Abstract
Delirium, a syndrome characterized by an acute change in attention, awareness and cognition, is caused by a medical condition that cannot be better explained by a pre-existing neurocognitive disorder. Multiple predisposing factors (for example, pre-existing cognitive impairment) and precipitating factors (for example, urinary tract infection) for delirium have been described, with most patients having both types. Because multiple factors are implicated in the aetiology of delirium, there are likely several neurobiological processes that contribute to delirium pathogenesis, including neuroinflammation, brain vascular dysfunction, altered brain metabolism, neurotransmitter imbalance and impaired neuronal network connectivity. The Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) is the most commonly used diagnostic system upon which a reference standard diagnosis is made, although many other delirium screening tools have been developed given the impracticality of using the DSM-5 in many settings. Pharmacological treatments for delirium (such as antipsychotic drugs) are not effective, reflecting substantial gaps in our understanding of its pathophysiology. Currently, the best management strategies are multidomain interventions that focus on treating precipitating conditions, medication review, managing distress, mitigating complications and maintaining engagement to environmental issues. The effective implementation of delirium detection, treatment and prevention strategies remains a major challenge for health-care organizations globally.
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Change history
01 December 2020
An Erratum to this paper has been published: https://doi.org/10.1038/s41572-020-00236-z.
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Acknowledgements
J.E.W. acknowledges salary support from the Vanderbilt Clinical and Translational Research Scholars program (1KL2TR002245) and from NIH grants (GM120484 and HL111111). M.F.M. acknowledges training and salary support from the Vanderbilt Clinical and Translational Training Program in Pulmonary Medicine (NIH 5T32HL087738) and research funding from the Vanderbilt University Medical Center Arthur and Lisa Wheeler Critical Care Research Fund. C.C. acknowledges research grants from the NIH (AG050626), WT SRF090907 and ARUK. Y.S. acknowledges research grants from the National Health and Medical Research Council of Australia. T.D.G. acknowledges support from NIH grants (HL135144 and HL143507). A.M.J.M. acknowledges funding from the Medical Research Council and the National Institute for Health Research. E.W.E. discloses additional funding for his time from NIH grant AG027472 and salary support from the Tennessee Valley Healthcare System Geriatric Research Education and Clinical Center (GRECC).
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Introduction (J.E.W., A.J.C.S., A.M.J.M. and E.W.E.); Epidemiology (J.E.W., A.M.J.M. and E.W.E.); Mechanisms/pathophysiology (C.C. and A.J.C.S.); Diagnosis, screening and prevention (J.E.W., Y.S., A.M.J.M. and E.W.E.); Management (J.E.W., T.D.G., A.M.J.M. and E.W.E.); Quality of life (J.E.W., M.F.M. and E.W.E.); Outlook (J.E.W., A.M.J.M. and E.W.E.); Overview of Primer (J.E.W.). All authors listed above have contributed substantially to the conception or design of the work or to the acquisition, analysis, or interpretation of data for the work and have participated in drafting the work or revising it critically for important intellectual content. Additionally, each author has given their approval to the final version of the manuscript and has agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
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C.C. acknowledges a current research collaboration with IONIS pharmaceuticals. Y.S. acknowledges unrestricted research grants from Pfizer, Orion Pharma, and Brainstem Biometrics and travel reimbursements and speaker honorarium for educational non-promotional symposia from Pfizer and Orion Pharma. A.J.C.S. is an adviser for Prolira, a start-up company that develops an EEG-based delirium monitor; any (future) profits from EEG-based delirium monitoring will be used for future scientific research only. A.M.J.M. is the main author of the 4AT delirium assessment tool (this tool is free to use and there is no financial interest) and holds patents for computerized delirium assessment tools (any future profits will be used for future scientific research only). E.W.E. received honoraria from Orion and Hospira for continuing medical education activity but does not hold stock or consultant relationships with these companies. The other authors declare no competing interests.
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Nature Reviews Disease Primers thanks K. Neufeld, Y. Skrobik, M. Agar and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.
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Related links
Network for Investigation of Delirium: Unifying Scientists (NIDUS): https://deliriumnetwork.org/
Preserving your brain health during illness or surgery: GCBH recommendations to prevent and treat delirium: https://www.aarp.org/health/brain-health/global-council-on-brain-health/delirium/
The Critical Illness, Brain Dysfunction and Survivorship (CIBS) Center: https://www.icudelirium.org/cibs-center/overview
The Hospital Elder Life Program (HELP): https://www.hospitalelderlifeprogram.org
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Wilson, J.E., Mart, M.F., Cunningham, C. et al. Delirium. Nat Rev Dis Primers 6, 90 (2020). https://doi.org/10.1038/s41572-020-00223-4
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DOI: https://doi.org/10.1038/s41572-020-00223-4
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