Alzheimer's Disease:
The Silent Enemy
By Amanda
Muros-Bishoff
Alzheimer's Disease is a condition
that affects 50% of the population over the age of eighty five, which equals
four million Americans each year. It is becoming an important and high-profile
issue in today's society for everyone, especially with the news of former
President Ronald Reagan's diagnosis. There are rapid advancements
being made in the fight against this disease now more than ever, and the
purpose of this article is to educate the public on the background as well
as the new discoveries. There are many new drugs that are being tested
and studied every day which slow down, and may even halt the progress of
the disease.
In explaining this debilitating disease,
it seems there are certain major areas that need to be addressed such as
the history of the disease, the symptoms and diagnosis, as well as the
emotional and physical cost to the patient and to the family. The definition
of the illness seems to be unclear for many because the disease is so unpredictable.
Until recently a precise definition of the disease was unavailable due
to the difficulty in diagnosis. It is fairly complex, and despite many
new breakthroughs it still remains impossible to diagnose a patient with
certainty. A great deal of this is because the only exact diagnosis made
is after a post-mortem brain examination. Alzheimer's Disease is the most
overdiagnosed and misdiagnosed mental disorder in older adults because
it is often decided only by ruling out all other possibilities such as
dementias caused by medications, strokes, depression and other neurological
disorders.
However with new
research in detection and prevention, a clear
explication is now attainable for the public. Alzheimer's Disease is defined
as "A dementing disorder marked by certain brain changes, regardless
of the age of onset, that leads to the loss of mental and physical functions."(1)
There are two different types of the disease called early-onset and late-onset
Alzheimer's Disease. These relate to the age at which the disease first
manifests itself. The occasion of early-onset is much lower than that of
late-onset. There is a 10% occurrence rate for persons over the age of
sixty-five, and a 50% occurrence rate for those over age eighty five. Late-onset
Alzheimer's is often confused with senility due to old-age. This also makes
diagnosis difficult for older patients. However Alzheimer's is not an inevitable
part of the aging process, unlike a certain amount of senility. It can
be helped and with new research may be prevented.
The research into Alzheimer's Disease
has come a long way since 1906 when it is was discovered by Alois Alzheimer.
He detected microscopic brain tissue changes called senile and neuritic
plaques in deceased patients. These are chemical deposits consisting of
protein molecules called Amyloid Precursor Protein(APP) that are fundamental
components of a normal brain. However in the brain of an Alzheimer patient,
an enzyme cuts the APP apart and leaves fragments in the brain tissue.
These combined with degenerating nerve cells cause the plaques or lesions.
These lesions are found in many sections of the brain including the hippocampus
which regulates emotion and memory, the basal forebrain, and especially
the basal nucleus of Meynert and the cortex, where the memory function
is located.(2) Another sign of a diseased brain are neurofibrillary tangles,
which are malformations within nerve cells. Researchers also recently detected
a specific new protein found in the brains of deceased patients called
Alzheimer's Disease Associated Protein(ADAP) which may help in predetermining
people who will suffer from Alzheimer's before the onset of the disease.
Once these chemical changes begin to
take place in the brain, the patient begins to exhibit symptoms. Knowledge
of the physical impact of the disease is also an essential factor in this
fight. The degeneration of the nerve cells in the brain slow down the nerve
impulses that send messages to and from the brain. This causes many behavioral
and physical problems for the patients including forgetfulness, and difficulty
effectively performing simple tasks such as feeding oneself or holding
a conversation. Initial symptoms of the disease include significant recent
or short-term memory loss, impaired judgment and loss of intellect. Behavioral
changes include a "coarsening of personality", loss of spontaneity,
a sense of apathy and a withdrawal from social interactions. As the disease
progresses, later changes include problems in abstract thinking, agitation
and/or irritability, quarrelsomeness, inability to dress appropriately,
depression, paranoia and delusions. At the later stages victims may wander,
be disoriented about the date or the year, where they live or who they
are, be uncooperative and unable to converse, lose bladder and bowel control
and be completely unable to care for themselves.(3)
Although it becomes obvious as the
disease unfolds itself, in the beginning the symptoms can be ambiguous,
especially because when dealing with older people in whom many problems
such as arthritis, strokes or dementias can occur at the same time. Clinicians
diagnose Alzheimer's using three main guidelines. The first is the presence
of dementia which is defined as "a significant loss of intellectual
abilities such as memory capacity which is severe enough to interfere with
social or normal functioning."(4) Secondly, if the disease is insidious
in its onset with a subtle progression, including irreversible changes
and documented deterioration over time, doctors conclude that Alzheimer's
is a possibility. Thirdly, clinicians attempt to exclude all other causes
of dementia using a patient's history, a physical, laboratory tests and
psychometric studies.(5) Laboratory tests such as a CAT scan can rule out
other disorders and also later on in the progression of the disease can
detect an atrophied(or shrunken) brain with certain tissue indentations
called widened sulci, as well as fluid-filled chambers called enlarged
cerebral ventricles, which are characteristic of this particular disorder.
In fact, the pathological changes associated with Alzheimer's match exactly
those for Down Syndrome patients over the age of forty-five.
Although the progression of the disease
differs from patient to patient, doctors estimate that the average progression
from the time of diagnosis to the time of death is six to eight years,
but can deviate to as much as two to twenty years. Again it is difficult
to estimate an exact progression because many patients die of other complications
or health problems. However, in a March 1997 special edition of the Journal
of the American Medical Association devoted entirely to Alzheimer's Disease,
Dr. Yaakov Stern, Ph.D., published his recently developed algorithm. Dr.
Stern claims that this algorithm accurately predicts the timeline of the
progression of Alzheimer's Disease using information gathered from cognitive
test scores and other variables about his patients.(6)
Researchers have been working for years
to try to discover a link between Alzheimer's and genetics. Currently major
results are being published in this field which would enable doctors to
fight this disease before onset. In the March 1997 issue of the Journal
of the American Medical Association, geneticists announced that they have
isolated the gene ApoE-E4, which increased the risk of developing Alzheimer's
two-fold for a certain tested population. However only approximately 13.7%
of Alzheimer's Disease can be related to this gene. However research has
also indicated "three genes whose mutations could cause familial forms
of early-onset".(7) Researchers are working on several different genes
that could be the cause of the disease. As of now, only early-onset Alzheimer's
has been traced genetically in families, so late-onset can occur in any
person without notice, which is why it is imperative to find the cause
of this disease.
While some researchers are trying to
identify a gene in order to prevent the disease, there have been some breakthroughs
in terms of drug therapies to relieve symptoms. In a letter dated March
20, 1997 from the Chairman of the Board for the Alzheimer's
Association, Griff S. Healy explains,
"1996 has set a near record for
new discoveries. Some researchers are studying ways to detect Alzheimer's
earlier--and others are trying to prevent the onset by finding ways to
protect the brain cells of individuals who may eventually become victims".
In 1993 the drug Tacrine(trade name
Cognex) was approved by the FDA for use with Alzheimer's patients. This
drug was shown to improve levels of acetylcholine, which transmits nerve
impulses to the brain. Alzheimer's patients are shown to have diminished
levels of acetylcholine in their brains. However the drug showed little
improvement unless used in high doses, which caused elevated levels of
liver functioning, and in some cases cause significant adverse effects.
At the end of 1996 the FDA approved
a new drug called donepezil hydrochloride(trade name Aricept) used to treat
the symptoms of mild to moderate cases of Alzheimer's Disease. This drug
also increases acetylcholine levels in the brain by inhibiting an enzyme
called acetylcholinesterase, which limits levels of acetylcholine.(8) However
neither of these drugs is a cure for the disease; they both attempt to
alleviate symptoms and prolong the inevitable degeneration.
As recently as last week new information
about drug therapies is being publicized. Vitamin E has been unveiled as
a possibility to combat the disease. Research showed that the vitamin,
when given to patients already displaying symptoms, slowed progression
by seven months. A prescription drug called Eldepryl showed similar effects
but researchers are looking to vitamin E as more promising because it is
less dangerous(in terms of side-effects) than a prescription drug.
However, there is hope on the horizon
for future Alzheimer's sufferers. Several studies concluded that certain
changes in the brain which cause Alzheimer's may be detectable up to forty
years before the first manifestations of the disease. This would allow
doctors to identify people who would develop the disease later in life,
and "scientists believe they may be able to discover how to interfere
in the disease process and stop it before memory loss or cognitive impairment
occurs".(9) As well as this new development, two other important drug
therapies are being tested. A Columbia University study found that estrogen
may somehow protect the nerve cells in the brain from the damage which
the disease causes. Dr. Richard Mayeux, M.D. found that women taking estrogen
replacement therapy are less likely to develop the disease, but long-term
studies are needed to prove this hypothesis.
Also recently a research team at Johns
Hopkins School of Medicine showed non-steroidal anti-inflammatory drugs,
known as NSAID's (such as ibuprofen) to protect the nerve cells in the
brain against damage as well. Claudia Kawas M.D. found that users of ibuprofen,
as opposed to users of aspirin or acetaminophen, have lower risks of developing
the disease later in life. This research is also in the early stages of
development and needs further long-term study. However these studies demonstrate
major progress in the struggle against the onset of the illness.
As well as trying to prevent the progression
of the disease with drugs, researchers are also trying to devise ways of
fighting this disease by hypothesizing on possible causes. Right now the
main question about Alzheimer's remains why does this disease occur? One
theory is the chemical deficiencies and toxic excesses theory. It is possible
that later in life there is a decline in the growth-promoting factors which
keep the brain healthy and maintain normal activities, while simultaneously
a spontaneous increase occurs in substances which are toxic to brain cells.
Another theory suggests that there is am imbalance in certain people's
metabolism of calcium in the brain which causes degeneration and eventually
death of cells. The Slow-Virus theory suggests that there may be some type
of virus which attacks the brain, but no virus has been identified so this
theory has not been proven. The Blood-vessel theory presents the opinion
that there could be a defect in the membrane which acts as a blood-brain
barrier. This protective membrane guards the brain from foreign bodies
in the bloodstream and as a result of head trauma earlier in life, or simply
a genetic defect, it malfunctions. The Auto-Immune theory proposes that
the body might attack it's own tissue in the brain as a result of certain
changes in aging neurons later in life.(10) These theories each attempt
to provide answers for the seemingly inexplicable phenomenon that is Alzheimer's
Disease.
One of the final issues is the emotional
and financial burden which accompanies this affliction. From first-hand
experience, it is an agonizing process to watch someone go through. It
is so slow and yet so deadly because it destroys the victim's mind and
personality. It is frustrating for the patient and the family because there
is not much that can be done(until fairly recently), except wait for each
stage to occur. Earlier on it is difficult and embarrassing because the
patient is still lucid enough to realize the failure of his brain and knows
that he/she is forgetting but cannot prevent it. A simple conversation
with an Alzheimer's patient is painful because the same questions are asked
over and over again. One doctor explained this problem by saying, "It
is as if the brain does not record the answer given to the question, and
so for the patient, it is as if the question was never asked." Everyone
involved in this situation has many emotions, especially the patient, including
fits of rage and anger, depression and sadness, and helplessness.
After a certain point, Alzheimer's
sufferers cannot be alone because they become a danger to themselves and
others. Many can live for years after this point which is a huge financial
burden for most families. It is estimated that the cost of Alzheimer's
to society in general is one-hundred billion dollars per year. It causes
over one-hundred thousand deaths each year in the United States, making
it the fourth leading cause of death for adults.(11) All of these reasons
contribute to the urgency of this disease. The devastating impact of this
disease for all of society as well as each individual patient makes it
imperative to accelerate the search for a cause and a cure.
Footnotes
1. http://www.kcc.com.msu.edu/CAI/Pathology/Degen_F/Degen_2a.html
2. gopher://gopher.nimh.nih.gov/00/documents/nimh/other/alzh
3. http://www.kcc.com.msu.edu/CAI/Pathology/Degen_F/Degen
_2a.html
4. gopher://gopher.nimh.nih.gov/00/documents/nimh/other/alzh
5. Ibid
6. http://www.cais.com/adear/nianews11.html
7. http://www.cais.com/adear/nianews11.html
8. Advances in Alzheimer's Research
Spring 1997, Vol. 7, Number 1
9. Ibid
10. tornado.einet.net:8000/galaxy/medicine/Diseases-and-Disorders/Nervous-System-Diseases/
Central-Nervous-System-Diseases/Brain-Diseases/Alzheimer's
Disease.html
11. http://moe.csa.com/alzintro.html
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