Research paper fundamentals and methodology

Aricept

Alzheimer's Disease is a progressive form of pre-senile dementia, which similar to senile dementia, except that it usually starts in the 40s or 50s, and with initial symptoms of impaired memory, then impaired thought and speech and, finally, complete helplessness (Lexico Publishing Group LLC 2006). It is a disease in the brain, which makes the sufferer forget how to use a key, walk, talk or eat (Liebman 2002). Recent statistics showed that approximately a third of all people older than 85 have Alzheimer's or another type of dementia. Around 1,000 are diagnosed with it each day in the U.S. And records revealed that the number has been increasing. The projection is that there may be up to 14 million Americans with this disease by the year 2050, according to Neil Buckholtz, chief of the Dementias of Aging Branch at the National Institute on Aging. Seventy percent of all cases of dementia is Alzheimer's. Scientists are still in the dark as to what triggers it and they are agreed that it is not part of normal aging. Normal aging does not interfere with daily life, but Alzheimer's disturbs the afflicted person entirely. In most cases, the disease first attacks those parts of the brain, which are involved in memory and visual-spatial thinking, such as where things fit in space. Symptoms can be difficulty in reading a map or in negotiating off a highway because the person cannot interpret road signs. His memory fails more than usual in remembering when he left the key, the birth date of someone, how to turn the computer off or the name of someone dear to him. Memory loss is greater and spreads more quickly over time. The change is visible in someone after six months with early Alzheimer's and this is not the case with a normal person in that short span of time. In one out of 10 cases, the disease begins with changes in behavior. If it starts at the frontal lobe of the brain, that person may experience depression or psychosis. The disease then spreads to all parts of the brain. Records attested that 70% of patients become depressed at some time during the disease but memory and visual-spatial impairment eventually occurs in all of them. Hallmarks of Alzheimer's are plaques and tangles. It is, however, not clear that these cause Alzheimer's (Liebman, Delagarza 2003). The assumption was that inflammation around these plaques destroyed neighboring neurons. These plaques were composed of b-amyloid polypeptides, which formed as a result of disorders in processing b-amyloid and its precursor protein. The condition appeared to develop out of a genetic disposition and environmental influences. One of them may be sub-clinical ischemia, as patients with high blood pressure and high cholesterol levels tended to have increased risk for Alzheimer's. On the other hand, neurofibrillary tangles are partly a protein, which links together to form filaments. These filaments within neurons in the brain are directly proportionate with the severity of dementia. It is not known why tangles form, but the alleles of a gene known to create them have been demonstrated as likelier to tangle. It is also unclear whether tangles are linked to plaque formation (Delagarza).

Of the reported 4.5 million Americans afflicted with Alzheimer's, African-Americans are twice or thrice more affected than Caucasians in the next 30 years (Ebony 2005). The estimate was that African-Americans beyond 65 years would be more likely to develop it at twice the rate up to 6.9 million. African-Americans would also tend to be diagnosed at the later stages, where the cognitive function has already significantly declined. Although there has yet to be a specific cure for the disease, evidence showed that donepezil HCL, brand name Aricept, could benefit those with mild to moderate Alzheimer's. This was the finding of a recent study conducted with 126 African-American patients who demonstrated significant improvement in their memory and learning. The prescribed dosage is once a day. Aricept has been shown to be well-tolerated, although some patients reported side effects, such as stomach problems and fainting (Ebony). Four medications under the category of cholinesterase inhibitors have been approve as treatment of Alzheimer's, one of them being donepezil, the generic for Aricept (Vickrey 2002). These medications are not considered cures, but they were found to improve cognition, behavior and functioning in some patients. The activity of acetylcholine as a brain neurotransmitter plays an important role in learning and memory and found to be significantly decreased in Alzheimer's sufferers. Cholinesterase inhibitors appeared to break down acetylcholine and enhance cholinergic function (Vickrey).

Aricept is marketed by Eisai America, Inc. And has the approval of the Food and Drug Administration for treating mild to moderate symptoms of Alzheimer's Disease (FDA Consumer 1997). Aricept increases the levels of a neurotransmitter, which is essential to memory, judgment, the ability to reason and other cognitive functions. Aricept became the second drug approved for the treatment of the disease, the first was Tacrine, brand name for cognex, approved in 1993. A series of trials showed that most patients tolerated the drug's side effects, such as diarrhea and nausea, slowed heartbeat and fainting (FDA Consumer). This year, Aricept became the first and only treatment approved by the FDA for the full range of Alzheimer's from mild to severe (PR Newswire 2006). A six-month, multi-center, randomized, double-bind, placebo-controlled clinical trial was conducted in March this year with 248 Swedish nursing home patients with the severe stage of the disease. It revealed that the patients received more significant benefit than those on placebo. This test confirmed that Aricept was generally well tolerated and that the most commonly experience side effects were diarrhea, anorexia, vomiting, nausea and bruising. Aricept is said to help slow down the progression of the symptoms of the disease. The approved dosage for mild and moderate stages was 5 and 10 mg. Aricept 10 mg is the approved dosage for the severe stage after four to six weeks on 5 mg. It is said to inhibit the breakdown of acetylcholine and thus increase the available levels of the chemical in the brain. A link between the loss of acetylcholine and Alzheimer's was previously established (PR Newswire).

Although well tolerated, Aricept did not appear to be the choice medication for everyone with Alzheimer's (PR Newswire 2006). Those who suffer from stomach ulcers or stomach bleeding may be advised against its use. Some patients using Aricept were reported to have experienced nausea, vomiting, diarrhea, bruising, sleep problems, muscle cramps, loss of appetite or fatigue. Manufacturers, however, said that these side effects were mild and temporary. They explained that, in a progressively degenerative disease like Alzheimer's, improvement, stabilization or a decline over time should be viewed as positive responses to treatment. These responses were observed in patients taking or treated with Aricept, according to clinical trials. It is the number one prescribed medication for Alzheimer's worldwide and more than 3 billion patients have been on it. In the U.S. alone, close to 2.3 million people were reported to taking Aricept (PR Newswire).