Limbic predominant age-related TDP-43 encephalopathy neuropathological change (LATE-NC) is common in older adults and is associated with neurodegeneration, cognitive decline and dementia. In this MRI and pathology investigation we tested the hypothesis that LATE-NC is associated with abnormalities in white matter structural integrity and connectivity of a network of brain regions typically harboring TDP-43 inclusions in LATE, referred to here as the “LATE-NC network”. Ex-vivo diffusion MRI and detailed neuropathological data were collected on 184 community-based older adults. Linear regression revealed an independent association of higher LATE-NC stage with lower diffusion anisotropy in a set of white matter connections forming a pattern of connectivity that is consistent with the stereotypical spread of this pathology in the brain. Graph theory analysis revealed an association of higher LATE-NC stage with weaker integration and segregation in the LATE-NC network. Abnormalities were significant in stage 3, suggesting that they are detectable in later stages of the disease. Finally, LATE-NC network abnormalities were associated with faster cognitive decline, specifically in episodic and semantic memory.

中文翻译：

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边缘系统主导的年龄相关 TDP-43 脑病神经病理改变 (LATE-NC) 与白质结构完整性和连接性异常相关：体外扩散 MRI 和病理学研究


边缘系统主要与年龄相关的 TDP-43 脑病神经病理改变 (LATE-NC) 在老年人中很常见，与神经退行性变、认知能力下降和痴呆有关。在这项 MRI 和病理学研究中，我们测试了以下假设：LATE-NC 与白质结构完整性异常以及 LATE 中通常含有 TDP-43 内含物的大脑区域网络的连接性异常相关，此处称为“LATE-NC 网络” ”。收集了 184 名社区老年人的离体扩散 MRI 和详细的神经病理学数据。线性回归揭示了一组白质连接中较高的 LATE-NC 阶段与较低的扩散各向异性之间的独立关联，形成了一种与大脑中这种病理学的典型传播一致的连接模式。图论分析揭示了较高的 LATE-NC 阶段与 LATE-NC 网络中较弱的集成和分离之间的关联。异常现象在第三阶段很显着，表明它们在疾病的后期是可以检测到的。最后，LATE-NC 网络异常与更快的认知能力下降有关，特别是在情景记忆和语义记忆方面。