Treatment of mild cognitive impairment with transcutaneous vagal nerve stimulation

经皮迷走神经刺激治疗轻度认知障碍

• 批准号: 9388120
• 负责人: John B Williamson
• 金额: $ 22.88万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9388120
• 关键词: Affect; Aging; Alzheimer' s Disease; American; Area; Atrophic; Attention; Behavior; Biological; Brain; Brain Stem; Cell Nucleus; Clinical Trials; Cognition; Cognitive; Crossover Design; Data; Dementia; Deterioration; Development; Diagnosis; Diffusion Magnetic Resonance Imaging; Digit structure; Disease; Early Intervention; Effectiveness; Electrodes; Epilepsy; Episodic memory; Etiology; External Ear; Hippocampus (Brain); Impaired cognition; Impairment; Implant; Individual Differences; Injury; Intervention; Learning; Left; Leukoaraiosis; Magnetic Resonance Imaging; Medial; Mediating; Memory; Memory Loss; Memory impairment; Modification; Muscle; Nerve; Nerve Degeneration; Nerve Endings; Neurodegenerative Disorders; Neurons; Neuropsychological Tests; Norepinephrine; Nucleus solitarius; Operative Surgical Procedures; Participant; Patients; Performance; Phase; Population; Prefrontal Cortex; Process; Publishing; Quality of life; Research; Retrieval; Risk; Role; Short-Term Memory; Societies; Source; Structural defect; Structure; Synapses; System; Techniques; Technology; Therapeutic; Vagus nerve structure; Visuospatial; White Matter Hyperintensity; Withdrawal; aging population; amnestic mild cognitive impairment; base; clinical Diagnosis; cognitive enhancement; cognitive performance; cognitive testing; cost; disability; entorhinal cortex; frontal lobe; improved; improved functioning; locus ceruleus structure; memory encoding; memory recall; memory recognition; memory retrieval; mild cognitive impairment; multimodality; neuroimaging; pre-clinical; prevent; reduce symptoms; response; secondary analysis; sex; social engagement; support network; transcutaneous stimulation; treatment response; white matter

Patients with amnestic mild cognitive impairment (MCI) often have a compromised quality of life (QOL). Cognitive impairment is a major contributor to decrements in QOL and progression of MCI often leads to loss of independence and withdrawal from social participation. MCI, in many patients, is an early expression of neurodegenerative disease. Patients with MCI frequently convert to Alzheimer's disease (AD) (12-16 percent by some estimates per year). Treatments for MCI are of limited scope and availability and of limited effectiveness. Thus, there is great need for treatments that can improve cognition and extend QOL in patients with MCI. Early intervention (prior to the development of dementia) is more likely to successfully treat this population. We propose to investigate the effect of a non-invasive and safe intervention that should have direct influence on brain systems underlying AD, transcutaneous vagal nerve stimulation (tVNS). This promising approach has not yet been studied in patients with MCI. The hippocampus is a structure that deteriorates in AD. Further, studies have suggested that the locus coeruleus (LC), the brainstem nucleus that is the brain's sole source of norepinephrine (NE), may be one of the first structures that deteriorates in patients with AD. The release of NE in the hippocampus and frontal lobes has an important role in cognition and is critical in mediating memory and attention. The ascending portions of the vagus nerve form synapses within the nucleus of the solitary tract, which projects to the LC and to the hippocampus. The LC also projects directly to the hippocampus. Thus, vagal nerve stimulation (VNS) may ameliorate symptoms of MCI. We have demonstrated, in patients with epilepsy, that VNS improves memory; however, VNS has not been used to treat patients with MCI. VNS can now be performed without surgery by transcutaneous stimulation of the auricular branch with electrodes on the external ear. tVNS has the potential to improve cognition and may even alter the course of decline in patients with MCI. We will employ a multimodal MRI-based neuroimaging approach combined with comprehensive and targeted cognitive testing to assess changes with tVNS in cognition in patients with MCI. We will evaluate the effects of tVNS on 60 patients who have been diagnosed with MCI. To maximize statistical power, we will employ a cross-over design with tVNS and control stimulation conditions (stimulating an area on the external ear that does not have nerve endings that connect to the vagus). Very little in the way of mechanistic data or understanding of individual differences in response to tVNS in MCI/AD has been published. Thus, this is a necessary study to evaluate the potential utility of tVNS to enhance cognitive performance in patients with MCI. These data may serve as a platform for supporting the development of a clinical trial with this technology.

敏感轻度认知障碍（MCI）的患者通常具有损害的生活质量（QOL）。 认知障碍是导致QOL减少和MCI进展的主要原因，通常会导致损失 独立和退出社会参与。在许多患者中，MCI是 神经退行性疾病。 MCI患者经常转化为阿尔茨海默氏病（AD）（12-16％ 每年的一些估计）。 MCI治疗的范围和可用性有限，并且有限 效力。因此，非常需要治疗可以改善认知和扩展患者的质量 与MCI。早期干预（在痴呆症发展之前）更有可能成功对待这一点 人口。我们建议调查非侵入性和安全干预的影响，该措施应直接 对AD的脑系统的影响，经皮迷走神经刺激（TVNS）。这很有希望 MCI患者尚未研究方法。 海马是在AD中恶化的结构。此外，研究表明该基因座 COERULUS（LC）是大脑唯一的去甲肾上腺素（NE）的脑干核，可能是其中之一 在AD患者中恶化的第一结构。 NE在海马和额叶中的释放 在认知中起重要作用，对于中介记忆和注意力至关重要。上升部分 迷走神经形态在孤立区核内的突触，该突触向LC和液体投射到 海马。 LC还直接投射到海马。因此，迷走神经刺激（VNS）可能 MCI的改善症状。我们已经证明，在癫痫患者中，VNS改善了记忆。 但是，VNS尚未用于治疗MCI患者。现在可以通过不手术进行VN 外耳朵上有电极的耳部分支的经皮刺激。电视有潜力 为了改善认知，甚至可能改变了MCI患者的下降进程。我们将采用一个 基于多模式MRI的神经影像学方法与全面和有针对性的认知测试相结合 评估MCI患者认知中TVN的变化。 我们将评估TVN对60名被诊断为MCI的患者的影响。最大化 统计能力，我们将采用电视和控制刺激条件的跨界设计（刺激 外耳的区域没有连接到迷走神经的神经末端）。 很少 MCI/AD中对电视的响应的机械数据或对个体差异的理解已有 出版。因此，这是一项必要的研究，以评估TVN的潜在效用以增强认知 MCI患者的表现。这些数据可能是支持开发的平台 该技术的临床试验。