Open research questions in Intensive Care Unit Cognitive Disorders

What the literature leaves open

• A randomized trial is needed to enroll older patients undergoing non-cardiac surgery, - The trial should ascertain delirium at fixed intervals rather than by code, - The trial should randomize dose and treat discharge as a competing risk, - A formal test for trend should be conducted to settle the question of a U-shaped dose-response

  Comment on “The effect of intravenous low-dose steroids on post-operative delirium in older adult patients undergoing non-cardiac surgery: a retrospective cohort analysis” by Hsu et al · 2026 · DOI

• The paper identifies the gap in the current understanding of the association between intraoperative low-dose steroids and post-operative delirium. The authors argue that the current estimate of the association may be biased. The paper proposes a need for a randomized trial to settle the question.

  Comment on “The effect of intravenous low-dose steroids on post-operative delirium in older adult patients undergoing non-cardiac surgery: a retrospective cohort analysis” by Hsu et al · 2026 · DOI

• detecting delirium, particularly in hypoactive presentations - distinguishing delirium from dementia - managing complex clinical situations with limited support - navigating fragmented services and feeling professionally marginalised

  ‘Just a delirium’: a qualitative study of care home managers’ perspectives on barriers to delirium recognition and management in UK care homes · 2026 · DOI

• Further research on delirium recognition and management in care homes, - Investigation into the development of co-produced delirium education for care staff

  ‘Just a delirium’: a qualitative study of care home managers’ perspectives on barriers to delirium recognition and management in UK care homes · 2026 · DOI

• Further evaluation of a nurse-led, protocol-driven mobilization pathway, - Investigation of the effects of nurse-led early mobilization on neuromuscular and cognitive morbidity, - Multicenter studies to increase generalizability

  Nurse-led early mobilization and ICU-acquired weakness in mechanically ventilated adults: a retrospective before-after cohort study · 2026 · DOI

• Limited real-world evidence on nurse-led early mobilization in Asian ICUs. A need for further evaluation of nurse-led mobilization as a component of ICU care.

  Nurse-led early mobilization and ICU-acquired weakness in mechanically ventilated adults: a retrospective before-after cohort study · 2026 · DOI

• Prospective trials testing monitor-guided interventions, - Evaluation of multimodal biomarkers, - Investigation of the relationship between correcting signal abnormalities and reducing POD, DNR, or longer-term postoperative neurocognitive disorder

  Neurophysiological signatures of latent brain vulnerability in perioperative neurocognitive disorders: integrating EEG, cerebral oximetry, and processed EEG · 2026 · DOI

• The current evidence is limited by heterogeneous PND definitions, device-dependent signal processing, baseline variability, and a lack of prospective trials testing monitor-guided interventions. There is a need for a validated monitor-guided treatment algorithm for preventing PND. The paper identifies the gap in the current understanding of how to capture brain vulnerability in patients who appear cognitively normal before anesthesia and surgery.

  Neurophysiological signatures of latent brain vulnerability in perioperative neurocognitive disorders: integrating EEG, cerebral oximetry, and processed EEG · 2026 · DOI

• Limited research has compared the predicting value of different nutritional assessment tools for delirium in ICU patients. The study aims to fill this gap by exploring the relationship between four nutritional scores and ICU delirium.

  Comparative analysis of four nutritional scores in predicting delirium in ICU patients · 2025 · DOI

• While some participants experienced valuable support from individual healthcare professionals, many described fragmented services, limited information about recovery and uncertainty about where to seek ongoing support.

  Lived Experiences Following Sepsis: Burden, Challenges, and Care Needs - A Qualitative Study · 2026 · DOI

• However, limited research has explored how people with a history of sepsis and their families experience these longer-term consequences and engage with healthcare services in Ireland.

  Lived Experiences Following Sepsis: Burden, Challenges, and Care Needs - A Qualitative Study · 2026 · DOI

• Abstract Introduction Multiple Long-Term Conditions (MLTC) are a recognised risk factor for delirium, but little is known about the impact of MLTC on delirium screening.

  Understanding the impact of Multiple Long-Term Conditions (MLTC) on the completion of delirium screening documentation: analysis using routinely collected clinical data · 2026 · DOI

• CONCLUSIONS: Amantadine may mitigate anesthetic-associated spatial memory impairment and facilitate anesthetic recovery in the aging brain, supporting further investigation of neuromodulatory strategies targeting cognitive vulnerability in aged populations.

  Protective Effects of Amantadine Against Propofol-Associated Spatial Memory Impairment in Aged Mice · 2026 · DOI

• Propofol has been associated with hippocampus-dependent memory impairment in aged experimental models, yet pharmacological strategies to mitigate this vulnerability remain insufficiently explored.

  Protective Effects of Amantadine Against Propofol-Associated Spatial Memory Impairment in Aged Mice · 2026 · DOI

• Both studies reported shorter durations of IMV and ICU stay with remifentanil; however, their economic findings were inconsistent.

  Economic evaluations of remifentanil versus fentanyl for analgo‐sedation in mechanically ventilated adult ICU patients: a systematic review · 2026 · DOI

• Future research should explore comprehensive, multidisciplinary strategies to reduce rehospitalizations in this vulnerable population.

  Factors influencing the anticholinergic burden of medical prescriptions for older patients hospitalized for delirium · 2026 · DOI

• Furthermore, there is a lack of evidence in sub-Saharan Africa, including Ethiopia.

  Incidence and predictors of postoperative cognitive dysfunction among elderly elective surgical patients at selected governmental hospitals in Southern Ethiopia, 2023 GC: a multicenter prospective single arm cohort study · 2026 · DOI

• Introduction: Dysregulation of parvalbumin (PV) interneurons has been implicated in sepsis-associated encephalopathy (SAE), yet the underlying mechanisms remain poorly understood, and effective treatments are lacking.

  Mitochondrial fission inhibitor Mdivi-1 alleviates lipopolysaccharide-induced parvalbumin interneurons dysregulation and cognitive impairments in a mouse model of sepsis-associated encephalopathy · 2025 · DOI

• Background The nutritional assessment indicators for critically ill patients are diverse, with limited research about comparing the predicting value of different nutritional assessment tools for delirium in the intensive care unit (ICU).

  Comparative analysis of four nutritional scores in predicting delirium in ICU patients · 2025 · DOI

• Future research could explore the long-term effects of such interventions and assess patient satisfaction with the educational program.

  The effectiveness of a supportive training program on stress, anxiety, and depression of patients with COVID-19 hospitalized in Najaf hospitals · 2025 · DOI

• Multimodal techniques of anesthesia and long-term cognitive outcomes will also need to be studied in future studies to further delineate ketamine's definitive place in geriatric anesthesia.

  The impact of ketamine on cognitive outcomes in geriatric anesthesia: a comprehensive review · 2025 · DOI

• Background: Postoperative delirium (POD) is a serious neuropsychiatric complication in elderly surgical patients, yet its pathogenesis remains incompletely understood.

  Circulating tsRNAs serve as potential biomarkers for predicting postoperative delirium in elderly patients receiving lower extremity orthopedic surgery · 2025 · DOI

• However, its effect on postoperative delirium (POD) in older patients with fragile brain function after lung cancer remains unclear.

  The effects of esketamine on postoperative delirium in older patients with fragile brain function during the non-acute phase following lung cancer surgery: a randomized controlled trial · 2025 · DOI

• While most research focuses on acute-phase management, long-term recovery remains poorly understood.

  Understanding rehabilitation and support needs after an episode of delirium: a qualitative thematic analysis of interviews with older people with delirium, family carers and healthcare professionals · 2025 · DOI

• The effect of single interventions derived from multicomponent programs remains elusive, but it is essential to assess their effect to identify which components are meaningful.

  Reduced perioperative sensory impairment could lower postoperative delirium incidence: a before-and-after study in older patients with hip fracture · 2025 · DOI

Most-cited papers in Intensive Care Unit Cognitive Disorders

• ASSESSMENT OF COMA AND IMPAIRED CONSCIOUSNESS · The Lancet · 1974 · 9,837 citations
• Delirium in elderly people · The Lancet · 2013 · 3,233 citations
• Delirium in Mechanically Ventilated Patients · JAMA · 2001 · 2,708 citations
• Delirium as a Predictor of Mortality in Mechanically Ventilated Patients in the Intensive Care Unit · JAMA · 2004 · 2,519 citations
• A Multicomponent Intervention to Prevent Delirium in Hospitalized Older Patients · New England Journal of Medicine · 1999 · 2,369 citations
• Long-Term Cognitive Impairment after Critical Illness · New England Journal of Medicine · 2013 · 2,360 citations
• Daily Interruption of Sedative Infusions in Critically Ill Patients Undergoing Mechanical Ventilation · New England Journal of Medicine · 2000 · 2,350 citations
• Long-term Cognitive Impairment and Functional Disability Among Survivors of Severe Sepsis · JAMA · 2010 · 2,188 citations
• Long-term postoperative cognitive dysfunction in the elderly: ISPOCD1 study · The Lancet · 1998 · 1,964 citations
• Delirium in Elderly Patients and the Risk of Postdischarge Mortality, Institutionalization, and Dementia · JAMA · 2010 · 1,755 citations

Most recent work

• Development and multicenter validation of a dynamic nomogram for early postoperative neurocognitive disorder in older adults with hip fracture · BMC Geriatrics · 2026
• Frequent in dementia, deadliest without it: delirium and mortality in hospitalised older adults · Age and Ageing · 2026
• Repetitive transcranial magnetic stimulation to prevent postoperative delirium in elderly arthroplasty patients: study protocol for a single-centre, prospective, randomized controlled trial · BMC Geriatrics · 2026
• Efficacy and Safety of Remimazolam Tosylate versus Propofol for Sedation of Postoperative Mechanically Ventilated Patients in Intensive Care Units: A Multicenter, Randomized, Single-blind, Noninferiority, Phase 3 Trial · Anesthesiology · 2026
• Two Brief Steps, Better Foresight: Cognitive Screening and Adverse Outcomes in Older Adults Admitted From the Emergency Department · Journal of the American Geriatrics Society · 2026
• Reimagining intensive care unit recovery: The Critical Illness Survivorship Programme for humanising post-intensive care unit care - A discussion paper · International Journal of Nursing Studies · 2026
• Impact of preoperative sleep disturbance on perioperative neurocognitive disorders in older adults undergoing major non-cardiac surgery: A multicenter prospective cohort study · Journal of Clinical Anesthesia · 2026
• Using the ascertain dementia eight-item questionnaire to identify at-risk older surgical patients · Journal of Clinical Anesthesia · 2026
• New horizons: disrupted brain energy metabolism as a driver of delirium · Age and Ageing · 2026
• Dementia and postoperative outcomes in older adults: national estimates and mechanistic pathways from a US cohort study · Age and Ageing · 2026

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