Catecholamine activity in delirium with and without pre‐existing dementia

Abstract

AbstractBackgroundDelirium “acute confusion” is an unpleasant but common complication of acute illness in the aged population associated with prolonged hospitalization. Dementia is a substantial risk factor for delirium that may be apparent already in preclinical Alzheimer’s disease, but a delirium is also a risk factor for dementia. Effective agents for preventing and treating delirium are therefore searched. This include administration of antipsychotics targeting anticipated excessive dopaminergic activity in delirium and alpha‐2‐receptor (α2) agonists reducing noradrenergic activity. Data of noradrenergic and dopaminergic activity in delirium is however limited. We therefore aimed to characterize the cerebrospinal fluid (CSF) levels of dopamine and noradrenaline (norepinephrine) in delirium, with or without pre‐existing dementia.MethodCSF levels of dopamine and noradrenaline were determined by high‐performance‐liquid‐chromatography (HPLC) in: 1) cognitively healthy (controls; n=122) 2) Hip fracture patients (n=118) with and without delirium and pre‐fracture dementia 3) Patients with delirium precipitated by another medical condition (n=26). Non‐parametric statistical analyzes were applied.ResultPatients with delirium following a hip fracture and another medical condition had lower CSF dopamine levels relative to hip fracture patients without delirium and controls respectively. Stratified analyzes of hip fracture patients according to dementia status and separating patients with delirium before and after surgery showed differences in the two stratas. Interestingly there was a trend for higher levels of noradrenaline in incident delirium among those without pre‐fracture dementia, but there were few patients in this group (n=7).ConclusionThe lower levels of dopamine in CSF in delirium align with recent meta‐analyzes not recommending use of antipsychotics. Further evaluation of α2‐agonists for delirium prevention, in particular in those without pre‐existing dementia is supported, although the data should be reproduced in larger studies.