Evaluation of an in vivo biomarker of arteriolosclerosis (ARTS) and its associations with cognition and multimodal ATN(V) biomarkers in a cardiometabolic-risk enriched community cohort

Abstract

INTRODUCTION: We evaluated associations between an in vivo (magnetic resonance imaging [MRI]) marker of arteriolosclerosis (ARTS) and multimodal neuroimaging and plasma ATN(V) biomarkers. METHODS: Among 238 participants with both amyloid and tau positron emission tomography (PET) scans within 1 year of MRI, we examined multivariable adjusted models relating ARTS with structural MRI (cortical thickness/volume, white matter hyperintensities [WMH]), diffusion MRI (fractional anisotropy [FA], mean diffusivity [MD], NODDI free water [FW]), cerebral blood flow, plasma biomarkers (p-tau217, Aβ42/40, neurofilament light, glial fibrillary acidic protein [GFAP]), and PET imaging. RESULTS: As expected, ARTS was most strongly linked to age and greater WMH burden and diffusion-based indices of microstructural disruption (FA, MD, and FW). ARTS was elevated in ATN biomarker-positive groups (highest in A+T+N+) and was associated with greater neurodegeneration and higher plasma biomarker levels, GFAP in particular. DISCUSSION: ARTS relates to other markers of vascular brain injury, neurodegeneration, amyloid and tau pathology within the ATN(V) framework, and inflammation.