Progression of Brain Network Alterations in Cerebral Amyloid Angiopathy

Abstract

Background and Purpose 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. Methods Thirty-three patients with probable CAA underwent multimodal brain MRI at two 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 (FA) of posterior-posterior, frontal-frontal, and posterior-frontal network connections were calculated. Patients with moderate vs. severe CAA were defined based on microbleed count, dichotomized at the median (median=35). Results Global efficiency of the ICH-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 (Beta=0.46, p=0.03). Examination of subgroups of network connections revealed a decline in FA of posterior-posterior connections at both levels of CAA severity (−0.006 ± 0.002, p=0.017; group × time interaction p=0.16). The FA 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. Conclusions Brain network impairment in patients with CAA worsens measurably over just 1.3-year follow-up and appear to progress from posterior to frontal connections with increasing disease severity.

Relationship between white matter connectivity loss and cortical thinning in cerebral amyloid angiopathy

“…The FA-weighted connectivity strength of posterior network nodes declined between baseline and follow-up (mean difference 6 SEM: 20.005 6 0.002, P 5 0.02), but not of frontal network nodes (20.001 6 0.003, P 5 0.69), in line with our previous report (Reijmer et al, 2016b). With respect to cortical thickness, a similar posterior-to-frontal gradient was observed although with smaller effect sizes: a trend was found for thinning of the posterior cortex (20.23 6 0.013 mm, P 5 0.09), whereas no thinning was seen in the frontal cortex (20.004 6 0.012 mm, P 5 0.77).…”

“…In brief, 33 nondemented patients with probable CAA defined by the Boston criteria (Knudsen et al, 2001), recruited through the stroke clinic between May 2006 and March 2015, with available brain MRI sequences at two time points, including a diffusion-weighted imaging sequence and T1-weighted 3D spoiled gradient recalled-echo, were considered for the study (mean follow-up time was 1.3 6 0.4 years, range: 1-2 years). We have previously been able to detect changes in hemorrhages (Greenberg et al, 1999), WMH volume (Chen et al, 2006), and white matter connectivity (Reijmer et al, 2016b) in patients with CAA within this time period. Exclusion criteria for participation in the study were dementia, a diagnosis of neurological disease other than CAA, and contraindication to MRI.…”

“…High‐angular‐resolution diffusion imaging (HARDI) scans (60 directions, b value 700, 10 b 0 images, voxel size 2 × 2 × 2 mm) were analyzed and processed in ExploreDTI (http://www.exploredti.com) in accordance with our previous studies (Reijmer et al, ). In brief, HARDI scans were corrected for subject motion and eddy current induced geometric distortions and the diffusion tensors were calculated using the RESTORE approach (Chang et al, ).…”

“…An interesting characteristic of CAA is that the pathology preferentially affects the posterior cerebral territory, with the highest occurrence of amyloid in the vessels of the occipital cortex (Vinters and Gilbert, 1983). In line with the predominant posterior distribution of amyloid pathology, diffusion tensor imaging (DTI) studies have shown that white matter connections between posterior cortical regions are most prominently affected in CAA and show the greatest progression over time , Reijmer et al, 2016b. Cortical atrophy in CAA also appears to occur in posterior brain regions, and in the superior frontal cortex in patients compared to age-matched controls (Fotiadis et al, 2016).…”

Cerebral Amyloid Angiopathy: Similarity in African-Americans and Caucasians with Alzheimer’s Disease

“…CAA also is thought to be related to diminished drainage of cerebrospinal fluid along perivascular pathways, a mechanism by which the brain eliminates toxins and waste[32]. CAA contributes to cognitive decline[33–40], and it has been associated with cortical atrophy[41] and disruption of the cerebral connectome[42]. In AD, CAA most often afflicts arterioles coursing through the leptomeninges and parenchyma of the brain; veins and capillaries are less often affected[29, 39], but when present, capillary CAA appears to have distinctive pathobiologic features[43].…”