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

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.