Advancing specificity in delirium: The delirium subtyping initiative

Emily M L Bowman^{1

2}, Nathan E Brummel³, Gideon A Caplan⁴, Colm Cunningham⁵, Lis A Evered^{6

7

8}, Kirsten M Fiest^{9

10

11

12

13}, Timothy D Girard¹⁴, Thomas A Jackson¹⁵, Sara C LaHue^{16

17

18}, Heidi L Lindroth^{19

20}, Alasdair M J Maclullich²¹, Daniel F McAuley², Esther S Oh²², Mark A Oldham²³, Valerie J Page²⁴, Pratik P Pandharipande²⁵, Kelly M Potter¹⁴, Pratik Sinha²⁶, Arjen J C Slooter^{27

28}, Aoife M Sweeney¹, Zoë Tieges^{21

29}, Edwin Van Dellen^{27

28}, Mary Elizabeth Wilcox³⁰, Henrik Zetterberg^{31

32

33

34

35

36}, Emma L Cunningham¹

Affiliations

¹ Centre for Public Health, Queen's University Belfast, Block B, Institute of Clinical Sciences, Royal Victoria Hospital Site, Belfast, Northern Ireland.
² Centre for Experimental Medicine, Queen's University Belfast, Wellcome-Wolfson Institute for Experimental Medicine, Belfast, Northern Ireland.
³ The Ohio State University College of Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, Columbus, Ohio, USA.
⁴ Department of Geriatric Medicine, Prince of Wales Hospital, Sydney, Australia University of New South Wales, Sydney, Australia.
⁵ School of Biochemistry & Immunology, Trinity Biomedical Sciences Institute, Trinity College, Dublin, Republic of Ireland.
⁶ Department of Anesthesiology, Weill Cornell Medicine, New York, New York, USA.
⁷ Department of Critical Care, University of Melbourne, Melbourne, Australia.
⁸ Department of Anaesthesia & Acute Pain Medicine, St. Vincent's Hospital, Melbourne, Australia.
⁹ Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
¹⁰ Department of Critical Care Medicine, University of Calgary and Alberta Health Services, Calgary, Alberta, Canada.
¹¹ O'Brien Institute for Public Health, University of Calgary, Calgary, Alberta, Canada.
¹² Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
¹³ Department of Psychiatry, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
¹⁴ Clinical Research, Investigation, and Systems Modeling of Acute Illness (CRISMA) Center, Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
¹⁵ Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK.
¹⁶ Department of Neurology, School of Medicine, University of California, San Francisco, California, USA.
¹⁷ Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, California, USA.
¹⁸ Buck Institute for Research on Aging, Novato, California, USA.
¹⁹ Department of Nursing, Mayo Clinic, Rochester, Minnesota, USA.
²⁰ Center for Aging Research, Regenstrief Institute, School of Medicine, Indiana University, Indianapolis, Indiana, USA.
²¹ Edinburgh Delirium Research Group, Ageing and Health, Usher Institute, University of Edinburgh, Edinburgh, UK.
²² Departments of Medicine, Psychiatry and Behavioral Sciences and Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
²³ Department of Psychiatry, University of Rochester Medical Center, Rochester, New York, USA.
²⁴ Department of Anaesthetics, Watford General Hospital, Watford, UK.
²⁵ Departments of Anesthesiology and Surgery, Division of Anesthesiology Critical Care Medicine and Critical Illness, Brain Dysfunction, and Survivorship Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
²⁶ Division of Clinical and Translational Research, Washington University School of Medicine, St. Louis, Missouri, USA.
²⁷ Departments of Psychiatry and Intensive Care Medicine and UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
²⁸ Department of Neurology, UZ Brussel and Vrije Universiteit Brussel, Brussels, Belgium.
²⁹ School of Computing, Engineering and Built Environment, Glasgow Caledonian University, Glasgow, Scotland.
³⁰ Department of Critical Care Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
³¹ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
³² Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
³³ Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK.
³⁴ UK Dementia Research Institute at UCL, London, UK.
³⁵ Hong Kong Center for Neurodegenerative Diseases, Clear Water Bay, Hong Kong, China.
³⁶ Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.

PMID: 37522255
PMCID: PMC10917010
DOI: 10.1002/alz.13419

Advancing specificity in delirium: The delirium subtyping initiative

Emily M L Bowman et al. Alzheimers Dement. 2024 Jan.

. 2024 Jan;20(1):183-194.

doi: 10.1002/alz.13419. Epub 2023 Jul 31.

Authors

Affiliations

¹ Centre for Public Health, Queen's University Belfast, Block B, Institute of Clinical Sciences, Royal Victoria Hospital Site, Belfast, Northern Ireland.
² Centre for Experimental Medicine, Queen's University Belfast, Wellcome-Wolfson Institute for Experimental Medicine, Belfast, Northern Ireland.
³ The Ohio State University College of Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, Columbus, Ohio, USA.
⁴ Department of Geriatric Medicine, Prince of Wales Hospital, Sydney, Australia University of New South Wales, Sydney, Australia.
⁵ School of Biochemistry & Immunology, Trinity Biomedical Sciences Institute, Trinity College, Dublin, Republic of Ireland.
⁶ Department of Anesthesiology, Weill Cornell Medicine, New York, New York, USA.
⁷ Department of Critical Care, University of Melbourne, Melbourne, Australia.
⁸ Department of Anaesthesia & Acute Pain Medicine, St. Vincent's Hospital, Melbourne, Australia.
⁹ Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
¹⁰ Department of Critical Care Medicine, University of Calgary and Alberta Health Services, Calgary, Alberta, Canada.
¹¹ O'Brien Institute for Public Health, University of Calgary, Calgary, Alberta, Canada.
¹² Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
¹³ Department of Psychiatry, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
¹⁴ Clinical Research, Investigation, and Systems Modeling of Acute Illness (CRISMA) Center, Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
¹⁵ Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK.
¹⁶ Department of Neurology, School of Medicine, University of California, San Francisco, California, USA.
¹⁷ Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, California, USA.
¹⁸ Buck Institute for Research on Aging, Novato, California, USA.
¹⁹ Department of Nursing, Mayo Clinic, Rochester, Minnesota, USA.
²⁰ Center for Aging Research, Regenstrief Institute, School of Medicine, Indiana University, Indianapolis, Indiana, USA.
²¹ Edinburgh Delirium Research Group, Ageing and Health, Usher Institute, University of Edinburgh, Edinburgh, UK.
²² Departments of Medicine, Psychiatry and Behavioral Sciences and Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
²³ Department of Psychiatry, University of Rochester Medical Center, Rochester, New York, USA.
²⁴ Department of Anaesthetics, Watford General Hospital, Watford, UK.
²⁵ Departments of Anesthesiology and Surgery, Division of Anesthesiology Critical Care Medicine and Critical Illness, Brain Dysfunction, and Survivorship Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
²⁶ Division of Clinical and Translational Research, Washington University School of Medicine, St. Louis, Missouri, USA.
²⁷ Departments of Psychiatry and Intensive Care Medicine and UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
²⁸ Department of Neurology, UZ Brussel and Vrije Universiteit Brussel, Brussels, Belgium.
²⁹ School of Computing, Engineering and Built Environment, Glasgow Caledonian University, Glasgow, Scotland.
³⁰ Department of Critical Care Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
³¹ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
³² Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
³³ Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK.
³⁴ UK Dementia Research Institute at UCL, London, UK.
³⁵ Hong Kong Center for Neurodegenerative Diseases, Clear Water Bay, Hong Kong, China.
³⁶ Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.

PMID: 37522255
PMCID: PMC10917010
DOI: 10.1002/alz.13419

Abstract

Background: Delirium, a common syndrome with heterogeneous etiologies and clinical presentations, is associated with poor long-term outcomes. Recording and analyzing all delirium equally could be hindering the field's understanding of pathophysiology and identification of targeted treatments. Current delirium subtyping methods reflect clinically evident features but likely do not account for underlying biology.

Methods: The Delirium Subtyping Initiative (DSI) held three sessions with an international panel of 25 experts.

Results: Meeting participants suggest further characterization of delirium features to complement the existing Diagnostic and Statistical Manual of Mental Disorders Fifth Edition Text Revision diagnostic criteria. These should span the range of delirium-spectrum syndromes and be measured consistently across studies. Clinical features should be recorded in conjunction with biospecimen collection, where feasible, in a standardized way, to determine temporal associations of biology coincident with clinical fluctuations.

Discussion: The DSI made recommendations spanning the breadth of delirium research including clinical features, study planning, data collection, and data analysis for characterization of candidate delirium subtypes.

Highlights: Delirium features must be clearly defined, standardized, and operationalized. Large datasets incorporating both clinical and biomarker variables should be analyzed together. Delirium screening should incorporate communication and reasoning.

Keywords: acute encephalopathy; biomarkers; clinical features; cognitive change; delirium; endotype; subphenotype; subtype.

PubMed Disclaimer

Conflict of interest statement

T.D.G. receives research funding from Ceribell and served previously on an advisory board for Lungpacer Medical Inc. S.C.L. receives funding from the National Institute on Aging (R03AG074035), Larry L. Hillblom Foundation (A137420), UCSF Claude D. Pepper Older Americans Independence Center funded by National Institute on Aging (P30 AG044281), and the Bakar Aging Research Institute. She also receives royalties from Oxford University Press. H.L.L. receives funding from the National Institute on Aging (K23AG076662). E.S.O. receives funding from the National Institute on Aging and National Institutes of Health (R01AG076525, R01AG057725). K.M.P. receives funding from the National Heart, Lung, and Blood Institute (T32HL007820). H.Z. has served on scientific advisory boards and/or as a consultant for Abbvie, Acumen, Alector, Alzinova, ALZPath, Annexon, Apellis, Artery Therapeutics, AZTherapies, CogRx, Denali, Eisai, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pinteon Therapeutics, Prothena, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave; has given lectures in symposia sponsored by Cellectricon, Fujirebio, Alzecure, Biogen, and Roche; and is a co‐founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work). All other authors have no disclosures. Author disclosures are available in the supporting information.

Figures

**FIGURE 1**
A summary of the challenges, recommendations, and future goals established from each session of the Delirium Subtyping Initiative meeting.

See this image and copyright information in PMC

References

1. Wilson JE, Mart MF, Cunningham C, et al. Delirium. Nat Rev Dis Prim. 2020;6:90. - PMC - PubMed
1. Goldberg TE, Chen C, Wang Y, et al. Association of delirium with long‐term cognitive decline: a meta‐analysis. JAMA Neurol. 2020;77:1373‐1381. - PMC - PubMed
1. Bellelli G, Mazzola P, Morandi A, et al. Duration of postoperative delirium is an independent predictor of 6‐month mortality in older adults after hip fracture. J Am Geriatr Soc. 2014;62:1335‐1340. - PubMed
1. Witlox J, Eurelings LSM, de Jonghe JFM, et al. Delirium in elderly patients and the risk of postdischarge mortality, institutionalization, and dementia: a meta‐analysis. JAMA. 2010;304:443‐451. - PubMed
1. Oldham MA, Holloway RG. Delirium disorder. Neurology. 2020;95:173‐178. - PubMed

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Advancing specificity in delirium: The delirium subtyping initiative

Affiliations

Advancing specificity in delirium: The delirium subtyping initiative

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical