The effects of repetitive transcranial magnetic stimulation on executive functions in healthy and at-risk older adults: a systematic review and meta-analysis

Cognitive flexibility, inhibitory control, and working memory are core executive functions and early vulnerable cognitive domains across the continuum from healthy aging to mild cognitive impairment, highlighting the need for preventive interventions before substantial neurodegeneration occurs. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation technique inducing lasting changes in cortical excitability and network-level plasticity. Accordingly, this systematic review and meta-analysis examined the effects of rTMS, with or without behavioral training, on these core executive functions in healthy older adults and individuals at increased risk of dementia. Five electronic databases were searched for randomized controlled and crossover trials up to September 2025. Eligible studies involved rTMS in healthy older adults, individuals with subjective cognitive decline, or mild cognitive impairment aged ≥ 55 years. Effect sizes were calculated as Hedges’ g with 95% confidence intervals. Random-effects models used the DerSimonian–Laird estimator, whereas fixed-effect models were applied when heterogeneity was low. Methodological quality was assessed using the Physiotherapy Evidence Database scale. Seventeen studies involving 497 participants were included. Compared with sham conditions, rTMS showed small but statistically significant immediate effects on cognitive flexibility (Hedges’ g = 0.31, p = .049) and working memory (Hedges’ g = 0.30, p = .049), whereas no significant immediate effect was observed for inhibitory control. At follow-up, a significant effect was observed for cognitive flexibility (Hedges’ g = 0.33, p = .036). Subgroup analysis yielded a large effect estimate for high-frequency bilateral dorsolateral prefrontal cortex stimulation (DLPFC) on cognitive flexibility (Hedges’ g = 0.96, p = .001); however, this finding was based on only two studies. Available neuroimaging evidence provided preliminary indications of changes in frontoparietal and salience-network activity following high-frequency right or bilateral DLPFC stimulation. rTMS, with or without behavioral training, may modestly improve cognitive flexibility and working memory in healthy and at-risk older adults, with cognitive flexibility also showing a small follow-up effect. High-frequency bilateral DLPFC stimulation may represent a promising protocol for cognitive flexibility, although this subgroup finding requires prospective confirmation. Future studies should compare stimulation parameters, intervention approaches, and network-guided targeting strategies to determine optimal configurations for specific executive domains.

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Publication Details

Journal
Alzheimer s Research & Therapy
Published
2026-09-12
DOI
https://doi.org/10.1186/s13195-026-02186-2
Primary Topic
Transcranial Magnetic Stimulation Studies
Type
article
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article

The effects of repetitive transcranial magnetic stimulation on executive functions in healthy and at-risk older adults: a systematic review and meta-analysis

Jack Jiaqi ZHANG, Tenaw Gualu Melesse, Kenneth Nai Kuen Fong, Raymond Chung et al.
Alzheimer s Research & Therapy
Transcranial Magnetic Stimulation Studies
article

The effects of repetitive transcranial magnetic stimulation on executive functions in healthy and at-risk older adults: a systematic review and meta-analysis

Jack Jiaqi ZHANG, Tenaw Gualu Melesse, Kenneth Nai Kuen Fong, Raymond Chung, Hui-Chieh Ju, Hei Tong Pang
article en

Abstract

Cognitive flexibility, inhibitory control, and working memory are core executive functions and early vulnerable cognitive domains across the continuum from healthy aging to mild cognitive impairment, highlighting the need for preventive interventions before substantial neurodegeneration occurs. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation technique inducing lasting changes in cortical excitability and network-level plasticity. Accordingly, this systematic review and meta-analysis examined the effects of rTMS, with or without behavioral training, on these core executive functions in healthy older adults and individuals at increased risk of dementia. Five electronic databases were searched for randomized controlled and crossover trials up to September 2025. Eligible studies involved rTMS in healthy older adults, individuals with subjective cognitive decline, or mild cognitive impairment aged ≥ 55 years. Effect sizes were calculated as Hedges’ g with 95% confidence intervals. Random-effects models used the DerSimonian–Laird estimator, whereas fixed-effect models were applied when heterogeneity was low. Methodological quality was assessed using the Physiotherapy Evidence Database scale. Seventeen studies involving 497 participants were included. Compared with sham conditions, rTMS showed small but statistically significant immediate effects on cognitive flexibility (Hedges’ g = 0.31, p = .049) and working memory (Hedges’ g = 0.30, p = .049), whereas no significant immediate effect was observed for inhibitory control. At follow-up, a significant effect was observed for cognitive flexibility (Hedges’ g = 0.33, p = .036). Subgroup analysis yielded a large effect estimate for high-frequency bilateral dorsolateral prefrontal cortex stimulation (DLPFC) on cognitive flexibility (Hedges’ g = 0.96, p = .001); however, this finding was based on only two studies. Available neuroimaging evidence provided preliminary indications of changes in frontoparietal and salience-network activity following high-frequency right or bilateral DLPFC stimulation. rTMS, with or without behavioral training, may modestly improve cognitive flexibility and working memory in healthy and at-risk older adults, with cognitive flexibility also showing a small follow-up effect. High-frequency bilateral DLPFC stimulation may represent a promising protocol for cognitive flexibility, although this subgroup finding requires prospective confirmation. Future studies should compare stimulation parameters, intervention approaches, and network-guided targeting strategies to determine optimal configurations for specific executive domains.

Alzheimer s Research & Therapy
Hong Kong Polytechnic University (HK), National Taiwan University (TW)
Openalex Percentile: Top 13%
Transcranial Magnetic Stimulation Studies
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