Fallon Sean James, Plant Olivia, Tabi Younes A, Manohar Sanjay G, Husain Masud
Department of Experimental Psychology, University of Oxford, Oxford OX2 6GG, UK.
School of Psychology, University of Plymouth, Plymouth PL4 8AA, UK.
Brain Commun. 2023 Jul 27;5(4):fcad207. doi: 10.1093/braincomms/fcad207. eCollection 2023.
Cholinesterase inhibitors are frequently used to treat cognitive symptoms in Lewy body dementias (Parkinson's disease dementia and dementia with Lewy bodies). However, the selectivity of their effects remains unclear. In a novel rivastigmine withdrawal design, Parkinson's disease dementia and dementia with Lewy bodies patients were tested twice: once when taking rivastigmine as usual and once when they had missed one dose. In each session, they performed a suite of tasks (sustained attention, simple short-term recall, distractor resistance and manipulating the focus of attention) that allowed us to investigate the cognitive mechanisms through which rivastigmine affects attentional control. Consistent with previous literature, rivastigmine withdrawal significantly impaired attentional efficacy (quicker response latencies without a change in accuracy). However, it had no effects on cognitive control as assessed by the ability to withhold a response (inhibitory control). Worse short-term memory performance was also observed when patients were OFF rivastigmine, but these effects were delay and load independent, likely due to impaired visual attention. In contrast to previous studies that have examined the effects of dopamine withdrawal, cognitively complex tasks requiring control over the contents of working memory (ignoring, updating or shifting the focus of attention) were not significantly impaired by rivastigmine withdrawal. Cumulatively, these data support that the conclusion that cholinesterase inhibition has relatively specific and circumscribed-rather than global-effects on attention that may also affect performance on simple short-term memory tasks, but not when cognitive control over working memory is required. The results also indicate that the withdrawal of a single dose of rivastigmine is sufficient to reveal these impairments, demonstrating that cholinergic withdrawal can be an informative clinical as well as an investigative tool.
胆碱酯酶抑制剂常用于治疗路易体痴呆（帕金森病痴呆和路易体痴呆）的认知症状。然而，其作用的选择性仍不明确。在一项新的卡巴拉汀撤药设计中，对帕金森病痴呆和路易体痴呆患者进行了两次测试：一次是照常服用卡巴拉汀时，一次是漏服一剂时。在每个阶段，他们执行了一系列任务（持续注意力、简单短期记忆、抗干扰能力和注意力焦点控制），这使我们能够研究卡巴拉汀影响注意力控制的认知机制。与先前的文献一致，停用卡巴拉汀显著损害了注意力效能（反应潜伏期加快，准确性不变）。然而，就抑制反应能力（抑制控制）评估而言，它对认知控制没有影响。在停用卡巴拉汀时还观察到短期记忆表现更差，但这些影响与延迟和负荷无关，可能是由于视觉注意力受损。与先前研究多巴胺撤药影响的研究不同，需要控制工作记忆内容（忽略、更新或转移注意力焦点）的认知复杂任务并未因停用卡巴拉汀而受到显著损害。总体而言，这些数据支持以下结论：胆碱酯酶抑制对注意力具有相对特定和有限的而非全局性的影响，这也可能影响简单短期记忆任务的表现，但在需要对工作记忆进行认知控制时则不然。结果还表明，单次停用卡巴拉汀足以揭示这些损害，表明胆碱能撤药可以是一种有用的临床及研究工具。
