ASSOCIATION BETWEEN INFLAMMATORY BIOMARKERS IN PATIENTS WITH ICU DELIRIUM AND TWO-YEAR DIAGNOSIS OF MCI OR ADRD

Abstract

Introduction Delirium is characterized by acute onset of fluctuation in attention and cognition and is present in 60–87% of older adults in the intensive care unit (ICU).1 Delirium is associated with subsequent Alzheimer's disease (AD) and other related dementias (ADRD), but underlying mechanisms connecting the two disorders are poorly understood.2 Previous work has established a relationship between inflammatory biomarkers and delirium. Our study tested the hypothesis that inflammatory biomarkers measured during an episode of delirium would correlate with a diagnosis of mild cognitive impairment (MCI) or ADRD within two years of discharge from the ICU. Methods We performed a secondary data analysis of delirious patients enrolled in the Pharmacologic Management of Delirium (PMD) Trial l.3 ICD-9 codes for MCI and ADRD in the two years after discharge were obtained from the Indiana Network for Patient Care database. Prescriptions for memantine or anti-cholinesterase inhibitors were counted as evidence of MCI or ADRD. Patients who died at discharge or who had a prior diagnosis of MCI or dementia were excluded. To test for the association of the biomarkers, we used proportional hazards regression to model the time to dementia/MCI diagnosis. Patients who died were censored at their time of death. We performed a sensitivity analysis with logistic regression for patients who did not die during follow-up. Results were similar to the survival analysis, so we only report results from the proportional hazards regression. Models were adjusted for age, gender, race, Apache II, Charlson score, sepsis diagnosis, and usual care. Results A total of 251 patients were included in the analysis. Of these, 231 patients had blood samples collected on Day 1 post randomization to the PMD study, and 149 patients had blood samples collected on Day 8 or upon discharge, whichever was sooner. Within two years of ICU discharge, 12 patients were diagnosed with ADRD, and 43 were diagnosed with MCI. There was no association between inflammatory biomarkers (IL-6, IL-8, IL-10, TNF-Alpha, CRP) drawn on Day 1 and a diagnosis of MCI or ADRD. There was a trend toward significance for higher levels of interleukin-6 (IL-6) drawn at Day 8/discharge and a diagnosis of MCI or ADRD (p = 0.077). Conclusions This preliminary study suggests that higher levels of IL-6 may be associated with a diagnosis of MCI or ADRD after ICU discharge in patients with delirium. However, future larger-scale studies are needed to study the relationship between inflammatory biomarkers in patients with delirium and the subsequent development of MCI and ADRD. This research was funded by S.W. is supported by NIA 2P30AG010133 and NCATS UL1TR001108 (Project Development Team). L.S. is supported by NIA P30AG024827. B.K. is supported by NHLBI R01HL131730, and NIA R01AG055391. M.B. is supported by NIA R01AG034205. The authors declare no relevant financial interests related to this manuscript.