多奈哌齐对成人人工耳蜗使用者言语识别的影响：一项初步随机临床试验

文献信息

中文摘要

目的： 人工耳蜗植入后的言语识别结果在使用者之间差异很大，可能源于神经可塑性的差异。胆碱能系统在皮层重组和感觉学习中起关键作用；然而，其在人工耳蜗（CI）使用者中增强听觉可塑性的潜力尚未被探索。本研究旨在探讨胆碱能激动剂多奈哌齐对成人CI使用者言语感知和皮层可塑性的影响。
设计： 这项初步随机临床试验于2023年4月至2024年12月在一家三级学术中心进行。纳入标准为语后聋起病且设备使用经验至少6个月的成人CI接受者。参与者被随机分配至每日口服多奈哌齐5 mg（DPZ）或安慰剂（PL），持续90天。鼓励两组在研究期间增加每日设备使用时间。主要结局指标为植入耳辅音-元音-辅音词识别评分的变化。次要结局包括双耳词识别、安静环境下句子识别、噪声环境下句子识别的信噪比损失，以及与听力满意度、聆听疲劳和生活质量相关的问卷。问卷包括言语、空间和听力质量量表、范德堡疲劳量表和CI生活质量概况。使用功能性近红外光谱评估皮层可塑性。
结果： 13名有经验的CI使用者入选这项初步研究，其中9名完成了90天方案并纳入组描述性分析（DPZ：n = 4，PL：n = 5）。4名参与者（45%）为女性，中位年龄为68岁。所有研究参与者均增加了设备使用时间，两组平均每日增加3.1小时。多奈哌齐治疗与仅CI辅音-元音-辅音词识别平均提高14.5分相关，超过了10分的临床显著性阈值，而安慰剂组下降了0.8分（d = 0.88）。与PL组相比，DPZ组的双耳词识别、句子识别和噪声下言语表现也有所改善。主观测量显示，DPZ组在言语感知（言语、空间和听力质量量表）方面改善更大，聆听疲劳（范德堡疲劳量表）降低，而CI相关生活质量在两组间相似。神经影像分析显示显著的组×时间交互效应，DPZ在噪声下言语任务中增加了左侧额叶皮层激活（β = 3.721，p < 0.001）。
结论： 这些发现提供了初步证据，表明使用多奈哌齐增强胆碱能可能改善CI使用者的言语感知，并促进多感觉和认知脑区的神经可塑性。此外，神经影像分析支持DPZ治疗诱导的胆碱能神经可塑性。虽然这项初步研究样本量不足以确定多奈哌齐的临床疗效，但像多奈哌齐这样的药物干预代表了一种优化CI结局的有前景的新方法，我们为该人群的未来临床试验提供了建议。

英文摘要

OBJECTIVES: Speech recognition outcomes following cochlear implantation vary widely among users, potentially due to differences in neuroplasticity. The cholinergic system plays a critical role in cortical reorganization and sensory learning; yet, its potential to enhance auditory plasticity in cochlear implant (CI) users has not been explored. The aim of this study is to investigate the effects of donepezil, a cholinergic agonist, on speech perception and cortical plasticity in adults with CIs.
DESIGN: This pilot randomized clinical trial was conducted at a single tertiary academic center from April 2023 to December 2024. Adult CI recipients with a postlingual onset of deafness and at least 6 months of device experience were eligible for inclusion. Participants were randomized to oral donepezil 5 mg (DPZ) or placebo (PL) daily for 90 days. Both groups were encouraged to increase their daily device use during the study. The primary outcome measure was the change in consonant-nucleus-consonant word recognition scores for the implanted ear. Secondary outcomes included binaural word recognition, sentence recognition in quiet, signal to noise ratio loss for sentence recognition in noise, and questionnaires related to hearing satisfaction, listening fatigue, and quality of life. The questionnaires included the Speech, Spatial, and Quality of Hearing Scale, Vanderbilt Fatigue Scale, and CI Quality of Life Profile. Cortical plasticity was assessed using functional near-infrared spectroscopy.
RESULTS: Thirteen experienced CI users were enrolled in this pilot study, with nine completing the 90-day protocol and included in the group descriptive analyses (DPZ: n = 4, PL: n = 5). Four participants (45%) were female, and the median age was 68 years. All study participants increased their device use, with a mean increase of 3.1 hr per day in both groups. Donepezil treatment was associated with a 14.5-point increase in mean CI-only consonant-nucleus-consonant word recognition, surpassing the 10-point threshold for clinical significance, whereas the placebo group decreased by 0.8 points (d = 0.88). Binaural word recognition, sentence recognition, and speech-in-noise performance also improved in the DPZ group relative to PL. Subjective measures showed greater improvements in speech perception (Speech, Spatial, and Quality of Hearing Scale) and reduced listening fatigue (Vanderbilt Fatigue Scale) in the DPZ group, while CI-related quality of life was similar between groups. Neuroimaging analyses revealed significant Group × Time interaction effects, with DPZ increasing left frontal cortex activation during a speech-in-noise task (β = 3.721, p < 0.001).
CONCLUSIONS: These findings provide preliminary evidence that cholinergic enhancement with donepezil may improve speech perception and facilitate neuroplasticity in multisensory and cognitive brain regions in CI users. In addition, the neuroimaging analyses support cholinergic-induced neuroplasticity with DPZ treatment. While this pilot study was underpowered to determine the clinical efficacy of donepezil, pharmacological interventions like donepezil represent a promising novel approach to optimizing CI outcomes, and we offer recommendations for future clinical trials in this population.