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

Abstract

Background and objectives: 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).

Methods: 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.

Results: 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).

Discussion: 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.

Figure 1. Examples of Markers at Baseline and Follow-Up

Axial 3T-MRI scans showing examples of marker progression in different patients with CAA. (A) T1-weighted images showing the appearance of a recent symptomatic intracerebral hemorrhage in the left temporal lobe (A.b; arrow) of a patient with D-CAA at follow-up. (B) Susceptibility-weighted images showing a macrobleed in the left parietal lobe of a patient with sCAA at baseline (B.a; arrow) and the appearance of 2 more macrobleeds in the right frontal and frontoparietal lobe at follow-up (B.b; arrowheads). (C) Susceptibility-weighted images showing multiple CMBs in a patient with D-CAA at baseline (C.a) with an increase of CMBs at follow-up, particularly in the left frontal lobe (C.b; enhanced). (D) Susceptibility-weighted images showing cSS in the right frontal and parietal lobe at baseline in a patient with D-CAA (D.a; arrows) and at follow-up local extension of the cSS in the right hemisphere (D.b; arrowhead) as well as new foci of cSS in the right and left frontal lobes (D.b; arrows). (E) T2-weighted images showing category 4 (severe, >40 visible in 1 hemisphere) enlarged perivascular spaces in the centrum semiovale in a patient with D-CAA with no visible progression at follow-up. (F) T2-weighted images showing an increase of white matter hyperintensities in both hemispheres at follow-up (F.b, arrows) in a patient with D-CAA. CAA = cerebral amyloid angiopathy; CMB = cerebral microbleed; cSS = cortical superficial siderosis; D-CAA = Dutch-type hereditary CAA; sCAA = sporadic CAA.

Figure 2. Increase of CMBs (A) and WMH Volume (B) Compared to Baseline

CAA = cerebral amyloid angiopathy; CMB = cerebral microbleed; D-CAA = Dutch-type hereditary CAA; sCAA = sporadic CAA; WMH = white matter hyperintensity.

Figure 3. BOLD Parameter: Upslope

BOLD = blood oxygenation level–dependent; CAA = cerebral amyloid angiopathy; D-CAA = Dutch-type hereditary CAA; sCAA = sporadic CAA

Figure 4. Decrease of BOLD Upslope Compared With Baseline

BOLD = blood oxygenation level–dependent; CAA = cerebral amyloid angiopathy; D-CAA = Dutch-type hereditary CAA; sCAA = sporadic CAA.

Figure 5. Number of Participants With Progression per Marker

CAA = cerebral amyloid angiopathy; CMB = cerebral microbleed; D-CAA = Dutch-type hereditary CAA; EPVS = enlarged perivascular spaces; sCAA = sporadic CAA.