Despite the numerous pharmacological interventions targeting dementia, no disease-modifying therapy is available, and the prognosis remains unfavorable. A promising perspective involves tackling high-frequency gamma-band (> 30 Hz) oscillations involved in hippocampal-mediated memory processes, which are impaired from the early stages of typical Alzheimer’s Disease (AD). Particularly, the positive effects of gamma-band entrainment on mouse models of AD have prompted researchers to translate such findings into humans using transcranial alternating current stimulation (tACS), a methodology that allows the entrainment of endogenous cortical oscillations in a frequency-specific manner. This systematic review examines the state-of-the-art on the use of gamma-tACS in Mild Cognitive Impairment (MCI) and dementia patients to shed light on its feasibility, therapeutic impact, and clinical effectiveness. A systematic search from two databases yielded 499 records resulting in 10 included studies and a total of 273 patients. The results were arranged in single-session and multi-session protocols. Most of the studies demonstrated cognitive improvement following gamma-tACS, and some studies showed promising effects of gamma-tACS on neuropathological markers, suggesting the feasibility of gamma-tACS in these patients anyhow far from the strong evidence available for mouse models. Nonetheless, the small number of studies and their wide variability in terms of aims, parameters, and measures, make it difficult to draw firm conclusions. We discuss results and methodological limitations of the studies, proposing possible solutions and future avenues to improve research on the effects of gamma-tACS on dementia.

尽管有许多针对痴呆症的药物干预措施，但没有可用的疾病改善疗法，而且预后仍然不利。一个有前途的观点涉及解决海马体介导的记忆过程中涉及的高频伽马带（> 30 Hz）振荡，这些过程在典型的阿尔茨海默氏病（AD）的早期阶段受损。特别是，伽马能带夹带对 AD 小鼠模型的积极影响促使研究人员使用经颅交流电刺激 (tACS) 将这些发现转化为人类，这是一种允许以特定频率方式夹带内源性皮质振荡的方法。本系统评价检查了在轻度认知障碍 (MCI) 和痴呆症患者中使用 gamma-tACS 的最新技术，以阐明其可行性、治疗影响和临床有效性。从两个数据库进行的系统搜索产生了 499 条记录，导致 10 项纳入研究和总共 273 名患者。结果被安排在单会话和多会话协议中。大多数研究表明在接受 gamma-tACS 后认知能力有所改善，一些研究表明 gamma-tACS 对神经病理学标志物具有良好的影响，这表明 gamma-tACS 在这些患者中的可行性与小鼠模型可用的有力证据相去甚远。尽管如此，由于研究数量较少，而且它们在目标、参数和措施方面的差异很大，因此很难得出明确的结论。