Memory in Alzheimer's disease and mild cognitive impairment

描述（由申请人提供）： 许多患有轻度阿尔茨海默病（AD）和阿尔茨海默病前遗忘型轻度认知障碍（aMCI）的患者独自生活在社区中。记忆功能障碍是AD和aMCI的标志，当他们的记忆受到充分损害时，患有这些疾病的患者将需要提供额外的服务，与家人住在一起，或搬到辅助生活设施。尽管记忆功能障碍与AD相关已有超过世纪的历史，但在aMCI和轻度AD中观察到的特异性记忆障碍仅在最近才被研究。在我们先前工作的基础上，本提案将系统地操纵和评估记忆的不同组成部分（例如，熟悉性、回忆、监测、源记忆、独特性启发式），其可能受到AD病理学的不同影响。通过了解哪些记忆成分优先受损，哪些相对保留，未来的干预措施可以帮助这些患者更独立地生活。目的1将检验aMCI和轻度AD患者过度依赖熟悉的假设。实验1和实验2结合了联合收割机主观报告、行为测量和事件相关电位（ERP），以了解学习测试延迟时记忆中发生的变化（实验1）。1），或与几个操纵，以改变熟悉的项目，包括流畅性，重复的项目在不同的滞后，和不同的例子的项目（实验。2）。实验3将尝试使用深度编码来降低基于熟悉度的错误识别并提高真实识别。实验4将考察在超市场景中，元认知指令是否有助于使用图片的独特性来提高记忆。目的2将检验以下假设：aMCI和轻度AD患者的记忆受损部分是由于他们监测自己反应的能力差。实验5操纵的基本比率的研究未研究的项目在测试和查询主题关于他们的看法有多少旧的和新的项目，他们已经看到。实验6评估是否告知患者的研究与未研究的项目的潜在比例，可以减少错误识别，提高整体记忆时，有研究比未研究的项目。目的3将检验以下假设：aMCI和AD患者对想象活动的错误记忆因源记忆不良和过度依赖熟悉而增加，并因减少源记忆混乱的条件而减少。实验7评估了仅仅听到的和没有想象到的动作的真实和虚假记忆。实验8评估学习和测试时的警告是否可以减少与想象活动相关的错误记忆，从而提高整体记忆。总之，本提案中的实验产生的实验室结果提供了必要的转化步骤，以制定可能增强记忆并改善aMCI和轻度AD患者生活的策略。

DESCRIPTION (provided by applicant): Many patients with mild Alzheimer's disease (AD) and the pre-Alzheimer's state of amnestic mild cognitive impairment (aMCI) live alone in the community. Memory dysfunction is the hallmark of AD and aMCI, and when their memory is sufficiently impaired, patients with these disorders will need to be provided with additional services, live with family, or move to an assisted living facility. Although memory dysfunction has been related with AD for over a century, the specific memory impairment observed in aMCI and mild AD has only recently been investigated. Building upon our prior work, the present proposal will systematically manipulate and evaluate different components of memory (e.g., familiarity, recollection, monitoring, source memory, the distinctiveness heuristic) that may be differentially affected by AD pathology. By understanding which components of memory are preferentially impaired, and which are relatively preserved, future interventions can be designed to help these patients live more independently. Aim 1 will test the hypothesis that patients with aMCI and mild AD are over-reliant upon familiarity. Experiments 1 and 2 combine subjective reports, behavioral measures, and event-related potentials (ERPs) to understand the changes that occur in memory with a study-test delay (Expt. 1), or with several manipulations to alter the familiarity of items, includng fluency, repetition of items at various lags, and different exemplars of items (Expt. 2). Experiment 3 will attempt to lower familiarity-based false recognition and raise true recognition using deep encoding. Experiment 4 will examine whether metacognitive instructions can facilitate use of the distinctiveness of pictures to improve memory in a supermarket scenario. Aim 2 will test the hypothesis that memory is impaired in patients with aMCI and mild AD in part due to their poor ability to monitor their responses. Experiment 5 manipulates the underlying ratio of studied to unstudied items at test and queries subjects regarding their perception of how many old and new items they have seen. Experiment 6 evaluates whether informing patients of the underlying ratio of studied versus unstudied items can reduce false recognition and improve overall memory when there are fewer studied than unstudied items. Aim 3 will test the hypothesis that false memories of imagined activities in patients with aMCI and AD are increased by poor source memory and over- dependence upon familiarity, and reduced by conditions that diminish source memory confusion. Experiment 7 evaluates true and false memories of actions simply heard and not imagined. Experiment 8 evaluates whether warnings at study and test can reduce false memories associated with the imagined activities, thereby improving overall memory. Taken together, the laboratory findings generated from experiments in this proposal provide the necessary translational steps to develop strategies that may enhance memory and improve the lives of patients with aMCI and mild AD.