Peri-Operative Inflammatory Cytokines in Plasma of the Elderly Correlate in Prospective Study with Postoperative Changes in Cognitive Test Scores.
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.
Department of Anesthesiology, Perioperative Care and Pain Medicine, The New York University School of Medicine, USA.; New York University School of Medicine, Center for Cognitive Neurology.
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R
Kline
Department of Anesthesiology, Perioperative Care and Pain Medicine, The New York University School of Medicine, USA.; New York University School of Medicine, Center for Cognitive Neurology.
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Wong
Department of Anesthesiology, Perioperative Care and Pain Medicine, The New York University School of Medicine, USA.; New York University School of Medicine, Center for Cognitive Neurology.
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M
Haile
Department of Anesthesiology, Perioperative Care and Pain Medicine, The New York University School of Medicine, USA.
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Didehvar
Department of Anesthesiology, Perioperative Care and Pain Medicine, The New York University School of Medicine, USA.
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Farber
Department Neuropsychology, Weill Cornell Medical College.
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Sacks
Department of Anesthesiology, Perioperative Care and Pain Medicine1& Psychiatry of The New York University School of Medicine, USA.; New York University School of Medicine, Center for Cognitive Neurology and Center for Brain Health.
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Pirraglia
Department of Anesthesiology, Perioperative Care and Pain Medicine1& Psychiatry of The New York University School of Medicine, USA.; New York University School of Medicine, Center for Cognitive Neurology and Center for Brain Health.
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MJ
de Leon
Department of Anesthesiology Rutgers NJMS.
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Bekker
Cognitive Dysfunction; Cognitive Tests; Cytokines; Inflammation; Perioperative; Surgery