首次阿尔茨海默病神经影像检查的时机：遗传、认知与社会因素的多中心分析
Timing of First Alzheimer's Neuroimaging: A Multicenter Analysis of Genetic, Cognitive, and Social Factors
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中文总结 AI 辅助
本研究通过多中心贝叶斯竞争风险模型分析2万余名参与者，发现首次MRI时机主要由人口学、社会及中心因素决定，而非APOE ε4遗传风险，并强调需考虑竞争死亡以避免影像样本偏倚。
中文摘要 AI 辅助
背景。磁共振成像（MRI）在阿尔茨海默病研究和临床评估中占据核心地位，然而队列入组后首次MRI检查的时机差异显著。在老龄化队列中，许多参与者在影像检查前死亡，将死亡视为非信息性删失会扭曲对神经影像可及性的推断，并掩盖差异。目的。在考虑死亡这一竞争风险的同时，量化首次神经影像检查时机的个体层面决定因素和中心层面异质性。方法。我们分析了国家阿尔茨海默病协调中心统一数据集v3，该数据集与2015年至2025年3月期间的MRI记录相关联。研究纳入20,867名年龄在50-95岁之间、基线时无痴呆且已知APOE ε4状态的参与者。从基线到基线后首次MRI的时间为主要事件，MRI前死亡视为竞争事件。我们拟合了具有阿尔茨海默病中心随机截距的贝叶斯多水平原因特异性加速失效时间模型，分别对MRI时机和死亡使用Weibull和对数逻辑模型。敏感性分析采用频率学派加速失效时间模型和Cox模型。结果。APOE ε4与首次MRI时机无可靠关联。年龄较大、教育程度较低和非白人族裔与MRI获取延迟相关。中心层面的MRI时机变异显著。相反，APOE ε4纯合性与MRI前较早死亡相关，同时年龄和认知障碍也有较强影响。结论。阿尔茨海默病研究队列中首次MRI的时机主要由人口统计学、社会及中心层面因素驱动，而非遗传风险。考虑竞争性死亡和中心异质性对于避免偏倚的神经影像样本并支持公平的阿尔茨海默病研究是必要的。
英文摘要
Background. Magnetic resonance imaging (MRI) is central to Alzheimer's disease research and clinical evaluation, yet timing of first MRI after cohort entry varies substantially. In aging cohorts, many participants die before imaging, and treating death as noninformative censoring can distort inference on neuroimaging access and conceal disparities. Objective. To quantify individual-level determinants and center-level heterogeneity in timing of first neuroimaging while accounting for the competing risk of death. Methods. We analyzed National Alzheimer's Coordinating Center Uniform Data Set v3 linked to MRI records from 2015 through March 2025. The study included 20,867 participants aged 50-95 years without dementia at baseline and with known APOE ε4 status. Time from baseline to first post-baseline MRI was the primary event, with death before MRI treated as a competing event. We fit Bayesian multilevel cause-specific accelerated failure time models with Alzheimer's Disease Center random intercepts, using Weibull and log-logistic models for MRI timing and death, respectively. Frequentist accelerated failure time and Cox models were used for sensitivity analyses. Results. APOE ε4 was not credibly associated with timing of first MRI. Older age, lower educational attainment, and non-White race were associated with delayed MRI acquisition. Center-level variation in MRI timing was substantial. Conversely, APOE ε4 homozygosity was associated with earlier death prior to MRI, alongside strong effects of age and cognitive impairment. Conclusions. Timing of first MRI in Alzheimer's research cohorts is driven primarily by demographic, social, and center-level factors rather than genetic risk. Accounting for competing mortality and site heterogeneity is necessary to avoid biased neuroimaging samples and support equitable Alzheimer's research.
发表机构
- University of South Carolina（南卡罗来纳大学）
- University of Arizona（亚利桑那大学）
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