title: Incidence of cerebral microbleeds in preclinical Alzheimer disease.
abstract: OBJECTIVE
  We sought to determine the incidence and associations of lobar microbleeds (LMBs) in a longitudinal cohort with (11)C-Pittsburgh compound B (PiB) PET imaging.
  
  
  METHODS
  One hundred seventy-four participants from the observational Australian Imaging, Biomarkers and Lifestyle Study of Ageing (97 with normal cognition [NC], 37 with mild cognitive impairment [MCI], and 40 with Alzheimer disease [AD] dementia) were assessed at 3 time points over 3 years with 3-tesla susceptibility-weighted MRI and (11)C-PiB PET. MRIs were inspected for microbleeds, siderosis, infarction, and white matter hyperintensity severity, blind to clinical and PiB findings. Neocortical PiB standardized uptake value ratio, normalized to cerebellar cortex, was dichotomized as positive or negative (PiB+/-, standardized uptake value ratio >1.5). Annualized LMB incidence was calculated, and logistic regression was used to determine the association of incident LMBs with PiB, APOE ε4+ status, and cerebrovascular disease.
  
  
  RESULTS
  LMBs were present in 18.6% of NC, 24.3% of MCI, and 40% of AD participants (p < 0.05 vs NC). LMB incidence was 0.2 ± 0.6 per year in NC participants, 0.2 ± 0.5 in MCI, and 0.7 ± 1.4 in AD (p < 0.03 vs NC) and was 6-fold higher in PiB+ than PiB-NC. Incident LMBs were associated with age, APOE ε4+, PiB+, and baseline LMBs. Incidence of multiple LMBs was also associated with lacunar infarction and white matter hyperintensity severity.
  
  
  CONCLUSIONS
  Older age, baseline LMBs, higher β-amyloid burden, and concomitant cerebrovascular disease may all confer higher risk of incident LMBs. This should be considered when designing protocols for amyloid-modifying clinical trials.
authors.affiliation: From the Department of Nuclear Medicine and Centre for PET (P.A.Y., V.L.V., C.C.R.), Austin Health, Heidelberg; The University of Melbourne (P.A.Y., P.M.D., C.S., C.C.R.), Parkville; Department of Radiology (P.M.D., P.M.P., C.S.), Royal Melbourne Hospital, Parkville; National Ageing Research Institute (D.A.), Parkville; CSIRO Preventative Health Flagship (O.S.), Parkville; Florey Institute of Neuroscience and Mental Health (K.A.E., C.L.M., V.L.V.), The University of Melbourne, Parkville; Academic Unit for Psychiatry of Old Age (K.A.E., D.A.), Department of Psychiatry, The University of Melbourne, Kew, Victoria; Centre of Excellence for Alzheimer's Disease Research and Care (R.N.M.), School of Exercise, Biomedical and Health Sciences, Edith Cowan University, Australia.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Yates
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Desmond
authors.forename: Pramit M
authors.initials: PM
authors.lastname: Phal
authors.forename: Christopher
authors.initials: C
authors.lastname: Steward
authors.forename: Cassandra
authors.initials: C
authors.lastname: Szoeke
authors.forename: Olivier
authors.initials: O
authors.lastname: Salvado
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Ellis
authors.forename: Ralph N
authors.initials: RN
authors.lastname: Martins
authors.forename: Colin L
authors.initials: CL
authors.lastname: Masters
authors.forename: David
authors.initials: D
authors.lastname: Ames
authors.forename: Victor L
authors.initials: VL
authors.lastname: Villemagne
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Rowe
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000000981:diagnostic imaging*; D000682:Amyloid / Q000378:metabolism*; D000814:Aniline Compounds; D001315:Australia; D001921:Brain / Q000000981:diagnostic imaging* / Q000473:pathology; D059345:Cerebral Small Vessel Diseases / Q000150:complications / Q000175:diagnosis*; D005260:Female; D006801:Humans; D015994:Incidence; D020300:Intracranial Hemorrhages / Q000150:complications / Q000000981:diagnostic imaging* / Q000453:epidemiology; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods; D013844:Thiazoles
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D000682:Amyloid; D000814:Aniline Compounds; D013844:Thiazoles