A systematic review and meta-analysis of rTMS effects on cognitive enhancement in mild cognitive impairment and Alzheimer's disease

Abstract

Repetitive transcranial magnetic stimulation (rTMS), a noninvasive brain stimulation technique, has emerged as a promising treatment for mild cognitive impairment (MCI) and Alzheimer's disease (AD). Currently, however, the effectiveness of this therapy is unclear because of the low statistical power and heterogeneity of previous trials. The purpose of the meta-analysis was to systematically characterize the effectiveness of various combinations of rTMS parameters on different cognitive domains in patients with MCI and AD. Thirteen studies comprising 293 patients with MCI or AD were included in this analysis. Random-effects analysis revealed an overall medium-to-large effect size (0.77) favoring active rTMS over sham rTMS in the improvement of cognitive functions. Subgroup analyses revealed that (1) high-frequency rTMS over the left dorsolateral prefrontal cortex and low-frequency rTMS at the right dorsolateral prefrontal cortex significantly improved memory functions; (2) high-frequency rTMS targeting the right inferior frontal gyrus significantly enhanced executive performance; and (3) the effects of 5-30 consecutive rTMS sessions could last for 4-12 weeks. Potential mechanisms of rTMS effects on cognitive functions are discussed.

Keywords: Alzheimer's disease; Cognition; Dorsolateral prefrontal cortex; Intervention; Memory; Mild cognitive impairment; Plasticity; Therapy; Transcranial magnetic stimulation; Treatment.

Figure 1.

Flow diagram showing the search and selection procedure that was used for this meta-analysis. Diagram adapted from Moher et al.(Moher, et al., 2009).

Figure 2.

Forest plot. Individual and pooled rTMS effect sizes (SMDs) for cognitive function in patients with MCI or AD. The size of the squares increases with increasing sample size. Cotelli et al. (2008) reported statistics from mild AD (Cotelli et al., 2008a) and moderate-to-severe AD (Cotelli et al., 2008b) separately, and Ahmed et al. (2012) described statistics from 4 groups (Ahmed et al., 2012a = high-frequency rTMS in mild AD; Ahmed et al., 2012b = high-frequency rTMS in severe AD; Ahmed et al., 2012c = low-frequency rTMS in mild AD; Ahmed et al., 2012d = low-frequency rTMS in severe AD;), therefore, those data were included as multiple independent units in the meta-analysis.

Figure 3.

rTMS effect sizes for various combinations of stimulation site, frequency, and outcome measures. DLPFC = dorsolateral prefrontal cortex; ES = effect size; High-F = high-frequency rTMS; IFG = inferior frontal gyrus; Low-F = low-frequency rTMS.