Circadian disturbances, risk for postoperative delirium and conversion to dementia

Abstract

AbstractBackgroundDelirium is one of the most common complications in older adults after surgery. Circadian rest‐activity rhythms are known to be disrupted with age, and among individuals with mild cognitive impairment and Alzheimer’s disease (AD), major risk factors for postoperative delirium (POD). However, the relationship between prior circadian rest‐activity rhythm measures and POD, and whether these measures can predict conversion from delirium to dementia has not been systematically assessed.Method64,852 UK biobank participants between 2013‐2015 (mean 57.9y [SD = 8.0], 54.0% female) were assessed with actigraphy for 7 days, followed by at least one surgical event requiring hospitalization during follow‐up until 2021. Four measures were extracted from actigraphy to quantify circadian rest‐activity rhythms, which were amplitude (representing the strength), acrophase (representing peak activity time), interdaily stability (IS), and intradaily variability (IV; representing the fragmentation) of 24‐h rhythm. Earliest occurrence of delirium and dementia were determined using ICD‐10 coding from hospitalization records, and POD was defined as delirium within 3 days of an operation. Cox proportional hazards models were used to assess whether circadian disturbances in these rhythms predicted increased risk for delirium including POD, and logistic regression for the risk of conversion from delirium to dementia within 5 years of the first delirium occurrence.ResultRisk for new POD during hospitalization (n = 249) was increased with lower amplitude (1 SD decrease, hazard ratio [HR] 1.28, 95% CI: 1.10‐1.49, p = 0.002), and higher intradaily variability (1 SD increase, 1.30, 1.12–1.51, p<0.001) after controlling for demographics, lifestyle factors, cardiovascular risk, and morbidity burden. These results were consistent when all new delirium cases during hospitalization (n = 500) were included. Within 5 years, 47 developed incident dementia. Every 1‐SD decrease in amplitude within a cohort of was associated with increased odds of incident dementia (odds ratio 1.44, 1.06‐1.96, p = 0.02) independent of age at first delirium and sex.ConclusionThese results indicate a link between circadian disturbances and risk for delirium, as well as conversion to incident dementia. This is novel evidence that circadian disturbances are part of the shared common underlying pathophysiological mechanisms between delirium and dementia that warrant further investigation.