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

Abstract INTRODUCTION Despite ongoing debate about whether Parkinson's disease (PD) dementia (PDD) and dementia with Lewy bodies (DLB) are separable diseases or a single Lewy body dementia (LBD) spectrum, there are limited investigations of differences between these conditions. METHODS We used fixel‐based diffusion magnetic resonance imaging and plasma measures to examine white matter integrity and burden of amyloid pathology (using phosphorylated tau‐217 [p‐tau217]) in 47 patients with DLB, 21 with PDD, 29 with PD, and 23 age‐matched controls. RESULTS We show reduced fiber cross‐section in LBD versus PD, and increased concentrations of plasma neurofilament light chain and p‐tau217; with p‐tau217 and fiber cross‐section associated with cognition. Fiber density was reduced in PDD versus DLB, but neither plasma measures nor fiber cross‐section differed between LBD subtypes. DISCUSSION Our findings suggest that the presence of dementia in LBD is associated with poorer white matter macrostructure and may relate to pathological protein accumulation. Conversely, differences between DLB and PDD may be driven by other factors. Highlights Plasma neurofilament light and phosphorylated tau‐217 were increased in Lewy body dementia (LBD) relative to Parkinson's disease (PD) and controls. Magnetic resonance imaging (MRI) white matter macrostructure (fiber cross‐section) was reduced in LBD relative to PD. In contrast, MRI white matter microstructure (fiber density) was reduced in PD dementia compared to dementia with Lewy bodies. Differences between dementia with Lewy bodies and PD dementia were distinct compared with those between LBD and Parkinson's with normal cognition. Our findings suggest that dementia with Lewy bodies and Parkinson's dementia differ in underlying processes distinct from those driving dementia.