Possible Treatments for Alzheimer's Disease
At this time there is no treatment available to stop or reverse the mental deterioration of Alzheimer's disease. However, newresearch findings give reason for hope. Several drugs are being studied in clinical trials to find out whether they can slow the progression of the disease or improve memory for a period of time. One drug, Cognex® (a.k.a. tacrine or THA) was approved by the FDA in September 1993 for the treatment of mild to moderate Alzheimer's disease. In studies, some of the patients who tried the drug showed memory improvement, though only temporarily. The potential risks and benefits of this drug should be discussed with a doctor to decide whether a patient should try it. Other medications are now available to assist in managing some of the most troubling symptoms of Alzheimer's disease. Under a doctor's supervision, medication can be used to control depression, behavioral disturbance and sleeplessness. Physical exercise and social activity are important, as are proper nutrition and health maintenance. A calm and well-structured environment will help the affected person maintain as much comfort and dignity as possible.
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 besipirdine |
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 Huperzine A |
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 ondansetron |
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 nerve growth
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 tertiary amine
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 Some research
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Tacrine is the first drug approved by the FDA specifically for AD. Tacrine helps slow the breakdown of acetylcholine, a chemical necessary for brain-cell communication and one which is severely depleted in AD. The effects of the drug are far from dramatic. Generally, about half of patients who begin taking it withdraw mostly because of side effects, such as rashes and stomach problems. In those who continue, slight improvement occurs in less than half of patients with mild to moderate stages of the disease. Patients taking very high dosages of the drug (160 mg per day) show the most improvement, but they also have the highest risk for liver damage, a common and serious side effect of tacrine. Discontinuing the drug reverses liver problems.
In addition to tacrine, other drugs are being studied that affect acetylcholine and the cholinergic neurotransmitter system to which this chemical belongs. One of the most recent drugs in trials is besipirdine (HP 749) which mimics acetylcholine. Subjects for this trial must be over 41 years old, have had gradual onset of AD, and be in general good health. Caregivers should be prepared to make 15 to 18 visits to the clinic during a year-long experimental period. Physostigmine (Synapton) is a drug that protects acetylcholine and is also being tested. Patients must be 45 years old, in good health, and caregivers need to be available every one to two weeks. Trials using velnacrine (Mentane), which helped prevent the breakdown of acetylcholine, were discontinued in early 1994.
Huperzine A, a folk remedy from China made of club moss, may be in tests shortly. Many experts object to trying to find drugs that affect the cholinergic system, because such drugs will never alter the progress of the disease. Sabeluzole is a new drug aimed at protecting against brain damage, accelerating growth of nerve cells, and helping in transporting beneficial substances within cells. The drug is not expected to improve memory, but researchers hope it will slow the progression of AD. Those eligible must be younger than 85 years old, in stable medical condition, and must have caregivers who are at home at least 20 hours a week.
The drug ondansetron has been shown to improve memory and learning in animals. It, too, is not expected to cure AD but to alleviate symptoms. The action of this drug results in increased transmission of nerve-cell impulses to the parts of the brain involved with memory. Subjects for the test should be 50 years old or older, with a probable diagnosis of AD, in good health, and not living in a nursing home.
The figure shows a ribbon representation of a polypeptide backbone of nerve growth factor (NGF).NGF binds to two receptors, a low affinity receptor and a high affinity receptor known as TRK A.NGF has been shown to have trophic actions on some cholinergic systems including the basal forebrain system of the brain. For this reason, NGF has been mooted as a potential therapeutic agent. However, it is unclear what effects NGF may have on the proteolytic processing of the amyloid protein precursor.
Several tertiary amine compounds have been documented to have high muscarinic agonist activity and lipophilic properties that enable them to easily cross the blood-brain barrier. The naturally occurring alkaloid arecoline is one such compound (however, arecoline is not therapeutically usefull due to a short half-life through rapid in vivo hydrolysis). Other compounds displaying muscarinic agonist activity are currently undergoing clinical trials; especially heterocyclic derivatives and oxime ethers of quinuclidine and other azabicyclic substrates, and tetrahydropyridine derivatives (arecoline analogs).
Some research and development drugs that enhance the cholinergic function include:
Acetylcholinesterase inhibitors Tacrine (Parke-Davis) Velnacrine (Hoechst-Roussel) E2020 (Eisai) Heptylphysostigmine (Merck) Physostigmine (Forest) MDL 73,745 (Marion Merrell-Dow) Acetylcholine release effector Linopirdine (Dupont-Merck) Muscarinic agonists Xanomeline (Eli Lilly) AF102B (Fisher) Quinuclidine oximes (Warner-Lambert) Arecoline (Ciba-Geigy) RS 86 (Sandoz)
Home Treatment in Early Stages.
Often caregivers and professionals are tempted to treat AD patients as though they were children, but they are not. As adults with a degrading disease, their dignity should always be honored. If an AD patient expresses a need to know the truth, it should be disclosed. Both the caregiver and the victim can then begin to address the issues of this disabling disease, such as access to resources, support groups, and drug research. Moods change abruptly, and AD patients can become aggressive and angry. Some of this erratic behavior is caused by chemical changes in the brain. But, certainly, it can also be attributed to the terrible and real experience of losing the knowledge and understanding of their surroundings, causing fear and frustration that they can no longer express verbally. It is important for the caregiver to control the environment by keeping distractions and noise at a minimum and to speak clearly. Most experts recommend speaking slowly to an AD patient, but some caregivers suggest that AD patients respond better to clear, quickly spoken sentences they can more easily remember. Caregivers should maintain as natural an attitude as possible; many AD patients are highly sensitive to the caregiver's underlying emotions and react negatively to signals of patronization, anger, and frustration. Often the AD patient loses the sense of color and design and will put on odd or mismatched clothing. This may be very frustrating to a loved one, particularly since embarrassment is a common and painful emotion experienced by the caregiver. It is important for the caregiver to maintain a sense of humor and perspective and to learn which battles are worth fighting and which ones are best abandoned. An AD patient's incontinence is generally devastating to the caregiver and a primary reason why many caregivers decide to seek nursing home placement when the patient reaches this stage. When the patient first shows signs of incontinence, the doctor should as certain that it is not caused by an infection. Urinary incontinence may be controlled for some time by trying to monitor times of liquid intake, feeding, and urinating. Once a schedule has been established, the caregiver may be able to anticipate incontinent episodes and get the patient to the toilet before they occur. In many cases, the AD patient becomes uninhibited sexually; at the same time, the patient's physical deterioration and receding capacity to recognize the spouse as a known and loved individual may make sexual activity despairing and repellent for the caregiving spouse. Other patients may lose interest in sex. If sexual issues are a problem, they should be discussed openly with the physician and ways should be found to maintain non-sexual physical affection that can bring comfort to both the patient and the spouse.
Home Treatment during Later Stages. Even if the caregiver has the resources to keep the AD patient at home during later stages of the disease, outside help is still essential. The AD patient needs 24-hour a day attention. As the disease progresses, AD victims become immobile, literally forgetting how to move. Eventually, they become almost entirely wheelchair-bound or bedridden. Bedsores can be a major problem. Sheets must be kept clean, dry, and free of food. The patient's skin should be washed frequently, gently blotted thoroughly dry and moisturizers applied. The patient should be moved every two hours and the feet kept raised with pillows or pads. Exercises should be administered to the legs and arms to keep them flexible. Weight loss and the gradual inability to swallow are two major related problems in the late-stage AD victim. The patient can be fed through a feeding syringe, or the caregiver can encourage chewing action by pushing gently on the bottom of the patient's chin and on the lips. The caregiver should offer the patient foods of different consistency and flavor in case the patient can handle one form better than another. Because choking is a danger, the caregiver should learn to administer the Heimlich maneuver. Dehydration can also become a problem; it is essential to encourage fluid intake equal to eight glasses of water daily. Coffee and tea should not be counted, since they are diuretics and will deplete fluid. When the AD patient can no longer be cared for at home, a nursing home must be found. Financial considerations are frequently paramount, but equally important is the kind of care. Although fully half of all nursing home patients are victims of AD, not all nursing homes have programs specifically designed for them. Some institutions that claim that they do are simply grouping patients together without offering any special programs. If a caregiver manages to find a facility that offers good services, it may be located far from home, making visits difficult. The caregiver then must decide whether superior care at a distant institution is worth seeing the patient less frequently-still one more painful issue.
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