Biology 202

2006 Second Web Paper

On Serendip

More than four million Americans are afflicted with Alzheimer's disease. Alzheimer's patients suffer from a drastic decrease in the size of their limbic system due to hippocampus atrophy (8) . The limbic system influences emotion and is vital for memory (3) . Early stages of Alzheimer's are accompanied by relatively simple mental struggles, such as "chronic forgetfulness and difficulty handling routine chores" (10) . Late stage Alzheimer's patients exhibit loss of speech function and ability to walk or sit upright (10) . This progressive loss of language and motor skills and ability to reason is characteristic of the gradual, yet substantial, deterioration of mental capabilities in Alzheimer's patients (6) .

On a molecular level, Alzheimer's manifests itself as plaques and tangles present in the brain (4). These senile (6) or Amyloid-containing (7) plaques, as they are often called, may begin to form several decades before the patient exhibits Alzheimer's symptoms (4). Tangles are most concentrated "in the cerebral cortex and hippocampus regions", areas of the brain evidently impacted by the disease (10). Plaque formation clogs up the brain's pathways and prevents chemicals in the brain from doing their job (11).

Alzheimer's is a complicated disorder that is believed to be brought on by multiple genes working in concert with environmental factors (5). The possible role of the hormone estrogen in sustaining and even enhancing brain function has sparked much research. It has been shown that estrogen has the capacity to "[boost] cells' chemical function, [spur] their growth, and even [keep] them alive by shielding them from toxins" (12). In other words, estrogen may act to safeguard the very neurons that malfunction and form plaques (12), keeping the brain healthy. Estrogen levels in women decrease after menopause, making the brain more susceptible to plaque formation.

Studies have yielded data indicative of an overall improvement in short-term memory when both healthy postmenopausal females and female Alzheimer's patients underwent estrogen replacement therapy (3). Additionally, estrogen testing in animals of both sexes has demonstrated that increasing estrogen levels boosts both long- and short-term memory (3). Clinical trials of estrogen replacement therapy show improved "memory in both healthy women and female patients with Alzheimer's, and [that estrogen] may even stave off the disease if given to women after menopause" (12). Intensity of treatment is important to effective results; it is likely that Alzheimer's prevention can only be accomplished by estrogen replacement therapy lasting for at least ten years (10). Female patients "who received the highest estrogen doses over the longest periods of time were the most protected" from Alzheimer's (5).

There are significant drawbacks to hormone replacement therapies, such as an increased risk of developing breast cancer, heart disease, stroke, and blood clots (13). In this vein, the women who do develop one of these life-threatening conditions may not survive long enough to test whether they become Alzheimer's patients or not. Therefore, the studies do not account for the subset of women who did not survive hormone replacement therapy; not all the subjects studied survived to the end of the trial. It is important that researchers work to eliminate the disadvantages of hormone replacement therapy in order to market estrogen to patients at risk of developing Alzheimer's. Many women feel that the risks associated with hormone replacement therapy outweigh the benefits (provide relief from the side effects of menopause). Additionally, hormone replacement therapy was not found to be effective in women aged 65 or older in preventing dementia (1). This is consistent with the importance of length of time of treatment in averting Alzheimer's.

In spite of the downside to estrogen replacement therapy, estrogen's apparent role as a cognitive enhancer is a promising finding. Next, researchers must work to develop "drugs that might bolster brain function without promoting reproductive cancers in women...or feminine characteristics in men" (12). If this were possible, medicine could exploit estrogen's role in enhancing viability of neurons and, consequently, prolong a patient's functional life.

Once thought to simply be the female sex hormone, estrogen has far exceeded its expectations. Hopefully, this discovery will open new doors to research of hormones in general, and their potential to work in ways not originally considered. At this point in time, hormone replacement therapy is not yet sophisticated enough to use solely as a means of maintaining mental function. It is simply an unforeseen benefit of its use in menopause. It is evident that estrogen's impact on the body is wide-ranging, hence its numerous positive and negative side effects. If delaying the onset of such a destructive disease as Alzheimer's can be accomplished by supplementing the body's usual dose of estrogen, many lives would be saved. It is known that altering hormone levels does influence brain functioning, as seen in patients suffering from depression. Perhaps utilizing the scientific evidence that estrogen can make us "smarter" in our old age will change the course of Alzheimer's disease.

References

1)Sorting Out HRT Risks and Benefits: What Women Really Need to Know About Hormone Replacement Therapy

2)Managing Alzheimer's Patients

3)Seeking "Smart" Drugs

4) Soothing the Inflamed Brain: Anti-inflammatories may be the first drugs to halt the progression of Alzheimer's

5)At More Risk for Alzheimer's?

6)Researchers Hunt for Alzheimer's Disease Gene

7)Role of Alzheimer's Protein is Tangled

8)Setting a Standard: A British project produces a test for Alzheimer's disease

9)The Oldest Old

10)Preventing Good Brains from Going Bad

11)Alzheimer's Jam

12)Estrogen Stakes Claim to Cognition

13)Hormone replacement therapy: Benefits and alternatives


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