Institute of Clinical Neurobiology, Alberichgasse 5/13, 1150, Vienna, Austria.
J Neural Transm (Vienna). 2022 Aug;129(8):977-999. doi: 10.1007/s00702-022-02522-4. Epub 2022 Jun 20.
Cognitive impairment is one of the most salient non-motor symptoms of Parkinson disease (PD) that poses a significant burden on the patients and carers as well as being a risk factor for early mortality. People with PD show a wide spectrum of cognitive dysfunctions ranging from subjective cognitive decline and mild cognitive impairment (MCI) to frank dementia. The mean frequency of PD with MCI (PD-MCI) is 25.8% and the pooled dementia frequency is 26.3% increasing up to 83% 20 years after diagnosis. A better understanding of the underlying pathological processes will aid in directing disease-specific treatment. Modern neuroimaging studies revealed considerable changes in gray and white matter in PD patients with cognitive impairment, cortical atrophy, hypometabolism, dopamine/cholinergic or other neurotransmitter dysfunction and increased amyloid burden, but multiple mechanism are likely involved. Combined analysis of imaging and fluid markers is the most promising method for identifying PD-MCI and Parkinson disease dementia (PDD). Morphological substrates are a combination of Lewy- and Alzheimer-associated and other concomitant pathologies with aggregation of α-synuclein, amyloid, tau and other pathological proteins in cortical and subcortical regions causing destruction of essential neuronal networks. Significant pathological heterogeneity within PD-MCI reflects deficits in various cognitive domains. This review highlights the essential neuroimaging data and neuropathological changes in PD with cognitive impairment, the amount and topographical distribution of pathological protein aggregates and their pathophysiological relevance. Large-scale clinicopathological correlative studies are warranted to further elucidate the exact neuropathological correlates of cognitive impairment in PD and related synucleinopathies as a basis for early diagnosis and future disease-modifying therapies.
认知障碍是帕金森病（PD）最显著的非运动症状之一，它给患者和照护者带来了巨大负担，也是导致早期死亡的一个风险因素。PD 患者表现出广泛的认知功能障碍，从主观认知下降和轻度认知障碍（MCI）到明显痴呆。PD-MCI 的平均频率为 25.8%，合并痴呆的频率为 26.3%，在诊断后 20 年增加到 83%。更好地了解潜在的病理过程将有助于指导针对特定疾病的治疗。现代神经影像学研究显示，认知障碍 PD 患者的灰质和白质、皮质萎缩、代谢低下、多巴胺/胆碱能或其他神经递质功能障碍以及淀粉样蛋白负荷增加都有相当大的变化，但可能涉及多种机制。联合影像学和液体标志物分析是识别 PD-MCI 和帕金森病痴呆（PDD）的最有前途的方法。形态学底物是路易体和阿尔茨海默病相关以及其他共存病理学的结合，在皮质和皮质下区域聚集α-突触核蛋白、淀粉样蛋白、tau 和其他病理蛋白，导致关键神经元网络的破坏。PD-MCI 内的显著病理异质性反映了各种认知领域的缺陷。这篇综述强调了 PD 认知障碍的基本神经影像学数据和神经病理学变化、病理蛋白聚集体的数量和拓扑分布及其与生理病理的相关性。需要进行大规模的临床病理相关性研究，以进一步阐明 PD 认知障碍和相关突触核蛋白病的确切神经病理学相关性，为早期诊断和未来的疾病修饰治疗提供基础。
