Toward early structural MRI biomarkers of prodromal dementia with Lewy bodies. Insights from a preliminary voxel-based morphometry study

Aims: Dementia with Lewy bodies (DLB) is a complex neurodegenerative disorder, and identifying reliable biomarkers in its prodromal phase remains a challenge. As non-invasive magnetic resonance imaging (MRI) biomarkers are still considered potential, further investigation is warranted. This ongoing study aims to characterize brain alterations in prodromal DLB (pro-DLB) in comparison to the healthy population and prodromal Alzheimer’s disease (AD), with a focus on the distinct pro-DLB clinical presentations: mild cognitive impairment (MCI-DLB) and psychiatric onset (PSY). Materials: Fifty-four patients (20 MCI-DLB, 20 MCI-AD, 14 PSY) were recruited from Sapienza University Hospital of Rome. Fifteen healthy controls (HC) were also enrolled. Groups were matched for age, gender, education, and global cognitive functioning as assessed through the Mini-Mental State Examination. Method: We performed a preliminary Voxel-Based Morphometry (VBM) analysis using the Computational Anatomy Toolbox (CAT12) on SPM12. Gray matter volume (GMV) differences among groups were assessed via one-way ANOVA, including total intracranial volume as a covariate. Statistical significance was set at p < 0.05, corrected for multiple comparisons using the Family-Wise Error rate method. Results: VBM revealed structural damage in both MCI-DLB and PSY patients relative to HC. Shared frontal atrophy involved the right superior frontal gyrus, left supplementary motor area, right anterior and bilateral middle cingulum. Bilateral parietal GMV loss was found in the precuneus, with additional atrophy in the posterior parietal cortex in PSY and in the left posterior cingulum in MCI-DLB. Temporal atrophy was confined to the left inferior temporal and fusiform gyri, the latter extending into its occipital portion. PSY patients also exhibited further GMV reduction in the left medial temporal lobe. Occipital atrophy was observed in the right cuneus, with additional bilateral damage in the early visual cortex in MCI-DLB and middle occipital gyrus in PSY. Subcortical atrophy affected the right caudate and olfactory area. Remarkably, no volumetric differences were found between pro-DLB subgroups, while both showed relative hippocampal preservation compared to MCI-AD. Discussion: Pro-DLB is associated with a consistent pattern of frontal, parietal, and occipital atrophy, mirroring the core clinical and cognitive features observed in overt DLB. However, the lack of significant volumetric differences between phenotypes suggests that macro-structural imaging may not fully capture their underlying heterogeneity. Conclusions: Structural MRI biomarkers show promise for distinguishing pro-DLB from healthy aging and prodromal stages of other neurodegenerative disorders, like AD. Nevertheless, further research focusing on functional alterations is needed to detect phenotype-specific markers within pro-DLB.