BACKGROUND: Cognitive dysfunction occurs in elderly patients following general anesthesia, and this might be associated with genetics. Studies have shown that theε4 allele gene is closely associated with senile dementia.OBJECTIVE: To compare and analyze the correlations between cognitive dysfunction and single nucleotide polymorphism of apolipoprotein E (ApoE) following inhaJation or intravenous anesthesia.DESIGN, TIME AND SETTING: A randomized, controlled study was performed. The patients were recruited from the Department of Anesthesia, Second Affiliated Hospital, Medical College, Xi'an Jiaotong University, China between May 2005 and December 2008. Genetic analyses were conducted at the Departments of Neuroanatomy and Forensic Medicine, Medical College, Xi'an Jiaotong University, China.PARTICIPANTS: A total of 1 000 patients of ASA Ⅰ-Ⅱ grade, without genetic connection, were enrolled in this study, comprising 520 males and 480 females, aged (70.1±4.6) years and weighing (57.3±7.5) kg. No patients suffered from cognitive dysfunction.METHODS: The patients were equally and randomly divided into intravenous anesthesia and gas anesthesia groups. Total intravenous anesthesia and inhaled anesthesia were used. Genomic DNA from whole blood was extracted. The ApoE gene was amplified by PCR. Restriction fragment length polymorphism of ApoE gene was analyzed. Cognitive function was evaluated by Mini-Mental State Examination (MMSE). Patients scoring < 25 points were diagnosed with cognitive dysfunction.MAIN OUTCOME MEASURES: Correlation of ApoE gene frequency and ApoEε4 allele to MMSE scores was measured.RESULTS: MMSE scores in patients from the gas anesthesia group significantly decreased 3 days after surgery, compared with the intravenous anesthesia group. The proportion of patients that scored < 25 points was significantly greater in the gas anesthesia group compared with the intravenous anesthesia group 3 days after surgery. Reduced MMSE scores closely correlated with expression of the ApoEε4 allele in the gas anesthesia group (odds ratio=2.83; 95% confidence interval was 1.25-6.39, P0.05).CONCLUSION: Results demonstrated a correlation between cognitive dysfunction and ApoE single nucleotide polymorphism in elderly patients after gas anesthesia. However, no relationship between cognitive dysfunction and ApoE single nucleotide polymorphism was determined in elderly patients following intravenous anesthesia. Therefore, elderly patients, especially those expressing the ApoEε4 gene, should be cautiously exposed to gas anesthesia.