Brain arteriolosclerosis is associated with lower fractional anisotropy and higher trace of the diffusion tensor throughout white matter independently of other neuropathologies or white matter hyperintensities, with diffusion anomalies statistically significant even in mild arteriolosclerosis and becoming progressively stronger with higher severity.
Key Findings
Results
Brain arteriolosclerosis is independently associated with lower fractional anisotropy (FA) in white matter, even after accounting for other neuropathologies and visible white matter hyperintensities.
Study combined in-vivo diffusion MRI with detailed postmortem neuropathologic examination in 154 community-based older adults.
Participants were drawn from 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 was used to assess associations across white matter.
Associations remained independent of other age-related neuropathologies and visible white matter hyperintensities (WMH).
Results
Brain arteriolosclerosis is independently associated with higher trace of the diffusion tensor in white matter.
Higher trace (reflecting increased mean diffusivity) was found throughout white matter in association with arteriolosclerosis.
Associations were observed independently of other neuropathologies and WMH.
Severe arteriolosclerosis: trace β=146×10⁻⁶ mm²/s, p<0.001.
Results
Diffusion abnormalities associated with arteriolosclerosis were statistically significant even at mild severity and became progressively stronger with increasing arteriolosclerosis severity.
Mild arteriolosclerosis: FA β=-0.012, p=0.02.
Moderate arteriolosclerosis: FA β=-0.03, p<0.001.
Severe arteriolosclerosis: FA β=-0.033, p<0.001.
This dose-response pattern suggests a graded relationship between arteriolosclerosis severity and white matter microstructural damage.
Results
The diffusion abnormalities associated with arteriolosclerosis were more pronounced in white matter connections to frontal lobe regions.
Voxel-wise analysis identified spatial patterns of diffusion abnormalities.
Frontal lobe white matter connections showed stronger associations with arteriolosclerosis compared to other regions.
This regional specificity was observed after controlling for other neuropathologies and WMH.
Background
Brain arteriolosclerosis is common in older adults and is associated with lower cognitive and motor function and higher odds of dementia.
Arteriolosclerosis is described as a primary pathology of cerebral small vessel disease.
The study population consisted of community-based older adults.
These associations with cognitive and motor outcomes provided the rationale for investigating in-vivo imaging markers.
Conclusions
Diffusion imaging may have an important role in the development of markers for early detection and progression of arteriolosclerosis.
The findings highlight the 'independent deleterious impact of arteriolosclerosis on brain tissue integrity.'
Detection of diffusion abnormalities even at mild arteriolosclerosis severity supports potential for early detection.
The progressive strengthening of associations with severity supports utility for tracking disease progression.
Current in-vivo detection of arteriolosclerosis is limited, making imaging markers clinically valuable.
What This Means
This research studied how a type of small blood vessel disease in the brain, called arteriolosclerosis (hardening and thickening of tiny brain arteries), affects the structural integrity of white matter — the brain's communication 'wiring.' The researchers used a specialized MRI technique called diffusion imaging, which measures how water molecules move through brain tissue, combined with detailed brain tissue examination after death in 154 older adults. They found that arteriolosclerosis consistently disrupted white matter structure, showing lower fractional anisotropy (a measure of organized tissue structure) and higher diffusion trace (a measure of tissue damage or loosening), and these effects were independent of other common aging-related brain diseases and visible white matter lesions seen on standard MRI scans.
Importantly, the disruption to white matter was detectable even in people with only mild arteriolosclerosis and got progressively worse as the disease became more severe. The damage was particularly noticeable in white matter pathways connecting to the frontal lobes, regions involved in planning, decision-making, and motor control. These findings suggest that arteriolosclerosis independently harms brain tissue integrity beyond what other brain diseases contribute.
This research suggests that diffusion MRI could potentially serve as a tool to detect arteriolosclerosis early and track how it progresses over time, even before it reaches severe stages. Since arteriolosclerosis is linked to cognitive decline, motor problems, and dementia in older adults, having a way to detect and monitor it non-invasively in living people could be valuable for research and eventually for clinical care.
Tomash A, Tazwar M, Yasar M, Zhang S, Evia A, Leurgans S, et al.. (2026). Diffusion abnormalities associated with brain arteriolosclerosis: An in-vivo MRI and pathology study in community-based older adults.. Neurobiology of aging. https://doi.org/10.1016/j.neurobiolaging.2026.05.007