Efficacy of personalized acupuncture combined with accelerated deep transcranial magnetic stimulation in mild cognitive impairment: A randomized controlled trial

• First randomized trial integrating fMRI-guided personalized acupuncture with accelerated deep TMS for mild cognitive impairment • Synergistic cognitive enhancement surpassing single-modality or sham interventions • Mechanistic insights through correlated improvements in neuroelectrophysiological, metabolic, and neurotrophic markers • TCM-driven personalization reveals maximal efficacy in "Deficiency of Sea of Marrow" subtype • Favorable safety profile supporting clinical feasibility of the combined protocol This study evaluated the efficacy of combining personalized acupuncture with accelerated deep transcranial magnetic stimulation (adTMS) for mild cognitive impairment (MCI). In this randomized, double-blind, controlled trial, 120 MCI patients were assigned to a Combined group (personalized acupuncture + active adTMS), a Single Stimulation group (active adTMS + sham acupuncture), or a Placebo group (sham TMS + sham acupuncture). The primary outcome was the change in Montreal Cognitive Assessment (MoCA) score at 12 weeks. Secondary outcomes included P300 latency, magnetic resonance spectroscopy (MRS) NAA/Cr ratio, serum brain-derived neurotrophic factor (BDNF), C-reactive protein (CRP), interleukin-6 (IL-6), and the Modified Barthel Index (MBI). The Combined group showed a significantly greater improvement in MoCA scores (3.2 ± 1.3 points) compared to the Single Stimulation (1.9 ± 1.2 points; mean difference 1.3, 95% CI 0.4 to 2.2) and Placebo groups (1.1 ± 1.0 points; mean difference 2.1, 95% CI 1.2 to 3.0). The Combined group also demonstrated greater reductions in P300 latency and increases in NAA/Cr ratio and serum BDNF levels than the other groups. The combination of personalized acupuncture and adTMS significantly improves cognitive function in MCI patients, supported by positive changes in electrophysiological and metabolic markers. This integrative approach represents a promising non-pharmacological strategy for MCI. Trial registration: International Traditional Medicine Clinical Trials Registry (ITMCTR2025000652).