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Overview
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 and hippocampus, which atrophy
(lose mass, or shrink) 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.
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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.
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The parietal lobe, located
above the ear, receives and interprets
sensations of pain pressure, temperature, touch,
size, shape, and body part awareness.
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The temporal lobe, located
behind the ear, is involved in understanding
sounds and spoken words, as well as emotion and
memory.
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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
retrograde amnesia, that is, the inability to
retain new information.
Incidence and Prevalence
About 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.
Risk
factors:
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 hypertension
(high blood pressure) 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.
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.
Causes
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.
Symptoms
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:
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Aphasia (i.e., loss of ability in
comprehension of spoken or written language,
naming objects, fluency, etc.)
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Apraxia (e.g., inability to
perform physical tasks such as dressing, eating)
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Delusions
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Easily lost and confused
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Inability to learn new mental
tasks
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Loss of judgment, reason, and
cognitive abilities
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Loss of inhibitions and
belligerence
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Social withdrawal
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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.
Treatment
The U.S. Food and Drug
Administration has approved two drugs for
treatment of Alzheimer's disease, donepezil (Aricept®)
and tacrine (Cognex®). Both help increase the
level of acetylcholine (ACh) in the brain by
inhibiting the enzyme that breaks it down. The
effect on patients is modest. They do not improve
symptoms but may stabilize the condition for some
months. Both drugs produce side effects:
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Diarrhea
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Dizziness
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Drowsiness
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Fatigue
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Nausea
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Vomiting
Tacrine is taken four times a day
and requires monitoring of its effect on the
liver. Donepezil is taken once a day. Patients
with liver disease, peptic ulcer disease, chronic
obstructive pulmonary disease (COPD), and
bradycardia (slow heartbeat) should not take these
drugs.
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, and
benzodiazepines. These medications produce side
effects including 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. |
