If you have high cholesterol, you have the choice of several different medications to lower your cholesterol. If you have diabetes, you can choose from a modest list of drugs to tame your blood glucose control. But if you have Alzheimer’s disease, your treatment options are limited to only five medications at this time.
With the numbers of Alzheimer’s patients expected to explode in coming years, researchers across the nation are working furiously to develop a treatment that can delay the progression of the disease, or prevent it altogether. Researchers, doctors, and families afflicted by the disease dream of someday finding a cure or a vaccine that can put an end to Alzheimer’s. But at this time, the medications we have available can only minimize the cognitive and behavioral symptoms of the disease.
For people diagnosed in the early stages of Alzheimer’s, these drugs offer at least some hope for an improved quality of life. Granted, not everyone experiences relief from these medications. Some may need to experiment with several drugs and dosages before finding the right one. Others may not experience improvement in their cognitive functioning. Often it requires trial and error to figure out which one, if any, works for you, or whether a combination approach might be better.
Acetylcholine is a chemical messenger in the brain that is involved in the formation of memories, thought, and judgment. It is also involved in controlling muscle contractions and hormone secretion. When certain brain cells transmit messages to other brain cells, acetylcholine is released and then broken down by various enzymes, including one called acetylcholinesterase. The acetylcholine is then recycled and reused.
In the mid 1970s, scientists discovered that in people who have Alzheimer’s, levels of acetylcholine in some parts of the brain were dramatically lower than they are in healthy people. That’s because the brain cells in these regions are damaged or destroyed, causing levels of acetylcholine to drop. In fact, scientists have established that acetycholine is direcdy linked to the severity of dementia— the less you have, the worse your dementia.
In the quest for therapies, researchers began looking for drugs that could slow the breakdown of acetylcholine in order to lessen the symptoms of Alzheimer’s. The drugs that achieve this effect are known as cholinesterase inhibitors. These medications are used in the early to moderate stages of the disease and have been found to stabilize, even improve cognitive function. In randomized, double-blind, parallel-group clinical trials—considered the gold standard of research protocol—all of them have shown greater efficacy than placebo.
At this time, there remains some controversy regarding the efficacy of these drugs. But with no cure in sight, you may very well consider it worth the risk to take diese medications in the hopes that they will help improve your functioning and slow the progression of the disease. If that’s the case, be sure to talk it over with your doctor and to tell him about any other medicines you are taking and any preexisting conditions. Experts do know that diese drugs should be used with caution in patients who have had cardiac conduction abnormalities, asthma, seizures, active gastrointestinal disease, or in patients taking non-steroidal anti-inflammatory drugs.
Approved by the FDA in 1996, donezepil has emerged as the most commonly prescribed cholinesterase inhibitor for the treatment of Alzheimer’s. The drug is designed to improve memory and cognition, and help the patient do better performing the activities of daily living.
Although donepezil doesn’t cure Alzheimer’s, several studies have found it does improve cognitive functioning in some individuals and may delay nursing home placement. In some patients, the drug may demonstrate no effect, and in advanced cases of Alzheimer’s Disease, donepezil may not work at all.
Donepezil is a tablet given once a day, usually at night, at an intial dose of 5 mg. If the drug is well tolerated, the dosage may be increased after four to six weeks to 10 mg. a day.
Side effects from taking donepezil include diarrhea, vomiting, nausea, fatigue, insomnia, and anorexia. In some cases, side effects are mild and diminish with continued use of the drug. In others, these side effects may necessitate discontinuing the medication.
Rivastigmine was approved by the FDA in 2000. Like donezepil, it inhibits the action of acetylcholinesterase. But rivastigmine also inhibits butyrylcholinesterase, another enzyme involved in the breakdown of acetylcholine. The drug is used to treat mild to moderate Alzheimer’s and has been found to improve cognition and allow greater participation in day-to-day activities.
Rivastigmine is available as a capsule or a liquid. To minimize side effects, such as nausea, the dosage is initially low, about 1.5 mg. twice a day, and increased slowly—no more than once every two weeks—to no more than 12 mg. a day. At higher levels, you are more likely to experience side effects such as upset stomach, vomiting, loss of appetite, weight loss, diarrhea, dizziness, sweating, urinary incontinence, and fatigue.
In patients who do experience side effects, the drug may be discontinued for a few days. Then they may resume taking it again at the same dose or a lower dose. If you do not take it for several days, talk to your doctor before taking it again. Your doctor will probably recommend that you start at the lowest dose.
Galantamine is the newest cholesterinase inhibitor on the market, and was approved by the FDA in 2001. The drug is available in tablets in 4, 8, or 12 mg. doses. It is recommended that you begin at 4 mg., twice a day. If the drug is well tolerated after four weeks, the dose is usually bumped up to 8 mg. twice a day. And if the drug is still well tolerated after another four weeks, your doctor may recommend that you increase the dosage up to 12 mg. twice a day. The increased dosage should be at your doctor’s discretion.
Like the other drugs in this category, you may experience upset stomach, vomiting, loss of appetite, weight loss, diarrhea, dizziness, sweating, urinary incontinence, and fatigue.
In early 2005, the safety of galantamine was called into question after two studies on the drug’s effects on mild cognitive impairment found that more patients taking the drug had died than those who were taking a placebo. The “imbalance” in the number of deaths found that out of 2,000 patients, fifteen people taking galantamine died compared with five deaths in the group of people who were not taking it.
At the time of this writing, the makers of galantamine, Johnson & Johnson Pharmaceutical Research & Development, were “analyzing additional data from these studies, including information retrieved from subjects who had dropped out of the trials, and is discussing the results with regulatory authorities,” according to information on their Web site. Whether the imbalance was a statistical fluke or a bona fide medical concern remains uncertain.
Cognex was the first cholesterinase inhibitor to receive FDA approval back in 1993. Today the drug is rarely prescribed and no longer marketed because of its link to liver damage.
THE NMDA RECEPTOR ANTAGONIST
Memantine (Namenda) was first approved in Germany in 1982, and has since been used in Europe for the treat of several neurological disorders. In 2003 it was approved by the FDA for the treatment of moderate to severe Alzheimer’s. Like the other medications available for Alzheimer’s Disease, memantine does not stop the destruction of Alzheimer’s, but can alleviate the symptoms and improve cognitive functioning in some patients.
Memantine is not a cholinesterase inhibitor but rather an N-methyl D-aspartate (NMDA) antagonist that is believed to work by regulating levels of glutamate, a chemical dependent upon glutamate plays a critical role in our abilities to process, store and retrieve information. In healthy people, proper amounts of glutamate trigger receptor channels on the nerve cells called NMDA receptors. NMDA receptors, in turn, allow a controlled amount of calcium to enter a nerve cell, thereby creating an environment that allows for learning and memory. Without enough calcium, the chemical environment of the brain is not appropriate for the proper functions of learning and memory.
But in someone who has Alzheimer’s, it is theorized that there is excessive amounts of glutamate. The excess glutamate causes overstimulation of the NMDA receptors, which in turn, allows too much calcium into nerve cells. The excess calcium damages and destroys the nerve cells, leading to the symptoms we see in Alzheimer’s. Memantine is believed to work by partially blocking the NMDA receptors and helping maintain normal levels of glutamate thereby preventing neural dysfunction and damage.
Memantine comes in 5 and 10 mg. tablets and is usually taken once or twice a day with or without food. Patients usually start by taking 5 mg and gradually increase to the target dose of 10 mg twice a day by the fourth week. Side effects of the medication may include increased fatigue, dizziness, headache, constipation, and vomiting.
Because its actions differ considerably from those of the cholinesterase inhibitors, memantine may be used alone or in combination with these other medications. In fact, one study found that patients in the moderate to severe stages of Alzheimer’s fared better when they took memantine with donepezil than those who took donepezil with a placebo.
HOPE FOR A VACCINE?
Imagine a day when a simple genetic test would reveal that you were at risk for Alzheimer’s, then getting a vaccine that would shield you for life from ever developing the disease. The notion of eradicating Alzheimer’s with a simple shot, much in the same way that smallpox and rubella have largely been eliminated, is undoubtedly appealing. With a vaccine, you could train the immune system to recognize and attack even the slightest buildup of beta-amyloid plaque, thereby halting the deposits of amyloid and stopping the disease.
Initial results in mice were promising, but when the first vaccines were used in humans, brain inflammation occurred in some of the participants. The makers of the vaccine, Elan Pharmaceuticals, wisely decided to stop the trials. Scientists continued following some of the participants and found that some of those who received the vaccine did experience slower progression of the disease. Upon autopsy, those who had received the vaccines also had less Alzheimer pathology in their brains.
In the aftermath of the Elan experiment, researchers say they have learned a great deal about why the first vaccine may have caused brain inflammation. Recent studies show promise that an approach may be found to avoid the inflammation issue. Scientists have also found that monkeys may provide a valuable animal model for studying Alzheimer’s vaccines. In one study, vaccinated monkeys actually developed significant levels of antibodies to beta amyloid. These findings offer hope that someday a vaccine will be developed in the prevention of Alzheimer’s.