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

doi:10.1016/j.bja.2021.08.012

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

Anesthesiology

Producción científica: Article › revisión exhaustiva

15 Citas (Scopus)

Resumen

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.

Idioma original	English
Páginas (desde-hasta)	917-928
Número de páginas	12
Publicación	British Journal of Anaesthesia
Volumen	127
N.º	6
DOI	https://doi.org/10.1016/j.bja.2021.08.012
Estado	Published - dic 2021

Nota bibliográfica

Publisher Copyright:
© 2021 British Journal of Anaesthesia

Financiación

MB has received material support (i.e. EEG monitors) for a postoperative recovery study in older adults from Masimo, unrelated to this manuscript. MB has also received legal consulting fees related to postoperative cognition in older adults. JB acknowledges funding from Claret Medical , Inc. The other authors have no relevant conflicts to disclose. MB has received material support (i.e. EEG monitors) for a postoperative recovery study in older adults from Masimo, unrelated to this manuscript. MB has also received legal consulting fees related to postoperative cognition in older adults. JB acknowledges funding from Claret Medical, Inc. The other authors have no relevant conflicts to disclose.US National Institutes of Health (R01-HL130443 to JM and JB; U01-HL088942 to JM and JB; U01-AG050618 to JB), Duke Anaesthesiology departmental funds, and a mentored research grant from the International Anesthesia Research Society. MB acknowledges additional support from the Alzheimer's Drug Discovery Foundation (NIH grants T32 GM08600, R03AG050918, 1K76AG057022 to MB), Duke Claude D. Pepper Older American Independence Centre (P30AG028716), and William L. Young neuroscience research award from the Society for Neuroscience in Anaesthesiology and Critical Care (SNACC). US National Institutes of Health ( R01-HL130443 to JM and JB; U01-HL088942 to JM and JB; U01-AG050618 to JB), Duke Anaesthesiology departmental funds, and a mentored research grant from the International Anesthesia Research Society . MB acknowledges additional support from the Alzheimer’s Drug Discovery Foundation (NIH grants T32 GM08600 , R03AG050918 , 1K76AG057022 to MB), Duke Claude D. Pepper Older American Independence Centre ( P30AG028716 ), and William L. Young neuroscience research award from the Society for Neuroscience in Anaesthesiology and Critical Care (SNACC).

Financiadores	Número del financiador
Claret Medical, Inc.
Claret Medical, Inc.
Duke Anaesthesiology departmental funds
Duke Claude D. Pepper Older American Independence Centre	P30AG028716
National Institutes of Health (NIH)	1K76AG057022, T32 GM08600, U01-AG050618, U01-HL088942, R01-HL130443
National Institutes of Health (NIH)
National Institute on Aging	R03AG050918
National Institute on Aging
Alzheimer's Drug Discovery Foundation
International Anesthesia Research Society
Society for Neuroscience in Anesthesiology and Critical Care

ASJC Scopus subject areas

Anesthesiology and Pain Medicine

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10.1016/j.bja.2021.08.012

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@article{ac051fd995a9401d8356790ff7fa0de0,

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

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]; 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.",

keywords = "APOE4, Alzheimer's disease, cerebrospinal fluid, functional MRI, intrinsic functional connectivity, neuroimaging, perioperative neurocognitive disorders, surgery",

author = "Browndyke, \{Jeffrey N.\} and Wright, \{Mary C.\} and Rosa Yang and Ayesha Syed and John Park and Ashley Hall and Katherine Martucci and Devinney, \{Michael J.\} and Leslie Shaw and Teresa Waligorska and Moretti, \{Eugene W.\} and Whitson, \{Heather E.\} and Cohen, \{Harvey J.\} and Mathew, \{Joseph P.\} and Miles Berger and S. Bengali and E. Bennett and R. Brassard and B. Brigman and M. Bullock and J. Carter and J. Chapman and B. Colin and T. D'Amico and J. DeOrio and R. Esclamado and M. Ferrandino and J. Gadsden and J. Gardner and G. Garrigues and C. Giattino and S. Grant and J. Guercio and D. Gupta and A. Habib and D. Harpole and M. Hartwig and J. Hu and E. Iboaya and B. Inman and A. Khan and S. Lagoo-Deenadayalan and D. Laskowitz and P. Lee and W. Lee and J. Lemm and H. Levinson and C. Mantyh and D. McDonagh and M. Newman",

note = "Publisher Copyright: {\textcopyright} 2021 British Journal of Anaesthesia",

year = "2021",

month = dec,

doi = "10.1016/j.bja.2021.08.012",

language = "English",

volume = "127",

pages = "917--928",

number = "6",

}

TY - JOUR

T1 - Perioperative neurocognitive and functional neuroimaging trajectories in older APOE4 carriers compared with non-carriers

T2 - secondary analysis of a prospective cohort study

AU - Browndyke, Jeffrey N.

AU - Wright, Mary C.

AU - Yang, Rosa

AU - Syed, Ayesha

AU - Park, John

AU - Hall, Ashley

AU - Martucci, Katherine

AU - Devinney, Michael J.

AU - Shaw, Leslie

AU - Waligorska, Teresa

AU - Moretti, Eugene W.

AU - Whitson, Heather E.

AU - Cohen, Harvey J.

AU - Mathew, Joseph P.

AU - Berger, Miles

AU - Bengali, S.

AU - Bennett, E.

AU - Brassard, R.

AU - Brigman, B.

AU - Bullock, M.

AU - Carter, J.

AU - Chapman, J.

AU - Colin, B.

AU - D'Amico, T.

AU - DeOrio, J.

AU - Esclamado, R.

AU - Ferrandino, M.

AU - Gadsden, J.

AU - Gardner, J.

AU - Garrigues, G.

AU - Giattino, C.

AU - Grant, S.

AU - Guercio, J.

AU - Gupta, D.

AU - Habib, A.

AU - Harpole, D.

AU - Hartwig, M.

AU - Hu, J.

AU - Iboaya, E.

AU - Inman, B.

AU - Khan, A.

AU - Lagoo-Deenadayalan, S.

AU - Laskowitz, D.

AU - Lee, P.

AU - Lee, W.

AU - Lemm, J.

AU - Levinson, H.

AU - Mantyh, C.

AU - McDonagh, D.

AU - Newman, M.

PY - 2021/12

Y1 - 2021/12

N2 - 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.

AB - 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.

KW - APOE4

KW - Alzheimer's disease

KW - cerebrospinal fluid

KW - functional MRI

KW - intrinsic functional connectivity

KW - neuroimaging

KW - perioperative neurocognitive disorders

KW - surgery

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U2 - 10.1016/j.bja.2021.08.012

DO - 10.1016/j.bja.2021.08.012

M3 - Article

C2 - 34535274

AN - SCOPUS:85114997852

SN - 0007-0912

VL - 127

SP - 917

EP - 928

JO - British Journal of Anaesthesia

JF - British Journal of Anaesthesia

IS - 6

ER -

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

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Nota bibliográfica

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ASJC Scopus subject areas

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