Association of Poor Sleep Burden in Middle Age and Older Adults With Risk for Delirium During Hospitalization

Abstract

Background Delirium is a distressing neurocognitive disorder recently linked to sleep disturbances. However, the longitudinal relationship between sleep and delirium remains unclear. This study assessed the associations of poor sleep burden, and its trajectory, with delirium risk during hospitalization. Methods 321,818 participants from the UK Biobank (mean age 58±8y[SD]; range 37-74y) reported (2006-2010) sleep traits (sleep duration, excessive daytime sleepiness, insomnia-type complaints, napping, and chronotype–a closely-related circadian measure for sleep timing), aggregated into a sleep burden score (0-9). New-onset delirium (n=4,775) was obtained from hospitalization records during 12y median follow-up. 42,291 (mean age 64±8; range 44-83y) had repeat sleep assessment on average 8y after their first. Results In the baseline cohort, Cox proportional hazards models showed that moderate (aggregate scores=4-5) and severe (scores=6-9) poor sleep burden groups were 18% (hazard ratio 1.18 [95% confidence interval 1.08-1.28], p<0.001) and 57% (1.57 [1.38-1.80], p<0.001), more likely to develop delirium respectively. The latter risk magnitude is equivalent to two additional cardiovascular risks. These findings appeared robust when restricted to postoperative delirium and after exclusion of underlying dementia. Higher sleep burden was also associated with delirium in the follow-up cohort. Worsening sleep burden (score increase ≥2 vs. no change) further increased the risk for delirium (1.79 [1.23-2.62], p=0.002) independent of their baseline sleep score and time-lag. The risk was highest in those under 65y at baseline (p for interaction <0.001). Conclusion Poor sleep burden and worsening trajectory were associated with increased risk for delirium; promotion of sleep health may be important for those at higher risk.

Sleep and circadian phenotypes: risk factors for COVID-19 severity?

“…The findings of Liu et al build on prior work linking sleep to both COVID outcomes [ 1 ] and presenting conditions linked to severity [ 6 , 7 ]. This is also in keeping with prior association studies linking obstructive sleep apnea (OSA) and COVID-19 severity [ 8 , 9 ], given the potential overlap in symptomatology.…”

“…Although Liu et al have made a significant step forward, these findings still need replicating in an independent dataset, ideally considering follow-up sleep and health assessment proximal to COVID-19 as others have done with other diseases related to sleep [ 7 ]. Further studies incorporating objective sleep measures (collected more recently in 2013–2015 in the UK Biobank), to understand further how sleep and circadian phenotypes contribute to COVID-19 severity are ongoing.…”

Melatonin and Its Analogs for Prevention of Post-cardiac Surgery Delirium: A Systematic Review and Meta-Analysis

“…Although different doses of melatonin show the same preventive effect on delirium, preoperative melatonin administration appears to produce a more significant effect, possible due to the following factors: (a) Sleep disorder is associated with a high risk for delirium ( 56 ), and patients with various cardiac diseases invariably experience preoperative sleep disorders secondary to anxiety, depression, breathing disorders, or other factors ( 57 ); (b) The secretion of melatonin is delayed during anesthesia and surgery ( 58 ); (c) Postoperatively given melatonin absorption kinetics are greatly slowed, and peak plasma levels are reduced ( 59 ); and (d) Anesthesia and surgery may selectively cause functional reductions in the prefrontal cortex excitatory synaptic transmission and induce delirium ( 60 ). It is reasonable to initiate melatonin supplementation the night before cardiac surgery if conditions permit.…”

Plasma 5‐HIAA activity indicative of serotonergic disturbances in cognitively impaired, elderly patients experiencing postoperative delirium

“…Interindividual differences in sleep/wake‐cycle regulation could have affected our results as well, considering disruptions in sleep biology are an important risk factor for delirium, whereas sleep regulation is also directly linked to the serotonergic system via multiple pathways. 54 , 55 , 56 Disparities in 5‐HIAA levels among cognitively impaired patients may also result from different etiologies of cognitive decline, such as Alzheimer's disease, vascular dementia etc. Unfortunately, since the assessment of cognitive function was based on MMSE and IQCODE scores without further work‐up to reveal a clinical diagnosis, we were unable to explore this.…”