title: Incidental Cerebral Microbleeds and Cerebral Blood Flow in Elderly Individuals.
abstract: OBJECTIVE
  Cerebral microbleeds (CMBs) are collections of blood breakdown products that are a common incidental finding in magnetic resonance imaging of elderly individuals. Cerebral microbleeds are associated with cognitive deficits, but the mechanism is unclear. Studies show that individuals with CMBs related to symptomatic cerebral amyloid angiopathy have abnormal vascular reactivity and cerebral blood flow (CBF), but, to our knowledge, abnormalities in cerebral blood flow have not been reported for healthy individuals with incidental CMBs.
  
  
  OBJECTIVE
  To evaluate the association of incidental CMBs with resting-state CBF, cerebral metabolism, cerebrovascular disease, β-amyloid (Aβ), and cognition.
  
  
  METHODS
  A cross-sectional study of 55 cognitively normal individuals with a mean (SD) age of 86.8 (2.7) years was conducted from May 1, 2010, to May 1, 2013, in an academic medical center in Pittsburgh; data analysis was performed between June 10, 2013, and April 9, 2015.
  
  
  METHODS
  3-Tesla magnetic resonance imaging was performed with susceptibility-weighted imaging or gradient-recalled echo to assess CMBs, arterial spin labeling for CBF, and T1- and T2-weighted imaging for atrophy, white matter hyperintensities, and infarcts. Positron emission tomography was conducted with fluorodeoxyglucose to measure cerebral metabolism and Pittsburgh compound B for fibrillar Aβ. Neuropsychological evaluation, including the Clinical Dementia Rating scale, was performed.
  
  
  METHODS
  Magnetic resonance images were rated for the presence and location of CMBs. Lobar CMBs were subclassified as cortical or subcortical. Measurements of CBF, metabolism, and Aβ were compared with the presence and number of CMBs with voxelwise and region-of-interest analyses.
  
  
  RESULTS
  The presence of cortical CMBs was associated with significantly reduced CBF in multiple regions on voxelwise and region-of-interest analyses (percentage difference in global CBF, -25.3%; P = .0003), with the largest reductions in the parietal cortex (-37.6%; P < .0001) and precuneus (-31.8%; P = .0006). Participants with any CMBs showed a nonsignificant trend toward reduced CBF. Participants with cortical CMBs had a significant association with greater prevalence of infarcts (24% vs 6%; P = .047) and demonstrated a trend to greater prevalence of deficits demonstrated on the Clinical Dementia Rating scale (45% vs 19%; P = .12). There was no difference in cortical amyloid (measured by Pittsburgh compound B positron emission tomography) between participants with and without CMBs (P = .60).
  
  
  CONCLUSIONS
  In cognitively normal elderly individuals, incidental CMBs in cortical locations are associated with widespread reductions in resting-state CBF. Chronic hypoperfusion may put these people at risk for neuronal injury and neurodegeneration. Our results suggest that resting-state CBF is a marker of CMB-related small-vessel disease.
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Gregg
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Albert E
authors.initials: AE
authors.lastname: Kim
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Boston3Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: M Edip
authors.initials: ME
authors.lastname: Gurol
authors.affiliation: Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Oscar L
authors.initials: OL
authors.lastname: Lopez
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Aizenstein
authors.affiliation: Department of Radiology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Julie C
authors.initials: JC
authors.lastname: Price
authors.affiliation: Department of Radiology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Chester A
authors.initials: CA
authors.lastname: Mathis
authors.affiliation: Department of Radiology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: James
authors.affiliation: Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Beth E
authors.initials: BE
authors.lastname: Snitz
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Ann D
authors.initials: AD
authors.lastname: Cohen
authors.affiliation: Department of Human Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: M Ilyas
authors.initials: MI
authors.lastname: Kamboh
authors.affiliation: Department of Radiology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Davneet
authors.initials: D
authors.lastname: Minhas
authors.affiliation: Department of Biostatistics, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Weissfeld
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Erica L
authors.initials: EL
authors.lastname: Tamburo
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: William E
authors.initials: WE
authors.lastname: Klunk
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology*; D001057:Apolipoproteins E / Q000235:genetics; D016657:Cerebral Amyloid Angiopathy / Q000453:epidemiology / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000453:epidemiology* / Q000235:genetics / Q000473:pathology*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D021621:Imaging, Three-Dimensional; D015994:Incidence; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography
chemical_list: D001057:Apolipoproteins E