McKeith I, Del Ser T, Spano P, Emre M, Wesnes K, Anand R, Cicin-Sain A, Ferrara R, Spiegel R
Institute for the Health of the Elderly, University of Newcastle upon Tyne, UK.
Lancet. 2000 Dec 16;356(9247):2031-6. doi: 10.1016/S0140-6736(00)03399-7.
Dementia with Lewy bodies is a common form of dementia in the elderly, characterised clinically by fluctuating cognitive impairment, attention deficits, visual hallucinations, parkinsonism, and other neuropsychiatric features. Neuroleptic medication can provoke severe sensitivity reactions in patients with dementia of this type. Many deficits in cholinergic neurotransmission are seen in the brain of patients with Lewy-body dementia; therefore, drugs enhancing central cholinergic function represent a rationally-based therapeutic approach to this disorder. Rivastigmine, a cholinesterase inhibitor, was tested in a group of clinically characterised patients with Lewy-body dementia.
A placebo-controlled, double-blind, multicentre study was done in 120 patients with Lewy-body dementia from the UK, Spain, and Italy. Individuals were given up to 12 mg rivastigmine daily or placebo for 20 weeks, followed by 3 weeks rest. Assessment by means of the neuropsychiatric inventory was made at baseline, and again at weeks 12, 20, and 23. A computerised cognitive assessment system and neuropsychological tests were also used, and patients underwent close medical and laboratory safety analysis.
Patients taking rivastigmine were significantly less apathetic and anxious, and had fewer delusions and hallucinations while on treatment than controls. Almost twice as many patients on rivastigmine (37, 63%), than on placebo (18, 30%), showed at least a 30% improvement from baseline. In the computerised cognitive assessment system and the neuropsychological tests, patients were significantly faster and better than those on placebo, particularly on tasks with a substantial attentional component. Both predefined primary efficacy measures differed significantly between rivastigmine and placebo. After drug discontinuation differences between rivastigmine and placebo tended to disappear. Known adverse events of cholinesterase inhibitors (nausea, vomiting, anorexia) were seen more frequently with rivastigmine than with placebo, but safety and tolerability of the drug in these mostly multimorbid patients were judged acceptable.
Rivastigmine 6-12 mg daily produces statistically and clinically significant behavioural effects in patients with Lewy-body dementia, and seems safe and well tolerated if titrated individually.
路易体痴呆是老年人常见的痴呆形式，临床特征为认知功能波动、注意力缺陷、视幻觉、帕金森症及其他神经精神症状。抗精神病药物可引发此类痴呆患者的严重过敏反应。路易体痴呆患者大脑中可见许多胆碱能神经传递缺陷；因此，增强中枢胆碱能功能的药物是针对该疾病的一种合理治疗方法。卡巴拉汀，一种胆碱酯酶抑制剂，在一组具有临床特征的路易体痴呆患者中进行了试验。
在来自英国、西班牙和意大利的120例路易体痴呆患者中进行了一项安慰剂对照、双盲、多中心研究。患者每日服用最多12mg卡巴拉汀或安慰剂，持续20周，随后休息3周。在基线时以及第12、20和23周时通过神经精神科量表进行评估。还使用了计算机化认知评估系统和神经心理学测试，并且患者接受了密切的医学和实验室安全性分析。
与对照组相比，服用卡巴拉汀的患者在治疗期间冷漠和焦虑症状明显减轻，妄想和幻觉减少。服用卡巴拉汀的患者（37例，63%）至少比基线改善30%的人数几乎是服用安慰剂患者（18例，30%）的两倍。在计算机化认知评估系统和神经心理学测试中，患者比服用安慰剂的患者反应明显更快且表现更好，尤其是在具有大量注意力成分的任务上。卡巴拉汀和安慰剂在两种预先定义的主要疗效指标上均存在显著差异。停药后，卡巴拉汀和安慰剂之间的差异趋于消失。胆碱酯酶抑制剂的已知不良事件（恶心、呕吐、厌食）在服用卡巴拉汀的患者中比服用安慰剂的患者更常见，但该药物在这些大多患有多种疾病的患者中的安全性和耐受性被认为是可接受的。
每日6 - 12mg卡巴拉汀对路易体痴呆患者产生了具有统计学意义和临床意义的行为影响，并且如果进行个体化滴定，似乎安全且耐受性良好。
