Background: Alzheimer’s disease (AD) patients experiencing more rapid symptom progression are likely to have a poorer prognosis than those experiencing slow symptom progression. In a recent retrospective analysis, treatment effects of rivastigmine were more pronounced in AD patients with rapid cognitive decline than in those with slow cognitive decline. This warranted further investigation. Methods: Rapidly and slowly progressing patients were identified by rates of cognitive decline [≧4 points and <4 points, respectively, on the Alzheimer’s Disease Assessment Scale – cognitive subscale (ADAS-cog)] during 26 weeks of placebo treatment in four randomized controlled trials (weeks 0–26). This meta-analysis evaluated rates of cognitive decline in both subgroups during subsequent open-label rivastigmine 26-week extension studies (weeks 26–52). A longitudinal mixed effects model compared cognitive decline in rapidly and slowly progressing patients, including correction for possible regression to the mean. Results: 180 (75%) rapidly and 337 (78%) slowly progressing patients provided ADAS-cog data after 26 weeks of open-label rivastigmine treatment. Improvements in cognitive symptoms were observed during the first 12 weeks, which were more pronounced in patients with rapid progression than in those with slow progression. Rapidly progressing patients experienced significantly greater cognitive benefits than slowly progressing patients (p = 0.029), who experienced a modest decline in cognitive symptoms at the end of the study. Comment: Patients experiencing rapid symptom progression may receive greater benefit from rivastigmine than those with slow progression. In this study, cholinesterase inhibition appeared to be of particular utility in the management of AD patients whose symptoms were rapidly worsening.

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