Plasma cholinergic markers are associated with post-stroke walking recoveryrevisiting the STROKEWALK study

Sumonto Mitra^1*Taher Darreh-Shori¹Erik Lundstrom²Staffan Eriksson^3,4,5Tommy Cederholm⁶Maria Eriksdotter^1,7Birgit Vahlberg^3*

• ¹Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet, Huddinge, Sweden
• ²Department of Medical sciences, Neurology, Uppsala University, Uppsala, Sweden
• ³Department of Public Health and Caring Sciences, Geriatrics, Uppsala University,, Uppsala, Sweden
• ⁴Center for Clinical Research Sörmland, Uppsala University, Eskilstuna, Södermanland, Sweden
• ⁵Department of Community Medicine and Rehabilitation, Physiotherapy, Umeå University, Umea, 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

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). 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 three 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. 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. 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.