BACKGROUND Dementia with Lewy bodies (DLB) is the second most common form of dementia. Current symptomatic treatment with medications remains inadequate. Deep brain stimulation of the nucleus basalis of Meynert (NBM DBS) has been proposed as a potential new treatment option in dementias. OBJECTIVE To assess the safety and tolerability of low frequency (20 Hz) NBM DBS in DLB patients and explore its potential effects on both clinical symptoms and functional connectivity in underlying cognitive networks. METHODS We conducted an exploratory randomised, double-blind, crossover trial of NBM DBS in six DLB patients recruited from two UK neuroscience centres. Patients were aged between 50-80 years, had mild-moderate dementia symptoms and were living with a carer-informant. Patients underwent image guided stereotactic implantation of bilateral DBS electrodes with the deepest contacts positioned in the Ch4i subsector of NBM. Patients were subsequently assigned to receive either active or sham stimulation for six weeks, followed by a two week washout period, then the opposite condition for six weeks. Safety and tolerability of both the surgery and stimulation were systematically evaluated throughout. Exploratory outcomes included the difference in scores on standardised measurements of cognitive, psychiatric and motor symptoms between the active and sham stimulation conditions, as well as differences in functional connectivity in discrete cognitive networks on resting state fMRI. RESULTS Surgery and stimulation were well tolerated by all six patients (five male, mean age 71.33 years). One serious adverse event occurred: one patient developed antibiotic-associated colitis, prolonging his hospital stay by two weeks. No consistent improvements were observed in exploratory clinical outcome measures, but the severity of neuropsychiatric symptoms reduced with NBM DBS in 3/5 patients. Active stimulation was associated with functional connectivity changes in both the default mode network and the frontoparietal network. CONCLUSION Low frequency NBM DBS can be safely conducted in DLB patients. This should encourage further exploration of the possible effects of stimulation on neuropsychiatric symptoms and corresponding changes in functional connectivity in cognitive networks. TRIAL REGISTRATION NUMBER NCT02263937.

中文翻译：

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Meynert 脑深部刺激双侧基底核治疗路易体痴呆的随机临床试验

背景路易体痴呆（DLB）是痴呆的第二常见形式。目前的药物对症治疗仍然不足。Meynert 基底核 (NBM DBS) 的深部脑刺激已被提议作为痴呆症的潜在新治疗选择。目的 评估低频 (20 Hz) NBM DBS 在 DLB 患者中的安全性和耐受性，并探讨其对潜在认知网络的临床症状和功能连接的潜在影响。方法 我们对从英国两个神经科学中心招募的 6 名 DLB 患者进行了 NBM DBS 的探索性随机、双盲、交叉试验。患者年龄在 50-80 岁之间，有轻度至中度痴呆症状，并与护理人员一起生活。患者接受图像引导立体定向植入双侧 DBS 电极，最深接触位于 NBM 的 Ch4i 子扇区。随后，患者被分配接受主动或假刺激六周，然后是两周的清除期，然后是相反的条件六周。在整个过程中系统地评估了手术和刺激的安全性和耐受性。探索性结果包括主动刺激和假刺激条件之间认知、精神和运动症状的标准化测量分数的差异，以及静息状态 fMRI 上离散认知网络中功能连接的差异。结果 所有六名患者（五名男性，平均年龄 71.33 岁）均能很好地耐受手术和刺激。发生了一起严重的不良事件：一名患者出现了抗生素相关性结肠炎，住院时间延长了两周。在探索性临床结果测量中没有观察到一致的改善，但在 3/5 患者中使用 NBM DBS 降低了神经精神症状的严重程度。主动刺激与默认模式网络和额顶网络的功能连接变化有关。结论 低频 NBM DBS 可以安全地在 DLB 患者中进行。这应该鼓励进一步探索刺激对神经精神症状的可能影响以及认知网络中功能连接的相应变化。试用注册号 NCT02263937。在探索性临床结果测量中没有观察到一致的改善，但在 3/5 患者中使用 NBM DBS 降低了神经精神症状的严重程度。主动刺激与默认模式网络和额顶网络的功能连接变化有关。结论 低频 NBM DBS 可以安全地在 DLB 患者中进行。这应该鼓励进一步探索刺激对神经精神症状的可能影响以及认知网络中功能连接的相应变化。试用注册号 NCT02263937。在探索性临床结果测量中没有观察到一致的改善，但在 3/5 患者中使用 NBM DBS 降低了神经精神症状的严重程度。主动刺激与默认模式网络和额顶网络的功能连接变化有关。结论 低频 NBM DBS 可以安全地在 DLB 患者中进行。这应该鼓励进一步探索刺激对神经精神症状的可能影响以及认知网络中功能连接的相应变化。试用注册号 NCT02263937。主动刺激与默认模式网络和额顶网络的功能连接变化有关。结论 低频 NBM DBS 可以安全地在 DLB 患者中进行。这应该鼓励进一步探索刺激对神经精神症状的可能影响以及认知网络中功能连接的相应变化。试用注册号 NCT02263937。主动刺激与默认模式网络和额顶网络的功能连接变化有关。结论 低频 NBM DBS 可以安全地在 DLB 患者中进行。这应该鼓励进一步探索刺激对神经精神症状的可能影响以及认知网络中功能连接的相应变化。试用注册号 NCT02263937。