Carol K Chan1, Yiqing Song2, Ryan Greene3, Heidi Lindroth4, Sikandar Khan5, Gabriel Rios6, Babar Khan7, Sophia Wang8. 1. Carol K. Chan is a clinical fellow in geriatric psychiatry, Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, Maryland. 2. Yiqing Song is a professor, Fairbanks School of Public Health, Indiana University, Indianapolis. 3. Ryan Greene is an assistant professor, Department of Psychiatry, Indiana University School of Medicine, Indianapolis. 4. Heidi Lindroth is a postdoctoral fellow, Division of Pulmonary, Critical Care, Sleep and Occupational Medicine, Department of Medicine, Indiana University School of Medicine; Indiana Center for Aging Research, Regenstrief Institute, Indianapolis; and Center for Health Innovation and Implementation Science, Indianapolis. 5. Sikandar Khan is an assistant professor, Division of Pulmonary, Critical Care, Sleep and Occupational Medicine, Department of Medicine, Indiana University School of Medicine; Indiana Center for Aging Research, Regenstrief Institute, Indianapolis; and Center for Health Innovation and Implementation Science, Indianapolis. 6. Gabriel Rios is director, Ruth Lilly Medical Library, Indiana University School of Medicine. 7. Babar Khan is an associate professor, Division of Pulmonary, Critical Care, Sleep and Occupational Medicine, Department of Medicine, Indiana University School of Medicine; Indiana Center for Aging Research, Regenstrief Institute, Indianapolis; and Center for Health Innovation and Implementation Science, Indianapolis. 8. Sophia Wang is an assistant professor, Department of Psychiatry, Indiana University School of Medicine, and Indiana Alzheimer's Disease Research Center, Indiana University School of Medicine.
Abstract
BACKGROUND: Between 30% and 80% of survivors of critical illness experience cognitive impairment, but the underlying mechanisms remain unknown. OBJECTIVE: To determine whether intensive care unit (ICU) delirium biomarkers align with the National Institute on Aging-Alzheimer's Association (NIA-AA) research framework for diagnostic biomarkers for Alzheimer disease and other related dementias (ADRD). METHODS: Ovid MEDLINE, PsycInfo, Embase, and the Cochrane Library were systematically searched for articles published between January 1, 2000, and February 20, 2020, on the relationship between delirium and biomarkers listed in the NIA-AA framework. Only studies that addressed delirium in the ICU setting and fluid biomarkers were included in these analyses. RESULTS: Of 61 256 records screened, 38 studies met inclusion criteria, 8 of which were suitable for meta-analysis. In pooled analysis, significant associations were found between ICU delirium and amyloid β-peptide 1-40 (standard mean difference [SMD], 0.42; 95% CI, 0.09-0.75), interleukin (IL)-1 receptor antagonist (SMD, 0.58; 95% CI, 0.21-0.94), and IL-6 (SMD, 0.31; 95% CI, 0.06-0.56). No significant association was observed in pooled analyses between ICU delirium and the other biomarkers. Few studies have examined ICU delirium and pathologic tau or neurodegeneration biomarkers. CONCLUSIONS: Inflammatory biomarkers and amyloid β are associated with ICU delirium and point to potential overlapping mechanisms between delirium and ADRD. Critical care providers should consider integrating diagnostic approaches used in ADRD in their assessment of post-ICU cognitive dysfunction.
BACKGROUND: Between 30% and 80% of survivors of critical illness experience cognitive impairment, but the underlying mechanisms remain unknown. OBJECTIVE: To determine whether intensive care unit (ICU) delirium biomarkers align with the National Institute on Aging-Alzheimer's Association (NIA-AA) research framework for diagnostic biomarkers for Alzheimer disease and other related dementias (ADRD). METHODS: Ovid MEDLINE, PsycInfo, Embase, and the Cochrane Library were systematically searched for articles published between January 1, 2000, and February 20, 2020, on the relationship between delirium and biomarkers listed in the NIA-AA framework. Only studies that addressed delirium in the ICU setting and fluid biomarkers were included in these analyses. RESULTS: Of 61 256 records screened, 38 studies met inclusion criteria, 8 of which were suitable for meta-analysis. In pooled analysis, significant associations were found between ICU delirium and amyloid β-peptide 1-40 (standard mean difference [SMD], 0.42; 95% CI, 0.09-0.75), interleukin (IL)-1 receptor antagonist (SMD, 0.58; 95% CI, 0.21-0.94), and IL-6 (SMD, 0.31; 95% CI, 0.06-0.56). No significant association was observed in pooled analyses between ICU delirium and the other biomarkers. Few studies have examined ICU delirium and pathologic tau or neurodegeneration biomarkers. CONCLUSIONS: Inflammatory biomarkers and amyloid β are associated with ICU delirium and point to potential overlapping mechanisms between delirium and ADRD. Critical care providers should consider integrating diagnostic approaches used in ADRD in their assessment of post-ICU cognitive dysfunction.
Authors: Timothy D Girard; James C Jackson; Pratik P Pandharipande; Brenda T Pun; Jennifer L Thompson; Ayumi K Shintani; Sharon M Gordon; Angelo E Canonico; Robert S Dittus; Gordon R Bernard; E Wesley Ely Journal: Crit Care Med Date: 2010-07 Impact factor: 7.598
Authors: Anders M Fjell; Linda McEvoy; Dominic Holland; Anders M Dale; Kristine B Walhovd Journal: Prog Neurobiol Date: 2014-02-16 Impact factor: 11.685
Authors: P P Pandharipande; T D Girard; J C Jackson; A Morandi; J L Thompson; B T Pun; N E Brummel; C G Hughes; E E Vasilevskis; A K Shintani; K G Moons; S K Geevarghese; A Canonico; R O Hopkins; G R Bernard; R S Dittus; E W Ely Journal: N Engl J Med Date: 2013-10-03 Impact factor: 91.245
Authors: Harald Hampel; Sid E O'Bryant; José L Molinuevo; Henrik Zetterberg; Colin L Masters; Simone Lista; Steven J Kiddle; Richard Batrla; Kaj Blennow Journal: Nat Rev Neurol Date: 2018-11 Impact factor: 42.937
Authors: Amra Sakusic; Ognjen Gajic; Tarun D Singh; John C O'Horo; Gregory Jenkins; Gregory A Wilson; Ronald Petersen; John D Fryer; Rahul Kashyap; Alejandro A Rabinstein Journal: Crit Care Med Date: 2018-12 Impact factor: 7.598
Authors: Ramona O Hopkins; Lindell K Weaver; Dave Collingridge; R Bruce Parkinson; Karen J Chan; James F Orme Journal: Am J Respir Crit Care Med Date: 2004-11-12 Impact factor: 21.405
Authors: Clifford R Jack; David A Bennett; Kaj Blennow; Maria C Carrillo; Billy Dunn; Samantha Budd Haeberlein; David M Holtzman; William Jagust; Frank Jessen; Jason Karlawish; Enchi Liu; Jose Luis Molinuevo; Thomas Montine; Creighton Phelps; Katherine P Rankin; Christopher C Rowe; Philip Scheltens; Eric Siemers; Heather M Snyder; Reisa Sperling Journal: Alzheimers Dement Date: 2018-04 Impact factor: 21.566
Authors: Oskar Hansson; Sylvain Lehmann; Markus Otto; Henrik Zetterberg; Piotr Lewczuk Journal: Alzheimers Res Ther Date: 2019-04-22 Impact factor: 6.982
Authors: Peter Parbo; Rola Ismail; Kim V Hansen; Ali Amidi; Frederik H Mårup; Hanne Gottrup; Hans Brændgaard; Bengt O Eriksson; Simon F Eskildsen; Torben E Lund; Anna Tietze; Paul Edison; Nicola Pavese; Morten G Stokholm; Per Borghammer; Rainer Hinz; Joel Aanerud; David J Brooks Journal: Brain Date: 2017-07-01 Impact factor: 13.501
Authors: Monika Sadlonova; Jonathan Vogelgsang; Claudia Lange; Irina Günther; Adriana Wiesent; Charlotte Eberhard; Julia Ehrentraut; Mareike Kirsch; Niels Hansen; Hermann Esselmann; Charles Timäus; Thomas Asendorf; Benedict Breitling; Mohammed Chebbok; Stephanie Heinemann; Christopher Celano; Ingo Kutschka; Jens Wiltfang; Hassina Baraki; Christine A F von Arnim Journal: BMC Cardiovasc Disord Date: 2022-06-30 Impact factor: 2.174
Authors: Jennifer A Frontera; Allal Boutajangout; Arjun V Masurkar; Rebecca A Betensky; Yulin Ge; Alok Vedvyas; Ludovic Debure; Andre Moreira; Ariane Lewis; Joshua Huang; Sujata Thawani; Laura Balcer; Steven Galetta; Thomas Wisniewski Journal: Alzheimers Dement Date: 2022-01-13 Impact factor: 16.655