Cerebral metabolic covariance in delirium: pattern response to symptomatic changes

Area of Science:

• Neuroscience
• Gerontology
• Psychiatry

Background:

• Delirium is an acute neuropsychiatric condition associated with increased dementia risk, but its underlying mechanisms are not fully understood.
• Previous research suggests cerebral hypometabolism in delirium, but a specific metabolic signature has not been clearly defined.
• Understanding delirium's metabolic profile is crucial for developing targeted interventions and improving patient outcomes.

Purpose of the Study:

• To derive and characterize a delirium-specific metabolic pattern (DP) using 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET).
• To investigate the DP's expression in healthy controls, acutely unwell patients, and patients with delirium superimposed on dementia (DSD).
• To track the DP longitudinally to assess its relationship with clinical recovery from delirium.

Main Methods:

• Spatial covariance analysis of FDG-PET data was employed to identify intercorrelated metabolic patterns.
• Seventy participants were included: 30 healthy older adults (Con_healthy), 10 acutely unwell controls (Con_unwell), 13 delirium patients (Delirium), and 17 DSD patients.
• Voxel principal components (PCs) were used to derive the DP and evaluate its expression across different groups and over time.

Main Results:

• The DP distinguished delirium from acute illness, showing relative hypometabolism in default, frontoparietal, visual, and frontostriatal networks, and relative hypermetabolism in sensorimotor and limbic hubs.
• Both delirium and DSD groups exhibited significantly higher DP expression compared to healthy and acutely unwell controls.
• In participants with follow-up, clinical recovery from delirium was associated with a reduction in DP expression.

Conclusions:

• Delirium is characterized by a distinct metabolic profile reflecting widespread network dysfunction, consistent with a global brain failure model.
• The derived DP is primarily attributable to delirium itself, rather than acute illness or underlying dementia.
• The DP represents a clinically responsive and potentially modifiable marker of delirium-related brain dysfunction.