Imagine trying different medications to treat a specific illness, but none of them work quite as well as you hoped. That’s the situation with Alzheimer’s dementia patients in Japan, where current medications have proven to be insufficient. However, a new approach called repetitive transcranial magnetic stimulation (rTMS) is being investigated. In this study, researchers conducted a clinical trial to evaluate the efficacy and safety of rTMS for Japanese patients with Alzheimer’s dementia. The trial involved 42 patients who were randomly assigned to receive either active rTMS or a sham treatment. Various cognitive and functional assessments were administered throughout the study. While no significant differences were found between the groups overall, further analysis suggested that active rTMS had a positive effect on participants with higher baseline cognitive scores. Interestingly, this effect diminished after 20 weeks of treatment. The study concluded that rTMS appears to be safe for Japanese AD patients, and future research should focus on its potential benefits in moderate-mild stage individuals. This fascinating article provides more details on the study and its findings.

BackgroundSeveral medications have been applied to Alzheimer’s dementia patients (AD) but their efficacies have been insufficient. The efficacy and safety of 4 weeks of repetitive transcranial magnetic stimulation (rTMS) in Japanese AD were evaluated in this exploratory clinical trial.MethodsForty-two patients, aged 60–93 years (average, 76.4 years), who were taking medication (> 6 months) and had Mini-Mental State Examination (MMSE) scores ≤ 25 and Clinical Dementia Rating Scale scores (CDR-J) of 1 or 2, were enrolled in this single-center, prospective, randomized, three-arm study [i.e., 120% resting motor threshold (120% RMT), 90% RMT for the bilateral dorsolateral prefrontal cortex, and Sham]. Alzheimer’s Disease Assessment Scale-Japanese Cognitive (ADAS-J cog), Montreal Cognitive Assessment (MoCA-J), Clinical Global Impression of Change (CGIC), Neuropsychiatric inventory (NPI), and EuroQOL 5 Dimensions 5-Level (EQ-5D-5L) were administered. The primary endpoint was the mean change from baseline in the MMSE score (week 4). An active rTMS session involved applying 15 trains bilaterally (40 pulses/train at 10 Hz; intertrain interval, 26 s). Participants received ≥ 8 interventions within the first 2 weeks and at least one intervention weekly in the 3rd and 4th weeks. Full Analysis set (FAS) included 40 patients [120% RMT (n = 15), 90% RMT (n = 13), and Sham (n = 12)].ResultsIn the FAS, MMSE, ADAS-J cog, MoCA-J, CDR-J, CGIC, NPI, and EQ-5D-5L scores between the three groups were not significantly different. Two patients were erroneously switched between the 120% RMT and 90% RMT groups, therefore, “as treated” patients were mainly analyzed. Post hoc analysis revealed significant treatment efficacy in participants with MMSE scores ≥ 15, favoring the 120% RMT group over the Sham group. Responder analysis revealed 41.7% of the 120% RMT group had a ≥ 3-point improvement in the ADAS-J cog versus 0% in the Sham group (Fisher’s exact test, p = 0.045). The MoCA-J showed the same tendency but was not significant. Efficacy disappeared in week 20, based on the ADAS-cog and MoCA-J. No intervention-related serious adverse events occurred.ConclusionThis paper is the first report of using rTMS in Japanese AD patients. The treatment seems safe and moderate-mild stage AD should be target population of pivotal clinical trial with 120% RMT rTMS.

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