AbstractBackgroundPrior work has identified associations between sleep quality and amyloid‐beta (Aβ). However, how sleep efficiency relates to Aβ, cerebral blood flow (CBF), and cognition are not well understood. The objective of this study was to evaluate these relationships and the modifying role of APOE4 status.MethodObjective sleep efficiency, Aβ, CBF, and cognitive performance on neuropsychological assessments (MoCA, Flanker, CVLT, and Complex Figure) were examined in a sample of 52 non‐demented, older adults (age=66.5+6.82, 67% female, 27% APOE4 carriers). Sleep efficiency, defined as the percentage of time asleep within a given sleep period, was objectively measured using the GENEActiv tri‐axis accelerometer for an average of 30.25 days. Aβ was measured in vivo using positron emission tomography and the F‐18 florbetaben tracer to calculate composite SUVR scores. Global gray matter CBF was quantified using a pseudo‐continuous arterial spin labeling MRI scan. All analyses were adjusted for age, sex, and education (for cognitive measures).ResultOverall, higher sleep efficiency was associated with lower Aβ burden (p=.04), higher CBF (p=.03), higher MoCA scores (p=.05) and a trend for better Complex Figure Test recall (p=.07). There was a significant moderating effect of APOE4 status on the association between sleep and Aβ, such that poorer sleep efficiency was associated with higher Aβ burden in APOE4 carriers only (p=.01). APOE4 moderation was not observed for CBF. When stratified by high and low sleep efficiency levels (median split), APOE4 carrier status predicted Aβ burden only in individuals with low sleep efficiency (p =.02). Additionally, sleep efficiency predicted performance on long delay free recall of the CVLT and Complex Figure Test (p=.01) in the low sleep efficiency group only. No association between sleep efficiency and Flanker were observed.ConclusionThese results provide evidence that sleep efficiency is associated with brain health and cognition, and suggest a modifying effect of APOE4 on the relationship between sleep and amyloid. Mechanistic evidence from animal models and human studies suggests that impaired slow wave activity during NREM sleep may disrupt dynamic fluid oscillations important for amyloid clearance and brain blood flow. Future work is needed to understand the causal and temporal relationships between these processes.