Abstract

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 longterm 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.