Alzheimer's disease risk factors as mediators of subjective memory impairment and objective memory decline: A construct-level replication across four studies

项目摘要 主观记忆障碍（SMI），或在缺乏客观记忆的情况下感知记忆问题。 记忆缺陷与个人和社会意义的负面结果有关，包括 阿尔茨海默病（AD）的风险大大增加。然而，对调解人知之甚少， 将SMI与某些个体的记忆力下降联系起来，或者患有SMI的老年人的风险最大 记忆衰退老年人的SMI与几个可改变的AD风险因素相关：抑郁 症状，焦虑症状，减少活动参与（包括身体，社会和认知 活动）。虽然这些关联已经被横向研究过了，但是几乎没有纵向证据存在 有助于我们理解症状的暂时性。此外，迄今为止的研究还没有 认为这些症状相关性是AD风险的潜在贡献者，即使是情感性的， 症状和活动参与减少是AD的确定的可改变的风险因素。在这个早期阶段 和新的研究者申请，我们将检查可改变的AD风险因素（特别是情感症状 和活动参与）作为SMI和记忆力随时间下降之间联系的介质; 此外，我们将通过这一途径来描述记忆力下降风险最高的SMI亚组。研究 将利用四个由国家情报局资助的大型纵向数据集进行结构级复制分析， 最大限度地提高每个数据集的独特性，并测试多个数据集结果的可重复性。 人口，以建立普遍性。本研究有三个具体的目的：1）检验纵向预测 SMI对可改变的AD风险因素的效用; 2）确定SMI与AD风险因素之间关系的调节因子。 可改变的AD危险因素;和，3）测试SMI，个体特征， 可改变的AD风险因素和客观记忆。发现可调节的AD风险因素， SMI和记忆衰退（AD中最早和最中心的缺陷）之间的关联将提供明确的， 和潜在的新的干预目标。此外，识别负风险最高的个体 对SMI的反应将有助于丰富未来研究的样本，并有助于指导 SMI评估工具，以确定老年人在最大的风险，使人衰弱的结果。

PROJECT SUMMARY Subjective memory impairment (SMI), or the perception of memory problems in the absence of objective memory deficits, is associated with negative outcomes of individual and societal significance, including a substantially increased risk of Alzheimer's disease (AD). However, little is known regarding the mediators that link SMI and memory decline in some individuals, or which older adults with SMI are at greatest risk for memory decline. SMI in older adults is associated with several modifiable AD risk factors: depressive symptoms, anxiety symptoms, and reduced activity participation (including physical, social, and cognitive activities). Although these associations have been studied cross-sectionally, little longitudinal evidence exists to contribute to our understanding of the temporality of symptoms. Furthermore, research to date has not considered these symptomatic associations as potential contributors to AD risk, even though affective symptoms and reduced activity participation are established modifiable risk factors for AD. In this early stage and new investigator application, we will examine modifiable AD risk factors (specifically affective symptoms and activity participation) as mediators underlying linkages among SMI and memory decline over time; furthermore, we will characterize SMI subgroups at highest risk for memory decline via this pathway. The study will utilize four large NIA-funded longitudinal datasets in construct-level replication analyses in order to maximize the unique aspects of each dataset as well as test the reproducibility of findings across multiple populations to establish generalizability. Three specific aims guide this study: 1) Test the longitudinal predictive utility of SMI on modifiable AD risk factors; 2) Identify moderators of the relationships between SMI and modifiable AD risk factors; and, 3) Test the longitudinal relationships among SMI, individual characteristics, modifiable AD risk factors, and objective memory. Discovery of modifiable AD risk factors that mediate the association between SMI and memory decline (the earliest and most central deficit in AD) will provide explicit, and potentially novel, targets for intervention. Additionally, identifying individuals at highest risk for negative reactions to SMI will serve to enrich samples for future research as well as to help guide the development of SMI assessment tools to identify older adults at greatest risk for debilitating outcomes.