Executive dyscontrol in dementia, with emphasis on subcortical pathology and the role of butyrylcholinesterase.
Executive dyscontrol in dementia, with emphasis on subcortical pathology and the role of butyrylcholinesterase.
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DOI：
10.2174/156720507781077313
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发表时间：
2007-06
影响因子：
2.1
通讯作者：
R. Bullock;R. Lane
中科院分区：
文献类型：
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作者：
R. Bullock;R. Lane
执行功能描述了各种认知过程，负责围绕目标构建行为，并制定计划以实现与环境相关的目标。除了基底前脑胆碱能神经元输入到额叶皮质的缺陷外，执行功能的控制受损还与额叶皮质及其基底神经节-丘脑连接的病变有关。除了执行功能障碍外，暗示额叶皮层下病变的特征还包括认知严重减慢、注意力缺陷、冷漠和情绪变化。额叶皮质下系统易受白色物质改变、萎缩和某些形式的神经递质耗竭的影响。含有乙酰胆碱酯酶（AChE）的丘脑神经元的弥漫性和可能的非胆碱能投射支配所有皮层区域。丁酰胆碱酯酶（BuChE）活性在丘脑核团中相对较高，丘脑核团投射到涉及注意力、执行功能和行为的额叶皮质结构。然而，大脑中BuChE的最大池是在神经胶质中发现的，特别是在更深的皮质和皮质下结构中。这些结果表明，BuChE也可能是一个重要的治疗目标，在管理症状，由于皮质下病理。尽管“纯”阿尔茨海默病（AD）除了皮质病理学之外还可能涉及显著的皮质下病理学，但AD伴脑血管病、血管性痴呆（VaD）、帕金森病痴呆（PDD）和路易体痴呆（DLB）除了皮质病理学之外还可能涉及通常更大程度的皮质下病理学。可以假设，这些以执行功能障碍为特征的痴呆类型可能从胆碱酯酶抑制剂（如rivastigmine）中获得特别的益处，这些胆碱酯酶抑制剂除抑制AChE外还抑制BuChE。
Executive functions describe a variety of cognitive processes responsible for structuring behaviors around goals, and developing plans to achieve those goals in relation to the environment. In addition to deficits in basal forebrain cholinergic neuronal input into the frontal cortex, impaired control of executive function has been associated with lesions to the frontal cortex and its basal ganglia-thalamic connections. In addition to executive dysfunction, features that imply fronto-subcortical pathology include profound slowing of cognition, attentional deficits, apathy and changes in mood. Fronto-subcortical systems are vulnerable to white matter change, atrophy, and certain forms of neurotransmitter depletion. The diffuse, and likely non-cholinergic, projections of acetylcholinesterase (AChE)-containing thalamic neurons innervate all cortical areas. Butyrylcholinesterase (BuChE) activity is relatively high in thalamic nuclei that project to frontal cortical structures involved in attention, executive function, and behavior. However, the largest pool of BuChE in the brain is found in the glia, particularly those in deeper cortical and subcortical structures. These findings suggest that BuChE may also be an important therapeutic target in the management of symptoms due to subcortical pathology. Whereas 'pure' Alzheimer's disease (AD) may involve significant subcortical pathology in addition to cortical pathology, AD with cerebrovascular disease, vascular dementia (VaD), Parkinson's disease dementia (PDD) and dementia due to Lewy bodies (DLB) may involve a generally greater degree of subcortical, in addition to cortical, pathology. It may be hypothesized that these dementia types, which are characterized by executive dysfunction, might derive particular benefits from cholinesterase inhibitors such as rivastigmine that inhibit BuChE in addition to AChE.