Abstract 2891: Severity of Amyloid Deposition is Associated with Ischemic White Matter Disease in Cerebral Amyloid Angiopathy but Not in Healthy Elderly: a PET/MRI Correlative Study

Abstract

Background and Purpose: Cerebral Amyloid Angiopathy (CAA), characterized by accumulation of amyloid beta proteins in the walls of cortical/leptomeningeal vessels, is increasingly recognized as a cause of ischemic brain injury in addition to its classical role in lobar cerebral hemorrhages (ICH). Pittsburgh Compound B (PiB) is a PET ligand that has been shown to label the vascular amyloid deposits of CAA, allowing invivo quantification of the severity of CAA pathology. We hypothesized that there would be a dose-dependent relationship between vascular amyloid burden (measured by PiB) and brain ischemia (measured by extent of MRI markers of chronic ischemia) in patients diagnosed with CAA but not in healthy elderly without evidence of advanced CAA. Methods: Thirty-five non-demented patients (9 women) with a diagnosis of CAA according to Boston Criteria and 50 healthy elderly subjects (29 women) without lobar microhemorrhages or history of stroke/dementia who underwent a brain MRI scan and PiB-PET imaging were analyzed. Global cortical PiB retention was calculated using cerebellar cortex as the reference tissue input function and expressed as the distribution volume ratio (DVR). Quantitative analysis of white matter T2-hyperintensity (WMH) volume on MRI FLAIR sequences was performed using computer-assisted techniques. Presence of lacunar infarcts was also recorded in each subject. Multivariate linear regression was used to assess the association between PiB retention and WMH volume while controlling for other vascular risk factors within each group. Results: CAA patients were younger than healthy elderly (67±10 vs 73±7, p=0.004) but had higher amounts of WMH (19ml IQR:6.7-31.8 vs 3.2ml IQR:2-5.6, p<0.001) and mean global DVR (1.34±0.19 vs 1.17±0.13, p<0.001). In bivariate analyses, global DVR and WMH showed a strong correlation (Spearman's rho=0.52, p<0.001) in the CAA cohort. This association did not substantially change in a multivariate model that included age, gender, and vascular risk factors as covariates. Global DVR and WMH were not correlated (Spearman's rho=0.01, p=0.95) in the healthy elderly group. Nine CAA patients (26%) had a lacunar infarction on imaging against only 1 healthy control (2%), p=0.001. CAA patients with lacunes had higher mean DVR (p=0.03), but this association did not remain independent after adjustment for age. Conclusions: Our results indicate that global PiB retention independently correlates with volume of white matter disease on FLAIR in patients with CAA but not in healthy elderly. These findings support the idea that vascular amyloid burden directly contributes to chronic cerebral ischemia in the CAA population and highlights the possible utility of amyloid imaging as a marker of CAA severity.