Awareness of Deficit in Alzheimer's Disease

描述(由申请人提供)：记忆丧失的意识障碍是早期阿尔茨海默病(AD)患者的一种显著症状。这种元认知障碍威胁着患者的安全，给临床医生和照顾者带来了巨大的挑战，但对其病因、性质、临床相关性、神经解剖学基础或预后相关性几乎一无所知。这项拟议的研究旨在通过实施一种严格的方法学框架，客观地测量具有不同意识水平的患者的特定记忆监控能力，从而在AD的元认知研究中取得突破性进展。仔细操纵实验任务以评估在线错误识别和内隐学习，将有助于揭示导致AD患者记忆丧失意识紊乱的机制。这项拟议的研究还将通过评估与先前与自我意识相关的大脑特定区域的完整性相关的元认知变量，来研究意识紊乱发生的神经解剖学背景。将应用结构和功能成像方式来评估这一问题。 最后，这项拟议的研究将通过检查元记忆缺陷与决策能力和生活质量之间的关系来弥合认知评估和临床效用之间的差距，这两个问题是阿尔茨海默病患者日常生活中的两个关键问题。未来的神经成像、认知和元认知评估将在基于社区的纵向研究的背景下进行。这样的框架将有助于通过正常认知、记忆衰退和痴呆症诊断过程来研究个体的元认知变化，特别是在患者出现在临床之前的记忆丧失的早期阶段的意识缺陷。研究结果可能对轻度认知障碍(MCI)的诊断具有重要意义，MCI被认为是AD发病的先兆，但部分由主观记忆主诉来定义。研究结果还可用于评估AD患者对参与研究提供知情同意的能力。在某种程度上，意识障碍与特定的神经解剖学特征有关，意识障碍会降低决策能力，研究计划可能会系统性地排除AD的一个临床亚型。这项拟议的研究为研究这些和其他临床相关问题提供了一个跳板。

DESCRIPTION (provided by applicant): Disordered awareness of memory loss is a striking symptom displayed by a subset of patients with early Alzheimer's disease (AD). This metacognitive disturbance threatens patient safety and poses significant challenges for clinicians and caregivers, yet virtually nothing is known regarding its etiology, nature, clinical correlates, neuroanatomic substrates, or prognostic relevance. The proposed study aims to break ground in the study of metacognition in AD by implementing a rigorous methodological framework that will objectively measure specific memory monitoring abilities across patients with a range of awareness levels. Carefully manipulating the experimental task to assess online error recognition and implicit learning will shed light on the disrupted mechanisms that give rise to disordered awareness of memory loss in AD. The proposed study will also examine the neuroanatomic context in which disordered awareness occurs by evaluating metacognitive variables in relation to the integrity of specific areas of the brain previously linked with aspects of self-awareness. Structural and functional imaging modalities will be applied to evaluate this issue. Finally, the proposed study will bridge the gap between cognitive assesment and clinical utility by examining the manner in which deficits in metamemory relate to decision making capacity and quality of life, two critical issues in the everyday lives of persons with Alzheimer's disease. Future neuroimaging, cognitive and metacognitive evaluations will be done in the context of a community based, longitudinal study. Such a framework will facilitate study of metacognitive change in individuals through the course of normal cognition, memory decline, and dementia diagnosis, bearing particular light on awareness of deficit in the earliest stages of memory loss, before patients present to the clinic. Results may have significant implications for the diagnosis of Mild Cognitive Impairment (MCI), a condition which is believed to herald the onset of AD, but is defined in part by subjective memory complaint. Results may also inform the assessment of capacity to provide informed consent for research participation in persons with AD. To the extent that disordered awareness is associated with a particular neuroanatomic profile, and disordered awareness reduces decision making capacity, research programs may systematically exclude a clinical subtype, of AD. The proposed study serves as a spring board for studying these and other clinically relevant issues.