Zhang Fan, Meng Yao, Zhang Wei
Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Center for Cognitive Neurology, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Neural Regen Res. 2025 Jun 19. doi: 10.4103/NRR.NRR-D-24-01088.
Alzheimer's disease is the most common type of cognitive disorder, and there is an urgent need to develop more effective, targeted and safer therapies for patients with this condition. Deep brain stimulation is an invasive surgical treatment that modulates abnormal neural activity by implanting electrodes into specific brain areas followed by electrical stimulation. As an emerging therapeutic approach, deep brain stimulation shows significant promise as a potential new therapy for Alzheimer's disease. Here, we review the potential mechanisms and therapeutic effects of deep brain stimulation in the treatment of Alzheimer's disease based on existing clinical and basic research. In clinical studies, the most commonly targeted sites include the fornix, the nucleus basalis of Meynert, and the ventral capsule/ventral striatum. Basic research has found that the most frequently targeted areas include the fornix, nucleus basalis of Meynert, hippocampus, entorhinal cortex, and rostral intralaminar thalamic nucleus. All of these individual targets exhibit therapeutic potential for patients with Alzheimer's disease and associated mechanisms of action have been investigated. Deep brain stimulation may exert therapeutic effects on Alzheimer's disease through various mechanisms, including reducing the deposition of amyloid-β, activation of the cholinergic system, increasing the levels of neurotrophic factors, enhancing synaptic activity and plasticity, promoting neurogenesis, and improving glucose metabolism. Currently, clinical trials investigating deep brain stimulation for Alzheimer's disease remain insufficient. In the future, it is essential to focus on translating preclinical mechanisms into clinical trials. Furthermore, consecutive follow-up studies are needed to evaluate the long-term safety and efficacy of deep brain stimulation for Alzheimer's disease, including cognitive function, neuropsychiatric symptoms, quality of life and changes in Alzheimer's disease biomarkers. Researchers must also prioritize the initiation of multi-center clinical trials of deep brain stimulation with large sample sizes and target earlier therapeutic windows, such as the prodromal and even the preclinical stages of Alzheimer's disease. Adopting these approaches will permit the efficient exploration of more effective and safer deep brain stimulation therapies for patients with Alzheimer's disease.
阿尔茨海默病是最常见的认知障碍类型，迫切需要为患有这种疾病的患者开发更有效、更有针对性且更安全的治疗方法。深部脑刺激是一种侵入性手术治疗，通过将电极植入特定脑区然后进行电刺激来调节异常神经活动。作为一种新兴的治疗方法，深部脑刺激作为阿尔茨海默病潜在的新疗法显示出巨大的前景。在此，我们基于现有的临床和基础研究，综述深部脑刺激治疗阿尔茨海默病的潜在机制和治疗效果。在临床研究中，最常靶向的部位包括穹窿、迈内特基底核以及腹侧囊/腹侧纹状体。基础研究发现，最常靶向的区域包括穹窿、迈内特基底核、海马体、内嗅皮质以及丘脑前内侧核。所有这些个体靶点对阿尔茨海默病患者均显示出治疗潜力，并且已经对其相关作用机制进行了研究。深部脑刺激可能通过多种机制对阿尔茨海默病发挥治疗作用，包括减少β淀粉样蛋白的沉积、激活胆碱能系统、增加神经营养因子水平、增强突触活动和可塑性、促进神经发生以及改善葡萄糖代谢。目前，针对阿尔茨海默病的深部脑刺激临床试验仍然不足。未来，必须专注于将临床前机制转化为临床试验。此外，需要进行连续的随访研究，以评估深部脑刺激治疗阿尔茨海默病的长期安全性和有效性，包括认知功能、神经精神症状、生活质量以及阿尔茨海默病生物标志物的变化。研究人员还必须优先启动大样本量的深部脑刺激多中心临床试验，并针对更早的治疗窗口，如阿尔茨海默病的前驱期甚至临床前期。采用这些方法将能够有效地探索出更有效、更安全的深部脑刺激疗法，用于治疗阿尔茨海默病患者。
