PHYSIOLOGICAL BIOMARKERS FOR THE PREDICTION OF DELIRIUM

Abstract

Delirium is a complex, serious neurocognitive syndrome characterized by an abrupt decline in attention, awareness, and cognition (1,2). Delirium can be triggered by various stressors, including illness or surgery/anesthesia (postoperative). The incidence of delirium increases with age and is linked to increased risk of morbidity, mortality, and Alzheimer’s disease (AD) or other related dementias (ADRDs), but the underlying mechanisms remain unclear (3,4). Currently, no disease-modifying treatment exists, and it remains unclear why some are more likely to develop delirium and progress to AD/ADRD. As a result, delirium contributes to increased healthcare costs in the United States, with over $32.9 billion per year for postoperative delirium alone (2). There is a huge public health need to identify modifiable risk factors for delirium, which is essential for prevention, developing interventions, and slowing dementia progression. Previous work has focused on the predictive value of cognitive impairment or medical comorbidities, but physiological and behavioral biomarkers as potential predictors of delirium risk have not been extensively studied. One area of interest is cardiovascular health, given their overlapping risk factors and links to subsequent dementia and mortality (5). Studies have shown that poor cardiovascular health, such as hypertension, heart disease, and stroke, is associated with an increased risk of delirium (6). One common indicator for cardiovascular health is the heart’s response and recovery (HRR) to exercise, but how this relates to future delirium is unknown. Another area of interest is sleep and circadian health, which is intimately linked to cardiovascular health (7). We and others have shown that poor sleep traits or disturbances, such as extremes in duration, daytime napping, or somnolence, have been linked to an increased risk of delirium.(8,9) Disrupted circadian rest-activity rhythms (RAR), which regulate the body's internal clock and sleep/wake cycle, have also been associated with cognitive decline and dementia.(10,11) Whether these disturbances are related to delirium risk and progression to all-cause dementia is unknown. This body of work examined 1) HRR derived from exercise stress tests and 2) RAR and their associations with delirium risk. Collectively, the two research studies aimed to examine noninvasive and scalable physiological biomarkers that predict the risk of delirium. This can improve our understanding of early disease pathogenesis and risk stratification of older surgical patients to take preventive measures such as regular, targeted exercise and addressing circadian/sleep disturbances.