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Review
The increasing impact of cerebral amyloid angiopathy: essential new insights for clinical practice

Abstract

Cerebral amyloid angiopathy (CAA) has never been more relevant. The last 5 years have seen a rapid increase in publications and research in the field, with the development of new biomarkers for the disease, thanks to advances in MRI, amyloid positron emission tomography and cerebrospinal fluid biomarker analysis. The inadvertent development of CAA-like pathology in patients treated with amyloid-beta immunotherapy for Alzheimer’s disease has highlighted the importance of establishing how and why CAA develops; without this information, the use of these treatments may be unnecessarily restricted. Our understanding of the clinical and radiological spectrum of CAA has continued to evolve, and there are new insights into the independent impact that CAA has on cognition in the context of ageing and intracerebral haemorrhage, as well as in Alzheimer’s and other dementias. While the association between CAA and lobar intracerebral haemorrhage (with its high recurrence risk) is now well recognised, a number of management dilemmas remain, particularly when considering the use of antithrombotics, anticoagulants and statins. The Boston criteria for CAA, in use in one form or another for the last 20 years, are now being reviewed to reflect these new wide-ranging clinical and radiological findings. This review aims to provide a 5-year update on these recent advances, as well as a look towards future directions for CAA research and clinical practice.

  • cerebrovascular disease
  • amyloid
  • stroke
  • vascular dementia
  • superficial siderosis

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/

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Footnotes

  • Contributors GB contributed to the design and compilation of the article, and contributed the following individual sections: Abstract, Introduction, Related developments in CAA: imaging, ARIA: friend or foe?, Impact and interaction of CAA in AD, Transient focal neurological episodes, Statins, Immunotherapy, The next five years? and Conclusions. RC contributed the section and figure on perivascular clearance, and to revision of the final manuscript. CC contributed to the section CAA: an increasingly recognised important cause of cognitive impairment, and to revision of the final manuscript. SMG contributed to the revision of the manuscript for important intellectual content. JAS contributed to the revision of the manuscript for important intellectual content. EES contributed the sections on CAA: an increasingly recognised important cause of cognitive impairment and the management of CAA patients with indications for antithrombotics or anticoagulants, as well as to the revision of the final manscript. MvB and JvdG contributed the section on Insights from hereditary cerebral haemorrhage with amyloidosis-Dutch type (HCHWA-D). MMV contributed the section on Body fluid biomarkers in sporadic CAA, and to the revision of the final manuscript. DJW contributed to the design of the article and the revision of the manuscript for important intellectual content.

  • Funding GB receives funding from the Rosetrees Trust. CC is a member of the Institut Universitaire de France. SMG receives funding from the National Institutes of Health. EES is supported by the Kathy Taylor Chair in Vascular Dementia of the University of Calgary. MMV was financially supported by the Internationale Stichting Alzheimer Onderzoek (projects 12 506 and 14502), the American Alzheimer Association (project IIRG-10-1 73 389), and the CAVIA project (nr. 733050202; www.caviaproject.nl), which has been made possible by ZonMW. The CAVIA project is part of ‘Memorabel’, the research and innovation programprogramme for dementia, as part of the Dutch national ‘Deltaplan for Dementia’: zonmw.nl/dementiaresearch. The CAVIA project is a consortium of Radboudumc, LUMC, Erasmus MC, VUmc, ADX Neurosciences, Philips Healthcare, Stony Brook University and Massachusetts General Hospital. DJW receives research support from the Stroke Association, the British Heart Foundation and the Rosetrees Trust. Part of this work was undertaken at UCLH/UCL, which receives a proportion of funding from the Department of Health’s National Institute for Health Research (NIHR) Biomedical Research Centres funding scheme.

  • Competing interests CC was investigator in clinical trials A9951024 for Pfizer, AstraZeneca and Daiichi-Sankyo, and participated in the scientific boards for Bayer and Medtronic. Fees were paid to ADRINORD or Lille University Hospital research account (no personal funding). SMG serves on safety review committees for immunotherapy trials conducted by Biogen and Hoffman-La Roche. Massachusetts General Hospital participated in the trial of ponezumab under a Clinical Research Support Agreement with Pfizer. DJW was UK chief investigator for A9951024 (Pfizer) and has received consultancy and lecture fees from Bayer.

  • Provenance and peer review Commissioned; externally peer reviewed.

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