title: Cortical superficial siderosis: Prevalence and biomarker profile in a memory clinic population.
abstract: OBJECTIVE
  To gain further insight into cortical superficial siderosis (cSS), a new hemorrhagic neuroimaging marker of cerebral amyloid angiopathy (CAA), and to investigate the clinical, neuroimaging, genetic, and CSF biomarker profile of cSS in a large, consecutive memory clinic series.
  
  
  METHODS
  We included 1,504 memory clinic patients undergoing dementia investigation including a brain MRI in our center. Routine CSF biomarker analysis was performed in 1,039 patients and APOE genotyping in 520 patients. MRIs were systematically evaluated for presumed marker of small vessel disease: cSS, cerebral microbleeds, enlarged perivascular spaces, white matter hyperintensities, and lacunes.
  
  
  RESULTS
  cSS was detected in 40 patients (2.7%; 95% confidence interval [CI] 1.9-3.6); cSS was focal in 33 cases (2.2%; 95% CI 1.5-3.1) and disseminated in 7 (0.5%; 95% CI 0.2-1). Vascular dementia had the highest cSS prevalence (13%; 95% CI 5.4-24.9), followed by Alzheimer disease (5%; 95% CI 3.1-7.5). The most commonly affected area was the occipital lobe (70%; 95% CI 53.5-83.4). cSS was associated with lobar cerebral microbleeds (odds ratio [OR] 7.9; 95% CI 3.4-18.1; p < 0.001), high-degree centrum semiovale perivascular spaces (OR 1.7; 95% CI 1.2-2.6; p = 0.008), and white matter hyperintensities (OR 1.5; 95% CI 1.0-2.2; p = 0.062). APOE ε4/4 genotype was more common in cSS cases compared to those without. CSF β-amyloid 42 was lower in patients with cSS (coefficient -0.09; 95% CI -0.15 to -0.03; p = 0.004).
  
  
  CONCLUSIONS
  Our large series of memory clinic patients provides evidence that cSS is related to cerebrovascular disease and may be a manifestation of severe CAA, even in patients without intracerebral hemorrhage.
authors.affiliation: From the Department of Clinical Science, Intervention, and Technology, Division of Medical Imaging and Technology (S.S., J.M., L.C., T.G., M.S., Y.F., P.A., M.K.-W.), and Department of Neurobiology, Care Sciences, and Society (L.-O.W.), Karolinska Institutet; Department of Radiology (S.S., J.M., L.C., T.G., M.S., Y.F., P.A., M.K.-W.) and Division of Clinical Geriatrics (L.-O.W.), Karolinska University Hospital, Stockholm, Sweden; and Hemorrhagic Stroke Research Program (A.C.), Department of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston. sara.shams@ki.se.
authors.forename: Sara
authors.initials: S
authors.lastname: Shams
authors.affiliation: From the Department of Clinical Science, Intervention, and Technology, Division of Medical Imaging and Technology (S.S., J.M., L.C., T.G., M.S., Y.F., P.A., M.K.-W.), and Department of Neurobiology, Care Sciences, and Society (L.-O.W.), Karolinska Institutet; Department of Radiology (S.S., J.M., L.C., T.G., M.S., Y.F., P.A., M.K.-W.) and Division of Clinical Geriatrics (L.-O.W.), Karolinska University Hospital, Stockholm, Sweden; and Hemorrhagic Stroke Research Program (A.C.), Department of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston.
authors.forename: Juha
authors.initials: J
authors.lastname: Martola
authors.affiliation: From the Department of Clinical Science, Intervention, and Technology, Division of Medical Imaging and Technology (S.S., J.M., L.C., T.G., M.S., Y.F., P.A., M.K.-W.), and Department of Neurobiology, Care Sciences, and Society (L.-O.W.), Karolinska Institutet; Department of Radiology (S.S., J.M., L.C., T.G., M.S., Y.F., P.A., M.K.-W.) and Division of Clinical Geriatrics (L.-O.W.), Karolinska University Hospital, Stockholm, Sweden; and Hemorrhagic Stroke Research Program (A.C.), Department of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston.
authors.forename: Andreas
authors.initials: A
authors.lastname: Charidimou
authors.affiliation: From the Department of Clinical Science, Intervention, and Technology, Division of Medical Imaging and Technology (S.S., J.M., L.C., T.G., M.S., Y.F., P.A., M.K.-W.), and Department of Neurobiology, Care Sciences, and Society (L.-O.W.), Karolinska Institutet; Department of Radiology (S.S., J.M., L.C., T.G., M.S., Y.F., P.A., M.K.-W.) and Division of Clinical Geriatrics (L.-O.W.), Karolinska University Hospital, Stockholm, Sweden; and Hemorrhagic Stroke Research Program (A.C.), Department of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston.
authors.forename: Lena
authors.initials: L
authors.lastname: Cavallin
authors.affiliation: From the Department of Clinical Science, Intervention, and Technology, Division of Medical Imaging and Technology (S.S., J.M., L.C., T.G., M.S., Y.F., P.A., M.K.-W.), and Department of Neurobiology, Care Sciences, and Society (L.-O.W.), Karolinska Institutet; Department of Radiology (S.S., J.M., L.C., T.G., M.S., Y.F., P.A., M.K.-W.) and Division of Clinical Geriatrics (L.-O.W.), Karolinska University Hospital, Stockholm, Sweden; and Hemorrhagic Stroke Research Program (A.C.), Department of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston.
authors.forename: Tobias
authors.initials: T
authors.lastname: Granberg
authors.affiliation: From the Department of Clinical Science, Intervention, and Technology, Division of Medical Imaging and Technology (S.S., J.M., L.C., T.G., M.S., Y.F., P.A., M.K.-W.), and Department of Neurobiology, Care Sciences, and Society (L.-O.W.), Karolinska Institutet; Department of Radiology (S.S., J.M., L.C., T.G., M.S., Y.F., P.A., M.K.-W.) and Division of Clinical Geriatrics (L.-O.W.), Karolinska University Hospital, Stockholm, Sweden; and Hemorrhagic Stroke Research Program (A.C.), Department of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston.
authors.forename: Mana
authors.initials: M
authors.lastname: Shams
authors.affiliation: From the Department of Clinical Science, Intervention, and Technology, Division of Medical Imaging and Technology (S.S., J.M., L.C., T.G., M.S., Y.F., P.A., M.K.-W.), and Department of Neurobiology, Care Sciences, and Society (L.-O.W.), Karolinska Institutet; Department of Radiology (S.S., J.M., L.C., T.G., M.S., Y.F., P.A., M.K.-W.) and Division of Clinical Geriatrics (L.-O.W.), Karolinska University Hospital, Stockholm, Sweden; and Hemorrhagic Stroke Research Program (A.C.), Department of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston.
authors.forename: Yngve
authors.initials: Y
authors.lastname: Forslin
authors.affiliation: From the Department of Clinical Science, Intervention, and Technology, Division of Medical Imaging and Technology (S.S., J.M., L.C., T.G., M.S., Y.F., P.A., M.K.-W.), and Department of Neurobiology, Care Sciences, and Society (L.-O.W.), Karolinska Institutet; Department of Radiology (S.S., J.M., L.C., T.G., M.S., Y.F., P.A., M.K.-W.) and Division of Clinical Geriatrics (L.-O.W.), Karolinska University Hospital, Stockholm, Sweden; and Hemorrhagic Stroke Research Program (A.C.), Department of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston.
authors.forename: Peter
authors.initials: P
authors.lastname: Aspelin
authors.affiliation: From the Department of Clinical Science, Intervention, and Technology, Division of Medical Imaging and Technology (S.S., J.M., L.C., T.G., M.S., Y.F., P.A., M.K.-W.), and Department of Neurobiology, Care Sciences, and Society (L.-O.W.), Karolinska Institutet; Department of Radiology (S.S., J.M., L.C., T.G., M.S., Y.F., P.A., M.K.-W.) and Division of Clinical Geriatrics (L.-O.W.), Karolinska University Hospital, Stockholm, Sweden; and Hemorrhagic Stroke Research Program (A.C.), Department of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston.
authors.forename: Maria
authors.initials: M
authors.lastname: Kristoffersen-Wiberg
authors.affiliation: From the Department of Clinical Science, Intervention, and Technology, Division of Medical Imaging and Technology (S.S., J.M., L.C., T.G., M.S., Y.F., P.A., M.K.-W.), and Department of Neurobiology, Care Sciences, and Society (L.-O.W.), Karolinska Institutet; Department of Radiology (S.S., J.M., L.C., T.G., M.S., Y.F., P.A., M.K.-W.) and Division of Clinical Geriatrics (L.-O.W.), Karolinska University Hospital, Stockholm, Sweden; and Hemorrhagic Stroke Research Program (A.C.), Department of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston.
authors.forename: Lars-Olof
authors.initials: LO
authors.lastname: Wahlund
mesh_terms: D000368:Aged; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D001057:Apolipoproteins E / Q000235:genetics; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001921:Brain / Q000000981:diagnostic imaging*; D016657:Cerebral Amyloid Angiopathy / Q000134:cerebrospinal fluid / Q000000981:diagnostic imaging* / Q000453:epidemiology* / Q000235:genetics; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D016015:Logistic Models; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D010766:Phosphorylation; D015995:Prevalence; D012709:Serum Albumin / Q000378:metabolism; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D015415:Biomarkers; C054369:MAPT protein, human; D010446:Peptide Fragments; D012709:Serum Albumin; C075222:amyloid beta-protein (1-42); D016875:tau Proteins