Forgacs P B, Bodis-Wollner I
Department of Neurology, State University of New York, Downstate Medical Center, and Parkinson's Disease and Related Disorders Clinic, Center of Excellence, Kings County Hospital Center and SUNY, Brooklyn, NY 11203, USA.
J Neural Transm (Vienna). 2004 Oct;111(10-11):1317-31. doi: 10.1007/s00702-004-0169-0. Epub 2004 Jun 30.
Parkinson's Disease (PD) is associated with cognitive deficits. The earliest impairment is evident for executive abilities, visuospatial orientation and memory. Dopamine deficiency is unlikely to be singly responsible for all cognitive changes in PD. Acetyl-choline has an essential role in cognition, thus cholinergic transmission may have an important role in non-dopaminergic cognitive changes. If so, some cognitive defects could possibly be treated with choline-esterase inhibitors. A concern is the potential negative motor effect of cholinergic medication in PD. Surprisingly, these are reported only in a few patients studied. Establishing the relationship between select cognitive deficits and nicotinic neurotransmission may lay the foundation for rational pharmacotherapy of cognitive dysfunction in PD. We summarize anatomical, physiological and pharmacological aspects of nicotinic receptor function. The focus is on those nicotine receptor dependent cognitive dysfunctions which are likely to contribute to motor impairment. Lastly, we discuss hypotheses concerning cholinergic involvement in neuronal synchrony and sensorimotor integration in PD.
帕金森病(PD)与认知缺陷有关。最早出现的损害在执行能力、视觉空间定向和记忆方面最为明显。多巴胺缺乏不太可能是导致PD所有认知变化的唯一原因。乙酰胆碱在认知中起着至关重要的作用,因此胆碱能传递可能在非多巴胺能认知变化中起重要作用。如果是这样,一些认知缺陷可能可以用胆碱酯酶抑制剂治疗。一个担忧是胆碱能药物在PD中可能产生的负面运动效应。令人惊讶的是,这些仅在少数研究患者中有所报道。确定特定认知缺陷与烟碱神经传递之间的关系可能为PD认知功能障碍的合理药物治疗奠定基础。我们总结了烟碱受体功能的解剖学、生理学和药理学方面。重点关注那些可能导致运动障碍的依赖烟碱受体的认知功能障碍。最后,我们讨论了关于胆碱能参与PD神经元同步和感觉运动整合的假说。