The neural correlates of personal semantic memory across the lifecourse

尽管进行性记忆丧失是阿尔茨海默病（AD）的一个典型特征，但目前还没有普遍认可的诊断测试。研究和临床实践的一个主要挑战是很难区分健康衰老和阿尔茨海默病，两者都与记忆功能下降有关。因此，至关重要的是开发更具体的记忆功能测试，以区分与健康衰老相关的记忆概况和与AD风险相关的记忆概况。我们的长期记忆通常分为两类。一方面，语义记忆是我们对世界的一般认识（例如：“1984”是乔治·奥威尔写的一本书的书名）。这种知识被认为是脱离其获取背景的（即，我们不会记得我们是在何时何地学到它的），并且在文化上是共享的。另一方面，情景记忆涉及我们对特定情境的个人事件的记忆（我记得昨天在海德公园读了《1984》）。语义记忆和情景记忆这两种类型的长期记忆之间的区别现在已经确立。我们知道，这些记忆系统与不同的大脑区域有关，并且在健康衰老和阿尔茨海默病中受到不同的损害：语义记忆在衰老和早期阿尔茨海默病中往往保存良好，而情景记忆的表现往往随着年龄的增长而下降，并在阿尔茨海默病中受到损害。然而，最近的数据表明，在语义记忆和情景记忆之间可能存在其他形式的记忆。这些额外的类型，统称为个人语义，涉及一个人过去的知识(例如：“我和奥威尔一样出生于6月25日”；我曾经在中学学习过奥威尔的作品”，或者“我是一个快速阅读者”)。个人语义学与语义记忆和情景记忆具有共同的特征，但似乎是可以区分的。个人语义记忆是个人的（如情景记忆），但脱离了特定的习得背景（如语义记忆）。然而，这些形式的记忆还没有得到全面的研究，我们不知道它们是如何在大脑中表现出来的。为了更好地理解记忆，关键需要的是将不同类型的个人语义与语义和情景记忆过程进行比较的实验。此外，由于已知这些不同类型的记忆在衰老和阿尔茨海默病中进化不同，因此研究年轻人和老年人的个人语义并确定阿尔茨海默病风险个体的特定记忆概况非常重要。这就是我们在目前的研究项目中所要做的。我们将研究到目前为止所描述的不同类型的个人语义，并比较年轻人和老年人群体的神经基础，同时考虑到AD的遗传风险。为此，我们将招募60名年轻人（18-30岁）和100名老年人（65-80岁）参与者，其中一半有患AD的遗传风险。利用脑电图（EEG）和磁共振成像（MRI），我们将能够：1)揭示个人语义作为陈述性记忆的一个新组成部分是如何在大脑中表现的；2)确定个人语义如何随着年龄的增长以及与AD风险相关的人的变化；3)通过监测健康老年人的早期记忆偏离谱，为AD的临床诊断提供新的工具。至关重要的是，由于目前没有心理测试允许同时评估这三种类型的记忆（即语义，情景和个人语义），我们的结果将直接有助于开发新的记忆测试。综上所述，目前的项目将提供独特的机会，以更好地了解年轻人和老年人未被充分研究的记忆形式，同时也可以改善对健康老龄化和AD风险人群的记忆功能的评估。

Even though progressive memory loss is a defining feature of Alzheimer's disease (AD), there is currently no universally recognised diagnostic test. One major challenge for research and clinical practice is that it is difficult to differentiate healthy ageing from AD, both being associated with decline in memory function. It is thus critical to develop more specific tests of memory functions to differentiate memory profiles associated with healthy ageing and those associated with risk for AD. Our long-term memories are generally divided into two categories. On the one hand, semantic memory is our general knowledge of the world (for instance: "1984" is the title of a book written by George Orwell). This knowledge is considered to be detached from its context of acquisition (i.e., we would not remember when or where we have learned it) and to be culturally shared. On the other hand, episodic memory concerns our memories of context-specific personal events (I remember reading "1984" at Hyde Park yesterday). The distinction between these 2 types of long-term memory, semantic and episodic, is now well-established. We know that these memory systems are associated with different brain regions and are impaired differently in healthy ageing and AD: semantic memory tends to be well-preserved in ageing and in early AD, while episodic memory performance tends to decrease with advancing age and to be impaired in AD.However, recent data suggest that there may be additional forms of memory between the categories of semantic and episodic. These additional types, collectively referred to as personal semantics concerns knowledge of one's past (for instance: "I was born on the 25th of June like Orwell"; " I used to study Orwell's work at secondary school", or "'I am a fast reader"). Personal semantics share features with both semantic and episodic memory but appear to be distinguishable from them. Personal semantic memories are personal (like episodic memory), yet detached from a specific context of acquisition (like semantic memory). However, these forms of memories have not been comprehensively studied and we do not know how they are represented in the brain. What is crucially needed to better understand memory are experiments that compare different types of personal semantics against semantic and episodic memory processes. Moreover, since these distinct types of memory are known to evolve differently through ageing and AD, it is therefore important to study personal semantics in young and older adults and to identify the specific memory profiles of individuals at risk for AD. This is what we are proposing to do in the present research project. We will study the distinct types of personal semantics that have been described so far and compare their neural bases in groups of young and older adults, taking into account genetic risk for AD. For this, we will recruit 60 young (18-30) and 100 older (65-80) participants, half of which are at genetic risk for AD. Using electroencephalography (EEG) and magnetic resonance imaging (MRI), we will be able to: 1) Uncover how personal semantics, as a new component of declarative memory, is represented in the brain; 2) Identify how personal semantics evolve with age and in those associated with risk for AD; and 3) Propose new tools for the clinical diagnosis of AD by monitoring early departure from memory profiles observed in healthy older adults. Crucially, as no psychological test currently available allows the evaluation of the 3 types of memory together (i.e., semantic, episodic and personal semantics), our results will directly contribute to the development of new memory tests.Taken together, the present project will provide unique opportunities to better understand understudied forms of memory in younger and older adults, but also to improve the evaluation of memory functions in healthy ageing and in those at risk for AD.