Progressive mental deterioration in old age has been recognized and described
throughout history. However, in was not until the early part of the 20th century
that a collection of brain cell abnormalities were specifically identified by
Dr. Alois Alzheimer, a German physician, in 1906. He lectured about a woman
who had died after years of experiencing severe memory problems, confusion,
and difficulty understanding questions. Upon her death, he performed an autopsy
on her brain and described dense deposits outside and around the nerve cells
(neuritic plaques). Inside the nerve cells he noted the presence of twisted
bands of fibers (neurofibrillary tangles). Today, this degenerative brain disorder
bears his name. The observation of the plaques and tangles at autopsy is still
required to obtain a definitive diagnosis of Alzheimer's disease.
A great deal has been learned since the early part of this century concerning the nature of the plaques and tangles and the brain regions that become affected as the disease progresses. In addition, scientists are gaining greater insight into the genetic factors contributing to Alzheimer's disease. Familial Alzheimer’s disease (FAD) is a rare form of the disease, affecting less than 10 percent of Alzheimer’s disease patients. All FAD is early-onset, meaning the disease develops before age 65. It is caused by gene mutations on chromosomes 1, 14, and 21. Even if one of these mutated genes is inherited from a parent, the person will almost always develop early-onset Alzheimer’s disease. All offspring in the same generation have a 50/50 chance of developing FAD if one of their parents had it.
The majority of Alzheimer’s disease cases are late-onset, usually developing after age 65. Late-onset Alzheimer’s disease has no known cause and shows no obvious inheritance pattern. However, in some families, clusters of cases are seen. Although a specific gene has not been identified as the cause of late-onset Alzheimer’s disease, genetic factors do appear to play a role in the development of this form of the disease. A gene called Apolipoprotein E (ApoE) appears to be a risk factor for the late-onset form of AD. There are three forms of this gene: ApoE2, ApoE3 and ApoE4. Roughly one in four Americans has ApoE4 and one in twenty has ApoE2. While inheritance of ApoE4 increases the risk of developing AD, ApoE2 substantially protects against the disease. Scientists believe that several other genes may influence development of Alzheimer’s disease. Two of these genes, UBQLN1 and SORL1, are located on chromosomes 9 and 11. Researchers have also identified three genes on chromosome 10, one of which produces an insulin degrading enzyme that may contribute to the disease.
In 1993, the FDA approved the first drug to treat Alzheimer's disease, Cognex®* (tacrine), which increases the amount of the neurotransmitter acetylcholine in the brain and can slow cognitive decline. A second drug, Aricept® (donepezil), became available in 1996, and in 2000, the drug Exelon® (rivastigmine) was approved by FDA. A fourth drug, Razadyne®** (galantamine) was approved in early 2001. Cognex®, Aricept®, Exelon®, and Razadyne® work by increasing the amount of acetylcholine available in the brain. Cognex, though effective, has more adverse side effects than the other medications. In 1997, studies indicated that vitamin E and a drug normally used in the treatment of Parkinson's disease, Eldepryl® (selegiline), were found to be helpful in slowing mental deterioration in patients with moderate Alzheimer's disease; however, further studies are necessary to corroborate these findings.
In 2003, the FDA approved Namenda® (memantine), which is the first drug to treat moderate to severe Alzheimer's disease. Namenda® is an NMDA receptor antagonist, and appears to protect the brain's nerve cells against excess amounts of glutamate, a messenger chemical released in large amounts by cells damaged by this devastating neurological disease.
Aricept® was approved for the management of severe Alzheimer's disease symptoms in 2006, in addition to its previous approval for the treatment of mild to moderate symptoms, based on several clinical trials.
The Exelon®Patch (rivastigmine transdermal system) was approved in 2007 to deliver this medication through a skin patch as an option to the oral capsule.
Although the diagnosis of Alzheimer's can still only be made through an autopsy, clinicians can now make an accurate diagnosis 90% of the time by taking a history, performing a physical examination, utilizing medical tests, ruling out other causes, and measuring memory capabilities and psychological status. Early diagnosis is important because the treatments that are available work best at the earliest stages of the disease.
There is no known treatment that will cure Alzheimer's disease. For those who are currently suffering with the disease, medications can only help control symptoms and/or slow the progression of the disease.
*Cognex®, though effective, has more adverse side effects than the other medications in this category.
**Janssen-Ortho Inc. renamed Reminyl® to Razadyne® in April of 2005. The name was changed to help avoid confusion with the diabetes drug Amaryl®, which is marketed by Sanofi-Aventis.
Reviewed on 2/14/2008