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NCT Number: NCT07659431

Inflammatory and Genetic Predictors of 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.

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Key information

Conditions

Post-Intensive Care Syndrome (PICS) Cognition Disorders Cognitive Dysfunction Critical Illness Disease Attributes Mental Disorders Neurocognitive Disorders Pathologic Processes Pathological Conditions, Signs and Symptoms postintensive care syndrome

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Primary outcomes

  1. Cognitive Reserve

    Time frame: Within 24-48 hours after ICU discharge

    Rami- Cognitive Reserve Questionnaire Score range: 0-25

    Cognitive Reserve levels:

    Low: 0-6 Medium-low: 7-9 Medium-high: 10-14

Secondary outcomes

  1. Inflammatory phenotypes

    Time frame: Within 24-48 hours of ICU admission

    To characterize inflammatory and anti-inflammatory response phenotypes using transcriptomic and biomarker data

  2. APOE genotype

    Time frame: Within 24-48 hours of ICU admission

    To characterize pathological aging mechanisims with APOE genotype

  3. Level of consciousness

    Time frame: During ICU stay (up to 28 days)

    Measured using the Richmond Sedation-Agitation Scale (RASS) Score range: from -5 (unarousable) to +5 (agitated)

  4. Illness severity

    Time frame: During ICU stay (up to 28 days)

    Assessed using the Sequential Organ Failure Assessment (SOFA) questionnaire

    Score range: 0-24; 0-6: Mild organ dysfunction 7-9: Moderate severity 10-12: Significant organ dysfunction 13+: Severe illness with substantially increased mortality risk

  5. Comorbidity burden

    Time frame: During ICU stay (up to 28 days)

    Measured using the Charlson Comorbidity Index (CCI)

    0-1 point: Low comorbidity (absence of comorbidities or only very mild diseases).

    2-3 points: Moderate to low comorbidity. 4 points or more: Severe comorbidity or high risk.

  6. Frailty level

    Time frame: During ICU stay (up to 28 days)

    Assessed using the Rockwood Clinical Frailty Scale (CFS)

    Score range from 0 to 9; 1-3: Fit / Non-frail 4: Vulnerable / Very mild frailty 5: Mild frailty 6: Moderate frailty 7-8: Severe to very severe frailty 9: Terminal illness

  7. Presence of delirium

    Time frame: During ICU stay (up to 28 days)

    Assessed using the Confusion Assessment Method for the ICU (CAM-ICU) Recorded as Yes/No

  8. Need and type of mechanical ventilation

    Time frame: During ICU stay (up to 28 days)

    Categorised as:

    • no mechanical ventilation
    • invasive mechanical ventilation
    • high-flow oxygen therapy
    • non-invasive mechanical ventilation

  9. Sedation treatment

    Time frame: During ICU stay (up to 28 days)

    Type of sedative agents administered:

    • none
    • propofol
    • midazolam
    • remifentanil
    • dexmedetomidine

  10. Benzodiazepine use

    Time frame: During ICU stay (up to 28 days)

    Recorded as Yes/No

  11. Global cognitive function (MoCA)

    Time frame: At 3 months and 12 months after ICU discharge

    Assessed using the Montreal Cognitive Assessment (MoCA) Score range: 0-30

    Interpretation:

    26-30 Normal cognitive function 18-25 Mild cognitive impairment (possible) 10-17 Moderate cognitive impairment <10 Severe cognitive impairment

  12. Attention and working memory

    Time frame: At 3 months and 12 months after ICU discharge

    Assessed using Digit Span Forward and Backward (WAIS-IV); Scaled score range: 1-19. Higher scores indicate better performance; scores <8 suggest impairment.

  13. Verbal memory

    Time frame: At 3 months and 12 months after ICU discharge

    Assessed using the Rey Auditory Verbal Learning Test (RAVLT); Total score range recall varies (typically 0-75). Higher scores indicate better verbal learning and memory.

  14. Processing speed

    Time frame: At 3 months and 12 months after ICU discharge

    • Assessed using Coding (WAIS-IV); Scaled score range 1-19. Higher scores indicate better processing speed; scores <8 suggest impairment.
    • Assessed using the Symbol Digit Modalities Test (SDMT); Higher scores indicate better processing speed.

  15. Cognitive flexibility

    Time frame: At 3 and 12 months after ICU discharge

    Assessed using the Trail Making Test Part B (TMT-B); measured in seconds. Lower completion time indicates better performance.

  16. Inhibitory control

    Time frame: At 3 and 12 months after ICU discharge

    Assessed using the Stroop Colour and Word Test. Higher scores indicate greater impairment in inhibitory control.

  17. Verbal fluency

    Time frame: At 3 and 12 months after ICU discharge

    Assessed using the Phonetic Fluency (FAS) Test; measured as the number of words generated. Higher scores indicate better verbal fluency.

  18. Depression

    Time frame: At 3 and 12 months after ICU discharge

    Assessed using the Patient Health Questionnaire-9 (PHQ-9).

    Score range 0-27;

    0-4: None 5-9: Mild 10-14: Moderate 15-19: Moderately severe 20-27: Severe

  19. Anxiety

    Time frame: At 3 and 12 months after ICU discharge

    Assessed using the Generalized Anxiety Disorder-7 (GAD-7).

    Score range 0-21;

    0-4: Minimal 5-9: Mild 10-14: Moderate 15-21: Severe

  20. Post-traumatic stress disorder

    Time frame: At 3 and 12 months after ICU discharge

    Assessed using the Treatment-Outcome Posttraumatic Stress Disorder Scale (TOP-8) Score range 0-32. Higher scores indicate greater PTSD symptom severity.

  21. Perceived cognitive deficits

    Time frame: At 3 and 12 months after ICU discharge

    Assessed using the Perceived Deficits Questionnaire (PDQ-D5). Score range 0-20. Higher scores indicate greater perceived cognitive impairment.

  22. Fatigue

    Time frame: At 3 and 12 months after ICU discharge

    Assessed using the FACIT Fatigue Scale (FACIT-F). Score range 0-52. Lower scores indicate greater fatigue, while higher scores indicate less fatigue.

  23. Pain

    Time frame: At 3 and 12 months after ICU discharge

    Assessed using the Visual Analogue Scale (VAS-10).

    Score range 0-10;

    0: No symptoms 1-3: Mild 4-6: Moderate 7-10: Severe

  24. Dyspnea

    Time frame: At 3 and 12 months after ICU discharge

    Assessed using the Visual Analogue Scale (VAS-10).

    Score range 0-10;

    0: No symptoms 1-3: Mild 4-6: Moderate 7-10: Severe

  25. Sleep quality

    Time frame: At 3 and 12 months after ICU discharge

    Assessed using the Pittsburgh Sleep Quality Index (PSQI). Score range 0-21. Scores >5 indicate poor sleep quality.

  26. Resilience (post-traumatic growth)

    Time frame: At 3 and 12 months after ICU discharge

    Assessed using the Posttraumatic Growth Inventory (PTGI). Score range 0-105. Higher scores indicate greater post-traumatic growth.

  27. Quality of life

    Time frame: At 3 and 12 months after ICU discharge

    Assessed using the 12-Item Short Form Health Survey (SF-12). Score range 0-100. Higher scores indicate better health-related quality of life.

Study contacts

Contact information is provided by the study sponsor or research team.

Sol Fernández-Gonzalo, PhD

CONTACT

[email protected]

+34937236673

Sponsors and collaborators

Lead sponsor

Corporacion Parc Tauli

Other

Collaborators

  • Hospital Universitario Central de Asturias

Registry information

Official study title

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

Acronym: CORE-ICU

Important dates

Study start
2026
Primary completion
2027
Study completion
2028
First posted
Jun 22, 2026
Registry last updated
Jun 22, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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