The combined effect of six weeks of resistance training and Sudoku mental exercise on serum BDNF, IGF-1 levels, 
and working memory in university students

Arman, Sara; Shamsaei, Nabi; Abdi, Hadi

doi:10.22034/27.2.37

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Volume 27, Issue 2 (7-2025)

EBNESINA 2025, 27(2): 37-51

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The combined effect of six weeks of resistance training and Sudoku mental exercise on serum BDNF, IGF-1 levels, and working memory in university students

Sara Arman

, Nabi Shamsaei ^*

, Hadi Abdi

Department of Sports Physiology, Faculty of Humanities, Ilam University, Ilam, Iran , n.shamsaei@ilam.ac.ir

Keywords: Resistance training, Brain-Derived Neurotrophic Factor, Insulin-like growth factor-1, Memory

Full-Text [PDF 2013 kb] (75 Downloads) | Abstract (HTML) (197 Views)

Type of Study: Original | Subject: Military Medicine
Received: 2025/06/5 | Revised: 2025/09/29 | Accepted: 2025/07/26 | Published: 2025/07/27

Extended Abstract: (56 Views)

Introduction

Brain-derived neurotrophic factor (BDNF) is a key neuroplasticity factor that plays a critical role in learning and memory [5-7]. Similarly, insulin-like growth factor-1 (IGF-1) is an important mediator of nerve cell growth and survival [8]. Research indicates that both resistance training and cognitive activities can elevate the levels of these factors in the blood and brain. For years, intellectual games like chess and Sudoku have been recognized as effective tools for preventing dementia, promoting neurogenesis, and protecting neuronal health. These games engage multiple cognitive functions, enhance mental well-being, and play a crucial role in stimulating brain activity. Specifically, they contribute to strengthening working memory and verbal episodic memory. The cognitive benefits of intellectual games, including their role in boosting neurogenesis and cognitive performance, appear to be mediated by elevated levels of neurotrophic factors such as BDNF and IGF-1. Supporting this, Arazi et al. demonstrated that even a single session of chess significantly increased serum BDNF and IGF-1 levels in both elite and novice players [1].
However, the combined effects of these interventions on BDNF and IGF-1 levels, as well as their potential mechanisms for improving working memory, remain understudied. This study aimed to investigate the impact of six weeks of resistance training combined with Sudoku mental exercises on serum BDNF and IGF-1 levels and working memory in female students.

Methods

A total of 40 volunteers were randomly assigned to four groups (n=10 per group): resistance training alone, Sudoku training alone, combined training, and a non-intervention control group. The resistance training protocol was conducted over six weeks, with three sessions per week. For cognitive training, participants engaged in Sudoku exercises, with performance measured by improvements in puzzle-solving speed. Blood samples were collected under fasting conditions before the intervention (pre-test) and 48 hours after its completion (post-test). Serum was separated via centrifugation and stored at -70°C for subsequent analysis. Serum BDNF and IGF-1 levels were quantified using ELISA kits, while working memory was assessed using the N-Back test software. N-Back test software, developed in 2010 by Ferdowsi University of Mashhad and adapted for Iranian culture. This software, modeled after RoboMemo, assesses auditory, visual, and spatial memory through exercises involving numbers, letters, and shapes. The test features nine difficulty levels, which adjust automatically based on performance. The test consists of three steps: Back1 (matching the current stimulus to the previous one), Back2 (matching to the stimulus two steps back), and Back3 (matching to the stimulus three steps back). The test takes 10 minutes to complete, and the collected data includes the number of correct and incorrect responses, unanswered items, and average reaction time [20].
Descriptive statistics, including mean and standard deviation, were calculated. The Shapiro-Wilk test assessed data normality, while the Levene test evaluated homogeneity of variance between groups in both pre-test and post-test conditions. Within-group differences were analyzed using paired t-tests, and between-group differences were assessed via analysis of covariance (ANCOVA). Where ANCOVA results were significant, post-hoc Bonferroni tests were conducted to identify specific group differences at a significance level of p≤ 0.05. All statistical analyses were performed using SPSS software (version 22).

Results

For BDNF, a significant difference was observed between the exercise intervention groups and the control group (p < 0.001), indicating that resistance training, Sudoku, and their combination all influenced serum BDNF levels. In contrast, IGF-1 levels showed a significant difference only between the resistance training groups and the control group (p = 0.02) and between the combined group and the control (p < 0.001), with no significant effect from Sudoku alone (p = 0.13).
Regarding working memory, no significant difference was found between the resistance training group and the control (p = 0.47). However, the combined training group showed a significant improvement compared to the control (p < 0.001), while Sudoku alone did not reach statistical significance (p = 0.07).

Discussion and Conclusions

This study demonstrated that resistance training, Sudoku, and their combination significantly increased BDNF levels. While the physiological implications of these changes are not fully understood, their responsiveness to exercise is noteworthy. The rise in circulating BDNF may stem from exercise-induced upregulation of BDNF expression in the hippocampus, mediated by tyrosine kinase B receptor stimulation [23]. Additionally, mechanical stress and nerve damage from exercise could contribute to elevated BDNF levels [25]. These findings align with Castaño et al., who reported that combined strength and cognitive training synergistically boosted BDNF, possibly due to enhanced cerebral blood flow, neurogenesis, and synaptic strengthening [26].
Resistance training alone led to a non-significant increase in IGF-1 levels. Mechanistically, IGF-1 is primarily secreted by the liver, and exercise may modulate its expression. Elevated IGF-1 can cross the blood-brain barrier, promoting hippocampal BDNF expression and neurogenesis. One proposed mechanism involves growth hormone release during resistance training, which stimulates IGF-1 production via liver receptors [32].
Interestingly, Sudoku alone did not significantly affect IGF-1 levels, suggesting that cognitive stimuli may not independently alter this growth factor. However, the combination of resistance training and Sudoku yielded a significant IGF-1 increase, hinting at a synergistic effect. Similarly, the combined intervention improved working memory, supporting the notion that simultaneous physical and cognitive activities may activate complementary neurophysiological pathways. This aligns with the "facilitating effect" of exercise (neural activation, BDNF release) and the "guiding effect" of cognitive tasks (synapse formation) [26].
In summary, resistance training combined with Sudoku positively influenced BDNF, IGF-1, and working memory in female students at Ilam University. These findings underscore the importance of integrating physical and mental exercise programs into university health initiatives to promote student well-being.

Ethical Considerations

This study adhered to the ethical guidelines of the National Ethics Committee at Ilam University (code: IR.ILAM.REC.1403.015).

Funding

There is no funding support.

Authors’ Contribution

The first author contributed to project implementation and data collection, while the second author was involved in study design, initial research, and manuscript writing. The third author participated in study design, data analysis, and interpretation. All authors contributed equally to the conceptualization and writing of the article. Each author reviewed and approved the final manuscript, agreeing on all aspects of the work.

Conflict of Interest

Authors declared no conflict of interest.

Acknowledgments

This article is derived from Ms. Sara Arman’s master’s thesis. We extend our gratitude to the professors, instructors, and students who contributed to this research.

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Arman S, Shamsaei N, Abdi H. The combined effect of six weeks of resistance training and Sudoku mental exercise on serum BDNF, IGF-1 levels, and working memory in university students. EBNESINA 2025; 27 (2) :37-51
URL: http://ebnesina.ajaums.ac.ir/article-1-1403-en.html

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