孤独感作为连接听力下降与认知老化的通路：纵向与遗传学证据

文献信息

中文摘要

引言： 听力损失和孤独感是认知衰退和痴呆的潜在可改变风险因素，但孤独感是否构成连接听力损失与认知老化的因果通路，或这些关联是否反映共同易感性，仍不清楚。
方法： 我们将欧洲健康、老龄与退休调查（SHARE；N = 10,375）长达18年的数据与来自八个主要全基因组关联研究来源的汇总统计量以及用于敏感性分析的独立神经质数据集相结合。平行过程潜增长曲线模型检验了水平与变化的关联；其他分析评估了助听器调节作用、孟德尔随机化、多变量孟德尔随机化以及共定位。
结果： 在第7波，较差的听力、较强的孤独感和较差的词语回忆表现相互关联，并通过孤独感存在显著间接关联。协调性纵向中介的证据有限，主要的变化对变化间接效应不显著。当前（而非累积）助听器使用与较弱的同期听力-孤独感关联相关。遗传分析几乎没有提供听力表型对阿尔茨海默病或全因痴呆存在直接或由孤独感介导的因果效应的证据。结果更符合共同易感性，包括与神经质的重叠。
讨论： 研究结果支持晚年听力困难、孤独感与认知表现之间的关联，但提供的证据有限，不足以表明孤独感是连接听力损失与认知老化的主要因果通路。整合纵向与遗传学证据提示病因更为复杂，涉及共同易感性，并支持在干预研究中直接评估听力保健与社会联系。

英文摘要

INTRODUCTION: Hearing loss and loneliness are potentially modifiable risk factors for cognitive decline and dementia, but it remains unclear whether loneliness represents a causal pathway linking hearing loss to cognitive aging or whether these associations reflect shared vulnerability.
METHODS: We combined up to 18 years of data from the Survey of Health, Ageing and Retirement in Europe (SHARE; N = 10,375) with summary statistics from eight primary genome-wide association study sources and an independent neuroticism dataset used in sensitivity analyses. Parallel-process latent growth curve models examined level and change associations; additional analyses evaluated hearing-aid moderation, Mendelian randomization, multivariable Mendelian randomization, and colocalization.
RESULTS: At Wave 7, poorer hearing, greater loneliness, and poorer word-recall performance were associated, with a significant indirect association through loneliness. Evidence for coordinated longitudinal mediation was limited, and the primary change-to-change indirect effect was not significant. Current, but not cumulative, hearing-aid use was associated with a weaker concurrent hearing-loneliness association. Genetic analyses provided little evidence for direct or loneliness-mediated causal effects of hearing phenotypes on Alzheimer's disease or all-cause dementia. Results were more consistent with shared liability, including overlap with neuroticism.
DISCUSSION: The findings support late-life associations among hearing difficulty, loneliness, and cognitive performance but provide limited evidence that loneliness is a primary causal pathway linking hearing loss to cognitive aging. Integrating longitudinal and genetic evidence suggests a more complex etiology involving shared liability and supports direct evaluation of hearing care and social connection in intervention studies.