Chen Tzu-Hua, Chou Mei-Chuan, Lai Chiou-Lian, Wu Shyh-Jong, Hsu Chia-Ling, Yang Yuan-Han
Department of Family Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan; Department of Public Health, College of Health Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan.
Department of Neurology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan.
Kaohsiung J Med Sci. 2017 Jun;33(6):277-283. doi: 10.1016/j.kjms.2017.04.006. Epub 2017 May 22.
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.
卡巴拉汀已广泛用于轻至中度阿尔茨海默病(AD),但其治疗有效率在20%至60%之间。已有研究提示存在剂量依赖性效应,但既往研究未测定卡巴拉汀及其代谢产物NAP 226 - 90的血浆浓度。不同种族的各类研究中,治疗反应的影响因素复杂且不一致。因此,我们分析了63例临床诊断为AD且每日服用剂量为6 - 9 mg的患者,通过神经心理学评估测定的卡巴拉汀治疗反应,及其与卡巴拉汀和NAP 226 - 90的血浆浓度、载脂蛋白E(APOE)基因型和人口统计学特征的关系。我们的报告显示,通过简易精神状态检查表(MMSE)测定,41.3%的入组AD患者认知功能有所改善;通过临床痴呆评定量表框和得分(CDR - SB)测定,63.5%的患者整体状况有所改善。在认知方面,临床改善组的卡巴拉汀浓度显著更高[p = 0.049,优势比(OR)= 1.029,95%置信区间(CI)= 1.000 - 1.058],初始MMSE评分更低(p = 0.010,OR = 0.708,95%CI = 0.546 - 0.920),初始CDR - SB评分更低(p = 0.003,OR = 0.552,95%CI = 0.372 - 0.817)。携带APOE ε4等位基因的患者认知功能恶化(p = 0.037,OR = 3.870,95%CI = 1.082 - 13.840)。在整体状况方面,只有更高的教育程度(p = 0.043,OR = 1.222,95%CI = 1.007 - 1.484)与临床改善显著相关。总之,高浓度的卡巴拉汀可能有益于AD患者的认知功能,尤其是在APOE ε4(-)携带者中。