Enlarged Centrum Semiovale Perivascular Spaces as a Non- Invasive Imaging Marker of Vascular Amyloid Deposition in Amyloid-Positive Individuals Without CAA-Related Hemorrhages

Abstract With the increasing use of anti-amyloid therapy, there is a growing need for reliable methods to detect vascular amyloid in patients with early-stage Alzheimer's disease (AD). The reduction in cerebrospinal fluid (CSF) Aβ42 and Aβ40 levels is a well-documented characteristic of fluid biomarkers for cerebral amyloid angiopathy (CAA). However, the invasive nature of CSF collection hinders its feasibility for routine clinical applications. Alternatively, a high degree of MRI-visible perivascular spaces in the centrum semiovale (CSO-PVS), which are typically associated with CAA-related hemorrhages, is emerging as a promising non-invasive imaging biomarker. Nevertheless, the applicability of a high degree of CSO-PVS to reflect vascular amyloid accumulation in amyloid-positive individuals without definitive CAA-related hemorrhages remains unclear.This study retrospectively analyzed 30 participants diagnosed with mild cognitive impairment due to AD or mild AD characterized by reduced CSF Aβ42/40 ratio without CAA-related hemorrhagic manifestations. Participants were categorized into high- and low-degree CSO-PVS groups based on the median value of visually quantified CSO-PVS. CSF Aβ40 levels were significantly lower in the high-degree CSO-PVS group compared with the low-degree group (P = 0.0235), and CSF Aβ42 levels showed a trend toward lower values (P = 0.0502). These findings suggest that dilated CSO-PVS may serve as a potential surrogate marker for vascular amyloid deposition, offering a non-invasive alternative for monitoring patients undergoing anti-amyloid therapy.