Preoperative Cholinergic Signatures Drive Segregated Brain Architecture in Postoperative Delirium.

Area of Science:

• Neuroscience
• Gerontology
• Medical Imaging

Background:

• Delirium is common in hospitalized older adults, increasing mortality and cognitive decline risk.
• Age-related changes in the ascending arousal system (AAS) may predispose individuals to delirium.
• Understanding the neural underpinnings of delirium in aging is crucial.

Purpose of the Study:

• To investigate alterations in brain functional connectivity within the AAS in older adults at risk for delirium.
• To explore the relationship between network dynamics, cholinergic and noradrenergic function, and delirium development.
• To identify neural markers associated with increased vulnerability to delirium in aging.

Main Methods:

• Resting-state functional magnetic resonance imaging (fMRI) was used to analyze static and dynamic functional connectivity in 120 older adults (>65 years).
• Brain networks, focusing on cholinergic and noradrenergic systems, were examined.
• Gene expression data for cholinergic systems was correlated with network segregation.

Main Results:

• Individuals who developed delirium displayed more segregated brain networks compared to those who did not.
• Delirium patients showed hyperconnectivity in cholinergic pathways and hypoconnectivity in noradrenergic pathways.
• Altered temporal dynamics in these arousal systems differentiated between groups, suggesting disrupted network function.

Conclusions:

• Aging-related alterations in the AAS, potentially involving compensatory cholinergic overactivity, contribute to brain network changes that elevate delirium risk.
• These findings offer novel insights into the neural mechanisms linking aging, AAS dysfunction, and brain network disruption in delirium.
• The study suggests a need to re-evaluate current theories of delirium, emphasizing the role of arousal system dysregulation.