Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, IL, USA.
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
Neurobiol Aging. 2024 Aug;140:81-92. doi: 10.1016/j.neurobiolaging.2024.04.002. Epub 2024 Apr 10.
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.
边缘为主型年龄相关性 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，我们检验了以下假设：LATE-NC 与大脑中通常含有 TDP-43 包涵体的区域网络的白质结构完整性和连接异常有关，我们称这个网络为“LATE-NC 网络”。我们对 184 名社区老年人进行了离体扩散 MRI 和详细的神经病理学数据采集。线性回归显示，随着 LATE-NC 阶段的升高，与一组形成连接模式的白质连接的扩散各向异性降低，这与该病理学在大脑中的典型传播模式一致。图论分析显示，LATE-NC 阶段越高，LATE-NC 网络的整合和分离能力越差。在 3 期时异常明显，这表明在疾病的晚期可以检测到这些异常。最后，LATE-NC 网络的异常与认知能力下降更快有关，特别是在情景记忆和语义记忆方面。
