Bosboom J L W, Stoffers D, Wolters E Ch
Department of Neurology, Research Institute Neurosciences Vrije Universiteit, VU University Medical Center, Amsterdam, The Netherlands.
J Neural Transm (Vienna). 2004 Oct;111(10-11):1303-15. doi: 10.1007/s00702-004-0168-1. Epub 2004 Jun 30.
Parkinson's disease (PD) is a slowly progressive neurodegenerative disorder mainly characterized by degeneration of dopaminergic neurons in the substantia nigra and the ventral tegmental area, in combination with a varying loss of central noradrenergic (locus coeruleus), cholinergic (nucleus basalis of Meynert) and serotonergic (dorsal raphe nuclei) integrity, leading to a multitude of motor and non-motor behavioral disturbances. Apart from the clinical motor hallmarks, in the early stages of disease, subtle cognitive dysfunction might be seen comprising mainly executive dysfunction, with secondary visuospatial and mnemonic disturbances. In about 20-40% of patients, these problems may eventually proceed to dementia, which constitutes an important risk factor for caregiver distress, decreased quality of life and nursing home placement. Dementia in PD is typically characterized by a progressive dysexecutive syndrome with attentional deficits and fluctuating cognition, often accompanied by psychotic symptoms. It is thought to be the result of a combination of both subcortical and cortical changes. PD-related dopaminergic deficiency in the nucleus caudatus and mesocortical areas (due to degeneration of projections from the substantia nigra and ventral tegmental area) and cholinergic deficiency in the cortex (due to degeneration of ascending projections from the nucleus basalis of Meynert), combined with additional Alzheimer-pathology and cortical Lewy bodies, may greatly contribute to dementia. Current treatment of dementia in PD is based on compensation of the profound cholinergic deficiency. Recent studies with the cholinesterase inhibitors galantamine, donepezil and rivastigmine show promising results in improving cognition and ameliorating psychotic symptoms, which must further be confirmed in randomized controlled trials.
帕金森病（PD）是一种缓慢进展的神经退行性疾病，主要特征是黑质和腹侧被盖区的多巴胺能神经元变性，同时伴有中枢去甲肾上腺素能（蓝斑）、胆碱能（Meynert基底核）和5-羟色胺能（中缝背核）完整性的不同程度丧失，导致多种运动和非运动行为障碍。除了临床运动特征外，在疾病早期，可能会出现细微的认知功能障碍，主要包括执行功能障碍，继发视觉空间和记忆障碍。在约20%-40%的患者中，这些问题最终可能发展为痴呆，这是导致照料者痛苦、生活质量下降和入住养老院的重要危险因素。帕金森病中的痴呆通常表现为进行性执行功能障碍综合征，伴有注意力缺陷和认知波动，常伴有精神症状。它被认为是皮质下和皮质变化共同作用的结果。尾状核和中皮质区域的帕金森病相关多巴胺能缺乏（由于黑质和腹侧被盖区投射的变性）以及皮质中的胆碱能缺乏（由于Meynert基底核上行投射的变性），再加上额外的阿尔茨海默病病理和皮质路易小体，可能极大地促成痴呆。目前帕金森病痴呆的治疗基于对严重胆碱能缺乏的补偿。最近使用胆碱酯酶抑制剂加兰他敏、多奈哌齐和卡巴拉汀的研究在改善认知和减轻精神症状方面显示出有希望的结果，这必须在随机对照试验中进一步得到证实。
