TY - JOUR
T1 - The INTUIT Study
T2 - Investigating Neuroinflammation Underlying Postoperative Cognitive Dysfunction
AU - the INTUIT Investigators
AU - Berger, Miles
AU - Oyeyemi, Deborah
AU - Olurinde, Mobolaji O.
AU - Whitson, Heather E.
AU - Weinhold, Kent J.
AU - Woldorff, Marty G.
AU - Lipsitz, Lewis A.
AU - Moretti, Eugene
AU - Giattino, Charles M.
AU - Roberts, Kenneth C.
AU - Zhou, Junhong
AU - Bunning, Thomas
AU - Ferrandino, Michael
AU - Scheri, Randall P.
AU - Cooter, Mary
AU - Chan, Cliburn
AU - Cabeza, Roberto
AU - Browndyke, Jeffrey N.
AU - Murdoch, David M.
AU - Devinney, Michael J.
AU - Shaw, Leslie M.
AU - Cohen, Harvey Jay
AU - Mathew, Joseph P.
AU - Akinyemi, Oladayo
AU - Amundsen, Cindy
AU - Avasarala, Pallavi
AU - Barber, Matthew
AU - Beach, Rachel
AU - Berchuck, Andrew
AU - Blazer, Dan G.
AU - Bolognesi, Michael
AU - Brassard, Rachele
AU - Bullock, W. Michael
AU - Burke, Ashley
AU - Cai, Victor
AU - Cheong, Vanessa
AU - Christensen, Soren
AU - Cox, Mitchell
AU - Crabtree, Donna
AU - D'Amico, Thomas
AU - Davidson, Brittany
AU - Deorio, James
AU - Easley, Mark E.
AU - Ehieli, Eric
AU - Erdmann, Detlev
AU - Funk, Bonita
AU - Gadsden, Jeffrey
AU - Garrigues, Grant
AU - Greenup, Rachel
AU - Habib, Ashraf
N1 - Funding Information:
Financial Disclosure: This work was supported by grants from the National Institutes of Health (NIH): 1K76AG057022 (to Dr. Miles Berger) and the Physical Resilience Indicators and Mechanisms in the Elderly (PRIME) Collaborative (UH2AG0 56925; to Drs. Heather Whitson and Cathleen Colon-Emeric). Dr. Whitson also acknowledges support from the National Center for Advancing Translational Sciences of the NIH (UL1TR002553). Dr. Devinney acknowledges support from a research fellowship grant (from the Foundation for Anesthesia Education and Research). Dr. Murdoch acknowledges support from R01DA043241. Dr. Berger also acknowledges additional support from the Duke Claude D. Pepper Older American Independence Center (P30AG028716), a William L. Young neuroscience research award from the Society for Neuroscience in Anesthesiology and Critical Care (SNACC), and additional support from the Duke Anesthesiology Department.
Funding Information:
We thank Kathy Gage for editorial assistance and Dr. Cathleen Colon-Emeric for helpful discussions. We thank Peter Waweru and Tiffany Bisanar for assistance with sample storage, and we thank Twan Weaver and Prekshaben Patel for assistance with sample processing. Financial Disclosure: This work was supported by grants from the National Institutes of Health (NIH): 1K76AG057022 (to Dr. Miles Berger) and the Physical Resilience Indicators and Mechanisms in the Elderly (PRIME) Collaborative (UH2AG056925; to Drs. Heather Whitson and Cathleen Colon-Emeric). Dr. Whitson also acknowledges support from the National Center for Advancing Translational Sciences of the NIH (UL1TR002553). Dr. Devinney acknowledges support from a research fellowship grant (from the Foundation for Anesthesia Education and Research). Dr. Murdoch acknowledges support from R01DA043241. Dr. Berger also acknowledges additional support from the Duke Claude D. Pepper Older American Independence Center (P30AG028716), a William L. Young neuroscience research award from the Society for Neuroscience in Anesthesiology and Critical Care (SNACC), and additional support from the Duke Anesthesiology Department. Conflict of Interest: The authors have declared no conflicts of interest. Authors' Contributions: All authors contributed to the preparation of the manuscript. All authors read and approved the final manuscript. Sponsors' Role: The funding sources had no role in study design and methodology or in the sample analysis and preparation of this manuscript.
Publisher Copyright:
© 2019 The American Geriatrics Society
PY - 2019/4
Y1 - 2019/4
N2 - 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.
AB - 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.
KW - delirium
KW - monocyte
KW - monocyte chemoattractant protein 1
KW - neuroinflammation
KW - postoperative cognitive dysfunction
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U2 - 10.1111/jgs.15770
DO - 10.1111/jgs.15770
M3 - Article
C2 - 30674067
AN - SCOPUS:85060566022
SN - 0002-8614
VL - 67
SP - 794
EP - 798
JO - Journal of the American Geriatrics Society
JF - Journal of the American Geriatrics Society
IS - 4
ER -