Diffusion abnormalities associated with brain arteriolosclerosis: An in-vivo MRI and pathology study in community-based older adults

Brain arteriolosclerosis, a primary pathology of cerebral small vessel disease, is common in older adults and is associated with lower cognitive and motor function and higher odds of dementia. The purpose of this study was to test the hypothesis that arteriolosclerosis is associated with lower diffusion anisotropy and higher trace of the diffusion tensor in white matter, independently of other age-related neuropathologies and visible white matter hyperintensities (WMH). In-vivo diffusion MRI and detailed postmortem neuropathologic examination were combined in 154 community-based older adults participating in the Rush Memory and Aging Project, Religious Orders Study, Minority Aging Research Study, and Clinical Core of the Rush Alzheimer’s Disease Research Center. Voxel-wise analysis showed that brain arteriolosclerosis is associated with lower fractional anisotropy (FA) and higher trace of the diffusion tensor throughout white matter, independently of associations with other neuropathologies or WMH. The associations were more pronounced in white matter connections to frontal lobe regions. Diffusion anomalies were statistically significant even in mild arteriolosclerosis (FA: β=-0.012, p = 0.02) and became progressively stronger with higher arteriolosclerosis severity (FA: β=-0.03, p < 0.001 for moderate, and β=-0.033, p < 0.001 for severe arteriolosclerosis; trace: β=114 ×10 −6 mm²/s, p < 0.001, and β=146 ×10 −6 mm²/s, p < 0.001). The findings of this study highlight the independent deleterious impact of arteriolosclerosis on brain tissue integrity and suggest that diffusion imaging may have an important role in the development of markers for early detection and progression of the pathology.