Cortical Structure Alterations in Cerebral Amyloid Angiopathy

Background/Objective: Multiple lines of evidence suggest that Cerebral Amyloid Angiopathy (CAA) leads to ischemic subcortical tissue injury, but its relationship to cortical changes is unknown. We tested the hypothesis that CAA is associated with cortical tissue loss. Methods: Three age-matched cohorts of 63 subjects each (non-demented patients with probable CAA, Healthy Controls [HC] and patients with Alzheimer’s Disease [AD], the latter two from AD Neuroimaging Initiative) underwent multimodal MRI. FreeSurfer was used to calculate cortical thickness, white matter hyperintensity (WMH), and hippocampal volumes (HV). In patients with intracerebral hemorrhage, the measures were obtained from the contralateral hemisphere, and all were corrected for intracranial volume. CAA patients also had functional MRI to calculate Blood-Oxygen-Level-Dependent Time-to-Peak (BOLD-TTP), a measure of vascular reactivity. Lobar microbleeds (LMB) were counted on SWI. Results: The mean age of each cohort was 72±5. CAA patients had thinner cortices compared to HC (2.17±0.11 vs 2.31±0.07 in mm, p<0.001), especially in the occipital, temporal, posterior parietal, and medial frontal regions [Figure]. Patients with AD had significantly thinner cortices than both CAA and HC (2.1±0.14, p<0.01 for both comparisons, also see Figure). Similarly, HV was lower in CAA than controls but both CAA and HC had higher HV than AD (p<0.01 for all comparisons). The number of LMBs and WMH did not correlate with cortical measures in CAA (p>0.2). There was a significant negative correlation (r=-0.4) between BOLD-TTP delay and cortical thickness (p=0.005 after adjustment for covariates). Conclusions: Cortical thickness of CAA patients is significantly reduced when compared to age-matched HC but higher than in AD. Analyses within the CAA cohort suggest that CAA-related vascular dysfunction might contribute to cortical atrophy.