Sex and genetic differences in postoperative cognitive dysfunction: A longitudinal cohort analysis

Background: Postoperative cognitive dysfunction (POCD) is a common postoperative complication experienced by patients aged 65 years and older, and these older adults comprise more than one third of the surgical patients in the USA. Because not everyone with a history of exposure to surgery and anesthesia develops POCD, there are likely major biological risk factors involved. There are important gaps in our knowledge regarding whether genetic makeup, biological sex, or other Alzheimer's disease risk factors predispose older adults to developing POCD. We set out to determine whether biological sex and Apolipoprotein E-ϵ4 (APOE4) carrier status increase the risk of developing POCD in older adults. Methods: We performed a cohort analysis of 1033 participants of prospective longitudinal aging studies. Participants underwent regular cognitive test batteries and we compared the annual rate of change over time in various cognitive measures in the women exposed to surgery and general anesthesia compared to the men exposed to surgery and general anesthesia. Mixed-effects statistical models were used to assess the relationship between biological sex, APOE4 carrier status, surgery and anesthesia exposure, and the rate of change in cognitive test scores. Results: When comparing all men (n = 89) and women (n = 164) who had surgery, there were no significant sex differences in postoperative cognitive outcomes. However, men with an APOE4 allele performed significantly worse on cognitive testing following surgery and anesthesia than women APOE4 carriers, even after adjusting for age, education level, and comorbidities. Conclusions: Older men with APOE4 allele may be more vulnerable to postoperative cognitive dysfunction than older women with APOE4 allele.