Perioperative neurocognitive and functional neuroimaging trajectories in older APOE4 carriers compared with non-carriers: secondary analysis of a prospective cohort study.

Journal Article (Journal Article)

BACKGROUND: Cognitive dysfunction after surgery is a major issue in older adults. Here, we determined the effect of APOE4 on perioperative neurocognitive function in older patients. METHODS: We 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. RESULTS: There 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. CONCLUSIONS: Postoperative 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.

Full Text

Duke Authors

Cited Authors

  • Browndyke, JN; Wright, MC; Yang, R; Syed, A; Park, J; Hall, A; Martucci, K; Devinney, MJ; Shaw, L; Waligorska, T; Moretti, EW; Whitson, HE; Cohen, HJ; Mathew, JP; Berger, M; MADCO-PC Investigators,

Published Date

  • December 2021

Published In

Volume / Issue

  • 127 / 6

Start / End Page

  • 917 - 928

PubMed ID

  • 34535274

Pubmed Central ID

  • PMC8693648

Electronic International Standard Serial Number (EISSN)

  • 1471-6771

Digital Object Identifier (DOI)

  • 10.1016/j.bja.2021.08.012


  • eng

Conference Location

  • England