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.

遗忘型轻度认知功能障碍（MCI）患者的生活质量（QOL）通常会受到影响。 认知功能障碍是导致生活质量下降的主要因素，MCI的进展往往导致生活质量下降。 独立性和退出社会参与。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病（AD）（12- 16%）， 每年的估计）。MCI的治疗范围和可用性有限， 有效性因此，非常需要能够改善患者认知和延长QOL的治疗 关于MCI早期干预（在痴呆症发展之前）更有可能成功治疗这种疾病。 人口我们建议研究一种非侵入性和安全的干预措施的效果， 对AD潜在脑系统的影响，经皮迷走神经刺激（tVNS）。这个充满希望 这种方法尚未在MCI患者中进行研究。 海马体是在AD中恶化的结构。此外，研究表明， 蓝斑核（LC），脑干核，是大脑去甲肾上腺素（NE）的唯一来源，可能是其中一个。 AD患者的第一个结构恶化。海马和额叶NE的释放 在认知中具有重要作用，在调节记忆和注意力方面至关重要。的上升部分 迷走神经在孤束核内形成突触，孤束核投射到LC和 海马体。LC也直接投射到海马体。因此，迷走神经刺激（VNS）可 改善MCI的症状。我们已经证明，在癫痫患者中，迷走神经刺激可以改善记忆; 然而，VNS尚未用于治疗MCI患者。VNS现在可以在不手术的情况下进行， 用外耳上的电极经皮刺激耳分支。TVNS有潜力 改善认知，甚至可能改变MCI患者的衰退过程。我们将雇用一名 多模态MRI神经成像方法结合全面和有针对性的认知测试， 评估tVNS对MCI患者认知功能的影响。 我们将评估tVNS对60例确诊为MCI的患者的疗效。最大化 统计功效，我们将采用tVNS交叉设计并控制刺激条件（刺激 外耳上没有连接到迷走神经的神经末梢的区域）。 很少的方式 MCI/AD患者对tVNS反应的机制数据或个体差异的理解， 公开.因此，这是一个必要的研究，以评估潜在的效用tVNS，以提高认知 MCI患者的表现。这些数据可以作为一个平台，支持开发一个 进行临床试验