Response of patients with Alzheimer disease to rivastigmine treatment is predicted by the rate of disease progression

Background: Evidence suggests that disease severity predicts the response o f patients with Alzheimer disease (AD) to cholinesterase inhibitor treatmen t, raising the question of whether disease progression also predicts respon se to this treatment. Objective: To evaluate retrospectively whether rate of disease progression during placebo treatment affects response to subsequent rivastigmine tartra te therapy for patients with mild to moderately severe AD. Design: A 26-week, open-label extension study follow ing a 26-week, double- blind, randomized, placebo-controlled trial. Setting: Outpatient research centers at 22 sites in the United States. Patients: We studied 187 of 235 patients originally randomized to receive p lacebo treatment in the double-blind phase of the trial who continued with open-label (rivastigmine) extension therapy. Intervention: Placebo treatment for 26 weeks followed by rivastigmine treat ment, 2 to 12 mg/d, for 26 weeks. Main Outcome Measures: Alzheimer's Disease Assessment Scale-cognitive subsc ale (ADAS-Cog), Progressive Deterioration Scale, Mini-Mental State Examinat ion, and Global Deterioration Scale scores. Results: Rivastigmine administration during open-label extension therapy be nefited patients who had progressed slowly and those who had progressed rap idly during initial double-blind placebo treatment. Slowly progressive pati ents responded with a mean 1.03-point improvement in the week 26 tie, start of open-label rivastigmine treatment) ADAS-Cog score at 12 weeks of rivast igmine treatment (week 38 of treatment; P=.02 vs week 26). However, more ra pidly progressive patients had a significantly larger mean 4.97-point impro vement from the week 26 ADAS-Cog score at 12 weeks (with respect to week 26 of treatment and slowly progressive patient scores, P<.001 for both). Thus , a more rapid disease progression rate while receiving placebo treatment w as predictive of a significantly stronger patient response to rivastigmine therapy. This relation also was observed with the other 3 outcome measures and was still apparent when accounting for disease severity. Conclusions: Rate of disease progression for patients with mild to moderate AD seems to predict response to rivastigmine treatment. Patients with more rapidly progressive disease might be particularly likely to benefit from r ivastigmine therapy.