The early detection of Alzheimer's disease (AD) requires an understanding of the relationships between a wide range of features. Conditional independencies and partial correlations are suitable measures for these relationships, because they can identify the effects of confounding and mediating variables. This article presents a Bayesian approach to Gaussian copula graphical models (GCGMs) in order to estimate these conditional dependencies and partial correlations. This approach has two key advantages. First, it includes binary, discrete, and continuous variables. Second, it quantifies the uncertainty of the estimates. Despite these advantages, Bayesian GCGMs have not been applied to AD research yet. In this study, we design a GCGM to find the conditional dependencies and partial correlations among brain-region specific gray matter volume and glucose uptake, amyloid-beta levels, demographic information, and cognitive test scores. We applied our model to 1022 participants, including healthy and cognitively impaired, across different stages of AD. We found that aging reduces cognition through three indirect pathways: hippocampal volume loss, posterior cingulate cortex (PCC) volume loss, and amyloid-beta accumulation. We found a positive partial correlation between being woman and cognition, but also discovered four indirect pathways that dampen this association in women: lower hippocampal volume, lower PCC volume, more amyloid-beta accumulation, and less education. We found limited relations between brain-region specific glucose uptake and cognition, but discovered that the hippocampus and PCC volumes are related to cognition. These results show that the use of GCGMs offers valuable insights into AD pathogenesis.

翻译：阿尔茨海默病（AD）的早期检测需要理解广泛特征之间的关联关系。条件独立性与偏相关系数是衡量这些关系的合适指标，因为它们能够识别混杂变量与中介变量的影响。本文提出一种高斯Copula图模型（GCGM）的贝叶斯方法，用以估计这些条件依赖关系与偏相关系数。该方法具有两个关键优势：第一，能够同时处理二值变量、离散变量与连续变量；第二，可对估计结果的不确定性进行量化。尽管存在这些优势，贝叶斯GCGM尚未应用于AD研究领域。在本研究中，我们构建了一个GCGM模型，用于探索脑区特异性灰质体积与葡萄糖摄取量、β-淀粉样蛋白水平、人口统计学信息及认知测试分数之间的条件依赖关系与偏相关系数。我们将模型应用于1022名参与者（包括健康个体与处于AD不同阶段的认知障碍患者）。研究发现，衰老通过三条间接通路导致认知功能下降：海马体积萎缩、后扣带回皮层（PCC）体积萎缩以及β-淀粉样蛋白累积。我们观察到女性性别与认知功能存在正向偏相关，但同时发现四条削弱该关联的间接通路：较低的海马体积、较低的PCC体积、较高的β-淀粉样蛋白累积以及较低的教育水平。研究显示脑区特异性葡萄糖摄取与认知功能关联有限，但发现海马与PCC体积与认知功能存在明确关联。这些结果表明，GCGM的应用为理解AD发病机制提供了有价值的见解。