Author(s): Christian Lopez Aponte, MD, Andrew Chen, DO
Originally published: February 12, 2026 Last updated: February 12, 2026
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Disease/Disorder

Definition

Neurocognitive decline can be defined as deterioration of the level of cognitive functioning, affecting domains in execution, attention, perception, memory, and social cognition.1 The changes in these domains lead to significant consequences on quality of life, autonomy, and healthcare utilization.2

Etiology

The metabolic derangements, hypoxia, glucose dysregulation, use of medications like sedatives and narcotics, associated with critical illness have been associated with progressive cognitive decline.3 All of the aforementioned factors have also been linked with increased chances of developing delirium, which in itself is a risk factor for cognitive decline.3

Epidemiology including risk factors and primary prevention

The Bringing to Light the Risk Factors and Incidence of Neuropsychological Dysfunction in ICU Survivors (BRAIN-ICU) study showed that 1-year cognitive outcomes among ICU survivors are independent of age, similar in severity to mild Alzheimer’s-type dementia or moderate traumatic brain injury, and related to cortical loss, white-matter injury, or both. The most potent risk factor for cognitive dysfunction at 1 year is the duration of ICU delirium. Other risk factors include hypoxemia, blood glucose dysregulation, conservative fluid management, lack of statins, sepsis-induced encephalopathy, immobility, deep coma, sleep disruption, and separation from family.3

Patho-anatomy/physiology

Cognitive impairment represents dysfunction of the brain arising from a complex interplay of risk factors including the underlying disease, age, polypharmacy, pain, duration of intubation, environmental stimulation, and sleep deprivation. The pathophysiology of neurocognitive decline after ICU admission is not well known.1 Potential factors that have been suggested include functional anatomic deficits, neurotransmitter dysfunction, impaired cerebral oxidative metabolism and disruption of the blood brain barrier secondary to inflammation and cytokine dysfunction.3

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

New Onset/Acute

The acute phase is characterized by difficulty with attention, memory, processing speed and/or impaired sleep/wake cycles. At times, this leads to delirium which is defined as an acute brain dysfunction presenting with altered consciousness, disorganized thinking, fluctuating attention. Delirium is highly prevalent in ICU patients and is associated with triggers like hypoxia, sepsis, metabolic derangements, and sedative exposure.3–6 Septic encephalopathy and other neurologic complications (e.g., stroke, seizures) may also occur.5,6 The duration and severity of delirium are strongly linked to subsequent long-term cognitive impairment.3,4,7

Subacute

After ICU discharge, many survivors experience persistent cognitive deficits in memory, attention, and executive function. Objective assessments reveal cognitive impairment in up to 54% of patients at 3 months, with higher rates in those with ARDS or severe sepsis.7,8 Neuroimaging often shows white matter changes and cortical atrophy, likely related to hypoxic injury and systemic inflammation.8–10 Some patients show gradual improvement, while others remain significantly impaired.3,7,11

Chronic/Stable

Long-term cognitive impairment can persist for years, with 30–43% of patients affected at 12 months post-discharge.7,12 Functional changes include reduced independence, inability to return to work, and decreased quality of life.4,11,12 Risk factors for chronic impairment include older age, pre-existing frailty, prolonged delirium, and severity of illness.4,11,12 The underlying pathophysiology includes persistent neuroinflammation, white matter changes, and neuronal loss.10,11

Pre-Terminal

In the pre-terminal phase, neurocognitive decline may accelerate, often accompanied by worsening frailty, functional dependency, and multisystem failure.4,11 Cognitive impairment may be compounded by mood disorders, recurrent delirium, and progressive loss of independence, contributing to increased mortality and institutionalization.4,11

Specific secondary or associated conditions and complications

Cognitive dysfunction, mood disorders (depression, anxiety, PTSD), and renal dysfunction are frequently coexisting conditions that compound the overall morbidity.4

Essentials of Assessment

History

Obtain a detailed account of cognitive changes, including onset, progression, and associated factors. Review pre-existing cognitive or psychiatric conditions, medication exposures (especially sedatives and psychoactive agents), substance use, and prior functional status. Collateral information from family or caregivers is essential for establishing baseline cognition and identifying new deficits.5,9,13

Physical examination

Perform a comprehensive physical exam, focusing on vital signs and systemic findings that may contribute to encephalopathy (e.g., sepsis, metabolic derangements). The neurological exam should assess level of consciousness, attention, memory, executive function, cranial nerves, motor and sensory systems, and screen for focal deficits. Delirium and acute encephalopathy should be evaluated using validated tools such as CAM-ICU or ICDSC.6

Functional assessment

Evaluate activities of daily living (ADLs), instrumental ADLs, and overall functional status. The use of standardized cognitive screening instruments (e.g., Montreal Cognitive Assessment, Mini-Mental State Examination) help qualify the level of impairment. Assess for ICU-acquired weakness and physical disability, which often co-occur with cognitive deficits.5,14

Laboratory studies

Targeted laboratory tests help evaluate potential physiologic derangements, such as complete blood count, electrolytes, renal and hepatic panels, glucose, calcium, and markers of infection or inflammation. Additional studies (e.g., EEG, neuroimaging, CSF analysis) may be indicated for unexplained or severe encephalopathy, seizures, or focal neurological findings.4,5

Imaging

Imaging is not used to diagnose neurocognitive decline but may be useful to rule out differential diagnoses. Neuroimaging might be helpful in unexplained symptoms or prolonged recovery in order to assess for ischemic/hemorrhagic events, infection and others.

Supplemental assessment tools

Cognitive impairment is linked to worse rehabilitative outcomes. The Montreal Cognitive Assessment (MoCA) is the most widely recommended tool for evaluating cognitive impairment following intensive care unit (ICU), as endorsed by multiple consensus guidelines. The MoCA covers different domains, including attention, executive function, memory, and visuospatial skills. Serial assessments with MoCA could be used to track changes, especially in high-risk patients.14,15

Other validated screening instruments include the Mini-Mental State Examination (MMSE), though it is less sensitive than MoCA.14,15 The Johns Hopkins Adapted Cognitive Exam is specifically validated for critically ill patients and demonstrates high reliability and sensitivity for quantifying cognitive status.16

Early predictions of outcomes

Duration of delirium is consistently the strongest predictor of long-term cognitive dysfunction and impaired executive function.3,4Premorbid impairments, age, lower cognitive reserve and frailty also correlate with worse outcomes, including persistent deficits and limited recovery.4,13,16

Environmental

Increased frequency and therapy sessions as well as  reduction in the use of sedative and pain medications are associated with improved functional outcomes in the ICU. Environmental modifications to reduce noise, promote sleep and increase exposure to natural sunlight result in improvements in orientation and the ability to participate in rehabilitation.17

Social role and social support system

Assessments of social, financial, and caregiver resources are pivotal to effective planning following the ICU stay and acute hospitalization. In addition, early caregiver education and involvement promotes engagement with discharge planning and should facilitate optimal long-term functional outcomes.

Professional issues

In coordination with ICU staff, rehabilitation professionals may have the opportunity to participate in end-of-life discussions. While community discharge with family is generally preferred, rehabilitation professionals play a role in identifying post acute care options for a safe and educated return to the community.

Rehabilitation Management and Treatments

Available or current treatment guidelines at different disease stages

New Onset/Acute Phase

  • Potential curative interventions: There are no established curative treatments for neurocognitive decline in the acute phase. Prevention of delirium and minimization of risk factors are emphasized. The ABCDEF bundle (Assess, prevent, and manage pain; Both spontaneous awakening and breathing trials; Choice of analgesia and sedation; Delirium assessment, prevention, and management; Early mobility and exercise; Family engagement) and light sedation protocols potentially mitigate long-term cognitive decline.10
  • Symptom relief: The focus is mostly on non-pharmacologic strategies; pharmacologic agents (antipsychotics, alpha-2 agonists) have not shown clear benefit for cognitive outcomes and should be reserved for severe agitation.18
  • Rehabilitation strategies: Early mobilization protocols in the ICU are safe and feasible, with evidence suggesting reduced delirium duration and improved short-term function. This could be implemented safely as early as 24-48 hours after starting mechanical ventilation and has correlated with improved cognitive outcomes. 19  Early cognitive therapy is feasible but lacks strong evidence for efficacy.4,10

Subacute Phase

  • Secondary prevention/disease management: Serial screening for cognitive, functional, and mental health impairments is recommended, especially in high-risk patients, using tools like the Montreal Cognitive Assessment and functional status measures.13
  • Symptom relief: Ongoing management of neuropsychiatric symptoms (anxiety, depression, PTSD) is important, with referral to mental health services as needed.13
  • Rehabilitation strategies: Multidisciplinary rehabilitation (physical, cognitive, psychological) should be individualized. Technology-assisted cognitive training, physical exercise, and virtual reality are emerging as promising adjuncts. Post-ICU clinics and telehealth may support recovery, though evidence for improved cognition is limited.4,11

Chronic/Stable Phase

  • Secondary prevention/disease management: Continued monitoring and management of comorbidities, risk factors, and functional status are essential. Tailored rehabilitation and support for activities of daily living are recommended.4,13
  • Palliative strategies: For persistent, severe impairment, focus shifts to optimizing quality of life, supporting caregivers, and addressing psychosocial needs.4,11
  • Symptom relief: Management of chronic neuropsychiatric symptoms and cognitive dysfunction continues, with emphasis on non-pharmacologic interventions.11
  • Rehabilitation strategies: Long-term, multimodal cognitive rehabilitation (including technology-assisted and virtual reality approaches) and physical exercise may enhance function and well-being, though standardization and predictors of response are needed.11,20

Pre-Terminal or End-Of-Life Care

  • Symptom relief: Delirium is common and distressing. Non-pharmacologic measures may be less feasible; pharmacologic management (e.g., haloperidol, lorazepam) can be considered for terminal agitation, but evidence is limited and antipsychotics may worsen outcomes in some populations.

Coordination of care

Multidisciplinary teams made up of physicians, nurses, therapists, psychologists, social workers, and palliative care specialists are recommended to address the complex biopsychosocial needs of ICU survivors with neurocognitive impairment.11 The ABCDEF bundle correlates with improved cognitive and functional outcomes and should be maintained throughout the care continuum.4,10

Patient & family education

Patient and family involvement encompasses flexible visitation, structured education, active participation in care, and engagement in delirium detection.21 Family members can assist in recognition of changes and emotional support, facilitating timely intervention.22 This approach demonstrated a 24% reduction in delirium risk and fewer delirium days with family involvement.21

Measurement of treatment outcomes

Rehabilitation and environmental interventions in the ICU setting are associated with positive outcomes in cognition, physical functioning, and discharge destination.22 Patient outcomes can be measured in a multitude of ways, but the most common ways are duration of mechanical ventilation, muscle strength, physical function, and quality of life. These metrics are key for evaluating rehabilitation interventions in the ICU.17

Translation into practice: Practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills

Validated tools such as the MoCA, MMSE, the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and the Trail Making Test can all be used to evaluate cognitive decline after ICU discharge.13

The 4 E’s approach: Engage, Educate, Execute, and Evaluate, has also been shown to help in coordinating care within the ICU.22 Through the use of interactive learning, multidisciplinary hands on skills assessments and clinical benchmarks, quality changes are able to be implemented that lead to improve outcomes.

The ABCDEF bundle is a protocol focused on improving ICU care and correlates with lower delirium incidence/duration, mortality, and mechanical ventilation days.4,17

Cutting Edge/Emerging and Unique Concepts and Practice

Newer concepts include biomarker-driven research (e.g., inflammatory cytokines, white matter hyperintensities), precision phenotyping of delirium, advanced neuromonitoring, and multidisciplinary post-ICU care. Early mobilization and cognitive therapy remain promising but lack definitive evidence for reducing long-term impairment. There is increasing focus on individualized risk stratification and dedicated follow-up for post-intensive care syndrome and neuro-long COVID survivors.4,5,9,18

Gaps in the Evidence-Based Knowledge

  • Ability to measure a patient’s baseline status.
  • Understanding the optimal dose of rehabilitation interventions.
  • Development of reliable and feasible methods of measuring the intensity of rehabilitation dosing.
  • Unclear timing of initiation rehabilitation efforts in the ICU setting.
  • Understanding of cellular and molecular processes.
  • Use of neurostimulants and their potential efficacy.
  • Outcomes Research and Rehab QI in the ICU.

References

  1. Ramnarain D, Pouwels S, Fernandez-Gonzalo S, Navarra-Ventura G, Balanza-Martinez V. Delirium-related psychiatric and neurocognitive impairment and the association with post-intensive care syndrome-A narrative review. Acta Psychiatr Scand. 2023;147(5):460-474. doi:10.1111/acps.13534
  2. Pierre A, Favory R, Bourel C, et al. Muscle weakness after critical illness: unravelling biological mechanisms and clinical hurdles. Crit Care. 2025;29(1):248. doi:10.1186/s13054-025-05462-z
  3. Wilcox ME, Girard TD, Hough CL. Delirium and long term cognition in critically ill patients. BMJ. 2021;373:n1007. doi:10.1136/bmj.n1007
  4. Herridge MS, Azoulay E. Outcomes after Critical Illness. N Engl J Med. 2023;388(10):913-924. doi:10.1056/NEJMra2104669
  5. Fan TH, Premraj L, Roberts J. In-Hospital Neurologic Complications, Neuromonitoring, and Long-Term Neurologic Outcomes in Patients With Sepsis: A Systematic Review and Meta-Analysis. Crit Care Med. 2024;52(3):452-463. doi:10.1097/CCM.0000000000006096.
  6. Piva S, Bertoni M, Gitti N, Rasulo FA, Latronico N. Neurological Complications of Sepsis. Curr Opin Crit Care. 2023;29(2):75-84. doi:10.1097/MCC.0000000000001022.
  7. Honarmand K, Lalli RS, Priestap F. Natural History of Cognitive Impairment in Critical Illness Survivors. A Systematic Review. Am J Respir Crit Care Med. 2020;202(2):193-201. doi:10.1164/rccm.201904-0816CI.
  8. Fonsmark L, Christensen RHB. Neuropsychiatric and Cognitive Outcomes in Patients 6 Months After COVID-19 Requiring Hospitalization Compared With Matched Control Patients Hospitalized for Non–COVID-19 Illness. Nersesjan. 2022;V(5):486-497. doi:10.1001/jamapsychiatry.2022.0284.
  9. Andonovic M, Morrison H, Allingham W. Mechanisms Underlying Neurocognitive Dysfunction Following Critical Illness: A Systematic Review. Anaesthesia. 2025;80(2):188-196. doi:10.1111/anae.16494.
  10. Pandharipande P, Williams Roberson S, Harrison FE. Mitigating Neurological, Cognitive, and Psychiatric Sequelae of COVID-19-related Critical Illness. Respir Med. 2023;11(8):726-738. doi:10.1016/S2213-2600(23)00238-2.
  11. Tingey JL, Dasher NA, Bunnell AE, PM SAJ, R. Intensive Care-Related Cognitive Impairment: A Biopsychosocial Overview. J Inj Funct Rehabil. 2022;14(2):259-272. doi:10.1002/pmrj.12773.
  12. Rengel KF, Hayhurst CJ, Pandharipande PP. Long-Term Cognitive and Functional Impairments After Critical Illness. Anesth Analg. 2019;128(4):772-780. doi:10.1213/ANE.0000000000004066.
  13. Mikkelsen ME, Still M, Anderson BJ, et al. Society of Critical Care Medicine’s International Consensus Conference on Prediction and Identification of Long-Term Impairments After Critical Illness. Crit Care Med. 2020;48(11):1670-1679. doi:10.1097/CCM.0000000000004586
  14. Bornemann-Cimenti H, Lang J, Hammer S, et al. Consensus-Based Recommendations for Assessing Post-Intensive Care Syndrome: A Systematic Review. J Clin Med. 2025;14(10):3595. doi:10.3390/jcm14103595
  15. Lewin JJ, LeDroux SN, Shermock KM, et al. Validity and reliability of The Johns Hopkins Adapted Cognitive Exam for critically ill patients. Crit Care Med. 2012;40(1):139-144. doi:10.1097/CCM.0b013e31822ef9fc
  16. Peinkhofer C, Grønkjær CS, Bang LE, et al. Risk factors of long-term brain health outcomes after hospitalization for critical illness. J Neurol. 2024;272(1):71. doi:10.1007/s00415-024-12786-3
  17. Devlin JW, Skrobik Y, Gelinas C, et al. Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU. Crit Care Med. 2018;46(9):e825. doi:10.1097/CCM.0000000000003299
  18. Ankravs MJ, McKenzie CA, Kenes MT. Precision-based approaches to delirium in critical illness: A narrative review. Pharmacotherapy. 2023;43(11):1139-1153. doi:10.1002/phar.2807
  19. Patel BK, Wolfe KS, Patel SB, et al. Effect of Early Mobilisation on Long-Term Cognitive Impairment in Critical Illness: A randomised clinical trial. Lancet Respir Med. 2023; 11(6):563-572
  20. Pisano F, Rizzo G, Bilotta F. Cognitive rehabilitation for patients with acquired brain injury. Curr Opin Anaesthesiol. 2025;38(5):591-597. doi:10.1097/ACO.0000000000001520
  21. Rosa RG, Falavigna M, da Silva DB, et al. Effect of Flexible Family Visitation on Delirium Among Patients in the Intensive Care Unit: The ICU Visits Randomized Clinical Trial. JAMA. 2019;322(3):216-228. doi:10.1001/jama.2019.8766
  22. Hiser SL, Casey K, Nydahl P, Hodgson CL, Needham DM. Intensive care unit acquired weakness and physical rehabilitation in the ICU. BMJ. 2025;388:e077292. doi:10.1136/bmj-2023-077292

Author Disclosure

Christian Lopez Aponte, MD
Nothing to Disclose

Andrew Chen, DO
Nothing to Disclose