Refining Delirium: A Transtheoretical Model of Delirium Disorder with Preliminary Neurophysiologic Subtypes

The development of delirium indicates neurophysiologic disruption and predicts unfavorable outcomes. This relationship between delirium and its outcomes has inspired a generation of studies aimed at identifying, predicting, and preventing both delirium and its associated sequelae. Despite this, evidence on delirium prevention and management remains limited. No medication is approved for the prevention or treatment of delirium or for its associated psychiatric symptoms. This unmet need for effective delirium treatment calls for a refined approach. First, we explain why a one-size-fits-all approach based on a unitary biological model of delirium has contributed to variance in delirium studies and prevents further advance in the field. Next, in parallel with the shift from dementia to "major neurocognitive disorder," we propose a transtheoretical model of "delirium disorder" composed of interactive elements-precipitant, neurophysiology, delirium phenotype, and associated psychiatric symptoms. We explore how these relate both to the biopsychosocial factors that promote healthy cognition ("procognitive factors") and to consequent neuropathologic sequelae. Finally, we outline a preliminary delirium typology of specific neurophysiologic disturbances. Our model of delirium disorder offers several avenues for novel insights and clinical advance: it univocally differentiates delirium disorder from the phenotype of delirium, highlights delirium neurophysiology as a treatment target, separates the core features of delirium from associated psychiatric symptoms, suggests how procognitive factors influence the core elements of delirium disorder, and makes intuitive predictions about how delirium disorder leads to neuropathologic sequelae and cognitive impairment. Ultimately, this model opens several avenues for modern neuroscience to unravel this disease of antiquity.