Clinical-Radiological Spectrum of Cerebral Amyloid Angiopathy-Related Inflammation.

Abstract

To identify clinical and radiological features of cerebral amyloid angiopathy-related inflammation (CAA-ri), and compare these features with those of sporadic CAA, to improve the understanding, diagnosis, and clinical care of CAA-ri. We retrospectively reviewed routine clinical data from 37 patients with CAA-ri and 158 patients with sporadic CAA, including conventional vascular risk factors and comorbidities. We assessed brain magnetic resonance imaging for: radiological markers of CAA; features of amyloid-related imaging abnormalities with edema/effusion (ARIA-E) including parenchymal white matter hyperintensities, sulcal hyperintensities, and gyral swelling; and evidence of neurodegeneration (medial temporal atrophy and global cortical atrophy). Compared with patients with sporadic CAA, patients with CAA-ri had more numerous lobar cerebral microbleeds (median 207[IQR 33-811] vs 19[IQR 7-58], p < 0.001), and higher rates of medial temporal and global cortical atrophy. In comparison with sporadic CAA, all ARIA-E features were much more common in patients with CAA-ri (parenchymal hyperintensities 89% vs 3%, sulcal hyperintensities 78% vs 9%, and gyral swelling 86% vs 0.6%), as were conventional vascular risk factors (hypertension, dyslipidemia) and long-term comorbidities (inflammatory and infectious disorders, autoimmune or connective tissue disorders, or malignancies). Features of ARIA-E (parenchymal white matter hyperintensities, sulcal hyperintensities, and gyral swelling) are more common in CAA-ri in comparison with "non-inflammatory" sporadic CAA, suggesting shared mechanisms with Alzheimer's disease immunotherapy and a potential role in improving diagnostic accuracy for CAA-ri. The high prevalence of atrophy and lobar cerebral microbleeds suggests a potential mechanistic role for capillary CAA, Alzheimer's disease, or both, in CAA-ri. Cardiovascular risk factors and other long-term comorbidities may also be relevant to the underlying mechanisms of CAA-ri. ANN NEUROL 2026;99:148-158.