Gray matter atrophy as a distinctive biomarker of prodromal dementia with Lewy Bodies: preliminary MRI findings

Introduction. Prodromal dementia with Lewy bodies (pro-DLB) has gained attention in the field of dementia prevention, with research criteria for diagnosis proposed in 2020. However, magnetic resonance imaging (MRI) biomarkers remain classified as potential, requiring further validation for clinical application. One aim of this ongoing study was to characterize the brain features of pro-DLB patients compared to the healthy population and the prodromal stage of Alzheimer’s Disease (AD), focusing on pro-DLB phenotypical onset: mild cognitive impairment (MCI), psychiatric (PSY), and delirium. Methods. To date, we recruited 44 patients (18 MCI-DLB, 9 PSY, 17 MCI-AD) and 14 healthy controls (HC). Participants underwent structural and functional MRI. A preliminary Voxel-Based Morphometry (VBM) analysis was performed using the Computational Anatomy Toolbox (CAT12) running on SPM12. Gray matter volume (GMV) between groups was compared with an ANOVA. Results. Both MCI-DLB and PSY showed significant atrophy compared to HC. In frontal lobes, atrophy involved the superior/middle frontal gyrus, anterior/middle cingulate gyrus, supplementary motor area, and precentral gyrus. PSY showed right insular atrophy, while MCI-DLB was characterized by subcortical GMV loss in the right basal ganglia and nucleus accumbens. Reduced GMV was found in parietal (precuneus, postcentral gyrus, superior parietal lobule) and temporal (superior/inferior temporal gyrus, parahippocampus, fusiform gyrus) areas. In the occipital lobe, the middle/inferior occipital and fusiform gyri showed atrophy. Reduced cerebellar volume was observed in PSY patients. Notably, no differences emerged between pro-DLB subgroups, while atrophy was found in the hippocampus of MCI-AD relative to MCI-DLB and PSY. Discussion. Atrophy in pro-DLB is consistently found in frontal, parietal and occipital lobes relative to HC, coherent with core clinical and neuropsychological features1. Structural MRI biomarkers focusing on such areas could provide further support for diagnosis in the clinical practice. Lastly, differences between phenotypes might be associated with functional rather than structural alterations.