Memory in Alzheimer's disease and mild cognitive impairment

阿尔茨海默病和轻度认知障碍中的记忆

• 批准号: 8958788
• 负责人: Andrew Budson
• 金额: --
• 依托单位: VA BOSTON HEALTH CARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-10-01 至 2017-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8958788
• 关键词: Affect; Age; Alzheimer' s Disease; Assisted Living Facilities; Communities; Confusion; Dependence; Disease; Elderly; Event-Related Potentials; Familiarity; Family; Future; Health; Hearing; Instruction; Intervention; Laboratory Finding; Life; Measures; Memory; Memory Loss; Memory impairment; Monitor; Pathology; Patients; Perception; Pharmaceutical Preparations; Reporting; Retrieval; Services; Source; Supermarket; Testing; Veterans; Work; base; behavior measurement; design; heuristics; improved; mild cognitive impairment; older patient; research study; response; statistics

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.

描述（由申请人提供）： 许多患有轻度阿尔茨海默病 (AD) 和阿尔茨海默病前期遗忘性轻度认知障碍 (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，当记忆力严重受损时，患有这些疾病的患者将需要获得额外的服务、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 相关已有一个多世纪的历史，但在 aMCI 和轻度 AD 中观察到的特定记忆障碍直到最近才得到研究。基于我们之前的工作，本提案将系统地操纵和评估可能受到 AD 病理学不同影响的记忆的不同组成部分（例如熟悉度、回忆、监控、源记忆、独特性启发）。通过了解记忆的哪些部分优先受损，哪些部分相对保留，可以设计未来的干预措施来帮助这些患者更加独立地生活。目标 1 将检验 aMCI 和轻度 AD 患者过度依赖熟悉度的假设。实验 1 和 2 结合了主观报告、行为测量和事件相关电位 (ERP)，以了解学习测试延迟（实验 1）或通过多次操作来改变项目熟悉程度时记忆中发生的变化，包括流畅性、不同滞后的项目重复以及不同的项目示例（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 将检验元认知指令是否可以促进利用图片的独特性来提高超市场景中的记忆。目标 2 将检验以下假设：aMCI 和轻度 AD 患者的记忆力受损，部分原因是他们监测反应的能力较差。实验 5 操纵了测试中已研究项目与未研究项目的基本比率，并询问受试者对他们看到了多少旧项目和新项目的看法。实验 6 评估当研究的项目少于未研究的项目时，告知患者已研究项目与未研究项目的基本比例是否可以减少错误识别并改善整体记忆。目标 3 将检验以下假设：aMCI 和 AD 患者对想象活动的错误记忆会因源记忆不良和对熟悉程度的过度依赖而增加，并因减少源记忆混乱的条件而减少。实验 7 评估对简单听到的和未想象的动作的真实和错误记忆。实验 8 评估学习和测试中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。总而言之，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，以制定可增强记忆力并改善 aMCI 和轻度 AD 患者生活的策略。