Perioperative neurocognitive and functional neuroimaging trajectories in older APOE4 carriers compared with non-carriers: secondary analysis of a prospective cohort study. (December 2021)

• Record Type: Journal Article
• Authors: Browndyke, Jeffrey N.; Wright, Mary C.; Yang, Rosa; Syed, Ayesha; Park, John; Hall, Ashley; Martucci, Katherine; Devinney, Michael J.; Shaw, Leslie; Waligorska, Teresa; Moretti, Eugene W.; Whitson, Heather E.; Cohen, Harvey J.; Mathew, Joseph P.; Berger, Miles; Bengali, S.; Bennett, E.; Brassard, R.; Brigman, B.; Bullock, M.; Carter, J.; Chapman, J.; Colin, B.; D'Amico, T.; DeOrio, J.; Esclamado, R.; Ferrandino, M.; Gadsden, J.; Gardner, J.; Garrigues, G.; Giattino, C.; Grant, S.; Guercio, J.; Gupta, D.; Habib, A.; Harpole, D.; Hartwig, M.; Hu, J.; Iboaya, E.; Inman, B.; Khan, A.; Lagoo-Deenadayalan, S.; Laskowitz, D.; Lee, P.; Lee, W.; Lemm, J.; Levinson, H.; Mantyh, C.; McDonagh, D.; Migaly, J.; Mithani, S.; Moul, J.; Newman, M.; Ohlendorf, B.; Perez, A.; Peterson, A.; Preminger, G.; Quinones, Q.; Ray, A.; Roberts, K.; Robertson, C.; Roman, S.; Runyon, S.; Sandler, A.; Sbahi, F.; Scheri, R.; Smith, K.; Talbot, L.; Thacker, J.; Thomas, J.; Tong, B.; Toulgoat-Dubois, Y.; Tu, A.; Vaslef, S.; Woldorff, M.; Waldron, N.; Wang, X.; Young, C.;
• Is Part Of: British journal of anaesthesia. Volume 127:Number 6(2021)
• Page Start: 917
• Page End: 928
• Publication Date: 2021-12
• Subjects: Alzheimer's disease -- APOE4 -- cerebrospinal fluid -- functional MRI -- intrinsic functional connectivity -- neuroimaging -- perioperative neurocognitive disorders -- surgery; Anesthesiology -- Periodicals; Anesthesia -- Periodicals; 617.9605
• DOI: 10.1016/j.bja.2021.08.012
• Languages: English
• ISSNs: 0007-0912

Abstract

Abstract: 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]; P FWE =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]; P FWE =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.