Palacino Federica, Manganotti Paolo, Benussi Alberto
Neurology Unit, Department of Medical, Surgical and Health Sciences, University of Trieste, 34149 Trieste, Italy.
Medicina (Kaunas). 2025 Mar 20;61(3):547. doi: 10.3390/medicina61030547.
Alzheimer's disease (AD), the most prevalent form of dementia, is marked by progressive cognitive decline, affecting memory, language, orientation, and behavior. Pathological hallmarks include extracellular amyloid plaques and intracellular tau tangles, which disrupt synaptic function and connectivity. Neural oscillations, the rhythmic synchronization of neuronal activity across frequency bands, are integral to cognitive processes but become dysregulated in AD, contributing to network dysfunction and memory impairments. Targeting these oscillations has emerged as a promising therapeutic strategy. Preclinical studies have demonstrated that specific frequency modulations can restore oscillatory balance, improve synaptic plasticity, and reduce amyloid and tau pathology. In animal models, interventions, such as gamma entrainment using sensory stimulation and transcranial alternating current stimulation (tACS), have shown efficacy in enhancing memory function and modulating neuroinflammatory responses. Clinical trials have reported promising cognitive improvements with repetitive transcranial magnetic stimulation (rTMS) and deep brain stimulation (DBS), particularly when targeting key hubs in memory-related networks, such as the default mode network (DMN) and frontal-parietal network. Moreover, gamma-tACS has been linked to increased cholinergic activity and enhanced network connectivity, which are correlated with improved cognitive outcomes in AD patients. Despite these advancements, challenges remain in optimizing stimulation parameters, individualizing treatment protocols, and understanding long-term effects. Emerging approaches, including transcranial pulse stimulation (TPS) and closed-loop adaptive neuromodulation, hold promise for refining therapeutic strategies. Integrating neuromodulation with pharmacological and lifestyle interventions may maximize cognitive benefits. Continued interdisciplinary efforts are essential to refine these approaches and translate them into clinical practice, advancing the potential for neural oscillation-based therapies in AD.
阿尔茨海默病（AD）是最常见的痴呆形式，其特征是进行性认知衰退，影响记忆、语言、定向和行为。病理特征包括细胞外淀粉样斑块和细胞内tau缠结，它们会破坏突触功能和连接性。神经振荡，即神经元活动在不同频段的节律性同步，是认知过程不可或缺的一部分，但在AD中会失调，导致网络功能障碍和记忆受损。针对这些振荡已成为一种有前景的治疗策略。临床前研究表明，特定的频率调制可以恢复振荡平衡、改善突触可塑性并减少淀粉样蛋白和tau病理。在动物模型中，诸如使用感觉刺激和经颅交流电刺激（tACS）进行伽马同步等干预措施，已显示出在增强记忆功能和调节神经炎症反应方面的功效。临床试验报告了重复经颅磁刺激（rTMS）和深部脑刺激（DBS）在认知改善方面取得了有前景的成果，特别是当针对记忆相关网络中的关键节点，如默认模式网络（DMN）和额顶叶网络时。此外，伽马-tACS与胆碱能活性增加和网络连接性增强有关，这与AD患者认知结果的改善相关。尽管取得了这些进展，但在优化刺激参数、个性化治疗方案以及了解长期影响方面仍存在挑战。包括经颅脉冲刺激（TPS）和闭环自适应神经调节在内的新兴方法有望完善治疗策略。将神经调节与药物和生活方式干预相结合可能会最大化认知益处。持续的跨学科努力对于完善这些方法并将其转化为临床实践至关重要，这将推动基于神经振荡的AD治疗方法的潜力发展。
