Epidemiologic Study of Impaired Decision-Making in Preclinical Alzheimer's Diseas

描述（由申请人提供）：拟议的流行病学研究的总体目标是检查老年决策受损的原因和后果。决策是指产生和处理多个竞争方案并选择有利行为的能力。事实上，所有的行为都是决策过程的结果，有效的决策被认为是现代社会中保持独立，健康和幸福的关键。新出现的数据表明，老年人，甚至一些没有痴呆症，表现出决策能力受损，决策能力受损可能是临床前阿尔茨海默病（AD）的标志。然而，令人惊讶的是，很少有研究严格审查老年人的决策，纵向数据也非常缺乏。这项拟议的研究将量化一个大型社区老年人队列中财务、医疗保健和社会情感决策的变化率，并检验决策受损与不良健康结果相关的假设（即，幸福感下降、残疾、护理院安置、痴呆和死亡）。此外，我们将研究情感和背景因素在决策中的作用，并测试假设，即使在认知能力下降的情况下，选择情感和背景因素也可以维持决策。最后，在努力了解决策受损的神经生物学基础，我们将测试的假设，即AD病理有助于决策受损的老年人没有痴呆谁来尸检。这项拟议的研究将利用拉什记忆和衰老项目（R01AG17917）提供的独特基础设施，这是一项正在进行的关于衰老和AD的大型流行病学临床病理学研究，并将量化800多名社区参与者的决策和新的病理学指标，所有参与者都同意进行详细的年度临床评估，包括认知评估和大脑捐赠。通过将新收集的决策和大脑区域中有助于决策的AD病理学数据与记忆和衰老项目的可用数据联系起来，我们将有前所未有的机会来研究老年决策受损的原因和后果。了解决策受损的原因和后果，对于制定有效的干预措施以促进老年人的独立、健康和福祉至关重要。公共卫生相关性：拟议的研究有可能产生具有重要公共卫生意义的新知识。老年人面临着一系列决定，这些决定对于在现代社会中保持独立、健康和福祉至关重要，如果发现相当多的未患痴呆症的老年人表现出决策能力受损，则表明迫切需要采取干预措施和公共政策努力，促进老龄化问题的有效决策。此外，决策受损的原因和后果的知识是必不可少的，这样的干预措施的发展，并在一定程度上，AD病理学的决策受损的基础，可能表明，一个更大的人群，包括那些没有明显的痴呆症最终可能受益于有效的治疗和预防策略开发的AD。

DESCRIPTION (provided by applicant): The overall goal of the proposed epidemiologic study is to examine the causes and consequences of impaired decision-making in old age. Decision-making refers to the ability to generate and process multiple competing alternatives and choose a favorable behavior. Virtually all behaviors result from some decision-making process, and efficient decision-making is thought to be critical for maintaining independence, health and well-being in modern society. Emerging data suggest that older persons, even some without dementia, exhibit impaired decision-making, and impaired decision-making may be a sign of preclinical Alzheimer's disease (AD). However, surprisingly few studies have rigorously examined decision-making in older persons and longitudinal data are sorely lacking. The proposed study will quantify the rate of change in financial, healthcare, and socioemotional decision-making in a large cohort of community-based older persons without dementia and test the hypothesis that impaired decision-making is associated with adverse health outcomes (i.e., decreased well-being, disability, nursinghome placement, dementia, and death). Further, we will examine the role of affective and contextual factors in decision-making and test the hypothesis that select affective and contextual factors can sustain decision-making even in the face of cognitive decline. Finally, in an effort to understand the neurobiologic basis of impaired decision-making, we will test the hypothesis that AD pathology contributes to impaired decision-making in older persons without dementia who come to autopsy. The proposed study will capitalize on the unique infrastructure provided by the Rush Memory and Aging Project (R01AG17917), a large ongoing epidemiologic clinical-pathologic study of aging and AD, and will quantify decision-making and new pathologic indices in more than 800 community-based participants without dementia; all have agreed to detailed annual clinical evaluations including cognitive assessments and brain donation. By linking the newly collected data on decision-making and AD pathology in brain regions that subserve decision-making with the available data from the Memory and Aging Project, we will have an unprecedented opportunity to examine the causes and consequences of impaired decision-making in old age. Knowledge of the causes and consequences of impaired decision-making is essential for the development of effective interventions to promote independence, health, and well-being in old age. PUBLIC HEALTH RELEVANCE: The proposed study has the potential to generate new knowledge with important public health implications. Older persons are faced with a host of decisions that are critical for maintaining independence, health and well-being in modern society, and finding that a sizeable number of older persons without dementia exhibit impaired decision-making would suggest an immediate need for interventions and public policy efforts to promote efficient decision-making in aging. Further, knowledge of the causes and consequences of impaired decision-making is essential for the development of such interventions and, to the extent that AD pathology underlies impaired decision-making, may suggest that a much larger group of persons including those without overt dementia ultimately may benefit from effective treatment and prevention strategies developed for AD.