Neuroimaging and plasma biomarker differences and commonalities in Lewy body dementia subtypes

INTRODUCTION: Despite ongoing debate about whether Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB) are separable diseases or a single Lewy body dementia (LBD) spectrum, there are limited neuroimaging investigations of differences between these conditions. METHODS: We used fixel-based diffusion MRI and plasma measures to examine white matter integrity and burden of amyloid pathology (using tau phosphorylated at theonine-217 (p-tau217) in 47 patients with DLB, 21 PDD, 29 PD and 23 age-matched controls. RESULTS: We show reduced fibre cross-section in LBD versus PD, and increased concentrations of plasma neurofilament light chain and p-tau217; with p-tau217 and fibre cross-section associated with cognition. Fibre density was reduced in PDD versus DLB, but neither plasma measures nor fibre cross-section differed between LBD subtypes. DISCUSSION: Our findings suggest differences in white matter integrity between DLB and PDD that are driven by distinct processes from those causing changes in white matter integrity in LBD compared with PD.