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Between\u2010 and within\u2010group analyses were conducted in 51 adults with DS and 35 controls, divided into two age groups, using diffusion tensor imaging (DTI)\u2013derived metrics and local volumetric changes.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>DS participants exhibited extensive volumetric and DTI\u2010based differences affecting association fibers and commissures. Within\u2010group comparisons revealed further changes in older DS participants in these fibers. Reduced axial diffusivity (AxD) in temporal and commissural WM was reported for the first time in DS.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>DTI changes in the older DS cohort affect WM structures supporting language, memory, and executive functions and may be due to AD\u2010related atrophy. Reduced AxD may reflect neuroinflammation or atypical WM development.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Diffusion tensor\u2013based morphometry (D\u2010TBM) was applied for the first time in Down syndrome (DS) adults.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Diffusion tensor imaging alterations in DS affect structures for language, memory, and executive functions.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Increased radial diffusivity and mean diffusivity in older DS adults highlight Alzheimer's disease (AD)\u2010related neurodegeneration in key tracts.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>AD in DS affects commissural structures, including the genu of the corpus callosum.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Axial diffusivity reductions in DS may indicate neuroinflammation.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.70382","type":"journal-article","created":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T23:04:00Z","timestamp":1749769440000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["White matter trajectories in Down syndrome and Alzheimer's disease: Insights from diffusion tensor\u2013based morphometry"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0104-1405","authenticated-orcid":false,"given":"Fedal","family":"Saini","sequence":"first","affiliation":[{"name":"Institute of Psychiatry Psychology &amp; Neuroscience Department of Forensic and Neurodevelopmental Sciences King's College London  London UK"},{"name":"Institute of Psychiatry Psychology &amp; Neuroscience, Natbrainlab King's College London  London 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