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Title: Memantine Curbs Decline In Alzheimer's Patients

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N Engl J Med 2003;348:1333-1341.
04/03/2003 12:27:58 PM
By Anne MacLennan

Antiglutamatergic therapy may prove helpful in slowing the rate of decline in patients with moderate-to-severe Alzheimer's disease. Researchers in the United States and Germany make this suggestion following a 28-week placebo-controlled study among 252 such patients from 32 US centres. The researchers investigated treatment with memantine, because over- stimulation of the N-methyl-D-aspartate (NMDA) receptor by glutamate is implicated in neurodegenerative disorders, and memantine is an NMDA antagonist. To date, there is no treatment for patients with Alzheimer's disease that is moderate-to-severe, a stage that is both distressing for patients and burdensome for caregivers. Dr Barry Reisberg from the Department of Psychiatry, New York University School of Medicine, New York, led this multi-centre project for the Memantine Study Group. The patients, 67% women, mean age 76 years, were randomly assigned to receive either placebo or 20 mg of memantine daily for 28 weeks. Primary efficacy variables were the Clinician's Interview- Based Impression of Change Plus Caregiver Input and the Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory modified for severe dementia. Investigators assessed treatment differences between baseline and end point, and missing observations were imputed by using the most recent previous observation (the last observation carried forward). One hundred and eighty one patients (72%) completed the study and were evaluated at week 28. Seventy-one had discontinued treatment prematurely (42 taking placebo and 29 taking memantine). Among those who completed the study, memantine appeared to confer benefit in terms of activities of daily living and other measures. Analysis of the last observation carried forward for the whole group supported this conclusion. The treatment was not associated with a significant frequency of adverse events.

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