Medications for memory impairment
| May 1, 2008
In-Depth Report
Medications for memory impairment
The treatment for memory loss depends on the cause. Sometimes it's as simple as treating an underlying disorder such as high blood pressure, diabetes, high cholesterol, depression, or thyroid dysfunction. There is currently no approved prescription medication for treating normal age-related memory loss. But there are five FDA-approved medications that are moderately effective in reducing the symptoms of Alzheimer's disease (see below). Some of these medications are also prescribed for mild cognitive impairment. In addition, studies of ginkgo biloba, an herbal remedy, suggest it may slow the course of Alzheimer's (see "Ginkgo biloba"). The benefits of these treatments are only temporary, however; there are no currently approved drugs that have been proven to prevent or reverse the damage done by Alzheimer's disease.
Drugs may soon be readily available for people who are cognitively normal but who would nonetheless like to sharpen their memories. Some people already use prescription medications for promoting alertness, attention, and cognitive focus. However, it is unknown whether these drugs are safe for healthy people, especially over the long term. In addition, the use of such "cognitive enhancers" poses legal and ethical issues similar to those raised by the use of performance-enhancing drugs in athletic competition.
Ginkgo bilobaSeveral small studies have found that an extract from the nuts and leaves of the ginkgo biloba tree is somewhat beneficial to people with Alzheimer's disease. The extract may help protect memory by preventing formation of beta-amyloid in the brain, a key pathological feature and possible cause of Alzheimer's. A 2006 review of the existing research on ginkgo biloba concluded that the extract had no measurable benefits for people with dementia. However, a 2007 study showed that healthy people who took a 120-mg dose of ginkgo extract showed modest improvements in memory tests compared to a control group. A number of herbal supplements containing ginkgo biloba are sold over the counter as memory aids. Although ginkgo biloba is considered safe, use caution when purchasing these preparations. Since herbal remedies and supplements are not subject to the same FDA scrutiny as prescription medicines, there's no way to know how the specific content or composition of the product you're buying relates to findings from clinical research trials. |
Drugs for Alzheimer's disease
Thus far, no medication has been found to cure Alzheimer's disease or reverse the course of the cognitive and neurological damage it causes. But some drugs seem to temporarily slow the progress of the disease in some people.
Cholinesterase inhibitors. Four medications are available in the United States for treating the symptoms of mild to moderate Alzheimer's disease: rivastigmine (Exelon), galantamine (formerly Reminyl, renamed Razadyne), donepezil (Aricept), and tacrine (Cognex). All of these drugs are cholinesterase inhibitors. They work by preventing the breakdown of acetylcholine, a neurotransmitter that's important for memory and learning. These drugs are only moderately effective; they might delay the progress of Alzheimer's disease by a number of months, possibly enabling patients to maintain independence for a longer period. Some physicians also prescribe these drugs for mild cognitive impairment.
All four drugs show similar benefits in treating the symptoms of Alzheimer's disease. After taking one of them for several weeks, about half of patients are somewhat more alert and better able to care for themselves and engage in activities. The drugs may have other benefits too, according to a report in the Journal of the American Medical Association in 2003. This review of 29 studies found that these drugs might also ease some of the psychiatric symptoms of Alzheimer's, such as depression, anxiety, hallucinations, and delusions.
Where the drugs differ is in convenience of use and severity of side effects. Cognex, the first FDA-approved drug for the treatment of Alzheimer's disease, is rarely prescribed these days because it has the most severe side effects — it can cause liver damage. The side effects of the other drugs are primarily gastrointestinal symptoms, including nausea and diarrhea. Aricept and an extended-release formulation of Razadyne (Razadyne ER) are the most convenient of the drugs because they are taken just once a day, whereas standard Razadyne and Exelon are taken twice a day.
Memantine. Memantine (Namenda) is also FDA-approved for treating Alzheimer's disease. It is an NMDA-receptor antagonist, which blocks glutamate, a neurotransmitter, from attaching to NMDA receptors in the brain. Too much glutamate stimulating the receptors can damage neurons and synapses, leading to memory loss and problems with other brain functions. Doctors prescribe Namenda alone or in combination with one of the cholinesterase inhibitors for people with moderate to severe Alzheimer's.
Alzheimer's disease vaccine. A nasal spray vaccine against Alzheimer's disease was developed years ago in the hope of removing the accumulation of destructive beta-amyloid protein in the brain. The purpose was to induce the body to produce antibodies against the protein and destroy it before the pathological changes of Alzheimer's occurred. However, the clinical trial of this vaccine had to be stopped midway because of a serious inflammatory reaction in a number of participants.
Follow-up of the participants from the discontinued trial suggested that those who mounted an immune response from the vaccine performed better on some of the cognitive test measures and had a striking reduction of beta-amyloid levels in their brains and spinal fluid.
In 2006, researchers reported that they had developed a version of the vaccine that uses a nonviral formulation of the DNA codes for the beta-amyloid protein. In tests on specially bred mice, this "gentler" vaccine reduced the number of brain plaques by up to 50% without causing a systemwide immune reaction. A formulation of this vaccine has entered human clinical trials.
Vitamin E. As noted earlier, the notion that vitamin E supplements might prevent Alzheimer's disease remains in question (see "Vitamin E"). In fact, a 2007 analysis of multiple studies revealed that mega doses of vitamin E may slightly increase overall risk of death. Also, be aware that if you take more than 800 IU of Vitamin E per day, you risk side effects such as bleeding, headache, fatigue, and blurred vision. To be on the safe side, talk with your doctor before taking vitamin E supplements.
The National Institute on Aging PREADVISE study (Prevention of Alzheimer's Disease by Vitamin E and Selenium), a large-scale longitudinal study, should provide more definitive information on the potential for vitamin E to prevent the development of Alzheimer's disease in cognitively healthy people.
Statins. If you have high cholesterol as well as a memory disorder, taking one of the class of lipid-lowering medications known as statins might provide a double benefit: lowering your cholesterol level and slowing the progression of memory loss. A 2005 study compared the rate of cognitive decline among people with Alzheimer's disease who were taking statins (for high cholesterol) and people with the illness who were not taking statins. Those taking statins had a slower rate of decline each year for an average of three years. In addition, a team of researchers who examined brain tissue from 110 statin users who had donated their brains to research found significantly fewer plaques and tangles associated with Alzheimer's disease. In 2007, a small study upheld this connection, showing that the drug atorvastatin (Lipitor) had positive cognitive effects in people with mild-to-moderate Alzheimer's disease. A large ongoing study called CLASP (Cholesterol Lowering Agent to Slow Progression) is investigating the effectiveness of one of the statins, simvastatin (Zocor), to treat the symptoms of Alzheimer's.
Estrogen therapy and memoryDoes postmenopausal hormone replacement improve a woman's memory or other aspects of cognitive function? The Women's Health Initiative, a large national study of the role of hormone therapy on women's health, addressed this question. The results from the memory component of the project, WHIMS, published in 2003, showed that combination estrogen-progestin therapy (Prempro) not only didn't improve memory in postmenopausal women, it actually doubled women's risk for dementia. In 2004, the researchers reported that estrogen therapy without a progestogen was linked to an increased risk of dementia and also of stroke. A related study suggested that estrogen alone might also increase the risk of mild cognitive impairment. Although some critics have questioned the scientific methodology and conclusions of the WHIMS study, the FDA now requires menopausal hormone therapies to have labels warning that they do not prevent memory loss and may increase risk of dementia. The results of the Cognitive Complaints in Early Menopause Trial (COGENT), reported in Neurology in 2007, followed in a similar vein. In the largest study to date to look specifically at the issue of hormones and memory, 180 women between ages 45 and 55 were given either hormone therapy or a placebo for a period of four months. Researchers found no significant difference between the two groups on verbal memory tests. However, clinical trials have found that 45-year-old women who had undergone surgical menopause and took estrogen therapy had better verbal memory than similar women who did not take estrogen. In addition, preliminary research suggests that low levels of estrogen taken before menopause may protect brain cells from the formation of amyloid deposits that characterize Alzheimer's disease. This finding implies that estrogen therapy may have to be started soon after menopause to produce a memory-protective effect. Some researchers wonder if the same may be true of combination estrogen-progestin therapy started early in menopause. WHIMS looked only at women ages 65 and older. Additionally, drugs known as selective estrogen receptor modulators (SERMs) — which simulate estrogen's effects on some tissues while blocking its action in others — may help prevent cognitive decline. In 2005, researchers reported in The American Journal of Psychiatry that women who took 120 mg of raloxifene (Evista), a SERM used to treat osteoporosis, for three years were one-third less likely to have mild cognitive impairment; however, the drug did not seem to protect against Alzheimer's disease. So the estrogen story has not yet fully unfolded. In the meantime, doctors recommend that women take postmenopausal hormones only for short-term relief of severe menopausal symptoms such as hot flashes. |
Drugs for mild cognitive impairment
The cholinesterase inhibitors used for Alzheimer's disease are often prescribed for people with mild cognitive impairment. Many doctors have found that these drugs improve people's alertness and attentiveness. Some clinical trials have produced encouraging results. In 2005, a study published in The New England Journal of Medicine showed that people with mild cognitive impairment who took donepezil were less likely to develop Alzheimer's disease within a year than people who took either vitamin E supplements or a placebo. However, the benefit was short-lived: after three years, the rate of progression to Alzheimer's was no lower among those who took donepezil than it was among the other groups.
Treatment strategies that boost levels of dopamine are also being tested. Clinical studies of one, piribedil (Trivastal), suggest the drug may slow cognitive decline, at least for several months. No significant adverse effects have been reported. The drug is not approved for routine clinical use in the United States, but it is prescribed in about 30 other countries.
Review Date: 2008-05-01
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