Agrawal Sonal, Yu Lei, Leurgans Sue E, Nag Sukriti, Barnes Lisa L, Bennett David A, Schneider Julie A
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, USA.
Department of Pathology, Rush University Medical Center, Chicago, Illinois, USA.
Alzheimers Dement. 2025 Feb;21(2):e14500. doi: 10.1002/alz.14500. Epub 2025 Jan 30.
This study investigates the inter-related roles of hippocampal neuronal loss (HNL), limbic-predominant age-related TAR-DNA binding protein of 43 kDa (TDP-43) encephalopathy neuropathologic changes (LATE-NC), and Alzheimer's disease neuropathologic changes (ADNC) on cognitive decline.
Participants underwent annual cognitive testing and autopsy. HNL, ADNC, LATE-NC, and other age-related pathologies were evaluated. Regression and mixed-effects models examined the association of HNL with ADNC and LATE-NC, and separately with cognitive decline. Path analyses examined the extent to which associations of LATE-NC and ADNC with cognitive decline were attributable to HNL.
LATE-NC was associated with more severe HNL, but ADNC was associated only after excluding subjects with hippocampal sclerosis (HS). HNL was associated with faster decline in global cognition and episodic, semantic, and working memory. In path analyses, about 61% of the association of LATE-NC with cognitive decline was attributable to HNL, whereas for ADNC it was mostly independent of HNL.
HNL has an independent contribution to cognitive decline and acts as a major step in LATE-NC-related cognitive decline.
Hippocampal neuronal loss (HNL) is associated with cognitive decline. HNL is a prominent feature of limbic-predominant age-related TDP-43 encephalopathy neuropathologic changes (LATE-NC) and less so with Alzheimer's disease neuropathologic changes (ADNC). HNL acts as a major pathway in cognitive decline for LATE-NC. Differential mechanisms in hippocampal degeneration are associated with LATE-NC versus ADNC.
本研究调查海马神经元丢失（HNL）、边缘叶为主的年龄相关性43 kDa TAR-DNA结合蛋白（TDP-43）脑病神经病理改变（LATE-NC）以及阿尔茨海默病神经病理改变（ADNC）在认知衰退中的相互关联作用。
参与者每年接受认知测试和尸检。对HNL、ADNC、LATE-NC及其他年龄相关病理改变进行评估。回归模型和混合效应模型检验HNL与ADNC、LATE-NC的关联，并分别检验其与认知衰退的关联。路径分析检验LATE-NC和ADNC与认知衰退的关联在多大程度上可归因于HNL。
LATE-NC与更严重的HNL相关，但仅在排除海马硬化（HS）患者后，ADNC才与之相关。HNL与整体认知、情景记忆、语义记忆和工作记忆的更快衰退相关。在路径分析中，LATE-NC与认知衰退的关联约61%可归因于HNL，而ADNC与认知衰退的关联大多独立于HNL。
HNL对认知衰退有独立作用，且是LATE-NC相关认知衰退的主要环节。
海马神经元丢失（HNL）与认知衰退相关。HNL是边缘叶为主的年龄相关性TDP-43脑病神经病理改变（LATE-NC）的突出特征，与阿尔茨海默病神经病理改变（ADNC）的相关性较弱。HNL是LATE-NC认知衰退的主要途径。海马变性的不同机制与LATE-NC和ADNC相关。
