Extended anesthesia exposure for abdominal and pelvic procedures in older adults with colorectal cancer: Associations with chart dementia diagnoses

Background: We hypothesized that cumulative anesthesia exposure over the course of routine treatment of colorectal cancer in older adults can increase long-term risk of Alzheimer's disease (AD), Alzheimer's disease related dementias (ADRD), and other chronic neurocognitive disorders (CND).Methods: We conducted a SEER-Medicare-based retrospective cohort study of 84,770 individuals age 65 years and older diagnosed with colorectal cancer between 1998 and 2007 using a proportional hazards model with inverse probability weighted estimators. The primary exploratory variable was a time-variant measure of cumulative anesthesia exposure for abdominal and pelvic procedures, updated continuously.Results: Our primary outcomes, AD and ADRD, occurred in 6005/84,770 (7.1%) and 14,414/83,444 (17.3%) individuals respectively. No statistically significant association was found between cumulative anesthesia exposure and AD (hazard ratio [HR], 0.993; 95% CI, 0.973-1.013). However, it was moderately associated with the risk of ADRD (HR, 1.016; 95% CI, 1.004-1.029) and some secondary outcomes including most notably: cerebral degeneration (HR, 1.048; 95% CI, 1.033-1.063), hepatic encephalopathy (HR, 1.133; 95% CI, 1.101-1.167), encephalopathy-not elsewhere classified (HR,1.095; 95% CI: 1.076-1.115), and incident/perioperative delirium (HR, 1.022; 95% CI, 1.012-1.032). Furthermore, we observed an association between perioperative delirium and increased risk of AD (HR, 2.05; 95% CI, 1.92-2.09).Conclusion: Cumulative anesthesia exposure for abdominal and pelvic procedures was not associated with increased risk of AD directly and had a small but statistically significant association with ADRD and a number of other CNDs. Cumulative anesthesia exposure was also associated with perioperative delirium, which had an independent adverse association with AD risk.