Association between exposure to anaesthesia and surgery and long-term cognitive trajectories in older adults: report from the Mayo Clinic Study of Aging

Abstract

Background: The link between exposure to general anaesthesia and surgery (exposure) and cognitive decline in older adults is debated. We hypothesised that it is associated with cognitive decline.

Methods: We analysed the longitudinal cognitive function trajectory in a cohort of older adults. Models assessed the rate of change in cognition over time, and its association with exposure to anaesthesia and surgery. Analyses assessed whether exposure in the 20 yr before enrolment is associated with cognitive decline when compared with those unexposed, and whether post-enrolment exposure is associated with a change in cognition in those unexposed before enrolment.

Results: We included 1819 subjects with median (25th and 75th percentiles) follow-up of 5.1 (2.7-7.6) yr and 4 (3-6) cognitive assessments. Exposure in the previous 20 yr was associated with a greater negative slope compared with not exposed (slope: -0.077 vs -0.059; difference: -0.018; 95% confidence interval: -0.032, -0.003; P=0.015). Post-enrolment exposure in those previously unexposed was associated with a change in slope after exposure (slope: -0.100 vs -0.059 for post-exposure vs pre-exposure, respectively; difference: -0.041; 95% confidence interval: -0.074, -0.008; P=0.016). Cognitive impairment could be attributed to declines in memory and attention/executive cognitive domains.

Conclusions: In older adults, exposure to general anaesthesia and surgery was associated with a subtle decline in cognitive z-scores. For an individual with no prior exposure and with exposure after enrolment, the decline in cognitive function over a 5 yr period after the exposure would be 0.2 standard deviations more than the expected decline as a result of ageing. This small cognitive decline could be meaningful for individuals with already low baseline cognition.

Keywords: cognitive ageing; cognitive domains; cognitive z-scores; general anaesthesia; older adults.

Fig 1

Box plots for z-scores presented according to visit month (0, 15, 30, 45, and 60 months) and exposure to surgery and anaesthesia during the 20 years before enrolment. To ensure that the same individuals are represented at each time point, only individuals who had a cognitive assessment at the 60 month visit are included. Each time point represents a variety of individuals with variable global cognitive z-scores.

Fig 2

Simulated trajectories for four hypothetical patients under three scenarios: no prior surgery and anaesthesia, and none during follow-up; prior surgery and anaesthesia; and post-enrolment surgery and anaesthesia at 2 years after enrolment without prior surgery and anaesthesia. Follow-up is described from enrolment through 8 years. Exposure refers to exposure to surgery and anaesthesia. The four hypothetical patients were chosen to represent varying degrees of health at enrolment. Patient (Pt) 1 is an 80-year-old female, never a smoker, married, with ≥16 years of education, with no co-morbidities, APOE ε4 negative, and cognitively normal at enrolment. Pt 2 is an 80-year-old male, never a smoker, married, 13–15 years of education, with prior history of coronary artery disease and a Charlson Co-morbidity Index score of 2, APOE ε4 negative, and cognitively normal at enrolment. Pt 3 is an 80-year-old female, current smoker, single-partner status, 12 years of education, with prior history of stroke and a Charlson Co-morbidity Index score of 2, APOE ε4 positive, and cognitively normal at enrolment. Pt 4 is an 80-year-old male, former smoker, single-partner status, <12 years of education, prior history of coronary artery disease and a Charlson Co-morbidity Index score of 4, with midlife dyslipidaemia, APOE ε4 positive, and mild cognitive impairment at enrolment. The plot demonstrates that changes over time attributable to surgery and anaesthesia before enrolment or post-enrolment represent a subtle, although statistically significant, change in the average trajectory of cognitive z-scores relative to the variability in z-scores inherent in the population.

Supplementary Fig S1

Flow diagram of the Mayo Clinic Study of Aging. Participants in the present study. CN, cognitively normal; MCI, mild cognitive impairment.