Klinisk institutt 1

Midtveisevaluering - Irit Titlestad

Midtveisevaluering for ph.d.-graden ved Universitetet i Bergen for kandidat Irit Titlestad


Irit Titlestad er tilknyttet Klinisk institutt 1. Veiledere er Lasse Melvær Giil, Kristoffer Haugarvoll og Tone Merete Norekvål.


Biomarkers of delirium in hip fracture patients and validation of delirium in a large biobank of community-dwelling older adults


Background and Aims

Delirium is an acute neuropsychiatric syndrome that involves impaired cognitive ability and affects 40% of older hospitalized patients. However, biomarkers that predict the risk of delirium are understudied and such biomarkers can provide new potential insights into pathogenesis. There is evidence of glucose hypometabolism on positron emission tomography (PET), suggesting dysregulated glucose metabolism in the brain during delirium, while cerebrospinal fluid (CSF) glucose concentrations appear normal. Still, studies on relevant glucose and energy metabolites in CSF during delirium are lacking. Therefore, in this project, we will investigate the association between glucose metabolism-related markers and delirium (paper 1). Furthermore, we will examine the neuro-inflammatory marker neopterin which has been associated with delirium in previous studies (paper 2). However, as a biomarker of interferon-gamma mediated inflammation in monocytes and microglia, we aim to assess whether the association with delirium described in CSF is mainly due to an increased systemically (i.e., in serum). Finally, larger biomarker studies on delirium in patients that are not acutely ill are lacking. In a large collaborative study, we aim to identify and validate delirium cases (ICD-coded and non-coded) in the Hordaland Health Study subgroup with biobank samples to facilitate biomarker and genetic research on delirium (paper 3).


The first and the second papers use data from two prospective cohorts in a hospital setting among 450 patients admitted for acute hip fracture. Delirium was assessed daily, CSF was collected at the onset of spinal anesthesia, and blood samples were taken at admission. In the third paper, we used preliminary data from The road to Dementia project (data-gathering is still ongoing), a retrospective longitudinal follow-up of the Hordaland Health Studies consisting of 3300 patients.


The results from the first paper indicate an impaired glucose utilization in the brain and a shift in brain metabolism to using ketones with metabolic alterations in the CSF, suggestive of brain insulin resistance among patients with delirium. The second paper will assess the association between delirium among elderly hospitalized patients and the CSF and serum concentration of Neopterin. In a preliminary analysis for the third paper, we found that 30.5% of the patients underwent at least one delirium episode during hospitalization according to the review of electronic medical records, while only 12.1% of delirium cases were ICD coded in the discharge note.