New Frontiers in Research:Memantine, Hormone Replacement Therapy (HRT) and More
Reprinted with permission from the Big Sioux Chapter of the Alzheimer's Association.
(Fall 2003) - Research into possible treatments, preventions and even cures for Alzheimer's disease (AD) continues in laboratories across the world. This past spring (2003), however, has brought new developments -- some of them rather unexpected -- in several different fields of Alzheimer research.
Memantine. The pharmaceutical company developing memantine for the U.S. market reported that it might not be as effective for individuals with mild to moderate Alzheimer's disease as had previously been shown for persons in more advanced stages of the disease. These results, which were purely preliminary, reflected ongoing clinical testing of memantine used in combination with cholinesterase inhibitors - drugs like donepezil (Aricept, developed by Pfizer/Eisai), rivastigmine (Exelon, developed by Novartis) and galantamine (Reminyl, developed by Janssen) that have already been approved for the treatment of mild to moderate Alzheimer's.
Memantine, which was developed in Germany and has been approved for the treatment of severe Alzheimer's Disease throughout the European Union, has not yet been approved in the U.S. Preliminary trials suggested that in these more advanced cases, the stages where individuals develop problems with dressing, bathing and other daily activities and where behavioral symptoms tend to become significant, memantine showed promise both by itself and in combination. Nationwide Phase III clinical trials continue, and the Food and Drug Administration (FDA) is currently reviewing an earlier application for the approval of memantine for the treatment of moderately severe to severe Alzheimer's Disease.
Unlike previously approved medications, memantine is not a cholinesterase inhibitor, but rather the first of a new class of drug -- hence its use in combination therapy. Memantine appears to protect the brain's nerve cells against excess amounts of glutamate -- a messenger chemical released in large amounts by cells damaged by Alzheimer's disease or certain other neurological disorders.
Hormone Replacement Therapy (HRT). A recent issue of the Journal of the American Medical Association (JAMA) reported surprising results from the Women's Health Initiative Memory Study (WHIMS), which was designed to evaluate the effectiveness of estrogen-progestin hormone replacement therapy (HRT) in reducing the risk of AD or other dementias for at-risk women. Rather than reduce the risk of dementia, as previous data would have suggested, the study found evidence of an increased risk of dementia for those women using HRT versus a placebo. Why this happened is not yet known.
These results came earlier than expected, due to the stoppage of this portion of WHIMS (Women's Health Initiative Memory Study) research; some women using combination hormone replacement therapy as part of the trials experienced small increases in the risk of breast cancer, heart disease, stroke, and blood clots. (WHIMS research into estrogen-only therapy continues.) The Alzheimer's Association stressed that the greatest single risk factor remains age: for every five years after age 65, the risk of dementia doubles.
Non-steroid anti-inflammatory drugs (NSAIDs). JAMA also reported the results of clinical trials with two NSAIDs, naproxen (Aleve) and rofecoxib (Vioxx). NSAIDs include aspirin and aspirin-like compounds used to treat pain, inflammation, and fever. No slowing of the progression of Alzheimer's Disease was reported in those participants taking non-steroid anti-inflammatory drugs (NSAIDs) versus a placebo. The ultimate effectiveness of NSAIDs remains inconclusive, though, and more trials involving these drugs are in progress.
Exercise for the mind. On a more promising note, the benefits of remaining mentally active appear to be underscored by another study of older adults in the New York area. Although not yet conclusive, the results would appear to indicate a link between mentally stimulating activities (reading books, board and card games, crossword puzzles, playing a musical instrument) and a reduced risk of dementia in older adults. This supports an accumulating body of evidence linking mental agility with a reduced risk of dementia -- although researchers cautioned against interpreting their findings too quickly at this early stage.
"In the meantime," concludes a supporting editorial to the study, "seniors should be encouraged to read, play board games, and go dancing, because these activities, at the very least, enhance their quality of life, and they just might do more than that."
For more on these and other developments in Alzheimer research, see the Alzheimer's Association national web site at http://www.alz.org/index.asp