Research on the mechanism of delirium based on related serum biomarkers of the delirium_Journal of Biomedical Engineering

Authors：

WANG Yanyan ^1,2 , LIAO Yulin ¹ ,  YUE Jirong ^1,2

1. National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, P.R.China;
2. Medical Center for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, P.R.China;

Corresponding author：

YUE Jirong, Email: yuejirong11@hotmail.com

Keywords：

delirium; serum biomarker; delirium mechanism

DOI：

10.7507/1001-5515.201611065

Video：

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Delirium is an acute cognitive disorder caused by a variety of factors which lead to cerebral cortical dysfunction. At present the studies on the pathophysiology of delirium is still very few. But studies on serum biomarker of delirium can help to elucidate the pathophysiological mechanism of delirium, and the studies are significant for delirium diagnosis, severity classification and prediction of long-term outcome. This review examines three major groups of delirium related serum biomarkers: ① risk markers: those that are present or elevated prior to disease onset, including serum chemistries, genetic markers and so on; ② disease markers: those markers elevate with delirium onset and fall when delirium recovery, including acetylcholine and serum anticholinergic activity, serotonin, serum amino acids, and melatonin, interleukin, C-reactive protein; and ③ end products: those that rise in proportion to the consequences of disease, including S-100ß and neuron specific enolase. The three markers mentioned above are helpful to further investigate the mechanism of delirium.

Citation： WANG Yanyan, LIAO Yulin, YUE Jirong. Research on the mechanism of delirium based on related serum biomarkers of the delirium. Journal of Biomedical Engineering, 2017, 34(3): 465-470. doi: 10.7507/1001-5515.201611065 Copy

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2.	Trull T J, Verges A, Wood P K, et al. The structure of Diagnostic And Statistical Manual of Mental Disorders (4th edition, text revision) personality disorder symptoms in a large national sample. Personal Disord, 2012, 3(4): 355-369.
3.	Jackson T A, Wilson D, Richardson S, et al. Predicting outcome in older hospital patients with delirium: a systematic literature review. Int J Geriatr Psychiatry, 2016, 31(4): 392-399.
4.	Ma Lina, Zhang Ruili. Risk, diagnosis and treatment to postoperative delirium in elderly patients with gastrointestinal cancers. Hepatogastroenterology, 2015, 62(138): 529-535.
5.	Androsova G, Krause R, Winterer G, et al. Biomarkers of postoperative delirium and cognitive dysfunction. Front Aging Neurosci, 2015, 7(9): 112.
6.	Szczesny E, Basta-Kaim A, Slusarczyk J, et al. The impact of prenatal stress on insulin-like growth factor-1 and pro-inflammatory cytokine expression in the brains of adult male rats: the possible role of suppressors of cytokine signaling proteins. J Neuroimmunol, 2014, 276(1/2): 37-46.
7.	Yen T E, Allen J C, Rivelli S K, et al. Association between serum IGF-I levels and postoperative delirium in elderly subjects undergoing elective knee arthroplasty. Sci Rep, 2016, 6: 20736.
8.	Shen Huachun, Shao Yi, Chen Junping, et al. Insulin-like growth factor-1, a potential predicative biomarker for postoperative delirium among elderly patients with open abdominal surgery. Curr Pharm Des, 2016, 22(38): 5879-5883.
9.	Chu Chesheng, Liang C K, Chou M Y, et al. Lack of association between pre-operative insulin-like growth factor-1 and the risk of post-operative delirium in elderly Chinese patients. Psychiatry Investig, 2016, 13(3): 327-332.
10.	van Munster B C, Korevaar J C, Zwinderman A H, et al. The association between delirium and the apolipoprotein E epsilon 4 allele: new study results and a meta-analysis. Am J Geriatr Psychiatry, 2009, 17(10): 856-862.
11.	Stoicea N, Mcvicker S, Quinones A, et al. Delirium-biomarkers and genetic variance. Front Pharmacol, 2014, 5: 75.
12.	Ma Yunlong, Fan Rongli, Li M D. Meta-analysis reveals significant association of the 3’-UTR VNTR in SLC6A3 with alcohol dependence. Alcohol Clin Exp Res, 2016, 40(7): 1443-1453.
13.	van Munster B C, Korse C M, de Rooij S E, et al. Markers of cerebral damage during delirium in elderly patients with hip fracture. BMC Neurol, 2009, 9: 21.
14.	Watne L O, Hall R J, Molden E, et al. Anticholinergic activity in cerebrospinal fluid and serum in individuals with hip fracture with and without delirium. J Am Geriatr Soc, 2014, 62(1): 94-102.
15.	Qiu Yimin, Huang Xiaojing, Huang Lina, et al. 5-HT(1A) receptor antagonist improves behavior performance of delirium rats through inhibiting PI3K/Akt/mTOR activation-induced NLRP3 activity. IUBMB Life, 2016, 68(4): 311-319.
16.	Tomasi C D, Salluh J, Soares M, et al. Baseline acetylcholinesterase activity and serotonin plasma levels are not associated with delirium in critically ill patients. Rev Bras Ter Intensiva, 2015, 27(2): 170-177.
17.	Egberts A, Fekkes D, Wijnbeld E H, et al. Disturbed serotonergic neurotransmission and oxidative stress in elderly patients with delirium. Dement Geriatr Cogn Dis Extra, 2016, 5(3): 450-458.
18.	Balan S, Leibovitz A, Zila S O, et al. The relation between the clinical subtypes of delirium and the urinary level of 6-SMT. J Neuropsychiatry Clin Neurosci, 2003, 15(3): 363-366.
19.	de Rooij S E, van Munster B C, Korevaar J C, et al. Cytokines and acute phase response in delirium. J Psychosom Res, 2007, 62(5): 521-525.
20.	van den Boogaard M, Kox M, Quinn K L, et al. Biomarkers associated with delirium in critically ill patients and their relation with long-term subjective cognitive dysfunction; indications for different pathways governing delirium in inflamed and noninflamed patients. Crit Care, 2011, 15(6): R297.
21.	Cape E, Hall R J, van Munster B C, et al. Cerebrospinal fluid markers of neuroinflammation in delirium: a role for interleukin-1β in delirium after hip fracture. J Psychosom Res, 2014, 77(3): 219-225.
22.	Ritter C, Tomasi C D, Dal-Pizzol F, et al. Inflammation biomarkers and delirium in critically ill patients. Crit Care, 2014, 18(3): R106.
23.	Baranyi A, Rothenhäusler H B. The impact of soluble interleukin-2 receptor as a biomarker of delirium. Psychosomatics, 2014, 55(1): 51-60.
24.	Ritchie C W, Newman T H, Leurent B, et al. The association between C-reactive protein and delirium in 710 acute elderly hospital admissions. Int Psychogeriatr, 2014, 26(5): 717-724.
25.	Zhang Zhongheng, Pan Lifei, Deng Hongsheng, et al. Prediction of delirium in critically ill patients with elevated C-reactive protein. J Crit Care, 2014, 29(1): 88-92.
26.	Osse R J, Fekkes D, Tulen J H, et al. High preoperative plasma neopterin predicts delirium after cardiac surgery in older adults. J Am Geriatr Soc, 2012, 60(4): 661-668.
27.	Egberts A, Wijnbeld E H, Fekkes D, et al. Neopterin: a potential biomarker for delirium in elderly patients. Dement Geriatr Cogn Disord, 2015, 39(1/2): 116-124.
28.	Beaudeux J L, Laribi S. S100B protein serum level as a biomarker of minor head injury. Ann Biol Clin (Paris), 2013, 71(1): 71-78.
29.	van Munster B C, Korevaar J C, Korse C M, et al. Serum S100B in elderly patients with and without delirium. Int J Geriatr Psychiatry, 2010, 25(3): 234-239.
30.	Hall R J, Ferguson K J, Andrews M, et al. Delirium and cerebrospinal fluid S100B in hip fracture patients: a preliminary study. Am J Geriatr Psychiatry, 2013, 21(12): 1239-1243.
31.	Harrington C R, Storey J M, Clunas S, et al. Cellular models of aggregation-dependent template-directed proteolysis to characterize Tau aggregation inhibitors for treatment of Alzheimer disease. J Biol Chem, 2015, 290(17): 10862-10875.
32.	Wischik C M, Staff R T, Wischik D J, et al. Tau aggregation inhibitor therapy: an exploratory phase 2 study in mild or moderate Alzheimer’s disease. J Alzheimers Dis, 2015, 44: 705-720.
33.	Wang Junwen, Li Jun, Han Lin, et al. Serum τ protein as a potential biomarker in the assessment of traumatic brain injury. Exp Ther Med, 2016, 11(3): 1147-1151.

1. Vijayakumar B, Elango P, Ganessan R. Post-operative delirium in elderly patients. Indian J Anaesth, 2014, 58(3): 251-256.
2. Trull T J, Verges A, Wood P K, et al. The structure of Diagnostic And Statistical Manual of Mental Disorders (4th edition, text revision) personality disorder symptoms in a large national sample. Personal Disord, 2012, 3(4): 355-369.
3. Jackson T A, Wilson D, Richardson S, et al. Predicting outcome in older hospital patients with delirium: a systematic literature review. Int J Geriatr Psychiatry, 2016, 31(4): 392-399.
4. Ma Lina, Zhang Ruili. Risk, diagnosis and treatment to postoperative delirium in elderly patients with gastrointestinal cancers. Hepatogastroenterology, 2015, 62(138): 529-535.
5. Androsova G, Krause R, Winterer G, et al. Biomarkers of postoperative delirium and cognitive dysfunction. Front Aging Neurosci, 2015, 7(9): 112.
6. Szczesny E, Basta-Kaim A, Slusarczyk J, et al. The impact of prenatal stress on insulin-like growth factor-1 and pro-inflammatory cytokine expression in the brains of adult male rats: the possible role of suppressors of cytokine signaling proteins. J Neuroimmunol, 2014, 276(1/2): 37-46.
7. Yen T E, Allen J C, Rivelli S K, et al. Association between serum IGF-I levels and postoperative delirium in elderly subjects undergoing elective knee arthroplasty. Sci Rep, 2016, 6: 20736.
8. Shen Huachun, Shao Yi, Chen Junping, et al. Insulin-like growth factor-1, a potential predicative biomarker for postoperative delirium among elderly patients with open abdominal surgery. Curr Pharm Des, 2016, 22(38): 5879-5883.
9. Chu Chesheng, Liang C K, Chou M Y, et al. Lack of association between pre-operative insulin-like growth factor-1 and the risk of post-operative delirium in elderly Chinese patients. Psychiatry Investig, 2016, 13(3): 327-332.
10. van Munster B C, Korevaar J C, Zwinderman A H, et al. The association between delirium and the apolipoprotein E epsilon 4 allele: new study results and a meta-analysis. Am J Geriatr Psychiatry, 2009, 17(10): 856-862.
11. Stoicea N, Mcvicker S, Quinones A, et al. Delirium-biomarkers and genetic variance. Front Pharmacol, 2014, 5: 75.
12. Ma Yunlong, Fan Rongli, Li M D. Meta-analysis reveals significant association of the 3’-UTR VNTR in SLC6A3 with alcohol dependence. Alcohol Clin Exp Res, 2016, 40(7): 1443-1453.
13. van Munster B C, Korse C M, de Rooij S E, et al. Markers of cerebral damage during delirium in elderly patients with hip fracture. BMC Neurol, 2009, 9: 21.
14. Watne L O, Hall R J, Molden E, et al. Anticholinergic activity in cerebrospinal fluid and serum in individuals with hip fracture with and without delirium. J Am Geriatr Soc, 2014, 62(1): 94-102.
15. Qiu Yimin, Huang Xiaojing, Huang Lina, et al. 5-HT(1A) receptor antagonist improves behavior performance of delirium rats through inhibiting PI3K/Akt/mTOR activation-induced NLRP3 activity. IUBMB Life, 2016, 68(4): 311-319.
16. Tomasi C D, Salluh J, Soares M, et al. Baseline acetylcholinesterase activity and serotonin plasma levels are not associated with delirium in critically ill patients. Rev Bras Ter Intensiva, 2015, 27(2): 170-177.
17. Egberts A, Fekkes D, Wijnbeld E H, et al. Disturbed serotonergic neurotransmission and oxidative stress in elderly patients with delirium. Dement Geriatr Cogn Dis Extra, 2016, 5(3): 450-458.
18. Balan S, Leibovitz A, Zila S O, et al. The relation between the clinical subtypes of delirium and the urinary level of 6-SMT. J Neuropsychiatry Clin Neurosci, 2003, 15(3): 363-366.
19. de Rooij S E, van Munster B C, Korevaar J C, et al. Cytokines and acute phase response in delirium. J Psychosom Res, 2007, 62(5): 521-525.
20. van den Boogaard M, Kox M, Quinn K L, et al. Biomarkers associated with delirium in critically ill patients and their relation with long-term subjective cognitive dysfunction; indications for different pathways governing delirium in inflamed and noninflamed patients. Crit Care, 2011, 15(6): R297.
21. Cape E, Hall R J, van Munster B C, et al. Cerebrospinal fluid markers of neuroinflammation in delirium: a role for interleukin-1β in delirium after hip fracture. J Psychosom Res, 2014, 77(3): 219-225.
22. Ritter C, Tomasi C D, Dal-Pizzol F, et al. Inflammation biomarkers and delirium in critically ill patients. Crit Care, 2014, 18(3): R106.
23. Baranyi A, Rothenhäusler H B. The impact of soluble interleukin-2 receptor as a biomarker of delirium. Psychosomatics, 2014, 55(1): 51-60.
24. Ritchie C W, Newman T H, Leurent B, et al. The association between C-reactive protein and delirium in 710 acute elderly hospital admissions. Int Psychogeriatr, 2014, 26(5): 717-724.
25. Zhang Zhongheng, Pan Lifei, Deng Hongsheng, et al. Prediction of delirium in critically ill patients with elevated C-reactive protein. J Crit Care, 2014, 29(1): 88-92.
26. Osse R J, Fekkes D, Tulen J H, et al. High preoperative plasma neopterin predicts delirium after cardiac surgery in older adults. J Am Geriatr Soc, 2012, 60(4): 661-668.
27. Egberts A, Wijnbeld E H, Fekkes D, et al. Neopterin: a potential biomarker for delirium in elderly patients. Dement Geriatr Cogn Disord, 2015, 39(1/2): 116-124.
28. Beaudeux J L, Laribi S. S100B protein serum level as a biomarker of minor head injury. Ann Biol Clin (Paris), 2013, 71(1): 71-78.
29. van Munster B C, Korevaar J C, Korse C M, et al. Serum S100B in elderly patients with and without delirium. Int J Geriatr Psychiatry, 2010, 25(3): 234-239.
30. Hall R J, Ferguson K J, Andrews M, et al. Delirium and cerebrospinal fluid S100B in hip fracture patients: a preliminary study. Am J Geriatr Psychiatry, 2013, 21(12): 1239-1243.
31. Harrington C R, Storey J M, Clunas S, et al. Cellular models of aggregation-dependent template-directed proteolysis to characterize Tau aggregation inhibitors for treatment of Alzheimer disease. J Biol Chem, 2015, 290(17): 10862-10875.
32. Wischik C M, Staff R T, Wischik D J, et al. Tau aggregation inhibitor therapy: an exploratory phase 2 study in mild or moderate Alzheimer’s disease. J Alzheimers Dis, 2015, 44: 705-720.
33. Wang Junwen, Li Jun, Han Lin, et al. Serum τ protein as a potential biomarker in the assessment of traumatic brain injury. Exp Ther Med, 2016, 11(3): 1147-1151.

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