Abstract 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.
Morcillo‐Nieto et al. (Sun,) studied this question.