In 1906 a German physician made history performing an autopsy on the body of an elderly woman. Dr. Alois Alzheimer was the first to describe the pathological brain tissue structures that characterize the disease that now bears his name. More than half a century would pass before a reliable method of identifying Alzheimer's Disease in living patients would be developed. During those years, the condition was little understood; the dementia was broadly defined as "senility" or "hardening of the arteries," and wrongly assumed to be a natural consequence of aging. Even relatively recently, many doctors looking for hard evidence of the disease remained reluctant to diagnose AD.

Today, specialists can easily differentiate between Alzheimer's Disease (AD) and other dementia-inducing conditions such as depression, prescription drug interaction, thyroid imbalance and multi-infarct dementia (a series of small strokes). With this knowledge, however, came the discovery of just how widespread AD is.

Alzheimer's accounts for more than half of all adult dementia, affecting approximately 4 million Americans. Because the incidence of AD increases with age -- it afflicts 10% of 65-year-olds compared to 50% of those 85 and older -- the Alzheimer's population is expected to double as the Baby Boom generation matures over the next 20 years.

Alzheimer's is an irreversible, degenerative brain disease. Its early stages usually include short-term memory loss and difficulty learning new information. As the condition progresses and cognitive ability deteriorates, patients often experience confusion and disorientation, and are prone to personality changes such as agitation, depression and paranoia. In the final stages, Alzheimer's patients lose almost all cognitive function and require assistance performing even the most basic tasks. Some AD patients have lived as long as two decades with the disease, but most cases run their course in four to eight years. Always fatal, AD results in over 100,000 deaths a year, making it the nation's fourth leading cause of adult mortality.

When Dr. Alzheimer made his observations, he identified two unusual features. The first was a preponderance of neurofibrillary tangles, abnormally twisted protein fibers inside the nerve cells. The second, neuritic plaques, are clusters of degenerative nerve cell parts, often surrounding a core of beta amyloid -- a fragment of a protein known as amyloid percursors protein (APP). Later, it was discovered that these neurofibrillary tangles and neuritic plaques are often accompanied by abnormally low levels of acetylcholine, one of the chemical neurotransmitters that allow nerve cells to communicate with each other.

Recent advances in genetics indicate that there are at least two broad types of Alzheimer's Disease. Early-onset Familial Alzheimer's Disease (FAD) appears in a younger population, often still in their 30s and 40s. Relatively rare (less than 10% of all AD cases), FAD has been traced through certain families around the world, and scientists have been able to correlate its appearance to specific genetic mutations on chromosomes 1,14 and 21.

The genetic clues about the predominant type of AD are more complex. Scientists believe that non-familial, or sporadic Alzheimer's Disease, is the result of a coalescence of elements, including a gene located on chromosome 19. This gene, called APOE, is named for the protein it produces, ApolipoproteinE, which, perhaps significantly, binds with beta amyloid, the fragmented substance found in neuritic plaques.

In 1993, geneticists identified a link between the incidence of late-onset AD and APOE 4, one of three common alleles that can fill the APOE gene. APOE4 was discovered to be present in 40% of patients with late-onset Alzheimer's, even though it is found in only 15% of the population at large.

While meaningful, this discovery did not explain all sporadic AD cases; many other people with late-onset AD do not have the APOE4 allele at all. Therefore, scientists continue looking for other causes. Some are investigating environmental factors, such as exposure to aluminum, which is present in unusually high levels in AD patient brain tissue. Because Alzheimer's disease has symptoms similar to rare conditions like Creutzfeldt-Jakob disease and Kuru, it is possible that AD, too, may be the delayed consequence of a slow-acting virus.

While a thorough understanding of AD's causes remains elusive, several risk factors -- besides advancing age and the APOE4 allele -- have been identified. People with higher education are statistically less likely to get it. Having a family member with AD increases the risk. Some evidence suggests that women are more likely then men to get the disease. Scientists are even analyzing World War II veterans to explore the possibility that suffering a head injury earlier in life may increase the likelihood of contracting AD.

Unlike many other diseases, Alzheimer's still has no known medical markers -- the by-products that indicate a disease's presence. An examination of the brain tissue remains the only definitive diagnosis. Yet properly trained doctors and specialists can now make differential diagnoses with 80-90% accuracy. By integrating information from the patient's medical history, mental ability tests, and physical, psychological and neurological exams, doctors can exclude other causes of dementia and, by a careful and informed process of elimination, zero in on Alzheimer's Disease.

An early diagnosis of AD is a good idea, particularly for the benefits it provides in planning for the future. So while simple memory lapses are natural in older people, whenever there is evidence of unusual difficulty communicating, thinking or reasoning, a medical diagnosis should be sought as soon as possible.

Experts caution against premature genetic testing, however. Unless they are involved in clinical research, people who show no symptoms of Alzheimer's are discouraged from being screened for the APOE4 allele. Non-symptomatic persons with APOE4 may know their risk has increased, but within the limits of current science there is almost nothing they can do about it. Further, others might use the information adversely. An insurance company, for example, knowing that a symptom-free person carries the APOE4 allele, might be tempted to discontinue a health care policy in anticipation of a disease that may never occur.

For those who do develop Alzheimer's, treatment falls into two main categories: medical responses and social responses. To date, the Food and Drug Administration (FDA) has approved only two pharmaceutical treatments for Alzheimer's: tacrine (Cognex) and donepezil hydrochloride (Aricept). While neither halts or slows the disease, each can provide minor, temporary improvement in cognitive ability by inhibiting the breakdown of the neurotransmitter acetylcholine. (The FDA is currently investigating as may as 45 new drugs.) Other pharmaceutical treatments address behavioral problems. For example, anti-depressants and neuroleptics are often helpful for AD patients with depression, anxiety or sleep disorders.

The social approach to Alzheimer's treatment developed from the understanding that AD is a chronic condition: since the disease cannot be cured, long-term, non-medical accommodations must be made. These changes, intended to maximize the patients' quality of life, focus on creating supportive environments that help maintain their independence and minimize the impact of their disruptive behavior.

The scientific community is also investigating a number of non-traditional approaches to AD treatment. There is some evidence that anti-inflammatory drugs may reduce the disease's incidence. Anti-oxidants such as vitamin E are also being studied on evidence that beta amyloid may release oxygen free radicals -- volatile molecules with unpaired electrons that may instigate damaging molecular chain reactions by binding with other molecules. Evidence that women who take estrogen may be less likely to develop AD has prompted studies into hormonal therapy. Scientists are even studying Ginkgo Biloba, a traditional Chinese medicinal extract that was recently approved as an Alzheimer's treatment in Germany.

Alois Alzheimer's first step more than 90 years ago led the way for a wide variety of modern Alzheimer's research. Many of the disease's mysteries remain unresolved, but our investigative progress has been great, and our learning curve steep. There is reason to be optimistic that even as the challenges of Alzheimer's Disease grow, they will be met with knowledge, skill and compassion.