title: Pathogenesis of cerebral microbleeds: In vivo imaging of amyloid and subcortical ischemic small vessel disease in 226 individuals with cognitive impairment.
abstract: OBJECTIVE
  Cerebral microbleeds (CMBs) are a neuroimaging marker of small vessel disease (SVD) with relevance for understanding disease mechanisms in cerebrovascular disease, cognitive impairment, and normal aging. It is hypothesized that lobar CMBs are due to cerebral amyloid angiopathy (CAA) and deep CMBs are due to subcortical ischemic SVD. We tested this hypothesis using structural magnetic resonance imaging (MRI) markers of subcortical SVD and in vivo imaging of amyloid in patients with cognitive impairment.
  
  
  METHODS
  We included 226 patients: 89 with Alzheimer disease-related cognitive impairment (ADCI) and 137 with subcortical vascular cognitive impairment (SVCI). All subjects underwent amyloid imaging with [(11) C] Pittsburgh compound B (PiB) positron emission tomography, and MRI to detect CMBs and markers of subcortical SVD, including the volume of white matter hyperintensities (WMH) and the number of lacunes.
  
  
  RESULTS
  Parietal and occipital lobar CMBs counts were higher in PiB(+) ADCI with moderate WMH than PiB(+) ADCI with minimal WMH, whereas PiB(-) patients with SVCI (ie, "pure" SVCI) showed both lobar and deep CMBs. In multivariate analyses of the whole cohort, WMH volume and lacuna counts were positively associated with both lobar and deep CMBs, whereas amyloid burden (PiB) was only associated with lobar CMBs. There was an interaction between lacuna burden and PiB retention on lobar (but not deep) CMBs (p<0.001).
  
  
  CONCLUSIONS
  Our findings suggest that although deep CMBs are mainly linked to subcortical SVD, both subcortical SVD and amyloid-related pathologies (eg, CAA) contribute to the pathogenesis of lobar CMBs, at least in subjects with mixed lobar and deep CMBs. Furthermore, subcortical SVD and amyloid-related pathologies interact to increase the risk of lobar CMBs.
authors.affiliation: Department of Neurology, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Korea.
authors.forename: Jae-Hyun
authors.initials: JH
authors.lastname: Park
authors.forename: Sang Won
authors.initials: SW
authors.lastname: Seo
authors.forename: Changsoo
authors.initials: C
authors.lastname: Kim
authors.forename: Geon Ha
authors.initials: GH
authors.lastname: Kim
authors.forename: Hyun Jin
authors.initials: HJ
authors.lastname: Noh
authors.forename: Sung Tae
authors.initials: ST
authors.lastname: Kim
authors.forename: Ki-Chang
authors.initials: KC
authors.lastname: Kwak
authors.forename: Uicheul
authors.initials: U
authors.lastname: Yoon
authors.forename: Jong Min
authors.initials: JM
authors.lastname: Lee
authors.forename: Jong Weon
authors.initials: JW
authors.lastname: Lee
authors.forename: Ji Soo
authors.initials: JS
authors.lastname: Shin
authors.forename: Chi Hun
authors.initials: CH
authors.lastname: Kim
authors.forename: Young
authors.initials: Y
authors.lastname: Noh
authors.forename: Hanna
authors.initials: H
authors.lastname: Cho
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Cindy W
authors.initials: CW
authors.lastname: Yoon
authors.forename: Seung Jun
authors.initials: SJ
authors.lastname: Oh
authors.forename: Jae Seung
authors.initials: JS
authors.lastname: Kim
authors.forename: Yearn Seong
authors.initials: YS
authors.lastname: Choe
authors.forename: Kyung-Han
authors.initials: KH
authors.lastname: Lee
authors.forename: Jae-Hong
authors.initials: JH
authors.lastname: Lee
authors.forename: Michael
authors.initials: M
authors.lastname: Ewers
authors.forename: Michael W
authors.initials: MW
authors.lastname: Weiner
authors.forename: David J
authors.initials: DJ
authors.lastname: Werring
authors.forename: Duk L
authors.initials: DL
authors.lastname: Na
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications* / Q000000981:diagnostic imaging; D000682:Amyloid / Q000378:metabolism*; D000814:Aniline Compounds; D016657:Cerebral Amyloid Angiopathy; D002543:Cerebral Hemorrhage / Q000000981:diagnostic imaging* / Q000209:etiology*; D003072:Cognition Disorders / Q000000981:diagnostic imaging / Q000209:etiology*; D005260:Female; D006801:Humans; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D059409:Stroke, Lacunar / Q000000981:diagnostic imaging / Q000473:pathology; D013844:Thiazoles
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D000682:Amyloid; D000814:Aniline Compounds; D013844:Thiazoles