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 Type
OBSERVATIONAL
Enrollment
114
Cognitive Reserve
Rami- Cognitive Reserve Questionnaire Score range: 0-25 Cognitive Reserve levels: Low: 0-6 Medium-low: 7-9 Medium-high: 10-14
Time frame: Within 24-48 hours after ICU discharge
Inflammatory phenotypes
To characterize inflammatory and anti-inflammatory response phenotypes using transcriptomic and biomarker data
Time frame: Within 24-48 hours of ICU admission
APOE genotype
To characterize pathological aging mechanisims with APOE genotype
Time frame: 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)
Time frame: 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
Time frame: 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.
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: During ICU stay (up to 28 days)
Sedation treatment
Type of sedative agents administered: * none * propofol * midazolam * remifentanil * dexmedetomidine
Time frame: During ICU stay (up to 28 days)
Benzodiazepine use
Recorded as Yes/No
Time frame: 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
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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
Time frame: 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
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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
Time frame: 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
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: At 3 and 12 months after ICU discharge
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