Ivanhoe Broadcast News Transcript with
Lauren Krupp, M.D, Neurologist
Stony Brook University Hospital in Stony Brook, New York
TOPIC: Making Memories for MS Patients

What is multiple sclerosis?

Dr. Krupp: MS is a condition in which the immune system has, for reasons that are still unclear, gone against itself. In particular, it attacks the central nervous system, which is the brain and spinal cord. Typically, it affects people between 15 and 50, and typically it starts out with spells or attacks of neurologic dysfunction, which can last days to weeks and then generally improves. This is known as relapsing MS. There used to be no treatment for MS, but in the past 11 years, we’ve had a number of medications that have become available that decrease the frequency and severity of attacks. However, people with MS still experience a variety of different symptoms. They are very tired frequently, they can have trouble with bladder, and not infrequently, they can have trouble with things like memory, concentration and attention.

How common are memory problems in MS patients?

Dr. Krupp: About one out of two people with MS will have a memory problem or some other problem with thinking.

Is it short-term memory that they’re losing or long-term memory?

Dr. Krupp: For the most part, it’s short-term. This includes being able to remember where you put something, being able to pay attention to a crossword puzzle, and dealing with remembering appointments. Those are the kinds of problems people can have.

Does the memory loss ever get as severe as it is for Alzheimer’s patients?

Dr. Krupp: The good news is that the vast majority of people with MS never have memory difficulties as severe as people with Alzheimer’s. The majority, over 90 percent, experience much more mild difficulties. However, because these are people who are working, raising families, and active in the community, these memory problems can really make a difference and interfere with what they’re doing.

How does MS affect memory?

Dr. Krupp: The way MS affects memory has to do with the slowing of nerve conduction. What happens is that in MS, the nerves can be thought of as wires, and they have insulation. In MS, that insulation becomes unraveled, and as a result, the nerves transfer information from one part of the brain to another much less efficiently and much less quickly. Technically, people with MS say, “I can get the right answer, but it just takes me much longer,” and that can interfere with things like multi-tasking, taking notes while speaking to someone on the phone, it can interfere with getting the right answer in a timely manner, and it can interfere with giving a talk to your colleagues. So, the goal is to try to see if we can speed up the process.

Are there any treatments for the memory loss?

Dr. Krupp: There are a variety of different medicines that are used to help people with severe memory problems in conditions like Alzheimer’s Disease, which affects much older people and in whom their memory problem is much more severe. However, there hasn’t been any medication that’s been studied in any kind of detail to see whether it can help younger people with MS and their memory trouble. So while there are medicines on the market, we don’t know if they’re appropriate for people with MS.

Why did you start using the drug donepezil? What is it designed for?

Dr. Krupp: The medication donepezil was initially tested in people with Alzheimer’s disease to see if it would improve thinking. The reason for the use of that medication is that it increases a neurotransmitter in the brain that is thought to be important for memory, and in Alzheimer’s disease, that neurotransmitter is decreased. By the time somebody has Alzheimer’s disease, half of his neurons that are in a particular area of the brain responsible for memory have been damaged. In MS, however, those neurons are probably still there, maybe not in the full number as they should be, but they’re just not working as well. So we thought that if the medication could work in a really severe disease, maybe we could get some benefit in a disease that wasn’t as severe. The second reason we chose this medication is that the pathways of the brain that are affected in MS overlap in some respects to some of the pathways that might be affected in Alzheimer’s. Certainly, it’s not important to one connection, but there is a little bit of overlap. Finally, some years ago, there were some good results with a medication that had a similar mode of acting as donepezil, but had a lot more side effects. That treatment seemed to hold some promise for improving memory in people with MS, and when donepezil came along, we thought here is something with a similar approach but less side effects. We thought maybe it was worth looking at this whole category again, and the category is cholinergic medication.

What did you find in your study?

Dr. Krupp: In our first study, we found that people taking the medication clearly improved on a memory test compared to the people taking the placebo, so we enrolled individuals with MS who had varying degrees of severity of MS and various degrees of duration. All had a measurable problem with memory, not overwhelmingly severe, but more than it should have been. People were divided into two groups, one randomly took active medication with the donepezil and the other took a placebo. The group that got the placebo on average improved by about 14 percent in its memory performance, whereas the group that got the placebo improved only a couple percent. So there was a big difference in how they actually did on a very specific memory test, but even more persuasive is that the people felt they were doing better. About twice as many people getting the active drug noticed an improvement in things like remembering appointments, one person who is an avid crossword puzzle taker felt he was doing better on that, someone else was able to do better in planning her lesson plans for school, and one person was able to return to work. The kinds of improvements were pretty significant for not all the people, but for a sizeable amount of them.

What do you believe the drug actually does in the brain to help improve memory?

Dr. Krupp: We’re not entirely sure, but what we think it might do is increase the amount of a particular neurotransmitter, that probably along with others is decreased or disrupted in MS. This particular class of neurotransmitters is probably important in cognition.

Are there any side effects of the drug?

Dr. Krupp: For the most part, this is a medication that’s well-tolerated. There are some people who have some nausea or gastro-intestinal problems, changes in their sleeping, their dreams are sometimes more vivid, but almost no one had to discontinue the medicine. We lowered the dose for a couple people, but overall it was well tolerated.

What are the implications of making this connection that this drug that is normally used for Alzheimer’s could also possibly be helping a whole population of other people?

Dr. Krupp: It’s always very exciting when a medication that’s available is discovered to help more people than was originally thought when the medication was first tested. If we’re lucky, we’re in that situation with MS and donepezil, as well as other medications similar to it. In order to find out what the future of this medication is, we’ve got to study it a little bit more. The last thing I would want to do is tell people with MS to take this drug when they don’t really need it. Often, people are taking a variety of different pills, in addition to injections, and you don’t need to add on one more, unless it’s really going to work. So what we’d like to do is study it one more time, not just at one institution but at several, and examine the drug in a larger number of people where you can look at things in greater depth. If we do, then I would be the first to get on the stump and start telling doctors, you know, we can do something there to help people with MS. We can not only encourage exercise, and good diet, and memory aids, but we can also give them medication that can make a difference.

You’re confident that that is what will be the end result?

Dr. Krupp: I’m hoping.

If it does turn out to be the end result, is it something that the patient would be on medicine for the rest of their life, or does it hit a certain point where they can bring an end to it?

Dr. Krupp: The good news is that one of the areas of active research is medication to improve memory, so a lot of times what we say in medicine is, “Let’s take it for now until we have something better or until we understand things better and can come up with even a non-medication approach.” So for now, the idea would be to continue to use it, but keep track of how people are doing, and determine it’s cost-benefit ratio to see if the hassle of taking the medication is outweighed by the positive response to that medication. That’s always a question to keep on one’s mind, both for the patient and the prescriber.

This article was reported by Ivanhoe.com, who offers Medical Alerts by e-mail every day of the week. To subscribe, go to: http://www.ivanhoe.com/newsalert/.

If you would like more information, please contact:

Pat Melville
Department of Neurology
HSC T12-020
SUNY at Stony Brook
Stony Brook, NY 11794-8121
(631) 444-8164

[email protected]
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