title: Small vessel disease burden in cerebral amyloid angiopathy without symptomatic hemorrhage.
abstract: OBJECTIVE
  Cerebral amyloid angiopathy (CAA) is a common age-related small vessel disease (SVD). Patients without intracerebral hemorrhage (ICH) typically present with transient focal neurologic episodes (TFNEs) or cognitive symptoms. We sought to determine if SVD lesion burden differed between patients with CAA first presenting with TFNEs vs cognitive symptoms.
  
  
  METHODS
  A total of 647 patients presenting either to a stroke department (n = 205) or an outpatient memory clinic (n = 442) were screened for eligibility. Patients meeting modified Boston criteria for probable CAA were included and markers of SVD were quantified, including cerebral microbleeds (CMBs), perivascular spaces, cortical superficial siderosis (cSS), and white matter hyperintensities (WMHs). Patients were classified according to presentation symptoms (TFNEs vs cognitive). Total CAA-SVD burden was assessed using a validated summary score. Individual neuroimaging markers and total SVD burden were compared between groups using univariable and multivariable models.
  
  
  RESULTS
  There were 261 patients with probable CAA included. After adjustment for confounders, patients first seen for TFNEs (n = 97) demonstrated a higher prevalence of cSS (p< 0.0001), higher WMH volumes (p= 0.03), and a trend toward higher CMB counts (p= 0.09). The total SVD summary score was higher in patients seen for TFNEs (adjusted odds ratio per additional score point 1.46, 95% confidence interval 1.16-1.84,p= 0.013).
  
  
  CONCLUSIONS
  Patients with probable CAA without ICH first evaluated for TFNEs bear a higher burden of structural MRI SVD-related damage compared to those first seen for cognitive symptoms. This study sheds light on neuroimaging profile differences across clinical phenotypes of patients with CAA without ICH.
authors.affiliation: From the Hemorrhagic Stroke Research Program, Department of Neurology, Massachusetts General Hospital Stroke Research Center (G.B., A.C., M.J.J., L.X., D.R., P.F., M.P., A.A., K.M.S., J.R., M.E.G., S.M.G., A.V.), MIND Informatics, Massachusetts General Hospital Biomedical Informatics Core (M.E.M., J.R.), and Division of Neurocritical Care and Emergency Neurology, Massachusetts General Hospital (J.R.), Harvard Medical School, Boston, MA; Neuroradiology Department (G.B.), Université Paris Descartes, INSERM S894, Centre Hospitalier Sainte-Anne, Paris, France; and Faculty of Medicine (D.R.), Naresuan University, Phitsanulok, Thailand. gboulouis@mgh.harvard.edu.
authors.forename: Gregoire
authors.initials: G
authors.lastname: Boulouis
authors.affiliation: From the Hemorrhagic Stroke Research Program, Department of Neurology, Massachusetts General Hospital Stroke Research Center (G.B., A.C., M.J.J., L.X., D.R., P.F., M.P., A.A., K.M.S., J.R., M.E.G., S.M.G., A.V.), MIND Informatics, Massachusetts General Hospital Biomedical Informatics Core (M.E.M., J.R.), and Division of Neurocritical Care and Emergency Neurology, Massachusetts General Hospital (J.R.), Harvard Medical School, Boston, MA; Neuroradiology Department (G.B.), Université Paris Descartes, INSERM S894, Centre Hospitalier Sainte-Anne, Paris, France; and Faculty of Medicine (D.R.), Naresuan University, Phitsanulok, Thailand.
authors.forename: Andreas
authors.initials: A
authors.lastname: Charidimou
authors.affiliation: From the Hemorrhagic Stroke Research Program, Department of Neurology, Massachusetts General Hospital Stroke Research Center (G.B., A.C., M.J.J., L.X., D.R., P.F., M.P., A.A., K.M.S., J.R., M.E.G., S.M.G., A.V.), MIND Informatics, Massachusetts General Hospital Biomedical Informatics Core (M.E.M., J.R.), and Division of Neurocritical Care and Emergency Neurology, Massachusetts General Hospital (J.R.), Harvard Medical School, Boston, MA; Neuroradiology Department (G.B.), Université Paris Descartes, INSERM S894, Centre Hospitalier Sainte-Anne, Paris, France; and Faculty of Medicine (D.R.), Naresuan University, Phitsanulok, Thailand.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Jessel
authors.affiliation: From the Hemorrhagic Stroke Research Program, Department of Neurology, Massachusetts General Hospital Stroke Research Center (G.B., A.C., M.J.J., L.X., D.R., P.F., M.P., A.A., K.M.S., J.R., M.E.G., S.M.G., A.V.), MIND Informatics, Massachusetts General Hospital Biomedical Informatics Core (M.E.M., J.R.), and Division of Neurocritical Care and Emergency Neurology, Massachusetts General Hospital (J.R.), Harvard Medical School, Boston, MA; Neuroradiology Department (G.B.), Université Paris Descartes, INSERM S894, Centre Hospitalier Sainte-Anne, Paris, France; and Faculty of Medicine (D.R.), Naresuan University, Phitsanulok, Thailand.
authors.forename: Li
authors.initials: L
authors.lastname: Xiong
authors.affiliation: From the Hemorrhagic Stroke Research Program, Department of Neurology, Massachusetts General Hospital Stroke Research Center (G.B., A.C., M.J.J., L.X., D.R., P.F., M.P., A.A., K.M.S., J.R., M.E.G., S.M.G., A.V.), MIND Informatics, Massachusetts General Hospital Biomedical Informatics Core (M.E.M., J.R.), and Division of Neurocritical Care and Emergency Neurology, Massachusetts General Hospital (J.R.), Harvard Medical School, Boston, MA; Neuroradiology Department (G.B.), Université Paris Descartes, INSERM S894, Centre Hospitalier Sainte-Anne, Paris, France; and Faculty of Medicine (D.R.), Naresuan University, Phitsanulok, Thailand.
authors.forename: Duangnapa
authors.initials: D
authors.lastname: Roongpiboonsopit
authors.affiliation: From the Hemorrhagic Stroke Research Program, Department of Neurology, Massachusetts General Hospital Stroke Research Center (G.B., A.C., M.J.J., L.X., D.R., P.F., M.P., A.A., K.M.S., J.R., M.E.G., S.M.G., A.V.), MIND Informatics, Massachusetts General Hospital Biomedical Informatics Core (M.E.M., J.R.), and Division of Neurocritical Care and Emergency Neurology, Massachusetts General Hospital (J.R.), Harvard Medical School, Boston, MA; Neuroradiology Department (G.B.), Université Paris Descartes, INSERM S894, Centre Hospitalier Sainte-Anne, Paris, France; and Faculty of Medicine (D.R.), Naresuan University, Phitsanulok, Thailand.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Fotiadis
authors.affiliation: From the Hemorrhagic Stroke Research Program, Department of Neurology, Massachusetts General Hospital Stroke Research Center (G.B., A.C., M.J.J., L.X., D.R., P.F., M.P., A.A., K.M.S., J.R., M.E.G., S.M.G., A.V.), MIND Informatics, Massachusetts General Hospital Biomedical Informatics Core (M.E.M., J.R.), and Division of Neurocritical Care and Emergency Neurology, Massachusetts General Hospital (J.R.), Harvard Medical School, Boston, MA; Neuroradiology Department (G.B.), Université Paris Descartes, INSERM S894, Centre Hospitalier Sainte-Anne, Paris, France; and Faculty of Medicine (D.R.), Naresuan University, Phitsanulok, Thailand.
authors.forename: Marco
authors.initials: M
authors.lastname: Pasi
authors.affiliation: From the Hemorrhagic Stroke Research Program, Department of Neurology, Massachusetts General Hospital Stroke Research Center (G.B., A.C., M.J.J., L.X., D.R., P.F., M.P., A.A., K.M.S., J.R., M.E.G., S.M.G., A.V.), MIND Informatics, Massachusetts General Hospital Biomedical Informatics Core (M.E.M., J.R.), and Division of Neurocritical Care and Emergency Neurology, Massachusetts General Hospital (J.R.), Harvard Medical School, Boston, MA; Neuroradiology Department (G.B.), Université Paris Descartes, INSERM S894, Centre Hospitalier Sainte-Anne, Paris, France; and Faculty of Medicine (D.R.), Naresuan University, Phitsanulok, Thailand.
authors.forename: Alison
authors.initials: A
authors.lastname: Ayres
authors.affiliation: From the Hemorrhagic Stroke Research Program, Department of Neurology, Massachusetts General Hospital Stroke Research Center (G.B., A.C., M.J.J., L.X., D.R., P.F., M.P., A.A., K.M.S., J.R., M.E.G., S.M.G., A.V.), MIND Informatics, Massachusetts General Hospital Biomedical Informatics Core (M.E.M., J.R.), and Division of Neurocritical Care and Emergency Neurology, Massachusetts General Hospital (J.R.), Harvard Medical School, Boston, MA; Neuroradiology Department (G.B.), Université Paris Descartes, INSERM S894, Centre Hospitalier Sainte-Anne, Paris, France; and Faculty of Medicine (D.R.), Naresuan University, Phitsanulok, Thailand.
authors.forename: M Emily
authors.initials: ME
authors.lastname: Merrill
authors.affiliation: From the Hemorrhagic Stroke Research Program, Department of Neurology, Massachusetts General Hospital Stroke Research Center (G.B., A.C., M.J.J., L.X., D.R., P.F., M.P., A.A., K.M.S., J.R., M.E.G., S.M.G., A.V.), MIND Informatics, Massachusetts General Hospital Biomedical Informatics Core (M.E.M., J.R.), and Division of Neurocritical Care and Emergency Neurology, Massachusetts General Hospital (J.R.), Harvard Medical School, Boston, MA; Neuroradiology Department (G.B.), Université Paris Descartes, INSERM S894, Centre Hospitalier Sainte-Anne, Paris, France; and Faculty of Medicine (D.R.), Naresuan University, Phitsanulok, Thailand.
authors.forename: Kristin M
authors.initials: KM
authors.lastname: Schwab
authors.affiliation: From the Hemorrhagic Stroke Research Program, Department of Neurology, Massachusetts General Hospital Stroke Research Center (G.B., A.C., M.J.J., L.X., D.R., P.F., M.P., A.A., K.M.S., J.R., M.E.G., S.M.G., A.V.), MIND Informatics, Massachusetts General Hospital Biomedical Informatics Core (M.E.M., J.R.), and Division of Neurocritical Care and Emergency Neurology, Massachusetts General Hospital (J.R.), Harvard Medical School, Boston, MA; Neuroradiology Department (G.B.), Université Paris Descartes, INSERM S894, Centre Hospitalier Sainte-Anne, Paris, France; and Faculty of Medicine (D.R.), Naresuan University, Phitsanulok, Thailand.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Rosand
authors.affiliation: From the Hemorrhagic Stroke Research Program, Department of Neurology, Massachusetts General Hospital Stroke Research Center (G.B., A.C., M.J.J., L.X., D.R., P.F., M.P., A.A., K.M.S., J.R., M.E.G., S.M.G., A.V.), MIND Informatics, Massachusetts General Hospital Biomedical Informatics Core (M.E.M., J.R.), and Division of Neurocritical Care and Emergency Neurology, Massachusetts General Hospital (J.R.), Harvard Medical School, Boston, MA; Neuroradiology Department (G.B.), Université Paris Descartes, INSERM S894, Centre Hospitalier Sainte-Anne, Paris, France; and Faculty of Medicine (D.R.), Naresuan University, Phitsanulok, Thailand.
authors.forename: M Edip
authors.initials: ME
authors.lastname: Gurol
authors.affiliation: From the Hemorrhagic Stroke Research Program, Department of Neurology, Massachusetts General Hospital Stroke Research Center (G.B., A.C., M.J.J., L.X., D.R., P.F., M.P., A.A., K.M.S., J.R., M.E.G., S.M.G., A.V.), MIND Informatics, Massachusetts General Hospital Biomedical Informatics Core (M.E.M., J.R.), and Division of Neurocritical Care and Emergency Neurology, Massachusetts General Hospital (J.R.), Harvard Medical School, Boston, MA; Neuroradiology Department (G.B.), Université Paris Descartes, INSERM S894, Centre Hospitalier Sainte-Anne, Paris, France; and Faculty of Medicine (D.R.), Naresuan University, Phitsanulok, Thailand.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Greenberg
authors.affiliation: From the Hemorrhagic Stroke Research Program, Department of Neurology, Massachusetts General Hospital Stroke Research Center (G.B., A.C., M.J.J., L.X., D.R., P.F., M.P., A.A., K.M.S., J.R., M.E.G., S.M.G., A.V.), MIND Informatics, Massachusetts General Hospital Biomedical Informatics Core (M.E.M., J.R.), and Division of Neurocritical Care and Emergency Neurology, Massachusetts General Hospital (J.R.), Harvard Medical School, Boston, MA; Neuroradiology Department (G.B.), Université Paris Descartes, INSERM S894, Centre Hospitalier Sainte-Anne, Paris, France; and Faculty of Medicine (D.R.), Naresuan University, Phitsanulok, Thailand.
authors.forename: Anand
authors.initials: A
authors.lastname: Viswanathan
mesh_terms: D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging*; D016657:Cerebral Amyloid Angiopathy / Q000150:complications* / Q000175:diagnosis / Q000453:epidemiology / Q000523:psychology; D002543:Cerebral Hemorrhage / Q000150:complications* / Q000175:diagnosis / Q000453:epidemiology / Q000523:psychology; D059345:Cerebral Small Vessel Diseases / Q000150:complications* / Q000175:diagnosis / Q000453:epidemiology / Q000523:psychology; D003072:Cognition Disorders / Q000150:complications / Q000175:diagnosis / Q000453:epidemiology; D017281:Cost of Illness; D005260:Female; D006801:Humans; D016015:Logistic Models; D008279:Magnetic Resonance Imaging; D008297:Male; D015999:Multivariate Analysis; D015995:Prevalence; D011446:Prospective Studies; D012189:Retrospective Studies; D012720:Severity of Illness Index; D066127:White Matter / Q000000981:diagnostic imaging