美国All of Us队列中听力损失与孤独感在认知受损和痴呆发展中的作用：基于电子健康记录的前瞻性分析

文献信息

中文摘要

引言： 听力损失（HL）和孤独感均与认知下降独立相关，但孤独感在多大程度上介导HL-认知关系仍不确定。我们研究了HL、孤独感与 incident 痴呆和认知受损（IC）之间的前瞻性关联，并检验孤独感是否部分介导HL对这些结局的影响。
方法： 使用美国国立卫生研究院All of Us受控层级V.8数据集，我们拟合了调整后的Cox比例风险模型，分别以HL（首次电子健康记录（EHR）就诊）和孤独感（健康社会决定因素调查）作为不同的基线。孤独感采用UCLA孤独量表-8（ULS-8）测量，并以ULS-8均值进行分析。我们进行了四向分解中介分析，以划分总效应、直接效应和间接效应，并允许暴露-中介交互作用。结局（incident 痴呆和IC）在相关基线暴露后从EHR中确定。敏感性分析检查了种族/族裔亚组中的关联，移除了≥1年EHR随访要求，将死亡作为竞争风险加以考虑，并在Cox模型中使用时变HL。协变量包括年龄、性别、种族、教育、收入、吸烟和饮酒。
结果： EHR观察基础包括317 108名成年人（总体平均随访11.8年）；50 849人（16.0%）有EHR记录的HL，130 266人（41.1%）有可评分的ULS-8孤独感测量。我们观察到5663例 incident 痴呆和21 117例 incident IC事件。HL与更高的 incident 痴呆风险（HR=1.38，p<0.001）和IC风险（HR=1.67，p<0.001）相关。孤独感（ULS-8均值每增加1分）与更高的 incident 痴呆风险（HR=1.41，p=0.004）和IC风险（HR=1.48，p<0.001）相关。中介分析表明，HL通过孤独感产生的间接效应较小。痴呆的介导比例约为2.5%（pm=0.025，p=0.081），IC约为2.0%（pm=0.020，p<0.001）。亚组分析提示，在黑人/非裔美国人参与者中HL-痴呆关联更强，在亚裔和黑人/非裔美国人参与者中HL-IC关联更强，而敏感性分析结果在很大程度上具有验证性。
结论： 在这个大型、多样化队列中，HL和孤独感与 incident 痴呆和IC独立相关。孤独感仅介导了HL效应的一小部分，提示观察到的HL-认知结局关联的大部分可能通过孤独感以外的途径起作用。这些发现支持进一步评估听力康复和社会连接支持作为认知健康的互补策略，同时提示直接解决HL可能比仅针对孤独感产生更广泛的益处。

英文摘要

INTRODUCTION: Hearing loss (HL) and loneliness are independently associated with cognitive decline, yet the extent to which loneliness mediates the HL-cognition relationship remains uncertain. We examined prospective associations among HL, loneliness and incident dementia and impaired cognition (IC) and tested whether loneliness partially mediates the effect of HL on these outcomes.
METHODS: Using the National Institutes of Health All of Us Controlled Tier V.8 dataset, we fit adjusted Cox proportional hazards models with distinct baselines for HL (first electronic health record (EHR) visit) and loneliness (social determinants of health survey). Loneliness was measured with the UCLA Loneliness Scale-8 (ULS-8) and analysed as the ULS-8 mean. We conducted four-way decomposition mediation analyses to partition total, direct and indirect effects allowing for exposure-mediator interaction. Outcomes (incident dementia and IC) were ascertained from EHRs after the relevant baseline exposure. Sensitivity analyses examined associations in racial/ethnic subgroups, removed the ≥1 year EHR follow-up requirement, accounted for death as a competing risk and used time-varying HL in Cox models. Covariates included age, sex, race, education, income, smoking and alcohol use.
RESULTS: The EHR observation base included 317 108 adults (mean overall follow-up, 11.8 years); 50 849 (16.0%) had EHR-documented HL and 130 266 (41.1%) had a scoreable ULS-8 loneliness measure. We observed 5663 incident dementia and 21 117 incident IC events. HL was associated with higher risk of incident dementia (HR=1.38, p<0.001) and IC (HR=1.67, p<0.001). Loneliness (per 1-point increase in ULS-8 mean) was associated with higher incident dementia (HR=1.41, p=0.004) and IC (HR=1.48, p<0.001) risk. Mediation analyses indicated small indirect effects of HL via loneliness. The proportion mediated was approximately 2.5% for dementia (pm=0.025, p=0.081) and 2.0% for IC (pm=0.020, p<0.001). Subgroup analyses suggested stronger HL-dementia associations among black/African American participants and stronger HL-IC associations among Asian and black/African American participants, while results from sensitivity analyses were largely confirmatory.
CONCLUSIONS: In this large, diverse cohort, HL and loneliness were independently associated with incident dementia and IC. Loneliness mediated only a small fraction of the HL effect, suggesting that most of the observed HL-cognitive outcome association likely operates through pathways other than loneliness. These findings support further evaluation of hearing rehabilitation and social-connection supports as complementary strategies for cognitive health, while suggesting that addressing HL directly may yield broader benefits than targeting loneliness alone.