Michel B F, Estadieu M C, Gueriot C, Berthezène P, Allain H, Bongrand M C, Bonnefoy B, Bourrin J C, Chaix L, Graa K, Lejeune A, Messana M, Pras P, Ribiere J, Rihet P, Timon-David P, Tintignac A, Vincent S, Verdier J M, Gastaut J L
Unité de Neuro-Gériatrie, Service de Neurologie, Hôpital Sainte-Marguerite, Marseille.
Rev Neurol (Paris). 2001 Nov;157(11 Pt 1):1365-75.
We describe the follow-up of a cohort of 255 Alzheimer's disease (AD) patients (81 males, 174 females) treated by tacrine during 4 years. We performed the survey of hepatic, cholinergic and general tolérance. Drug efficacy was measured by MMS examination on weeks 0, 18, 30, 52, 104, 156 and 208. A total of 190 patients (74.5 percent) were dropped out of this study, 75 (29 percent) for adverse events. We found 85 hepatic (33 percent), 79 cholinergic (31 percent), 31 (12 percent) neuropsychiatric and 72 general (28 percent) side effects. In term of drug efficacy we observed a global decline of 2.5 MMS points during the first year and 2 MMS points between W52 and W156. Tacrine's symptomatic efficacy, defined as the number of patients improved or stabilized at W30, was present in 50 patients (46 percent) among the 109 patients reaching W30. The intensity of symptomatic efficacy was expressed by a 2.7 MMS points increase in 37 patients improved on W30. The long term effects of Tacrine, measured by the MMS score at one year, showed a positive impact as the MMS was 2.5 points above the expected score in non treated AD patients. This study raises the practical problem of optimal cholinesterase inhibitors use in AD and the theoretical question of long term action of cholinesterase inhibitors on cerebral lesions of AD.
我们描述了一组255例接受他克林治疗4年的阿尔茨海默病(AD)患者(81名男性,174名女性)的随访情况。我们进行了肝脏、胆碱能和总体耐受性调查。通过在第0、18、30、52、104、156和208周进行简易精神状态检查表(MMS)检查来衡量药物疗效。共有190名患者(74.5%)退出了本研究,其中75名(29%)是因为不良事件。我们发现85例(33%)有肝脏副作用,79例(31%)有胆碱能副作用,31例(12%)有神经精神副作用,72例(28%)有总体副作用。在药物疗效方面,我们观察到第一年MMS总分下降2.5分,在第52周和第156周之间下降2分。他克林的症状疗效定义为在第30周病情改善或稳定的患者数量,在达到第30周的109例患者中有50例(46%)出现症状疗效。症状疗效的强度表现为在第30周病情改善的37例患者MMS得分增加2.7分。以一年时的MMS评分衡量,他克林的长期效果显示出积极影响,因为该评分比未治疗的AD患者预期得分高2.5分。本研究提出了AD中胆碱酯酶抑制剂最佳使用的实际问题以及胆碱酯酶抑制剂对AD脑损伤长期作用的理论问题。