Miles Berger1,2,3, Deborah Oyeyemi1,4, Mobolaji O Olurinde5, Heather E Whitson2,4, Kent J Weinhold6, Marty G Woldorff7,8, Lewis A Lipsitz9,10,11, Eugene Moretti1, Charles M Giattino3,8, Kenneth C Roberts3, Junhong Zhou9,10,11, Thomas Bunning1, Michael Ferrandino6, Randall P Scheri6, Mary Cooter1, Cliburn Chan12, Roberto Cabeza7,8, Jeffrey N Browndyke7, David M Murdoch4, Michael J Devinney1, Leslie M Shaw13, Harvey Jay Cohen2,4, Joseph P Mathew1. 1. Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina. 2. Center for the Study of Aging and Human Development, Duke University Medical Center, Durham, North Carolina. 3. Center for Cognitive Neuroscience, Duke University Medical Center, Durham, North Carolina. 4. Department of Medicine, Duke University Medical Center, Durham, North Carolina. 5. Department of Anesthesiology, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania. 6. Department of Surgery, Duke University Medical Center, Durham, North Carolina. 7. Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina. 8. Department of Psychology and Neuroscience, Duke University, Durham, North Carolina. 9. Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, Massachusetts. 10. Division of Gerontology, Beth Israel Deaconess Medical Center, Boston, Massachusetts. 11. Harvard Medical School, Boston, Massachusetts. 12. Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina. 13. Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Abstract
BACKGROUND/ OBJECTIVES: Every year, up to 40% of the more than 16 million older Americans who undergo anesthesia/surgery develop postoperative cognitive dysfunction (POCD) or delirium. Each of these distinct syndromes is associated with decreased quality of life, increased mortality, and a possible increased risk of Alzheimer's disease. One pathologic process hypothesized to underlie both delirium and POCD is neuroinflammation. The INTUIT study described here will determine the extent to which postoperative increases in cerebrospinal fluid (CSF) monocyte chemoattractant protein 1 (MCP-1) levels and monocyte numbers are associated with delirium and/or POCD and their underlying brain connectivity changes. DESIGN: Observational prospective cohort. SETTING: Duke University Medical Center, Duke Regional Hospital, and Duke Raleigh Hospital. PARTICIPANTS: Patients 60 years of age or older (N = 200) undergoing noncardiac/nonneurologic surgery. MEASUREMENTS: Participants will undergo cognitive testing before, 6 weeks, and 1 year after surgery. Delirium screening will be performed on postoperative days 1 to 5. Blood and CSF samples are obtained before surgery, and 24 hours, 6 weeks, and 1 year after surgery. CSF MCP-1 levels are measured by enzyme-linked immunosorbent assay, and CSF monocytes are assessed by flow cytometry. Half the patients will also undergo pre- and postoperative functional magnetic resonance imaging scans. 32-channel intraoperative electroencephalogram (EEG) recordings will be performed to identify intraoperative EEG correlates of neuroinflammation and/or postoperative cognitive resilience. Eighty patients will also undergo home sleep apnea testing to determine the relationships between sleep apnea severity, neuroinflammation, and impaired postoperative cognition. Additional assessments will help evaluate relationships between delirium, POCD, and other geriatric syndromes. CONCLUSION: INTUIT will use a transdisciplinary approach to study the role of neuroinflammation in postoperative delirium and cognitive dysfunction and their associated functional brain connectivity changes, and it may identify novel targets for treating and/or preventing delirium and POCD and their sequelae. J Am Geriatr Soc 67:794-798, 2019.
BACKGROUND/ OBJECTIVES: Every year, up to 40% of the more than 16 million older Americans who undergo anesthesia/surgery develop postoperative cognitive dysfunction (POCD) or delirium. Each of these distinct syndromes is associated with decreased quality of life, increased mortality, and a possible increased risk of Alzheimer's disease. One pathologic process hypothesized to underlie both delirium and POCD is neuroinflammation. The INTUIT study described here will determine the extent to which postoperative increases in cerebrospinal fluid (CSF) monocyte chemoattractant protein 1 (MCP-1) levels and monocyte numbers are associated with delirium and/or POCD and their underlying brain connectivity changes. DESIGN: Observational prospective cohort. SETTING: Duke University Medical Center, Duke Regional Hospital, and Duke Raleigh Hospital. PARTICIPANTS: Patients 60 years of age or older (N = 200) undergoing noncardiac/nonneurologic surgery. MEASUREMENTS: Participants will undergo cognitive testing before, 6 weeks, and 1 year after surgery. Delirium screening will be performed on postoperative days 1 to 5. Blood and CSF samples are obtained before surgery, and 24 hours, 6 weeks, and 1 year after surgery. CSF MCP-1 levels are measured by enzyme-linked immunosorbent assay, and CSF monocytes are assessed by flow cytometry. Half the patients will also undergo pre- and postoperative functional magnetic resonance imaging scans. 32-channel intraoperative electroencephalogram (EEG) recordings will be performed to identify intraoperative EEG correlates of neuroinflammation and/or postoperative cognitive resilience. Eighty patients will also undergo home sleep apnea testing to determine the relationships between sleep apnea severity, neuroinflammation, and impaired postoperative cognition. Additional assessments will help evaluate relationships between delirium, POCD, and other geriatric syndromes. CONCLUSION: INTUIT will use a transdisciplinary approach to study the role of neuroinflammation in postoperative delirium and cognitive dysfunction and their associated functional brain connectivity changes, and it may identify novel targets for treating and/or preventing delirium and POCD and their sequelae. J Am Geriatr Soc 67:794-798, 2019.
Authors: M F Newman; J L Kirchner; B Phillips-Bute; V Gaver; H Grocott; R H Jones; D B Mark; J G Reves; J A Blumenthal Journal: N Engl J Med Date: 2001-02-08 Impact factor: 91.245
Authors: Serge A R B Rombouts; Frederik Barkhof; Rutger Goekoop; Cornelis J Stam; Philip Scheltens Journal: Hum Brain Mapp Date: 2005-12 Impact factor: 5.038
Authors: E W Ely; S K Inouye; G R Bernard; S Gordon; J Francis; L May; B Truman; T Speroff; S Gautam; R Margolin; R P Hart; R Dittus Journal: JAMA Date: 2001-12-05 Impact factor: 56.272
Authors: M F Newman; H P Grocott; J P Mathew; W D White; K Landolfo; J G Reves; D T Laskowitz; D B Mark; J A Blumenthal Journal: Stroke Date: 2001-12-01 Impact factor: 7.914
Authors: András Palotás; Helton J Reis; Gábor Bogáts; Barna Babik; Mihály Racsmány; Linda Engvau; Eva Kecskeméti; Anna Juhász; Luciene B Vieira; Antônio L Teixeira; Marat A Mukhamedyarovi; Albert A Rizvanov; Mehmet E Yalvaç; Melissa M Guimarães; Cláudia N Ferreira; Andrey L Zefirov; Andrey P Kiyasov; Lan Wang; Zoltán Janka; János Kálmán Journal: J Alzheimers Dis Date: 2010 Impact factor: 4.472
Authors: Terri G Monk; B Craig Weldon; Cyndi W Garvan; Duane E Dede; Maria T van der Aa; Kenneth M Heilman; Joachim S Gravenstein Journal: Anesthesiology Date: 2008-01 Impact factor: 7.892
Authors: Miles Berger; David M Murdoch; Janet S Staats; Cliburn Chan; Jake P Thomas; Grant E Garrigues; Jeffrey N Browndyke; Mary Cooter; Quintin J Quinones; Joseph P Mathew; Kent J Weinhold Journal: Anesth Analg Date: 2019-11 Impact factor: 5.108
Authors: 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 Journal: Br J Anaesth Date: 2021-09-14 Impact factor: 9.166
Authors: Rosalía Fernández-Calle; Sabine C Konings; Javier Frontiñán-Rubio; Juan García-Revilla; Lluís Camprubí-Ferrer; Martina Svensson; Isak Martinson; Antonio Boza-Serrano; José Luís Venero; Henrietta M Nielsen; Gunnar K Gouras; Tomas Deierborg Journal: Mol Neurodegener Date: 2022-09-24 Impact factor: 18.879
Authors: Chloe K Nobuhara; W Michael Bullock; Thomas Bunning; Brian Colin; Mary Cooter; Michael J Devinney; Michael N Ferrandino; Jeffrey Gadsden; Grant Garrigues; Ashraf S Habib; Eugene Moretti; Judd Moul; Brian Ohlendorf; Aaron Sandler; Randall Scheri; Bharat Sharma; Jake P Thomas; Christopher Young; Joseph P Mathew; Miles Berger Journal: J Neurol Date: 2020-03-20 Impact factor: 4.849
Authors: Keith W VanDusen; Sarada Eleswarpu; Eugene W Moretti; Michael J Devinney; Donna M Crabtree; Daniel T Laskowitz; Marty G Woldorff; Kenneth C Roberts; John Whittle; Jeffrey N Browndyke; Mary Cooter; Frank W Rockhold; Oke Anakwenze; Michael P Bolognesi; Mark E Easley; Michael N Ferrandino; William A Jiranek; Miles Berger Journal: J Alzheimers Dis Date: 2020 Impact factor: 4.472
Authors: Annemieke M Peters van Ton; Harmke B Duindam; Julia van Tuijl; Wilson Wl Li; Hendrik-Jan Dieker; Niels P Riksen; Fj Anton Meijer; Roy Pc Kessels; Nils Kohn; Johannes G van der Hoeven; Peter Pickkers; Mark Rijpkema; Wilson F Abdo Journal: BMJ Open Date: 2021-05-11 Impact factor: 2.692
Authors: Keith W VanDusen; Yi-Ju Li; Victor Cai; Ashley Hall; Sarah Hiles; J Will Thompson; M Arthur Moseley; Mary Cooter; Leah Acker; Jerrold H Levy; Kamrouz Ghadimi; Quintin J Quiñones; Michael J Devinney; Stacey Chung; Niccolò Terrando; Eugene W Moretti; Jeffrey N Browndyke; Joseph P Mathew; Miles Berger Journal: J Alzheimers Dis Date: 2021 Impact factor: 4.472
Authors: Sarinnapha M Vasunilashorn; Michael J Devinney; Leah Acker; Yoojin Jung; Long Ngo; Mary Cooter; Richard Huang; Edward R Marcantonio; Miles Berger Journal: J Am Geriatr Soc Date: 2020-06-01 Impact factor: 7.538
Authors: Jan Menzenbach; Stilla Frede; Janine Petras; Vera Guttenthaler; Andrea Kirfel; Claudia Neumann; Andreas Mayr; Maria Wittmann; Mark Coburn; Sven Klaschik; Tobias Hilbert Journal: Biomedicines Date: 2021-05-15