White matter trajectories in Down syndrome and Alzheimer's disease: Insights from diffusion tensor–based morphometry

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INTRODUCTION: Diffusion magnetic resonance imaging studies investigating Down syndrome (DS) and Alzheimer's disease (AD) have mainly relied on white matter (WM) skeleton-based techniques, potentially overlooking broader WM architecture. METHOD: We applied diffusion tensor-based morphometry (D-TBM), a novel whole-volume WM registration technique, to characterize WM properties in DS. Between- and within-group analyses were conducted in 51 adults with DS and 35 controls, divided into two age groups, using diffusion tensor imaging (DTI)-derived metrics and local volumetric changes. RESULTS: DS participants exhibited extensive volumetric and DTI-based differences affecting association fibers and commissures. Within-group 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. DISCUSSION: DTI changes in the older DS cohort affect WM structures supporting language, memory, and executive functions and may be due to AD-related atrophy. Reduced AxD may reflect neuroinflammation or atypical WM development. HIGHLIGHTS: Diffusion tensor-based morphometry (D-TBM) was applied for the first time in Down syndrome (DS) adults. Diffusion tensor imaging alterations in DS affect structures for language, memory, and executive functions. Increased radial diffusivity and mean diffusivity in older DS adults highlight Alzheimer's disease (AD)-related neurodegeneration in key tracts. AD in DS affects commissural structures, including the genu of the corpus callosum. Axial diffusivity reductions in DS may indicate neuroinflammation.

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