Microbleeds in Alzheimer Disease Are More Related to Cerebral Amyloid Angiopathy than Cerebrovascular Disease

Abstract

Cerebral amyloid angiopathy (CAA) is one of the cardinal pathological features in the vascular components of Alzheimer's disease (AD). CAA itself results in disrupted microvasculature, mainly in the cerebral cortex, eventually leading to a brain cortical or subcortical hemorrhage in a population of elderly people, but clinically overt brain hemorrhages are not so frequent in AD patients. Here we assessed 50 AD patients and 26 controls to detect latent brain hemorrhages with gradient-echo T(2)*-weighted images, a sensitive magnetic resonance imaging technique to detect hemosiderin components in the brain. Microbleeds, demarcated as low-intensity spots in T(2)*-weighted images, were detected in 16.7% of AD patients without cerebrovascular disease (CVD) and in 12.5% of those with CVD, while no microbleeding was detected in the control subjects. No significant difference was observed between the microbleed-positive group and the microbleed-negative counterpart in their clinical background, such as hypertension, the use of antiplatelet drugs and smoking. In addition, white matter high intensities in the T(2)-weighted image were significantly more confluent in the microbleed-positive AD group than its negative counterpart. In conclusion, our evaluation of AD brains revealed that latent microbleeds in AD patients are more frequent than in normal controls. Microbleeds not being related to common hemorrhagic risk factors, but being significantly related to white matter pathologies suggested that microbleeds in AD may be associated with CAA, but not with hypertension or CVD.