Inflammatory and Genetic Predictors of Cognitive and Emotional Recovery After Critical Illness

Unraveling the Role of Cognitive Reserve, Inflammatory Phenotype and Genetic Vulnerability on Cognitive and Emotional Recovery After Critical Illness

Survivors of critical illness frequently develop persistent cognitive and emotional impairments, known as post-intensive care syndrome (PICS), which substantially impact quality of life and long-term recovery. While prior research has mainly focused on identifying risk factors, the mechanisms underlying resilience to these sequelae remain poorly understood. Emerging evidence suggests that biological factors, including inflammatory responses and genetic vulnerability, together with cognitive reserve, may play a key role in shaping recovery trajectories.

The aim of this multicenter, prospective observational study is to investigate how cognitive reserve, inflammatory phenotype, and genetic profiles interact to influence cognitive and emotional recovery after critical illness. Adult patients will be recruited at Intensive Care Unit (ICU) admission across two centers in Spain. Clinical and sociodemographic data will be collected during the ICU stay, and biological samples obtained early after admission will undergo transcriptomic and genetic analyses. Cognitive and emotional outcomes will be assessed at hospital discharge and at 3 and 12 months post-discharge using standardised neuropsychological and telemedicine-based evaluations.

By integrating clinical, biological, and cognitive data, this study seeks to identify recovery phenotypes and resilience mechanisms in PICS. The results may contribute to improved risk stratification, inform personalized interventions, and support the development of future strategies aimed at reducing the long-term burden of critical illness.

Inclusion Criteria:

• Adult patients (≥18 years)
• Admitted to a medical-surgical ICU or cardiac ICU for causes of critical illness (e.g., acute pulmonary oedema, myocardial infarction, aortic dissection)
• With or without the need for invasive mechanical ventilation
• With an expected ICU stay of ≥48 hours
• Resident in Catalonia or the Principality of Asturias
• Who speak Catalan and/or Spanish
• Who are able to provide informed consent personally or through an authorised representative (e.g., a family member)

Exclusion Criteria:

• Non-authorisation by the patient and/or relatives for inclusion in the study
• Patients admitted to a neurocritical ICU
• History of severe neurological disease (including dementia or focal brain injury with functional and cognitive impairment) prior to ICU admission
• History of severe psychiatric disorders (schizophrenia, bipolar disorder, major depressive disorder)
• Intellectual disability (IQ <80) or other neurodevelopmental disorders, such as autism spectrum disorder
• Patients who develop secondary complications (e.g., infections, stroke, traumatic brain injury, or other non-transient acquired brain injury) after ICU discharge that may compromise the results of emotional and neuropsychological evaluations during the recovery phase
• Moderate to severe cognitive impairment (Short-IQCODE >57) preventing independent participation in telemedicine or face-to-face follow-up
• Readmission to the ICU within 12 months after ICU discharge
• Language barrier (non-Spanish- and/or non-Catalan-speaking patients)
• Patients with a life expectancy <1 year or not eligible for active treatment measures