Abstract
The association between surgery with general anesthesia (exposure) and cognition (outcome) among older adults has been studied with mixed conclusions. We revisited a recent analysis to provide missing data education and discuss implications of biostatistical methodology for informative dropout following dementia diagnosis. We used data from the Mayo Clinic Study of Aging, a longitudinal study of prevalence, incidence, and risk factors for mild cognitive impairment (MCI) and dementia. We fit linear mixed effects models (LMMs) to assess the association between anesthesia exposure and subsequent trajectories of cognitive z-scores assuming data missing at random, hypothesizing that exposure is associated with greater decline in cognitive function. Additionally, we used shared parameter models for informative dropout assuming data missing not at random. A total of 1948 non-demented participants were included. Median age was 79 years, 49% were female, and 16% had MCI at enrollment. Among median follow-up of 4 study visits over 6.6 years, 172 subjects developed dementia, 270 died, and 594 participants underwent anesthesia. In LMMs, exposure to anesthesia was associated with decline in cognitive function over time (change in annual cognitive z-score slope = -0.063, 95% CI: (-0.080, -0.046), p < 0.001). Accounting for informative dropout using shared parameter models, exposure was associated with greater cognitive decline (change in annual slope = -0.081, 95% CI: (-0.137, -0.026), p = 0.004). We revisited prior work by our group with a focus on informative dropout. Although the conclusions are similar, we demonstrated the potential impact of novel biostatistics methodology in longitudinal clinical research.
Highlights
Recent research studies have reported that surgery with general anesthesia is associated with subsequent cognitive decline in older adults [1,2]
When refitted in the shared parameter approach for ignorable missing data, estimates of the association with cognitive decline were more pronounced (change in annual slope = −0.081, 95% Credible Interval (CrI): (−0.137, −0.026), p = 0.004). These results suggest, on average, exposure to surgery with general anesthesia is associated with more than double the expected rate of change in cognitive decline compared to pre-exposure among older adults
We showed that when accounting for potential informative dropout due to death or dementia, the estimated association was 29% larger than the results under a missing at random (MAR) assumption, both lead to similar qualitative conclusions
Summary
Recent research studies have reported that surgery with general anesthesia is associated with subsequent cognitive decline in older adults [1,2]. Several studies have reported contradictory results [3,4]. Further supporting the hypothesis that anesthesia is associated with subsequent cognitive decline is a preclinical study in which cell lines exposed to inhalational anesthesia demonstrate enhancement of brain neuropathology implicated in Alzheimer’s dementia [5] and a systematic review of short-term perioperative cognitive dysfunction [6]. Recent clinical research studies have used longitudinally collected data to assess this hypothesis. Longitudinal studies obtain repeated assessments on subjects over time. Longitudinal data could be collected at several scheduled study visits or at multiple encounters with the medical system. While a sample of subjects may be enrolled into a longitudinal study either prospectively or by defining a retrospective cohort, some subjects may drop out, as the study progresses during the follow-up period
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
