Alzheimer's Drug May Help Memory in MS Patients

April 27, 2004

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


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