Distinct patterns of voxel‐ and connection‐based white matter hyperintensity distribution and associated factors in early‐onset and late‐onset Alzheimer's disease

Abstract Introduction The distribution of voxel‐ and connection‐based white matter hyperintensity (WMH) patterns in early‐onset Alzheimer's disease (EOAD) and late‐onset Alzheimer's disease (LOAD), as well as factors associated with these patterns, remain unclear. Method We analyzed the WMH distribution patterns in EOAD and LOAD at the voxel and connection levels, each compared with their age‐matched cognitively unimpaired participants. Linear regression assessed the independent effects of amyloid and vascular risk factors on WMH distribution patterns in both groups. Results Patients with EOAD showed increased WMH burden in the posterior region at the voxel level, and in occipital region tracts and visual network at the connection level, compared to controls. LOAD exhibited extensive involvement across various brain areas in both levels. Amyloid accumulation was associated WMH distribution in the early‐onset group, whereas the late‐onset group demonstrated associations with both amyloid and vascular risk factors. Discussion EOAD showed posterior‐focused WMH distribution pattern, whereas LOAD was with a wider distribution. Amyloid accumulation was associated with connection‐based WMH patterns in both early‐onset and late‐onset groups, with additional independent effects of vascular risk factors in late‐onset group. Highlights Both early‐onset Alzheimer's disease (EOAD) and late‐onset AD (LOAD) showed increased white matter hyperintensity (WMH) volume compared with their age‐matched cognitively unimpaired participants. EOAD and LOAD exhibited distinct patterns of WMH distribution, with EOAD showing a posterior‐focused pattern and LOAD displaying a wider distribution across both voxel‐ and connection‐based levels. In both EOAD and LOAD, amyloid accumulation was associated with connection‐based WMH patterns, with additional independent effects of vascular risk factors observed in LOAD.