Abstract
The aim of this small pilot study was to evaluate the association between plasma concentrations of rivastigmine and its metabolite, NAP 226-90, and cognitive function in patients with Alzheimer's disease (AD). Rivastigmine-treated AD patients, who had been maintained on a fixed regimen of twice daily rivastigmine (6 to 12 mg/d) for ≥6 months, were eligible for evaluation. The assessments included Cognitive Assessment Screening Instrument (CASI) and Clinical Dementia Rating scale, conducted at baseline and at 6-month follow-up. The 9 subdomains of CASI at baseline and follow-up were analyzed in relation to the plasma concentrations of rivastigmine and NAP 226-90, as measured by capillary electrophoresis. Logistic regression was performed to adjust for age, gender, education level, apolipoprotein E ε4 genotype status, and baseline CASI score to investigate the association between plasma rivastigmine and NAP 226-90 concentrations and the cognitive response. The total sample consisted of 53 clinically diagnosed AD patients taking rivastigmine only at doses of 6 mg to 9 mg/d because of intolerability at 12 mg/d. Higher rivastigmine concentration was significantly associated with improved or preserved short-term memory and worsened abstraction/judgment (p < 0.05), but not with changes in other domains (p > 0.05). Higher NAP 226-90 concentration was significantly associated with worsened abstraction/judgment (p < 0.05), but not with changes in other domains. Higher plasma rivastigmine concentration was significantly associated with improved or preserved short-term memory but worsened abstraction/judgment. An optimal concentration of rivastigmine should be quantified for each patient because of differential cognitive responses.