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July 13, 2004





Alzheimer's Drug May Help Memory in MS Patients




Melissa Schorr

April 27, 2004 (San Francisco) — Donepezil (Aricept), a drug used to treat dementia in patients with Alzheimer's disease, improved memory and cognition deficits in patients with multiple sclerosis (MS), according to clinical trial research presented here at the American Academy of Neurology (AAN) annual meeting.

"This is the first time a randomized, placebo-controlled clinical trial has been successfully completed in patients with MS and cognitive impairment, showing a benefit that can make people better," lead author Lauren Krupp, MD, director of neuropsychology research at the State University of New York in Stony Brook, said during a presentation.

Half of patients with multiple sclerosis will face some degree of cognitive impairment, with 10% having severe cognitive impairment.

The researchers conducted a double-blind clinical trial of 69 MS patients with mild to moderate verbal learning or memory impairments and without clinical depression.

The patients were randomized to receive a 10-mg daily dose of donepezil or placebo for 24 weeks. Donepezil dosing began at 5 mg and was titrated to 10 mg daily after four weeks.

The Selective Reminding Test (SRT) of verbal memory function was administered, and the researchers also looked at secondary outcomes such as additional cognitive measures from the Brief Repeatable Battery (BRB), the Perceived Deficits Questionnaire (PDQ) of the MS Quality of Life Inventory, patient- and clinician-reported impression of clinical changes, affect, and fatigue.

An analysis revealed that patients in the donepezil group had a statistically significant change in memory improvement on the SRT verbal memory test compared with those in the placebo group. The treated patients showed about a 10% improvement on the memory test, while the placebo group had only about a 1% improvement, Dr. Krupp said.

More than 65% of the patients in the donepezil group also self-reported that their memory had improved with treatment compared with 32% of those in the placebo group.

The researchers reported cognitive improvement in almost twice as many patients receiving donepezil compared with those receiving placebo, and there was a statistically insignificant trend for the patients receiving donepezil to report a greater decrease in cognitive deficits on the PDQ inventory.

The benefit of donepezil over placebo remained significant after controlling for age, EDSS, baseline SRT score, reading ability, education, MS subtype, sex, and the simultaneous use of interferon-beta therapy.

Donepezil treatment had no impact on measures of affect or fatigue, although patients reported an increase in vivid dreams. There were also no significant findings on the BRB cognitive tasks, except for a trend toward improvement on the Paced Auditory Serial Addition Test.

"Clearly, this study has to be replicated in a larger sample size across many institutions," Dr. Krupp concluded. "If this is replicated, then we have some major changes to advocate in how we identify and treat people with MS who have these difficulties."

J. D. Bartleson, MD, associate professor of neurology at the Mayo Clinic in Rochester, Minnesota, and chair of the AAN's practice improvement subcommittee, said in an interview that it was somewhat surprising that a drug believed to work cortically in patients with Alzheimer's disease would also work for patients with MS.

"It was somewhat unexpected, but practically, it gives us something to use," said Dr. Bartleson, who was not affiliated with the study. "We're fond of taking a winner and trying it in a new illness."

The researchers disclosed funding support from the National Institutes of Health, the National Institute on Disability and Rehabilitation Research, the National Multiple Sclerosis Society, and the National Center for Research Resources.

AAN 56th Annual Meeting: Abstract S20.003. Presented April 27, 2004.

Reviewed by Gary D. Vogin, MD

Melissa Schorr is a freelance writer for Medscape.




Related Links
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American Academy of Neurology 56th Annual Meeting


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I just wanted to post this for FYI purposes. When I was first diagnosed, actually prior to diagnosis, my most persistant symptom was cognitive dysfunction. There were times I would be driving home from work, and I would forget how to get to my home. I remembered where I lived, I just could not remember how to get home. I had a real problem with numbers and names, which I still have, but not that bad. I have not gotten lost in about 2 years now, but it still scares me. They did a clinical trial, about 50 patients, at a hospital here in Florida, which showed this drug did NOT help MS, therefore, I initially could not get anyone to presecribe. Until I found the neuro I am now seeing, who put me on this drug right away. I was able to keep my job because ofthis drug and the cognitive training I received. I have been off the drug for about a year now. I still have memory problems, which become worse if I am having a bad day, but not like before. I just wanted everyone to know, and I am sure like everything else this will not work for everyone, but its worth a try if your life is changing due to cognitive issues alone.

Am I the only one who suffers from this?

Cathy,

Nope....you're not alone. I suffered (continual decline) for over three years with cognitive problems. Believe me, I know EXACTLY what you are talking about!! That was my biggest concern because I can lose my legs, but not my MIND! I make my living with my cognitive functions! Lose those, and I'm on the street! (I'm a single mother and sole wage earner)

Anyway, I was doing the best I could to try to compensate and cope, and you know what miraculously (and I'm not exaggerating...it's nothing less than miraculous) totally reversed my three year cognitive dysfunction?

Keppra (levetiracetam). I started taking Keppra for pain and spasticity (and for those twitches and shooting pains and pins and needles and crap), and then after about a month and a half, my mind was BACK. And I mean TOTALLY back! I haven't been able to think and remember things this clearly for about five years all total! So....I thought, what in the world?

I researched Keppra. You know what Keppra has in it? "Racetam". If you look up racetam, that's exactly what it is. A nootropic (cognitive enhancer). My MRI initially even showed the (we thought) permanent damage to the cognitive centers of my brain. A second MRI done only a month later (after taking Keppra for that time) showed totally clear.....and I mean totally. My neuro was astounded. Damage repaired!

Until Keppra, racetam has not been legal in the U.S. Keppra is the only drug on the market here in the U.S. with racetam in it. Levetiracetam is currently undergoing constant research, because it's so new, I do see now that the researchers are now beginning to see the same things I could have told them. The cognitive benefits of Keppra.

So...........yep. I know what you mean. My cognitive problems were horrid for a long time. Very long time. But not anymore!

Deb

I will keep the keppra in mind. I so not have any numbness or tingling, or that kind of thing, but I do have spasicity, which causes joint pain and makes me miserable. I take baclofen for that, but when I am off it, then need to restart, it makes me sooooo sleepy unitl I get used to it again, and by that time, ido not usally need to keep taking it. Does keppra make you sleepy? I took neurontin for awhile, and I couldn't keep my head off my desk after about an hour.

Well, it didn't make ME sleepy. I think the biggest side effect complaint (that wears off quickly) with Keppra, is it makes you feel a little off-balance (although not dizzy) for the first week or so, then that subsides and then it's rare that anybody has any side-effects.

Keppra is an AED, though. You can't keep going on and off of it. Once you take it, you need to stay on it. Actually, I'm surprised you're going on and off of baclofen and neurontin, too! But that's neither here nor there, I guess.

Keppra is a REALLY safe drug, though, because unlike most others, it does not metabolize in the liver at all.

It helps with neurological pain and phasic spasticity, but not necessarily tonic spasticity. Tonic is the type that draws your leg up or something, and you can't straighten it. Phasic is more those painful cramp-like things you get here and there. That's how I describe them anyway.

Of course, just like any drug (no matter how safe to your body it is), different people may experience different things. But overall, is Keppra known to exhibit much of a side-effect profile at all? Nope. That's what all the excitement about Keppra was (and still is). The extreme safety of it and overall lack of side effects. And it doesn't interact with other drugs, so it can be prescribed in combination with just about anything.

Here....go to this website. http://www.topix.net/drug/keppra

There are a couple of articles on there that are really good. The one regarding MS pain and spasticity is the one I originally saw somewhere else (back in January) and thought, "Hey, I wanna try THAT one"! The rest is history.

Now I see a brand new discovery regarding levetiracetam is there, also (regarding additional benefits of levetiracetam with CNS diseases). Yep.....I knew it would only be a matter of time.

Again, I refer to my original research Arron so graciously posted for me on the home page here, regarding my suspicions about levetiracetam (especially in combination with desipramine). Just a matter of time before they all catch up with me. hehehe.......

Deb

P.S. In my ongoing conversations with the NMSS, I had mentioned once that I noticed that one of the two drugs I was taking (either desipramine or levetiracetam) had now stopped my tremors, too. I suspected it was probably levetiracetam, and now I think I was correct. Some other recent research that I ran across recently that came out on levetiracetam found that it helps dyskinesia in Parkinsons's (some Parkinson's tremors are made worse by taking the very drug they need to take to HELP the disease, and combining levetiracetam with it, helps to negate that particular side-effect from the original drug), and now this more recent news article makes reference in the footnotes about perhaps having found some substantiation for suspecting levetiracetam might prove beneficial for essential tremor. Hmmmmmmmmm......well, I'll be darned! I'm being proven correct again for my suspicions that Keppra helped my tremors, too. I'll be darned!

Your too funny!! They may never catch up with you, by the way. The neurontin I did not stop and start-I just tried different doses and times of the day to take it, but I just could not tolerate it. I have the phasic spasicity that you decribed. But quite honestly, I had not had problems with this in a long time until this summer. It is so hot here, and I am having trouble with the heat despite being on LDN as well. Like this morning I was my usual achy self when I woke up, but now its really bothering me, when it usually goes away once I get up and start moving. I am in AC all day at work, but do have to walk across the street to the parent company at times during the day. I took 10mg of baclofen just a bit ago, mostly because my joints bothering me. I know baclofen is one of those drugs you have to taper off, but I seem to do fine just taking it here and there. If I do take it continually for awhile, I do taper off. I am going to ask about the keppra teh next time I see my neuro-sounds like a dream drug really. Thanks for the info, and keep well.

Hey....same to you, Cathy!

Yea...ya know.....at least it's worth a shot (Keppra). I mean, it's so doggoned safe, you've got nothing much to lose by giving it a try.

Plus, if you CAN take it with no major side-effects, you'll get the added benefit of "racetam"....hehehe....

They'll catch up with us on that, too, eventually.

Keep me posted!!

Deb

My new neuro prescribed aricept and things better after a week or so. My memory is much improved now, although still not like before MS. After a month she added Namenda to try and further improve things, but that did
not help at all and made me feel worse, so I stopped taking it before the trial pack was finished. But aricept is a winner, and it's nice to see articles
popping up about it now. My only surprise is that the insurance pays for it
since it is not yet listed as being for MS. I've been taking it for about 3 months now.