Discrimination between dementia with Lewy bodies and Alzheimer’s disease based on biofluid monoamines, biomarker values and cognitive parameters

Abstract

AbstractBackgroundDespite disease‐specific symptoms, differentiation between Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB) remains challenging, especially in early, prodromal stages. This is fueled by overlapping pathology in both diseases (Slaets et al., 2013). Monoamine neurotransmitters are significantly altered between DLB and AD and are capable of distinguishing DLB from AD, when added to the panel of cerebrospinal fluid (CSF) dementia biomarkers (Aβ1‐40, Aβ1‐42, T‐tau, P‐tau) and as standalone biomarkers (Janssens et al., 2018). Additionally, cognitive and behavioral differences linked to monoaminergic changes between DLB, AD patients and non‐demented control individuals, have been previously described (Engelborghs et al., 2006, Vermeiren et al., 2015).This study aimed to further explore these dissimilarities for improving discrimination between prodromal and advanced DLB and AD stages.MethodMonoamine neurotransmitter levels were measured in CSF and plasma of 160 prodromal AD (proAD), prodromal DLB (proDLB), AD and DLB patients and 40 non‐demented individuals, using ultra‐high‐performance liquid chromatography. CSF biomarker levels were determined through ELISA. A battery of cognitive and behavioral tests was performed. Monoaminergic, biomarker, cognitive and demographic data were integrated in stepwise regression models to discriminate between (prodromal) DLB and AD.ResultSignificant serotonergic differences in CSF between DLB and AD, as well as noradrenergic, dopaminergic and serotonergic differences in plasma between DLB and AD and with non‐demented individuals were noted. CSF dementia biomarkers levels differed significantly between proAD, proDLB, DLB and AD stages and with non‐demented individuals. There were no CSF, plasma monoamines or CSF biomarker changes between proDLB versus DLB, and proAD versus AD stages. Cognitive functioning differed significantly between prodromal and advanced DLB and AD stages and with non‐demented individuals. Stepwise regression identified that models including plasma and CSF serotonergic components, as well as cognitive tests were the most accurate at discriminating between proDLB versus DLB, proAD versus AD, proDLB versus proAD and DLB versus AD, with area under the curve (AUC), sensitivity and specificity values > 0.9.ConclusionThese findings support differentially affected monoaminergic, pathological biomarker levels and cognitive abilities between (prodromal) AD and DLB, and with non‐demented individuals. In addition, this study provides robust models for discrimination between (prodromal) DLB and AD.