• Jeffrey N Browndyke, Mary C Wright, Rosa Yang, Ayesha Syed, John Park, Ashley Hall, Katherine Martucci, Michael J Devinney, Leslie Shaw, Teresa Waligorska, Eugene W Moretti, Heather E Whitson, Harvey J Cohen, Joseph P Mathew, Miles Berger, and MADCO-PC Investigators.
• Department of Psychiatry and Behavioural Medicine, Division of Behavioural Medicine & Neurosciences, Duke University Medical Centre, Durham, NC, USA; Centre for Cognitive Neuroscience, Duke University, Durham, NC, USA; Duke Brain Imaging and Analysis Centre, Durham, NC, USA; Duke Institute for Brain Sciences, Durham, NC, USA. Electronic address: j.browndyke@duke.edu.
• Br J Anaesth. 2021 Dec 1; 127 (6): 917928917-928.

BackgroundCognitive dysfunction after surgery is a major issue in older adults. Here, we determined the effect of APOE4 on perioperative neurocognitive function in older patients.MethodsWe enrolled 140 English-speaking patients ≥60 yr old scheduled for noncardiac surgery under general anaesthesia in an observational cohort study, of whom 52 underwent neuroimaging. We measured cognition; Aβ, tau, p-tau levels in CSF; and resting-state intrinsic functional connectivity in six Alzheimer's disease-risk regions before and 6 weeks after surgery.ResultsThere were no significant APOE4-related differences in cognition or CSF biomarkers, except APOE4 carriers had lower CSF Aβ levels than non-carriers (preoperative median CSF Aβ [median absolute deviation], APOE4 305 pg ml-1 [65] vs 378 pg ml-1 [38], respectively; P=0.001). Controlling for age, APOE4 carriers had significantly greater preoperative functional connectivity than non-carriers between several brain regions implicated in Alzheimer's disease, including between the left posterior cingulate cortex and left angular gyrus (β [95% confidence interval, CI], 0.218 [0.137-0.230]; PFWE=0.016). APOE4 carriers, but not non-carriers, experienced significant connectivity decreases from before to 6 weeks after surgery between several brain regions including between the left posterior cingulate cortex and left angular gyrus (β [95% CI], -0.196 [-0.256 to -0.136]; PFWE=0.001). Most preoperative and postoperative functional connectivity differences did not change after controlling for preoperative CSF Aβ levels.ConclusionsPostoperative change trajectories for cognition and CSF Aβ, tau or p-tau levels did not differ between community dwelling older APOE4 carriers and non-carriers. APOE4 carriers showed greater preoperative functional connectivity and greater postoperative decreases in functional connectivity in key Alzheimer's disease-risk regions, which occur via Aβ-independent mechanisms.Copyright © 2021 British Journal of Anaesthesia. All rights reserved.

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