Abstract

Background Delirium is common in hospitalised older people and is associated with a poor prognosis. It remains poorly characterised at a molecular level. We studied the metabolic signature of delirium using 1H-Magnetic Resonance Spectroscopy (MRS) in a prospective case-control study. Methods Medical inpatients aged ≥65 with and without delirium (DSM-5) were recruited and assessed for illness severity, frailty and prior cognitive decline. Metabolite concentrations in parietal white matter were obtained using MRS with diffusion MRI used to assess structural changes via the ADC. Results Out of 38 participants, 25 completed the MRS protocol (13 males and 12 females, mean age 80.5, SD = 6.47). Patients with delirium (n = 13) had greater pre-admission frailty than those without (n = 12) (median Clinical Frailty Scale 5 vs. 4.5; P = .049). There were no significant differences in age, sex, measures of MRS quality, atrophy and white matter disease. In a General Linear Model using the MRS voxel ADC to account for white matter lesion effects, glutamate was higher in delirium patients (P = 0.024). There were no other between-group differences in metabolite concentrations. For patients with and without delirium combined, glutamine increased with age and decreased with cortical atrophy, whilst Myo-inositol decreased with age and increased with median ADC. Conclusions Our results suggest that delirium is characterised by elevated brain glutamate concentration. This could cause excitotoxic brain injury and contribute to post-delirium cognitive decline and is a potentially modifiable process that merits further investigation.