Neurogranin in cerebrospinal fluid as a marker of synaptic

Authors

Mathias N P Hella, Nathalie B Halaas, Hogne Soennesyn, Anne K Bergland, Hanne B Hetland, Kaj Blennow, Henrik Zetterberg, Audun O Vik-Mo, Ane-Victoria Idland, Christian T Pollmann, Marius Myrstad, Bjørn E Neerland, Dag Aarsland, Leiv O Watne

Abstract

BMJ Open. 2025 Nov 11;15(11):e097579. doi: 10.1136/bmjopen-2024-097579.

ABSTRACT

OBJECTIVES: Neurogranin (Ng) has a role in synaptic plasticity and is considered a biomarker of synaptic dysfunction, a process hypothesised to be important in delirium. Few studies examining Ng in delirium exist, with mixed findings. This study aimed to investigate associations between cerebrospinal fluid (CSF) Ng concentrations and delirium in acutely admitted hip fracture patients.

DESIGN: Cross-sectional study.

SETTING: Acutely admitted orthopaedic patients with hip fracture recruited from four participating hospitals in eastern Norway, representing secondary and tertiary care settings.

PARTICIPANTS: This study included 392 hip fracture patients. All admitted hip fracture patients operated in spinal anaesthesia were, regardless of age, considered for inclusion.

METHODS: An in-house ELISA was used to measure CSF Ng concentration in patients acutely admitted with a hip fracture (n=392). Delirium status was evaluated daily according to The Diagnostic and Statistical Manual of Mental Disorders, Fifth Editions criteria independently by two experienced geriatricians. A value > 3.44 on The Informant Questionnaire on Cognitive Decline in the Elderly was used as a surrogate marker of probable dementia.

RESULTS: 180 patients (46 %) developed delirium and 70% of these had dementia. CSF Ng concentration did not differ significantly between those with and without delirium (176 pg/mL vs 164 pg/mL), with an estimated difference in medians of 12 (95% CI -5.8 to 29.8), p=0.185. Analyses adjusted for age, gender and dementia status did not show a statistically significant difference in Ng concentrations between the patients.

CONCLUSIONS: We did not find an association between delirium and CSF concentrations of Ng. This could imply that synaptic dysfunction and degeneration, involving Ng, are not key processes in the development of delirium. Further studies on other synaptic proteins are warranted to better explore synaptic dysfunction's potential role in the pathophysiology of delirium.

PMID:41218946 | DOI:10.1136/bmjopen-2024-097579