Meta-analysis of ICU delirium biomarkers and their alignment with the NIA-AA research framework

Abstract

Background Between 30% and 80% of survivors of critical illness experience cognitive impairment, but the under-lying mechanisms remain unknown. Objective To determine whether intensive care unit (ICU) delirium biomarkers align with the National Institute on Aging–Alzheimer’s Association (NIA-AA) research framework for diagnostic biomarkers for Alzheimer disease and other related dementias (ADRD). Methods Ovid MEDLINE, PsycInfo, Embase, and the Cochrane Library were systematically searched for arti-cles published between January 1, 2000, and February 20, 2020, on the relationship between delirium and bio-markers listed in the NIA-AA framework. Only studies that addressed delirium in the ICU setting and fluid bio-markers were included in these analyses. Results Of 61 256 records screened, 38 studies met inclu-sion criteria, 8 of which were suitable for meta-analysis. In pooled analysis, significant associations were found between ICU delirium and amyloid β-peptide 1-40 (stan-dard mean difference [SMD], 0.42; 95% CI, 0.09-0.75), interleukin (IL)-1 receptor antagonist (SMD, 0.58; 95% CI, 0.21-0.94), and IL-6 (SMD, 0.31; 95% CI, 0.06-0.56). No significant association was observed in pooled analyses between ICU delirium and the other biomarkers. Few studies have examined ICU delirium and pathologic tau or neurodegeneration biomarkers. Conclusions Inflammatory biomarkers and amyloid β are associated with ICU delirium and point to potential overlapping mechanisms between delirium and ADRD. Critical care providers should consider integrating diagnostic approaches used in ADRD in their assessment of post–ICU cognitive dysfunction.