Impaired glucose utilization in the brain of patients with delirium following hip fracture

Author:

Titlestad Irit123ORCID,Watne Leiv Otto345,Caplan Gideon A67,McCann Adrian8ORCID,Ueland Per Magne8,Neerland Bjørn Erik3,Myrstad Marius9,Halaas Nathalie Bodd34,Pollmann Christian Thomas10,Henjum Kristi34ORCID,Ranhoff Anette Hylen1112,Solberg Lene B13,Figved Wender414,Cunningham Colm15,Giil Lasse M211

Affiliation:

1. Department of Clinical Medicine, University of Bergen , 5020 Bergen , Norway

2. Neuro-SysMed, Department of Internal Medicine, Haraldsplass Deaconess Hospital , 5009 Bergen , Norway

3. Oslo Delirium Research Group, Department of Geriatric Medicine, Oslo University Hospital , 0424 Oslo , Norway

4. Institute of Clinical Medicine, University of Oslo , 0318 Oslo , Norway

5. Department of Geriatric Medicine, Akershus University Hospital , 1478 Lørenskog , Norway

6. Department of Geriatric Medicine, Prince of Wales Hospital , 2031 Sydney , Australia

7. Prince of Wales Clinical School, University of New South Wales , 2031 Sydney , Australia

8. Bevital AS , 5021 Bergen , Norway

9. Department of Internal Medicine, Bærum Hospital Vestre Viken Hospital Trust , 1346 Gjettum , Norway

10. Department of Orthopedic Surgery, Akershus University Hospital , 1478 Lørenskog , Norway

11. Department of Clinical Science, University of Bergen , 5020 Bergen , Norway

12. Geriatric Unit, Clinic of Medicine, Diakonhjemmet Hospital , 0319 Oslo , Norway

13. Division of Orthopaedic Surgery, Oslo University Hospital , 0424 Oslo , Norway

14. Orthopaedic Department, Bærum Hospital, Vestre Viken Hospital Trust , 1349 Gjettum , Norway

15. School of Biochemistry & Immunology, Trinity Biomedical Sciences Institute and Trinity College Institute of Neuroscience, Trinity College Dublin , D02 R590 Dublin , Ireland

Abstract

Abstract Alterations in brain energy metabolism have long been proposed as one of several neurobiological processes contributing to delirium. This is supported by previous findings of altered CSF lactate and neuron-specific enolase concentrations and decreased glucose uptake on brain-PET in patients with delirium. Despite this, there are limited data on metabolic alterations found in CSF samples, and targeted metabolic profiling of CSF metabolites involved in energy metabolism has not been performed. The aim of the study was to investigate whether metabolites related to energy metabolism in the serum and CSF of patients with hip fracture are associated with delirium. The study cohort included 406 patients with a mean age of 81 years (standard deviation 10 years), acutely admitted to hospital for surgical repair of a hip fracture. Delirium was assessed daily until the fifth postoperative day. CSF was collected from all 406 participants at the onset of spinal anaesthesia, and serum samples were drawn concurrently from 213 participants. Glucose and lactate in CSF were measured using amperometry, whereas plasma glucose was measured in the clinical laboratory using enzymatic photometry. Serum and CSF concentrations of the branched-chain amino acids, 3-hydroxyisobutyric acid, acetoacetate and β-hydroxybutyrate were measured using gas chromatography-tandem mass spectrometry (GC-MS/MS). In total, 224 (55%) patients developed delirium pre- or postoperatively. Ketone body concentrations (acetoacetate, β-hydroxybutyrate) and branched-chain amino acids were significantly elevated in the CSF but not in serum among patients with delirium, despite no group differences in glucose concentrations. The level of 3-hydroxyisobutyric acid was significantly elevated in both CSF and serum. An elevation of CSF lactate during delirium was explained by age and comorbidity. Our data suggest that altered glucose utilization and a shift to ketone body metabolism occurs in the brain during delirium.

Funder

Norwegian Health Association

South-Eastern Norway Regional Health Authorities

University of Bergen

Neuro-SysMed

Norwegian Research Council

Publisher

Oxford University Press (OUP)

Subject

Neurology (clinical)

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