Sleep Fragmentation Associated with Cognitive Impairment in ICU Survivors

Early sleep fragmentation, estimated by actigraphy, was found to be associated with worse cognitive impairment shortly after critical illness.

Early sleep fragmentation, estimated by actigraphy, was found to be associated with worse cognitive impairment shortly after critical illness, according to study results published in Chest.

Sleep disturbances were previously found to be associated with cognitive impairment, 2 issues that are commonly seen in intensive care unit (ICU) survivors after hospitalization. Furthermore, evidence has suggested that the apolipoprotein E (APOE) genotype may be associated with the acute cognitive status of critically ill patients.

The objective of the current study ( Identifier: NCT02086877) was to explore the association between sleep, long-term cognitive function, and APOE status in a group of ICU survivors. Cognitive function was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and Trail Making Tests (TMT) A and B.

Of the 150 patients who had been mechanically ventilated for ≥3 days, 102 (median age, 57 years; 44% women) survived to ICU discharge. All study participants completed actigraphy and cognitive testing at 7 days, 6 months, and 12 months after ICU discharge. In addition, the APOE genotype was determined for each participant.

The mean RBANS total score was 79.6 at 7 days, 93.0 at 6 months, and 94.0 at 12 months follow-up. The mean actigraphy-estimated total sleep time was 6.1 hours at 7 days after ICU discharge, 8.0 hours at 6 months, and 8.4 hours at 12 months follow-up. Sleep efficiency improved from a mean of 44% to >65% at both the 6- and 12-month follow-up after ICU discharge. Interdaily stability remained consistent throughout the follow-up period.

Cognitive impairments were documented in 58% of participants at 7 days after ICU discharge, and there was a significant increase in all cognitive scores at long-term follow-up, with most gain seen by 6 months (P <.001).

The data also suggested an association between actigraphically-estimated sleep fragmentation and worse early cognitive impairment, as measured by RBANS total score and TMT B at 7 days after ICU discharge (P =.02 and P <.001, respectively). However, there was no association between actigraphy-estimated sleep variables at 7 days with cognitive performance at 6 or 12 months. Neither total sleep time nor interdaily stability were associated with cognitive impairment at any time point.

There was no significant association between APOE genotype and sleep disturbances. In addition, no increased risk for cognitive impairment was reported in patients with the APOE ε4 allele.

Researchers acknowledged several study limitations, including the lack of adjustment for multiple comparisons, limited internal validity because of high losses to follow-up and unanticipated deaths, and high attrition rates that limited the ability to detect significant associations or changes in cognitive impairment at 6 and 12 months.

“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,” concluded the researchers.


Wilcox ME, McAndrews MP, Van J, et al. Sleep fragmentation and cognitive trajectories after critical illness. Chest. Published online July 24, 2020. doi:10.1016/j.chest.2020.07.036