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. 2025 Apr 9;14(8):2580.
doi: 10.3390/jcm14082580.

Effects of Mindfulness and Exercise on Growth Factors, Inflammation, and Stress Markers in Chronic Stroke: The MindFit Project Randomized Clinical Trial

Affiliations

Effects of Mindfulness and Exercise on Growth Factors, Inflammation, and Stress Markers in Chronic Stroke: The MindFit Project Randomized Clinical Trial

Adrià Bermudo-Gallaguet et al. J Clin Med. .

Abstract

Background/Objectives: Stroke often leads to persistent cognitive and emotional impairments, which rehabilitation may mitigate. However, the biological mechanisms underlying such improvements remain unclear. This study investigated whether supplementing computerized cognitive training (CCT) with mindfulness-based stress reduction (MBSR) or physical exercise (PE) modulated biomarkers of neuroplasticity, inflammation, and stress in patients with chronic stroke compared to CCT alone. We also explored whether biomarker changes mediated or correlated with behavioral improvements. Methods: In a three-arm, single-blind, randomized controlled trial (NCT04759950), 141 patients with chronic stroke were randomized (1:1:1) to MBSR+CCT, PE+CCT, or CCT-only for 12 weeks. Plasma levels of brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), C-reactive protein (CRP), interleukin-6 (IL-6), and cortisol were measured at baseline and post-intervention. Cognitive, mental health, mindfulness, and fitness outcomes were also assessed. Between- and within-group changes were analyzed using ANCOVA and paired t-tests. Per-protocol and complete-case analyses were conducted. Results: Among the 109 participants with ≥80% adherence, the only significant between-group difference was for VEGF: it remained stable in the MBSR+CCT group but declined in PE+CCT and CCT-only. Within-group analyses showed significant decreases in cortisol in MBSR+CCT and PE+CCT, while IGF-1 levels declined across all groups. In contrast, BDNF, IL-6, and CRP did not show significant changes, and biomarker changes were not significantly associated with behavioral improvements. Complete-case analysis (n = 126) yielded similar findings. Conclusions: Our findings suggest that combining MBSR or PE with CCT may modulate certain biological processes relevant to stroke recovery. MBSR may help maintain VEGF levels, which could support vascular health, while MBSR and PE may contribute to lowering cortisol levels. However, since no clear association with behavioral improvements was found, further research is needed to determine the clinical relevance of these biomarker changes in stroke recovery.

Keywords: computerized cognitive training; growth factors; inflammation; mindfulness; neuroplasticity; physical exercise; stress; stroke.

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Conflict of interest statement

The authors declare no conflicts of interest. The funders had no role in the study’s design, data collection, analysis, and interpretation, manuscript writing, or decision to publish the results.

Figures

Figure 1
Figure 1
Mediation analysis of intervention effects on behavioral outcomes via biomarker changes. Panel (A): MBSR+CCT and PE+CCT are compared to the CCT-only group. Paths a1 and a2 represent the intervention effects on the biomarker, while path b captures the relationship between the biomarker change and the behavioral outcome. Paths c1’ and c2’ illustrate the direct effects of the interventions on the behavioral outcome, controlling for the mediator. Indirect effects are calculated as a1 × b and a2 × b. Panel (B): The reference group is changed to PE+CCT, comparing MBSR+CCT and CCT-only against PE+CCT. Path a2 remains consistent with Panel A but has an inverted sign, resulting in inverted indirect effects (a2 × b). Abbreviations: CCT, computerized cognitive training; MBSR, Mindfulness-Based Stress Reduction; PE, physical exercise.
Figure 2
Figure 2
Trial flow diagram. Abbreviations: CC-A, complete-case analysis; CCT, computerized cognitive training; MBSR, Mindfulness-Based Stress Reduction; PE, physical exercise; PP-A, per-protocol analysis.
Figure 3
Figure 3
Changes in blood biomarkers across intervention groups (per-protocol sample). Mean levels of biomarkers at baseline (white bars) and post-intervention (purple bars) are shown for the MBSR+CCT, PE+CCT, and CCT-only groups. Error bars represent 95% confidence intervals. Significant within-group changes, adjusted for multiple comparisons using the FDR correction, are marked as follows: * p < 0.05, ** p < 0.01. Abbreviations: CCT, computerized cognitive training; FDR, false discovery rate; MBSR, Mindfulness-Based Stress Reduction; PE, physical exercise.

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