Iron-related biomarkers and Lewy body dementia: a scoping review

Abstract

Iron dysregulation is implicated in neurodegenerative disease pathophysiology, but its role in Lewy body dementia (LBD) remains poorly characterized. This review mapped iron-related measures across blood, cerebrospinal fluid (CSF), and brain compartments and evaluate their potential relevance as biomarkers in LBD. A scoping review was conducted according to PRISMA-ScR guidelines using PubMed and Web of Science. Studies reporting iron-related biomarkers in individuals with LBD were eligible regardless of biological compartment; review articles and non-LBD studies were excluded. Of 222 identified records, 24 met inclusion criteria. Data were charted using a standardized extraction framework and due to methodological heterogeneity, were synthesized qualitatively across blood and CSF measures, postmortem brain analyses, and in vivo neuroimaging. Brain-based measures showed the most consistent iron-related alterations, particularly quantitative susceptibility mapping (QSM), with abnormalities across cortical, limbic, and subcortical regions, although findings were not universal. Susceptibility-weighted imaging (SWI) provided complementary evidence of nigrosome-1 abnormalities. Peripheral and CSF measures were heterogeneous and showed no consistent directional pattern. No study directly compared measures across all three compartments within the same cohort. Iron dysregulation in LBD appears more pronounced in brain than systemic compartments, though within-cohort cross-compartment comparisons are lacking. Brain iron accumulation extends beyond the substantia nigra, aligning with Lewy body pathology and potentially explaining LBD’s distinctive cognitive and neuropsychiatric features. QSM and SWI are promising candidate imaging biomarkers, though current evidence reflects group-level differences rather than individual-patient diagnostic accuracy. Longitudinal, cross-compartment studies are needed to clarify their clinical significance in LBD.