Galantamine Can Help in Unexpected Ways

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.

*The technical term for this phenomenon is perseveration, meaning the tendency to continue or repeat some response, such as a word, phrase, or gesture, when the appropriate stimulus for that response is no longer present. It’s usually caused by brain injury or other organic disorder, such as dementia.

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.*

*For more on the benefits of galantamine for caregivers as well as patients, see “Galantamine Eases the Burden on Alzheimer’s Caregivers” (July 2004), “Galantamine Helps Maintain Our Independence” (September 2004), “Galantamine Improves Attention in Alzheimer’s” (December 2005), and “Galantamine Works Well in Real Life” (February 2007).

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.¹ 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.² 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,²

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.³ 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.

References

1. 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.
2. 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; 68:1116-21.
3. Anon. More than 5 million have Alzheimer’s in U.S. Reuters Health Report, March 20, 2007.