Mediators and Moderators of Auditory Training

本研究旨在了解听觉训练（AT）的机制，以及AT减轻听力问题的潜力，听力问题促进阿尔茨海默病和相关痴呆（ADRD）的发展风险。《柳叶刀》委员会（Livingstone及其同事，2020年）和其他人的报告显示，中年听力损失是晚年痴呆的最大预测因素之一，助听器可以防止ADRD的发展。虽然这推动了助听器的更大分布，但盖茨及其同事（2011）的研究表明，中枢听力过程可能比外周听力（通过助听器解决）更能预测ADRD的发病。中枢听觉处理能力是理解言语、欣赏音乐和区分竞争环境声源的基础。随着年龄的增长，尤其是在嘈杂的环境中理解语言，听力挑战会导致人际语言交流的挫折，并对功能独立性、认知能力和整体生活质量产生不利的长期影响，包括增加患ADRD的风险。然而，尽管在多个领域进行了广泛的研究，临床医生和研究人员仍然对解决个人一生中面临的各种听力困难的最佳方法存在分歧。当前建议的指导前提是需要稳健和可靠的数据集来阐明AT的潜在机制，并确定影响培训结果的中介和调节因子。本提案的总体目标是更好地理解AT的机制，重点关注竞争中的言语，可以解决人们随着年龄增长而报告的最普遍的听力投诉，从而缓解向ADRD的过渡。为了解决这个问题，我们将招募大量不同的老年人样本，包括那些患有前驱期ADRD的老年人，以及一组比较年轻的成年人（1260名参与者，不同的训练条件，包括年轻人和老年人的单独样本）。我们将研究基线认知和听力测量如何预测训练结果（调节因子）以及它们如何与训练方法（调节因子）相互作用。为了提高严谨性和可重复性，我们将发布数据集和培训/评估工具，使其他研究人员能够进行分析，复制我们的研究，并使用共同的结果测量来测试他们自己的培训方法。拟议的研究将解决四个具体目标。目的1 -确定刺激复杂性和AT结果的关系。目标2 -确定AT训练结构与AT结果的关系。目标3 -确定参与者特征（调节因子）和AT方法（调节因子）对培训结果的关系。目标4 -创建一个AT平台，促进忠实的复制和建模。通过收集和传播一个庞大、独特和全面的数据集，该建议有可能通过澄清AT的调节因子和中介因子产生变革性影响，并将提供转化机会，有助于减轻可能有ADRD发展风险的个体的听力和认知能力下降。

This proposal seeks to understand mechanisms of auditory training (AT) and potential of AT to mitigate hearing issues that promote risk of development of Alzheimer’s disease and related dementias (ADRD). Reports from the Lancet Commission (Livingstone and colleagues, 2020), and others, show midlife hearing loss is one of the greatest predictors of late-life dementia, and hearing aids protect against development of ADRD. While this has promoted a push for greater distribution of hearing aids, research from Gates and colleagues (2011) suggests that central hearing processes may be greater predictors of onset of ADRD than peripheral hearing (as addressed through hearing aids). Central auditory processing abilities are fundamental to understand speech, appreciate music, and separate competing environmental sound sources. Hearing challenges experienced with increasing age, especially understanding speech in noisy ambient environments, cause frustration with interpersonal verbal communication and detrimental long-term effects on functional independence, cognitive abilities, and overall quality of life, including increased risk for ADRD. Nevertheless, despite extensive research conducted across multiple fields, clinicians and researchers still disagree about the best ways to address the diversity of hearing difficulties individuals face throughout their lives. The guiding premise of the current proposal is the need for robust and reliable data sets to clarify the underlying mechanisms of AT and to identify the mediators and moderators that impact training outcomes. The overarching goal of this proposal is that better understanding of mechanisms of AT, with focus on speech in competition, can address the most prevalent hearing complaints reported by people as they age, and in turn mitigate transition to ADRD. To address this, we will recruit a large and diverse sample of older adults, including those with prodromal ADRD, and a comparison group of younger adults (1260 participants across training conditions, including separate samples of young and older adults). We will research how baseline cognitive and hearing measures predict training outcomes (moderators) and how these interact with training methods (mediators). To enhance rigor and reproducibility, we will release data sets and training/assessment tools to enable other researchers to conduct analyses, replicate our studies, and test their own training methods using common outcome measures. The proposed research will address four Specific Aims. Aim 1 – Determine the relationship of stimulus complexity and AT outcomes. Aim 2 – Determine the relationship of AT training structures and AT outcomes. Aim 3 – Determine relationships between participant characteristics (moderators) and AT approaches (mediators) on training outcomes. Aim 4 – Create an AT platform that facilitates faithful replication and modelling. Through the collection and dissemination of a large, unique, and comprehensive dataset, this proposal has potential for transformative impact by clarifying moderators and mediators of AT, and will afford translational opportunities to contribute to the mitigation of hearing and cognitive decline in individuals who may be at risk for the development of ADRD.