Efficacy and Evidence Certainty of High‐Frequency rTMS for Cognitive Impairment Across Neuropsychiatric Disorders: An Umbrella Review
Lin‐ling Wu, Xin‐cheng Huang, Juan‐juan Bi, Pei‐yuan HeABSTRACT
Background
High‐frequency repetitive transcranial magnetic stimulation (HF‐rTMS) is a promising intervention for cognitive impairment across neuropsychiatric disorders. However, existing evidence remains fragmented within disease‐specific reviews, lacking cross‐disorder synthesis and rigorous evaluation of evidence certainty.
Objective
This umbrella review systematically evaluates the efficacy of HF‐rTMS on cognitive function across six neuropsychiatric disorders with sufficient meta‐analytic evidence on cognitive outcomes, including Alzheimer's disease, vascular cognitive impairment, Parkinson's disease, schizophrenia spectrum disorders, major depressive disorder, and attention‐deficit/hyperactivity disorder—and assesses the certainty of evidence.
Methods
We systematically searched CNKI, Cochrane Library, Embase, PubMed, and Web of Science from inception to March 1, 2026, for systematic reviews or meta‐analyses reporting cognitive outcomes. Re‐meta‐analyses were performed using a random‐effects model to calculate standardized mean differences (SMDs) with 95% confidence intervals (CIs). Study quality was appraised via AMSTAR‐2, and evidence certainty was graded using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. The corrected covered area (CCA) was calculated to quantify overlap of primary studies across reviews.
Results
Twenty‐nine meta‐analyses comprising 54 outcome indicators met the inclusion criteria. Pooled analysis indicated that HF‐rTMS significantly improved global cognitive function (SMD = 0.68, 95% CI: 0.53–0.83, p < 0.001), though with substantial heterogeneity ( I 2 = 88.5%). Subgroup analyses highlighted distinct disease‐specific effects: the most robust benefits were observed in Alzheimer's disease (SMD = 0.91) and vascular cognitive impairment (VCI) (SMD = 0.81). We found small‐to‐moderate effects in schizophrenia spectrum disorders (SSD) and Attention‐Deficit/Hyperactivity Disorder (ADHD), but no significant improvements for Parkinson's disease or major depressive disorder. Domain‐specific analyses showed that VCI patients benefited across attention, memory, and executive function, whereas SSD patients primarily improved in memory and executive domains. While sensitivity analyses and publication bias adjustments slightly attenuated effect sizes, the overall conclusions remained stable. Notably, the GRADE assessment revealed a paucity of high‐quality evidence (1.9%), with 40.7% of outcomes rated as very low quality, largely due to inconsistency (substantial unexplained heterogeneity, I 2 > 50%), risk of bias (methodological limitations including lack of protocol registration and inadequate assessment of primary study bias), and imprecision (wide confidence intervals crossing the null). Overlap across reviews was low (CCA = 4.08%).
Conclusion
HF‐rTMS appears to provide consistent cognitive benefits in Alzheimer's disease and VCI, whereas its efficacy in other neuropsychiatric disorders remains uncertain. Given the low certainty of evidence and substantial heterogeneity, findings should be interpreted with caution. Future large‐scale, multicenter randomized controlled trials with standardized protocols are needed to confirm efficacy and support clinical implementation.