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 of patients with Alzheimer disease (AD) to cholinesterase inhibitor treatment, raising the question of whether disease progression also predicts response to this treatment.


OBJECTIVE
To evaluate retrospectively whether rate of disease progression during placebo treatment affects response to subsequent rivastigmine tartrate therapy for patients with mild to moderately severe AD.


METHODS
A 26-week, open-label extension study following a 26-week, double-blind, randomized, placebo-controlled trial.


METHODS
Outpatient research centers at 22 sites in the United States.


METHODS
We studied 187 of 235 patients originally randomized to receive placebo treatment in the double-blind phase of the trial who continued with open-label (rivastigmine) extension therapy.


METHODS
Placebo treatment for 26 weeks followed by rivastigmine treatment, 2 to 12 mg/d, for 26 weeks.


METHODS
Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog), Progressive Deterioration Scale, Mini-Mental State Examination, and Global Deterioration Scale scores.


RESULTS
Rivastigmine administration during open-label extension therapy benefited patients who had progressed slowly and those who had progressed rapidly during initial double-blind placebo treatment. Slowly progressive patients responded with a mean 1.03-point improvement in the week 26 (ie, start of open-label rivastigmine treatment) ADAS-Cog score at 12 weeks of rivastigmine treatment (week 38 of treatment; P =.02 vs week 26). However, more rapidly progressive patients had a significantly larger mean 4.97-point improvement 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 was 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 rivastigmine therapy.
Department of Neurology, Indiana University School of Medicine, CL583, 541 Clinical Dr., Indianapolis, IN 46202-5111, USA. mfarlow@iupui.edu
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Farlow
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Hake
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Messina
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Hartman
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Veach
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Anand
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology; D002219:Carbamates / Q000008:administration & dosage*; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage*; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D048448:Phenylcarbamates; D011237:Predictive Value of Tests; D011379:Prognosis; D000068836:Rivastigmine; D016896:Treatment Outcome
D002219:Carbamates; D002800:Cholinesterase Inhibitors; D048448:Phenylcarbamates; D000068836:Rivastigmine