ABSTRACT

Background

Perseverations in speech production tasks represent a pervasive symptom of chronic aphasia. Semantic perseverations (SPs) are defined as repetitive and unconscious production of specific linguistic forms previously produced, heard, or seen which share semantic relatedness with the target word. Neurochemically, SPs have been attributed to weakened activation of the target word due to the depletion of neurotransmitter systems (acetylcholine and dopamine) occurring in the context of activation of semantic competitors.

Aims

The present pilot study seeks to evaluate the effectiveness of a cholinergic enhancing drug combined with speech language therapy in reducing SPs and other non-perseverative semantic errors in a person with chronic post-stroke aphasia.

Methods & Procedures

Combined therapy of the cholinesterase inhibitor donepezil and conventional speech-language therapy (SLT) (2 hours/week) over 16 weeks was administered to a woman with chronic fluent post-stroke aphasia showing high rate of semantic errors. Aphasia and SPs assessments were performed at four different time-points across the study: at baseline, after donepezil 5 mg, donepezil 10 mg, and after 4-weeks of washout. The changes induced by the treatments on the occurrence of SPs and semantic paraphasias during a picture naming task were evaluated. By using a specific statistical methodology, we performed a fine-grained analysis of the frequency of SPs and their temporal course at the different time-points to dissect changes induced by the treatment.

Results

At baseline, there were significantly more SPs than expected by a random distribution, whereas a marked reduction of these errors was found in the three following evaluations. A significant reduction in aphasia severity was also found with high donepezil doses and this improvement maintained after a 4-week washout period. Everyday communication improved with low doses of donepezil.

Conclusion

Our findings suggest that decreased activity of the cholinergic system may exert a permissive role for the production of SPs and highlight the importance of combining cholinergic agents with speech-language therapy to reduce SPs in aphasia at the time that other language deficits are also improved.

中文翻译：

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控制过去、拥有现在和未来：胆碱能调节降低中风后失语症患者的语义持久性

摘要

背景

对语言产生任务的坚持是慢性失语症的普遍症状。语义保持（SPs）被定义为重复和无意识地产生先前产生、听到或看到的特定语言形式，这些形式与目标词具有语义相关性。在神经化学上，SP 归因于在语义竞争者激活的情况下神经递质系统（乙酰胆碱和多巴胺）的消耗导致目标词的激活减弱。

目标

本试验性研究旨在评估胆碱能增强药物与语言治疗相结合在减少慢性卒中后失语症患者的 SP 和其他非持续性语义错误方面的有效性。

方法和程序

胆碱酯酶抑制剂多奈哌齐和常规语言治疗 (SLT) (2 小时/周) 的联合治疗超过 16 周，对一名表现出高语义错误率的慢性流利中风后失语症女性进行了治疗。失语症和 SPs 评估在整个研究的四个不同时间点进行：基线时、多奈哌齐 5 mg 后、多奈哌齐 10 mg 后和 4 周清除后。评估了在图片命名任务期间治疗对 SP 和语义失语的发生所引起的变化。通过使用特定的统计方法，我们对 SP 的频率及其在不同时间点的时间过程进行了细粒度分析，以剖析治疗引起的变化。

结果

在基线时，随机分布的 SP 明显多于预期，而在以下三个评估中发现这些错误显着减少。还发现高剂量多奈哌齐可显着降低失语症的严重程度，并且这种改善在 4 周的清除期后得以维持。低剂量的多奈哌齐改善了日常沟通。

结论

我们的研究结果表明，胆碱能系统活性的降低可能对 SPs 的产生起到了允许的作用，并强调了在其他语言缺陷也得到改善的同时，将胆碱能药物与语言治疗相结合以减少失语症中 SPs 的重要性。