Preclinical and translational models for delirium: Recommendations for future research from the NIDUS delirium network

Sarinnapha M Vasunilashorn; Nadia Lunardi; John C Newman; Gregory Crosby; Leah Acker; Ted Abel; Seema Bhatnagar; Colm Cunningham; Rafael de Cabo; Laura Dugan; Joseph A Hippensteel; Yumiko Ishizawa; Shouri Lahiri; Edward R Marcantonio; Zhongcong Xie; Sharon K Inouye; Niccolò Terrando; Roderic G Eckenhoff; NIDUS Delirium Network

doi:10.1002/alz.12941

Preclinical and translational models for delirium: Recommendations for future research from the NIDUS delirium network

Alzheimers Dement. 2023 May;19(5):2150-2174. doi: 10.1002/alz.12941. Epub 2023 Feb 17.

Authors

Sarinnapha M Vasunilashorn^{1

2

3}, Nadia Lunardi⁴, John C Newman^{5

6}, Gregory Crosby^{2

7}, Leah Acker⁸, Ted Abel⁹, Seema Bhatnagar^{10

11}, Colm Cunningham^{12

13}, Rafael de Cabo¹⁴, Laura Dugan^{15

16

17}, Joseph A Hippensteel¹⁸, Yumiko Ishizawa^{2

19}, Shouri Lahiri²⁰, Edward R Marcantonio^{1

2

1

21}, Zhongcong Xie^{2

19}, Sharon K Inouye^{2

1

21}, Niccolò Terrando^{22

23

24

25}, Roderic G Eckenhoff¹¹; NIDUS Delirium Network

Affiliations

¹ Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
² Harvard Medical School, Boston, Massachusetts, USA.
³ Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA.
⁴ Department of Anesthesiology, University of Virginia, Charlottesville, Virginia, USA.
⁵ Department of Medicine, University of California, San Francisco, California, USA.
⁶ Buck Institute for Research on Aging, Novato, California, USA.
⁷ Department of Anesthesiology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
⁸ Department of Anesthesiology, Duke University, Durham, Massachusetts, USA.
⁹ Department of Neuroscience and Pharmacology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
¹⁰ Department of Anesthesiology and Critical Care, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
¹¹ Department of Anesthesiology and Critical Care, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
¹² School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Dublin, Ireland.
¹³ Trinity College Institute of Neuroscience, Trinity College, Dublin, Ireland.
¹⁴ Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, Baltimore, Maryland, USA.
¹⁵ Vanderbilt Brain Institute, Vanderbilt University, Nashville, Tennessee, USA.
¹⁶ Division of Geriatric Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
¹⁷ VA Tennessee Valley Geriatric Research, Education, and Clinical Center (GRECC), Nashville, Tennessee, USA.
¹⁸ Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
¹⁹ Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
²⁰ Department of Neurology, Neurosurgery, and Biomedical Sciences, Cedar-Sinai Medical Center, Los Angeles, California, USA.
²¹ Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, Massachusetts, USA.
²² Department of Anesthesiology, Duke University, Durham, North Carolina, USA.
²³ Department of Cell Biology, Duke University, Durham, North Carolina, USA.
²⁴ Department of Immunology, Duke University, Durham, North Carolina, USA.
²⁵ Duke Center for the Study of Aging and Human Development, Duke University School of Medicine, Durham, USA.

Abstract

Delirium is a common, morbid, and costly syndrome that is closely linked to Alzheimer's disease (AD) and AD-related dementias (ADRD) as a risk factor and outcome. Human studies of delirium have advanced our knowledge of delirium incidence and prevalence, risk factors, biomarkers, outcomes, prevention, and management. However, understanding of delirium neurobiology remains limited. Preclinical and translational models for delirium, while challenging to develop, could advance our knowledge of delirium neurobiology and inform the development of new prevention and treatment approaches. We discuss the use of preclinical and translational animal models in delirium, focusing on (1) a review of current animal models, (2) challenges and strategies for replicating elements of human delirium in animals, and (3) the utility of biofluid, neurophysiology, and neuroimaging translational markers in animals. We conclude with recommendations for the development and validation of preclinical and translational models for delirium, with the goal of advancing awareness in this important field.

Keywords: animal models; biomarkers; delirium.

Publication types

Review
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease* / complications
Animals
Delirium* / epidemiology
Humans
Incidence
Neuroimaging
Risk Factors

Abstract

Publication types

MeSH terms

Grants and funding