Which Memory System is Impaired First in Alzheimer's Disease?
Which Memory System is Impaired First in Alzheimer's Disease?
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DOI：
10.3233/jad-2011-110557
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发表时间：
2011-01-01
影响因子：
4
通讯作者：
Ceccaldi, Mathieu
中科院分区：
文献类型：
--
作者：
Didic, Mira;Barbeau, Emmanuel J.;Ceccaldi, Mathieu
随着疾病修饰剂的开发，阿尔茨海默病（AD）早期阶段的诊断变得越来越重要。在这一研究领域，许多临床和神经影像学研究集中在海马功能障碍的标志物。然而，在AD的“transentorhinal阶段”期间，与tau蛋白病理学相关的神经元缠结（NFT）在海马体之前的前海马下（嗅周/内嗅）皮质中发展。NFT与临床症状密切相关。因此，准确了解经内嗅功能障碍的行为相关性，有助于疾病的早期诊断。最近在动物和人类脑损伤患者中的研究结果表明，前海马下区，功能整合到前mesiotemporal网络，涉及基于对象的上下文无关的记忆。在这篇文章中，我们评估的假设，根据该tau蛋白沉积在前海马下区在最常见的形式的AD的最早阶段，与主要MTL功能障碍，将导致涉及上下文无关的记忆的神经网络功能障碍。我们质疑情景记忆受损是早期AD标志的观点。相反，提出了一种模型，该模型集成了内侧颞叶（MTL）内的NFT的定位和时间序列。除了海马下前区NFT的发展外，背景无关、基于物体的记忆受损可能是AD的第一个可检测的体征。在随后的“海马”阶段，丰富的背景、情节和空间记忆也发生了变化。问题的“情节”性质的“情节记忆任务”也得到解决。
Diagnosis of Alzheimer's disease (AD) in its earliest stages becomes increasingly important as disease modifying agents are being developed. In this area of research, many clinical and neuroimaging studies focus on markers of hippocampal dysfunction. However, during the "transentorhinal stage" of AD, neurofibrillary tangles (NFT), related to tau protein pathology, develop in the anterior subhippocampal (perirhinal/entorhinal) cortex before the hippocampus. NFT are tightly correlated with clinical symptoms. Therefore, an accurate understanding of the behavioral correlate of transentorhinal dysfunction could critically contribute to the early diagnosis of the disease. Recent findings from studies in animals and human brain-damaged patients suggest that the anterior subhippocampal region, functionally integrated into an anterior mesiotemporal network, is involved in object based context-free memory. In this article, we evaluate the hypothesis according to which tau deposition in the anterior subhippocampal region during the earliest stages of the most common form of AD, with predominant MTL dysfunction, will lead to dysfunction of neural networks implicated in context-free memory. We challenge the view that impaired episodic memory is the hallmark of early AD. Instead, a model that integrates the localization and temporal sequence of NFT within the mesial temporal lobe (MTL) is proposed. Paralleling the development of NFT in anterior subhippocampal areas, impaired context-free, object-based, memory could be the first detectable sign in AD. In a subsequent, "hippocampal" stage, context-rich, episodic and spatial memory, becomes altered as well. The question as to the "episodic" nature of "episodic memory tasks" is also addressed.