Correlation analyses between MIBG myocardial scintigraphy and monoamine levels in dementia with Lewy bodies show potential link with the serotonergic system

Abstract

Setting: Dementia with Lewy bodies (DLB) remains poorly understood and frequently misdiagnosed, complicated by co-pathology with other dementia forms. DLB patients often present with autonomic dysfunction and peripheral Lewy body pathology alongside central lesions. Monoaminergic neurotransmitter systems seem an early target for DLB pathology, especially the noradrenergic system. Noradrenaline analogue ¹²³I-metaiodobenzylguanidine (MIBG) is considered an indicative biomarker for peripheral noradrenergic sympathetic denervation.

Objectives: Our aim was to measure paired monoaminergic levels and MIBG scintigraphy values in DLB patients, exploring a possible link between noradrenergic neurotransmission and peripheral denervation.

Design: 44 patients with a possible DLB diagnosis entered the study. Peripheral uptake of ¹²³I-MIBG was determined by the heart-to-mediastinum (H/M) ratio, as a measure for noradrenergic sympathetic denervation. In cerebrospinal fluid (CSF), serum and plasma samples, monoamines ((nor)adrenaline ((N)A), 5-hydroxytryptamin (5-HT, serotonin), dopamine (DA)) and respective metabolites (3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC)), were measured by means of reversed-phase ultrahigh-performance liquid chromatography with electrochemical detection.

Results: We found significant correlations between the H/M ratio and serum 5-HIAA, plasma 5-HT, plasma 5-HIAA/5-HT and plasma HVA/5-HIAA, but no further correlations with the noradrenergic system. CSF-serum MHPG, CSF-serum DOPAC, CSF-serum HVA, CSF-plasma MHPG, CSF plasma NA, CSF-plasma DOPAC, CSF-plasma MHPG/NA and CSF-plasma DOPAC/DA were significantly correlated.

Conclusions: These results show an association between the H/M ratio and serotonergic system, but not between peripheral noradrenergic denervation and circulating noradrenergic levels.

Keywords: 5-HIAA; 5-HT; Biogenic amines; DLB; Dopamine; H/M ratio; Noradrenaline; Norepinephrine; Serotonin; UPLC.

Fig. 1

Correlations between H/M ratio, blood 5-HIAA, 5-HT levels and 5-HIAA/5-HT and HVA/5-HIAA ratios. Correlation strength is visualized by color shade and correlation coefficients. Significance values are classified as P ≤ 0.05, P ≤ 0.01 and P ≤ 0.001 and are indicated by one, two or three asterisk symbols, respectively. Abbreviations: H/M = heart-to-mediastinum, 5-HIAA = 5-hydroxyindoleacetic acid, DA = dopamine, HVA = homovanillic acid, 5-HT = 5-hydroxytryptamine (serotonin).