Plasma 5-HIAA activity indicative of serotonergic disturbances in cognitively impaired, elderly patients experiencing postoperative delirium

Abstract

Objectives: Delirium frequently arises in older demented and non-demented patients in postoperative, clinical settings. To date, the underlying pathophysiological mechanisms remain poorly understood. Monoamine neurotransmitter alterations have been linked to delirium and cognitive impairment. Our aim was to investigate if this holds true in cognitively normal and impaired patients experiencing delirium following hip surgery.

Methods: Monoamines and metabolites were measured in plasma samples of 181 individuals by means of reversed-phase ultra-high-performance liquid chromatography with electrochemical detection. Delirium and delirium severity were scored with the Confusion Assessment Method and Delirium Rating Scale-Revised-1998. Cognitive function was assessed using the Informant Questionnaire on Cognitive Decline and the Mini-Mental State Examination, multimorbidity with the Charlson Comorbidity Index.

Results: Plasma 5-hydroxyindoleacetic acid (5-HIAA), the major metabolite of serotonin (5-HT), was significantly higher in delirious and non-delirious cognitively impaired subjects as compared to control individuals without delirium and cognitive impairment (p < 0.001 and p = 0.007), which remained highly significant after excluding patients taking psychotropic medication (p < 0.0001 and p = 0.003). No significant differences were found for cognitively normal delirious patients, although serotonergic levels were numerically higher compared to control counterparts.

Conclusions: Our findings indicate a general serotonergic disturbance in delirious and non-delirious postoperative patients suffering from cognitive impairment. We observed a similar, but less pronounced difference in delirious patients, which suggests serotonergic disturbances may be further aggravated by the co-occurrence of delirium and cognitive impairment.

Keywords: HPLC; UPLC; ageing; biogenic amines; biomarker; cognitive impairment; delirium; monoamine neurotransmitters.

FIGURE 1

Study population selection. From a total of 2860 samples obtained from de Jonghe et al., 181 samples were included in the present study. Abbreviations: CI, cognitive impairment; D⁺CI⁺, delirium and cognitive impairment; D⁻CI⁺, no delirium but cognitive impairment; D⁺CI⁻, delirium but no cognitive impairment; D⁻CI⁻, no delirium or cognitive impairment; daywrtsurgery, day with regard to surgery

FIGURE 2

Boxplots visualizing plasma 5‐HIAA levels across all four groups. Data which remained statistically significant following post‐hoc Bonferroni correction are denoted by asterisks (* for p ≤ 0.00833, ** for p ≤ 0.001, respectively). Abbreviations: 5‐HIAA, 5‐hydroxyindoleacetic acid; CI, cognitive impairment; D⁺CI⁺, delirium and cognitive impairment; D⁻CI⁺, no delirium but cognitive impairment; D⁺CI⁻, delirium but no cognitive impairment; D⁻CI⁻, no delirium or cognitive impairment

FIGURE 3

Boxplots visualizing plasma 5‐HIAA levels across psychotropic medication‐free patients in D⁺CI⁺, D⁻CI⁺ and D⁻CI⁻ groups. Data which remained statistically significant following post‐hoc Bonferroni correction are denoted by asterisks (* for p ≤ 0.00833, ** for p ≤ 0.0001, respectively). D⁺CI⁻ group was not included as it consisted of only one patient free from psychotropic medication. Abbreviations: 5‐HIAA, 5‐hydroxyindoleacetic acid; CI, cognitive impairment; D⁺CI⁺, delirium and cognitive impairment; D⁻CI⁺, no delirium but cognitive impairment; D⁺CI⁻, delirium but no cognitive impairment; D⁻CI⁻, no delirium or cognitive impairment