Peri-Operative Inflammatory Cytokines in Plasma of the Elderly Correlate in Prospective Study with Postoperative Changes in Cognitive Test Scores.

Abstract

Increasingly, postoperative cognitive dysfunction (POCD) is recognized as a complication after surgery in the elderly; but it's etiology remains unclear. Here we examine changes in cytokine levels during both the pre-operative and postoperative period, comparing them with long term variation in cognitive test scores. Forty-one patients aged 65 and older undergoing major surgery with general anesthesia were recruited after written consent in this IRB approved study. Thirty went on to complete this prospective, non-interven-tional and non-randomized study. Plasma levels of cytokines Il-6, Il-8, Il-10, and TNF were determined using ELISA with MILLIPLEX Multi-Analyte Profiling (Billerica, MA). All subjects had neurocognitive tests pre-operatively and 6 months post-surgery, including Paragraph Recall Immediate and Delayed, Digit Span Forward (DSF) and Backward (DSB), and Trail Making A and B. Spearman's Rho and repeated measure rank analysis were used to examine the dependence of z score changes in cognitive tests (baseline versus 6 months) as a function of 3 cytokine time points (presurgical, post anesthesia care unit (PACU), and post-operative day one (POD1)). A greater increase in PACU inflammatory burden correlated with a greater decline in performance on the DSB (IL6, IL8; r>-0.560; p<= 0.008). DSF changes correlated slightly better with pre-surgical cytokines, declining more with higher cytokines (IL6, r= -0.551, p=0.002; IL8, -0.468, 0.009). TNF, examining all 3 values, changed only slightly postoperatively, but still correlated with a decline in DSB (p=0.014). Thus, cognitive performance, over 6 months post surgery, declines with elevated perioperative inflammation. Specific cytokines at specific perioperative times may impact specific cognitive functions, serving as diagnostics as well as contributing causation.