Apolipoprotein E ε4 and cognitive function after surgery in middle-aged and elderly Danish twins

BACKGROUND Transient cognitive impairment is common in adult patients of all ages following anaesthesia and surgery. Apolipoprotein E (APOE) epsilon 4 carriers may have a larger deterioration in short-term cognitive function after major surgery compared with APOE epsilon 4 noncarriers. OBJECTIVES The aim was to examine the effect of APOE epsilon 4 on the association between exposure to surgery and anaesthesia, and subsequent cognitive functioning. A more pronounced deterioration in cognitive function in APOE epsilon 4 carriers was hypothesised. DESIGN An observational cross-sectional and a 6 to 10 years longitudinal twin cohort design. SETTING Survey and register study of 2936 Danish twins aged 45 to 92 years. MAIN OUTCOME MEASURES Cognitive function was assessed using five age-sensitive cognitive tests. In the cross-sectional study, we compared twins exposed to surgery with a reference group (unexposed). Linear regression models were used adjusting for sex and age and stratified by APOE epsilon 4 carrier status. In the longitudinal cognitive follow-up study 1671 twins participated. Intrapair analyses were also performed using 70 same-sexed twin pairs concordant for APOE epsilon 4 carrier status, but discordant for major surgery. RESULTS APOE epsilon 4 carriers had lower cognitive scores compared with noncarriers, and this was statistically significant in elderly twins 70+ years of age (mean difference, -0.67; 95% CI, -1.14 to -0.17). There was no significant impact on cognitive function after surgery according to APOE epsilon 4 carrier status in the cross-sectional study. Similarly, there was no APOE epsilon 4 modification in the longitudinal study. Also, in the intrapair analyses no evidence was found of lower cognitive score after major surgery compared with the nonexposed cotwins among APOE epsilon 4 carriers. CONCLUSION No evidence was found of more pronounced long-term deterioration in cognitive function after surgery among APOE epsilon 4 carriers, but elderly APOE epsilon 4 carriers in general performed worse on the cognitive tests than noncarriers.