Sleep Fragmentation and Cognitive Trajectories After Critical Illness

Abstract

Background: ICU survivors can experience both cognitive dysfunction and persistent sleep disturbances after hospitalization. Sleep disturbances have been linked with cognitive impairment in various patient populations, and the apolipoprotein E (APOE) genotype has been linked to sleep-related impairments in cognition.

Research question: Is there an association between sleep, long-term cognition, and APOE status in ICU survivors?

Study design and methods: We enrolled 150 patients from five centers who had been mechanically ventilated for at least 3 days; 102 patients survived to ICU discharge. Actigraphy and cognitive testing were undertaken at 7 days, 6 months, and 12 months after ICU discharge, and sleep duration, quality, and timing were estimated by actigraphy. APOE single nucleotide polymorphisms were assessed for each patient.

Results: Actigraphy-estimated sleep fragmentation, but not total sleep time or interdaily stability (estimate of circadian rhythmicity), was associated with worse cognitive impairment at 7 days of ICU discharge. No actigraphy-estimated variable of sleep estimation at 7 days post-ICU discharge predicted cognitive impairment or persistent sleep abnormalities at 6 and 12 months of follow-up in subsequently assessed survivors. Possessing the APOE ε4 allele was not significantly associated with sleep disturbances and its presence did not modify the risk of sleep-related cognitive impairment at follow-up.

Interpretation: Sleep fragmentation estimated by actigraphy was associated with worse cognitive performance in hospital, but not at later time intervals. Further research is needed to better delineate the relationship between persistent sleep disturbances and cognition in larger numbers of ICU survivors.

Trial registry: ClinicalTrials.gov; No.: NCT02086877; URL: www.clinicaltrials.gov.

Keywords: ICU; ICU survivors; cognition; sleep fragmentation.