One-Year Radiologic Progression in Sporadic and Hereditary Cerebral Amyloid Angiopathy

Knowledge on the short-term progression of cerebral amyloid angiopathy (CAA) is important for clinical practice and the design of clinical treatment trials. We investigated the 1-year progression of CAA-related MRI markers in sporadic (sCAA) and Dutch-type hereditary (D-CAA).

Participants were included from 2 prospective cohort studies. 3T-MRI was performed at baseline and after 1 year. We assessed macrobleeds, cerebral microbleeds (CMBs), cortical superficial siderosis (cSS), convexity subarachnoid hemorrhages (cSAHs), white matter hyperintensities (WMH), enlarged centrum semiovale perivascular spaces (CSO-EPVS), and visually stimulated blood oxygenation level-dependent (BOLD) fMRI parameters. Progression was defined as increase in number of macrobleeds or CMBs, new focus or extension of cSS, increase in CSO-EPVS category, or volume increase of >10% of WMH. Multivariable regression analyses were performed to determine factors associated with progression and the association between events related to parenchymal injury (cSAH, macrobleeds) and radiologic progression.

We included 98 participants (47% women): 55 with sCAA (mean age 70 years), 28 with symptomatic D-CAA (mean age 59 years), and 15 with presymptomatic D-CAA (mean age 45 years). Progression of >1 MRI markers was seen in all 83 (100%) participants with sCAA and symptomatic D-CAA and in 9 (60%) with presymptomatic D-CAA. The number of CMBs showed the largest progression in sCAA (98%; median increase 24) and symptomatic D-CAA (100%; median increase 58). WMH volume (>10% increase in 70%; mean increase 1.2 mL) was most progressive in presymptomatic D-CAA. A decrease in the upslope of the visually evoked BOLD response was observed for most patients. Symptomatic D-CAA status was associated with more overall progression (adjusted odds ratio [aOR] 9.7; 95% CI 1.7-54.2), CMB (adjusted relative risk [aRR] 2.47; 95% CI 1.5-4.1), and WMH volume progression (β 2.52; 95% CI 0.3-4.8). Baseline CMB count (aRR 1.002; 95% CI 1.001-1.002) was associated with CMB progression and cSS presence at baseline (aOR 8.16; 95% CI 2.6-25.4) with cSS progression. cSS progression was also associated with cSAH and macrobleeds (aOR 21,029; 95% CI 2.042-216.537).

CAA is a radiologically progressive disease even in the short-term. After 1 year, all symptomatic and most of the presymptomatic participants showed progression of at least 1 MRI-marker. CMBs and WMH volume (in symptomatic CAA) and WMH volume (in presymptomatic CAA) are the most promising markers to track short-term progression in future trials.