Department of Neurology, School of Medicine, Istanbul Health and Technology University, 34093 Istanbul, Turkey.
Parkinson's Disease and Movement Disorders Unit, Neurology Clinic, Sisli Kolan International Hospital, 34384 Istanbul, Turkey.
Medicina (Kaunas). 2023 Oct 1;59(10):1756. doi: 10.3390/medicina59101756.
Cognitive impairment in patients with Parkinson's disease (PD) is one of the commonest and most disabling non-motor manifestations during the course of the disease. The clinical spectrum of PD-related cognitive impairment includes subjective cognitive decline (SCD), mild cognitive impairment (MCI) and PD dementia (PDD). As the disease progresses, cognitive decline creates a significant burden for the family members and/or caregivers of patients with PD, and has a great impact on quality of life. Current pharmacological treatments have demonstrated partial efficacy and failed to halt disease progression, and novel, effective, and safe therapeutic strategies are required. Accumulating preclinical and clinical evidence shows that several agents may provide beneficial effects on patients with PD and cognitive impairment, including ceftriaxone, ambroxol, intranasal insulin, nilotinib, atomoxetine, mevidalen, blarcamesine, prasinezumab, SYN120, ENT-01, NYX-458, GRF6021, fosgonimeton, INT-777, Neuropeptide S, silibinin, osmotin, cordycepin, huperzine A, fibroblast growth factor 21, Poloxamer 188, ginsenoside Rb1, thioredoxin-1, tangeretin, istradefylline and Eugenia uniflora. Potential underlying mechanisms include the inhibition of a-synuclein aggregation, the improvement of mitochondrial function, the regulation of synaptic plasticity, an impact on the gut-brain axis, the modulation of neuroinflammation and the upregulation of neurotrophic factors, as well as cholinergic, dopaminergic, serotoninergic and norepinephrine neurotransmission. In this updated overview, we aim to cover the clinical aspects of the spectrum of PD-related cognitive impairment and discuss recent evidence on emerging treatment approaches that are under investigation at a preclinical and clinical level. Finally, we aim to provide additional insights and propose new ideas for investigation that may be feasible and effective for the spectrum of PD-related cognitive impairment.
帕金森病（PD）患者的认知障碍是疾病过程中最常见和最致残的非运动症状之一。PD 相关认知障碍的临床谱包括主观认知下降（SCD）、轻度认知障碍（MCI）和 PD 痴呆（PDD）。随着疾病的进展，认知能力下降给 PD 患者的家属和/或照顾者带来了巨大的负担，并对生活质量产生了重大影响。目前的药物治疗已显示出部分疗效，但未能阻止疾病进展，因此需要新的、有效和安全的治疗策略。越来越多的临床前和临床证据表明，几种药物可能对 PD 伴认知障碍患者有有益的影响，包括头孢曲松、氨溴索、鼻内胰岛素、尼洛替尼、托莫西汀、美维仑嗪、布拉克梅辛、普拉斯单抗、SYN120、ENT-01、NYX-458、GRF6021、福司可林、INT-777、神经肽 S、水飞蓟宾、ossmotin、虫草素、石杉碱甲、成纤维细胞生长因子 21、泊洛沙姆 188、人参皂苷 Rb1、硫氧还蛋白-1、橙皮素、异丁司特、尤金尼亚 uniflora。潜在的潜在机制包括抑制 a-突触核蛋白聚集、改善线粒体功能、调节突触可塑性、影响肠道-大脑轴、调节神经炎症和上调神经营养因子，以及胆碱能、多巴胺能、5-羟色胺能和去甲肾上腺素能神经递质。在本次更新的综述中，我们旨在涵盖 PD 相关认知障碍谱的临床方面，并讨论新兴治疗方法的最新证据，这些方法正在临床前和临床水平进行研究。最后，我们旨在为 PD 相关认知障碍谱提供额外的见解，并提出新的研究思路，这些思路可能对 PD 相关认知障碍谱是可行和有效的。
