Chitnis Shilpa, Rao Jayaraman
UT Southwestern Medical Center-Neurology, 5323 Harry Hines Blvd, Dallas, Texas 75390-9036, USA.
Expert Opin Drug Metab Toxicol. 2009 Aug;5(8):941-55. doi: 10.1517/17425250903105420.
Parkinson's disease has now evolved beyond what was considered to be a traditional motor disorder. It is being increasingly recognized that non-motor symptoms such as cognitive impairment, frank dementia, psychosis, depression, autonomic dysfunction and sleep disturbances are just as integral to the disease spectrum. The cholinergic system has been proposed to play a pivotal role in cognitive dysfunction. Based on interpretation of clinical studies in patients with Alzheimer's, cholinesterase inhibitors have also been studied for dementia associated with Parkinson's disease. Most of these include large and small placebo-controlled studies and several pilot studies have indicated that cholinesterase inhibitors have a favorable effect on cognition, psychiatric symptoms and global function in Parkinson's disease dementia. A large randomized placebo-controlled clinical trial showed that rivastigmine had moderate improvement in dementia associated with Parkinson's disease. The magnitude of effects in terms of scores for the cognitive subscale of the Alzheimer's disease assessment scale and Alzheimer's disease cooperative study-clinicians global impression of change were similar to those observed among patients with Alzheimer's disease who were treated with cholinesterase inhibitors. A transdermal patch which gradually releases rivastigmine over the application period is now available for use in mild to moderate dementia associated with Parkinson's disease and Alzheimer's disease.
帕金森病如今已发展到超出传统运动障碍的范畴。人们越来越认识到,认知障碍、明显的痴呆、精神病、抑郁、自主神经功能障碍和睡眠障碍等非运动症状在该疾病谱中同样不可或缺。胆碱能系统被认为在认知功能障碍中起关键作用。基于对阿尔茨海默病患者临床研究的解读,胆碱酯酶抑制剂也被用于研究与帕金森病相关的痴呆。其中大多数研究包括大小不等的安慰剂对照试验,多项初步研究表明,胆碱酯酶抑制剂对帕金森病痴呆的认知、精神症状和整体功能有积极作用。一项大型随机安慰剂对照临床试验表明,卡巴拉汀对帕金森病相关痴呆有中度改善作用。在阿尔茨海默病评估量表认知子量表得分以及阿尔茨海默病协作研究——临床医生对变化的总体印象方面,其效果程度与接受胆碱酯酶抑制剂治疗的阿尔茨海默病患者中观察到的情况相似。一种在使用期间能逐渐释放卡巴拉汀的透皮贴剂现已可用于治疗与帕金森病和阿尔茨海默病相关的轻至中度痴呆。