What are the Treatment and management options available for Alzheimer's disease?
The management of Alzheimer's
disease consists of medication based and non-medication based treatments.
1) Medication based treatment
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.
Partial glutamate antagonists
Glutamate is the major excitatory
neurotransmitter in the brain. One theory suggests that too much glutamate may
be bad for the brain and cause deterioration of nerve cells.
Memantine (Namenda) works by partially
decreasing the effect of glutamate to activate nerve cells. It has not been
proven that memantine slows down the rate of progression of Alzheimer's
disease. Studies have demonstrated that some patients on memantine can care for
themselves better than patients on sugar pills (placebos).
Memantine is approved for
treatment of moderate and severe dementia, and studies did not show it was
helpful in mild dementia. It is also possible to treat patients with both AchEs
and memantine without loss of effectiveness of either medication or an increase
in side effects.
VITAMIN E
Vitamin E, an antioxidant, is thought to mitigate the inflammatory effects
of plaque formation in the brain. In vitro, vitamin E protects nerve cells from
the effects of b; -amyloid, but it does not protect against other central
nervous system diseases such as Parkinson's disease, in which oxidation is
thought to play a part in neuronal destruction.
The argument for the use of vitamin E comes from the Alzheimer's Disease
Cooperative Study,which evaluated the effects of 10 mg of selegiline once daily
and/or 1,000 IU of vitamin E twice daily as treatments for Alzheimer's disease.
The researchers concluded that these agents delayed disability and nursing home
placement but not deterioration of cognitive function.
The study population
appeared to be highly selected: the subjects were younger but had more severe
dementia than control patients and were not taking psychoactive medication.
Consequently, there have been questions about whether the results of the study
are applicable to a clinical setting.
A recent Cochrane review concluded that after adjusting for differences
between patient groups in the Alzheimer's Disease Cooperative Study, there was
insufficient evidence to recommend vitamin E. The Cochrane review also found
weak evidence of side effects associated with the use of vitamin E. The risks
may be higher in the general population, in which many patients with
Alzheimer's disease also have serious coexisting illnesses.
SELEGILINE
A number of studies have examined evidence for the use of selegiline
(Eldepryl), a selective monoamine oxidase inhibitor, in the treatment of
Alzheimer's disease. Most of these studies have shown some improvement in
cognition, behavior, and mood, but little evidence of a global benefit in
cognition, functional ability, and behavior.
In 2000, the authors of a
meta-analysis of 15 clinical trials concluded that there was not enough
evidence to recommend selegiline as a treatment for Alzheimer's disease.
Because of the risk of stupor, rigidity, severe agitation, and elevated
temperature, selegiline therapy is contraindicated in patients who are taking
meperidine (Demerol), and this precaution often is extended to other opioids.
Concurrent use of selegiline with tricyclic antidepressants and selective
serotonin reuptake inhibitors also should be avoided.These restrictions may
limit the use of selegiline in patients with Alzheimer's disease.
Non-medication based treatments:
Non-medication based treatments
include maximizing patients' opportunities for social interaction and
participating in activities such as walking, singing, dancing that they can
still enjoy. Cognitive rehabilitation, (whereby a patient practices on a
computer program for training memory), may or may not be of benefit. Further
studies of this method are needed.
Symptoms of Alzheimer's disease
include agitation, depression, hallucinations, anxiety, and sleep disorders.
Standard psychiatric drugs are
widely used to treat these symptoms although none of these drugs have been
specifically approved by the FDA for treating these symptoms in patients with
Alzheimer's disease. If these behaviors are infrequent or mild, they often do
not require treatment with medication. Non-pharmacologic measures can be very
useful.
Nevertheless, frequently these
symptoms are so severe that it becomes impossible for caregivers to take care
of the patient, and treatment with medication to control these symptoms becomes
necessary. Agitation is common, particularly in middle and later stages of
Alzheimer's disease.
Many different classes of agents
have been tried to treat agitation including:
- Antipsychotics,
- Mood-stabilizing anticonvulsants,
- Trazodone (Desyrel),
- Anxiolytics, and
- Beta-blockers.
Studies are conflicting about the
usefulness of these different drug classes. It was thought that newer, atypical
antipsychotic agents such as clozapine (Clozaril), risperidone (Risperdal), olanzapine (Zyprexa, Zydis), quetiapine (Seroquel), and ziprasidone (Geodon) might have advantages
over the older antipsychotic agents because of their fewer and less severe side
effects and the patients' ability to tolerate them.
Apathy and difficulty
concentrating occur in most Alzheimer's disease patients and should not be
treated with antidepressant medications. However, many Alzheimer's disease
patients have other symptoms of depression including sustained feelings of
unhappiness and/or inability to enjoy their usual activities. Such patients may
benefit from a trial of antidepressant medication.
Most physicians will try
selective serotonin reuptake inhibitors (SSRIs), such as sertraline (Zoloft), citalopram (Celexa), or fluoxetine (Prozac), as first-line agents
for treating depression in Alzheimer's disease.
Anxiety is another symptom in
Alzheimer's disease that occasionally requires treatment. Benzodiazepines such as diazepam (Valium) or lorazepam (Ativan) may be associated with
increased confusion and memory impairment. Non-benzodiazepine anxiolytics, such
as buspirone (Buspar) or SSRIs, are probably
preferable.
Difficulty sleeping (insomnia) occurs in many patients with
Alzheimer's disease at some point in the course of their disease. Many Alzheimer's
disease specialists prefer the use of sedating atypical antidepressants such as
trazodone (Desyrel). However, other
specialists may recommend other classes of medications. Sleep improvement
measures, such as sunlight, adequate treatment of pain, and limiting
nighttime fluids to prevent the need for urination, should also be implemented.
Potential and future
therapies for Alzheimer's disease.
A variety of clinical
research trials are underway with agents that try either to decrease
the amount of Aβ1-42 produced or increase the amount of Aβ1-42 removed. It is
hoped that such therapies may slow down the rate of progression of Alzheimer's
disease.
As of June 2007, it is not known
how well such therapies may work.
Caring for the caregiver is an
essential element of managing the patient with Alzheimer's disease.
Caregiving is a distressing experience. On
the other hand, caregiver education delays nursing home placement of
Alzheimer's disease patients.
The 3Rs - Repeat, Reassure, and
Redirect - can help caregivers reduce troublesome behaviors and limit the use
of medications. The short-term educational programs are well liked by family
caregivers and can lead to a modest increase in disease knowledge and greater
confidence among caregivers. Educational training for staffs of long-term care
facilities can decrease the use of antipsychotics in Alzheimer's disease
patients.
Alzheimer's Disease At A
Glance:
There are 10 classic warning
signs of Alzheimer's disease: 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, and loss of initiative.
Patients with symptoms of dementia
should be thoroughly evaluated before they become inappropriately or
negligently labeled Alzheimer's disease.
Although there is no cure for
Alzheimer's disease, treatments are available to alleviate many of the symptoms
that cause suffering.
The management of Alzheimer's
disease consists of medication based and non-medication based treatments
organized to care for the patient and family. Treatments aimed at changing the
underlying course of the disease (delaying or reversing the progression) have
so far been largely unsuccessful.
Medicines that restore the
defect, or malfunctioning, in the chemical messengers of the nerve cells have
been shown to improve symptoms. Finally, medications are available that deal
with the psychiatric manifestations of Alzheimer's disease.
Thankyou...
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