Alzheimer's Treatment Options: Benefits and Risks
For now, no treatment can prevent or halt the mental deterioration associated with Alzheimer’s disease. Instead, drug therapy is focused on preventing the destruction of nerve cells, with the ultimate goal of preserving cognitive function for as long as possible and managing the disease’s cognitive and behavioral symptoms.
One Alzheimer’s treatment approach is based on the theory that memory problems associated with the disease result in part from a deficiency of the neurotransmitter acetylcholine, a chemical that is linked to the formation of new memories. Here’s more on the latest Alzheimer’s treatment evidence:
1. Cholinesterase inhibitor drugs
Cholinesterase inhibitors were the first medications approved by the Food and Drug Administration for the treatment of Alzheimer’s disease. The drugs work by slowing the breakdown of acetylcholine and may ease some of the symptoms associated with Alzheimer’s, but they do not halt progression of the disease. Cholinesterase inhibitors seem to improve symptoms for about six to 12 months in one-third to one-half of the people who take them.
Tacrine (Cognex), the first FDA-approved cholinesterase inhibitor, works in only about 20 to 40 percent of people with Alzheimer’s disease and causes liver damage in some individuals. It is rarely used now that a second generation of cholinesterase inhibitors is available.
Second-generation cholinesterase inhibitors produce fewer and less severe side effects. The first one approved by the FDA, donepezil (Aricept), is now approved to treat all stages of Alzheimer’s disease. Clinical trials have shown significant improvements in cognitive and overall functioning in people receiving Aricept (compared with those who received a placebo), with fewer adverse effects than with Cognex.
In one 24-week study, at least 80 percent of the Aricept patients suffered no cognitive decline compared with 57 percent of patients taking a placebo, a difference of 23 percent. Improvement was greater with higher dosages of the drug: 54 percent of the patients taking 10 mg of Aricept improved slightly in one cognitive test compared with 38 percent of those taking 5 mg and 27 percent of those taking the placebo. In another study, individuals who took 10 mg of Aricept for one year were half as likely to experience disease progression as those who received a placebo.
In 2010, the FDA approved a higher dose of Aricept—23 mg, which is meant to be taken once a day. The approval was based on the results of a study of 1,400 people with moderate to severe Alzheimer’s. The 23-mg dose improved cognitive functioning better than the 10-mg dose but did not improve overall functioning. A major downside is that the side effects of bleeding and weight loss are more common with the higher dose. Some side effects improve after taking the medication for a while. Generic donepezil has also been approved to treat Alzheimer’s as an orally disintegrating tablet that may be easier for patients who have trouble swallowing. In the future, a patch that would deliver the drug through the skin may become available.
The second of these medications to be approved was rivastigmine (Exelon), which is for mild to moderate Alzheimer’s. In four placebo-controlled clinical trials involving a total of 3,900 people, those taking Exelon had significantly better scores on standard tests of cognitive function than people taking a placebo. One of these trials, which included 725 people with Alzheimer’s disease, found that 24 percent of the people in the Exelon group showed significant improvements in cognitive function over a 26-week period compared with 16 percent of those taking a placebo, a difference of 8 percent.
The newest cholinesterase inhibitor to be approved for Alzheimer’s treatment is galantamine (Razadyne), which is approved to treat mild to moderate Alzheimer’s. Its approval was based on data from four placebo controlled clinical trials involving more than 2,650 people. Patients taking Razadyne scored better on measures of cognitive performance and daily functioning than people taking a placebo.
The most common adverse effects of cholinesterase inhibitors are nausea, vomiting, loss of appetite, diarrhea and weight loss. A recent Canadian study also found that people taking cholinesterase inhibitors for dementia have a significantly higher risk of falls and bradycardia (slow heartbeat); those side effects should be considered before taking a cholinesterase inhibitor.
2. NMDA receptor antagonist
In 2003, the FDA approved memantine (Namenda) for the treatment of moderate to severe Alzheimer’s disease. The drug has been the mainstay of Alzheimer’s treatment in Germany for years, and the European Union approved it for Alzheimer’s disease in 2002. The medication helps block the activity of the neurotransmitter glutamate by binding to N-methyl-D-aspartate (NMDA) receptors on the surface of brain cells. Glutamate, at appropriate levels, plays an important role in learning and memory. If glutamate levels are too low, cognitive problems develop. However, if levels are too high, glutamate overstimulates nerve cells, leading to cell death.
Because Namenda has been on the market in the United States for much less time than the cholinesterase inhibitors, less information is available about its long-term cognitive effects. Overall, it is less beneficial than the cholinesterase inhibitors. In one 28-week study comparing Namenda with a placebo, people taking the drug showed significantly less cognitive decline during that time period. By the study’s end, about 20 percent of the patients taking Namenda showed some improvement in cognition and/or activities of daily living.
Another study found that people taking Namenda plus Aricept averaged less cognitive decline over 24 weeks than individuals taking a placebo plus Aricept. About 40 percent of people in the Namenda plus Aricept group experienced cognitive improvements, and 30 percent showed improvements in daily functioning.
Some people who take Namenda may experience improvements over the short term, but most can expect to see only a modest delay in the deterioration of memory and the ability to perform activities of daily living. The medication may extend the time patients can spend at home before requiring assisted living. However, Namenda does not reverse or halt the degeneration that occurs in the brain.
3. Vitamin E and selegiline
The antioxidant properties of vitamin E made it the focus of a well-designed study published in The New England Journal of Medicine in 1997 and in JAMA in 2014. In the New England Journal of Medicine study, people with moderately severe Alzheimer’s disease were assigned to one of four treatment groups: a daily dose of 2,000 IU of vitamin E, 10 mg a day of selegiline (Eldepryl, a medication used to treat Parkinson’s disease), a combination of vitamin E and Eldepryl, or a placebo.
Taking either vitamin E or Eldepryl prolonged the time before institutionalization became necessary and increased survival by about seven months. Furthermore, vitamin E and Eldepryl when taken independently reduced—by 25 percent—the number of people who lost the ability to perform daily activities, such as handling money or bathing. Unfortunately, combining vitamin E and Eldepryl did not further improve results.
On the basis of this study, the American Academy of Neurology concluded that sound evidence supports the use of vitamin E in an attempt to slow the progression of Alzheimer’s disease. It also appears to increase the survival of Alzheimer’s patients. A recent study found that people with Alzheimer’s who took 1,000 IU of vitamin E twice a day along with a cholinesterase inhibitor lived longer than those who didn’t take the supplement. The evidence for Eldepryl in slowing the progression of Alzheimer’s is weaker, and the drug has more side effects than vitamin E. Furthermore, if vitamin E is already being used, Eldepryl offers no additional advantage.
In the 2014 JAMA study, all participants took donepezil. Vitamin E alone was associated with a slower decline in function but not better memory. There was no additional benefit when memantine was added to vitamin E.
There is not good evidence that vitamin E can help forestall dementia among people who are at high risk. Indeed, the highly anticipated preliminary results from the Memory Impairment Study were disappointing in that regard. The study was a randomized, placebo-controlled trial of vitamin E and the cholinesterase inhibitor Aricept. It was designed to determine whether Aricept or vitamin E could slow the progression of Alzheimer’s disease among individuals with mild cognitive impairment. The study found no benefit to vitamin E supplementation. Despite this setback, researchers are continuing to study vitamin E and its potential for warding off dementia.
Although vitamin E is generally safe, large doses can increase the risk of bleeding, especially in some people who are deficient in vitamin K. Take vitamin E supplements only under your doctor’s supervision. Consider eating a diet rich in vitamin E. A recent study published in the Archives of Neurology found that people who got the most vitamin E in their diet (18.5 mg per day, on average) from foods such as margarine, sunflower oil, soybean oil and mayonnaise were 25 percent less likely to develop dementia.