Introduction: Cerebral amyloid angiopathy (CAA) is a common form of small vessel disease. We recently showed that CAA is associated with functionally relevant brain network alterations, in particular affecting white matter connections in posterior regions. Here we examined how these brain network alterations progress over time.
Hypothesis: Brain white matter network alterations in CAA progress from posterior to frontal regions.
Methods: Thirty-three patients with probable CAA (16 with intracerebral hemorrhage (ICH)) underwent multimodal brain MRI at two time points (mean follow-up time: 1.3±0.4 years). Brain networks were reconstructed using graph theory and the global efficiency and mean fractional anisotropies (FA) of posterior-posterior, frontal-frontal, and posterior-frontal connections of the ICH-free hemisphere were calculated. Microbleed count, dichotomized at the median, was used as a marker of CAA severity. We evaluated changes in FA and global efficiency over time in patients with moderate (n<35) vs. high (n≥35) microbleed counts with repeated measures analysis adjusted for age.
Results: For all CAA patients, the FA of posterior-posterior connections declined between baseline and follow-up (effect of time: p=0.02; time x group interaction: p=0.16). A decline in FA of posterior-frontal and frontal-frontal connections was observed for patients with high but not moderate microbleed counts (time x group interaction: p=0.007 and p=0.005). A similar time x group interaction effect was observed for global network efficiency (p=0.03). Associations were independent of ICH, white matter hyperintensity volume, or total brain volume.
Conclusions: Brain network alterations in patients with CAA worsen measurably over just 1.3-year follow-up and appear to progress from posterior to frontal regions with increasing disease severity.