2363a4c864accaf576e0a4dbe6facb31 321346.pdf cfd0180972d303ca494d087dbc6889379cc8b3d6 321346.pdf 0276f7333bf637ef0200318a421d97f80703d6408df339ca0094003e681f4d1d 321346.pdf Title: Effects of Mindfulness and Exercise on Growth Factors, Inflammation, and Stress Markers in Chronic Stroke: The MindFit Project Randomized Clinical Trial Subject: 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: stroke; mindfulness; physical exercise; computerized cognitive training; neuroplasticity; growth factors; inflammation; stress Author: Adrià Bermudo-Gallaguet, Mar Ariza, Daniela Agudelo, Neus Camins-Vila, Maria Boldó, Sarah Peters, Angelika Katarzyna Sawicka, Rosalia Dacosta-Aguayo, Juan José Soriano-Raya, Marc Via, Imma C. Clemente, Alberto García-Molina, Maria José Durà Mata, Pere Torán-Monserrat, Kirk I. Erickson and Maria Mataró Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Wed Apr 9 12:34:47 2025 CEST ModDate: Wed Apr 9 12:50:19 2025 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 28 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1348208 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- WNWTFR+VnURWPalladioL-Bold Type 1 Custom yes yes yes 10 0 LWZMTU+VnURWPalladioL Type 1 Custom yes yes yes 16 0 TQGNSO+URWPalladioL-Roma Type 1 Custom yes yes yes 21 0 IWOMVT+URWPalladioL-Bold Type 1 Custom yes yes yes 27 0 BRNODA+URWPalladioL-Ital Type 1 Custom yes yes yes 32 0 WSLXGC+CMSY10 Type 1 Builtin yes yes yes 37 0 CKBPVA+EURM10 Type 1 Builtin yes yes yes 81 0 FNTSBS+PalatinoLinotype-Bold CID TrueType Identity-H yes yes yes 97 0 FNTSBS+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 103 0 FNTSBS+PalatinoLinotype-Italic CID TrueType Identity-H yes yes yes 109 0 FNTSBS+PalatinoLinotype-Bold CID TrueType Identity-H yes yes yes 147 0 FNTSBS+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 153 0 FNTSBS+PalatinoLinotype-Italic CID TrueType Identity-H yes yes yes 159 0 LGCQJJ+URWPalladioL-BoldItal Type 1 Custom yes yes yes 278 0 LRMGWC+PazoMath-Italic Type 1 Builtin yes yes yes 286 0 KRSDCP+PazoMath-BoldItalic Type 1 Builtin yes yes yes 294 0 HYYHEA+CMBSY10 Type 1 Builtin yes yes yes 302 0 FNTSBS+PalatinoLinotype-Bold CID TrueType Identity-H yes yes yes 312 0 FNTSBS+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 318 0 FNTSBS+PalatinoLinotype-Italic CID TrueType Identity-H yes yes yes 324 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2026-02-12 04:20:29 CET RepresentationInformation: 321346.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2026-02-11 13:55:36 CET Size: 1348208 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 758 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Children: Item: Title: Design and Setting Destination: subsection.2.1 Item: Title: Recruitment Destination: subsection.2.2 Item: Title: Eligibility Criteria Destination: subsection.2.3 Item: Title: Randomization and Blinding Destination: subsection.2.4 Item: Title: Interventions Destination: subsection.2.5 Children: Item: Title: General Overview Destination: subsubsection.2.5.1 Item: Title: Mindfulness-Based Stress Reduction Destination: subsubsection.2.5.2 Item: Title: Physical Exercise Destination: subsubsection.2.5.3 Item: Title: Computerized Cognitive Training Destination: subsubsection.2.5.4 Item: Title: Intervention Adherence and Safety Destination: subsection.2.6 Item: Title: Assessments and Outcome Measures Destination: subsection.2.7 Children: Item: Title: Baseline Measures Destination: subsubsection.2.7.1 Item: Title: Biomarker Outcomes Destination: subsubsection.2.7.2 Item: Title: Behavioral Outcomes Destination: subsubsection.2.7.3 Item: Title: Statistical Analysis Destination: subsection.2.8 Item: Title: Results Destination: section.3 Children: Item: Title: Participants Destination: subsection.3.1 Item: Title: Intervention Adherence and Safety Destination: subsection.3.2 Item: Title: Between-Group Changes in Biomarkers Destination: subsection.3.3 Item: Title: Within-Group Changes in Biomarkers Destination: subsection.3.4 Item: Title: Mediation and Correlational Analyses Destination: subsection.3.5 Item: Title: Discussion Destination: section.4 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: appendix.A. Info: Title: Effects of Mindfulness and Exercise on Growth Factors, Inflammation, and Stress Markers in Chronic Stroke: The MindFit Project Randomized Clinical Trial Author: Adrià Bermudo-Gallaguet, Mar Ariza, Daniela Agudelo, Neus Camins-Vila, Maria Boldó, Sarah Peters, Angelika Katarzyna Sawicka, Rosalia Dacosta-Aguayo, Juan José Soriano-Raya, Marc Via, Imma C. Clemente, Alberto García-Molina, Maria José Durà Mata, Pere Torán-Monserrat, Kirk I. Erickson and Maria Mataró Subject: 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. 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