Alzheimer’s disease risk factors as mediators of subjective memory impairment and objective memory decline: protocol for a construct-level replication analysis

Abstract Background 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. In this study, 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. Methods This study utilizes a series of construct-level replication analyses across four large longitudinal datasets to maximize the unique aspects of each dataset as well as test the reproducibility of findings across multiple populations to establish generalizability. The current study’s sample (n > 40,000) is drawn from the Einstein Aging Study, Health and Retirement Study, Minority Aging Research Study, and National Health and Aging Trends Study. Participants must meet the following basic criteria for inclusion: age 55 or older and no evidence of cognitive impairment at baseline. We will use multilevel modeling to determine whether higher levels of SMI are related to increased affective symptoms and decreased activity participation, as well as whether this relationship is moderated by neuroticism, family history of AD, and race/ethnicity. Finally, we will test our full conceptual model that examines whether changes in affective symptoms and activity participation mediate the relationship between SMI and objective memory decline. Specifically, we will test moderated mediation as we hypothesize these relationships to hold among subgroups of older adults. Discussion 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