Epidemiologic Study of Decision Making in Preclinical Alzheimer's Disease

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相互竞争的备选方案并选择有利行为的能力。几乎所有的行为都是由某种决策过程产生的，高效的决策被认为是现代社会保持独立、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的人，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)的迹象。然而，令人惊讶的是，几乎没有研究严格检查老年人的决策，而且非常缺乏纵向数据。这项拟议的研究将量化大量非痴呆症社区老年人在财务、医疗保健和社会情感决策方面的变化率，并测试决策受损与不良健康结果(即幸福感降低、残疾、养老院安置、痴呆症和死亡)相关的假设。此外，我们将考察情感和语境因素在决策中的作用，并检验这样一种假设，即选择情感和语境因素即使在认知衰退的情况下也可以维持决策。最后，为了了解决策受损的神经生物学基础，我们将测试AD病理有助于尸检的非痴呆症老年人决策受损的假设。这项拟议的研究将利用Rush Memory and Aging Project(R01AG17917)提供的独特基础设施，这是一项正在进行的关于老龄化和AD的大型流行病学临床病理学研究，并将量化800多名非痴呆症社区参与者的决策和新的病理指标；所有人都同意进行详细的年度临床评估，包括认知评估和脑捐赠。通过将新收集的决策和大脑辅助决策区域的AD病理数据与记忆和老龄化项目的现有数据联系起来，我们将有一个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、健康和幸福至关重要。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影响的新知识。老年人面临着许多对在现代社会中保持独立、健康和福祉至关重要的决定，如果发现相当数量的非痴呆症老年人的决策受到损害，则表明迫切需要采取干预措施和公共政策努力，以促进老龄问题的有效决策。此外，对决策受损的原因和后果的了解对于制定此类干预措施至关重要，而且，由于AD病理是决策受损的基础，因此可能表明，更多的人，包括那些没有明显痴呆的人，最终可能受益于为AD制定的有效治疗和预防战略。

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.