Association of an in vivo classifier for ARTerioloSclerosis (ARTS) with cortical thickness and cognition in older adults

Brain arteriolosclerosis, a prominent small vessel pathology in the aging brain, is associated with cognitive impairment. Understanding the link between arteriolosclerosis and neurodegeneration may be crucial towards unravelling pathways by which arteriosclerosis contributes to cognitive impairment. Using a novel magnetic resonance imaging (MRI) in-vivo classifier for ARTerioloSclerosis termed ARTS, we examined cross-sectional associations between ARTS, cortical thickness, and cognition. Data came from 1054 older participants who were enrolled in one of five ongoing Rush Alzheimer's Disease Center cohort studies, underwent an in-vivo 3 T MRI scan, met the data requirements for ARTS and FreeSurfer processing, and completed cognitive evaluation within a year of MRI. Focusing on the last, most recent MRI scan, we assessed cross-sectional associations of ARTS score with cortical thickness (whole brain and regional measures) and cognitive outcomes (global and domain-specific), using separate linear regression models. Further, we examined whether cortical thickness mediates the relationship between ARTS and global cognition. Models were all adjusted for demographics, vascular risk factors, and scanners. At last analytic MRI scan, participants were on average 80 years old (SD=7) and 80 % were women. Higher ARTS score was associated with lower whole brain cortical thickness (estimate per 1-SD increase=-0.029, 95 % CI: -0.036, -0.022), and across each of the lobes (all P < .01), particularly in temporal lobe regions. Higher ARTS scores were associated with worse global cognition (estimate per 1-SD increase=-0.079, 95 % CI: -0.122, -0.035); also, more specifically higher ARTS score was related to poorer performance in the domains of semantic memory, perceptual speed, and visuospatial ability. In mediation analyses, cortical thickness accounted for 32 % of the association between ARTS score and global cognition. More cerebral arteriolosclerosis-related changes, measured by in-vivo ARTS, is associated with lower cortical thickness and cognitive functions. The association between ARTS and cognition is partially mediated by cortical thickness. Findings suggest that cerebral small vessel disease may contribute to cortical thickness, a marker of neurodegeneration, and contribute both directly and indirectly, to cognitive impairment.