Department of Pathology, University of Washington School of Medicine, Seattle, WA 98104, USA.
Brain Pathol. 2010 May;20(3):660-71. doi: 10.1111/j.1750-3639.2009.00370.x.
Cognitive impairment, including dementia, is commonly seen in those afflicted with Parkinson disease (PD), particularly at advanced disease stages. Pathologically, PD with dementia (PD-D) is most often associated with the presence of cortical Lewy bodies, as is the closely related dementia with Lewy bodies (DLB). Both PD-D and DLB are also frequently complicated by the presence of neurofibrillary tangles and amyloid plaques, features most often attributed to Alzheimer disease. Biomarkers are urgently needed to differentiate among these disease processes and predict dementia in PD as well as monitor responses of patients to new therapies. A few clinical assessments, along with structural and functional neuroimaging, have been utilized in the last few years with some success in this area. Additionally, a number of other strategies have been employed to identify biochemical/molecular biomarkers associated with cognitive impairment and dementia in PD, e.g. targeted analysis of candidate proteins known to be important to PD pathogenesis and progression in cerebrospinal fluid or blood. Finally, interesting results are emerging from preliminary studies with unbiased and high throughput genomic, proteomic and metabolomic techniques. The current findings and perspectives of applying these strategies and techniques are reviewed in this article, together with potential areas of advancement.
认知障碍,包括痴呆,在帕金森病(PD)患者中很常见,尤其是在疾病晚期。从病理学上看,伴有痴呆的帕金森病(PD-D)最常与皮质路易体的存在有关,与密切相关的路易体痴呆(DLB)也是如此。PD-D 和 DLB 也经常伴有神经纤维缠结和淀粉样斑块的存在,这些特征通常归因于阿尔茨海默病。目前迫切需要生物标志物来区分这些疾病过程,并预测 PD 中的痴呆以及监测患者对新疗法的反应。在这方面,近年来已经使用了一些临床评估以及结构和功能神经影像学,取得了一定的成功。此外,还采用了许多其他策略来识别与 PD 认知障碍和痴呆相关的生化/分子生物标志物,例如在脑脊液或血液中对已知对 PD 发病机制和进展很重要的候选蛋白进行靶向分析。最后,使用无偏和高通量基因组、蛋白质组学和代谢组学技术的初步研究也出现了有趣的结果。本文综述了应用这些策略和技术的当前发现和观点,以及潜在的进展领域。