Accelerated intermittent theta burst stimulation combined with cognitive training modulates cortical plasticity and brain activation in patients with amnestic mild cognitive impairment

Amnestic mild cognitive impairment (aMCI) is the prodromal period of Alzheimer's disease without effective treatment. This research aimed to investigate the effects of accelerated intermittent theta burst stimulation (iTBS) combined with adaptive cognitive training (COG) on cognitive function in aMCI patients and explore the underlying neural mechanisms. Twenty-four aMCI patients participated in either the real (n = 12) or sham (n = 12) stimulation group. Both groups received adaptive COG, which comprised three sessions of real or sham iTBS delivered on the left dorsolateral prefrontal cortex (DLPFC) once a day for 14 days. The primary outcomes were the Montreal Cognitive Assessment (MoCA) and Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) scores. Secondary outcomes were changes in cortical plasticity measured by transcranial magnetic stimulation and brain activation monitored by functional near-infrared spectroscopy (fNIRS). Patients were evaluated before and after the intervention. Patients with aMCI who received iTBS combined with COG had a significant improvement in cognitive performance, as assessed by the ADAS-Cog and N-back. In the iTBS+COG group, cortical plasticity measured 30 min post-intervention correlated with ADAS-Cog changes (r = -0.59, p = 0.043). Furthermore, this plasticity was associated with 1-back activation (r = -0.58, p = 0.050), and 2-back activation correlated with ADAS-Cog changes (r = -0.59, p = 0.042). Accelerated iTBS targeted to the left DLPFC combined with adaptive COG promoted cognitive improvement in aMCI patients more effectively by modulating cortical plasticity and brain activation. Cortical plasticity and brain activation might be valuable measurements for understanding cognitive function (Chinese Clinical Trial Registry: ChiCTR2400087943).