World Stroke Organization The Paper of The Month – September
25 Sep 2025Cerebral Amyloid Angiopathy: A Practice-Facing Statement from the International CAA Association and the World Stroke Organization
Cerebral Amyloid Angiopathy: A Practice-Facing Statement from the International CAA Association and the World Stroke Organization
Prof. Octavio Marques Pontes-Neto, MD, PhD – Editor-in-Chief, World Stroke Academy
This article is a commentary on the following: Diagnosis and management of cerebral amyloid angiopathy: a scientific statement from the International CAA Association and the World Stroke Organization. Int J Stroke. 2025 Oct;20(8):949-967. doi: 10.1177/17474930251365861. Epub 2025 Jul 28. PMID: 40721902.
Commentary:
Cerebral amyloid angiopathy (CAA) is an increasingly common cause of lobar intracerebral hemorrhage (ICH), convexity subarachnoid hemorrhage (cSAH), transient focal neurological episodes (TFNEs), and cognitive decline in aging populations. A new scientific statement recently published on the Internatitonal Journal of Stroke and jointly issued by the International CAA Association and the World Stroke Organization provides a consolidated, practice-oriented roadmap that spans diagnosis, risk prediction, antithrombotic decision-making, vascular risk management, treatment of clinical manifestations, and the recognition and management of CAA-related inflammation (CAA-ri). It is an expert consensus grounded in the best available evidence, designed to standardize care while acknowledging areas where data remain limited.
On diagnosis, the statement places MRI, particularly susceptibility-sensitive sequences, at the center of clinical evaluation and endorses the Boston Criteria version 2.0 as the primary noninvasive framework for probable CAA. Importantly, Boston v2.0 incorporates not only hemorrhagic markers (lobar microbleeds, cortical superficial siderosis) but also specific non-hemorrhagic MRI features (centrum semiovale enlarged perivascular spaces and a “multispot” pattern of white-matter hyperintensities), allowing earlier identification along the disease spectrum. When MRI is not feasible after lobar ICH, simplified Edinburgh criteria based on CT features can aid diagnosis. The document cautions that while amyloid biomarkers (CSF Aβ, amyloid-PET) show promise, routine use is not yet recommended; rather, their role is reserved for atypical cases in which Boston criteria cannot be applied or competing etiologies need adjudication.
Risk prediction is framed around imaging phenotype more than any single clinical variable. Disseminated cortical superficial siderosis emerges as the strongest predictor of future hemorrhage, while “probable CAA with microbleeds alone” appears to confer the lowest subsequent ICH risk among CAA phenotypes. The statement underscores the absence of validated multivariable models for individualized risk and encourages clinicians to weigh cSS patterning, prior hemorrhage burden, and overall phenotype when counseling patients. This imaging-led stratification not only guides prognosis but also underpins the nuanced antithrombotic recommendations that follow.
Antithrombotic guidance is deliberately individualized. Antiplatelets are not advised for primary prevention in probable CAA. For secondary prevention when there is a clear ischemic indication and no history of CAA-related ICH or disseminated cSS, antiplatelet or anticoagulant therapy may be reasonable, with careful appraisal of net clinical benefit. After CAA-related ICH, antiplatelet monotherapy can be considered in selected patients; anticoagulation for atrial fibrillation remains uncertain, and if chosen, a DOAC is preferred over a vitamin K antagonist, with left atrial appendage closure as a possible, but as yet unproven, alternative. In acute ischemic stroke due to large-vessel occlusion, the statement favors thrombectomy without intravenous thrombolysis in probable CAA, while allowing case-by-case consideration of thrombolysis when EVT is not an option and there is no prior ICH.
Beyond antithrombotics, the statement elevates vascular risk management as a central pillar of care. Long-term blood pressure control to ≤130/80 mm Hg is recommended to lower recurrence risk, with home monitoring encouraged to reduce variability and improve adherence. Evidence around lipid-lowering therapies and SSRI use remains inconclusive in CAA; decisions should reflect the strength of the cardiovascular indication, while chronic NSAID use should be avoided given hemorrhagic risk. For clinical manifestations, TFNEs warrant vigilant recognition, especially when associated with cSAH/cSS, prompt blood pressure management aligned with ICH care, short-term antiseizure therapy in distressing recurrent episodes, and strict avoidance of antithrombotics in the acute phase. The statement also addresses the growing interface with anti–β-amyloid immunotherapies in Alzheimer’s disease, advising against their use for CAA itself and highlighting heightened ARIA risk in patients with prior ICH, multiple microbleeds, or cSS.
Finally, the consensus devotes a dedicated section to CAA-related inflammation (CAA-ri), advocating early recognition through characteristic clinical–radiologic patterns, structured MRI protocols, CSF testing to exclude mimics, and timely immunosuppression with corticosteroids (with escalation to steroid-sparing agents in relapsing or refractory disease). Across the document, the authors repeatedly emphasize that recommendations are guides, strong where evidence is mature, weak where data are evolving, and should not replace clinical judgment. For a disorder that sits at the crossroads of stroke medicine, cognitive neurology, and neuroimmunology, this statement offers the most comprehensive, interdisciplinary framework to date, while clearly marking the urgent research agenda: robust risk models, therapeutic trials tailored to CAA phenotypes, and safer pathways for comorbid conditions that demand antithrombotic or anti-amyloid therapies.
References:
Cordonnier C, Klijn C, Smith EE, Al-Shahi Salman R, Chwalisz BK, van Etten E, Muir RT, Piazza F, Schreiber S, Schreuder FH, Selim M, Shoamanesh A, Viswanathan A, Wermer M, Zandi M, Charidimou A, Greenberg SM, Werring D. Diagnosis and management of cerebral amyloid angiopathy: a scientific statement from the International CAA Association and the World Stroke Organization. Int J Stroke. 2025 Oct;20(8):949-967. doi: 10.1177/17474930251365861. Epub 2025 Jul 28. PMID: 40721902.
Webinar coming soon in December:
WSO Scientific Statement Spotlight: Diagnosis and Management of Cerebral Amyloid Angiopathy (CAA)
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