Galantamine Can Help in Unexpected Ways
Galantamine May Lighten
Herbal supplement helps reduce verbal repetition in
Alzheimer’s patients, alleviating stress all around
By Hyla Cass, M.D.
Suppose you were an idiot, and suppose you
were a member of Congress. But I repeat myself.
— Mark Twain
here used to be a comedian with a shtick that involved always repeating what he had just said, always repeating what he had just said. It sounds silly, but the way he did it was funny—for awhile. Some things get old pretty quickly, and then they become annoying. Unfortunately, the same could also be said of some people, because some of us age more rapidly than others—and not always as gracefully as we (or others) would like.
That is particularly, and tragically, true of those who are afflicted by dementia, such as Alzheimer’s disease, the most prevalent of all the dementias. The victims of this terrible disease gradually lose their memory and their ability to function effectively in the normal activities of daily living, and, through no fault of their own, they often also develop odd behavioral traits that others find frustrating and annoying.
One such trait commonly seen in Alzheimer’s disease is frequent verbal repetition, such as a simple comment (e.g., “That’s a beagle.”) uttered many times during the day.* Or it could be an entire, oft-heard story (“One time, when I was eleven, it was cold outside, and I was wearing the long scarf that Aunt Jean had given me, and this goofy dog, it was a beagle, came running up and grabbed the scarf and ran off with it, and I chased him down the street, and …”). Often such stories are brought up out of context within a given conversation and are told exactly the same way as every time before, as though being read from a script.
How to Make Things Worse
Such incidents are hard enough to have to endure for the umpteenth time, but what can really drive family or friends up the wall is when the patient asks the same question (e.g., “When is my doctor appointment?”) over and over, perhaps a dozen times or more in a short time span. You answer the question repeatedly, patiently, until finally you can’t stand it any more and snap back that you’ve already answered the question ten times. The patient then feels hurt or angry, and you feel guilty and ashamed. An already sad, difficult situation is made even worse.
Add to that little scenario countless others, ranging from the merely annoying to the potentially dangerous, that contribute to the caregiver’s daily problems. The cumulative burden—physical, emotional, and financial—can become so crushing and debilitating that the health and life expectancy of the caregiver, not just the patient, are seriously undermined. Good nutrition often takes a back seat, and sleep deprivation, which is common in patient and caregiver alike, only makes things worse. It’s a downward spiral that is very hard to control.
How to Make Things Better—Galantamine
Thus, anything that can ameliorate the symptoms of the disease—including, perhaps, reducing the patient’s tendency toward verbal repetition—may be seen as a bit of blessed relief for the caregiver. There are no therapies that target individual symptoms, but different therapies may have different effects on different symptoms. Physicians must therefore evaluate each patient’s particular constellation of symptoms with a view to choosing the therapy they think will work best in that case.
One therapy that has gained wide acceptance for safety and efficacy in the treatment of mild to moderate (and even “advanced moderate”) Alzheimer’s disease is the nutritional supplement galantamine, which is also sold as a prescription drug under the name Razadyne ER. Galantamine is a natural plant alkaloid isolated from a variety of flowers, notably snowdrops, daffodils, and spider lilies. Although it cannot cure Alzheimer’s (nothing can), it is remarkably effective in temporarily halting or even reversing the progression of the disease, for periods of up to a year, and possibly longer, before the inevitable decline resumes.*
GAS—A Personalized Approach to Problems
In 2006, researchers in Canada published the results of a 4-month, randomized, double-blind, placebo-controlled trial of galantamine called the VISTA (Video-Imaging Synthesis of Treated Alzheimer’s Disease) trial. The subjects were 130 community-dwelling (i.e., not institutionalized) patients with mild to moderate Alzheimer’s; their average age was 77. Following the 4-month period as a placebo-controlled trial, the study was extended for another 4 months as an open-label trial, in which all the patients received galantamine. (Ethical considerations dictated that patients could not be kept on placebo for more than 4 months.) The galantamine dosage was 8 mg/day for the first 4 weeks, 16 mg/day for the next 4 weeks, and variably from 16 to 24 mg/day thereafter.
The study was based on a method called Goal Attainment Scaling (GAS), in which specific problems identified by the patients, the caregivers, or the treating physicians are assessed bimonthly to see how well (or not) they are being alleviated by the treatment. The point of this approach is to identify those cognitive or behavioral problems (e.g., repetitive questioning) of greatest concern to the parties affected and to try to find the treatment that will best alleviate them. This is a largely subjective process, especially since some problems are difficult to specify and quantify. Verbal repetition, however, is not one of those—by its nature, it provides a ready target for the GAS approach.
What GAS measures is not the problems themselves, but the degree to which the problem-related goals, whatever they may be, have been attained. In the case of repetitive questioning, an obvious goal would be to reduce the number of times a question is repeated during the day. All it takes to measure this is a counter.
Higher Goal Attainment with Galantamine . . .
In this study, there was a significantly greater improvement in overall goal attainment in patients who were taking galantamine than in those who were not. Curiously, however, this result was observed by physicians but not by patients or caregivers. The researchers followed up with a secondary analysis of the data pertaining to a particular goal—reduction of verbal repetition—which they published separately. The purpose was to determine how commonly a reduction of verbal repetition was defined as a treatment goal for the 130 Alzheimer’s patients, how commonly that goal was attained, whether attainment of the goal could be attributed to galantamine, and whether its attainment was indicative of an overall positive treatment response for the disease.
The researchers found that a reduction of verbal repetition was a treatment goal for 44% of the patients, and that repetitive questioning was by far the most commonly reported problem (88% of the time) in this particular domain. After 4 months of galantamine therapy, the rate of goal attainment was significantly higher (58%) in the galantamine group than in the placebo group (24%). After 8 months, this difference was effectively erased, however, owing to a “catch-up” effect of the patients who had previously been on placebo and to imbalances in the baseline characteristics of the two groups, despite the randomization process. (Another weakness in the trial was its small size.)
. . . Could Be a Useful Marker of Positive Treatment Response
The authors pointed out that a reduction in verbal repetition is not necessarily a sign of success—it could even be the opposite if it were the result of a more generalized loss of language function as the disease progressed. That was not the case in this study, however: videotapes of the interviews of improved patients at 4 and 8 months showed no evidence that diminished verbal repetition was due to a general loss of language.
Despite the study’s weaknesses, which the authors acknowledged, they noted that the reduction in verbal repetition was associated with other improvements in the patients’ condition, suggesting that it might be useful as a clinical marker of a positive treatment response in Alzheimer’s disease (AD). They concluded,
It is easy to inquire about repetitive questioning. Improvement in verbal repetition appears to indicate clinically detectable improvement in general. Although inadequate on its own as an assessment of treatment response, tracking changes in verbal repetition in patients in whom it is identified as a problem offers a convenient way to begin discussions about treatment and a valid example for patients and families about the sorts of benefits that treatment with galantamine can offer some patients with mild to moderate AD.
A Growing Problem, A Growing Problem
The Alzheimer’s Association, a national organization devoted to educating the public about the disease, has recently revised its estimates of the prevalence of AD in the United States. It now estimates that there are more than 5 million Alzheimer’s victims, up about 10% from its previous estimate in 2000, and it says that there are about 400,000 new cases annually. With the aging of the baby boomers, the overall number is trending upward and is expected to hit about 7.7 million by 2030 unless a cure or preventive measure is found.
Alzheimer’s is the seventh leading cause of death in the United States—and that does not include the indirect toll on caregivers, many of whom suffer greatly and die prematurely, as indicated above. When we think about ways to fight the scourge of Alzheimer’s disease, we should keep the caregivers and their burdens in mind too. What a blessing it is that galantamine can help in this regard. You can say that again.
- Rockwood K, Fay S, Song X, MacKnight C, Gorman M. Attainment of treatment goals of people with Alzheimer’s disease receiving galantamine: a randomized controlled trial. Can Med Assoc J 2006;174:1099-1105.
- Rockwood K, Fay S, Jarrett P, Asp E. Effect of galantamine on verbal
repetition in AD: a secondary analysis of the VISTA trial. Neurology 2007;
- Anon. More than 5 million have Alzheimer’s in U.S. Reuters Health
Report, March 20, 2007.
Lithium’s Pharmacologic Bonus
In bipolar disorder (also called manic-depressive illness or manic depression), the patient’s mood and behavior alternate between the extremes of mania (a kind of exaggerated and unfounded elation) and depression, usually in cycles of months or years. For half a century, a common treatment for this disease has been the mineral lithium, and to this day, lithium (as lithium carbonate) is still often used, despite the advent of numerous synthetic drugs designed to alleviate the symptoms.
Like most other serious mood disorders, bipolar disorder is known to be organic in nature, i.e., it’s not “all in your mind” but rather in your physical brain. It’s a neurodegenerative disease with a biochemical basis, and it produces actual brain damage. The same is true of Alzheimer’s disease, for which lithium may also be beneficial—experimental studies have shown that it can inhibit the formation of neuritic plaques and neurofibrillary tangles, which are hallmarks of the disease. Lithium can even promote neurogenesis (the formation of new neurons) in the brain, especially in the hippocampus, the brain region most affected by Alzheimer’s.*
Researchers at the University of São Paulo in Brazil wondered whether chronic lithium treatment might help protect elderly bipolar patients against Alzheimer’s disease. For their study, they recruited 118 such patients, average age 68, and tested their cognitive function. The patients were classified as having normal cognitive function (70 individuals), mild cognitive impairment (a common precursor to dementia; 25 individuals), or clinical dementia (23 individuals). Those with dementia were further classified as having either Alzheimer’s disease (19 individuals) or vascular dementia (4 individuals), and the latter were excluded from the analysis, leaving 114.
Of the 114 patients, 66 had received lithium treatment continuously for an average of 71 months, and the other 48 had received other treatments for at least the past 6 months; of these 48 “nonlithium” patients, 15 had never received lithium, and 33 had received it in the past (for an average of 54 months) but had been off it for an average of 59 months. The question was: had the continuous lithium treatment for bipolar disorder significantly reduced the risk for Alzheimer’s, as a kind of pharmacologic bonus, in the lithium group compared with the nonlithium group?
The answer appeared to be yes. In the lithium-treated group, the incidence of AD was 5%, while in the nonlithium group, it was 33%—a statistically significant difference. (For mild cognitive impairment, these figures were 20% and 25%, respectively, a statistically insignificant difference.)
The overall incidence of AD in the study population was 19%, compared with 7% in the general Brazilian population of the same age range. This jibes with our knowledge that bipolar disorder is itself a significant risk factor for AD (as is clinical depression, by the way). What lithium therapy appears to have done, according to the researchers, was to reduce the incidence of AD in this elderly bipolar population to levels seen in the elderly general population. That’s remarkable.
Here in the United States, the daily lithium intake for average-sized adults has been estimated to range from 650 to 3100 mcg (micrograms). That 5-fold range reflects the variable distribution of lithium in soils and, therefore, in the plants that grow in them (the chief dietary sources of lithium are grains and vegetables). No diseases are attributable to lithium deficiency, and it is believed that the minimum adult human requirement is less than 100 mcg/day; higher intakes, however, are required in order to obtain lithium’s beneficial effects, and it has been proposed that a provisional RDA of 1000 mcg (1 mg) per day be adopted.
- Nunes PV, Forlenza OV, Gattaz WF. Lithium and risk for Alzheimer’s
disease in elderly patients with bipolar disorder. Br J Psychiatry 2007;
- Saunders DS. Letter: United States Environmental Protection Agency.
Office of Pesticide Programs, 1985.
- Schrauzer GN. Lithium: occurrence, dietary intakes, nutritional essentiality. J Am Coll Nutr 2002;21:14-21.
Dr. Hyla Cass is a nationally recognized expert in integrative medicine, an assistant clinical professor of psychiatry at the UCLA School of Medicine, and the author or coauthor of several popular books, including Natural Highs: Supplements, Nutrition, and Mind-Body Techniques to Help You Feel Good All the Time and 8 Weeks to Vibrant Health: A Woman’s Take-Charge Program to Correct Imbalances, Reclaim Energy, and Restore Well-Being.