Cerebral amyloid angiopathy (CAA) is characterized by deposition of amyloid protein in vessel walls of leptomeningeal and cortical small arteries; it was first described in 1907.1 A variety of distinct clinical phenotypes have been attributed to this CNS vasculopathy, with spontaneous recurrent lobar hemorrhage in the elderly patient being the most widely recognized.1 More recent studies have established that, in CAA associated with leukoencephalopathy, an inflammatory variant of CAA can be distinguished.2–4 Mean age at disease onset is about 67 years.1–4 A clinico-radiological-histopathological syndrome has been described, consisting of a clinical phenotype of rapidly-progressive dementia, extensive and markedly asymmetric T2 hyperintense white-matter lesions, together with multiple scattered cortical/subcortical microbleeds on MR-imaging (Figure 1) and typical vascular amyloid deposits associated with perivascular inflammatory changes on histopathological examination.2–4 Although the diagnostic gold standard remains histopathological examination, it has been suggested that in the appropriate clinical setting, typical imaging findings, as outlined above, might be sufficient to diagnose CAA-related inflammation, without necessitating brain biopsy.3,5 A diagnostic entity termed “probable CAA-related inflammation” has been proposed.3,5 Thus, initiating a short treatment trial with high-dose steroids, without performing brain biopsy, can be done if further studies (e.g., blood pressure, laboratory, CSF) make an infectious, hypertensive, or neoplastic etiology unlikely. Most patients respond well to immunosuppressive therapy in the acute phase; only a few need long-term maintenance therapy.2
The first priority of diagnostic evaluation of dementia syndrome is the identification of potentially treatable causes. Cerebral amyloid angiopathy (CAA)-related inflammation is associated with a clinical phenotype of rapidly-progressive dementia, and most patients respond well to immunosuppressive therapy. It has been suggested that it might be diagnosed non-invasively, based on a constellation of typical clinical and radiological findings. Thus, careful neuroradiological evaluation for microbleeds in patients with rapidly-progressive dementia and leukoencephalopathy can help to define a potentially treatable cause of rapidly-progressive dementia syndrome.