Effects of non-invasive brain stimulation combined with cognitive training on cognitive functions in older people with mild cognitive impairment: a systematic review with meta-analysis

Population aging is accelerating globally, increasing the prevalence of cognitive decline. Mild cognitive impairment (MCI) represents a transitional state between normal aging and dementia, affecting 15–24% of older adults and carrying elevated risk of progression. Effective, scalable interventions are needed to preserve cognitive function and delay decline. Prior work supports physical activity and cognitive stimulation for MCI, and recent technology-based strategies such as non-invasive brain stimulation (NIBS) can modulate cortical excitability and neural networks. Combining NIBS with cognitive training may enhance memory, attention, and executive functions. This study asks whether NIBS plus cognitive training improves cognitive outcomes in older people with MCI and synthesizes the evidence via systematic review and meta-analysis.

Background literature indicates that NIBS modalities (e.g., tDCS, rTMS, low-intensity ultrasound) can modulate cortical excitability and behavior. Studies suggest that NIBS alone and, more notably, NIBS combined with functional activities (e.g., cognitive tasks, physical activity) can enhance cognitive performance in older adults and those with MCI. Reported benefits span memory, attention, verbal fluency, and global cognition, though effects can be task- and domain-specific. The rationale for combining NIBS with cognitive training is to pair neuromodulatory plasticity with task-driven network activation for greater, clinically replicable gains.

Design: Systematic review and meta-analysis following Cochrane and PRISMA guidance; protocol registered in PROSPERO (CRD42024563219). Eligibility (PICOS): Population—older adults (mean age ≥60) with MCI; Intervention—NIBS combined with cognitive training for ≥4 weeks; Comparators—active or sham/inactive controls; Outcomes—at least one cognitive assessment; Study design—randomized controlled trials with pre- and post-assessments; Level of evidence targeted: 1a. Exclusions: non-RCTs, case studies, protocols, reviews, abstracts, studies without baseline or control data, or with non-MCI primary pathology or mean age <60. Search: Medline/PubMed, Scopus, Cochrane Library, Web of Science (core), EBSCOhost, CINAHL, ProQuest to May 2025 using MeSH and free-text terms for NIBS, cognition, aging, and MCI (detailed Boolean string provided). Study selection: Two independent reviewers screened titles/abstracts and full texts; disagreements resolved by consensus; PRISMA flow documented. Data extraction: Standardized Excel form captured authors, country, design, sample, group allocation, age, intervention/control details, training volume (frequency, duration, intensity), NIBS type/dose, cognitive assessments, and outcomes; performed independently by two reviewers with third-party oversight. Quality appraisal: Oxford Centre for Evidence-Based Medicine levels; risk of bias assessed via Cochrane RoB 2 by two reviewers with adjudication; certainty of evidence graded via GRADE (downgrading for bias, inconsistency, imprecision, indirectness, publication bias). Meta-analysis: Random-effects model (DerSimonian–Laird) using standardized mean differences (SMDs) and mean differences; significance threshold p < 0.05; pooling performed when ≥3 studies per outcome. Heterogeneity assessed with Q and I² (low <25%, moderate 25–50%, high >50%). Publication bias assessed via Egger’s regression.

- Included studies: 10 RCTs; total sample n = 722 (71.4% female), mean age 69.5 years (range across studies). Interventions included tDCS + cognitive training, rTMS, and combined programs (e.g., Tai Chi or walking paired with tDCS). Typical tDCS doses: 1–2 mA; durations 4–12 weeks; sessions 20–60 min, 3–5 times/week. - Risk of bias: 3 studies low risk across all domains; 7 with some concerns; none high risk. Overall moderate RoB. - Meta-analytic effects: • MoCA (5 studies; n = 277): ES = 0.52 (95% CI 0.34 to 1.17), p = 0.05; I² = 76.6%; Egger’s p = 0.00. • TMT-A (4 studies; n = 294): ES = 0.54 (95% CI 0.003 to 1.08), p = 0.04; I² = 76.6%; Egger’s p = 0.00. • TMT-B (5 studies; n = 328): ES = 0.05 (95% CI –0.35 to 0.45), p = 0.80; I² = 65.6%; Egger’s p = 0.02. - Interpretation: Moderate improvements in processing speed/attention (TMT-A) and indications of improved global cognition (MoCA), with no significant effect on cognitive flexibility/task-switching (TMT-B). Heterogeneity was high, and small-study effects/publication bias were suggested by Egger’s tests. - Adherence and safety: Mean adherence 87.7%; no adverse effects reported.

The review addressed whether combining NIBS with cognitive training enhances cognition in older adults with MCI. Results indicate domain-specific benefits: moderate gains in attention and processing speed (TMT-A) and signals of improvement in global cognition (MoCA), while effects on more complex executive control (TMT-B) were not significant. These findings align with neurophysiological mechanisms whereby NIBS modulates cortical excitability and network plasticity, potentially augmenting training-induced improvements in attentional and working memory systems. However, high heterogeneity, moderate risk of bias, and potential publication bias temper confidence. The results support NIBS as a promising adjunct to cognitive training, warranting refined protocols, targeted outcome selection, and larger, longer RCTs to establish durability and generalizability.

Combining non-invasive brain stimulation with cognitive training yields beneficial effects on specific cognitive domains in older people with MCI, particularly processing speed and attention (TMT-A) and potentially global cognition (MoCA). No significant improvements were detected for TMT-B. Given heterogeneity and moderate certainty of evidence, further high-quality, adequately powered RCTs with standardized protocols and longer follow-up are needed to confirm efficacy, clarify domain specificity, and guide clinical implementation.

- Small number of included trials limits statistical power. - Substantial heterogeneity in NIBS modalities, electrode targets, training tasks, intensity, and duration complicates comparisons. - Evidence certainty rated low to moderate due to methodological concerns and short follow-up (≤3 months). - Generalizability limited by geographic concentration and sample imbalances. - Potential publication bias (Egger’s tests significant for several outcomes). - High equipment costs and requirement for specialized training may hinder broad implementation. - Biological variability (e.g., cranial anatomy) may influence stimulation efficacy.