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Alzheimer's Disease

Alzheimer's Disease

Alzheimer's disease (AD) is a slowly progressive disease of the brain that is characterized by impairment of memory and eventually by disturbances in reasoning, planning, language, and perception.

 

Many scientists believe that Alzheimer's disease results from an increase in the production or accumulation of a specific protein (beta-amyloid protein) in the brain that leads to nerve cell death.

 

The likelihood of having Alzheimer's disease increases substantially after the age of 70 and may affect around 50% of persons over the age of 85. Nonetheless, Alzheimer's disease is not a normal part of aging and is not something that inevitably happens in later life. For example, many people live to over 100 years of age and never develop Alzheimer's disease.

Symptoms

The Alzheimer's Association has developed the following list of warning signs that include common symptoms of Alzheimer's disease. Individuals who exhibit several of these symptoms should see a physician for a complete evaluation.

 

  • Memory loss.
  • Difficulty performing familiar tasks.
  • Problems with language.
  • Disorientation to time and place.
  • Poor or decreased judgment.
  • Problems with abstract thinking.
  • Misplacing things.
  • Changes in mood or behavior.
  • Changes in personality.
  • Loss of initiative.

 

It is normal for certain kinds of memory, such as the ability to remember lists of words, to decline with normal aging. In fact, normal individuals 50 years of age will recall only about 60% as many items on some kinds of memory tests as individuals 20 years of age.

 

Furthermore, everyone forgets, and every 20 year old is well aware of multiple times he or she couldn't think of an answer on a test that he or she once knew. Almost no 20 year old worries when he/she forgets something, that he/she has the 'early stages of Alzheimer's disease, whereas an individual 50 or 60 years of age with a few memory lapses may worry that they have the 'early stages of Alzheimer's disease.

 

There is no "typical" person with Alzheimer's. There is tremendous variability among people with Alzheimer's in their behaviors and symptoms. At present, there is no way to predict how quickly the disease will progress in any one person or the exact changes that will occur. We do know, however, that many of these changes will present problems for caregivers. Therefore, knowledge and prevention are critical to safety.

 

People with Alzheimer's disease have memory problems and cognitive impairment (difficulties with thinking and reasoning), and eventually they will not be able to care for themselves. They often experience confusion, loss of judgment, and difficulty finding words, finishing thoughts, or following directions. They also may experience personality and behavior changes.

 

For example, they may become agitated, irritable, or very passive. Some people with Alzheimer's may wander from home and become lost. Others may not be able to tell the difference between day and night — they may wake up, get dressed, and start to leave the house in the middle of the night thinking that the day has just started. People with Alzheimer's also can have losses that affect vision, smell, or taste.

 

These disabilities are very difficult, not only for the person with Alzheimer's, but for the caregiver, family, and other loved ones as well. Caregivers need resources and reassurance to know that while the challenges are great, specific actions can reduce some of the safety concerns that accompany Alzheimer's disease.

Causes

The cause(s) of Alzheimer's disease is (are) not known. The "amyloid cascade hypothesis" is the most widely discussed and researched hypothesis about the cause of Alzheimer's disease. The strongest data supporting the amyloid cascade hypothesis comes from the study of early-onset inherited (genetic) Alzheimer's disease.

 

Mutations associated with Alzheimer's disease have been found in about half of the patients with early-onset disease. In all of these patients, the mutation leads to excess production in the brain of a specific form of a small protein fragment called ABeta (Aβ).

 

Many scientists believe that in the majority of sporadic (for example, non-inherited) cases of Alzheimer's disease (these make up the vast majority of all cases of Alzheimer's disease) there is too little removal of this Aβ protein rather than too much production. In any case, much of the research in finding ways to prevent or slow down Alzheimer's disease has focused on ways to decrease the amount of Aβ in the brain.

Treatment

The management of Alzheimer's disease consists of medication based and non-medication based treatments. Two different classes of pharmaceuticals are approved by the FDA for treating Alzheimer's disease: cholinesterase inhibitors and partial glutamate antagonists.

 

Neither class of drugs has been proven to slow the rate of progression of Alzheimer's disease. Nonetheless, many clinical trials suggest that these medications are superior to placebos (sugar pills) in relieving some symptoms.

 

Cholinesterase inhibitors

 

In patients with Alzheimer's disease there is a relative lack of a brain chemical neurotransmitter called acetylcholine. Neurotransmitters are chemical messengers produced by nerves that the nerves use to communicate with each other in order to carry out their functions.

 

Substantial research has demonstrated that acetylcholine is important in the ability to form new memories. The cholinesterase inhibitors (ChEIs) block the breakdown of acetylcholine. As a result, more acetylcholine is available in the brain, and it may become easier to form new memories.

 

Four ChEIs have been approved by the FDA, but only donepezil hydrochloride (Aricept), rivastigmine (Exelon), and galantamine (Razadyne - previously called Reminyl) are used by most physicians because the fourth drug, tacrine (Cognex) has more undesirable side effects than the other three.

 

Most experts in Alzheimer's disease do not believe there is an important difference in the effectiveness of these three drugs. Several studies suggest that the progression of symptoms of patients on these drugs seems to plateau for six to 12 months, but inevitably progression then begins again.

 

Of the three widely used AchEs, rivastigmine and galantamine are only approved by the FDA for mild to moderate Alzheimer's disease, whereas donepezil is approved for mild, moderate, and severe Alzheimer's disease. It is not known whether rivastigmine and galantamine are also effective in severe Alzheimer's disease, although there does not appear to be any good reason why they shouldn't.

 

The principal side effects of ChEIs involve the gastrointestinal system and include nausea, vomiting, cramping, and diarrhea. Usually these side effects can be controlled with change in size or timing of the dose or administering the medications with a small amount of food. Between 75% and 90% of patients will tolerate therapeutic doses of ChEIs.

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