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We recently showed that cerebral amyloid angiopathy (CAA) is associated with functionally relevant brain network impairments, in particular affecting posterior white matter connections. Here we examined how these brain network impairments progress over time.Thirty-three patients with probable CAA underwent multimodal brain magnetic resonance imaging at 2 time points (mean follow-up time: 1.3±0.4 years). Brain networks of the hemisphere free of intracerebral hemorrhages were reconstructed using fiber tractography and graph theory. The global efficiency of the network and mean fractional anisotropies of posterior–posterior, frontal–frontal, and posterior–frontal network connections were calculated. Patients with moderate versus severe CAA were defined based on microbleed count, dichotomized at the median (median=35).Global efficiency of the intracerebral hemorrhage–free hemispheric network declined from baseline to follow-up (−0.008±0.003; P=0.029). The decline in global efficiency was most pronounced for patients with severe CAA (group×time interaction P=0.03). The decline in global network efficiency was associated with worse executive functioning (β=0.46; P=0.03). Examination of subgroups of network connections revealed a decline in fractional anisotropies of posterior–posterior connections at both levels of CAA severity (−0.006±0.002; P=0.017; group×time interaction P=0.16). The fractional anisotropies of posterior–frontal and frontal–frontal connections declined in patients with severe but not moderate CAA (group×time interaction P=0.007 and P=0.005). Associations were independent of change in white matter hyperintensity volume.Brain network impairment in patients with CAA worsens measurably over just 1.3-year follow-up and seem to progress from posterior to frontal connections with increasing disease severity.