Cerebrospinal Fluid Concentration of Neurogranin in Hip Fracture Patients with Delirium

Article type: Research Article

Authors: Halaas, Nathalie Bodd^{a; b; c; *} | Zetterberg, Henrik^{d; e; f; g} | Idland, Ane-Victoria^{a; c} | Knapskog, Anne-Brita^h | Watne, Leiv Otto^a | Blennow, Kaj^{d; e}

Affiliations: [a] Oslo Delirium Research Group, Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway | [b] Research Group for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Oslo, Norway | [c] Institute of Clinical Medicine, University of Oslo, Oslo, Norway | [d] Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden | [e] Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden | [f] Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, United Kingdom | [g] UK Dementia Research Institute at UCL, London, United Kingdom | [h] Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway

Correspondence: [*] Correspondence to: Nathalie Bodd Halaas, University of Oslo, Campus Ullevål, Department of Geriatric Medicine, PB 4956 Nydalen, Norway. Tel.: +47 98640857; E-mail: [email protected].

Abstract: Background:Delirium is associated with an increased risk of incident dementia and accelerated progression of existing cognitive symptoms. Reciprocally, dementia increases the risk of delirium. Cerebrospinal fluid (CSF) concentration of the dendritic protein neurogranin has been shown to increase in early Alzheimer’s disease (AD), likely reflecting synaptic dysfunction and/or degeneration. Objective:To elucidate the involvement of synaptic dysfunction in delirium pathophysiology, we tested the association between CSF neurogranin concentration and delirium in hip fracture patients with different AD-biomarker profiles, while comparing them to cognitively unimpaired older adults (CUA) and AD patients. Methods:The cohort included hip fracture patients with (n = 70) and without delirium (n = 58), CUA undergoing elective surgery (n = 127), and AD patients (n = 46). CSF was collected preoperatively and diagnostically in surgery and AD patients respectively. CSF neurogranin concentrations were analyzed in all samples with an in-house ELISA. Delirium was assessed pre-and postoperatively in hip fracture patients by trained investigators using the Confusion Assessment Method. Hip fracture patients were further stratified based on pre-fracture dementia status, delirium subtype, and AD fluid biomarkers. Results:No association was found between delirium and CSF neurogranin concentration (main analysis: delirium versus no delirium, p = 0.68). Hip fracture patients had lower CSF neurogranin concentration than AD patients (p = 0.001) and CUA (p = 0.035) in age-adjusted sensitivity analyses. Conclusion:The findings suggest that delirium is not associated with increased CSF neurogranin concentration in hip fracture patients, possibly due to advanced neurodegenerative disease and age and/or because synaptic degeneration is not an important pathophysiological process in delirium.

Keywords: Alzheimer’s disease, biomarkers, cerebrospinal fluid proteins, delirium, neurotransmitter agents

DOI: 10.3233/JAD-201341

Journal: Journal of Alzheimer's Disease, vol. 81, no. 2, pp. 667-677, 2021