Controlling the past, owning the present, and future: cholinergic modulation decreases semantic perseverations in a person with post-stroke aphasia

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.

KEYWORDS:

• Stroke
• aphasia
• aphasia therapy
• donepezil
• neuropharmacology
• perseverations

Acknowledgments

This study was conducted as an independent research grant funded by Pfizer and Eisai. The work was also supported in part by the Ministerio de Economía, Industria y Competitividad, Instituto de Salud Carlos III, Spain under Grant: PI16/01514. MB has been supported by funds from the European Social Fund (FEDER). DSM and ABC were fellows of the Cathedra ARPA of Aphasia, University of Malaga (Spain). LE has been funded by a PhD scholarship from the Spanish Ministry of Education, Culture, and Sport under the FPU program (FPU17/04136). DL-B was supported by I+D+i Project, Andalusia and European Union Funds (FEDER) (UMA18-FEDERJA-221). MT-P has been funded by a postdoctoral fellowship from the University of Malaga and by a postdoctoral fellowship under the program Plan Andaluz de Investigación, Desarrollo e Innovación (PAIDI 2020) (DOC_00421).

Disclosure statement

The authors declare that this study received funding from Pfizer/Eisai (Spain). The funders were not involved in the study design, collection, analysis, or interpretation of the data.