阿尔茨海默病风险的运动言语标志物

文献信息

中文摘要

背景： 运动变化日益被认为是阿尔茨海默病（AD）表型的一部分，然而运动言语功能及其在早期AD风险分层中的临床效用仍未被充分探索。本横断面研究调查了基于家庭的快速音节重复（轮替运动[DDK]）任务中的运动言语表现指标是否与已确立的AD风险指标——主观认知下降（SCD）、载脂蛋白E ε4（APOE ε4）携带状态和血浆磷酸化tau 181（p-tau181）——相关。方法：来自岛屿研究链接衰老与神经退行性疾病的社区样本共339名认知未受损成人（238名无症状对照（AC），66.3±6.5岁，71.4%女性；101名SCD，66.0±6.6岁，72.3%女性）远程自我管理了四项DDK任务（“pa”、“ta”、“ka”、“pataka”），这些任务来自自我管理的在线塔斯马尼亚测试方案。自我报告的认知变化用于将受试者分类为AC或SCD组。我们进行了非参数分析和百分位-LASSO多重回归，以从运动言语表现指标预测风险指标，并允许年龄、性别、教育、焦虑和抑郁的影响。结果：在多重比较校正后，没有非参数关联与SCD或APOE ε4保持显著。一个相对重复变异性指标与血浆p-tau181保持显著相关。在协变量调整的回归分析中，运动言语指标与SCD（AUC 0.700）、APOE ε4（AUC 0.715）和自然对数转换的p-tau181（MAE 0.323）相关。对听力损失、不完整数据和抑郁筛查亚组的敏感性分析揭示了抑郁和血液生物标志物数据可用性偏倚的潜在缓解效应。结论：这表明需要额外的工作，特别是纵向随访，以验证这些初步发现，从而寻找可扩展的临床前痴呆风险筛查工具。

英文摘要

Motor changes are increasingly recognized as part of the Alzheimer's disease (AD) phenotype, yet motor speech function and its clinical utility for early AD risk stratification remain underexplored. This cross-sectional study investigated whether measures of motor speech performance in home-based rapid syllable repetition (diadochokinesis [DDK]) tasks are associated with the established AD risk indicators of subjective cognitive decline (SCD), apolipoprotein E ε4 (APOE ε4) carriage, and plasma phosphorylated tau 181 (p-tau181). A community sample of 339 cognitively unimpaired adults (238 asymptomatic control (AC), 66.3 ± 6.5 years, 71.4% female; 101 SCD, 66.0 ± 6.6 years, 72.3% female) from the Island Study Linking Aging and Neurodegenerative Disease remotely self-administered four DDK tasks ("pa", "ta", "ka", "pataka") from the self-administered online Tasmanian Test protocol. Self-reported cognitive changes were used to classify AC or SCD groups. We conducted nonparametric analyses and percentile-LASSO multiple regression to predict risk indicators from motor speech performance measures, allowing for age, sex, education, anxiety, and depression. No nonparametric associations with SCD or APOE ε4 remained significant after adjustment for multiple comparisons. One measure of relative repetition variability remained significantly associated with plasma p-tau181. In covariate-adjusted regression analyses, motor speech measures were associated with SCD (AUC 0.700), APOE ε4 (AUC 0.715), and natural log-transformed p-tau181 (MAE 0.323). Sensitivity analyses for hearing loss, incomplete data, and depression-screened subsets revealed potentially mitigating effects of depression and blood biomarker data availability bias. This indicates that additional work, especially longitudinal follow-up, is needed to verify these preliminary findings in the search for scalable screening tools for preclinical dementia risk.