Abstract
BACKGROUND: The diagnosis of Dementia with Lewy Bodies (DLB) is primarily based on clinical features. The main driver of DLB is alpha-synuclein-related pathology, but cerebrovascular disease (CVD) and Alzheimer's Disease (AD) co-pathologies are often found in patients with DLB. Fluid biomarkers and magnetic resonance imaging (MRI) can provide mechanistic and diagnostic information beyond clinical features. Therefore, the aim of this study was to investigate the association of plasma biomarkers (GFAP, NfL, Aβ42/40, pTau231, pTau181) with MRI markers of neurodegeneration and CVD in DLB and in patients with AD as a control group. We also evaluated the ability of biomarkers and clinical features to discriminate between DLB and AD. METHODS: We included 134 patients from the European DLB consortium (DLB (n = 92) and AD (n = 43)) with plasma biomarkers determined with Simoa and MRI assessed with radiological scales for medial temporal lobe atrophy (MTA), global cortical atrophy scale - frontal subscale (GCA-F), posterior atrophy (PA), and cerebrovascular disease (Fazekas scale). Associations between plasma and MRI biomarkers were assessed with the Mann-Whitney U test, and group differences and the discrimination between DLB and AD were assessed with ANCOVA, Random Forest, and ROC analyses. RESULTS: In DLB, plasma concentrations of GFAP and NfL were associated with MTA, GCA-F, and Fazekas scale; and the Aβ42/40 ratio was associated with PA and Fazekas. Most of these associations were not statistically significant in AD. Individually, plasma and MRI biomarkers had a limited ability to discriminate DLB from AD. Plasma biomarkers helped increase the low specificity of core clinical features from 68% up to 79%, keeping the high sensitivity of 90%. CONCLUSIONS: Plasma biomarkers of AD co-pathology, glial processes and unspecific neurodegeneration are associated with MRI biomarkers of atrophy and cerebrovascular disease in DLB patients. Plasma biomarkers increase the ability of core clinical features to discriminate between DLB and AD.