CAA is vascular disease of the brain in which beta-amyloid is deposited in the walls of small arteries and capillaries. The amyloid replaces smooth muscle cells, causing vessel wall thickening and stiffness. This can result in leaks and reduced blood flow in these small blood vessels. Tiny hemorrhages and small strokes are seen surrounding the affected blood vessels. In the elderly, CAA is a major cause of serious bleeding in the various lobes of the brain. Genetically, it can occur sporadically or in families. There is often but not always an overlap with Alzheimer’s disease.

However, there is a darker side to anti-amyloid monoclonal antibodies including lecanemab. ARIA, an acronym for amyloid-related imaging abnormalities, have occurred in all trials of anti-amyloid MABs. They occur in two forms, swelling (edema) of the brain (ARIA-E) and microhemorrhages (ARIA-H). Most of the time they are harmless and without symptoms, and they usually resolve within a month or two after stopping the drug. Rarely, they can be severe. As described in a case study, I was one of the subjects in the aducanumab trial who had severe ARIA of both types, swelling and bleeding. I required ICU care for two days, but I eventually fully recovered over the next few months. So far, three research subjects have died during the lecanemab clinical trial.