Divergent enlarged perivascular spaces volumes in early versus late age-of-onset Alzheimer’s disease

STRUCTURED ABSTRACT INTRODUCTION Enlarged perivascular spaces (EPVS) are considered a conduit for the brain’s waste clearance system. With aging, the brain’s ability to clear molecules is thought to decline, contributing to the retention of Alzheimer’s disease (AD) neuropathology. However, the role of EPVS in late-onset AD (LOAD) is complicated by co-morbidities. Early-onset AD (EOAD) offers a unique opportunity to understand the role of EPVS in AD. METHODS Automatically-segmented EPVS volumes in biomarker-confirmed EOAD ( n =58), LOAD ( n =43), and age-matched controls ( n =60) were correlated with amyloid and tau PET and cognition. Linear regression models were used. RESULTS In LOAD, higher EPVS volumes were associated with better memory and functional performance. However, this association was not observed in EOAD. Additionally, higher tau was linked to increased EPVS in LOAD, but not in EOAD. DISCUSSION EOAD and LOAD demonstrate distinct associations between EPVS, AD hallmarks, and cognition, suggesting differences in EPVS’s role in these AD subtypes, necessitating further investigation.