researchers have reported a delay of up to 22 months in going to nursing homes, he adds.

Another drug, Namenda (memantine), is approved to treat people with moderate-to-severe Alzheimer's disease. This drug is thought to work by blocking the action of glutamate, a brain chemical that may be overactive in people with AD.

Continued