Françoise Forette — Page 2

PubMed2002

Presence or absence of at least one epsilon 4 allele and gender are not predictive for the response to donepezil treatment in Alzheimer's disease.

The objective was to evaluate the effects of the apolipoprotein E (ApoE) genotype and gender on the response to donepezil treatment in Alzheimer's disease. ApoE genotyping was performed on 117 patients with mild to moderate Alzheimer's disease who were included in a 36-week open label trial of donepezil therapy. Of these 117 patients, who constituted the intent-to-treat population (ITT), 80 completed the trial, and constituted the evaluable population. Patients were treated blindly in relation to ApoE genotype. Outcome measures were Alzheimer's disease Assessment Scale-Cognitive Component (ADAS-Cog), the Mini Mental State Examination, Instrumental Activities of Daily Living, and the Caregiver-rated Clinical Global Impression of Change. ITT analysis did not reveal significant differences between the responses of epsilon 4- and epsilon 4+ carriers according to the ADAS-Cog (P = 0.28). No differences were found either between the responses of men and women (P = 0.81), and there was no significant interaction between genotype and gender (P = 0.09). Other outcome measures all exhibited similar patterns of change to those seen using the ADAS-Cog. Consequently, these results do not support the hypothesis that the ApoE phenotype and gender are predictors of the response to donepezil in Alzheimer's disease patients.

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PubMed2002

Efficacy and safety of memantine in patients with mild to moderate vascular dementia: a randomized, placebo-controlled trial (MMM 300).

BACKGROUND AND PURPOSE: Based on the hypothesis of glutamate-induced neurotoxicity (excitotoxicity) in cerebral ischemia, this study examined the efficacy and tolerability of memantine, an uncompetitive N-methyl-D-aspartate antagonist, in the treatment of mild to moderate vascular dementia. METHODS: In this multicenter, 28-week trial carried out in France, 321 patients received 10 mg/d memantine or placebo twice a day; 288 patients were valid for intent-to-treat analysis. Patients had to meet the criteria for probable vascular dementia and have a Mini-Mental State (MMSE) score between 12 and 20 at inclusion. The 2 primary end points were the cognitive subscale of the Alzheimers Disease Assessment Scale (ADAS-cog) and the global Clinician's Interview Based Impression of Change (CIBIC-plus). RESULTS: After 28 weeks, the mean ADAS-cog scores were significantly improved relative to placebo. In the intention-to-treat population, the memantine group mean score had gained an average of 0.4 points, whereas the placebo group mean score had declined by 1.6 points, ie, a difference of 2.0 points (95% confidence interval, 0.49 to 3.60). The response rate for CIBIC-plus, defined as improved or stable, was 60% with memantine compared with 52% with placebo (P=0.227, intention to treat). Among the secondary efficacy parameters, which were analyzed in the per-protocol subset, MMSE was significantly improved with memantine compared with deterioration with placebo (P=0.003). The Gottfries-Brane-Steen Scale intellectual function subscore and the Nurses' Observation Scale for Geriatric Patients disturbing behavior dimension also showed differences in favor of memantine (P=0.04 and P=0.07, respectively). Memantine was well tolerated with a frequency of adverse events comparable to placebo. CONCLUSIONS: In patients with mild to moderate vascular dementia, memantine 20 mg/d improved cognition consistently across different cognitive scales, with at least no deterioration in global functioning and behavior. It was devoid of concerning side effects.

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