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Background and Purpose: Cholinesterase inhibitors (ChEI) are currently the mainstream symptomatic treatment of patients with Alzheimer’s disease (AD). To this end, the response to the treatment with ChEI is clinically difficult to predict. Several demographic, clinical and biological variables have been proposed as pre-treatment predictors of long-term therapy efficacy. The aim of the study was to confirm our initial observations of the significance of a change in plasma levels of beta-amyloid (Abeta) peptides after initial treat-ment with rivastigmine for predicting clinical response to ChEI.; Material and Methods: Fifty-four carefully selected subjects (37 females) satisfying criteria for mild (n = 25) or moderate (n = 29) AD were included in the study. Rivastigmine was prescribed at the initial dose of 3 mg/day b.i.d.; the dose was escalated to the maximum tolerated one in at least 4-week intervals. The response to treatment was assessed using the ADAS-Cog and CDR scales. Whole blood samples were collected twice: before the first rivastigmine dose and at the 2nd week on active treatment. Levels of Abeta(1-40) and Abeta(1-42) were measured in plasma using a commercially available ELISA.; Results: We confirmed that higher initial disease severity (higher ADAS-Cog scores) and the increase in the con-centration of plasma Abeta(1-42) peptide following 2 weeks of treatment with an initial dose of rivastigmine increased the chance of a clinically meaningful response to ChEI therapy in AD patients after 2 years of follow-up.; Conclusions: A change in plasma Abeta(1-42) level might constitute a novel biochemical predictor of long-term rivastigmine treatment efficacy in AD.;