Alzheimer Disease [ AD ]
Based on textbook.
- Proggresive brain disease.
Characterized by :
- Development of amyloid plaque.
- Loss of connection between nerve cells in the brain and the death of these nerve cell.
Caused by :
- A number of different gene mutations, each of mutation causes abnormal folded proteins to be formed.
Alzheimer disease is identified as protein misfolding disease. Caused by :
- Accumulation of abnormally folded proteins in the brain called Amyloid Precursor Protein (APP), which is critical to the neuron growth, survival dan post-injury repair.
- This abnormal folded protein will the be degraded into smaller fragments called beta-amyloid which form plaques around neuron.
Alzheimer's disease (AD), also known in medical literature as Alzheimer disease, is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death. It was first described by German psychiatrist and neuropathologist Alois Alzheimer in 1906 and was named after him.
Most often, AD is diagnosed in people over 65 years of age, although the less-prevalent early-onset Alzheimer's can occur much earlier. In 2006, there were 26.6 million sufferers worldwide. Alzheimer's is predicted to affect 1 in 85 people globally by 2050.
Although Alzheimer's disease develops differently for every individual, there are many common symptoms. Early symptoms are often mistakenly thought to be 'age-related' concerns, or manifestations of stress. In the early stages, the most common symptom is difficulty in remembering recent events. When AD is suspected, the diagnosis is usually confirmed with tests that evaluate behaviour and thinking abilities, often followed by a brain scan if available.
The first symptoms are often mistakenly attributed to ageing or stress. Detailed neuropsychological testing can reveal mild cognitive difficulties up to eight years before a person fulfils the clinical criteria for diagnosis of AD. These early symptoms can affect the most complex daily living activities. The most noticeable deficit is memory loss, which shows up as difficulty in remembering recently learned facts and inability to acquire new information.
Subtle problems with the executive functions of attentiveness, planning, flexibility, and abstract thinking, or impairments in semantic memory (memory of meanings, and concept relationships) can also be symptomatic of the early stages of AD.Apathy can be observed at this stage, and remains the most persistent neuropsychiatric symptom throughout the course of the disease.The preclinical stage of the disease has also been termed mild cognitive impairment, but whether this term corresponds to a different diagnostic stage or identifies the first step of AD is a matter of dispute.
In people with AD the increasing impairment of learning and memory eventually leads to a definitive diagnosis. In a small portion of them, difficulties with language, executive functions, perception (agnosia), or execution of movements (apraxia) are more prominent than memory problems. AD does not affect all memory capacities equally. Older memories of the person's life (episodic memory), facts learned (semantic memory), and implicit memory (the memory of the body on how to do things, such as using a fork to eat) are affected to a lesser degree than new facts or memories.
Language problems are mainly characterised by a shrinking vocabulary and decreased word fluency, which lead to a general impoverishment of oral and written language. In this stage, the person with Alzheimer's is usually capable of communicating basic ideas adequately.
While performing fine motor tasks such as writing, drawing or dressing, certain movement coordination and planning difficulties (apraxia) may be present but they are commonly unnoticed. As the disease progresses, people with AD can often continue to perform many tasks independently, but may need assistance or supervision with the most cognitively demanding activities.
Progressive deterioration eventually hinders independence, with subjects being unable to perform most common activities of daily living. Speech difficulties become evident due to an inability to recall vocabulary, which leads to frequent incorrect word substitutions (paraphasias). Reading and writing skills are also progressively lost.Complex motor sequences become less coordinated as time passes and AD progresses, so the risk of falling increases. During this phase, memory problems worsen, and the person may fail to recognise close relatives.Long-term memory, which was previously intact, becomes impaired.
Behavioural and neuropsychiatric changes become more prevalent. Common manifestations are wandering, irritability and labile affect, leading to crying, outbursts of unpremeditated aggression, or resistance to caregiving. Sundowning can also appear. Approximately 30% of people with AD develop illusionary misidentifications and other delusional symptoms. Subjects also lose insight of their disease process and limitations (anosognosia). Urinary incontinence can develop.
These symptoms create stress for relatives and caretakers, which can be reduced by moving the person from home care to other long-term care facilities.
During the final stage of AD, the person is completely dependent upon caregivers. Language is reduced to simple phrases or even single words, eventually leading to complete loss of speech. Despite the loss of verbal language abilities, people can often understand and return emotional signals.Although aggressiveness can still be present, extreme apathy and exhaustion are much more common results. People with AD will ultimately not be able to perform even the simplest tasks without assistance. Muscle mass and mobility deteriorate to the point where they are bedridden, and they lose the ability to feed themselves AD is a terminal illness, with the cause of death typically being an external factor, such as infection of pressure ulcers or pneumonia, not the disease itself.
|Classification and external resources : Comparison of a normal aged brain (left) and the brain of a person with Alzheimer's (right). Differential characteristics are pointed out|
|PET (positron emission tomography)scan of the brain of a person with AD showing a loss of function in the temporal lobe|
|Enzymes act on the APP (amyloid precursor protein) and cut it into fragments. The beta-amyloid fragment is crucial in the formation of senile plaques in AD.|
|In Alzheimer's disease, changes in tau protein lead to the disintegration of microtubules in brain cells.|
What is 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.
Who develops Alzheimer's disease?
The main risk factor for Alzheimer's disease is increased age. As a population ages, the frequency of Alzheimer's disease continues to increase. Ten percent of people over 65 years of age and 50% of those over 85 years of age have Alzheimer's disease. Unless new treatments are developed to decrease the likelihood of developing Alzheimer's disease, the number of individuals with Alzheimer's disease in the United States is expected to be 14 million by the year 2050.
There are also genetic risk factors for Alzheimer's disease. Most patients develop Alzheimer's disease after age 70. However, 2%-5% of patients develop the disease in the fourth or fifth decade of life (40s or 50s). At least half of these early onset patients have inherited gene mutations associated with their Alzheimer's disease. Moreover, the children of a patient with early onset Alzheimer's disease who has one of these gene mutations has a 50% risk of developing Alzheimer's disease.
There is also a genetic risk for late onset cases. A relatively common form of a gene located on chromosome 19 is associated with late onset Alzheimer's disease. In the majority of Alzheimer's disease cases, however, no specific genetic risks have yet been identified.
How is the diagnosis of Alzheimer's disease made?
As of June 2007, there is no specific "blood test" or imaging test that is used for the diagnosis of Alzheimer's disease. Alzheimer's disease is diagnosed when:
1) a person has sufficient cognitive decline to meet criteria for dementia;
2) the clinical course is consistent with that of Alzheimer's disease;
3) no other brain diseases or other processes are better explanations for the dementia.
What other conditions should be screened for?
There are many conditions that can cause dementia, to include the following:
Neurological disorders: Parkinson's disease, cerebrovascular disease and strokes, brain tumors, blood clots, and multiple sclerosis can sometimes be associated with dementia although many patients with these conditions are cognitively normal.
Infectious diseases: Some brain infections such as chronic syphilis, chronic HIV, or chronic fungal meningitis can cause dementia.
What are risk factors for Alzheimer's disease?
The biggest risk factor for Alzheimer's disease is increased age. The likelihood of developing Alzheimer's disease doubles every 5.5 years from 65 to 85 years of age. Whereas only 1%-2% of individuals 70 years of age have Alzheimer's disease, in some studies around 40% of individuals 85 years of age have Alzheimer's disease. Nonetheless, at least half of people who live past the 95 years of age do not have Alzheimer's disease.
What are the Symptoms 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.
What treatment and management options are available for Alzheimer's disease?
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.
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.
General Safety Concerns
People with Alzheimer's disease become increasingly unable to take care of themselves. However, the disease progresses differently in each person. As a caregiver, you face the ongoing challenge of adapting to each change in the person's behavior and functioning. The following general principles may be helpful.
1) Think prevention.
It is very difficult to predict what a person with Alzheimer's might do. Just because something has not yet occurred does not mean it should not be cause for concern. Even with the best-laid plans, accidents can happen. Therefore, checking the safety of your home will help you take control of some of the potential problems that may create hazardous situations.
2) Adapt the environment.
It is more effective to change the environment than to change most behaviors. While some Alzheimer's behaviors can be managed with special medications prescribed by a doctor, many cannot. You can make changes in an environment to decrease the hazards and stressors that accompany these behavioral and functional changes.
3) Minimize danger.
By minimizing danger, you can maximize independence. A safe environment can be a less restrictive environment where the person with Alzheimer's disease can experience increased security and more mobility.