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Estrogen
Hormone Replacement Therapy May Diminish Alzheimer's Disease Risk
What is Alzheimer's?
Alzheimer's
disease is the most diagnosed form of dementia in the world. As of
yet there is no cure for the disease, but researchers worldwide are
spending their entire careers attempting to discover ways to
alleviate or even cure the syndrome. Our knowledge of the disease
grows more quickly by the year and there is significant hope that
within the coming generation our world's greatest minds will
discover a means to defeat this dreaded degenerative condition.
Alzheimer's develops in a different pattern and at a different
speed for every patient, but the common symptoms are:
Increased
aggression and irritability
High
levels of confusion and disorientation
Rapid
changes in mood
Atrophy
of language ability
Long
term, and eventually short term memory loss 
In
later stages, a loss of physiological control, in which over time,
the patient is eventually completely dependent upon a caregiver
There
are three primary hypotheses regarding the cause of Alzheimer's:
Cholinergenic
Hypothesis:
This
was the original hypothesis regarding Alzheimer's disease, and
treatment approaches using this theory as a starting point produce
only minimal beneficial effects. This hypothesis predicts that
Alzheimer's disease is largely the result of a reduced ability for
the brain to synthesize acetylcholine.
Tau
Hypothesis:
This
hypothesis centers around the idea that abnormalities in a certain
type of protein known as Tau Protein can cause the effects of
Alzheimer's disease. It is hypothesized that hyperphosphorylated
tau interacts with other forms of tau protein, creating clumps of
protein known as neurofibrillary tangles inside of nerve cells. These
tangles disrupt the function of nerve cells, clogging up the active
transport system and preventing neuronal messages from reaching
target destinations. At first, this leads to misdirected neuron
firing but can eventually lead to the death of the neurons
themselves.
The
Amyloid hypothesis
The
Amyloid Hypothesis is the most widely researched and studied
hypothesis, and is the hypothesis for which the research discussed in
this article is related to. According to this hypothesis, Alzheimer's
is primarily caused by the formation of Beta-Amyloid deposits in the
brain which clog up neuronal pathways, leading to the detrimental
effects of the disease. One of the primary reasons why this
hypothesis carries so much weight is because individuals who display
an increased proclivity for the formation of these proteins display a
greatly increased risk of the disease. Individuals with Down syndrome
have three copies of this genetic abnormality, and as a result, these
patients display symptoms of Alzheimer's at an age as early as 40.
New
Study: APoE4 Precursor for Alzheimer's and Advanced Aging
Endocrinologists
have made a number of discoveries regarding the effect of Estrogen
Replacement Therapy on Alzheimer's, and New clinical research
provides evidence that Estrogen Hormone Treatments may be able to
slow down the process of aging in middle-aged females who are at
increased risk of Alzheimer's disease. In this clinical study,
otherwise healthy female patients who were going through menopause
while also harboring a genetic increased risk of Alzheimer's did
not succumb to the disease when treated with Hormone Replacement
Therapy.
The
genetic abnormality APoE4 has been linked to processes which speed up
the natural aging process in women. Hormone Replacement Therapy
featuring Estrogen may counteract the detrimental effects of this
genetic condition and help older women avoid the ravages of
Alzheimer's disease.
What
is APoE4?
AP0e4
is the strongest causal genetic link for developing Alzheimer's
disease. This gene is responsible for the production of an enzyme
known as Apolipoprotein E Type 4. Apolipoprotein E is primarily
released by macrophages and the liver in order to break down
triglycerides. Ap0E4 performs this function, but is also correlated
with creating devastating protein abnormalities in the brain which
lead to Alzheimer's. Those who carry 2 copies of the Ap0E4 gene
have a ten to thirty times increased likelihood of developing
Alzheimer's disease.
Ap0E4
is so strongly correlated with Alzheimer's disease that James
Watson, one member of the duo of scientists who first discovered the
existence of DNA, refuses to be tested for the genetic abnormality.
Individuals who have an active Ap0E4 gene have a 90% chance of
developing Alzheimer's by the age of eighty without treatment.
Although Alzheimer's research is incredibly active, there are still
more questions than answers in regard to this devastating disease.
APoE4
Slowly Degrades the Body
According
to Dr. Natalie Rasgon, ApoE4 affects women at the cellular level long
before these changes affect the body to a noticeable extent,
increasing the physiological age of the cells long before this aging
process becomes apparent and symptomatic. Dr. Rasgon is a professor
of behavioral science and psychiatry at the Stanford School of
Medicine in California.
This
new study provides further evidence that Estrogen Replacement Therapy
may be able to shield many older women from the effects of
Alzheimer's diseaseespecially those who harbor this critical
gene.
One
of a Number of Studies Linking APoE4 to Alzheimer's
There
have been a number of previously conducted studies which have shown
that ApoE4 likely plays a role in Alzheimer's disease and general
cognitive decline as a result of the aging process.
In
another similar study, not directly related to ApoE4, 472 female
patients were followed for 16 years. Some of the participants
utilized Hormone Replacement Therapy while others did not utilize the
treatment. Researchers found that patients who used Estrogen in
addition to other forms of Hormone Replacement Therapy had an
incidence of Alzheimer's which was fifty percent lower than those
patients which did not use the therapy.
This
gene is incredibly common among Alzheimer's patients, and is active
in around forty percent of patients that are afflicted with the
disease.
Dr.
Rasgon's laboratory group focused primarily on telomeres, which are
caps which close off the ends of chromosomes and are responsible for
genetic stability. These telomeres function like genetic fuses over
time. Each time that a cell reproduces, the telomeres become slightly
shorter in length.
What
are Telomeres?
Telomeres
are areas of DNA which are at the ends of chromosome strands which
consist of repeating lines of genetic data which are inert. These
lines form a sort of cap on the ends of the chromosomes in order to
prevent them from breaking down. During the process of cell
replication, the enzymes which encourage the reproduction of
chromosomes are unable to perform their function all the way to the
very ends of cells, leaving a very brief portion of the chromosome
un-copied.
If
chromosomes did not have telomeres which featured this inert genetic
data, then every time the cells divided, our chromosomes would lose
vital genetic code and our bodies would deteriorate. These telomeres
are partially consumed by the enzymes which encourage cell
replication, but there are other cellular enzymes which are
responsible for rebuilding telomeres. These cells are known as
Telomerase Reverse Transcriptase. Under normal circumstances,
telomeres set a soft limit on the natural life spans of animals,
including humans. Telomeres play a major role in the aging process.
Studies
such as those performed by Dr. Ragson help us understand more about
telomeres and how we can extend our lifespans by manipulating the
rate at which telomeres break down. There is also ongoing research
regarding ways that telomeres can be adequately preserved or even
lengthened in order to extend the lifespan. In many ways Hormone
Replacement Therapy and Telomere Maintenance appear to be related.
Alzheimer's
Correlated to Quicker Aging
The
current body of scientific knowledge suggests that Alzheimer's and
the biological aging process are likely correlated in a large subset
of female patients.
If
the telomeres reach a certain abridged size, the cells can begin to
die off, or in other cases, the cells may lose their ability to
continue to divide.
When
the cells start to function abnormally as a result of the aging
process, the signs of aging begin to become physiologically apparent
on a holistic level. Symptoms of aging such as loss of muscle tone
and cognitive sharpness, as well as wrinkled skin start to manifest,
in addition to other negative side-effects which affect every system
of the human body.
The
rate at which the telomeres shorten is highly variable among
individuals, and this can be used in order to accurately measure
biological age, which is systematically different from chronological
age, affecting each individual at a unique rate not entirely
dependent upon simply time.
The
researchers studied telomeres sampled from white blood cells drawn
from seventy completely healthy women, generally aged between forty
five and sixty five. All seventy were taking Estrogen Hormone
Replacement Therapy.
How
Might Estrogen Prevent Alzheimer's?
When
menopause begins, estrogen levels decline at a rapid pace. There are
a number of symptoms that almost all women are aware of, including
cold sweats, hot flashes, mood instability, and lapses in memory.
What most women probably do not realize is that menopause can
increase the risks of a number of other medical issues as well,
including Alzheimer's disease. In the past, there have been a few
small scale studies that suggested that Estrogen Replacement Therapy
may be a treatment option for those who suffer from Alzheimer's
disease.
Although
the benefits in regard to reversing the effects of Alzheimer's with
Estrogen Replacement Therapy seem to be slim, there is growing
evidence that Estrogen may be able to prevent the disease or slow its
progression, especially when utilized during the period of Menopause.
These benefits may persist later in life as well, when Estrogen HRT
is utilized in smaller doses.
New
studies have also shown that Estrogen provides a number of benefits
to the brain in addition to safeguarding it against the threat of
Alzheimer's. There has been a significant amount of animal research
performed in regard to the Effects of Estrogen on Brain Cells, and it
is apparent that the hormone plays a major role in protecting and
supporting the function of brain cells.
Estrogen
Associated with Healthy Acetylcholine Levels
Healthy
Estrogen levels are associated with optimal levels of acetylcholine
in the brain, which is important to the maintenance of cognition and
memory. Estrogen also apparently has the ability to shut down the
formation of plaques known as Beta Amyloids, which cause the symptoms
of Alzheimer's disease. Beta Amyloid plaques are the result of an
enzyme abnormality which causes the enzymes to produce malfunctioning
proteins which breakdown the function of the brain, eventually
leading to total cognitive breakdown and death.
Although
Estrogen alone may not be a proper treatment for active Alzheimer's,
there is still promise that Estrogen HRT when utilized in combination
with other forms of Alzheimer's medical treatment such as Aricept
(donepezil) may be able to improve health outcomes for patients with
Alzheimer's disease.
APoE4
Study Parameters
The
seventy women on Estrogen HRT were split into two variable groups.
The first group of women stayed on Hormone Replacement Treatments,
while the second group stopped all hormone therapy.
After
two years, the participants had their white blood cells drawn a
second time, and the scientists measured the rate by which the length
of the telomeres shortened.
Among
the healthy patients who halted Hormone Replacement Therapy, those
with the active Alzheimer's gene were found to be 6 times as likely
to have telomeres which shortened at an abnormally rapid pace than
participants who did not have an active Alzheimer's gene.
For
these women who did have the active ApoE4 gene, the telomeres reduced
in length at a rate which would normally be expected over the course
of a decade, rather than simply two years. Physiologically, these
women were aging at a rate which was five times as fast as those with
the deactivated gene.
Estrogen
Slows Down Biological Aging Associated with APoE4
Hormone
Replacement Therapy featuring Estrogen was shown to alleviate this
issue, however. In patients who were at enhanced risk of Alzheimer's
yet remained on Estrogen HRT, telomere length shortened at a normal
rate which correlated with their cohorts with the deactivated gene.
This
is powerful evidence that Hormone Replacement Treatments with
Estrogen may have the ability to delay or prevent Alzheimer's
disease, although much more study is needed in order to prove the
hypothesis.
Professor
Rasgon says that this study increases our knowledge of the benefits
of Estrogen Replacement Therapy and in the future will help us
pinpoint exactly which patients are likely to receive the maximum
benefit from the hormone treatment.
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