Repetitive Transcranial Magnetic Stimulation for Improving Cognitive Function in Patients With Mild Cognitive Impairment: A Systematic Review

Abstract

Background: Mild cognitive impairment (MCI) is an early stage of Alzheimer's disease. Repetitive transcranial magnetic stimulation (rTMS) has been widely employed in MCI research. However, there is no reliable systematic evidence regarding the effects of rTMS on MCI. The aim of this review was to evaluate the efficacy and safety of rTMS in the treatment of MCI.Methods: A comprehensive literature search of nine electronic databases was performed to identify articles published in English or Chinese before June 20, 2019. The identified articles were screened, data were extracted, and the methodological quality of the included trials was assessed. The meta-analysis was performed using the RevMan 5.3 software. We used the GRADE approach to rate the quality of the evidence.Results: Nine studies comprising 369 patients were included. The meta-analysis showed that rTMS may significantly improve global cognitive function (standardized mean difference [SMD] 2.09, 95% confidence interval [CI] 0.94 to 3.24, p = 0.0004, seven studies, n = 296; low-quality evidence) and memory (SMD 0.44, 95% CI 0.16 to 0.72, p = 0.002, six studies, n = 204; moderate-quality evidence). However, there was no significant improvement in executive function and attention (p > 0.05). Subgroup analyses revealed the following: (1) rTMS targeting the left hemisphere significantly enhanced global cognitive function, while rTMS targeting the bilateral hemispheres significantly enhanced global cognitive function and memory; (2) high-frequency rTMS significantly enhanced global cognitive function and memory; and (3) a high number of treatments ≥20 times could improve global cognitive function and memory. There was no significant difference in dropout rate (p > 0.05) between the rTMS and control groups. However, patients who received rTMS had a higher rate of mild adverse effects (risk ratio 2.03, 95% CI 1.16 to 3.52, p = 0.01, seven studies, n = 317; moderate-quality evidence).Conclusions: rTMS appears to improve global cognitive function and memory in patients with MCI and may have good acceptability and mild adverse effects. Nevertheless, these results should be interpreted cautiously due to the relatively small number of trials, particularly for low-frequency rTMS.

Cognitive Enhancement of Repetitive Transcranial Magnetic Stimulation in Patients With Mild Cognitive Impairment and Early Alzheimer’s Disease: A Systematic Review and Meta-Analysis

“…Thus, the cognitive training might be able to modulate the effect of rTMS, and might explain why the rTMS studies with cognitive training seemed to be more consistent than those studies without cognitive training. Besides, our current subgroup analysis of session number revealed that rTMS with more than 20 sessions might be able to produce cognitive enhancement in patients with MCI or early AD, which is consistent with previous studies (Lin et al, 2019;Wang et al, 2020;Jiang et al, 2021). However, the effect size of trials with 30 sessions seemed to be smaller than the effect size of trials with 20 session and with 40 sessions.…”

“…A series of literature has suggested the positive effects of rTMS on AD patients and with the growing body of the rTMS studies in MCI and AD recently, several meta-analyses have investigated the effects of rTMS in older adults with MCI or AD and demonstrated a beneficial effect of rTMS on the cognitive function of patients (Lin et al, 2019;Chou et al, 2020;Wang et al, 2020;Jiang et al, 2021). However, most of them included patients within different stages of AD and resulted in large variety of pretreatment cognitive capability (Lin et al, 2019;Wang et al, 2020).…”

“…However, most of them included patients within different stages of AD and resulted in large variety of pretreatment cognitive capability (Lin et al, 2019;Wang et al, 2020). Few studies have focused on the patients with MCI (Jiang et al, 2021). Previous studies have declared that the synaptic plasticity and cortical excitability, which play important roles in the rTMS-underlying mechanism, might be impaired in the early course of AD, even in MCI (Nardone et al, 2014;Koch et al, 2020).…”

Repetitive transcranial magnetic stimulation increases the brain’s drainage efficiency in a mouse model of Alzheimer’s disease

“…The effectiveness of high-frequency rTMS treatment has been examined in clinical studies. Notably, patients diagnosed with early stage AD received rTMS stimulation bilaterally to the dorsal lateral prefrontal cortex showed cognitive improvement relative to their baseline state while patients with sham treatment showed no improvement [ 32 , 58 ]. Together with our findings that rTMS treatment prevented the cognitive decline in 5xFAD mice, we hypothesize that the still limited accumulation of toxic Aβ, neuroinflammation and neuronal damage at early stage of AD may allow for better therapeutic effect of rTMS.…”

Effects of Repetitive Transcranial Magnetic Stimulation in Patients With Mild Cognitive Impairment: A Meta-Analysis of Randomized Controlled Trials

“…The studies included patients with MCI and AD in most previous meta-analyses, and few studies analyzed patients with MCI independently (Chou et al, 2020 ). A recent meta-analysis reported the effect of rTMS on cognition in patients with MCI (Jiang et al, 2020 ), but the studies included were not exclusively randomized controlled trials (RCTs). Furthermore, different interventions were used as controls in some of the included studies, indicating high heterogeneity across the studies.…”