RESUMO
INTRODUCTION: Neuro-navigated repetitive transcranial magnetic stimulation (rTMS) is effective in alleviating cognitive deficits in Alzheimer's disease (AD). However, the strategy for target determination and the mechanisms for cognitive improvement remain unclear. METHODS: One hundred and thirteen elderly subjects were recruited in this study, including both cross-sectional (n = 79) and longitudinal experiments (the rTMS group: n = 24; the sham group: n = 10). The cross-sectional experiment explored the precise intervention target based on the cortical-hippocampal network. The longitudinal experiment investigated the clinical efficacy of neuro-navigated rTMS treatment over a four-week period and explored its underlying neural mechanism using seed-based and network-based analysis. Finally, we applied connectome-based predictive modeling to predict the rTMS response using these functional features at baseline. RESULTS: RTMS at a targeted site of the left angular gyrus (MNI: -45, -67, 38) significantly induced cognitive improvement in memory and language function (p < 0.001). The improved cognition correlated with the default mode network (DMN) subsystems. Furthermore, the connectivity patterns of DMN subsystems (r = 0.52, p = 0.01) or large-scale networks (r = 0.85, p = 0.001) at baseline significantly predicted the Δ language cognition after the rTMS treatment. The connectivity patterns of DMN subsystems (r = 0.47, p = 0.019) or large-scale networks (r = 0.80, p = 0.001) at baseline could predict the Δ memory cognition after the rTMS treatment. CONCLUSION: These findings suggest that neuro-navigated rTMS targeting the left angular gyrus could improve cognitive function in AD patients. Importantly, dynamic regulation of the intra- and inter-DMN at baseline may represent a potential predictor for favorable rTMS treatment response in patients with cognitive impairment.