Inflammatory and Genetic Predictors of Cognitive and Emotional Recovery After Critical Illness (CORE-ICU)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Critical Illness; Post-Intensive Care Syndrome (PICS)

• Study Type: Observational
• Enrollment (Estimated): 114

Contacts and Locations

• Study Contact: Name: Sol Fernández-Gonzalo, PhD; Phone Number: +34937236673; Email: msfernandez@tauli.cat

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Critically ill patients admitted to the medical / post-surgical ICU of the Parc Tauli Hospital (Sabadell, Spain), and to the Hospital Universitario Central de Asturias.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Critically ill patients (Parc Taulí Hospital)
Critically ill patients (Hospital Universitario Central de Asturias)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognitive Reserve	Rami- Cognitive Reserve Questionnaire Score range: 0-25 Cognitive Reserve levels: Low: 0-6 Medium-low: 7-9 Medium-high: 10-14	Within 24-48 hours after ICU discharge

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Inflammatory phenotypes	To characterize inflammatory and anti-inflammatory response phenotypes using transcriptomic and biomarker data	Within 24-48 hours of ICU admission
APOE genotype	To characterize pathological aging mechanisims with APOE genotype	Within 24-48 hours of ICU admission
Level of consciousness	Measured using the Richmond Sedation-Agitation Scale (RASS) Score range: from -5 (unarousable) to +5 (agitated)	During ICU stay (up to 28 days)
Illness severity	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	During ICU stay (up to 28 days)
Comorbidity burden	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.	During ICU stay (up to 28 days)
Frailty level	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	During ICU stay (up to 28 days)
Presence of delirium	Assessed using the Confusion Assessment Method for the ICU (CAM-ICU) Recorded as Yes/No	During ICU stay (up to 28 days)
Need and type of mechanical ventilation	Categorised as: no mechanical ventilation; invasive mechanical ventilation; high-flow oxygen therapy; non-invasive mechanical ventilation	During ICU stay (up to 28 days)
Sedation treatment	Type of sedative agents administered: none; propofol; midazolam; remifentanil; dexmedetomidine	During ICU stay (up to 28 days)
Benzodiazepine use	Recorded as Yes/No	During ICU stay (up to 28 days)
Global cognitive function (MoCA)	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	At 3 months and 12 months after ICU discharge
Attention and working memory	Assessed using Digit Span Forward and Backward (WAIS-IV); Scaled score range: 1-19. Higher scores indicate better performance; scores <8 suggest impairment.	At 3 months and 12 months after ICU discharge
Verbal memory	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.	At 3 months and 12 months after ICU discharge
Processing speed	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.	At 3 months and 12 months after ICU discharge
Cognitive flexibility	Assessed using the Trail Making Test Part B (TMT-B); measured in seconds. Lower completion time indicates better performance.	At 3 and 12 months after ICU discharge
Inhibitory control	Assessed using the Stroop Colour and Word Test. Higher scores indicate greater impairment in inhibitory control.	At 3 and 12 months after ICU discharge
Verbal fluency	Assessed using the Phonetic Fluency (FAS) Test; measured as the number of words generated. Higher scores indicate better verbal fluency.	At 3 and 12 months after ICU discharge
Depression	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	At 3 and 12 months after ICU discharge
Anxiety	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	At 3 and 12 months after ICU discharge
Post-traumatic stress disorder	Assessed using the Treatment-Outcome Posttraumatic Stress Disorder Scale (TOP-8) Score range 0-32. Higher scores indicate greater PTSD symptom severity.	At 3 and 12 months after ICU discharge
Perceived cognitive deficits	Assessed using the Perceived Deficits Questionnaire (PDQ-D5). Score range 0-20. Higher scores indicate greater perceived cognitive impairment.	At 3 and 12 months after ICU discharge
Fatigue	Assessed using the FACIT Fatigue Scale (FACIT-F). Score range 0-52. Lower scores indicate greater fatigue, while higher scores indicate less fatigue.	At 3 and 12 months after ICU discharge
Pain	Assessed using the Visual Analogue Scale (VAS-10). Score range 0-10; 0: No symptoms 1-3: Mild 4-6: Moderate 7-10: Severe	At 3 and 12 months after ICU discharge
Dyspnea	Assessed using the Visual Analogue Scale (VAS-10). Score range 0-10; 0: No symptoms 1-3: Mild 4-6: Moderate 7-10: Severe	At 3 and 12 months after ICU discharge
Sleep quality	Assessed using the Pittsburgh Sleep Quality Index (PSQI). Score range 0-21. Scores >5 indicate poor sleep quality.	At 3 and 12 months after ICU discharge
Resilience (post-traumatic growth)	Assessed using the Posttraumatic Growth Inventory (PTGI). Score range 0-105. Higher scores indicate greater post-traumatic growth.	At 3 and 12 months after ICU discharge
Quality of life	Assessed using the 12-Item Short Form Health Survey (SF-12). Score range 0-100. Higher scores indicate better health-related quality of life.	At 3 and 12 months after ICU discharge

Collaborators and Investigators

• Sponsor: Corporacion Parc Tauli
• Collaborators: Hospital Universitario Central de Asturias

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: May 28, 2026
• First Submitted That Met QC Criteria: June 16, 2026
• First Posted (Actual): June 22, 2026

Study Record Updates

• Last Update Posted (Actual): June 22, 2026
• Last Update Submitted That Met QC Criteria: June 16, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Critical illness; APOE; cognitive impairment; Cognitive reserve; ICU survivors; Inflammation biomarkers; Emotional Outcomes; Post-intensive care syndrome (PICS)
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Disease Attributes; Neurocognitive Disorders; Cognition Disorders; Pathological Conditions, Signs and Symptoms; Cognitive Dysfunction; Critical Illness; postintensive care syndrome
• Other Study ID Numbers: PID2024-160948OA-I00

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

IPD Plan Description

The data generated will be deposited in recognized open access repositories, accompanied by clear and standardized metadata, which will facilitate its discovery and reuse by other researchers (Institutional reference repository: CORA https://dataverse.csuc.cat/).

These measures not only ensure responsible treatment of data, but also guarantee their reuse and control

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No