Awareness of Deficit in Alzheimer's Disease

描述（由申请人提供）：记忆丧失意识障碍是早期阿尔茨海默病（AD）患者的一个显著症状。这种元认知障碍威胁着患者的安全，并给临床医生和护理人员带来了重大挑战，但关于其病因、性质、临床相关性、神经解剖学底物或预后相关性，几乎一无所知。该研究旨在通过实施严格的方法学框架，客观地测量具有不同意识水平的患者的特定记忆监测能力，从而在阿尔茨海默病的元认知研究中取得突破性进展。仔细操作实验任务来评估在线错误识别和内隐学习将揭示导致AD患者记忆丧失的意识紊乱的机制。拟议的研究还将通过评估与先前与自我意识方面相关的大脑特定区域的完整性相关的元认知变量，来检查意识紊乱发生的神经解剖学背景。结构和功能成像模式将应用于评估这一问题。

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.