胆碱能系统对帕金森病噪声中言语加工的贡献

文献信息

中文摘要

背景： 在具有挑战性的聆听环境中，言语感知表现随年龄下降，并在帕金森病中尤其受损，导致沟通困难和认知负担。尽管外周听力损失对这些缺陷有贡献，但中枢胆碱能系统功能障碍可能起关键作用。帕金森病的特征是早期且广泛的胆碱能退变。因此，进一步描述胆碱能完整性对功能性听力的贡献，可能更好地揭示感觉与认知衰退之间的机制联系，并为靶向治疗提供信息。方法：29名帕金森病患者（20名男性，9名女性；年龄范围60-76岁）被纳入在密歇根大学功能性神经影像、认知与移动实验室开展的一项横断面研究。参与者完成纯音测听、鼓室压测量和快速噪声中言语测试，以评估外周和功能性听力。胆碱能系统完整性使用[18F]-氟乙氧基苯扎米考[18F]-FEOBV正电子发射断层成像量化，磁共振成像用于解剖共配准。统计参数映射识别了在校正高频纯音平均阈值后胆碱能结合与噪声中言语表现相关的区域。多元回归和分层模型比较检验了外周听力与胆碱能完整性的独立和交互效应。结果：高频纯音平均解释了快速噪声中言语信噪比损失方差的21.6%[β = 0.494（0.151-0.838），P = 0.006]。校正听力阈值后，听觉、丘脑、颞顶和小脑区域[18F]-FEOBV结合降低与更大的信噪比损失显著相关（簇水平家庭wise误差校正P < 0.01）。胆碱能完整性在外周听力之外额外解释了27.5%的方差[F = 15.596，P < 0.001；β = -0.533（-0.811至-0.256），P = 0.001]。听力阈值与胆碱能完整性之间的交互作用进一步解释了12.7%的方差（F = 9.671，P = 0.005），表明较高的胆碱能完整性减轻了听力损失对噪声中言语理解的负面影响。事后混杂因素回归分析发现，观察到的效应独立于年龄和整体认知。结论：中枢胆碱能完整性是帕金森病噪声中言语表现的主要决定因素，既独立发挥作用，也与外周听力功能交互作用。这些发现表明，噪声中言语缺陷可能反映早期皮层下和皮层胆碱能功能障碍，而不仅仅是外周听觉衰退。认识到这一关系强调了胆碱能增强或神经刺激疗法改善神经退行性疾病中沟通和认知结局的潜力。

英文摘要

Speech perception performance in challenging listening environments declines with age and is particularly impaired in Parkinson's disease, leading to communication difficulties and cognitive strain. Although peripheral hearing loss contributes to these deficits, dysfunction of the central cholinergic system may play a key role. Parkinson's disease is characterized by early and widespread cholinergic degeneration. Accordingly, further describing the contribution of cholinergic integrity to functional hearing may offer better insight into the mechanistic link between sensory and cognitive decline and inform targeted therapeutic approaches. Twenty-nine individuals with Parkinson's disease (20 men, nine women; age range 60-76 years) were enrolled in a cross-sectional study conducted at the University of Michigan Functional Neuroimaging, Cognitive and Mobility Laboratory. Participants completed pure-tone audiometry, tympanometry and Quick Speech-in-Noise testing to assess peripheral and functional hearing. Cholinergic system integrity was quantified using [18F]-fluoroethoxybenzovesamicol [18F]-FEOBV positron emission tomography imaging, and magnetic resonance imaging was used for anatomical co-registration. Statistical parametric mapping identified regions where cholinergic binding correlated with speech-in-noise performance after adjusting for high-frequency pure-tone average thresholds. Multiple regression and hierarchical model comparisons tested independent and interactive effects of peripheral hearing and cholinergic integrity. High-frequency pure-tone average explained 21.6% of the variance in Quick Speech-in-Noise signal-to-noise ratio loss [β = 0.494 (0.151-0.838), P = 0.006]. After adjustment for hearing thresholds, reduced [18F]-FEOBV binding in auditory, thalamic, temporoparietal and cerebellar regions was significantly associated with greater signal-to-noise ratio loss (cluster-level family-wise error corrected P < 0.01). Cholinergic integrity accounted for an additional 27.5% of the variance beyond peripheral hearing [F = 15.596, P < 0.001; β = -0.533 (-0.811 to -0.256), P = 0.001]. An interaction between hearing thresholds and cholinergic integrity explained a further 12.7% of the variance (F = 9.671, P = 0.005), showing that higher cholinergic integrity mitigated the detrimental effects of hearing loss on speech-in-noise understanding. Observed effects were found to be independent of age and global cognition in the post hoc confounder regression analysis. Central cholinergic integrity is a major determinant of speech-in-noise performance in Parkinson's disease, acting both independently and interactively with peripheral hearing function. These findings indicate that speech-in-noise deficits may reflect early subcortical and cortical cholinergic dysfunction rather than only peripheral auditory decline. Recognition of this relationship underscores the potential for cholinergic-enhancing or neurostimulation-based therapies to improve communication and cognitive outcomes in neurodegenerative disorders.