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

J Alzheimers Dis. 2020;73(4):1363-1372. doi: 10.3233/JAD-190941.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / psychology
  • Anesthesia
  • Biomarkers / cerebrospinal fluid
  • Delirium / cerebrospinal fluid*
  • Delirium / psychology
  • Dementia / cerebrospinal fluid*
  • Dementia / psychology
  • Depression / cerebrospinal fluid
  • Depression / complications
  • Female
  • Healthy Volunteers
  • Hip Fractures / complications
  • Hip Fractures / surgery
  • Humans
  • Inflammation / cerebrospinal fluid
  • Interleukin-1beta / cerebrospinal fluid
  • Interleukin-8 / cerebrospinal fluid*
  • Male
  • Mental Status and Dementia Tests
  • Neuropsychological Tests
  • Psychiatric Status Rating Scales
  • Tumor Necrosis Factor-alpha / cerebrospinal fluid


  • Biomarkers
  • CXCL8 protein, human
  • IL1B protein, human
  • Interleukin-1beta
  • Interleukin-8
  • Tumor Necrosis Factor-alpha