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

项目总结 主观记忆障碍(SMI)，或在没有客观因素的情况下感觉到的记忆问题 记忆缺陷与具有个人和社会意义的负面后果有关，包括 极大地增加了阿尔茨海默病(AD)的风险。然而，关于调解人的情况却知之甚少 一些个体的SMI和记忆力下降有关，或者患有SMI的老年人患SMI的风险最大 记忆力衰退。老年人的SMI与几个可修改的AD风险因素有关：抑郁 症状、焦虑症状和活动参与度降低(包括身体、社交和认知 活动)。尽管已经对这些关联进行了横断面研究，但几乎没有纵向证据。 有助于我们理解症状的暂时性。此外，到目前为止，研究还没有 认为这些症状关联是AD风险的潜在贡献者，即使是情感上的 症状和活动参与减少是AD的可改变的危险因素。在这个早期阶段 和新的调查员应用程序，我们将检查可修改的AD风险因素(特别是情感症状 和活动参与)作为SMI和记忆力衰退之间潜在联系的中介； 此外，我们将通过这一途径来描述记忆衰退风险最高的SMI亚组。这项研究 将利用NIA资助的四个大型纵向数据集进行构造级复制分析，以便 最大限度地发挥每个数据集的独特性，并测试多个数据集的结果的重复性 种群以建立泛化能力。指导本研究的三个具体目标：1)检验纵向预测 SMI对可修改的AD风险因素的效用；2)确定SMI和SMI之间关系的调节因素 可修改的AD危险因素；3)检验SMI、个体特征、 可修改的AD风险因素和客观记忆。发现可改变的AD危险因素，调节 SMI和记忆力下降(AD中最早和最主要的缺陷)之间的关联将提供明确的， 而且可能是新的干预目标。此外，确定感染阴性的风险最高的人 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，以确定老年人具有最大的风险，使结果衰弱。

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.