Abstract: Mild cognitive impairment (MCI) is an intermediate state between normal aging and dementia, which does not affect activities of daily living. Patients with MCI typically show deficits in memory, attention, executive function, language and speech, which are related to the altered connectivity of large-scale brain networks, such as salience network, frontal-parietal network, and default mode network. MCI is associated with an increased risk of Alzheimer's disease, but there lacks effective pharmacologic therapy of MCI. Repetitive transcranial magnetic stimulation (rTMS) is widely applied to enhance cognitive functions by modulating synaptic plasticity. However, there is a lack of studies examining effects of rTMS on MCI, and no consensus on its effectiveness and mechanisms has been reached. To address this problem, a literature review was conducted by searching literature in databases of Web Of Science, PubMed, PsycINFO, China National Knowledge Infrastructure, and by assessing the quality of included studies using the Cochrane Collaboration's tool.
The results showed that the studies included in this review had a low risk of bias. Performing high-frequency rTMS on inferior frontal cortex (IFG) and superior temporal cortex (STG) improved attention in patients with MCI, by increasing the excitability of the attention network. High-frequency rTMS of dorsolateral prefrontal cortex (dlPFC) improved executive function. rTMS-excitation of dlPFC and precuneus enhanced episodic memory in MCI patients, and its underlying mechanism might be that rTMS improved the encoding function of dlPFC and the retrieving function of ventral precuneus. Based on that the increasing activity of right dlPFC is associated with the decreasing activity of hippocampus, the inhibition of dlPFC improved long-term memory in patients with MCI. Conducting high-frequency rTMS on medial prefrontal cortex (mPFC) could strengthen the connectivity among neuronal subpopulations in mPFC, improving the short-term memory of patients with MCI. Based on the strong functional connectivity between posterior parietal cortex (PPC) and hippocampus, performing high-frequency rTMS on parietal cortex could activate hippocampus by the PPC-hippocampus connection, which improves associative memory of patients with MCI. High-frequency rTMS over prefrontal cortex (PFC) improved associative memory, which was related to the additional activation of right IFG and middle frontal gyrus, reflecting a compensatory mechanism in associative memory.
rTMS shows effects in improving attention, executive function, episodic memory, long-term and short-term memory, and associative memory in patients with MCI. The improving effects could keep for 30 days, 8 weeks, or 6 months. No significant adverse effects of rTMS were reported in these studies. The major strengths of this review included that the inclusion and the quality assessment of studies followed standard protocol, and that the examinations of the rTMS effects on MCI and its underlying mechanisms were conducted comprehensively in terms of the affected multiple cognitive domains. Future studies should optimize the localization for TMS, extend the evaluation period of intervention effects, and explore how rTMS works in the treatment of MCI combining with neuroimaging technologies.

Key words: mild cognitive impairment, nonpharmacological intervention, transcranial magnetic stimulation (TMS)