The neurobiological basis of cognitive impairment in Parkinson's disease.
The neurobiological basis of cognitive impairment in Parkinson's disease.
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DOI：
10.1002/mds.25857
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发表时间：
2014-04-15
影响因子：
8.6
通讯作者：
Adler, Charles H.
中科院分区：
文献类型：
--
作者：
Halliday, Glenda M.;Leverenz, James B.;Schneider, Jay S.;Adler, Charles H.
最近对帕金森病合并痴呆(PD-D)的临床标准的正式化编撰了许多关于这一主题的研究，包括那些评估生物学相关性的研究。这些研究表明，PD-D的出现是在严重的多巴胺缺乏的背景下发生的，认知功能下降的主要病理驱动因素是α-突触核蛋白与阿尔茨海默病病理之间的协同作用。这些病理的存在与边缘和皮质投射的多巴胺、去甲肾上腺素、5-羟色胺和乙酰胆碱神经元的显著丢失有关，尽管这些关系的确切时间仍有待确定。遗传因素，如α-突触核蛋白基因的三倍体，导致PD-D风险明显增加，而其他因素，如Parkin突变，与PD-D风险降低相关。最近对伴有轻度认知障碍的帕金森病(PD-MCI)的临床标准的正规化只允许对其生物学和遗传学基础进行推测。动物模型的关键评估显示，随着时间的推移，长期低剂量MPTP治疗灵长类动物可重现PD-MCI，强化了PD-MCI的当前生物学概念，即在额纹状体通路中增加了多巴胺缺乏以及其他神经递质系统的参与。来自其他动物模型的数据支持多个递质参与帕金森病认知障碍。尽管多巴胺在帕金森病发病中的作用十分明显，但其他神经递质系统、神经退行性病变和遗传因素在帕金森病-MCI中的作用仍未完全阐明。
The recent formalization of clinical criteria for PD with dementia (PD-D) codifies many studies on this topic, including those assessing biological correlates. These studies show that the emergence of PD-D occurs on the background of severe dopamine deficits with the main pathological drivers of cognitive decline being a synergistic effect between α -synuclein and Alzheimer's disease pathology. The presence of these pathologies correlates with a marked loss of limbic and cortically projecting dopamine, noradrenaline, serotonin and acetylcholine neurons, although the exact timing of these relationships remains to be determined. Genetic factors, such as triplications in the α-synuclein gene, lead to a clear increased risk of PD-D, while others, such as parkin mutations, are associated with a reduced risk of PD-D. The very recent formalization of clinical criteria for PD with mild cognitive impairment (PD-MCI) allows only speculation on its biological and genetic bases. Critical assessment of animal models shows that chronic low dose MPTP treatment in primates recapitulates PD-MCI over time, enhancing the current biological concept of PD-MCI as having enhanced dopamine deficiency in frontostriatal pathways as well as involvement of other neurotransmitter systems. Data from other animal models support multiple transmitter involvement in cognitive impairment in PD. While dopamine dysfunction has been highlighted because of its obvious role in PD, the role of the other neurotransmitter systems, neurodegenerative pathologies and genetic factors in PD-MCI remain to be fully elucidated.
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影响因子：
9.9
作者：
Alcalay, R. N.;Caccappolo, E.;Marder, K.
通讯作者：
Marder, K.
影响因子：
168.9
作者：
Chartier-Harlin, MC;Kachergus, J;Destée, A
通讯作者：
Destée, A
影响因子：
4.1
作者：
Bedard, Catherine;Wallman, Marie-Josee;Parent, Martin
通讯作者：
Parent, Martin
DOI：
10.1080/13803390903521018
发表时间：
2010-01-01
影响因子：
2.2
作者：
Alcalay, Roy N.;Mejia-Santana, Helen;Caccappolo, Elise
通讯作者：
Caccappolo, Elise
影响因子：
12.7
作者：
Amador-Ortiz C;Ahmed Z;Zehr C;Dickson DW
通讯作者：
Dickson DW