Asian J Psychiatr. 2025 Oct 28;114:104758. doi: 10.1016/j.ajp.2025.104758. Online ahead of print.
ABSTRACT
OBJECTIVE: This meta-analysis aimed to systematically evaluate the specific, adjunctive efficacy of repetitive transcranial magnetic stimulation (rTMS) when combined with non-pharmacological interventions-namely, transcranial direct current stimulation (tDCS), Tai Chi, or cognitive training (CT)-in patients with Alzheimer’s disease (AD) or mild cognitive impairment (MCI). The goal is to isolate the net therapeutic contribution of rTMS beyond the effects of the base interventions alone.
METHODS: A comprehensive search of Chinese and English databases was conducted from their inception until April 26, 2025. Randomized controlled trials (RCTs) that compared “a non-pharmacological intervention plus active rTMS” versus “the same non-pharmacological intervention plus sham rTMS”.This “add-on” study design was selected to precisely isolate the effect of rTMS. The risk of bias was assessed using the PEDro scale and Cochrane tools. Statistical analyses were performed using Review Manager 5.4 software.
RESULTS: 9 studies involving 391 participants were included. The pooled analysis revealed that the adjunctive use of rTMS was significantly superior to the sham control in improving global cognitive function at the immediate post-treatment assessment (SMD=0.38, 95 %CI[0.20,0.56], P < .001, n = 9). This benefit was consistent across the MMSE (SMD=0.38, n = 6), MoCA (SMD=0.37, n = 2), and ADAS-cog (SMD=0.39, n = 3) scores. Subgroup analysis suggested that the rTMS-tDCS combination might offer a short-term advantage in improving MMSE scores (MD=4.67, P = .008). Furthermore, the adjunctive effect of rTMS was sustained, as particularly evidenced by the ADAS-cog at follow-up (SMD=0.74, P = .02). The pooled analysis indicated that rTMS combined with non-pharmacological therapy demonstrated a short-term, sustained (4-8weeks) improvement in global cognitive function (SMD=0.34, 95 % CI[0.07, 0.60], P = .01). Subgroup analysis revealed that this sustained benefit reached statistical significance on the ADAS-cog scale (SMD = 0.41, 95 %CI[0.01, 0.81], P = .04) but showed a non-significant positive trend on the MMSE (SMD=0.26, 95 %CI[-0.19, 0.72], P = .26). However, a key limitation was that most studies did not systematically report outcomes related to activities of daily living or behavioral function.
CONCLUSION: The evidence indicates that rTMS as an adjunct to non-pharmacological interventions provides a significant specific effect on global cognitive function in patients with AD and MCI shortly after treatment, which may be sustained in the short-term. However, long-term follow-up data are extremely limited, and the effect on activities of daily living remains to be validated. The combination of rTMS and tDCS shows promise,but conclusions are constrained by the small number of studies,limited sample sizes,and heterogeneity in intervention protocols. Future large-scale studies incorporating long-term, standardized follow-up and assessments of daily living abilities are warranted to confirm the specific clinical value of rTMS as an augmentative therapy.
PMID:41192010 | DOI:10.1016/j.ajp.2025.104758
