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Prior dementia with Lewy bodies (DLB) diffusion tensor imaging studies yielded mixed results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>We employed free\u2010water (FW) imaging to assess DLB progression and correlate with clinical decline in DLB.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Baseline and follow\u2010up MRIs were obtained at 12 and\/or 24 months for 27 individuals with DLB or mild cognitive impairment with Lewy bodies (MCI\u2010LB). 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We followed 23 participants to 12\u2009months and 16 participants to 24\u2009months. Both groups had worsening in Montreal Cognitive Assessment (MoCA) and Movement Disorder Society\u2010Unified Parkinson's Disease Rating Scale (MDS\u2010UPDRS) 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\u2010group 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\u2010UPDRS and MoCA scores.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>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. \u00a9 2024 International Parkinson and Movement Disorder Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.29763","type":"journal-article","created":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T07:40:01Z","timestamp":1710315601000},"page":"836-846","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Longitudinal Free\u2010Water Changes in Dementia with Lewy Bodies"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6143-9867","authenticated-orcid":false,"given":"Shannon Y.","family":"Chiu","sequence":"first","affiliation":[{"name":"Department of Neurology University of Florida  Gainesville Florida USA"},{"name":"Department of Neurology Mayo Clinic  Scottsdale Arizona 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