Work

Exposure to surgery with regional anesthesia and cortical thickness in older adults

Year: 2020

Type: article

Abstract: Exposure of animals to inhalational anesthetics is associated with brain accumulation of amyloid β (Aβ) protein consistent with Alzheimer's disease (AD) neuropathology.1 This finding raises the possibility that clinical exposure to surgery with general anesthesia (surgery/GA) may contribute to accelerated cognitive decline including AD. We have published analyses using data from the Mayo Clinic Study of Aging (MCSA),2 a population-based longitudinal study of cognition. Longitudinal analyses of cognition found small but statistically significant associations between exposure of older adults to surgery/GA and accelerated decline in global cognition, specifically in memory and attention/executive domains.3 In a follow-up study, published recently in Alzheimer's & Dementia,4 we found that an accelerated cognitive decline was also observed after exposure to surgery with regional anesthesia (surgery/RA), with the magnitude of decline similar to that observed after exposure to surgery/GA. As part of the MCSA, various forms of brain imaging are now routinely obtained for most study participants. In a recent analysis, using brain magnetic resonance imaging (MRI), we found that older study participants with prior exposure to surgery/GA (during midlife and/or older age) had a small but statistically significant cortical thinning in AD signature region (ie, brain sub-regions in temporal cortex typically affected in early stage of development of AD) compared to those not exposed to surgery/GA (difference of −0.023 mm for surgery/GA vs not).5 In the analysis data set there were 478 participants who were not exposed to surgery/GA in the 20 years prior to their MRI scanning. Of these, 96 had been exposed to surgery/RA and 382 had no surgical exposure at all. A statistical power calculation determined that using samples of size N = 96 (exposed) and N = 382 (non-exposed) would provide power (two-tailed, α = 0.05) of only 22% to detect a decrease in cortical thickness similar to the magnitude of the effect seen with surgery/GA. Nonetheless, we believe a comparison of cortical thickness between those with exposure to surgery/RA versus not may provide additional insights that are worth exploring. Therefore, we used an identical methodological and statistical approach as in our earlier study5 to assess whether cortical thickness differs between those exposed to surgery/RA compared to those with no surgical exposure. Our primary end point was cortical thickness in the AD signature region treated as a continuous variable. From adjusted analyses, the estimated difference in cortical thickness for those exposed to surgery/RA in the prior 20 years versus not was −0.011 (−0.046 to 0.025) mm, which is directionally consistent with our prior findings comparing those exposed to surgery/GA versus not (−0.023 [−0.041 to −0.005] mm) (Table 1). We also analyzed cortical thickness using a dichotomous variable (normal vs abnormal) using a previously defined cut-off value.6 For this end point, the effect size estimate for abnormal cortical thickness in the AD signature region after exposure to surgery/RA (odds ratio [OR] = 1.36, 95% confidence interval [CI] 0.78 to 2.37) was also consistent with that previously found for exposure to surgery/GA (OR = 1.45, 95% CI 1.10 to 1.90). In conclusion, our previous findings have shown that cognitive decline is accelerated after exposure to either surgery with GA or RA,3, 4 and cortical thickness in the AD signature regions is reduced in those with prior exposure to surgery/GA.5 Our current results, presented in this Letter, although not statistically significant, suggest that cortical thickness in the AD signature region may also be reduced in those with prior exposure to surgery/RA. Our findings are only suggestive of this conclusion; future adequately powered studies are necessary to fully elucidate the association between surgery, anesthesia, and subsequent neurodegeneration.

Source: Alzheimer s & Dementia Translational Research & Clinical Interventions

DOI: 10.1002/trc2.12012