Cani Ilaria, Grotteschi Nicola, Calandra-Buonaura Giovanna, Guarino Maria, Guaraldi Pietro, Giannini Giulia, Baldelli Luca, Donati Monia, Cortelli Pietro, Camerlingo Maria Domenica, Nonino Francesco, Sambati Luisa
U.O.C. Clinica Neurologica Rete Metropolitana (NeuroMet), IRCCS Istituto Delle Scienze Neurologiche di Bologna, Bologna, Italy.
Department of Biomedical and Neuromotor Sciences (DIBINEM), Alma Mater Studiorum Università di Bologna, Bologna, Italy.
BMJ Neurol Open. 2025 Aug 3;7(2):e001079. doi: 10.1136/bmjno-2025-001079. eCollection 2025.
Parkinson's disease (PD) is primarily characterised by parkinsonism due to nigro-striatal dopaminergic denervation. While therapeutic strategies have traditionally focused on compensating for dopaminergic deficit, growing evidence reveals an involvement of cholinergic and glutamatergic pathways in the pathogenesis of the motor and non-motor manifestations of the disease. The purpose of this review is to provide an overview of the efficacy of cholinesterase inhibitors (ChIs) and memantine (glutamate receptor antagonist) in patients affected by PD without dementia on motor (gait, balance) and non-motor (cognitive, behavioural, sleep and autonomic) symptoms usually poorly responsive to levodopa.
A systematic review of randomised controlled trials (RCTs) was conducted. The search was performed on PubMed, Cochrane Library and Embase databases for articles published between January 1996 and October 2024, using predefined inclusion and exclusion criteria. Risk of bias was assessed with the Cochrane Risk of Bias tool. Results are presented narratively.
12 RCTs were included in this review, with 10 (774 patients) focusing on ChIs and 2 (65 patients) on memantine. Some studies highlighted the beneficial effects of ChI on mild cognitive impairment and suggested potential improvements in apathy and gait disturbances. However, the findings regarding the impact of ChI and memantine on other non-motor symptoms were inconsistent.
Available RCTs suggest that ChIs may have a valuable role in managing cognitive impairment, apathy and gait disorders in PD patients without dementia. However, due to the lack of strong evidence, a cautious and individualised approach is advisable when considering these treatments.Cite Now.
帕金森病（PD）主要特征是由于黑质纹状体多巴胺能神经支配缺失导致的帕金森综合征。传统上治疗策略主要集中于补偿多巴胺能缺陷，但越来越多的证据表明胆碱能和谷氨酸能通路参与了该疾病运动和非运动表现的发病机制。本综述的目的是概述胆碱酯酶抑制剂（ChIs）和美金刚（谷氨酸受体拮抗剂）对无痴呆的帕金森病患者运动（步态、平衡）和非运动（认知、行为、睡眠和自主神经）症状的疗效，这些症状通常对左旋多巴反应不佳。
进行了一项随机对照试验（RCTs）的系统评价。使用预定义的纳入和排除标准，在PubMed、Cochrane图书馆和Embase数据库中检索1996年1月至2024年10月发表的文章。使用Cochrane偏倚风险工具评估偏倚风险。结果以叙述形式呈现。
本综述纳入了12项RCT，其中10项（774例患者）关注胆碱酯酶抑制剂，2项（65例患者）关注美金刚。一些研究强调了胆碱酯酶抑制剂对轻度认知障碍的有益作用，并提示可能改善淡漠和步态障碍。然而，关于胆碱酯酶抑制剂和美金刚对其他非运动症状影响的研究结果并不一致。
现有RCT表明，胆碱酯酶抑制剂在管理无痴呆的帕金森病患者的认知障碍、淡漠和步态障碍方面可能具有重要作用。然而，由于缺乏有力证据，在考虑这些治疗时，建议采取谨慎和个体化的方法。立即引用。
