A Phase I Trial of Deep Brain Stimulation of Memory Circuits in Alzheimer's Disease
A Phase I Trial of Deep Brain Stimulation of Memory Circuits in Alzheimer's Disease
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DOI：
10.1002/ana.22089
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发表时间：
2010-10-01
影响因子：
11.2
通讯作者：
Lozano, Andres M.
中科院分区：
文献类型：
--
作者：
Laxton, Adrian W.;Tang-Wai, David F.;Lozano, Andres M.
目的：阿尔茨海默病（Alzheimer disease，AD）是一种以认知和记忆功能为基础的神经元和神经回路功能障碍为特征的疾病。我们假设，穹窿/下丘脑脑深部电刺激（DBS）可以调节这些病理circuits. Methods的神经生理活动，并可能产生临床benefits.Methods：我们进行了一项I期试验，6例轻度AD患者接受持续的药物治疗。患者接受连续刺激12个月。进行了三项主要调查，包括：（1）使用标准化低分辨率电磁断层扫描来映射其生理功能被刺激调制的脑区域，（2）使用正电子发射断层扫描（PET）来评估DBS是否可以纠正AD中脑葡萄糖代谢的局部改变，3）使用临床量表和仪器测量DBS对认知功能随时间推移的影响。DBS驱动记忆回路中的神经活动，包括内嗅和海马区，并激活大脑的默认模式网络。PET扫描显示，在连续刺激12个月后，颞叶和顶叶的葡萄糖利用受损出现了早期和显著的逆转。阿尔茨海默病评估量表认知子量表和简易精神状态检查的评价表明，在一些患者中，6个月和12个月时认知下降的速度可能有所改善和/或减缓。没有严重的不良事件。解释：有一个迫切需要新的治疗方法，AD。在这种疾病中，DBS调节病理性脑活动值得进一步研究。神经网络2010;68：521-534
Objective: Alzheimer disease (AD) is characterized by functional impairment in the neural elements and circuits underlying cognitive and memory functions. We hypothesized that fornix/hypothalamus deep brain stimulation (DBS) could modulate neurophysiological activity in these pathological circuits and possibly produce clinical benefits.Methods: We conducted a phase I trial in 6 patients with mild AD receiving ongoing medication treatment. Patients received continuous stimulation for 12 months. Three main lines of investigation were pursued including: (1) mapping the brain areas whose physiological function was modulated by stimulation using standardized low-resolution electromagnetic tomography, (2) assessing whether DBS could correct the regional alterations in cerebral glucose metabolism in AD using positron emission tomography (PET), and 3) measuring the effects of DBS on cognitive function over time using clinical scales and instruments.Results: DBS drove neural activity in the memory circuit, including the entorhinal, and hippocampal areas and activated the brain's default mode network. PET scans showed an early and striking reversal of the impaired glucose utilization in the temporal and parietal lobes that was maintained after 12 months of continuous stimulation. Evaluation of the Alzheimer's Disease Assessment Scale cognitive subscale and the Mini Mental State Examination suggested possible improvements and/or slowing in the rate of cognitive decline at 6 and 12 months in some patients. There were no serious adverse events.Interpretation: There is an urgent need for novel therapeutic approaches for AD. Modulating pathological brain activity in this illness with DBS merits further investigation. ANN NEUROL 2010;68:521-534