title: Cerebral Microbleeds, CSF p-Tau, and Cognitive Decline: Significance of Anatomic Distribution.
abstract: OBJECTIVE
  Cerebral microbleeds are associated with aging, hypertension, and Alzheimer disease. Microbleeds in a lobar distribution are believed to reflect underlying amyloid angiopathy, whereas microbleeds in the deep gray matter and infratentorial brain are commonly seen with hypertension. However, it is unknown how microbleeds in either distribution are related to Alzheimer pathogenesis. The purpose of this analysis was to test whether lobar and deep gray/infratentorial microbleeds demonstrate differential associations with CSF amyloid-β and phosphorylated tau 181 protein levels and longitudinal cognitive decline.
  
  
  METHODS
  A total of 626 subjects (151 cognitively normal, 389 with mild cognitive impairment, and 86 with Alzheimer disease) from the Alzheimer's Disease Neuroimaging Initiative who had undergone 3T MR imaging and lumbar puncture were included in the analysis. The number and location of microbleeds were assessed visually. Associations between lobar or deep gray/infratentorial microbleeds with CSF amyloid-β levels, abnormal CSF phosphorylated tau 181 protein levels, and longitudinal cognitive decline were assessed by using ordinary least-squares, logistic, and mixed-effects regression models while adjusting for covariates.
  
  
  RESULTS
  Having ≥3 lobar microbleeds was associated with lower levels of CSF amyloid-β (P = .001). After adjusting for CSF amyloid-β level, lobar microbleeds were independently associated with a higher likelihood of having an abnormal CSF phosphorylated tau 181 protein level (P = .004). Lobar microbleeds were associated with accelerated longitudinal cognitive decline (P = .007). Deep gray/infratentorial microbleeds revealed no significant associations.
  
  
  CONCLUSIONS
  The distribution of microbleeds revealed different associations with amyloid-β and phosphorylated tau 181 protein levels and cognition. Lobar and deep gray/infratentorial microbleeds should be considered separately with regard to Alzheimer disease pathogenesis.
authors.affiliation: From the Department of Radiology (G.C.C.), Division of Neuroradiology, Weill Cornell Medical College, New York-Presbyterian Hospital, New York, New York gcc9004@med.cornell.edu.
authors.forename: G C
authors.initials: GC
authors.lastname: Chiang
authors.affiliation: Department of Biomedical Engineering (J.C.C.H.), Cornell University, Ithaca, New York.
authors.forename: J C
authors.initials: JC
authors.lastname: Cruz Hernandez
authors.affiliation: Department of Radiology (K.K., C.R.J.), Mayo Clinic, Rochester, Minnesota.
authors.forename: K
authors.initials: K
authors.lastname: Kantarci
authors.affiliation: Department of Radiology (K.K., C.R.J.), Mayo Clinic, Rochester, Minnesota.
authors.forename: C R
authors.initials: CR
authors.lastname: Jack
authors.affiliation: Department of Radiology and Biomedical Imaging (M.W.W.), University of California, San Francisco, California.
authors.forename: M W
authors.initials: MW
authors.lastname: Weiner
mesh_terms: D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D002543:Cerebral Hemorrhage / Q000134:cerebrospinal fluid* / Q000209:etiology / Q000473:pathology*; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D016875:tau Proteins