Decision-making abilities in Alzheimer's disease and related dementias: From clinical standards to decision neuroscience

项目概要/摘要 阿尔茨海默病和相关痴呆症的特征是早期和重大的决策障碍， 这通常会给患者及其家人带来灾难性的后果。虽然最近的研究在决策 神经科学和神经经济学为阐明这些潜在的神经机制提供了巨大的希望。 障碍（最终，为了实现更深入的理解，可以产生改善的策略， 患者的决定），在许多情况下，仍然不清楚如何神经科学的发现可以应用于 患者在真实的生活中所表现出的决策错误。这种前沿研究与 和临床实践将在拟议的工作中通过将当前的决策神经科学与 临床标准通常用于评估患者的决策能力。在广泛的- 在痴呆症和其他认知障碍中，公认的标准、受损的决定可能是由于未能： (1)理解决策的相关特征，（2）理解这与自己的情况有何关系，（3） 理性地操纵信息以达成决策，或（4）始终如一地证明选择。这些标准 反映了临床医生对患者损伤的专业知识，并体现了关于如何 人们做出决策，以及决策如何在疾病中受到影响-现在可以 使用决策神经科学的工具进行了实证研究。研究计划围绕 三个具体目标代表了当前神经科学与公认的临床标准之间的联系： 1（赏析）：以价值观为基础研究不同痴呆综合征的元认知障碍 选择2（推理）：阐明将相关信息应用于决策的机制， 在老年痴呆症中被破坏。3（选择）：评估不同偏好中的不一致性 痴呆综合征在这项工作中，我们将从阿尔茨海默氏症患者的良好特征队列中提取 疾病，额颞叶痴呆患者和健康的老年对照，所有这些都与临床和 神经成像数据。多个队列将允许综合征或靶向大脑之间的特定关联 结构和异常的决定;否则，疾病或认知能力下降的一般影响往往不能 被排除在外。目标1和3将采用基于计算机的行为测试与决策 任务，而目标2将在决策任务期间使用基于任务的功能磁共振成像。创新 这种方法将提高外部效度（通过将结果与临床专家关于决策的工作联系起来）。 患者在日常生活中表现出的损伤）和僵硬（使用跨疾病的比较来确保 研究结果反映了特定的神经效应，而不是其他混乱）。因此，拟议的工作准备 通过将决策神经科学与广泛接受的临床标准联系起来， 推进我们对临床决策障碍机制的理解，最终导致 改进评估工具，并确定未来干预措施的目标，以防止对患者造成严重伤害。

PROJECT SUMMARY/ABSTRACT Alzheimer’s disease and related dementias are marked by early and significant impairments in decision- making, often with disastrous consequences for patients and their families. While recent research in decision neuroscience and neuroeconomics holds great promise for elucidating neural mechanisms underlying these impairments (and ultimately, for achieving a deeper understanding that can yield strategies for improving patients’ decisions), in many cases it remains unclear how neuroscientific findings can be applied to the decision-making errors that patients exhibit in real life. This translational gap between cutting-edge research and clinical practice will be addressed in the proposed work by linking current decision neuroscience to clinical standards routinely applied in the assessment of patients’ decision-making abilities. On a widely- accepted standard, impaired decisions in dementia and other cognitive disorders can result from failures to: (1) understand relevant features of a decision, (2) appreciate how this relates to one’s own situation, (3) rationally manipulate information to arrive at a decision, or (4) consistently evidence a choice. These criteria reflect clinicians’ expertise with patients’ impairments and embody mechanistic assumptions about how people make decisions and how decision-making is compromised in disease—assumptions that can now be investigated empirically using tools of decision neuroscience. The proposed research is organized around three specific aims that represent links between current neuroscience and accepted clinical standards: 1 (Appreciation): Investigate metacognitive impairments in different dementia syndromes in value-based choice. 2 (Reasoning): Elucidate mechanisms for applying relevant information to decision-making, which are disrupted in Alzheimer’s disease. 3 (Choice): Assess inconsistency in revealed preferences in different dementia syndromes. In this work we will draw from well-characterized cohorts of patients with Alzheimer’s disease, patients with frontotemporal dementia, and healthy older controls, all with linked clinical and neuroimaging data. Multiple cohorts will allow for specific associations between syndromes or targeted brain structures and abnormal decisions; otherwise, generic effects of illness or diminished cognition often cannot be excluded. Aims 1 & 3 will be pursued using computer-based behavioral testing with decision-making tasks, while Aim 2 will be pursued using task-based fMRI during a decision-making task. The innovative approach will enhance external validity (by linking results to the work of clinical experts about the decisional impairments that patients exhibit in daily life) and rigor (using comparisons across diseases to assure that findings reflect specific neural effects rather than other confounds). The proposed work is therefore poised to make a significant contribution by linking decision neuroscience with widely-accepted clinical standards to advance our understanding of mechanisms of clinical decision-making impairments, ultimately resulting in improved assessment tools and in targets for future interventions to prevent serious harms to patients.