The Boston criteria version 2.0 for cerebral amyloid angiopathy: a multicentre, retrospective, MRI–neuropathology diagnostic accuracy study

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Andreas Charidimou - , Harvard University (Author)
  • Gregoire Boulouis - , Harvard University, GHU Paris Psychiatrie & Neuro sciences (Author)
  • Matthew P. Frosch - , Harvard University (Author)
  • Jean Claude Baron - , GHU Paris Psychiatrie & Neuro sciences (Author)
  • Marco Pasi - , Harvard University, Université de Lille (Author)
  • Jean Francois Albucher - , Center Hospitalo-Universitaire (CHU) de Toulouse (Author)
  • Gargi Banerjee - , University College London (Author)
  • Carmen Barbato - , University College London (Author)
  • Fabrice Bonneville - , Center Hospitalo-Universitaire (CHU) de Toulouse (Author)
  • Sebastian Brandner - , University College London (Author)
  • Lionel Calviere - , Center Hospitalo-Universitaire (CHU) de Toulouse (Author)
  • François Caparros - , Université de Lille (Author)
  • Barbara Casolla - , Université de Lille (Author)
  • Charlotte Cordonnier - , Université de Lille (Author)
  • Marie Bernadette Delisle - , Center Hospitalo-Universitaire (CHU) de Toulouse (Author)
  • Vincent Deramecourt - , Université de Lille (Author)
  • Martin Dichgans - , Ludwig Maximilian University of Munich, German Center for Neurodegenerative Diseases (DZNE) (Author)
  • Elif Gokcal - , Harvard University (Author)
  • Jochen Herms - , Ludwig Maximilian University of Munich (Author)
  • Mar Hernandez-Guillamon - , Autonomous University of Barcelona (Author)
  • Hans Rolf Jäger - , University College London (Author)
  • Zane Jaunmuktane - , University College London (Author)
  • Jennifer Linn - , Institute and Polyclinic of Diagnostic and Interventional Neuroradiology (Author)
  • Sergi Martinez-Ramirez - , Harvard University, National Institutes of Health (NIH) (Author)
  • Elena Martínez-Sáez - , Autonomous University of Barcelona (Author)
  • Christian Mawrin - , Otto von Guericke University Magdeburg (Author)
  • Joan Montaner - , Autonomous University of Barcelona, Hospital Universitario Virgen Macarena (Author)
  • Solene Moulin - , Université de Lille (Author)
  • Jean Marc Olivot - , Center Hospitalo-Universitaire (CHU) de Toulouse (Author)
  • Fabrizio Piazza - , University of Milan - Bicocca (Author)
  • Laurent Puy - , Université de Lille (Author)
  • Nicolas Raposo - , Center Hospitalo-Universitaire (CHU) de Toulouse (Author)
  • Mark A. Rodrigues - , University of Edinburgh (Author)
  • Sigrun Roeber - , Ludwig Maximilian University of Munich (Author)
  • Jose Rafael Romero - , National Institutes of Health (NIH) (Author)
  • Neshika Samarasekera - , University of Edinburgh (Author)
  • Julie A. Schneider - , Rush University (Author)
  • Stefanie Schreiber - , Otto von Guericke University Magdeburg (Author)
  • Frank Schreiber - , Otto von Guericke University Magdeburg (Author)
  • Corentin Schwall - , GHU Paris Psychiatrie & Neuro sciences (Author)
  • Colin Smith - , University of Edinburgh (Author)
  • Levente Szalardy - , University of Szeged (Author)
  • Pascale Varlet - , GHU Paris Psychiatrie & Neuro sciences (Author)
  • Alain Viguier - , Center Hospitalo-Universitaire (CHU) de Toulouse (Author)
  • Joanna M. Wardlaw - , University of Edinburgh (Author)
  • Andrew Warren - , Harvard University (Author)
  • Frank A. Wollenweber - , Ludwig Maximilian University of Munich, Dr. Horst Schmidt Klinik GmbH (Author)
  • Marialuisa Zedde - , IRCCS Azienda Unità Sanitaria Locale di Reggio Emilia (Author)
  • Mark A. van Buchem - , Leiden University (Author)
  • M. Edip Gurol - , Harvard University (Author)

Abstract

Background: Cerebral amyloid angiopathy (CAA) is an age-related small vessel disease, characterised pathologically by progressive deposition of amyloid β in the cerebrovascular wall. The Boston criteria are used worldwide for the in-vivo diagnosis of CAA but have not been updated since 2010, before the emergence of additional MRI markers. We report an international collaborative study aiming to update and externally validate the Boston diagnostic criteria across the full spectrum of clinical CAA presentations. Methods: In this multicentre, hospital-based, retrospective, MRI and neuropathology diagnostic accuracy study, we did a retrospective analysis of clinical, radiological, and histopathological data available to sites participating in the International CAA Association to formulate updated Boston criteria and establish their diagnostic accuracy across different populations and clinical presentations. Ten North American and European academic medical centres identified patients aged 50 years and older with potential CAA-related clinical presentations (ie, spontaneous intracerebral haemorrhage, cognitive impairment, or transient focal neurological episodes), available brain MRI, and histopathological assessment for CAA diagnosis. MRI scans were centrally rated at Massachusetts General Hospital (Boston, MA, USA) for haemorrhagic and non-haemorrhagic CAA markers, and brain tissue samples were rated by neuropathologists at the contributing sites. We derived the Boston criteria version 2.0 (v2.0) by selecting MRI features to optimise diagnostic specificity and sensitivity in a prespecified derivation cohort (Boston cases 1994–2012, n=159), then externally validated the criteria in a prespecified temporal validation cohort (Boston cases 2012–18, n=59) and a geographical validation cohort (non-Boston cases 2004–18; n=123), comparing accuracy of the new criteria to the currently used modified Boston criteria with histopathological assessment of CAA as the diagnostic standard. We also assessed performance of the v2.0 criteria in patients across all cohorts who had the diagnostic gold standard of brain autopsy. Findings: The study protocol was finalised on Jan 15, 2017, patient identification was completed on Dec 31, 2018, and imaging analyses were completed on Sept 30, 2019. Of 401 potentially eligible patients presenting to Massachusetts General Hospital, 218 were eligible to be included in the analysis; of 160 patient datasets from other centres, 123 were included. Using the derivation cohort, we derived provisional criteria for probable CAA requiring the presence of at least two strictly lobar haemorrhagic lesions (ie, intracerebral haemorrhages, cerebral microbleeds, or foci of cortical superficial siderosis) or at least one strictly lobar haemorrhagic lesion and at least one white matter characteristic (ie, severe visible perivascular spaces in centrum semiovale or white matter hyperintensities in a multispot pattern). The sensitivity and specificity of these criteria were 74·8% (95% CI 65·4–82·7) and 84·6% (71·9–93·1) in the derivation cohort, 92·5% (79·6–98·4) and 89·5% (66·9–98·7) in the temporal validation cohort, 80·2% (70·8–87·6) and 81·5% (61·9–93·7) in the geographical validation cohort, and 74·5% (65·4–82·4) and 95·0% (83·1–99·4) in all patients who had autopsy as the diagnostic standard. The area under the receiver operating characteristic curve (AUC) was 0·797 (0·732–0·861) in the derivation cohort, 0·910 (0·828–0·992) in the temporal validation cohort, 0·808 (0·724–0·893) in the geographical validation cohort, and 0·848 (0·794–0·901) in patients who had autopsy as the diagnostic standard. The v2.0 Boston criteria for probable CAA had superior accuracy to the current Boston criteria (sensitivity 64·5% [54·9–73·4]; specificity 95·0% [83·1–99·4]; AUC 0·798 [0·741–0854]; p=0·0005 for comparison of AUC) across all individuals who had autopsy as the diagnostic standard. Interpretation: The Boston criteria v2.0 incorporate emerging MRI markers of CAA to enhance sensitivity without compromising their specificity in our cohorts of patients aged 50 years and older presenting with spontaneous intracerebral haemorrhage, cognitive impairment, or transient focal neurological episodes. Future studies will be needed to determine generalisability of the v.2.0 criteria across the full range of patients and clinical presentations. Funding: US National Institutes of Health (R01 AG26484).

Details

Original languageEnglish
Pages (from-to)714-725
Number of pages12
JournalThe Lancet Neurology
Volume21
Issue number8
Publication statusPublished - Aug 2022
Peer-reviewedYes

External IDs

PubMed 35841910

Keywords

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