Objective: To characterize longitudinal diffusion microstructural changes in individuals with dementia with Lewy bodies (DLB).

Background: Diffusion-weighted MRI (dMRI) examines tissue microstructure integrity in vivo. Prior studies of dementia with Lewy bodies (DLB) have yielded mixed results using conventional diffusion tensor imaging approach. Less is known about longitudinal white and grey matter microstructural changes in DLB.

Method: dMRI scans were collected on individuals with DLB from the Mayo Clinic Longitudinal Imaging Biomarkers of DLB Program. Demographics, clinical evaluations, and MRI were collected at baseline, 12- and/or 24-months. Free-water (FW) was analyzed using 122 bilateral regions from the Mayo Clinic Adult Lifespan Template. Primary outcomes were differences in FW between baseline and 12- or 24-months.

Results: We identified 23 individuals with DLB or mild cognitive impairment with Lewy bodies from baseline to 12-months [mean age 69.3 years (SD 9.5); 95.8% male], and 16 individuals from baseline to 24-months [mean age 67.5 years (SD 9.3); 100% male]. Participants at both time-points showed worsening in Montreal Cognitive Assessment (MoCA) and Movement Disorders Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) motor scores (p<0.05). We found significant increases in FW at both time-points compared to baseline in the insula, putamen, parahippocampal, and rolandic operculum regions (pfdr<0.05). We found additional, more widespread microstructural changes from baseline to 24-months only, with increased FW in the amygdala, entorhinal, mid and posterior cingulum, inferior frontal, hippocampal, pallidum, precuneus and retrosplenial regions (pfdr<0.05). Additionally, FW changes at baseline predicted worsening of total MoCA, MDS-UPDRS total and motor scores, at 24-months only.

Conclusion: FW increases over time in gray and white matter regions in DLB, possibly due to neurodegenerative pathology associated with disease progression. Additionally, FW at baseline is associated with a decline in motor and cognitive progression at 24-months. These findings support dMRI as a promising, non-invasive tool to track DLB disease progression.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/longitudinal-free-water-changes-in-dementia-with-lewy-bodies/