Collins Lucy M, Williams-Gray Caroline H
John Van Geest Centre for Brain Repair, University of Cambridge , Cambridge , UK.
Front Psychiatry. 2016 May 20;7:89. doi: 10.3389/fpsyt.2016.00089. eCollection 2016.
Cognitive dysfunction is a common feature of Parkinson's disease (PD) with mild cognitive impairment affecting around a quarter of patients in the early stages of their disease, and approximately half developing dementia by 10 years from diagnosis. However, the pattern of cognitive impairments and their speed of evolution vary markedly between individuals. While some of this variability may relate to extrinsic factors and comorbidities, inherited genetic heterogeneity is also known to play an important role. A number of common genetic variants have been identified, which contribute to cognitive function in PD, including variants in catechol-O-methyltransferase, microtubule-associated protein tau, and apolipoprotein E. Furthermore, rarer mutations in glucocerebrosidase and α-synuclein and are strongly associated with dementia risk in PD. This review explores the functional impact of these variants on cognition in PD and discusses how such genotype-phenotype associations provide a window into the mechanistic basis of cognitive heterogeneity in this disorder. This has consequent implications for the development of much more targeted therapeutic strategies for cognitive symptoms in PD.
认知功能障碍是帕金森病（PD）的一个常见特征，轻度认知障碍影响约四分之一疾病早期的患者，并且从诊断起10年内约有一半患者会发展为痴呆。然而，认知障碍的模式及其演变速度在个体之间存在显著差异。虽然这种变异性部分可能与外在因素和合并症有关，但遗传异质性也起着重要作用。已经鉴定出一些常见的基因变异，它们对PD的认知功能有影响，包括儿茶酚-O-甲基转移酶、微管相关蛋白tau和载脂蛋白E的变异。此外，葡萄糖脑苷脂酶和α-突触核蛋白的罕见突变与PD的痴呆风险密切相关。本综述探讨了这些变异对PD认知的功能影响，并讨论了这种基因型-表型关联如何为该疾病认知异质性的机制基础提供一个窗口。这对开发更具针对性的PD认知症状治疗策略具有重要意义。
