Skip to main content Accessibility help

A longitudinal study of delirium phenomenology indicates widespread neural dysfunction

  • Maeve Leonard (a1) (a2) (a3), Dimitrios Adamis (a3) (a4) (a5), Jean Saunders (a6), Paula Trzepacz (a7) (a8) (a9) and David Meagher (a1) (a2) (a3)...



Delirium affects all higher cortical functions supporting complex information processing consistent with widespread neural network impairment. We evaluated the relative prominence of delirium symptoms throughout episodes to assess whether impaired consciousness is selectively affecting certain brain functions at different timepoints.


Twice-weekly assessments of 100 consecutive patients with DSM-IV delirium in a palliative care unit used the Delirium Rating Scale Revised-98 (DRS-R98) and Cognitive Test for Delirium (CTD). A mixed-effects model was employed to estimate changes in severity of individual symptoms over time.


Mean age = 7 0.2 ± 10.5 years, 51% were male, and 27 had a comorbid dementia. A total of 323 assessments (range 2–9 per case) were conducted, but up to 6 are reported herein. Frequency and severity of individual DRS-R98 symptoms was very consistent over time even though the majority of patients (80%) experienced fluctuation in symptom severity over the course of hours or minutes. Over time, DRS-R98 items for attention (88–100%), sleep–wake cycle disturbance (90–100%), and any motor disturbance (87–100%), and CTD attention and vigilance were most frequently and consistently impaired. Mixed-effects regression modeling identified only very small magnitudes of change in individual symptoms over time, including the three core domains.

Significance of results:

Attention is disproportionately impaired during the entire episode of delirium, consistent with thalamic dysfunction underlying both an impaired state of consciousness and well-known EEG slowing. All individual symptoms and three core domains remain relatively stable despite small fluctuations in symptom severity for a given day, which supports a consistent state of impaired higher cortical functions throughout an episode of delirium.


Corresponding author

Address correspondence and reprint requests to: Dimitrios Adamis, University of Limerick Medical School, Limerick, Ireland. E-mail:


Hide All
Adamis, D. (2009). Statistical methods for analysing longitudinal data in delirium studies. International Review of Psychiatry, 21(1), 7485.
American Psychiatric Association (APA) (1987). Diagnostic and statistics manual of mental disorders (DSM-III-R), 3rd rev. ed.Washington, DC: American Psychiatric Association.
American Psychiatric Association (APA) (1994). Diagnostic and statistical manual of mental disorders (DSM-IV), 4th ed.Washington, DC: American Psychiatric Association.
Barnes, J., Kite, S. & Kumar, M. (2010). The recognition and documentation of delirium in hospital palliative care inpatients. Palliative & Supportive Care, 8(2), 133136.
Boettger, S., Passik, S. & Breitbart, W. (2009). Delirium superimposed on dementia versus delirium in the absence of dementia: Phenomenological differences. Palliative & Supportive Care, 7(4), 495500.
Boettger, S., Passik, S. & Breitbart, W. (2011). Treatment characteristics of delirium superimposed on dementia. International Psychogeriatrics, 23(10):16711676.
Breitbart, W. & Alici, Y. (2008). Agitation and delirium at the end of life: “We couldn't manage him.” The Journal of the American Medical Association, 300(24), 2898–910.
Breitbart, W. & Alici, Y. (2012). Evidence-based treatment of delirium in patients with cancer. Journal of Clinical Oncology, 30(11), 12061214.
Breitbart, W., Rosenfeld, B., Roth, A., et al. (1997). The Memorial Delirium Assessment Scale. Journal of Pain and Symptom Management, 13(3), 128137.
de Jonghe, J.F., Kalisvaart, K.J., Dijkstra, M., et al. (2007). Early symptoms in the prodromal phase of delirium: A prospective cohort study in elderly patients undergoing hip surgery. The American Journal of Geriatric Psychiatry, 15(2), 112121.
Ely, E.W., Shintani, A., Truman, B., et al. (2004). Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. The Journal of the American Medical Association, 291(14), 17531762.
Fann, J.R., Alfano, C.M., Burington, B.E., et al. (2005). Clinical presentation of delirium in patients undergoing hematopoietic stem cell transplantation. Cancer, 103(4), 810820.
Franco, J.G., Trzepacz, P.T., Mejia, M.A., et al. (2009). Factor analysis of the Colombian translation of the Delirium Rating Scale (DRS), Revised–98. Psychosomatics, 50(3), 255262.
Franco, J.G., Valencia, C., Bernal, C., et al. (2010). Relationship between cognitive status at admission and incident delirium in older medical inpatients. The Journal of Neuropsychiatry and Clinical Neurosciences, 22(3), 329337.
Franco, J.G., Trzepacz, P.T., Meagher, D.J., et al. (2013). Three core domains of delirium validated using exploratory and confirmatory factor analyses. Psychosomatics, 54, 227238.
Gaudreau, J.D., Gagnon, P., Harel, F., et al. (2005). Psychoactive medications and risk of delirium in hospitalized cancer patients. Journal of Clinical Oncology, 23(27), 67126718.
Greicius, M.D., Supekar, K., Menon, V., et al. (2009). Resting-state functional connectivity reflects structural connectivity in the default mode network. Cerebral Cortex, 19(1), 7278.
Hart, R.P., Levenson, J.L., Sessler, C.N., et al. (1996). Validation of a cognitive test for delirium in medical ICU patients. Psychosomatics, 37(6), 533546.
Hedeker, D.R. & Gibbons, R.D. (2006). Longitudinal data analysis. Hoboken, NJ: Wiley-Interscience.
Inouye, S.K., van Dyck, C.H., Alessi, C.A., et al. (1990). Clarifying confusion: The confusion assessment method. A new method for detection of delirium. Annals of Internal Medicine, 113(12), 941948.
Irwin, S.A., Rao, S., Bower, K.A., et al. (2008). Psychiatric issues in palliative care: Recognition of delirium in patients enrolled in hospice care. Palliative & Supportive Care, 6(2), 159164.
Jabbar, F., Leonard, M., Meehan, K., et al. (2011). Neuropsychiatric and cognitive profile of patients with DSM-IV delirium referred to an old age psychiatry consultation–liaison service. International Psychogeriatrics, 23(7), 11671174.
Jorm, A.F. (1994). A short form of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE): Development and cross-validation. Psychological Medicine, 24(1), 145153.
Katz, I.R., Curyto, K.J., TenHave, T., et al. (2001). Validating the diagnosis of delirium and evaluating its association with deterioration over a one-year period. The American Journal of Geriatric Psychiatry, 9(2), 148159.
Katzman, R., Brown, T., Fuld, P., et al. (1983). Validation of a short orientation-memory-concentration test of cognitive impairment. The American Journal of Psychiatry, 140(6), 734739.
Kean, J., Trzepacz, P.T., Murray, L.L., et al. (2010). Initial validation of a brief provisional diagnostic scale for delirium. Brain Injury, 24(10), 12221230.
Kiely, D.K., Marcantonio, E.R., Inouye, S.K., et al. (2009). Persistent delirium predicts greater mortality. Journal of the American Geriatrics Society, 57(1), 5561.
MacLullich, A.M., Beaglehole, A., Hall, R.J., et al. (2009). Delirium and long-term cognitive impairment. International Review of Psychiatry, 21(1), 3042.
Matsushima, E., Nakajima, K., Moriya, H., et al. (1997). A psychophysiological study of the development of delirium in coronary care units. Biological Psychiatry, 41(12), 12111217.
Mattoo, S.K., Grover, S., Chakravarty, K., et al. (2012). Symptom profile and etiology of delirium in a referral population in northern India: Factor analysis of the DRS-R98. The Journal of Neuropsychiatry and Clinical Neurosciences, 24(1), 95101.
McCusker, J., Cole, M., Bellavance, F., et al. (1998). Reliability and validity of a new measure of severity of delirium. International Psychogeriatrics, 10(4), 421433.
Meagher, D.J. & Trzepacz, P.T. (2009). Delirium. In Oxford textbook of psychiatry, 2nd ed.Geddes, J.J. et al. (eds.), pp. 325332. Oxford: Oxford University Press.
Meagher, D.J., Moran, M., Raju, B., et al. (2007). Phenomenology of delirium: Assessment of 100 adult cases using standardised measures. British Journal of Psychiatry, 190, 135141.
Rudberg, M.A., Pompei, P., Foreman, M.D., et al. (1997). The natural history of delirium in older hospitalized patients: A syndrome of heterogeneity. Age and Ageing, 26(3), 169174.
Schiff, N.D. & Plum, F. (2000). The role of arousal and “gating” systems in the neurology of impaired consciousness. Journal of Clinical Neurophysiology, 17(5), 438452.
Sherer, M., Yablon, S.A. & Nakase-Richardson, R. (2009). Patterns of recovery of posttraumatic confusional state in neurorehabilitation admissions after traumatic brain injury. Archives of Physical Medicine and Rehabilitation, 90(10), 17491754.
Siddiqi, N., House, A.O. & Holmes, J.D. (2006). Occurrence and outcome of delirium in medical inpatients: A systematic literature review. Age and Ageing, 35(4), 350364.
Smith, H.A., Fuchs, D.C., Pandharipande, P.P., et al. (2009). Delirium: An emerging frontier in the management of critically ill children. Critical Care Clinics, 25(3), 593614.
Sylvestre, M.P., McCusker, J., Cole, M., et al. (2006). Classification of patterns of delirium severity scores over time in an elderly population. International Psychogeriatrics, 18(4), 667680.
Trzepacz, P.T. (1994). The neuropathogenesis of delirium. A need to focus our research. Psychosomatics, 35(4), 374391.
Trzepacz, P.T. (1999). Update on the neuropathogenesis of delirium. Dementia and Geriatric Cognitive Disorders, 10(5), 330334.
Trzepacz, P.T. & Meagher, D. (2008). Neuropsychiatric aspects of delirium. In Textbook of neuropsychiatry and behavioural neurosciences, 5th ed.Yudofsky, S. & Hales, R. (eds.), pp. 445–417. Washington, DC: American Psychiatric Publishing.
Trzepacz, P.T., Baker, R.W. & Greenhouse, J. (1988). A symptom rating scale for delirium. Psychiatry Research, 23(1), 8997.
Trzepacz, P.T., Mulsant, B.H., Dew, M.A., et al. (1998). Is delirium different when it occurs in dementia? A study using the delirium rating scale. The Journal of Neuropsychiatry and Clinical Neurosciences, 10(2), 199204.
Trzepacz, P.T., Mittal, D., Torres, R., et al. (2001). Validation of the Delirium Rating Scale–revised-98: Comparison with the Delirium Rating Scale and the Cognitive Test for Delirium. The Journal of Neuropsychiatry and Clinical Neurosciences, 13(2), 229242.
World Medical Association (2004). Declaration of Helsinki: Ethical principles for medical research involving human subjects.



Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed