Centrum Semiovale Perivascular Spaces Predict First Hemorrhagic Lesions in Amyloid-Positive Adults

Identifying cerebral amyloid angiopathy (CAA) before hemorrhagic lesions develop remains challenging. Researchers conducted a secondary analysis of the A4 randomized trial involving 932 cognitively unimpaired, amyloid-positive older adults without baseline hemorrhagic lesions. Mean age was 71.7 years, and 61.3% were female. The primary outcome was incident strictly lobar cerebral microbleeds or cortical superficial siderosis; longitudinal cognition was assessed using the Preclinical Alzheimer Cognitive Composite.

At baseline, 101 participants (10.8%) had severe enlarged perivascular spaces in the centrum semiovale (EPVS-CSO). During a median 5.1-year follow-up, 33.7% of this group developed hemorrhagic lesions, compared with 13.6% of those with nonsevere EPVS-CSO (adjusted hazard ratio 2.85, 95% CI 1.91–4.25). Severe basal ganglia perivascular spaces, evaluated as a topographical negative control, were not associated with incident lesions (adjusted hazard ratio 0.87, 95% CI 0.35–2.18).

Severe EPVS-CSO was not associated with early cognitive differences, although participants who developed hemorrhagic lesions showed more pronounced cognitive decline. These findings suggest a potential imaging marker for prehemorrhagic CAA in this selected population. However, this observational secondary analysis does not establish causality or demonstrate that marker-guided prevention improves outcomes. The endpoint comprised microbleeds or superficial siderosis, not necessarily symptomatic hemorrhage; full-text methods were unavailable for assessment.