Quantitative susceptibility mapping reveals differences between subtypes of Lewy body dementia

Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) are subtypes of Lewy body dementia, and are considered two ends of a disease spectrum. However, conventional MRI neuroimaging, mainly focused on grey matter volume and thickness, has failed to establish whether underlying processes differ between them. Understanding these differences could enable targeted and subtype-specific treatments to be developed. We applied quantitative susceptibility mapping (QSM), an advanced neuroimaging technique sensitive to tissue iron, to examine differences in tissue composition between these Lewy body dementia subtypes. We performed both voxel-wise and region of interest analyses to compare QSM values in 66 people with Lewy body dementia (45 DLB; 21 PDD), 86 people with Parkinson's disease with normal cognition (PD-NC) and 37 healthy controls. We also assessed relationships between QSM values and measures of both cognitive performance and overall disease severity in people with Lewy body dementia. We found that people with Lewy body dementia had higher QSM values in widespread brain regions, compared with cognitively normal people with PD, and that people with PDD had higher QSM values across many brain regions, compared with people with DLB. Further, we showed a positive relationship between QSM values and overall disease severity, measured using the Movement Disorder Society Unified Parkinson's Disease Rating Scale in people with Lewy body dementia, in the right thalamus, left pallidum, bilateral substantia nigra, bilateral middle frontal, temporal and lateral occipital lobes, right precentral and superior frontal cortices. In a region of interest analysis, we showed that people with PDD had higher QSM values than cognitively normal people with PD and controls in the substantia nigra pars reticulata. Our findings indicate neurobiological differences between subtypes of Lewy body dementia, that can be detected by exploiting QSM's sensitivity to tissue composition. Based on this, DLB and PDD could be considered as distinct conditions in the clinic and in clinical trials, and may respond to different treatments. Our finding that QSM values relate to real-world measures of overall disease severity in Lewy body dementia indicates its potential as an imaging biomarker for clinical trials of Lewy body dementia interventions.