Longitudinal Free-Water Changes in Dementia with Lewy Bodies

Abstract

Background: Diffusion-weighted magnetic resonance imaging (dMRI) examines tissue microstructure integrity in vivo. Prior dementia with Lewy bodies (DLB) diffusion tensor imaging studies yielded mixed results.

Objective: We employed free-water (FW) imaging to assess DLB progression and correlate with clinical decline in DLB.

Methods: Baseline and follow-up MRIs were obtained at 12 and/or 24 months for 27 individuals with DLB or mild cognitive impairment with Lewy bodies (MCI-LB). FW was analyzed using the Mayo Clinic Adult Lifespan Template. Primary outcomes were FW differences between baseline and 12 or 24 months. To compare FW change longitudinally, we included 20 cognitively unimpaired individuals from the Alzheimer's Disease Neuroimaging Initiative.

Results: We followed 23 participants to 12 months and 16 participants to 24 months. Both groups had worsening in Montreal Cognitive Assessment (MoCA) and Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) scores. We found significant FW increases at both time points compared to baseline in the insula, amygdala, posterior cingulum, parahippocampal, entorhinal, supramarginal, fusiform, retrosplenial, and Rolandic operculum regions. At 24 months, we found more widespread microstructural changes in regions implicated in visuospatial processing, motor, and cholinergic functions. Between-group analyses (DLB vs. controls) confirmed significant FW changes over 24 months in most of these regions. FW changes were associated with longitudinal worsening of MDS-UPDRS and MoCA scores.

Conclusions: FW increased in gray and white matter regions in DLB, likely due to neurodegenerative pathology associated with disease progression. FW change was associated with clinical decline. The findings support dMRI as a promising tool to track disease progression in DLB. © 2024 International Parkinson and Movement Disorder Society.

Keywords: Lewy body disease; dementia with Lewy bodies; diffusion‐weighted imaging; magnetic resonance imaging.

Figure 1

A-L: Regions of interest (ROIs) in DLB/MCI-LB with significant increase in FW from baseline to 12-(blue) and 24-months (orange). For each significant ROI, the corresponding plot on the left shows mean FW changes for each follow-up time-point with standard error bars; and the corresponding plot on the right shows FW changes for each participant from baseline to 12- and 24-months.

Figure 2.

T1-structural MRI (axial) showing larger network of ROIs in DLB/MCI-LB identified with significant FW increases at 24-months (3D paired t test for baseline to 24-months, right), compared to 12-months (3D paired t test for baseline to-12 months, left). Overlay is displaying the mean difference in FW at p<0.001 (uncorrected). The coordinate system is in MNI space (with a left posterior inferior orientation). Consistent longitudinal FW increases at both time-points were seen in amygdala, posterior cingulum, entorhinal cortex, parahippocampus, insula, fusiform, retrosplenial cortex, rolandic operculum, and supramarginal gyrus regions. At 24-months, additional FW increases were seen in the pallidum, putamen, mid cingulum, hippocampus, inferior frontal, superior temporal, and thalamus regions.