Temporal dynamics of white matter hyperintensities related to Alzheimer's disease in adults with Down syndrome

INTRODUCTION: White matter hyperintensities (WMH) are common in Down syndrome (DS), yet their longitudinal evolution and associations with Alzheimer's disease (AD) remain unclear. METHODS: Longitudinal MRI study, including 80 DS adults and 53 euploid controls. WMH were segmented on serial FLAIR using a longitudinal pipeline. We assessed the effects of demographic, genetic factors, AD clinical stage, AD-related fluid, and cerebrovascular biomarkers on annual WMH volume changes. RESULTS: In DS, annual WMH changes were relatively stable until age 40, and then exhibited fluctuations, with a significant decrease at the group level. Declines were larger in symptomatic cases, particularly in periventricular and fronto-parieto-occipital regions. Higher baseline WMH and microbleeds presence related to greater WMH reduction. Visual ratings and adjustment for white matter volume supported the robustness of the results. DISCUSSION: WMH trajectories were heterogeneous in DS and declined over time with AD symptoms. This unexpected reduction may reflect different underlying pathological processes, including neurodegeneration or neuroinflammation.