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The association between C-reactive protein and delirium in 710 acute elderly hospital admissions

Published online by Cambridge University Press:  24 January 2014

C.W. Ritchie*
Affiliation:
Centre for Mental Health, Imperial College London, London, UK
T.H. Newman
Affiliation:
Centre for Mental Health, Imperial College London, London, UK
B. Leurent
Affiliation:
Marie Curie Palliative Care Research Unit, UCL Mental Health Sciences Unit, University College Medical School, Charles Bell House, London, UK
E.L. Sampson
Affiliation:
Marie Curie Palliative Care Research Unit, UCL Mental Health Sciences Unit, University College Medical School, Charles Bell House, London, UK Barnet Enfield and Haringey Mental Health Trust, St Ann's Hospital, St Ann's Road, London, UK
*
Correspondence should be addressed to: Dr Craig W Ritchie, Centre for Mental Health, Imperial College London, Claybrook Centre, 37, Claybrook Road, Hammersmith, London W6 8LN, UK. Phone: +44-0207-430-1630. Email: [email protected].

Abstract

Background:

Delirium is a common neuropsychiatric syndrome associated with poor outcomes. Evidence supports a neuroinflammatory etiology, but the role of the inflammatory marker C-reactive protein (C-RP) remains unclear. We investigated the relationship between C-RP and delirium and its severity as well as interaction with medical diagnosis.

Methods:

From an existing database (710 patients over 70 years old admitted to a Medical Acute Admissions Unit) we analyzed data which included C-RP levels, delirium (using the Confusion Assessment Method), and other clinical and demographic factors. Primary diagnoses were grouped (cardiovascular, musculoskeletal, infection, metabolic, and other).

Results:

There was a strong association between elevated C-RP and delirium (t = 5.09; p < 0.001), independent of other potential risk factors for delirium (odds ratio (OR) = 1.32 (95% CI: 1.10–1.58) p = 0.003). There was no significant association between C-RP and delirium severity, and between C-RP and delirium in the populations with cardiovascular disease, infection upon admission, or from the metabolic group despite an OR of 2.24 (95% CI: 0.92–5.45). There was an association in the musculoskeletal group (OR 2.19 (95% CI: 1.19–4.02)).

Conclusions: There is an association between elevated C-RP and delirium. This is strongest in patients admitted with musculoskeletal disease but not in others, implying that C-RP is involved in the genesis of delirium in musculoskeletal disease, but that other factors or processes may be more important in those with cardiovascular disease or infection.

Type
Research Article
Copyright
Copyright © International Psychogeriatric Association 2014 

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References

Adamis, D. et al. (2009). Cytokines and IGF-I in delirious and non-delirious acutely ill older medical inpatients. Age and Ageing, 38, 326332; discussion 251. doi:10.1093/ageing/afp014.CrossRefGoogle ScholarPubMed
Aldemir, M., Ozen, S., Kara, I. H., Sir, A. and Bac, B. (2001). Predisposing factors for delirium in the surgical intensive care unit. Critical Care (London, England), 5, 265270.CrossRefGoogle ScholarPubMed
Alexander, J. J., Anderson, A. J., Barnum, S. R., Stevens, B. and Tenner, A. J. (2008). The complement cascade: yin-yang in neuroinflammation–neuro-protection and degeneration. Journal of Neurochemistry, 107, 11691187. doi:10.1111/j.1471-4159.2008.05668.x.CrossRefGoogle ScholarPubMed
Ballou, S. P. and Lozanski, G. (1992). Induction of inflammatory cytokine release from cultured human monocytes by C-reactive protein. Cytokine, 4, 361368.CrossRefGoogle ScholarPubMed
Black, S., Kushner, I. and Samols, D. (2004). C-reactive protein. The Journal of Biological Chemistry, 279, 4848748490. doi:10.1074/jbc.R400025200.CrossRefGoogle ScholarPubMed
Bruce, A. J., Ritchie, C. W., Blizard, R., Lai, R. and Raven, P. (2007). The incidence of delirium associated with orthopedic surgery: a meta-analytic review. International Psychogeriatrics, 19, 197214. doi:10.1017/S104161020600425X.CrossRefGoogle ScholarPubMed
Cerejeira, J., Firmino, H., Vaz-Serra, A. and Mukaetova-Ladinska, E. B. (2010). The neuroinflammatory hypothesis of delirium. Acta Neuropathologica, 119, 737754. doi:10.1007/s00401-010-0674-1.CrossRefGoogle ScholarPubMed
Cerejeira, J., Nogueira, V., Luis, P., Vaz-Serra, A. and Mukaetova-Ladinska, E. B. (2012). The cholinergic system and inflammation: common pathways in delirium pathophysiology. Journal of the American Geriatrics Society, 60, 669675. doi:10.1111/j.1532-5415.2011.03883.x; 10.1111/j.1532-5415.2011.03883.x.CrossRefGoogle ScholarPubMed
Charlson, M. E. (1987). Studies of prognosis: progress and pitfalls. Journal of General Internal Medicine, 2, 359361.CrossRefGoogle ScholarPubMed
Clyne, B. and Olshaker, J. S. (1999). The C-reactive protein. The Journal of Emergency Medicine, 17, 10191025.CrossRefGoogle ScholarPubMed
Collins, N., Blanchard, M. R., Tookman, A. and Sampson, E. L. (2010). Detection of delirium in the acute hospital. Age and Ageing, 39, 131135. doi:10.1093/ageing/afp201.CrossRefGoogle ScholarPubMed
de Groot, V., Beckerman, H., Lankhorst, G. J. and Bouter, L. M. (2003). How to measure comorbidity: a critical review of available methods. Journal of Clinical Epidemiology, 56, 221229.CrossRefGoogle ScholarPubMed
de Rooij, S. E., van Munster, B. C., Korevaar, J. C. and Levi, M. (2007). Cytokines and acute phase response in delirium. Journal of Psychosomatic Research, 62, 521525. doi:10.1016/j.jpsychores.2006.11.013.CrossRefGoogle ScholarPubMed
Elie, M., Cole, M. G., Primeau, F. J. and Bellavance, F. (1998). Delirium risk factors in elderly hospitalized patients. Journal of General Internal Medicine, 13, 204212.CrossRefGoogle ScholarPubMed
Hopstaken, R. M., Muris, J. W., Knottnerus, J. A., Kester, A. D., Rinkens, P. E. and Dinant, G. J. (2003). Contributions of symptoms, signs, erythrocyte sedimentation rate, and C-reactive protein to a diagnosis of pneumonia in acute lower respiratory tract infection. The British Journal of General Practice, 53, 358364.Google ScholarPubMed
Hshieh, T. T., Fong, T. G., Marcantonio, E. R. and Inouye, S. K. (2008). Cholinergic deficiency hypothesis in delirium: a synthesis of current evidence. The Journals of Gerontology. Series A: Biological Sciences and Medical Sciences, 63, 764772.CrossRefGoogle ScholarPubMed
Inouye, S. K., van Dyck, C. H., Alessi, C. A., Balkin, S., Siegal, A. P. and Horwitz, R. I. (1990). Clarifying confusion: the confusion assessment method. A new method for detection of delirium. Annals of Internal Medicine, 113, 941948.CrossRefGoogle Scholar
Juma, W. M., Lira, A., Marzuk, A., Marzuk, Z., Hakim, A. M. and Thompson, C. S. (2011). C-reactive protein expression in a rodent model of chronic cerebral hypoperfusion. Brain Research, 1414, 8593. doi:10.1016/j.brainres.2011.07.047.CrossRefGoogle Scholar
Knaus, W. A., Draper, E. A., Wagner, D. P. and Zimmerman, J. E. (1985). APACHE II: a severity of disease classification system. Critical Care Medicine, 13, 818829.CrossRefGoogle ScholarPubMed
Kuhlmann, C. R. et al. (2009). Mechanisms of C-reactive protein-induced blood-brain barrier disruption. Stroke, 40, 14581466. doi:10.1161/STROKEAHA.108.535930.CrossRefGoogle ScholarPubMed
Kushner, I., Jiang, S. L., Zhang, D., Lozanski, G. and Samols, D. (1995). Do post-transcriptional mechanisms participate in induction of C-reactive protein and serum amyloid A by IL-6 and IL-1?. Annals of the New York Academy of Sciences, 762, 102107.CrossRefGoogle ScholarPubMed
Lee, H. et al. (2007). Directed differentiation and transplantation of human embryonic stem cell-derived motoneurons. Stem Cells (Dayton, Ohio), 25, 19311939. doi:10.1634/stemcells.2007-0097.CrossRefGoogle ScholarPubMed
Macdonald, A., Adamis, D., Treloar, A. and Martin, F. (2007). C-reactive protein levels predict the incidence of delirium and recovery from it. Age and Ageing, 36, 222225. doi:10.1093/ageing/afl121.CrossRefGoogle Scholar
Mold, C., Gewurz, H. and Du Clos, T. W. (1999). Regulation of complement activation by C-reactive protein. Immunopharmacology, 42, 2330.CrossRefGoogle ScholarPubMed
Pepys, M. B. and Hirschfield, G. M. (2003). C-reactive protein: a critical update. Journal of Clinical Investigation, 111, 18051812. doi:10.1172/JCI18921.CrossRefGoogle ScholarPubMed
Perry, V. H. (2004). The influence of systemic inflammation on inflammation in the brain: implications for chronic neurodegenerative disease. Brain, Behavior, and Immunity, 18, 407413. doi:10.1016/j.bbi.2004.01.004.CrossRefGoogle ScholarPubMed
Pisani, M. A., Murphy, T. E., Van Ness, P. H., Araujo, K. L. and Inouye, S. K. (2007). Characteristics associated with delirium in older patients in a medical intensive care unit. Archives of Internal Medicine, 167, 16291634. doi:10.1001/archinte.167.15.1629.CrossRefGoogle Scholar
Quan, N. and Banks, W. A. (2007). Brain-immune communication pathways. Brain, Behavior, and Immunity, 21, 727735. doi:10.1016/j.bbi.2007.05.005.CrossRefGoogle ScholarPubMed
Rudolph, J. L., Salow, M. J., Angelini, M. C. and McGlinchey, R. E. (2008). The anticholinergic risk scale and anticholinergic adverse effects in older persons. Archives of Internal Medicine, 168, 508513. doi:10.1001/archinternmed.2007.106; 10.1001/archinternmed.2007.106.CrossRefGoogle ScholarPubMed
Salmon, J. E. and Pricop, L. (2001). Human receptors for immunoglobulin G: key elements in the pathogenesis of rheumatic disease. Arthritis and Rheumatism, 44, 739750.3.0.CO;2-O>CrossRefGoogle ScholarPubMed
Sampson, E. L., Blanchard, M. R., Jones, L., Tookman, A. and King, M. (2009). Dementia in the acute hospital: prospective cohort study of prevalence and mortality. The British Journal of Psychiatry, 195, 6166. doi:10.1192/bjp.bp.108.055335.CrossRefGoogle ScholarPubMed
Sanders, R. D. (2011). Hypothesis for the pathophysiology of delirium: role of baseline brain network connectivity and changes in inhibitory tone. Medical Hypotheses, 77, 140143. doi:10.1016/j.mehy.2011.03.048.CrossRefGoogle ScholarPubMed
Sanderson, C. and Dixon, J. (2000). Conditions for which onset or hospital admission is potentially preventable by timely and effective ambulatory care. Journal of Health Services Research & Policy, 5, 222230.CrossRefGoogle ScholarPubMed
Seo, W. K. et al. (2012). C-reactive protein is a predictor of early neurologic deterioration in acute ischemic stroke. Journal of Stroke and Cerebrovascular Diseases, 21, 181186. doi:10.1016/j.jstrokecerebrovasdis.2010.06.002.CrossRefGoogle ScholarPubMed
Siddiqi, N., House, A. O. and Holmes, J. D. (2006). Occurrence and outcome of delirium in medical in-patients: a systematic literature review. Age and Ageing, 35, 350364. doi:10.1093/ageing/afl005.CrossRefGoogle ScholarPubMed
Speciale, S., Bellelli, G., Guerini, F. and Trabucchi, M. (2008). C-reactive protein levels and delirium in a rehabilitation ward. Age and Ageing, 37, 122123. doi:10.1093/ageing/afm176.CrossRefGoogle Scholar
Thomas, C., Kreisel, S. H., Oster, P., Driessen, M., Arolt, V. and Inouye, S. K. (2012). Diagnosing delirium in older hospitalized adults with dementia: adapting the Confusion Assessment Method to International Classification of Diseases, Tenth Revision, Diagnostic Criteria. Journal of the American Geriatrics Society, 60, 14711477. doi:10.1111/j.1532-5415.2012.04066.x; 10.1111/j.1532-5415.2012.04066.x.CrossRefGoogle ScholarPubMed
Tilvis, R. S., Kahonen-Vare, M. H., Jolkkonen, J., Valvanne, J., Pitkala, K. H. and Strandberg, T. E. (2004). Predictors of cognitive decline and mortality of aged people over a 10-year period. Journals of Gerontology. Series A: Biological Sciences and Medical Sciences, 59, 268274.CrossRefGoogle ScholarPubMed
Uchikado, H. et al. (2004). Activation of vascular endothelial cells and perivascular cells by systemic inflammation – an immunohistochemical study of postmortem human brain tissues. Acta Neuropathologica, 107, 341351. doi:10.1007/s00401-003-0815-x.CrossRefGoogle ScholarPubMed
van Gool, W. A., van de Beek, D. and Eikelenboom, P. (2010). Systemic infection and delirium: when cytokines and acetylcholine collide. Lancet, 375, 773775. doi:10.1016/S0140-6736(09)61158-2.CrossRefGoogle ScholarPubMed
Volanakis, J. E. (1982). Complement activation by C-reactive protein complexes. Annals of the New York Academy of Sciences, 389, 235250.CrossRefGoogle ScholarPubMed
Wei, L. A., Fearing, M. A., Sternberg, E. J. and Inouye, S. K. (2008). The Confusion Assessment Method: a systematic review of current usage. Journal of the American Geriatrics Society, 56, 823830. doi:10.1111/j.1532-5415.2008.01674.x.CrossRefGoogle Scholar
White, S., Eeles, E., O'Mahony, S. and Bayer, A. (2008). Delirium and C-reactive protein. Age and Ageing, 37, 123124; author reply 124. doi:10.1093/ageing/afm178.CrossRefGoogle ScholarPubMed
Willard, L. B., Hauss-Wegrzyniak, B. and Wenk, G. L. (1999). Pathological and biochemical consequences of acute and chronic neuroinflammation within the basal forebrain cholinergic system of rats. Neuroscience, 88, 193200.CrossRefGoogle ScholarPubMed
Wright, R. J. and Frier, B. M. (2008). Vascular disease and diabetes: is hypoglycaemia an aggravating factor? Diabetes/Metabolism Research and Reviews, 24, 353363. doi:10.1002/dmrr.865.CrossRefGoogle ScholarPubMed
Yeh, K. H. et al. (2012). Comparison of acute versus convalescent stage high-sensitivity C-reactive protein level in predicting clinical outcome after acute ischemic stroke and impact of erythropoietin. Journal of Translational Medicine, 10, 6. doi:10.1186/1479-5876-10-6.CrossRefGoogle ScholarPubMed