Cognitive Improvement is Correlated with Increased Dynamic Functional Connectivity of Default Mode Network by Personalized rTMS in Alzheimer's Disease

Background Repetitive transcranial magnetic stimulation (rTMS) is thought to be a promising therapeutic approach for Alzheimer's disease patients. Methods In the present report, a double-blind, randomized, sham-controlled rTMS trial was conducted in mild-to-moderate Alzheimer's disease patients. High-frequency rTMS was delivered to a subject-specific left lateral parietal region that demonstrated highest functional connectivity with the hippocampus using resting-state fMRI. The Mini Mental State Examination (MMSE) and Philadelphia Verbal Learning Test (PVLT) were used to evaluate patients’ cognitive functions. Results Patients receiving active rTMS treatment (n = 31) showed a significant increase in the MMSE, PVLT-Immediate recall, and PVLT-Short Delay recall scores after two weeks of rTMS treatment, whereas patients who received sham rTMS (n = 27) did not show significant changes in these measures. Dynamic functional connectivity (dFC) magnitude of the default mode network (DMN) in the active-rTMS group showed a significant increase after two weeks of rTMS treatment, and no significant changes were found in the sham-rTMS group. There was a significantly positive correlation between changes of the MMSE and changes of the dFC magnitude of DMN in the active-rTMS group, but not the sham-rTMS group. Conclusions Our findings are novel in demonstrating the feasibility and effectiveness of the fMRI-guided rTMS treatment in Alzheimer's disease patients, and DMN might play a vital role in therapeutic effectiveness of rTMS in Alzheimer’s disease. Trial registration: China National Medical Research Platform (http://114.255.48.20/login, No:MR-33-20-004217), retrospectively registered 2020-12-23.