Biology 202
2001 Third Web Report
On Serendip

Since ancient times, it has been clear that some people lose mental sharpness (cognitive function) as they age. However, in 1906, the German neurologist Alois Alzheimer began an autopsy of a woman from Frankfurt, that had died after several years of progressive mental deterioration. From the accounts of the doctor, family, and friends of the woman, Alzheimer put together her mental state prior to death, and described the woman as being marked by increased confusion, disorientation, and memory loss.Taking advantage of staining techniques that had recently been established, Alzheimer noticed an odd disorganization of the nerve cells in the womanís cerebral cortex, the part of the brain responsible for reasoning and memory. The cells appeared bunched like rope tied in knots. These strange nerve bundles he called ìneurofibrillary tangles.î Along with the neurofibrillary tangles, Alzheimer noticed an unexpected accumulation of cellular debris which he termed ìsenile plaques.î In 1907 Alzheimer published his findings in a medical journal, where he speculated that the nerve tangles and plaques were responsible for the womanís dementia">(3).Though, Alzheimer had completed the first step in recognizing this new disease he did not recognize the full scale of its destructiveness. Later, as more autopsies of individuals with severe dementia began to show the same cerebral abnormalities, Emil Kraepelin, one of the most publicized German psychiatrists of the time, suggested naming the disease in honor of his countryman, Alzheimer">(3).

Alois Alzheimer had no idea what caused the abnormal clumps and irregular knots to form in the brain, he assumed they had caused the womanís dementia, but they might also have been an effect of it. Although scientists have taken great steps towards determining a cause for AD, to this day itís still not entirely clear whether these changes in brain tissue are a cause or a result of the disease. Researchers are devoting a great deal of effort to understanding how and why they develop, in order to prevent their development and return damaged brain tissues to normal. Normally, nerve cells in the brain are arranged quite orderly, while in AD the cells become disorganized and tortured looking and stop functioning. When these cells stop working, the brain begins to die and the activities those cells controlled--memory, reasoning, and ability to take care of oneself--die as well">(9).Recent research has linked neurofibrillary tangles to an abnormal accumulation of a protein called tau. Tau is detectable in cerebrospinal fluid, and in AD patients the levels of tau are comparatively high. The senile plaques are accumulations of cellular debris surrounding a central core of beta-amyloid peptide, a molecular fragment of a large protein found in a normal brain. There are several types of beta-amyloid peptide, each differing in molecular length, but it is the longer form known as beta-amyloid-42 that is most associated with causing AD. Like tau protein, beta-amyloid-42 is detectable in cerebrospinal fluid, giving researchers hope that in the future a diagnosis for AD may be obtained by a combination test for high levels of tau, and low levels of beta-amyloid-42, instead of todayís soul method for truly diagnosing AD; autopsy after death">(4).

The disease named after Alzheimer is a brain disorder, which gradually destroys the ability to reason, remember, imagine, and learn. Suffers of the disease no longer recognize themselves or much of the world around them, and as a result suffer deep boughts of depression, anxiety, and paranoia. Noted by abnormal clumps (sineal plaques) and irregular knots (neurofibrillary tangles), the disease begins as these plaques and tangles overtake healthy brain tissue in the areas of the brain associated with intellectual function. Though the disease is slightly more common in women, it is no respector of sex, striking both men and women">(1).Also, this disability can set in anytime after the age of forty, though most sufferers are over the age of sixty-five. In most patients, the disease progresses slowly, taking between three to eighteen years to advance from its earliest symptoms">(1) .Like many immunodeficiency diseases, the sufferer does not die as a result of the disease, but dies due to a secondary illness such as pneumonia or even urinary tract infection">(2).Right now, treatment of AD focuses on slowing down the progression and coping with the symptoms. Its increasing prevalence has led epidemiologists to call AD the disease of the century">(2) .

Though any person can acquire AD, certain people are at greater risk than others, making prevention a necessary step in stopping the disease. People, who are increasing in age, have a family history of AD, are genetically inferior (due to inbreeding or genetic disorder), or have Down syndrome are at the greatest risk of acquiring AD">(7).There is no sure fire way to prevent AD, but doctors do recommend decreasing caffeine intake around forty, and getting at least eight hours of rest each night. Another preventative measure taken is the use of increased estrogen levels in aging women, which does seem to have promising affects. Since there is no cure for AD, many of the available therapies attempt to improve the patientís quality of life, by keeping him safe, and making care giving easier. Support from a caregiver is very important, but at a certain stage of the disease the physician may recommend that the patient be placed outside the home in a professional nursing care facility. These nursing homes cost the patients family an average of forty-two thousand dollars a year, and from diagnosis to death, the average cost of care for an AD patient is 174,000 dollars, with neither Medicare or most insurance companies paying for any long term care. Experts estimate that AD costs Americans between eighty and one hundred billion dollars each year, while the money that the government puts in to the diseaseís research fund is only 400 million dollars">(6).

Though prior to death it is difficult to determine whether a patient has AD, doctors do identify several warning signs which often precede the full onset of the disease. The first sign of AD is when a person experiences recent memory loss that affects their performance on the job. Sufferers of AD can forget telephone numbers or names and never remember them, or repeatedly ask the same question, not remembering the answer, or the fact that they already asked the question. Another sign that a person might have AD is that they have difficulty performing a familiar task">(5).For example, a person with AD might begin to cook a meal, and mid-use forget how to use the stove, or that they were cooking at all. AD suffers may also experience problems with language usage, where they may forget a common word that the wish to use, or may substitute a word that is not appropriate for another word mid-sentence. Disorientation of time and place is another symptom of AD">(5).Though many people will loose track of what day it is, a person with AD will forget which street they live on, how to get to work, or their way around a familiar shopping mall. AD also affects a persons judgment, where a person may become immersed in a phone conversation and momentarily forget a child they are watching, a person with AD in the same situation may go to the store or to dinner and never remember that they have left a child alone. A further sign of AD is trouble with abstract thinking"> (1).For example, a normal person may experience confusion when balancing their checkbook becomes a little more difficult than normal, but a person with AD may forget what the number represent, or what they relate to. People with AD also often misplace belongings in inappropriate places, such as placing an iron in the freezer, or putting the dog in a closet. Another almost sure sign of AD is increased mood or behavior changes, where the person may be content one moment, in a rage the next, and then in the next moment, be weeping">(5).The final factor that is used to diagnose AD is loss of initiative, which may occur as a result of the other symptoms, sufferers require cues and prompting to become involved in activities. Though a true diagnosis of AD can only be obtained from an autopsy, today, physicians who specialize in dementing illnesses are much better at distinguishing AD from other dementing diseases.

The doctors that diagnose AD will work with a patient through out the disease, constantly keeping track of the progression that the disorder has taken. Though doctors disagree on the number of stages that AD should be subdivided in to for my purposes, I will divide the stage in to three categories, Early AD, Moderate AD, and Severe AD. Each of these divisions contain aspects relating to a personís ability to function in society, as well as the effects that the disease inflicts on the personís mental health. However, it is difficult to place a person with AD into a specific category, but symptoms do seem to progress in a recognizable pattern, providing a frame work for understanding the disease.

The first recognizable stage of Alzheimerís Disease is called Early Alzheimerís Disease. It is the patients first deviations form the life of a normal aging adult in to the effects of dementia. Early stage AD is the first step in the normal progression of AD and is not to be confused with Early-Onset AD (which affects people before the age of sixty) or Newly-Diagnosed AD (which is the name given to a person who may have severe AD, and has just recently been diagnosed by a specialist). People with Early stage AD have only a mild impairment due to the symptoms of the disease. They may still be working, driving and need only minimal assistance. These people are aware of their diagnosis and also their abilities. Various symptoms may affect these sufferers, but most commonly they experience, recent memory loss, locational confusion, loss of spontaneity, loss of initiative, poor judgment, and trouble handling money. Though these people are capable of living independently, they often feel safer being close to a loved one or friend">(5).

The second stage of AD is known as Moderate AD and typically occurs two to ten years after diagnosis. Suffers begin by experiencing mild complications, where they require assistance with complicated tasks such as handling finances and planning social events. However, the person quickly becomes more dependent on others as they cannot make decisions for themselves, and must even have their attire chosen each morning. A patient may have a noticeably shorter attention span, and problems recognizing close friends or family. At night these people may be restless, experiencing sleepwalking or insomnia. Due to an increased difficulty organizing thoughts, the patient may begin to make up stories to fill in missing information they cannot recall, or may develop reading, writing, and numerical problems. Along with their inability to dress themselves, the suffer experiences many problems that may require the help of a part time nurse, such as poor impulse control or a fear of bathing. Typically, towards the end of this stage is when doctors recommend that patients be placed in nursing care facilities, where they can receive twenty-four hour care">(5).

The final stage of Alzheimerís Disease, known as the Severe stage or Terminal stage, is perhaps the most devastating and emotional, as the family experiences the complete degradation of their loved one as they prepare for his or her death. During Severe AD, a person experiences a decline in speech abilities, being able to recall approximately half-dozen intelligible words, which the patient continually repeats. Progressively, they loose the ability to walk, sit up, hold up their own head, or even smile. This final stage last only about one to three years, however, the person does not seem human at this stage. The patient can no longer recognize himself in a mirror and often looses vast amounts of weight even with a good diet. They have no capacity for self-care, and cannot control their bowels or bladder. Finally, the sufferer may experience seizures, and as a result may often groan or scream. This final stage though the shortest for the sufferer is the most persistent for the family, because after the persons death these are what family members will remember last of their loved ones">(5).

The most common questions asked among the aging population are, ìCan this disease be prevented?î and, ìAm I at risk?î. Though at the moment there is no cure for Alzheimerís disease, doctors have recognized a series of traits that can make a person more prone to acquiring the disease as they age. These features, called risk factors, are traits or behaviors that may make a person statistically more likely than others in the general population to have a certain condition. The degree of information that is known about a risk factor distinguishes its placement with in one of three categories: 1) well-established, 2) probable, and 3) controversial. It is important to understand that though these factors may have existed from the time of the patients birth they are not necessarily the cause of the condition, but may be a reaction to the cause.

There are four clear risk factors for Alzheimerís disease; increasing age, genetics, being female, and environmental factors, all increase oneís chances of developing the condition. The major risk factor of AD is increasing age. >From the ages of 64-74, only three percent of the population are documented as having the disease. These numbers steeply increase after age 74 to twenty percent, and by age 85 nearly half of the population has been diagnosed AD positive. Family history also is a large contributor to the likelihood of a person acquiring AD. By age eighty, a person with two parents affected by AD is five times as likely to have the disease than a person with two unaffected parents. Research into this phenomenon has focused on specific abnormalities of genes on the first, fourteenth, and twenty-first chromosomes. Chromosome twenty-one also causes the disorder known as Downs Syndrome, which usually results in the death of the sufferer around the age of thirty, however, with new revelations in science patients with DS are living longer than ever. In cases where DS patients live into their forties and fifties they almost always develop AD. On the fourteenth chromosome, however, there is known to exist a gene called presenilin-1 that occurs in nearly eighty percent of all early-onset AD cases. In a strange twist, the Cherokee Indians appear to have an almost total resistance to the disorder. Though it is unknown why this has occurred studies have shown that as the amount of Cherokee ancestry increases in an individual, the chances of AD decrease. In another study done by MIRAGE, shows that at all ages, women have a higher risk of AD than men. By age 93 a womanís risk of having AD is thirteen percent higher than a male that was genetically identical. Environmental factors have also been proven to act on the onset on AD. In a 1996 study of elderly Japanese men living in Hawaii, researchers found that thirty years after the experiment began in 1965, of 4000 men 3,734 were still alive. Of the survivors, 5.4% had been diagnosed with AD, which is incredibly high when compared to the cases of AD in the same age group of men in Hisayama, Japan, which was only 1.5%. Though each of these risk factors has been highly documented, none have been known as a cause of the disease, each are merely known as possible effects of the disorder">(7).

The next category of risk factors are known as probable risk factors, and is constituted of considerable evidence that strongly suggests that the factors increase the likelihood of AD. Among these factors is the presence of apolopoprotien E, which comes in three varieties, called alleles e2, e3, and e4. This gene plays a role in cholesterol metabolism. Another thing that the gene is known for is binding to amyloid, the peptide associated with the senile plaques of AD. Depending on the type of apoE allele one has in the body chances for acquiring AD differ. If one has an abundance of e2 alleles the likelihood of him developing AD decreases. Having e3 gives an individual a fifty-fifty chance of having the disorder, while having just two e4 alleles can increase that number ten fold. Another factor that scientists site as a possible effect of AD is the absence of nonsteroidal anti-inflammatory drug use in a personís daily life. Over the counter pain relievers such as, Motrin, Advil, and Aleve are examples of a group of medications that cause an anti-inflammatory reaction in the body. When a person experiences such afflictions as headache, migraine, fever, muscle pain, or menstrual pain anti-inflammatory medication is used to abate the symptoms of the problem, usually acting as a pain killer. The usefulness of NSAIDs in the fight against AD was first discovered in arthritis and leprosy patients, both of which require high doses of NSAIDs. Researchers in Japan recognized that the number of lepers and arthritics that also develop AD were almost zero. One theory as to why this occurs is that inflammation of brain tissue plays a key role in the development of the neurofibrillary tangles and beta-amyloid plaques that are the hallmark of the disease. These observations suggest that NSAIDs might prevent, or at least delay the inset of AD. On a similar note, another drug therapy that has shown improvement in AD patients is estrogen replacement therapy in women in their post-menopausal years. Women who underwent at least one year of estrogen replacement after menopause were significantly less likely to develop AD than women who did not take the therapy. Animal studies suggest that this is so because estrogen improves the circulation of blood flow to the brain and stimulates nerve cell growth in areas of the brain most affected by Alzheimerís disease. These findings are particularly important, due to the fact that post-menopausal women make up almost sixty percent of AD cases">(8).

A final group of risk factors that scientists identify are called controversial risk factors. Some research suggests that low educational levels, a history of seizures, and exposure to large amounts of zinc or aluminum can significantly contribute to a personís development of AD. Several studies show that actively using the mind for extended periods of time can aid in the preservation of cognition, but the true accuracy of the theory that education relates directly to the development of Alzheimerís disease is still highly debatable. Another theory whose validity is under scrutiny is the relation between AD and seizure sufferers. Both seizures and Alzheimerís disease affect the brainís activity, causing researchers to wonder if a correlation exists between the two afflictions. In recent studies, people with AD were found to be six times more likely to have experienced seizures at some time in their adult life than people who do not have AD. Outside factors such as exposure to chemicals in the environment are also considered controversial risk factors. The two minerals that most researchers focus much of their research upon are zinc and aluminum. Australian researchers have discovered that an unusually large intake of zinc promotes brain alterations similar to the neurofibrillary tangles of AD. In test tube studies it was found that beta-amyloid, which is found in soluble form in the normal brain, forms plaque-like clumps at zinc concentrations only slightly higher than those typical of the normal brain, a result of beta- amyloidís chemical affinity for zinc. Exposure to aluminum, which is unusually uncommon in the nerofibrillary tangles of AD affected brain tissue. At least one study published in the prestigious medical journal Lancet linked an increased risk of AD to drinking water with more than eleven micrograms of aluminum per liter. Though these factors are considered controversial, it does not make them invalid, simply not enough research has been done in to these theories to label them reliably established">(8).

To combat AD, researchers are creating new drug therapies that focus less on curing the disease and more on lessening the effects of the disease on the patients everyday life. Only one drug, which is called Cognex and is modestly effective at best, has been approved for treating AD, researchers in academia, government, and the pharmaceutical industry are now devising a host of new drug strategies that might improve patientsí symptoms. Among the drugs now moving into clinical testing are the anti-inflammatory steroid prednisone, antioxidants such as vitamin E, and estrogen supplements. As mentioned previously, NSAIDs such as prednisone are thought to protect the brain against AD by preventing inflammatory damage to neurons. Vitamin E is an antioxidant that may protect the brain tissue from damage by free radicals. In females, drugs such as estrogen and premarin , both female hormones, promote neuron survival. Even if none of these treatments result in the complete prevention the disease entirely, they could still have an enormous impact, because Alzheimerís symptoms do not usually become apparent until late in life, simply delaying their onset by five years could reduce the number of cases by as much as fifty percent">(5).

Though today the race to find a cure to AD is a fast and furious one, sufferers of the disease are still left almost hopelessly lost in a confused world of dementia. From the earliest days, when Dr. Alzheimer was still completing his autopsy, to today where scientists are discovering new drugs to combat the disease very little has been uncovered as to what is the diseaseís cause. In an area where the majority of research money goes towards AIDS and Cancer research, the majority of Americans are most afraid of developing Alzheimerís disease. Perhaps around the proverbial corner lies the answer to the most plaguing question of our generation, Will we be living in the fear of this disease? ">(YOUR REFERENCE NUMBER).

WWW Sources

2)Th e surgeon generals report, The actual surgeon generals report on the disease and its impact

3), A good article that gives good information

4), A good article which gives some details

5)Veritas Medicine, An actual doctor group that is doing research

6), A group set up to help doctors and care givers

7)The Alzheimers forum, some good information

8)The official Alzheimers website, The real site gives good links and references

9), Good site with basic details

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