24.jpg)
Original Date of Publication: 02 Jan 2000 Original Source: http://www.neurologychannel.com/alzheimers/index.shtm
Reviewed by: Stanley J. Swierzewski, III, M.D.
Alzheimer's disease (AD) is an irreversible, progressive disorder in which brain cells (neurons) deteriorate, resulting in the loss of cognitive functions, primarily memory, judgment and reasoning, movement coordination, and pattern recognition. In advanced stages of the disease, all memory and mental functioning may be lost.
The condition predominantly affects the cerebral cortex andhippocampus, which lose mass and shrink (atrophy) as the disease advances.
Plaques and Tangles
The two most significant physical findings in the cells of brains affected by Alzheimer's disease are neuritic plaques and neurofibrillary tangles. Another significant factor in AD is the greatly reduced presence of acetylcholine in the cerebral cortex. Acetylcholine is necessary for cognitive function.
While some neuritic plaques, or patches, are commonly found in brains of elderly people, they appear in excessive numbers in the cerebral cortex of Alzheimer's disease patients. A protein called beta amyloid occupies the center of these plaques. Surrounding the protein are fragments of deteriorating neurons, especially those that produce acetylcholine (ACh), a neurotransmitter essential for processing memory and learning. Neurotransmitters are chemicals that transport information or signals between neurons.
Neurofibrillary tangles (NFTs) are twisted remnants of a protein called tau, which is found inside brain cells and is essential for maintaining proper cell structure and function. An abnormality in the tau protein disrupts normal cell activity.
Anatomy
The cerebral cortex is an extremely convoluted and complicated structure associated with the "higher" functions of the mind—thought, reasoning, sensation, and motion. Each hemisphere of the cerebral cortex contains areas that control certain types of activity. These areas are referred to as the frontal lobe, parietal lobe, temporal lobe, and occipital lobe.
- The frontal lobe, located behind the forehead, is involved with controlling responses to input from the rest of the central nervous system (brain and spinal cord). It is responsible for voluntary movement, emotion, planning and execution of behavior, intellect, memory, speech, and writing.
- The parietal lobe, located above the ear, receives and interprets sensations of pain pressure, temperature, touch, size, shape, and body part awareness.
- The temporal lobe, located behind the ear, is involved in understanding sounds and spoken words, as well as emotion and memory.
- The occipital lobe, located at the back of the head, is involved in understanding visual images and the meaning of the written word.
The hippocampus plays a crucial role in learning and in processing various forms of information as long-term memory. Damage to the hippocampus produces global amnesia.
Incidence and Prevalence
According to the Alzheimer's Association, about 5.2 million people in the United States suffer from Alzheimer's disease. Approximately 10% of all people over the age of 65 and as many as 50% of those over the age of 85 are diagnosed with the condition, which is the seventh leading cause for death.
Risk Factors, Causes, Signs and Symptoms, Complications |     |
Risk Factors
The risk for Alzheimer's disease increases with each decade of adult life. People with a family history of Alzheimer's have a greater risk, implying that a genetic factor is involved. A clear inherited pattern of AD exists in less than 10% of cases. Some involve a mutation of the gene for the protein APP, found on chromosome 21.
Nearly all people with Down's syndrome (trisomy 21) who live into their 40s develop the disease. Others involve a defect on chromosome 14. The gene for the protein Apo E, found on chromosome 19, is a risk factor that may be involved in modifying the age of onset.
Untreated chronic high blood pressure (hypertension) has been identified as a risk factor for loss of mental function in older people. Treatment reduces the risk. Adults who have had head injuries are three times more likely to develop Alzheimer's disease. Studies also have shown that diabetes may increase the risk for Alzheimer's and other forms of dementia.
It is thought that gender plays a role because several studies suggest that women are afflicted with Alzheimer's disease more often than men. However, the evidence is inconsistent and some studies report that the disease is more prevalent in men. Therefore, more research is needed to obtain conclusive evidence regarding prevalence in gender.
Genetic factors are known to play a role in some cases of Alzheimer's. The APP gene found on chromosome 21 is implicated in the occurrence of AD in Down's syndrome patients who survive beyond 40 years. Some families with a history of early-onset AD have a mutation on the APP gene and others have a mutation in the presenilin-1 gene (PS-1) found on chromosome 14. Another gene, the Apo E gene on chromosome 19, also has been implicated in the disease. Apo E is a protein found with beta amyloid in neuritic plaques.
It is not known whether the characteristic neuritic plaques and neurofibrillary tangles are the cause or the result of the disease process.
Early symptoms, such as memory loss, may be attributed to the forgetfulness associated with ageing. Gradually, the loss of cognitive function disrupts the patient's ability to perform common daily activities, such as paying bills, driving, and housekeeping. Some people remain unaware of their symptoms, while others are painfully aware of the fact that they are losing mental function.
Symptoms of Alzheimer's disease include the following:
- Apraxia (inability to perform physical tasks such as dressing, eating)
- Aphasia (loss of ability in comprehension of spoken or written language)
- Delusions
- Easily lost and confused
- Inability to learn new mental tasks
- Loss of judgment, reason, and cognitive abilities
- Loss of inhibitions and belligerence
- Social withdrawal
- Visual hallucinations
In end-stage Alzheimer's disease, patients may become bedridden and need help with eating and getting out of bed to use the bathroom. Patients also may experience convulsions and seizures and may become incontinent.
Complications
Depression is common in patients with Alzheimer's disease, especially during the earlier stages when they may be aware of losing mental functions.
Diagnosis
The diagnosis involves taking a detailed history of symptoms and ruling out other treatable medical and psychological conditions that cause loss of cognitive function (dementia), such as the following:
- Depression
- Head trauma
- Infection (e.g., HIV, syphilis)
- Intoxication or withdrawal from medication, poison, or substance of abuse
- Kidney disease
- Liver disease
- Neurodegenerative diseases (e.g., Creutzfeldt-Jakob, Huntington's)
- Seizures
- Thiamine or vitamin B deficiency
- Thyroid disease
- Tumor
Normal effects of aging must be ruled out as well.
A mental status examination reviews systems of higher mental function. This involves asking questions to evaluate mental functions and making observations of the patient's behavior, appearance, and attitude. Questions are designed to assess orientation, memory, attention and concentration, insight and judgment, general intellectual functions (e.g., calculation; common knowledge, such as What is the capital of the United States?; identifying similarities and differences between words).
Slowly progressive loss of memory and orientation, normal lab test results, and brain imaging scans that show atrophy of the cerebral cortex and hippocampus indicate a diagnosis of Alzheimer's disease.
Tests
Routine blood, serum, and plasma analyses can identify the presence of most diseases mentioned. Brain imaging studies are capable of identifying the presence of tumor, head trauma, and neurological conditions.
Magnetic resonance imaging (MRI) or computed tomography (CT) scans show diffuse atrophy of the cerebral cortex and hippocampus in Alzheimer's disease. Neuroimaging may be normal early in the disease.
Treatment
There is no cure for Alzheimer's disease. The U.S. Food and Drug Administration (FDA) has approved donepezil (Aricept®), galantamine (Razadyne® ER, formerly branded as Reminyl®), and rivastigmine (Exelon®) for treatment of mild-to-moderate Alzheimer's disease.
The Exelon® Patch (rivastigimine transdermal system) is also approved for mild-to-moderate dementia associated with Alzheimer's. This patch is applied to the skin (usually on the back, chest, or upper arm) and delivers medication continuously for 24 hours.
In October of 2006, Aricept® was approved for treatment of severe dementia in patients who have advanced disease.
These medications help increase the level of acetylcholine (ACh) in the brain by inhibiting the enzyme that breaks it down. They may help patients with early or moderate Alzheimer's disease maintain function longer and may slow progression of the disease for a few months to a few years.
Side effects include the following:
- Diarrhea
- Dizziness
- Drowsiness
- Fatigue
- Nausea
- Vomiting
Patients with liver disease, peptic ulcer disease, chronic obstructive pulmonary disease (COPD), and slow heartrate (bradycardia) should not take these drugs.
Memantine (Namenda®) is the only medication approved by the FDA to treat moderate-to-severe symptoms of Alzheimer's disease. It can be used alone or in combination with other medications (e.g., donepezil).
Memantine helps protect nerve cells in the brain from excess glutamate, which is a neurotransmitter that plays a role in neurodegenerative diseases. Clinical studies have shown that it can improve memory and function and prolong the ability of Alzheimer's patients to perform some tasks independently. Side effects include headache, constipation, confusion, and dizziness.
Neurobehavioral symptoms associated with Alzheimer's disease interfere with normal daily activities and sleeping.Depression that occurs during the early stages are commonly treated with antidepressant medication, such as selective serotonin reuptake inhibitors (SSRIs) and the tricyclics. Benadryl is used to help relieve insomnia. These medications produce side effects including drowsiness, dry mouth, and constipation.
Agitation and belligerence are sometimes treated with antipsychotic medication, such as haloperidol, risperidone (Risperdal®), benzodiazepines, and newer antipsychotic drugs (e.g., olanzapine [Zyprexa®], quetiapine [Seroquel®], ziprasadone [Zeldox®, Geodon®]). Antipsychotics are not FDA-approved to treat symptoms of Alzheimer's disease and may increase the risk for death in elderly dementia patients. Side effects include sedation, confusion, and increased muscle tone.
Safety and Quality of Life
Memory aids such as notepads and reminders posted in specific locations are helpful. A careful evaluation of the home is essential for safety, especially the kitchen, bathroom, and bedroom. Some therapists and social service workers are trained to perform this service. People with Alzheimer's are often afraid to be alone or fear they'll be forced to leave their homes.
Loss of independence and changes in their environment, such as being placed in a nursing home, can cause distress, anger, confusion, and agitation. Patients need well-managed orientation to a new environment and constant reassurance. Family involvement and support services help patients and their caregivers cope.
Prognosis
Patients may survive 8 to 10 years with Alzheimer's disease. Some have been known to live 25 years with the disease. Death usually occurs due to secondary infections, heart disease, or malnutrition.
No comments:
Post a Comment