Davidson Benjamin, Vetkas Artur, Germann Jürgen, Tang-Wai David, Lozano Andres M
Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Canada.
Krembil Research Institute, Toronto, ON, Canada.
Expert Rev Med Devices. 2024 Apr;21(4):285-292. doi: 10.1080/17434440.2024.2337298. Epub 2024 Apr 4.
Alzheimer's disease (AD) requires novel therapeutic approaches due to limited efficacy of current treatments.
This article explores AD as a manifestation of neurocircuit dysfunction and evaluates deep brain stimulation (DBS) as a potential intervention. Focusing on fornix-targeted stimulation (DBS-f), the article summarizes safety, feasibility, and outcomes observed in phase 1/2 trials, highlighting findings such as cognitive improvement, increased metabolism, and hippocampal growth. Topics for further study include optimization of electrode placement, and the role of stimulation-induced autobiographical-recall. Nucleus basalis of Meynert (DBS-NBM) DBS is also discussed and compared with DBS-f. Challenges with both DBS-f and DBS-NBM are identified, emphasizing the need for further research on optimal stimulation parameters. The article also reviews alternative DBS targets, including medial temporal lobe structures and the ventral capsule/ventral striatum.
Looking ahead, a phase-3 DBS-f trial, and the prospect of closed-loop stimulation using EEG-derived biomarkers or hippocampal theta activity are highlighted. Recent FDA-approved therapies and other neuromodulation techniques like temporal interference and low-intensity ultrasound are considered. The article concludes by underscoring the importance of imaging-based diagnosis and staging to allow for circuit-targeted therapies, given the heterogeneity of AD and varied stages of neurocircuit dysfunction.
由于目前治疗方法的疗效有限，阿尔茨海默病（AD）需要新的治疗方法。
本文探讨AD作为神经回路功能障碍的一种表现，并评估深部脑刺激（DBS）作为一种潜在干预措施。本文聚焦于穹窿靶向刺激（DBS-f），总结了1/2期试验中观察到的安全性、可行性和结果，突出了认知改善、代谢增加和海马体生长等发现。进一步研究的主题包括电极放置的优化以及刺激诱导的自传性回忆的作用。还讨论了梅纳特基底核（DBS-NBM）DBS，并与DBS-f进行了比较。确定了DBS-f和DBS-NBM两者面临的挑战，强调需要对最佳刺激参数进行进一步研究。本文还回顾了其他DBS靶点，包括内侧颞叶结构和腹侧囊/腹侧纹状体。
展望未来，强调了一项3期DBS-f试验，以及使用脑电图衍生生物标志物或海马体θ活动进行闭环刺激的前景。考虑了最近美国食品药品监督管理局（FDA）批准的疗法以及其他神经调节技术，如时间干扰和低强度超声。鉴于AD的异质性和神经回路功能障碍的不同阶段，本文强调基于成像的诊断和分期对于实现针对回路的治疗的重要性，以此作为结论。
