Identifying early structural biomakers of prodromal dementia with Lewy bodies. Preliminary evidence from voxel-based morphometry

Objectives: Dementia with Lewy bodies (DLB) is a complex neurodegenerative disorder, and the identification of reliable biomarkers in its prodromal phase (pro-DLB) remains challenging. As non-invasive magnetic resonance imaging (MRI) biomarkers are still considered potential, this ongoing study aims to characterize brain alterations in pro-DLB compared to the healthy population and prodromal Alzheimer’s disease (AD), with a specific focus on the distinct clinical presentations of pro-DLB: mild cognitive impairment (MCI-DLB) and psychiatric onset (PSY). Methods: We recruited 54 patients (20 MCI-DLB, 20 MCI-AD, 14 PSY) and 15 healthy controls (HC). All participants underwent structural and functional MRI. A preliminary Surface-Based Morphometry (SBM) analysis was performed using CAT12 within SPM12. Cortical thickness (CTh) differences among groups were assessed via one-way ANOVA. Results: SBM analysis revealed no significant CTh reductions in either MCI-DLB or PSY patients relative to HC, with similar CTh profiles between the two pro-DLB phenotypes. In contrast, MCI-AD showed widespread CTh reductions compared to HC. A relative preservation of CTh was observed in MCI-DLB and PSY patients compared to MCI-AD patients in the bilateral parahippocampal gyrus and the right frontal pole. Furthermore, MCI-AD patients exhibited reduced CTh in the left supramarginal gyrus compared to MCI-DLB patients, and in the right rostral middle frontal cortex and left middle temporal gyrus compared to PSY patients. Conclusions: This preliminary analysis suggests that CTh alone may not be sufficient to distinguish pro-DLB from the HC or to differentiate between pro-DLB subtypes. However, the pattern of relative CTh preservation observed in pro-DLB compared to MCI-AD may represent a supportive biomarker for differentiating these clinical populations, although it requires integration with more robust biomarkers to enhance diagnostic accuracy.