title: Patients with Alzheimer disease with multiple microbleeds: relation with cerebrospinal fluid biomarkers and cognition.
abstract: OBJECTIVE
  Microbleeds (MBs) are commonly observed in Alzheimer disease. A minority of patients has multiple MBs. We aimed to investigate associations of multiple MBs in Alzheimer disease with clinical and MRI characteristics and cerebrospinal fluid biomarkers.
  
  
  METHODS
  Patients with Alzheimer disease with multiple (>or=8) MBs on T2*-weighted MRI were matched for age, sex, and field strength with patients with Alzheimer disease without MBs on a 1:2 basis. We included 21 patients with multiple MBs (73+/-7 years, 33% female) and 42 patients without MBs (72+/-7 years, 38% female). Mini-Mental State Examination was used to assess dementia severity. Cognitive functions were assessed using neuropsychological tests. Medial temporal lobe atrophy (0 to 4), global cortical atrophy (0 to 3), and white matter hyperintensities (0 to 30) were assessed using visual rating scales. In a subset, apolipoprotein E genotype and cerebrospinal fluid amyloid beta 1-42, total tau and tau phosphorylated at threonine 181 were determined.
  
  
  RESULTS
  Patients with multiple MBs performed worse on Mini-Mental State Examination (multiple MB: 17+/-7; no MB: 22+/-4, P<0.05) despite similar disease duration. Atrophy was not related to presence of MBs, but patients with multiple MBs had more white matter hyperintensities (multiple MB: 8.8+/-4.8; no MB: 3.2+/-3.6, P<0.05). Adjusted for age, sex, white matter hyperintensities, and medial temporal lobe atrophy, the multiple MB group additionally performed worse on Visual Association Test object naming and animal fluency. Patients with multiple MBs had lower cerebrospinal fluid amyloid beta 1-42 levels (307+/-61) than patients without MBs (505+/-201, P<0.05). Adjusted for the same covariates, total tau, and tau phosphorylated at threonine 181 were higher in the multiple MB group.
  
  
  CONCLUSIONS
  Microbleeds are associated with the clinical manifestation and biochemical hallmarks of Alzheimer disease, suggesting possible involvement of MBs in the pathogenesis of Alzheimer disease.
authors.affiliation: Department of Neurology and Alzheimer Center, VU University Medical Center, Amsterdam, The Netherlands. j.goos@vumc.nl
authors.forename: Jeroen D C
authors.initials: JD
authors.lastname: Goos
authors.forename: M I
authors.initials: MI
authors.lastname: Kester
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
authors.forename: Martin
authors.initials: M
authors.lastname: Klein
authors.forename: Marinus A
authors.initials: MA
authors.lastname: Blankenstein
authors.forename: Philip
authors.initials: P
authors.lastname: Scheltens
authors.forename: Wiesje M
authors.initials: WM
authors.lastname: van der Flier
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000150:complications / Q000523:psychology; D015415:Biomarkers / Q000134:cerebrospinal fluid; D016022:Case-Control Studies; D002543:Cerebral Hemorrhage / Q000134:cerebrospinal fluid* / Q000150:complications / Q000523:psychology; D003072:Cognition Disorders / Q000134:cerebrospinal fluid* / Q000150:complications / Q000523:psychology; D005260:Female; D006801:Humans; D008297:Male; D008833:Microcirculation; D012189:Retrospective Studies
chemical_list: D015415:Biomarkers