BackgroundModeling the dynamics of Alzheimer’s disease (AD) biomarkers over the entire continuum of AD progression is important, yet challenging due to limited resources to collect longitudinal biomarkers from the aging population with fully observed clinical spectrum of AD. This study proposed and applied a synchronized sigmoidal mixed‐effects model to characterize dynamics of longitudinal memory performance using data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). The model leveraged time to AD onset as the time scale and additionally allowed inclusion of participants without AD onset, drastically expanding future applications.MethodADNI participants with observed mild cognitive impairment (MCI) and/or AD onset (n = 312, mean (SD) baseline age 74.9 (6.44) years) were included (Table 1). A memory composite previously built in ADNI was leveraged for all analyses. A synchronized sigmoidal mixed‐effects model was constructed for dynamics of memory performance with parameters for initial memory level, magnitude of decline, and half‐life of decline. For participants with observed MCI but not AD onset, an additional parameter (t0
) quantifying the time from MCI onset to AD was incorporated (Figure 1). We considered random effects for all parameters and allowed t0
to vary by age at MCI onset (nonlinearly), sex, apolipoprotein E (APOE)‐ε4 status and their interactions.ResultThe mean initial harmonized memory score is 0.24 (95% CI: 0.17‐0.32). The mean decline in the harmonized memory score is 1.53 (95% CI: 1.43‐1.64). The mean time when the harmonized memory score declined by half is 0.57 years before AD onset (95% CI: 0.32‐0.82). Female is associated with faster progression from MCI onset to AD (p = 0.002). Age at MCI onset is nonlinearly associated with MCI‐to‐AD progression (p < 0.001) and APOE‐ε4 status interacts with age at MCI onset on MCI‐to‐AD progression (p = 0.002) (Figure 2).ConclusionThe proposed synchronized sigmoidal mixed effect model can be used to characterize dynamics of AD biomarkers relative to AD onset using participants with and without AD onset. A model to estimate duration of MCI‐to‐AD progression can be simultaneously included for synchronization purpose, which identified gender, age at MCI onset and APOE‐ε4 status as factors associated with MCI‐to‐AD progression.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.