Sepsis-Associated Encephalopathy and Cognitive Dysfunctions

Sepsis-associated encephalopathy (SAE) encompasses diffuse brain dysfunction arising in the context of systemic infection in the absence of direct central nervous system invasion. It manifests acutely as delirium, altered consciousness and electroencephalographic slowing, while a subset of survivors develops persistent cognitive deficits, memory impairment and executive dysfunction. The pathophysiology is multifactorial, involving disruption of the blood–brain barrier, maladaptive neuroinflammatory cascades, dysregulated microglial and astrocyte responses, oxidative stress and metabolic derangements within vulnerable neuronal networks. Breakdown of cerebral perfusion, endothelial activation and release of pro-inflammatory mediators such as high-mobility group box-1 protein and interleukins further contribute to synaptic injury and neuronal apoptosis. Long-term sequelae may include reductions in hippocampal volume, impairment of long-term potentiation and increased risk of dementia. Clinically, early recognition relies on neurological examination, electroencephalography and, where indicated, neuroimaging. The global burden of SAE is substantial, reflecting the high incidence of sepsis and rising numbers of survivors who require neurocognitive rehabilitation and long-term follow-up.

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Sepsis-Associated Encephalopathy and Cognitive Dysfunctions publication trend

The graph below shows the total number of articles in sepsis-associated encephalopathy and cognitive dysfunctions across all publications each year (not limited to Nature Index journals).

Technical terms

Blood–brain barrier: A selective endothelial interface that regulates molecular and cellular traffic between the circulation and central nervous system.

Microglia: Innate immune cells of the brain responsible for surveillance, phagocytosis and modulation of neuroinflammation.

Astrocyte autophagy: A lysosome-dependent degradation process in astrocytes that removes damaged organelles and protein aggregates.

Synaptic pruning: The elimination of unnecessary or dysfunctional synaptic connections by glial cells during development or in disease.

Long-term potentiation: A lasting increase in synaptic strength following high-frequency stimulation, underlying learning and memory.

C1q complement tagging: An initiation step in the classical complement pathway marking synapses for microglial engulfment.

References

1. AQP4 Aggravates Cognitive Impairment in Sepsis‐Associated Encephalopathy through Inhibiting Nav1.6‐Mediated Astrocyte Autophagy. Advanced Science (2023).
2. Microglia mediate neurocognitive deficits by eliminating C1q-tagged synapses in sepsis-associated encephalopathy. Science Advances (2023).
3. HMGB1 mediates synaptic loss and cognitive impairment in an animal model of sepsis-associated encephalopathy. Journal of Neuroinflammation (2023).
4. The spectrum of sepsis-associated encephalopathy: a clinical perspective. Critical Care (2023).
5. Sepsis-Associated Encephalopathy: From Delirium to Dementia?. Journal of Clinical Medicine (2020).