When Can We Expext a Cure for Alzheimer's?

Contributed by: Dennis Fortier, President, Medical Care Corporation

There is no definitive answer to this ubiquitous question. The best we can do is to watch the advance of science through the published literature and to follow the clinical trials from which the answer will one day emerge.

While the pathology of Alzheimer's disease is still not well understood, scientists have developed a host of well-grounded theories. Several treatment agents, based on those theoretical foundations, are currently in development or in clinical trial. Here is a short summary of the three leading treatment hypotheses:

The Cholinergic hypothesis proposes that AD is caused by reduced function of a certain chemical in the brain called acetylcholine. The chemical is known to be important in memory formation and brains of patients with AD have less acetylcholine. In fact, most medications currently approved for AD act by increasing acetylcholine levels in the brain. However, their ability to treat the disease has been limited, indicating other factors at play.

The Amyoid Hypothesis states that a buildup of deposits (amyloid) is the fundamental cause of Alzheimer’s disease. It is a compelling theory because a gene associated with this form of amyloid is located on chromosome 21 and people with an extra copy of this gene (those with Down Syndrome) almost universally exhibit AD by 40 years of age. Also, APOE4, the major genetic risk factor for AD, leads to excess amyloid buildup in the brain before AD symptoms arise. Thus, amyloid buildup precedes clinical AD.

The Tau Hypothesis encompasses the idea that tau protein abnormalities form damaging tangles inside nerve cells. When this occurs, the cell's transport systems disintegrate and malfunction which may disrupt communications between cells and later cause cell death.

While these are the primary theoretical drivers of drug development, there are other agents in clinical trial that were not developed on the basis of a particular theoretical approach to the disease. Dimebon, currently in Phase III FDA trial is a pre-approved antihistamine that was shown to correlate with low dementia prevalence. Although scientists are not sure how or why it might effectively treat Alzheimer’s disease, results of the Phase I and II trials were positive and Dimebon may in fact be the next approved treatment for Alzheimer’s disease.

While it is premature to say that a cure is imminent, it should be clear that several treatment agents are in advanced stages of clinical trial. However, predicting the results of these trials is hampered by our vague understanding of what causes Alzheimer's Disease. On the bright side, one or another of these agents may be surprisingly effective in altering the disease course and could be available in two to five years. On the dark side, they may all turn out to be ineffective in which case we would be more than five years away from a meaningful new medication. Only time will tell.

In the meantime, we all need to be proactive in identifying and managing our risk factors for cognitive decline and physicians must be vigilant about acting on evidence or suspicion of decline among their patients. Until better treatments are discovered, we must intervene as early as possible with the current medications to maximally delay the progression of Alzheimer's disease.

Remember, we need a cure but there is much we can do while we await its arrival. Current treatments are more effective than many headlines suggest. With early intervention and a robust therapeutic regimen (including physical exercise, mental and social activity, a healthy diet, and currently approved medications), we can already meaningfully delay the progression of this terrible disease.

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