Cognitive Effect of Repetitive Transcranial Magnetic Stimulation with Cognitive Training: Long-Term Mitigation Neurodegenerative Effects of Mild Alzheimer's Disease

Background: Despite several studies having reported on the cognitive effects of repetitive transcranial magnetic stimulation (rTMS) in Alzheimer's disease (AD), no studies, to date have addressed the long-term effects of rTMS with cognitive training (CT). This study was aimed to investigate the long-term effects of rTMS-CT in mild AD. Methods: Patients with mild AD (Mini-mental Status Examination [MMSE] score of 21-26), diagnosed based on the diagnostic and statistical manual of mental disorders-IV, were recruited and randomly allocated to two groups, treatment and sham, in a 2:1 ratio. We matched the acetylcholinesterase inhibitor (AChEI)-only group to the treatment group to comparing the long-term effect of rTMS-CT. Treatment group was treated for 6 weeks with high-frequency (10 Hz) rTMS-CT, whereas the other group received 6 weeks of the sham management. These groups underwent neuropsychological tests at baseline, immediately after rTMS-CT, and 6 weeks after the last rTMS-CT. Data of AChEI-only and treatment groups were analyzed changes of cognitive scores (MMSE, and clinical dementia rating-sum of boxes scales) over 3 years. Results: Among the 44 enrolled mild AD (mean age, 72.5 years; females, 36.4%), the rTMS-CT group (n = 30) showed improvement on the ADAS-Cog score for 12 weeks compared with the sham group (n = 14). The rTMS-CT group showed slower rates of neurodegeneration than those in the AChEI-only group (n = 60) during the 3 years of follow-up. Conclusions: Compared to the administration of AChEI only, the use of rTMS-CT might be a useful supplementary interventional strategy in mild AD for long-term mitigation of neurodegeneration.