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Alzheimer's Disease History
The symptoms of the disease as a distinct entity were first identified by
Emil Kraepelin, and the characteristic neuropathology was first observed by
Alois Alzheimer, a German psychiatrist, in
1906. In this
sense, the disease was co-discovered by Kraepelin and Alzheimer, who worked in
Kraepelin's laboratory. Because of the overwhelming importance Kraepelin
attached to finding the neuropathological basis of psychiatric disorders,
Kraepelin made the generous decision that the disease would bear Alzheimer's
name (J. Psychiat. Res., 1997, Vol 31, No. 6, pp. 635-643).
For most of the twentieth century, the diagnosis of Alzheimer's disease was
reserved for individuals between the ages of 45-65 who developed symptoms of
presenile dementia, which was considered to be a more or less normal outcome
of the aging process. In the 1970s and early 1980s, however, the name
"Alzheimer's disease" began to be used, within and outside the medical
profession, equally for individuals age 65 and older with senile dementia, and
was eventually adopted formally for all individuals with the common symptom
pattern and disease course in the psychiatric and neurological nomenclature.
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. The ApoE gene on chromosome
19 has three forms— ApoE2, ApoE3 and ApoE4. Studies have shown that people who
inherit the E4 version of the gene are more likely to develop the late-onset
form of Alzheimer’s disease. Scientists estimate that an additional four to
seven genes influence the risk of developing late-onset Alzheimer’s disease. One
of these genes is called UBQLN1 and is located on chromosome 9. Genetic risk
factors alone are not enough to cause the late-onset form of Alzheimer’s
disease, so researchers are actively exploring education, diet, and environment
to learn what role they might play in the development of this 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 Reminyl 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 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.
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.
*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.
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