Plasma cholinergic markers are associated with post-stroke walking recovery—revisiting the STROKEWALK study

But you gave us NOTHING ON HOW TO ASSIST IN GETTING PROPER BDNF LEVELS! Useless. I'd have you all fired!

 Plasma cholinergic markers are associated with post-stroke walking recovery—revisiting the STROKEWALK study

Sumonto Mitra1*†, Taher Darreh-Shori1, Erik Lundström2†, Staffan Eriksson3,4,5†, Tommy Cederholm6, Maria Eriksdotter1,7 and Birgit Vahlberg3*†

1Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet, Center for Alzheimer Research, Huddinge, Sweden

2Department of Medical Sciences, Neurology, Uppsala University, Uppsala, Sweden

3Department of Public Health and Caring Sciences, Geriatrics, Uppsala University, Uppsala, Sweden

4Centre for Clinical Research, Sörmland, Uppsala University, Eskilstuna, Sweden

5Department of Community Medicine and Rehabilitation, Physiotherapy, Umeå University, Umeå, Sweden

6Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden

7Theme Inflammation and Aging, Karolinska University Hospital, Huddinge, Sweden

Edited by

Haipeng Liu, Coventry University, United Kingdom

Reviewed by

Nazareno Paolocci, Johns Hopkins University, United States

Patricia Concepción García Suárez, University of Kansas, United States

Maria Luisa Garo, Mathsly Research, Italy

Abdur Raheem Khan, Integral University, India

*Correspondence

Birgit Vahlberg, birgit.vahlberg@pubcare.uu.se; Sumonto Mitra, Sumonto.mitra@ki.se

†ORCID

Sumonto Mitra, orcid.org/0000-0001-6381-5344

Erik Lundström, orcid.org/0000-0002-5313-9052

Staffan Eriksson, orcid.org/0000-0003-3572-8918

Birgit Vahlberg, orcid.org/0000-0002-1508-1435

Received 10 March 2025

Accepted 14 May 2025

Published 30 May 2025

Citation

Mitra S, Darreh-Shori T, Lundström E, Eriksson S, Cederholm T, Eriksdotter M and Vahlberg B (2025) Plasma cholinergic markers are associated with post-stroke walking recovery—revisiting the STROKEWALK study. Front. Neurol. 16:1568401. doi: 10.3389/fneur.2025.1568401

Introduction: Optimizing post-stroke rehabilitation strategies remains imperative for improving patient outcomes. Physical exercise, including outdoor walking, represents a promising intervention; however, its clinical efficacy, along with the utility of SMS-guided instructions to support adherence, requires further investigation. This study aims to elucidate the association of BDNF levels and cholinergic markers in the plasma of patients with previously reported post-stroke walking recovery (STROKEWALK study).

Methods: Post-stroke patients were randomly selected to receive SMS-guided exercise instructions (intervention group, n = 31) or not (control group, n = 31) at the time of stroke (baseline) and continued for the next 3 months. Plasma samples were collected at baseline (n = 28) and at 3-month follow-up (n = 28) and analyzed for Brain-Derived-Neurotrophic-Factor (BDNF) protein as a primary outcome. Secondary outcomes included enzyme activities of choline acetyltransferase (ChAT) and Butyrylcholinesterase (BChE), and the six-minute walking test (6MWT), which was assessed at the same time as the plasma sampling.

Results: A significant decline in BDNF was observed at 3 months in the total population (n = 56), primarily driven by the control group. Stratifying groups as intervention or control displayed no significant difference in BDNF protein levels, nor in ChAT or BChE activities at baseline or at 3-month follow-up, except for a significant correlation between BChE and Body-Mass Index (BMI). Patient stratification based on 6MWT performance displayed higher BDNF levels in the intervention group versus the control group, especially among females but not males. Females showed higher BChE than the males in the control group, but not in the intervention. Interestingly, the change in ChAT activity and cholinergic index (ChAT/BChE) from baseline to follow-up is significantly correlated with 6MWT performance.

Discussion: We conclude that SMS-guided exercise training improves post-stroke walking performance (6MWT) which attenuates the decline in BDNF levels. Cholinergic function correlates with improved walking performance and could be a useful marker to evaluate rehabilitation outcomes.(Why the indirect step? Just ask the patient if they recovered 100% walking! See how simple this can be?)

Keywords
brain-derived neurotrophic factor (BDNF); stroke; cholinergic index; exercise; rehabilitation