title: Multiple or mixed cerebral microbleeds and dementia in patients with vascular risk factors.
abstract: OBJECTIVE
  To investigate whether cerebral microbleeds (CMBs) are independently associated with incident dementia in patients with vascular risk factors.
  
  
  METHODS
  Using data from a Japanese cohort of participants with vascular risk factors in an observational study from 2001, we evaluated the association between CMBs at baseline and incident dementia. Baseline brain MRI was used to determine small-vessel disease (CMBs, lacunar infarcts, and white matter hyperintensities) and brain atrophy. Cox proportional hazards analyses were performed for predictors of dementia adjusting for age, sex, APOE ε4 allele, educational level, baseline Mini-Mental State Examination score, cerebrovascular events, vascular risk factors, and MRI findings.
  
  
  RESULTS
  Of the 524 subjects (mean age 68 ± 8.3 years, 57.6% male, 12.8 ± 2.6 years of schooling, 21.6% CMBs), 44 patients with incident dementia (20 Alzheimer disease, 18 vascular dementia, 3 mixed-type, and 3 other) were diagnosed during the median 7.5-year follow-up. In multivariate analysis, the presence of overall CMBs was not associated with an increased risk of incident all-cause dementia (p = 0.15). However, multiple CMBs (≥ 2) or mixed (lobar and deep) CMBs were associated with the increased risk of all-cause dementia, whereas strictly lobar CMBs showed no association with any dementia.
  
  
  CONCLUSIONS
  Multiple CMBs or mixed CMBs independently showed higher risk of all-cause dementia. Our results reinforce the hypothesis that CMBs exert deleterious effects on dementia incidence, suggesting that this association may be mediated by vascular burden.
authors.affiliation: From the Department of Neurology and Stroke Center (K.M., M.T., S.O., Y.Y., M.S., H.M.), Osaka University Graduate School of Medicine; and Department of Neurology (K.K.), Tokyo Women's Medical University, Japan. miwa@osaka-njm.net kkitagawa@nij.twmu.ac.jp.
authors.forename: Kaori
authors.initials: K
authors.lastname: Miwa
authors.affiliation: From the Department of Neurology and Stroke Center (K.M., M.T., S.O., Y.Y., M.S., H.M.), Osaka University Graduate School of Medicine; and Department of Neurology (K.K.), Tokyo Women's Medical University, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: From the Department of Neurology and Stroke Center (K.M., M.T., S.O., Y.Y., M.S., H.M.), Osaka University Graduate School of Medicine; and Department of Neurology (K.K.), Tokyo Women's Medical University, Japan.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Okazaki
authors.affiliation: From the Department of Neurology and Stroke Center (K.M., M.T., S.O., Y.Y., M.S., H.M.), Osaka University Graduate School of Medicine; and Department of Neurology (K.K.), Tokyo Women's Medical University, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Yagita
authors.affiliation: From the Department of Neurology and Stroke Center (K.M., M.T., S.O., Y.Y., M.S., H.M.), Osaka University Graduate School of Medicine; and Department of Neurology (K.K.), Tokyo Women's Medical University, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Sakaguchi
authors.affiliation: From the Department of Neurology and Stroke Center (K.M., M.T., S.O., Y.Y., M.S., H.M.), Osaka University Graduate School of Medicine; and Department of Neurology (K.K.), Tokyo Women's Medical University, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Mochizuki
authors.affiliation: From the Department of Neurology and Stroke Center (K.M., M.T., S.O., Y.Y., M.S., H.M.), Osaka University Graduate School of Medicine; and Department of Neurology (K.K.), Tokyo Women's Medical University, Japan. miwa@osaka-njm.net kkitagawa@nij.twmu.ac.jp.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kitagawa
mesh_terms: D000368:Aged; D001921:Brain / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000453:epidemiology* / Q000473:pathology; D003704:Dementia / Q000453:epidemiology* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007564:Japan / Q000453:epidemiology; D053208:Kaplan-Meier Estimate; D008279:Magnetic Resonance Imaging; D008297:Male; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D012307:Risk Factors; D014652:Vascular Diseases / Q000453:epidemiology* / Q000473:pathology