Parietal-hippocampal repetitive transcranial magnetic stimulation (rTMS) improves cognitive function in Alzheimer's disease (AD), however, the underlying therapeutic mechanism has not been elucidated. A double-blind, randomized, sham-controlled parietal-hippocampal rTMS trial (five sessions/week for a total of 10 sessions) of mild-to-moderate AD patients was conducted in the study. High-frequency rTMS was applied to a subject-specific left lateral parietal region with the highest functional connectivity with the hippocampus based on resting-state fMRI. A multimodal MRI scan and a complete neuropsychological battery of tests were conducted at baseline, immediately after the intervention and 12-week follow-up after the rTMS treatment. Compared to sham treatment (n = 27), patients undergoing active rTMS treatment (n = 29) showed higher Mini Mental State Examination (MMSE) score and dynamic functional connectivity (dFC) magnitude of the default mode network (DMN) after two weeks of rTMS treatment, but not at 12-week follow-up. A significant positive correlation was observed between changes in MMSE and changes in the dFC magnitude of DMN in patients who underwent active-rTMS treatment, but not in those who received sham-rTMS treatment. The findings of the current study indicate that fMRI-guided rTMS treatment improves cognitive function of AD patients in the short term, and DMN functional connectivity contributes to therapeutic effectiveness of rTMS.
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