Beyond hemorrhage: cognitive and structural insights in hereditary and sporadic cerebral amyloid angiopathy

Abstract

Cerebral amyloid angiopathy (CAA) is a cerebral small vessel disease characterized by amyloid-β deposition in cortical and leptomeningeal vessels. Although CAA is primarily known for its association with intracerebral hemorrhage, its broader effects on cognition, behavior, and brain structure remain incompletely understood. This thesis investigates these consequences in hereditary Dutch-type CAA (D-CAA) and sporadic CAA (sCAA), with particular attention to disease progression beyond overt hemorrhage.

Longitudinal cognitive analyses showed that patients with D-CAA who had experienced intracerebral hemorrhage demonstrated decline in memory and processing speed over five years, whereas patients without hemorrhage and those with sCAA were comparatively stable. Neuropsychiatric symptoms, particularly apathy and irritability, were common and associated with poorer processing speed and executive functioning. Structural MRI analyses further examined brain atrophy over time, revealing measurable volume loss but no clear differences in atrophy trajectories between CAA subgroups. In addition, APOE ε4 did not show a clear association with disease severity in D-CAA across different stages of CAA disease progression.

Together, these findings demonstrate that CAA affects more than the risk of hemorrhage alone. Cognitive, neuropsychiatric, and structural changes form an important part of the disease spectrum and should be considered in research, clinical monitoring, and future therapeutic strategies.