DTI-ALPS associates with AD-signature region volumes, plasma biomarkers, and white matter hyperintensity progression

Motivation: The role of brain glymphatic function in the pathogenesis of Alzheimer's disease (AD) remains unknown. Goal(s): To investigate the associations of glymphatic function with imaging and plasma biomarkers of AD. Approach: The diffusion tensor imaging along the perivascular space (DTI-ALPS) index was correlated with baseline and annual percent change in AD-signature region volumes, white matter hyperintensity (WMH), and plasma biomarkers. Results: The DTI-ALPS index positively correlated with volumes in the basal forebrain, entorhinal cortex, and hippocampus, and negatively correlated with WMH, plasma ptau181 and ptau217. Baseline DTI-ALPS index negatively associated with annual WMH progression. Impact: Worse glymphatic function indicates decreased AD-signature region volumes, severe WMH lesions, higher plasma ptau, and accelerated WMH progression. Therapies targeting the glymphatic system may prevent cognitive decline through the clearance of AD pathological proteins and the deceleration of WMH lesions.