Epidemiologic Study of Decision Making in Preclinical Alzheimer's Disease

 描述（由申请人提供）：许多生活中最复杂和最有影响力的决定是在老年做出的，矛盾的是，就像神经病理学积累和认知功能下降一样。尽管越来越多的人认识到，老年人的决策能力差构成了一个关键的公共卫生和经济挑战，但令人惊讶的是，决策能力在老龄化研究中几乎没有得到科学关注。在第一个资助期内，我们评估了来自记忆和衰老项目（一项正在进行的衰老纵向临床病理研究）的800多名非痴呆老年人的决策。我们报告说，决策需要不同的资源（即，认知、情感和情境），并且许多没有痴呆症的老年人在对独立性和幸福感至关重要的领域中表现出糟糕的决策（例如，金融、医疗保健）。糟糕的决策也与阿尔茨海默病（AD）和轻度认知障碍的风险大幅增加有关，这表明它可能是临床前痴呆的早期表现。拟定延续研究（R01AG33678）的总体目标是检查随时间推移决策中年龄相关变化的原因和后果。我们将量化没有痴呆症的老年人的大型队列多年来决策的变化，并记录决策变化与关键健康和心理结果的关联。接下来，基于令人信服的初步数据显示，AD和脑血管疾病（CVD）的神经病理学与决策有关，我们将测试的假设，即常见的神经病理学有助于决策的年龄相关的变化。此外，基于研究表明的重要作用，胺能系统作为调制器的决策，我们将测试的假设，胺能系统有助于维护决策在面对神经病理学。最后，我们将研究背景因素和其他行为因素如何与神经生物学指标相互作用以影响决策。拟议的研究提供了一个独特的机会，将长达12年的年度决策和临床数据与已知损害老年功能的最常见神经病理学的神经生物学指标（即，AD、CVD、路易体病理学）和胺能系统（即，多巴胺，去甲肾上腺素），以确定神经生物学基础和决策中年龄相关变化的后果。我们不知道其他可以进行类似分析的研究。这项研究是独一无二的准备告知的后果和原因与年龄有关的决策变化，并将促进新的治疗方法，以促进独立，健康和幸福的老年人。

 DESCRIPTION (provided by applicant): Many of life's most complex and influential decisions are made in old age, paradoxically just as neuropathology accumulates and cognitive function declines. Despite increased recognition that poor decision making in old age poses a critical public health and economic challenge, decision making has received surprisingly little scientific focus in aging research. In the first funding period, we assessed decision making in >800 older persons without dementia from the Memory and Aging Project, an ongoing longitudinal clinical-pathologic study of aging. We reported that decision making requires diverse resources (i.e., cognitive, affective, and contextual), and that many older persons without dementia exhibit poor decision making in domains critical for independence and well being (e.g., financial, healthcare). Poor decision making also is associated with a substantially increased risk of Alzheimer's disease (AD) and mild cognitive impairment, suggesting that it may be an early manifestation of preclinical dementia. The overall goal of the proposed continuation (R01AG33678) is to examine the causes and consequences of age-related changes in decision making over time. We will quantify changes in decision making over many years in a large cohort of older persons without dementia and document the association of change in decision making with critical health and psychological outcomes. Next, based on compelling preliminary data showing that the neuropathologies of AD and cerebrovascular disease (CVD) are associated with decision making, we will test the hypothesis that common neuropathologies contribute to age-related changes in decision making. Further, based on research demonstrating the important role of aminergic systems as modulators of decision making, we will test the hypothesis that aminergic systems help preserve decision making in the face of neuropathology. Finally, we will examine how contextual and other behavioral factors interact with neurobiologic indices to influence decision making. The proposed study offers a unique opportunity to integrate up to 12 years of annual decision making and clinical data with neurobiologic indices of the most common neuropathologies known to impair function in old age (i.e., AD, CVD, Lewy body pathology) and aminergic systems (i.e., dopamine, norepinephrine) in order to identify the neurobiologic basis and consequences of age-related changes in decision making. We are not aware of other studies in which similar analyses could be performed. This study is uniquely poised to inform on the consequences and causes of age-related changes in decision making and will facilitate new therapeutic approaches to promote independence, health and well-being in old age.