Alzheimer’s disease is the most common cause of dementia, the medical term for a decline in memory, thinking, decision-making, and reasoning. As many as 5.1 million Americans have Alzheimer’s disease, according to the National Institute on Aging. That number is projected to substantially increase in the coming years because the U.S. population is aging, which increases the risk of developing Alzheimer’s.
Relatively Minor (usually go away in time or are short-lived)
Potentially Severe (can be annoying or dangerous and should be reported to a doctor)
Despite decades of research, it remains unclear what causes Alzheimer's. What is known is that once the disease begins, it causes progressive destruction of brain cells, which leads to a decline in memory and cognitive functioning, as well as changes in personality and behavior. Research indicates that Alzheimer's can run in families, and the tendency to get it is inherited. However, even if you have a family history of Alzheimer’s, that does not mean you will get it. Studies suggest, for example, that regular physical and mental activity that keeps your mind engaged — such as doing crossword puzzles or playing bridge — as well as strong social ties and personal relationships, may help to prevent its onset.
Smoking, high cholesterol, and diabetes increase the risk of developing dementia. Quitting smoking, and controlling high cholesterol and diabetes with a healthy lifestyle and proper treatment, which might include medication, can help reduce the risk of developing dementia.
Many people, as they age, worry they might be developing Alzheimer’s disease when they start forgetting simple things, such as phone numbers, or when they start misplacing things, such as keys and eye glasses. Those problems are common and usually do not indicate any memory or brain disorder, even if they worsen as you age. Actually, the symptoms of Alzheimer’s are quite distinct. Table 1 on the next page gives you a quick assessment of the differences and the various stages of Alzheimer’s disease. It typically progresses from early-stage disease characteristics, to middle-stage, to, finally, late-stage.
Based on the evidence of their effectiveness, side effects, tolerability, flexibility of use, and cost, we are unable to choose any of the Alzheimer's medications as Consumer Reports Best Buy Drugs selections. The available studies indicate that most people will receive no benefit at all from taking a medication. Balanced against their relatively high price tag and the risk of side effects, including rare but serious safety concerns, we cannot endorse any of the medications.
Of the five available Alzheimer’s medications, tacrine (Cognex) is ruled out due to the risk it poses to the liver. Your doctor is unlikely to prescribe this drug because it has been linked to liver damage. Should it be recommended, we advise a thorough conversation with your doctor about the choice, and a second opinion.
As mentioned earlier, all of the Alzheimer’s drugs, except memantine (Namenda), are indicated for treatment early in the course of the disease. Donepezil is the only generic drug specifically approved by the FDA for treatment of middle-stage and late stage Alzheimer’s (Namenda is also approved for middle-stage and late-stage but it is not available as a generic), although the other medicines are also commonly prescribed for people with later-stage disease.
That means you and your doctor have a choice of three drugs intended for early use: donepezil (Aricept), galantamine (Razadyne), and rivastigmine (Exelon). Of these three, rivastigmine had the highest incidence of several side effects when compared to both placebo and in studies that compared it to the other two. For example, in one analysis, 20 percent of people taking rivastigmine had nausea and vomiting, compared to 13 percent of those taking galantamine and 7 percent taking donepezil.
All five drugs have been shown to slow cognitive decline, but usually only slightly. All have also been found to generally improve a patient’s overall response to treatment — both nondrug and using a variety of medicines to control or ease symptoms (such as antidepressants or anti-anxiety drugs).
Our analysis found inconsistent evidence on how these drugs compare in their ability to improve patients’ daily functioning, behavior, or quality of life. A few of the drugs have been studied more extensively than others in these areas. Unfortunately, few studies directly, and comprehensively, compared one drug to another, which leaves open the question of whether any one is superior in effectiveness to the others.
Most of the evidence, however, suggests that there’s no substantial difference among the five drugs in their ability to produce improvements in memory and other cognitive functions. Compared to placebo, all five are capable of yielding noticeable changes in cognitive ability between two to six weeks after treatment starts.
But, as stated earlier, most people who take the medications, versus those who take a placebo, do not show a meaningful improvement in cognitive ability.
To assess whether patients are improving overall— known as global response to treatment—studies rely on the opinions of the treating physician and the caregiver, often a family member.
In general, all of the Alzheimer’s medicines have been shown to improve a patient’s well-being. However, most patients will not have this improvement. Studies have shown that only about 10 percent of patients are considered to be “better” when assessed by their doctor or caregiver. Although others may not decline as much as they would have without drug treatment, overall improvement likely will not be noted for most patients.
There were no high quality studies comparing the different treatments head-to-head in their ability to improve overall well-being. Several studies evaluated physician and caregiver satisfaction with a drug when compared with another. Two compared donepezil (Aricept) to galantamine (Razadyne), and one compared donepezil to rivastigmine (Exelon). In two of these studies, donepezil performed somewhat better.
Daily functioning refers to the ability to perform normal activities of daily living, such as getting dressed, preparing food, shopping, housekeeping, or handling money. In the early stages of the disease, it is more difficult to determine whether a treatment can significantly affect these abilities. But as the disease progresses, this measure becomes more useful in assessing a drug’s impact.
Daily functioning has not been measured in every study. And studies where it has been used have produced inconsistent results, partly because improvement can vary so much among people.
For example, donepezil (Aricept) was found to improve daily functioning in two studies, but not in three others; three galantamine (Razadyne) studies found improvement in daily functioning while two others did not. And in one year-long study comparing these two drugs, there was no difference between them.
Evaluation of behavior may be more relevant in people with severe Alzheimer’s disease, and since most of the drugs have been studied in earlier stages of the illness, behavior was not always measured.
The drugs’ impact on behavior was assessed in seven studies: four with donepezil (Aricept), two with galantamine (Razadyne), and one with memantine (Namenda). Compared to no treatment, these drugs produced only minimal improvements. There was only one study that compared two drugs’ effects on patients’ behavior. In that year-long trial, there was no significant difference between donepezil and galantamine.
Quality of Life
There is scant evidence that the Alzheimer’s drugs improve patients’ quality of life. Seven studies — six of donepezil (Aricept) and one of tacrine (Cognex) — compared those drugs to placebo. Aricept appeared to significantly improve patients’ quality of life in two of the studies, but they only lasted 12 to 15 weeks. There are no studies that compare one drug to another in the area of quality of life.
Age, Race, and Gender Differences
Most Alzheimer’s drug studies have been conducted in people who are 70 to 75 years old. Although some studies have tested Alzheimer’s drugs in older people or more critically ill people who live in nursing homes, none has been able to determine if age makes a difference in how well the drugs work, or if they are more or less safe.
No direct evidence suggests that any Alzheimer’s drug has better or worse efficacy for any gender or racial group.
The Alzheimer’s medications can cause several side effects. While the most common are minor and might be short-lived, for some people, they might persist or be intolerable. These medications can also pose more serious side effects in rare cases.
Commonly reported adverse events in clinical studies include gastrointestinal side effects (nausea, vomiting, diarrhea), dizziness, fatigue, insomnia, loss of appetite, muscle cramps, tremor, vertigo, and weight loss. Nausea and vomiting occurred frequently in trials of donepezil, galantamine, and rivastigmine. Between 10 to 50 percent of people who took one of those medications experienced nausea or vomiting. Studies also suggest that side effects are more likely to occur when a person is taking a high dose of these medications.
The available evidence suggests that there might be some differences in side effect profiles of the Alzheimer’s medications. Studies indicate that galantamine and rivastigmine pose a higher risk of gastrointestinal side effects than donepezil. Memantine might carry a lower risk of side effects than the other medications. In one study, the only adverse events reported by more than 10 percent of people who took memantine included agitation, diarrhea, drowsiness, and urinary incontinence. Overall, no side effect was reported more in memantine-treated people than in those who took a placebo pill.
The most serious safety concern in this drug class is the liver toxicity associated with tacrine (Cognex), which, as we previously noted, is now rarely prescribed because of this risk. Liver toxicity has not been reported for donepezil, galantamine, rivastigmine, or memantine.
Other rare but potentially serious adverse events associated with Alzheimer’s medications include cardiovascular problems, such as a slower than normal heartbeat, and a condition called heart block. These medications can also cause gastrointestinal bleeding and ulcers. The labeling of these drugs cautions that they might have the potential to cause convulsions or seizures.
Although Alzheimer’s drugs are generally safe, they may interact with other medicines or dietary supplements in ways that can be dangerous. Be sure to tell your doctor about all the other medications you are taking, including all vitamins and herbal therapies.
The main drugs to be concerned about are:
Consumer Reports. Treating Alzheimer’s Disease. Surprising facts about the effectiveness and safety of these commonly used drugs. Published July 2012.