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

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.

Indole-3-Propionic acid, A Gut Microbiota Metabolite, Protects Against the Development of Postoperative Delirium

“…First, for the human study, we only collected data on postoperative days 1 and 2, as these patients were typically discharged from hospital at day 3. Second, Rodent models do not completely recapitulate all clinical features of POD in humans 61,62 . Several different rodent models have been used to study POD, including the Z score system that we used in this study, 28 and 5-choice serial reaction time task for inattention aspect of delirium 63 .…”

Blood tau‐PT217 contributes to the anesthesia/surgery‐induced delirium‐like behavior in aged mice

“…There has been no ideal animal model to study postoperative delirium‐like behavior 77 . Despite the need for an ideal animal model to study postoperative delirium‐like behavior, our lab has developed an animal behavioral test battery.…”

“…There has been no ideal animal model to study postoperative delirium-like behavior. 77 Despite the need for an ideal animal model to study postoperative delirium-like behavior, our lab has developed an animal behavioral test battery. This battery includes natural behaviors such as buried food and an open-field test to evaluate attention and awareness, as well as a learned behavior test (Y maze) to assess cognition.…”

Exploring the Pathophysiology of Delirium: An Overview of Biomarker Studies, Animal Models, and Tissue-Engineered Models

“…These models were recently reviewed. 103 Here, we performed a literature search of animal models that have been reported for the study of delirium with an early animal model reported over 30 years ago and more recent studies published in the last 10 years (Table 2). Approaches to diagnose and define the severity of delirium in these animal models rely predominately on behavioral assessments, such as the attentional set-shifting task and 5-choice serial reaction time task, which are designed to evaluate executive functioning and cognitive deficits.…”