Mayo Clinic School of Medicine, Mayo Clinic Movement Disorders Division, Scottsdale, AZ, USA.
Parkinsonism Relat Disord. 2014 Jan;20 Suppl 1:S39-43. doi: 10.1016/S1353-8020(13)70012-9.
Advancements in neuroscience have uncovered an amazing complexity of connectivity between nuclei sites and circuits within the brain. Moreover, clinical and neuropathological study has revealed diffuse involvement of the nervous system in Parkinson's disease associated with early and/or significant clinical symptoms. Behavior manifestations in Parkinson's disease include cognitive decline and unwanted positive behaviors such as hallucinations and impulse-control disorders. The pathophysiology of Parkinson's disease can be conceptualized at multiple levels that include: (1) Molecular pathogenesis, (2) Cellular/Tissue abnormalities, (3) Neurochemical changes, (4) Site and circuit dysfunction, and (5) Network dysfunction. Currently, there is only a vague correlation with genetic abnormalities that manifest worse Parkinson's disease behavior problems, but abnormalities in misfolded proteins such as α-synuclein and Aβ peptide that are increased in cortical and subcortical areas do correlate with worse behavior signs and symptoms. Both Lewy-type synucleinopathy and Alzheimer's disease pathologies, along with loss of synaptic integrity, seem to correlate with Parkinson's disease cognitive decline. Neurochemical changes of dopamine, acetylcholine, and other monoamines are associated. The frontostriate circuit is most commonly implicated in Parkinson's disease behavior. However, there is now beginning to be evidence that diffuse global network dysfunction is possibly the unifying pathophysiology from all of these level abnormalities.
神经科学的进步揭示了大脑核团之间以及脑内回路之间令人惊讶的复杂连接性。此外，临床和神经病理学研究揭示了帕金森病患者的神经系统弥漫性受累，与早期和/或显著的临床症状有关。帕金森病的行为表现包括认知能力下降和不想要的阳性行为，如幻觉和冲动控制障碍。帕金森病的病理生理学可以在多个层面上进行概念化，包括：（1）分子发病机制，（2）细胞/组织异常，（3）神经化学变化，（4）部位和回路功能障碍，以及（5）网络功能障碍。目前，只有与遗传异常的模糊相关性，这些异常表现出更严重的帕金森病行为问题，但异常折叠的蛋白质，如α-突触核蛋白和 Aβ肽，在皮质和皮质下区域增加，与更严重的行为迹象和症状相关。路易体型突触核蛋白病和阿尔茨海默病病理，以及突触完整性丧失，似乎与帕金森病认知能力下降有关。多巴胺、乙酰胆碱和其他单胺类神经递质的神经化学变化与之相关。额纹状体回路最常与帕金森病的行为有关。然而，现在开始有证据表明，弥漫性全网络功能障碍可能是所有这些水平异常的统一病理生理学。
