Given the limited research on accelerated iTBS for MCI, a crucial rst step in advancing this promising and minimally burdensome neuromodulation therapy is to systematically assess its safety and carefully evaluate factors that may inuence its implementation. A recent Phase I open-label trial involving 24 elderly individuals diagnosed with amnestic MCI (aMCI) explored the feasibility of accelerated iTBS targeting the left dorsolateral prefrontal cortex. The protocol consisted of eight stimulation sessions, each delivering 600 pulses of iTBS per day over 3 consecutive days [34]. The study’s ndings conrm the safety, feasibility, and acceptability of accelerated iTBS in individuals with aMCI, and also provide evidence of target engagement, as demonstrated by enhanced cognitive function following treatment. These promising results offer valuable insights for future trials aimed at optimizing treatment parameters.

For AD, recent research has not only explored the efcacy of iTBS in improv­ing cognitive function but also sought to elucidate the underlying mechanisms [35, 46, 47, 48]. However, the long-term effects of iTBS on cognitive decline and brain structure in patients with AD remain poorly understood. A recent study assessed the potential of repeated administration of accelerated iTBS every 3months to mitigate cognitive decline in patients with AD [35]. This randomized, assessor-blinded, controlled trial involved 42 patients with AD who received iTBS to the left DLPFC over 14-day periods, spaced 13weeks apart. Assessment tools included the MoCA, a comprehensive neuropsychological battery, and hippocam­pal grey matter volume (GMV) measurements. The results indicated that the iTBS group maintained MoCA scores while showing reduced hippocampal atrophy, a nding that was signicantly correlated with changes in the global degeneration scale. These results suggest that DLPFC-iTBS could serve as a viable and easily implementable non- pharmacological intervention to help mitigate the progressive cognitive decline and deterioration in quality of life associated with AD.Decits in associative memory (AM) are one of the earliest and most prominent symptoms of AD.In a randomized, double-blind, sham-controlled trial, iTBS was applied to the left DLPFC of patients with AD over a 14-day period [47]. The active stimula­tion group demonstrated signicantly greater improvements in AM compared to the sham group by the second week, with these enhancements persisting until the tenth week. Growing evidence suggests that neural network dysfunction may directly contribute to cognitive impairment in AD, making it a promising treat­ment target. A recent study further investigated the impact of iTBS on functional connectivity and cognition in mild to moderate AD [46]. In this double-blind, randomized, sham-controlled trial, 58 participants received either active or sham iTBS targeting the left and right dorsolateral prefrontal cortex and posterior pari­etal cortex. Neurobiological, cognitive, and behavioral assessments were per­formed at the beginning and end of treatment. The results showed that active iTBS enhanced resting-state gamma connectivity and improved delayed recall in an episodic memory task. Baseline gamma connectivity and its changes were predic­tive of better delayed recall following active treatment. These ndings underscore the need for further research to rene iTBS protocols for AD, with the potential to optimize therapeutic outcomes.

quickly after treatment [64, 65]. In patients with neurocognitive disorders, these side effects are similar to those experienced by healthy individuals, suggesting that elderly or cognitively impaired populations tolerate tDCS effectively. Serious adverse effects are rare, and no signicant cognitive or neurological deterioration has been linked to tDCS use [66]. However, caution is warranted for patients with implanted medical devices, epilepsy, or other neurological conditions. The long-term safety of repeated sessions remains an area of ongoing research, and future studies should continue to assess potential cumulative effects over extended periods.

30min [71]. A key concern with tDCS is its lack of focality, which has led to the development of HD-tDCS.This technique employs ve smaller electrodes arranged in a circular conguration to improve focality and target the surrounding cortex, with the central and peripheral electrodes set at opposite polarities [72].