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Objective It has been shown that accumulation of endogenous formaldehyde can lead to human cognitive impairment and memory loss in animals.The purpose of this study is to assess cognitive outcome in elderly noncardiac surgical patients and to investigate the correlation between endogenous formaldehyde level and post-operative cognitive dysfunction.Methods We studied ninety-five elderly patients aged between 65 and 80 who were undergoing major orthopedic surgery or abdominal surgery.One day before and one week after the surgery, all patients were subjected to a neuropsychological test.Urine samples were obtained one day before surgery and on day 1, day 2 and day 7 after surgery.Concentrations of urine formaldehyde for all enrolled patients were analyzed by high-performance liquid chromatography.The formaldehyde concentration after surgery divided by that before surgery was used as a ratio ([FA]A/[FA]B) to assess changes in endogenous formaldehyde.Results Ninety-five patients were included in the study and 30 (31.6%) were diagnosed with POCD.The urine formaldehyde level of all patients with and without POCD increased markedly on day 1 and day 2 after surgery.The urine formaldehyde level from baseline (before surgery) of patients with POCD was significantly higher (n =30, P < 0.01) than patients without POCD (n =65); and strikingIy, the ratio [FA]A/[FA]B was significantly greater (n =30, P < 0.001) on day 7 after surgery.Conclusion Levels of urine formaldehyde were elevated under the stress of surgery, and the increase on day 7 may provide a new marker for diagnosing POCD.