The role of quantitative susceptibility mapping in dementia with Lewy Bodies

Iron overload has been implicated in the pathology of several neurodegenerative diseases, and quantitative susceptibility mapping (QSM), an MRI-based technique, has identified abnormal iron overload in alpha-synucleinopathies. However, there is a limited understanding of the significance of changes in magnetic susceptibility, assessed by QSM, in patients with Dementia with Lewy Bodies (DLB). In this study, 39 DLB patients (58-88 years) and 30 cognitively unimpaired older adults (OA) (56-86 years) underwent an advanced MRI protocol that included T1w and QSM sequences, and a comprehensive neuropsychological evaluation. This study investigated (1) differences in whole-brain magnetic susceptibility and brain volumes between DLB patients and OA; (2) associations between regional changes in magnetic susceptibility and brain volumes, symptom duration, and cognitive functioning; (3) whether regional changes in magnetic susceptibility could differentiate DLB phenotypes based on earlier symptoms. DLB patients showed higher magnetic susceptibility values than OA in the bilateral substantia nigra, globus pallidus, thalamus, brainstem, and hippocampus, as well as in posterior cortical regions. No significant associations were observed between QSM susceptibility values and brain volumes, symptom duration, or cognitive functions. Using classificatory algorithms, different DLB phenotypes were identified based on iron accumulation values in the basal ganglia, thalamus, brainstem, and frontal cortical regions. Our findings suggest that QSM, assessing in vivo changes in brain iron accumulation, could serve as a useful noninvasive diagnostic biomarker in DLB patients. Longitudinal studies, including the prodromal phase of DLB, are needed to understand the interplay between brain volumetric loss, iron accumulation, and clinical manifestations.