Lalli Stefania, Albanese Alberto
Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Fondazione IRCCS Istituto Neurologico Carlo Besta Università Cattolica del Sacro Cuore, Milano, Italy.
Expert Rev Neurother. 2008 Aug;8(8):1181-8. doi: 10.1586/14737175.8.8.1181.
Dementia associated with Parkinson's disease (PD) ultimately develops in approximately 70% of patients with PD older than 80 years of age. The neuropathology of PD dementia (PDD) is likely multifactorial and affects several neuronal populations. There is evidence that PDD is associated with a cholinergic deficit, supporting the therapeutic role of cholinesterase inhibitors, which are already first-line agents in the treatment of Alzheimer's disease. Open-label and small controlled studies suggested a clinical efficacy of cholinesterase inhibitors in PDD. One large randomized placebo-controlled trial of 541 patients demonstrated that oral rivastigmine improved cognition, attention and executive functions, activities of daily living and behavioral symptoms after 6 months of treatment. Rivastigmine is a dual cholinesterase inhibitor, being effective on both acetylcholinesterase and butyrylcholinesterase. This paper reviews the pharmacokinetic and pharmacodynamic properties of rivastigmine (oral and transdermal administration). It also reviews evidence on clinical efficacy, safety and tolerability of the oral administration in PDD patients at doses of 3-12 mg/day.
帕金森病(PD)相关的痴呆最终在约70%的80岁以上PD患者中发生。帕金森病痴呆(PDD)的神经病理学可能是多因素的,且影响多个神经元群体。有证据表明PDD与胆碱能缺陷有关,这支持了胆碱酯酶抑制剂的治疗作用,而胆碱酯酶抑制剂已是治疗阿尔茨海默病的一线药物。开放标签和小型对照研究提示胆碱酯酶抑制剂在PDD中有临床疗效。一项针对541例患者的大型随机安慰剂对照试验表明,口服卡巴拉汀在治疗6个月后可改善认知、注意力和执行功能、日常生活活动及行为症状。卡巴拉汀是一种双重胆碱酯酶抑制剂,对乙酰胆碱酯酶和丁酰胆碱酯酶均有效。本文综述了卡巴拉汀(口服和透皮给药)的药代动力学和药效学特性。还综述了PDD患者口服剂量为3 - 12mg/天时的临床疗效、安全性和耐受性的证据。