Tau neurofibrillary tangles have a central role in the pathogenesis of Alzheimer’s Disease (AD). Mounting evidence indicates that the propagation of tau is assisted by brain connectivity with weakened white-matter integrity along the propagation pathways. Recent advances in tau positron emission tomography tracers and diffusion magnetic resonance imaging allow the visualization of tau pathology and white-matter connectivity of the brain in vivo. The current study aims to investigate how tau deposition and structural connectivity are associated with memory function in prodromal AD. In this study, tau accumulation and structural connectivity data from 83 individuals (57 cognitively normal participants and 26 participants with mild cognitive impairment) were associated with neurocognitive test scores. Statistical analyses were performed in 70 cortical/subcortical brain regions to determine: 1. the level of association between tau and network metrics extracted from structural connectivity and 2. the association patterns of brain memory function with tau accumulation and network metrics. The results showed that tau accumulation and network metrics were correlated in early tau deposition regions. Furthermore, tau accumulation was associated with worse performance in almost all neurocognitive tests performance evaluated in the study. In comparison, decreased network connectivity was associated with declines in the delayed memory recall in Craft Stories and Benson Figure Copy. Interaction analysis indicates that tau deposition and dysconnectivity have a synergistic effect on the delayed Benson Figure Recall. Overall, our findings indicate that both tau deposition and structural dysconnectivity are associated with neurocognitive dysfunction. They also suggest that tau-PET may have better sensitivity to neurocognitive performance than diffusion MRI-derived measures of white-matter connectivity.

Tau 神经原纤维缠结在阿尔茨海默病 (AD) 的发病机制中具有核心作用。越来越多的证据表明，大脑连接有助于 tau 的传播，而大脑连接沿着传播路径减弱了白质完整性。tau 正电子发射断层扫描示踪剂和扩散磁共振成像的最新进展使 tau 病理学和体内大脑白质连接的可视化成为可能。目前的研究旨在研究 tau 沉积和结构连接如何与前驱 AD 中的记忆功能相关联。在这项研究中，来自 83 名个体（57 名认知正常参与者和 26 名轻度认知障碍参与者）的 tau 积累和结构连接数据与神经认知测试分数相关。对 70 个皮质/皮质下脑区进行了统计分析，以确定：1. 从结构连接中提取的 tau 和网络指标之间的关联水平；2. 脑记忆功能与 tau 积累和网络指标的关联模式。结果表明，tau 积累和网络指标在早期 tau 沉积区域是相关的。此外，在研究中评估的几乎所有神经认知测试表现中，tau 积累与较差的表现有关。相比之下，网络连接性下降与 Craft Stories 和 Benson Figure Copy 中延迟记忆回忆的下降有关。相互作用分析表明，tau 沉积和连接障碍对延迟的 Benson Figure Recall 具有协同作用。全面的，我们的研究结果表明，tau 蛋白沉积和结构性连接障碍都与神经认知功能障碍有关。他们还表明，tau-PET 对神经认知性能的敏感性可能比扩散 MRI 衍生的白质连接性测量更好。