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.
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