Cerebral amyloid angiopathy (CAA) is an age-related small vessel disease in which beta-amyloid protein accumulates in the walls of blood vessels in the brain. For its diagnosis, the Boston criteria are used, which were first established in the 1990s and last updated in 2010. Recently, a new paper published in Lancet Neurology has proposed an update, with the incorporation of new MRI markers, to increase sensitivity in the diagnosis of this pathology. The study, led by the Massachusetts General Hospital (Boston, United States), has involved researchers from the Neurovascular Diseases and Translational Molecular Pathology groups of the Vall d'Hebron Research Institute (VHIR).

As in other neurodegenerative diseases, the definitive diagnosis of CAA is based on the analysis of autopsies or brain biopsies. "The goal of the Boston criteria is to facilitate a probable diagnosis of CAA that can be applied when the patient is alive and noninvasively. Diagnosis during life is important to improve patient care and allow their participation in research, and thus advance in the diagnosis and treatment of the disease", explains Dr. Mar Hernández Guillamon, researcher of the Neurovascular Diseases group at VHIR and one of the authors of the paper.

To improve the Boston criteria used so far, a retrospective, multicenter, international study was carried out in which clinical, MRI and neuropathological data were analyzed, and in which different clinical presentations of CAA with and without intracerebral hemorrhage were explored. They studied 341 patients older than 50 years who had clinical presentations compatible with CAA (spontaneous intracerebral hemorrhage, cognitive impairment or transient focal neurological episodes such as temporary problems in movement, sensation, vision or language...) and in all of them MRI images and brain tissue (obtained by biopsy or autopsy) were available.

Initially, the researchers studied 159 cases from Massachusetts Hospital from 1994-2012 to establish a set of new criteria. These were then validated in a cohort of 59 patients from the same hospital, but from 2012-2018 (temporal validation cohort) and in 123 cases from other hospitals from 2004-2018 (geographic validation cohort).

The Boston 2.0 criteria incorporate new brain MRI markers. On the one hand, it includes as a novelty the detection of subarachnoid hemorrhages or the presence of blood-derived products (superficial siderosis). It also includes the detection of lesions in the white matter of the brain, such as the presence of severe visible perivascular spaces in centrum semiovale or white matter hyperintensities in a multispot pattern. 

"To analyze the sensitivity and specificity of this new method, it is compared in all cases with the standard diagnosis provided by autopsy. It is observed that, with the new criteria, the sensitivity in detecting probable CAA is increased compared to the 2010 criteria, i.e. detection of more cases with CAA. Moreover, despite taking into account different clinical presentations of the disease, specificity is not compromised: the number of false positives is not significantly increased", says Dr. Elena Martinez Sáez, researcher of the Translational Molecular Pathology group at VHIR and neuropathologist at the Anatomic Pathology Department of Vall d'Hebron University Hospital and one of the authors of the publication.

The validation of this updated criteria in other centers around the world has confirmed that the diagnostic power is similar and therefore, it is possible to apply it among different geographic populations. Future studies will have to evaluate these criteria in other patient subgroups, such as other ethnic groups or in those patients presenting with mixed pathology or without clear symptoms of CAA. Future updates will also consider the use of other biomarkers, such as amyloid detection by positron emission tomography (PET) or in cerebrospinal fluid in this type of patient.