Factors affecting therapeutic response to Rivastigmine in Alzheimer's disease patients in Taiwan

Abstract

Rivastigmine has been widely used in mild-to-moderate Alzheimer's disease (AD), but the therapeutic response rate varies from 20 to 60%. A dose-dependent effect has been suggested, but the plasma concentration of rivastigmine and its metabolite, NAP 226-90, were not measured in previous studies. The influencing factors of therapeutic response are complicated and discordant in various studies among different ethnic groups. Hence, we analyzed the therapeutic responses of rivastigmine, measured by neuropsychological assessments, among 63 clinically diagnosed AD patients taking a daily dosage of 6-9 mg in relation to their plasma concentration of rivastigmine and NAP 226-90, apolipoprotein E (APOE) genotype and demographic characteristics. Our reports revealed that 41.3% of recruited AD patients had improvement in cognition, measured by Mini-Mental Status Examination (MMSE), and 63.5% in global status, by Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) score. In cognition, the clinically improving group had a significantly higher rivastigmine concentration [p = 0.049, odds ratio (OR) = 1.029, 95%CI = 1.000-1.058], lower initial MMSE score (p = 0.010, OR = 0.708, 95%CI = 0.546-0.920), and lower initial CDR-SB score (p = 0.003, OR = 0.552, 95%CI = 0.372-0.817). The patients with APOE ε4 allele had worsening cognition (p = 0.037, OR = 3.870, 95%CI = 1.082-13.840). In global status, only higher education (p = 0.043, OR = 1.222, 95%CI = 1.007-1.484) was significantly associated with clinical improvement. In conclusion, high concentrations of rivastigmine may benefit cognitive function of AD patients, especially in APOE ε4 (-) carriers.

Keywords: Alzheimer's disease; Apolipoprotein E; Mini-Mental Status Examination (MMSE); NAP 226-90; Rivastigmine.