Cerebrospinal Fluid Levels of Interleukin-8 in Delirium, Dementia, and Cognitively Healthy Patients

Article type: Research Article

Authors: Sajjad, Muhammad Umar^{a; *} | Blennow, Kaj^{b; c} | Knapskog, Anne Brita^d | Idland, Ane-Victoria^{a; e} | Chaudhry, Farrukh Abbas^{a; h} | Wyller, Torgeir Bruun^e | Zetterberg, Henrik^{b; c; f; g} | Watne, Leiv Otto^{a; e}

Affiliations: [a] Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway | [b] Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden | [c] Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden | [d] Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway | [e] Department of Geriatric Medicine, Oslo Delirium Research Group, Oslo University Hospital, Oslo, Norway | [f] Department of Neurodegenerative Disease, UCL Institute of Neurology, London, United Kingdom | [g] UK Dementia Research Institute at UCL, London, United Kingdom | [h] Department of Plastic and Reconstructive Surgery, Oslo University Hospital, Oslo, Norway

Correspondence: [*] Correspondence to: Muhammad Umar Sajjad, Institute of Basic Medical Sciences, Department of Molecular Medicine, University of Oslo, Postboks 1110, Blindern, 0317, Oslo, Norway. Tel.: +47 93038867; E-mail: [email protected].

Abstract: Background:Delirium is a common and serious complication in geriatric patients. The pathophysiology of delirium is not known. Objective:The objective of the current study was to test the hypothesis that cerebrospinal fluid (CSF) levels of inflammatory markers at the time of spinal anesthesia for hip surgery are associated with delirium. Methods:In total 133 hip fracture patients and 125 cognitively healthy controls undergoing elective surgery, together with 73 Alzheimer’s disease (AD) dementia patients, were recruited at Oslo University Hospital and Diakonhjemmet Hospital, Oslo, Norway. Delirium was evaluated daily in hip fracture patients by the Confusion Assessment Method (CAM). Depression was evaluated by Cornell Scale for Depression in Dementia (CSDD). Tumor necrosis factor alpha (TNF-α), interleukin-1beta (IL-1β), and interleukin-8 (IL-8) levels were measured in CSF using a Mesoscale Discovery (MSD) immunoassay. Results:Hip fracture patients had significantly higher IL-8 levels (p < 0.001) compared to cognitively healthy controls or patients with stable AD dementia. Furthermore, preoperative IL-8 levels were significantly higher (p = 0.013) in hip fracture patients who developed delirium (incident delirium) after surgery as compared to patients with no delirium. However, subgroup analyses showed that IL-8 levels were only significantly higher in delirium patients without dementia (p = 0.006). In contrast, depression subgroup analysis showed that IL-8 concentration was significantly higher (p = 0.002) in delirium patients with depression. Both TNF-α and IL-1β were undetected in most patients. Conclusions:Our study suggests that IL-8 levels are associated with delirium onset and that underlying depression or dementia influences IL-8 levels.

Keywords: Alzheimer’s disease, cytokines, delirium, depression

DOI: 10.3233/JAD-190941

Journal: Journal of Alzheimer's Disease, vol. 73, no. 4, pp. 1363-1372, 2020