Cortical superficial siderosis: Prevalence and biomarker profile in a memory clinic population

Neurology. 2016 Sep 13;87(11):1110-7. doi: 10.1212/WNL.0000000000003088. Epub 2016 Aug 17.

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.

MeSH terms

  • Aged
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Apolipoproteins E / genetics
  • Biomarkers / cerebrospinal fluid
  • Brain / diagnostic imaging*
  • Cerebral Amyloid Angiopathy / cerebrospinal fluid
  • Cerebral Amyloid Angiopathy / diagnostic imaging*
  • Cerebral Amyloid Angiopathy / epidemiology*
  • Cerebral Amyloid Angiopathy / genetics
  • Cross-Sectional Studies
  • Female
  • Humans
  • Logistic Models
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Peptide Fragments / cerebrospinal fluid
  • Phosphorylation
  • Prevalence
  • Serum Albumin / metabolism
  • tau Proteins / cerebrospinal fluid

Substances

  • Amyloid beta-Peptides
  • Apolipoproteins E
  • Biomarkers
  • MAPT protein, human
  • Peptide Fragments
  • Serum Albumin
  • amyloid beta-protein (1-42)
  • tau Proteins